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American Diabetes Association (ADA): Annual Scientific Sessions
Markers predict hypoglycemia on intensive glycemic therapy
SAN FRANCISCO – Patients with type 2 diabetes who were insulin deficient were 36 times more likely to develop severe hypoglycemia on treatment and to fail to get hemoglobin A1c levels below 6% after starting intensive therapy in a retrospective analysis of data on 1,401 patients.
In addition, patients with any of four antibodies against islet cells at baseline were 4-12 times more likely to develop severe hypoglycemia and fail to reach the glycemic target on intensive therapy, compared with patients without those biomarkers, Dr. Lisa Chow reported at the annual scientific sessions of the American Diabetes Association.
The study defined insulin deficiency as a fasting C-peptide level no higher than 0.45 ng/mL. Investigators measured levels of three of the autoantibodies and considered the fourth – insulin autoantibody (IAA) – to be present if the patient used insulin at baseline.
In unadjusted analyses, the likelihood of severe hypoglycemia and failure to reach the glycemic target was four times higher in patients with IAA or antibodies against glutamic acid decarboxylase (GAD) or zinc transporter 8 (ZnT8), compared with patients without those autoantibodies. Severe hypoglycemia and failure to get hemoglobin A1c (HbA1c) below 6% were 11 times more likely in patients with antibodies against tyrosine phosphatase–related islet antigen 2 (IA-2), reported Dr. Chow, an endocrinologist at the University of Minnesota, Minneapolis.
She and her associates studied data on 1,401 patients who were randomized to the intensive glycemic control arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. They compared 326 patients ("cases") who developed severe hypoglycemia and whose HbA1c levels did not reach the target of less than 6% with 1,075 control patients (matched 4:1 by age, race, and body mass index) who did not have severe hypoglycemia and who reached the HbA1c target.
Overall, 17% of cases and 1% of controls were insulin deficient. Excluding IAA (present in 62% of cases and 26% of controls), the most common islet antibody was GAD, in 17% of cases and 6% of controls. IA-2 was present in 4% of cases and 0.4% of controls, and ZnT8 was present in 2% of cases and 0.7% of controls.
"We propose that measuring C-peptide and GAD antibodies in patients with type 2 diabetes may serve as a biomarker to help tailor and individualize therapy" by predicting which patients are more likely to have adverse outcomes on intensive glycemic treatment, Dr. Chow said.
At baseline, the case group was significantly more likely to use insulin, compared with controls (89% and 24%, respectively) and less likely to be male (50% vs. 59%). The case patients had a higher HbA1c at baseline, compared with controls (8.54% vs. 8.08%, respectively) and a longer duration of diabetes (15 vs. 9 years).
After adjusting for the effects of age and body mass index, the combined outcome of severe hypoglycemia and failure to reach the glycemic target was 32 times more likely in patients with insulin deficiency at baseline, 3 times more likely in patients with GAD or ZnT8, 5 times more likely in patients with IAA, and 9 times more likely in patients with IA-2, compared with patients without those markers, Dr. Chow said.
A third analysis removed data for any case patients who died and their associated controls and found that severe hypoglycemia and failure to reach the glycemic target was 30 times more likely in patients with insulin deficiency at baseline, 4 times more likely in patients with GAD or ZnT8, 5 times more likely in patients with IAA, and 12 times more likely in patients with IA-2, compared with patients without those markers.
The study defined severe hypoglycemia as any hypoglycemia requiring assistance. Patients who developed severe hypoglycemia were four times less likely to get their HbA1c levels below 6%.
Dr. Chow reported having no financial disclosures. The National Institutes of Health funded the study.
I don’t think this study means that we automatically should test everybody with type 2 diabetes for their insulin levels and their autoantibodies because we would need a study to show that if you did that, versus not doing that, people actually do better.
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I think what this study tells us is that there is a fair amount of slow-burn type 1 diabetes amongst people who we think have type 2 diabetes. Perhaps unsurprisingly, those people tend to have more hypoglycemia and trouble.
The study defined poor glycemic control as not being able to get an HbA1c of less than 6%. To be fair, that’s what the ACCORD trial said. Clinically, nobody would consider someone with an HbA1c of 6.2% to have poor glycemic control.
One take-home message might be that if your patient has poor glycemic control and severe hypoglycemia, consider checking for autoantibodies.
Dr. Amanda Adler is consultant physician at Cambridge University’s Addenbrooke’s Hospital and chair of the technology appraisals committee for the National Institute for Health and Clinical Excellence, England. She gave these comments in an interview at the meeting.
I don’t think this study means that we automatically should test everybody with type 2 diabetes for their insulin levels and their autoantibodies because we would need a study to show that if you did that, versus not doing that, people actually do better.
|
|
I think what this study tells us is that there is a fair amount of slow-burn type 1 diabetes amongst people who we think have type 2 diabetes. Perhaps unsurprisingly, those people tend to have more hypoglycemia and trouble.
The study defined poor glycemic control as not being able to get an HbA1c of less than 6%. To be fair, that’s what the ACCORD trial said. Clinically, nobody would consider someone with an HbA1c of 6.2% to have poor glycemic control.
One take-home message might be that if your patient has poor glycemic control and severe hypoglycemia, consider checking for autoantibodies.
Dr. Amanda Adler is consultant physician at Cambridge University’s Addenbrooke’s Hospital and chair of the technology appraisals committee for the National Institute for Health and Clinical Excellence, England. She gave these comments in an interview at the meeting.
I don’t think this study means that we automatically should test everybody with type 2 diabetes for their insulin levels and their autoantibodies because we would need a study to show that if you did that, versus not doing that, people actually do better.
|
|
I think what this study tells us is that there is a fair amount of slow-burn type 1 diabetes amongst people who we think have type 2 diabetes. Perhaps unsurprisingly, those people tend to have more hypoglycemia and trouble.
The study defined poor glycemic control as not being able to get an HbA1c of less than 6%. To be fair, that’s what the ACCORD trial said. Clinically, nobody would consider someone with an HbA1c of 6.2% to have poor glycemic control.
One take-home message might be that if your patient has poor glycemic control and severe hypoglycemia, consider checking for autoantibodies.
Dr. Amanda Adler is consultant physician at Cambridge University’s Addenbrooke’s Hospital and chair of the technology appraisals committee for the National Institute for Health and Clinical Excellence, England. She gave these comments in an interview at the meeting.
SAN FRANCISCO – Patients with type 2 diabetes who were insulin deficient were 36 times more likely to develop severe hypoglycemia on treatment and to fail to get hemoglobin A1c levels below 6% after starting intensive therapy in a retrospective analysis of data on 1,401 patients.
In addition, patients with any of four antibodies against islet cells at baseline were 4-12 times more likely to develop severe hypoglycemia and fail to reach the glycemic target on intensive therapy, compared with patients without those biomarkers, Dr. Lisa Chow reported at the annual scientific sessions of the American Diabetes Association.
The study defined insulin deficiency as a fasting C-peptide level no higher than 0.45 ng/mL. Investigators measured levels of three of the autoantibodies and considered the fourth – insulin autoantibody (IAA) – to be present if the patient used insulin at baseline.
In unadjusted analyses, the likelihood of severe hypoglycemia and failure to reach the glycemic target was four times higher in patients with IAA or antibodies against glutamic acid decarboxylase (GAD) or zinc transporter 8 (ZnT8), compared with patients without those autoantibodies. Severe hypoglycemia and failure to get hemoglobin A1c (HbA1c) below 6% were 11 times more likely in patients with antibodies against tyrosine phosphatase–related islet antigen 2 (IA-2), reported Dr. Chow, an endocrinologist at the University of Minnesota, Minneapolis.
She and her associates studied data on 1,401 patients who were randomized to the intensive glycemic control arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. They compared 326 patients ("cases") who developed severe hypoglycemia and whose HbA1c levels did not reach the target of less than 6% with 1,075 control patients (matched 4:1 by age, race, and body mass index) who did not have severe hypoglycemia and who reached the HbA1c target.
Overall, 17% of cases and 1% of controls were insulin deficient. Excluding IAA (present in 62% of cases and 26% of controls), the most common islet antibody was GAD, in 17% of cases and 6% of controls. IA-2 was present in 4% of cases and 0.4% of controls, and ZnT8 was present in 2% of cases and 0.7% of controls.
"We propose that measuring C-peptide and GAD antibodies in patients with type 2 diabetes may serve as a biomarker to help tailor and individualize therapy" by predicting which patients are more likely to have adverse outcomes on intensive glycemic treatment, Dr. Chow said.
At baseline, the case group was significantly more likely to use insulin, compared with controls (89% and 24%, respectively) and less likely to be male (50% vs. 59%). The case patients had a higher HbA1c at baseline, compared with controls (8.54% vs. 8.08%, respectively) and a longer duration of diabetes (15 vs. 9 years).
After adjusting for the effects of age and body mass index, the combined outcome of severe hypoglycemia and failure to reach the glycemic target was 32 times more likely in patients with insulin deficiency at baseline, 3 times more likely in patients with GAD or ZnT8, 5 times more likely in patients with IAA, and 9 times more likely in patients with IA-2, compared with patients without those markers, Dr. Chow said.
A third analysis removed data for any case patients who died and their associated controls and found that severe hypoglycemia and failure to reach the glycemic target was 30 times more likely in patients with insulin deficiency at baseline, 4 times more likely in patients with GAD or ZnT8, 5 times more likely in patients with IAA, and 12 times more likely in patients with IA-2, compared with patients without those markers.
The study defined severe hypoglycemia as any hypoglycemia requiring assistance. Patients who developed severe hypoglycemia were four times less likely to get their HbA1c levels below 6%.
Dr. Chow reported having no financial disclosures. The National Institutes of Health funded the study.
SAN FRANCISCO – Patients with type 2 diabetes who were insulin deficient were 36 times more likely to develop severe hypoglycemia on treatment and to fail to get hemoglobin A1c levels below 6% after starting intensive therapy in a retrospective analysis of data on 1,401 patients.
In addition, patients with any of four antibodies against islet cells at baseline were 4-12 times more likely to develop severe hypoglycemia and fail to reach the glycemic target on intensive therapy, compared with patients without those biomarkers, Dr. Lisa Chow reported at the annual scientific sessions of the American Diabetes Association.
The study defined insulin deficiency as a fasting C-peptide level no higher than 0.45 ng/mL. Investigators measured levels of three of the autoantibodies and considered the fourth – insulin autoantibody (IAA) – to be present if the patient used insulin at baseline.
In unadjusted analyses, the likelihood of severe hypoglycemia and failure to reach the glycemic target was four times higher in patients with IAA or antibodies against glutamic acid decarboxylase (GAD) or zinc transporter 8 (ZnT8), compared with patients without those autoantibodies. Severe hypoglycemia and failure to get hemoglobin A1c (HbA1c) below 6% were 11 times more likely in patients with antibodies against tyrosine phosphatase–related islet antigen 2 (IA-2), reported Dr. Chow, an endocrinologist at the University of Minnesota, Minneapolis.
She and her associates studied data on 1,401 patients who were randomized to the intensive glycemic control arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. They compared 326 patients ("cases") who developed severe hypoglycemia and whose HbA1c levels did not reach the target of less than 6% with 1,075 control patients (matched 4:1 by age, race, and body mass index) who did not have severe hypoglycemia and who reached the HbA1c target.
Overall, 17% of cases and 1% of controls were insulin deficient. Excluding IAA (present in 62% of cases and 26% of controls), the most common islet antibody was GAD, in 17% of cases and 6% of controls. IA-2 was present in 4% of cases and 0.4% of controls, and ZnT8 was present in 2% of cases and 0.7% of controls.
"We propose that measuring C-peptide and GAD antibodies in patients with type 2 diabetes may serve as a biomarker to help tailor and individualize therapy" by predicting which patients are more likely to have adverse outcomes on intensive glycemic treatment, Dr. Chow said.
At baseline, the case group was significantly more likely to use insulin, compared with controls (89% and 24%, respectively) and less likely to be male (50% vs. 59%). The case patients had a higher HbA1c at baseline, compared with controls (8.54% vs. 8.08%, respectively) and a longer duration of diabetes (15 vs. 9 years).
After adjusting for the effects of age and body mass index, the combined outcome of severe hypoglycemia and failure to reach the glycemic target was 32 times more likely in patients with insulin deficiency at baseline, 3 times more likely in patients with GAD or ZnT8, 5 times more likely in patients with IAA, and 9 times more likely in patients with IA-2, compared with patients without those markers, Dr. Chow said.
A third analysis removed data for any case patients who died and their associated controls and found that severe hypoglycemia and failure to reach the glycemic target was 30 times more likely in patients with insulin deficiency at baseline, 4 times more likely in patients with GAD or ZnT8, 5 times more likely in patients with IAA, and 12 times more likely in patients with IA-2, compared with patients without those markers.
The study defined severe hypoglycemia as any hypoglycemia requiring assistance. Patients who developed severe hypoglycemia were four times less likely to get their HbA1c levels below 6%.
Dr. Chow reported having no financial disclosures. The National Institutes of Health funded the study.
AT THE ADA ANNUAL SCIENTIFIC SESSION
Fractures Increased With Two Diabetes Drugs
SAN FRANCISCO – Adults who started taking sulfonylurea drugs for diabetes were 9% more likely to develop fractures within 5 years, and patients starting thiazolidinediones were 9% more likely to have fractures, compared with patients on other medications in a retrospective study of 99,892 adults.
Those significantly increased risks emerged after adjusting for the effects of multiple factors including age, gender, region, medical conditions, and concomitant medications, Sandhya Mehta, Ph.D. and her associates reported at the annual scientific sessions of the American Diabetes Association. Patients had no prior history of fracture.
The longitudinal retrospective analysis of a large administrative claims database found a 10% incidence of fracture on sulfonylureas and 11% on thiazolidinediones, compared with 7% on biguanides (metformin), 8% on dipeptidyl peptidase-4 (DPP-4) inhibitors, 11% on meglitinide analogues, and 6% on incretin mimetic agents. After adjusting for the confounders, the hazard ratios for each of the other three types of drugs hovered around 1 and were not statistically significantly different but increased to 1.09 for sulfonylureas and 1.4 for thiazolidinediones, reported Dr. Mehta of Inovalon Inc. in Bowie, Md., a health care data analytics company.
In the cohort as a whole, 7% of patients developed fractures. Roughly 15% of patients started sulfonylureas, 3% took thiazolidinediones, 78% were on metformin, 3% took DPP-4 inhibitors, 1% were on incretin mimetics, and 1% took meglitinides.
Previous reports have shown an increased risk of fracture in patients on thiazolidinediones, compared with those on metformin, and the current results support the hypothesis that thiazolidinediones decrease bone mineral density, stimulate adipocyte and osteoclast differentiation, and inhibit osteoblast differentiation to make fracture more likely, Dr. Mehta said.
The association between sulfonylureas and increased fracture risk appears to be new, however, and deserves further study, she added.
The study did not look at the effects of combination drug therapy.
Data came from the Medical Outcomes Research for Effectiveness and Economics (MORE) Registry, which is owned by Inovalon, drawing from the years 2008-2012.
Dr. Mehta reported having no financial disclosures.
On Twitter @sherryboschert
Dr. Amanda Adler
This study confirms that we observe more fracture risks with thiazolidinediones. To my knowledge, this is the first time that this has been shown for sulfonylureas.
One concern about the study is so-called residual confounding. The confounders were not entirely clear in the presentation. One possible confounder is what might have preceded the fracture. If, in fact, patients on sulfonylureas were having more low blood glucose values and consequently fell, then that would be interesting to know. Unfortunately, the investigators couldn’t tell us that.
With thiazolidinediones, I’ve been told that a cell that hasn’t decided yet whether it’s going to be a bone cell or a fat cell might, in the presence of a thiazolidinedione, go on to be a fat cell instead of a bone cell. In which case, you would possibly have a problem with fewer bone cells. This study set out to look at bone metabolism but, to be fair, it could not show anything about that. That was rather ambitious.
I think there is no clinical message from this as yet. The investigators might want to look back at trials that randomized people to sulfonylureas or something else and meta-analyze that to see if there were differences in fractures.
The study suggests that the other second-line agents are okay, but again, we can’t really know what they’re doing to bones without knowing if there’s something else going on. If you took a drug that made you more likely to topple over, your bones could be equally strong as those who didn’t fall over, yet you end up with a fracture.
I’m not going to change my practice on the basis of this study.
Dr. Amanda Adler is consultant physician at Cambridge University’s Addenbrooke’s Hospital and chair of the technology appraisals committee for the National Institute for Health and Clinical Excellence in England. She gave these comments in an interview at the meeting.
This study confirms that we observe more fracture risks with thiazolidinediones. To my knowledge, this is the first time that this has been shown for sulfonylureas.
|
|
One concern about the study is so-called residual confounding. The confounders were not entirely clear in the presentation. One possible confounder is what might have preceded the fracture. If, in fact, patients on sulfonylureas were having more low blood glucose values and consequently fell, then that would be interesting to know. Unfortunately, the investigators couldn’t tell us that.
With thiazolidinediones, I’ve been told that a cell that hasn’t decided yet whether it’s going to be a bone cell or a fat cell might, in the presence of a thiazolidinedione, go on to be a fat cell instead of a bone cell. In which case, you would possibly have a problem with fewer bone cells. This study set out to look at bone metabolism but, to be fair, it could not show anything about that. That was rather ambitious.
I think there is no clinical message from this as yet. The investigators might want to look back at trials that randomized people to sulfonylureas or something else and meta-analyze that to see if there were differences in fractures.
The study suggests that the other second-line agents are okay, but again, we can’t really know what they’re doing to bones without knowing if there’s something else going on. If you took a drug that made you more likely to topple over, your bones could be equally strong as those who didn’t fall over, yet you end up with a fracture.
I’m not going to change my practice on the basis of this study.
Dr. Amanda Adler is consultant physician at Cambridge University’s Addenbrooke’s Hospital and chair of the technology appraisals committee for the National Institute for Health and Clinical Excellence in England. She gave these comments in an interview at the meeting.
This study confirms that we observe more fracture risks with thiazolidinediones. To my knowledge, this is the first time that this has been shown for sulfonylureas.
|
|
One concern about the study is so-called residual confounding. The confounders were not entirely clear in the presentation. One possible confounder is what might have preceded the fracture. If, in fact, patients on sulfonylureas were having more low blood glucose values and consequently fell, then that would be interesting to know. Unfortunately, the investigators couldn’t tell us that.
With thiazolidinediones, I’ve been told that a cell that hasn’t decided yet whether it’s going to be a bone cell or a fat cell might, in the presence of a thiazolidinedione, go on to be a fat cell instead of a bone cell. In which case, you would possibly have a problem with fewer bone cells. This study set out to look at bone metabolism but, to be fair, it could not show anything about that. That was rather ambitious.
I think there is no clinical message from this as yet. The investigators might want to look back at trials that randomized people to sulfonylureas or something else and meta-analyze that to see if there were differences in fractures.
The study suggests that the other second-line agents are okay, but again, we can’t really know what they’re doing to bones without knowing if there’s something else going on. If you took a drug that made you more likely to topple over, your bones could be equally strong as those who didn’t fall over, yet you end up with a fracture.
I’m not going to change my practice on the basis of this study.
Dr. Amanda Adler is consultant physician at Cambridge University’s Addenbrooke’s Hospital and chair of the technology appraisals committee for the National Institute for Health and Clinical Excellence in England. She gave these comments in an interview at the meeting.
This study confirms that we observe more fracture risks with thiazolidinediones. To my knowledge, this is the first time that this has been shown for sulfonylureas.
|
|
One concern about the study is so-called residual confounding. The confounders were not entirely clear in the presentation. One possible confounder is what might have preceded the fracture. If, in fact, patients on sulfonylureas were having more low blood glucose values and consequently fell, then that would be interesting to know. Unfortunately, the investigators couldn’t tell us that.
With thiazolidinediones, I’ve been told that a cell that hasn’t decided yet whether it’s going to be a bone cell or a fat cell might, in the presence of a thiazolidinedione, go on to be a fat cell instead of a bone cell. In which case, you would possibly have a problem with fewer bone cells. This study set out to look at bone metabolism but, to be fair, it could not show anything about that. That was rather ambitious.
I think there is no clinical message from this as yet. The investigators might want to look back at trials that randomized people to sulfonylureas or something else and meta-analyze that to see if there were differences in fractures.
The study suggests that the other second-line agents are okay, but again, we can’t really know what they’re doing to bones without knowing if there’s something else going on. If you took a drug that made you more likely to topple over, your bones could be equally strong as those who didn’t fall over, yet you end up with a fracture.
I’m not going to change my practice on the basis of this study.
Dr. Amanda Adler is consultant physician at Cambridge University’s Addenbrooke’s Hospital and chair of the technology appraisals committee for the National Institute for Health and Clinical Excellence in England. She gave these comments in an interview at the meeting.
SAN FRANCISCO – Adults who started taking sulfonylurea drugs for diabetes were 9% more likely to develop fractures within 5 years, and patients starting thiazolidinediones were 9% more likely to have fractures, compared with patients on other medications in a retrospective study of 99,892 adults.
Those significantly increased risks emerged after adjusting for the effects of multiple factors including age, gender, region, medical conditions, and concomitant medications, Sandhya Mehta, Ph.D. and her associates reported at the annual scientific sessions of the American Diabetes Association. Patients had no prior history of fracture.
The longitudinal retrospective analysis of a large administrative claims database found a 10% incidence of fracture on sulfonylureas and 11% on thiazolidinediones, compared with 7% on biguanides (metformin), 8% on dipeptidyl peptidase-4 (DPP-4) inhibitors, 11% on meglitinide analogues, and 6% on incretin mimetic agents. After adjusting for the confounders, the hazard ratios for each of the other three types of drugs hovered around 1 and were not statistically significantly different but increased to 1.09 for sulfonylureas and 1.4 for thiazolidinediones, reported Dr. Mehta of Inovalon Inc. in Bowie, Md., a health care data analytics company.
In the cohort as a whole, 7% of patients developed fractures. Roughly 15% of patients started sulfonylureas, 3% took thiazolidinediones, 78% were on metformin, 3% took DPP-4 inhibitors, 1% were on incretin mimetics, and 1% took meglitinides.
Previous reports have shown an increased risk of fracture in patients on thiazolidinediones, compared with those on metformin, and the current results support the hypothesis that thiazolidinediones decrease bone mineral density, stimulate adipocyte and osteoclast differentiation, and inhibit osteoblast differentiation to make fracture more likely, Dr. Mehta said.
The association between sulfonylureas and increased fracture risk appears to be new, however, and deserves further study, she added.
The study did not look at the effects of combination drug therapy.
Data came from the Medical Outcomes Research for Effectiveness and Economics (MORE) Registry, which is owned by Inovalon, drawing from the years 2008-2012.
Dr. Mehta reported having no financial disclosures.
On Twitter @sherryboschert
Dr. Amanda Adler
This study confirms that we observe more fracture risks with thiazolidinediones. To my knowledge, this is the first time that this has been shown for sulfonylureas.
One concern about the study is so-called residual confounding. The confounders were not entirely clear in the presentation. One possible confounder is what might have preceded the fracture. If, in fact, patients on sulfonylureas were having more low blood glucose values and consequently fell, then that would be interesting to know. Unfortunately, the investigators couldn’t tell us that.
With thiazolidinediones, I’ve been told that a cell that hasn’t decided yet whether it’s going to be a bone cell or a fat cell might, in the presence of a thiazolidinedione, go on to be a fat cell instead of a bone cell. In which case, you would possibly have a problem with fewer bone cells. This study set out to look at bone metabolism but, to be fair, it could not show anything about that. That was rather ambitious.
I think there is no clinical message from this as yet. The investigators might want to look back at trials that randomized people to sulfonylureas or something else and meta-analyze that to see if there were differences in fractures.
The study suggests that the other second-line agents are okay, but again, we can’t really know what they’re doing to bones without knowing if there’s something else going on. If you took a drug that made you more likely to topple over, your bones could be equally strong as those who didn’t fall over, yet you end up with a fracture.
I’m not going to change my practice on the basis of this study.
Dr. Amanda Adler is consultant physician at Cambridge University’s Addenbrooke’s Hospital and chair of the technology appraisals committee for the National Institute for Health and Clinical Excellence in England. She gave these comments in an interview at the meeting.
SAN FRANCISCO – Adults who started taking sulfonylurea drugs for diabetes were 9% more likely to develop fractures within 5 years, and patients starting thiazolidinediones were 9% more likely to have fractures, compared with patients on other medications in a retrospective study of 99,892 adults.
Those significantly increased risks emerged after adjusting for the effects of multiple factors including age, gender, region, medical conditions, and concomitant medications, Sandhya Mehta, Ph.D. and her associates reported at the annual scientific sessions of the American Diabetes Association. Patients had no prior history of fracture.
The longitudinal retrospective analysis of a large administrative claims database found a 10% incidence of fracture on sulfonylureas and 11% on thiazolidinediones, compared with 7% on biguanides (metformin), 8% on dipeptidyl peptidase-4 (DPP-4) inhibitors, 11% on meglitinide analogues, and 6% on incretin mimetic agents. After adjusting for the confounders, the hazard ratios for each of the other three types of drugs hovered around 1 and were not statistically significantly different but increased to 1.09 for sulfonylureas and 1.4 for thiazolidinediones, reported Dr. Mehta of Inovalon Inc. in Bowie, Md., a health care data analytics company.
In the cohort as a whole, 7% of patients developed fractures. Roughly 15% of patients started sulfonylureas, 3% took thiazolidinediones, 78% were on metformin, 3% took DPP-4 inhibitors, 1% were on incretin mimetics, and 1% took meglitinides.
Previous reports have shown an increased risk of fracture in patients on thiazolidinediones, compared with those on metformin, and the current results support the hypothesis that thiazolidinediones decrease bone mineral density, stimulate adipocyte and osteoclast differentiation, and inhibit osteoblast differentiation to make fracture more likely, Dr. Mehta said.
The association between sulfonylureas and increased fracture risk appears to be new, however, and deserves further study, she added.
The study did not look at the effects of combination drug therapy.
Data came from the Medical Outcomes Research for Effectiveness and Economics (MORE) Registry, which is owned by Inovalon, drawing from the years 2008-2012.
Dr. Mehta reported having no financial disclosures.
On Twitter @sherryboschert
Dr. Amanda Adler
This study confirms that we observe more fracture risks with thiazolidinediones. To my knowledge, this is the first time that this has been shown for sulfonylureas.
One concern about the study is so-called residual confounding. The confounders were not entirely clear in the presentation. One possible confounder is what might have preceded the fracture. If, in fact, patients on sulfonylureas were having more low blood glucose values and consequently fell, then that would be interesting to know. Unfortunately, the investigators couldn’t tell us that.
With thiazolidinediones, I’ve been told that a cell that hasn’t decided yet whether it’s going to be a bone cell or a fat cell might, in the presence of a thiazolidinedione, go on to be a fat cell instead of a bone cell. In which case, you would possibly have a problem with fewer bone cells. This study set out to look at bone metabolism but, to be fair, it could not show anything about that. That was rather ambitious.
I think there is no clinical message from this as yet. The investigators might want to look back at trials that randomized people to sulfonylureas or something else and meta-analyze that to see if there were differences in fractures.
The study suggests that the other second-line agents are okay, but again, we can’t really know what they’re doing to bones without knowing if there’s something else going on. If you took a drug that made you more likely to topple over, your bones could be equally strong as those who didn’t fall over, yet you end up with a fracture.
I’m not going to change my practice on the basis of this study.
Dr. Amanda Adler is consultant physician at Cambridge University’s Addenbrooke’s Hospital and chair of the technology appraisals committee for the National Institute for Health and Clinical Excellence in England. She gave these comments in an interview at the meeting.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Hypoglycemia Common After Bariatric Surgery
SAN FRANCISCO – Hypoglycemic episodes were common and largely unnoticed after bariatric surgery, a controlled study of 45 patients found.
During a 3-day period of "normal living," symptomatic hypoglycemias occurred in 22% of 15 patients after gastric bypass surgery, 20% of 15 patients after biliopancreatic diversion with duodenal switch, and in none of 15 obese, nondiabetic control patients matched to the surgical patients by body mass index.
Continuous glucose monitoring showed that patients in both postsurgery groups spent significant amounts of time in hypoglycemia, Dr. Niclas Abrahamsson and his associates reported at the annual scientific session of the American Diabetes Association.
After gastric bypass, patients averaged 42 minutes per day with glucose levels lower than 3.3 mmol/L and 21 minutes per day with levels lower than 2.8 mmol/L. After duodenal switch surgery, patients averaged 85 minutes per day with glucose levels lower than 3.3 mmol/L and 39 minutes per day with levels lower than 2.8 mmol/L. No patients in the control group had glucose levels that low, reported Dr. Abrahamsson of the University of Uppsala, Sweden.
"We were very surprised that they had so many hypoglycemic episodes, especially since the controls had none," he said. Patients were unaware of approximately 80% of the hypoglycemic episodes, he added.
"The clinical significance should be that one should be alert to any hypoglycemia symptoms," Dr. Abrahamsson said.
Patients in the post–duodenal switch group had the lowest mean glucose level (4.6 mmol/L) and mean hemoglobin A1c level (29 mmol/mol), compared with the post–gastric bypass group (mean glucose 5.3 mmol/L and HbA1c 36 mmol/mol) and the control group (mean glucose 5.9 mmol/L and HbA1c 38 mmol/mol).
Glucose curves on continuous monitoring were more variable in the post–gastric bypass group, compared with controls, and less variable in the post–duodenal switch group, compared with controls. That difference between the two surgical groups probably relates to the different glucose absorption capabilities after surgery, he suggested.
Dr. Abrahamsson has been a speaker for Eli Lilly and Sanofi and has held stock in AstraZeneca.
On Twitter @sherryboschert
Dr. Thomas Barber
The finding that patients with recent duodenal switch surgery spent 85 minutes per day with hypoglycemia, compared with 42 minutes per 24 hours for patients in the gastric bypass group, is quite alarming. Although these hypoglycemias were largely unnoticed, we know that hypoglycemia can affect brain function, cognition, and motor function.
This study has safety and legal implications for things like driving and operating machinery and raises questions of how we can best manage patients in terms of mitigating the effects of hypoglycemia. I think it opens up a whole area of questions at which we need to look.The problem with continuous glucose monitoring is that it’s a research tool, but it’s not very practical to be doing in every single patient who’s had a gastric bypass surgery. The problem with doing blood glucose measurement is that it’s a snapshot and you can potentially miss hypoglycemia. So, this has a lot of clinical implications as to how we investigate such patients.
I think this study will change my practice. It has opened my eyes. I was quite shocked at the data. At my center, we don’t tend to do many duodenal switches. We do many more sleeve gastrectomies than the bypass procedures. But, certainly, following a bypass procedure, I will be much more cognizant of the potential for hypoglycemia and caution our patients regarding driving and about monitoring their sugars closely following the procedure.
Dr. Thomas Barber is an associate professor and honorary consultant endocrinologist at the University of Warwick, England. These comments are excerpted from an interview at the meeting. Dr. Barber reported having no financial disclosures.
The finding that patients with recent duodenal switch surgery spent 85 minutes per day with hypoglycemia, compared with 42 minutes per 24 hours for patients in the gastric bypass group, is quite alarming. Although these hypoglycemias were largely unnoticed, we know that hypoglycemia can affect brain function, cognition, and motor function.
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The problem with continuous glucose monitoring is that it’s a research tool, but it’s not very practical to be doing in every single patient who’s had a gastric bypass surgery. The problem with doing blood glucose measurement is that it’s a snapshot and you can potentially miss hypoglycemia. So, this has a lot of clinical implications as to how we investigate such patients.
This study has safety and legal implications for things like driving and operating machinery and raises questions of how we can best manage patients in terms of mitigating the effects of hypoglycemia. I think it opens up a whole area of questions at which we need to look.
I think this study will change my practice. It has opened my eyes. I was quite shocked at the data. At my center, we don’t tend to do many duodenal switches. We do many more sleeve gastrectomies than the bypass procedures. But, certainly, following a bypass procedure, I will be much more cognizant of the potential for hypoglycemia and caution our patients regarding driving and about monitoring their sugars closely following the procedure.
Dr. Thomas Barber is an associate professor and honorary consultant endocrinologist at the University of Warwick, England. These comments are excerpted from an interview at the meeting. Dr. Barber reported having no financial disclosures.
The finding that patients with recent duodenal switch surgery spent 85 minutes per day with hypoglycemia, compared with 42 minutes per 24 hours for patients in the gastric bypass group, is quite alarming. Although these hypoglycemias were largely unnoticed, we know that hypoglycemia can affect brain function, cognition, and motor function.
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|
The problem with continuous glucose monitoring is that it’s a research tool, but it’s not very practical to be doing in every single patient who’s had a gastric bypass surgery. The problem with doing blood glucose measurement is that it’s a snapshot and you can potentially miss hypoglycemia. So, this has a lot of clinical implications as to how we investigate such patients.
This study has safety and legal implications for things like driving and operating machinery and raises questions of how we can best manage patients in terms of mitigating the effects of hypoglycemia. I think it opens up a whole area of questions at which we need to look.
I think this study will change my practice. It has opened my eyes. I was quite shocked at the data. At my center, we don’t tend to do many duodenal switches. We do many more sleeve gastrectomies than the bypass procedures. But, certainly, following a bypass procedure, I will be much more cognizant of the potential for hypoglycemia and caution our patients regarding driving and about monitoring their sugars closely following the procedure.
Dr. Thomas Barber is an associate professor and honorary consultant endocrinologist at the University of Warwick, England. These comments are excerpted from an interview at the meeting. Dr. Barber reported having no financial disclosures.
The finding that patients with recent duodenal switch surgery spent 85 minutes per day with hypoglycemia, compared with 42 minutes per 24 hours for patients in the gastric bypass group, is quite alarming. Although these hypoglycemias were largely unnoticed, we know that hypoglycemia can affect brain function, cognition, and motor function.
|
|
The problem with continuous glucose monitoring is that it’s a research tool, but it’s not very practical to be doing in every single patient who’s had a gastric bypass surgery. The problem with doing blood glucose measurement is that it’s a snapshot and you can potentially miss hypoglycemia. So, this has a lot of clinical implications as to how we investigate such patients.
This study has safety and legal implications for things like driving and operating machinery and raises questions of how we can best manage patients in terms of mitigating the effects of hypoglycemia. I think it opens up a whole area of questions at which we need to look.
I think this study will change my practice. It has opened my eyes. I was quite shocked at the data. At my center, we don’t tend to do many duodenal switches. We do many more sleeve gastrectomies than the bypass procedures. But, certainly, following a bypass procedure, I will be much more cognizant of the potential for hypoglycemia and caution our patients regarding driving and about monitoring their sugars closely following the procedure.
Dr. Thomas Barber is an associate professor and honorary consultant endocrinologist at the University of Warwick, England. These comments are excerpted from an interview at the meeting. Dr. Barber reported having no financial disclosures.
SAN FRANCISCO – Hypoglycemic episodes were common and largely unnoticed after bariatric surgery, a controlled study of 45 patients found.
During a 3-day period of "normal living," symptomatic hypoglycemias occurred in 22% of 15 patients after gastric bypass surgery, 20% of 15 patients after biliopancreatic diversion with duodenal switch, and in none of 15 obese, nondiabetic control patients matched to the surgical patients by body mass index.
Continuous glucose monitoring showed that patients in both postsurgery groups spent significant amounts of time in hypoglycemia, Dr. Niclas Abrahamsson and his associates reported at the annual scientific session of the American Diabetes Association.
After gastric bypass, patients averaged 42 minutes per day with glucose levels lower than 3.3 mmol/L and 21 minutes per day with levels lower than 2.8 mmol/L. After duodenal switch surgery, patients averaged 85 minutes per day with glucose levels lower than 3.3 mmol/L and 39 minutes per day with levels lower than 2.8 mmol/L. No patients in the control group had glucose levels that low, reported Dr. Abrahamsson of the University of Uppsala, Sweden.
"We were very surprised that they had so many hypoglycemic episodes, especially since the controls had none," he said. Patients were unaware of approximately 80% of the hypoglycemic episodes, he added.
"The clinical significance should be that one should be alert to any hypoglycemia symptoms," Dr. Abrahamsson said.
Patients in the post–duodenal switch group had the lowest mean glucose level (4.6 mmol/L) and mean hemoglobin A1c level (29 mmol/mol), compared with the post–gastric bypass group (mean glucose 5.3 mmol/L and HbA1c 36 mmol/mol) and the control group (mean glucose 5.9 mmol/L and HbA1c 38 mmol/mol).
Glucose curves on continuous monitoring were more variable in the post–gastric bypass group, compared with controls, and less variable in the post–duodenal switch group, compared with controls. That difference between the two surgical groups probably relates to the different glucose absorption capabilities after surgery, he suggested.
Dr. Abrahamsson has been a speaker for Eli Lilly and Sanofi and has held stock in AstraZeneca.
On Twitter @sherryboschert
Dr. Thomas Barber
The finding that patients with recent duodenal switch surgery spent 85 minutes per day with hypoglycemia, compared with 42 minutes per 24 hours for patients in the gastric bypass group, is quite alarming. Although these hypoglycemias were largely unnoticed, we know that hypoglycemia can affect brain function, cognition, and motor function.
This study has safety and legal implications for things like driving and operating machinery and raises questions of how we can best manage patients in terms of mitigating the effects of hypoglycemia. I think it opens up a whole area of questions at which we need to look.The problem with continuous glucose monitoring is that it’s a research tool, but it’s not very practical to be doing in every single patient who’s had a gastric bypass surgery. The problem with doing blood glucose measurement is that it’s a snapshot and you can potentially miss hypoglycemia. So, this has a lot of clinical implications as to how we investigate such patients.
I think this study will change my practice. It has opened my eyes. I was quite shocked at the data. At my center, we don’t tend to do many duodenal switches. We do many more sleeve gastrectomies than the bypass procedures. But, certainly, following a bypass procedure, I will be much more cognizant of the potential for hypoglycemia and caution our patients regarding driving and about monitoring their sugars closely following the procedure.
Dr. Thomas Barber is an associate professor and honorary consultant endocrinologist at the University of Warwick, England. These comments are excerpted from an interview at the meeting. Dr. Barber reported having no financial disclosures.
SAN FRANCISCO – Hypoglycemic episodes were common and largely unnoticed after bariatric surgery, a controlled study of 45 patients found.
During a 3-day period of "normal living," symptomatic hypoglycemias occurred in 22% of 15 patients after gastric bypass surgery, 20% of 15 patients after biliopancreatic diversion with duodenal switch, and in none of 15 obese, nondiabetic control patients matched to the surgical patients by body mass index.
Continuous glucose monitoring showed that patients in both postsurgery groups spent significant amounts of time in hypoglycemia, Dr. Niclas Abrahamsson and his associates reported at the annual scientific session of the American Diabetes Association.
After gastric bypass, patients averaged 42 minutes per day with glucose levels lower than 3.3 mmol/L and 21 minutes per day with levels lower than 2.8 mmol/L. After duodenal switch surgery, patients averaged 85 minutes per day with glucose levels lower than 3.3 mmol/L and 39 minutes per day with levels lower than 2.8 mmol/L. No patients in the control group had glucose levels that low, reported Dr. Abrahamsson of the University of Uppsala, Sweden.
"We were very surprised that they had so many hypoglycemic episodes, especially since the controls had none," he said. Patients were unaware of approximately 80% of the hypoglycemic episodes, he added.
"The clinical significance should be that one should be alert to any hypoglycemia symptoms," Dr. Abrahamsson said.
Patients in the post–duodenal switch group had the lowest mean glucose level (4.6 mmol/L) and mean hemoglobin A1c level (29 mmol/mol), compared with the post–gastric bypass group (mean glucose 5.3 mmol/L and HbA1c 36 mmol/mol) and the control group (mean glucose 5.9 mmol/L and HbA1c 38 mmol/mol).
Glucose curves on continuous monitoring were more variable in the post–gastric bypass group, compared with controls, and less variable in the post–duodenal switch group, compared with controls. That difference between the two surgical groups probably relates to the different glucose absorption capabilities after surgery, he suggested.
Dr. Abrahamsson has been a speaker for Eli Lilly and Sanofi and has held stock in AstraZeneca.
On Twitter @sherryboschert
Dr. Thomas Barber
The finding that patients with recent duodenal switch surgery spent 85 minutes per day with hypoglycemia, compared with 42 minutes per 24 hours for patients in the gastric bypass group, is quite alarming. Although these hypoglycemias were largely unnoticed, we know that hypoglycemia can affect brain function, cognition, and motor function.
This study has safety and legal implications for things like driving and operating machinery and raises questions of how we can best manage patients in terms of mitigating the effects of hypoglycemia. I think it opens up a whole area of questions at which we need to look.The problem with continuous glucose monitoring is that it’s a research tool, but it’s not very practical to be doing in every single patient who’s had a gastric bypass surgery. The problem with doing blood glucose measurement is that it’s a snapshot and you can potentially miss hypoglycemia. So, this has a lot of clinical implications as to how we investigate such patients.
I think this study will change my practice. It has opened my eyes. I was quite shocked at the data. At my center, we don’t tend to do many duodenal switches. We do many more sleeve gastrectomies than the bypass procedures. But, certainly, following a bypass procedure, I will be much more cognizant of the potential for hypoglycemia and caution our patients regarding driving and about monitoring their sugars closely following the procedure.
Dr. Thomas Barber is an associate professor and honorary consultant endocrinologist at the University of Warwick, England. These comments are excerpted from an interview at the meeting. Dr. Barber reported having no financial disclosures.
AT THE ADA ANNUAL SCIENTIFIC SESSION
Islet transplants aided type 1 diabetes patients
SAN FRANCISCO – Half of 48 adults with type 1 diabetes, impaired awareness of hypoglycemia, and a history of severe hypoglycemia were able to stop insulin therapy after experimental transplantation of human pancreatic islet cells in a prospective, phase III trial.
The National Institute of Health’s Clinical Islet Transplantation Consortium reported partial, initial results from 365 days of follow-up after islet-cell transplantation in the eight-center study. Speaking for the consortium at the annual scientific sessions of the American Diabetes Association, Dr. Bernhard J. Hering withheld results for the primary outcome measure (the proportion of patients who had a hemoglobin A1c of less than 7% at day 365 and no severe hypoglycemia in days 28 through 365 after the first islet transplant) pending its publication, he said.
Still, results for secondary measures of effectiveness and safety were good enough that "islet transplantation should be considered in this subgroup of patients when other treatment options have failed," said Dr. Hering, a professor of surgery and director of the Islet Cell Transplantation Program at the University of Minnesota, Minneapolis.
The study included patients who had had type 1 diabetes for at least 5 years, with stimulated C-peptide levels below 0.3 ng/mL (considered "absent") and at least one episode of severe hypoglycemia in the prior year with documentation of reduced hypoglycemia awareness and/or marked glycemic lability, if they didn’t meet any of 32 exclusion criteria. All patients underwent immunosuppression as part of the transplantation protocol.
Of the 48 patients, 26 received a second islet cell transplantation, and 1 received a third transplantation. Islet grafts were functioning in more than 90% of patients at day 365 of follow-up, he and his associates reported.
At day 365, roughly 50% of patients were insulin free. Insulin use decreased significantly to a median of 0 unit/kg per day at day 365.
Serum glucose levels and C-peptide secretion during mixed-meal tolerance tests improved over time after transplantation. Clarke scores and Ryan scores to assess patient awareness of hypoglycemia both improved significantly by day 365, as did measures of the glycemic lability index and the mean amplitude of glycemic excursions.
The median percentage of time spent within the desired glucose range increased from about 50% at baseline to nearly 95% at day 365, Dr. Hering reported.
The 19 serious adverse events included 5 that were procedure related (bleeding after percutaneous cannulation of a portal vein), 13 transient events related to immunosuppression (neutropenia, cytokine release, or elevated liver function test results), and 1 episode of hypoglycemia in a patient on insulin. None of these events caused death, disability, or permanent sequelae. Among other adverse events, a small but statistically significant drop in glomerular function test results was associated with the start of immunosuppression, six patients had calculated panel reactive antibodies above zero, and one patient developed acute kidney injury for unclear reasons.
The investigators plan further long-term follow-up.
Registry data suggest that approximately 35% of U.S. patients with type 1 diabetes each year report severe hypoglycemia requiring assistance, Dr. Hering said.
Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
On Twitter @sherryboschert
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This is another of the government-funded trials looking at clinical islet-cell transplantation, which are critically important because they have some success in some patients. This does offer promise for people who have hypoglycemia unawareness to the point where they are unable to function in their lives, but we need to find that out from the primary outcome results, which have not been presented. I would not use this treatment at this time.
The indication for islet-cell transplantation was severe hypoglycemia in someone with type 1 diabetes. This identifies a group that may have particular risks with standard therapy, in whom there may be justification for exposing them to the potential side effects of the transplant. That approach changes the risk-benefit ratio – that’s the way I interpret it.
The other exciting piece from this particular study is that it was a multisite project, and they had to do islet isolation at each site under standardized conditions, which is new. If we’re ever going to bring islet transplantation forward as a therapy and have it be approved by the Food and Drug Administration, there must be tremendous standardization in how islets are harvested and prepared for use. The fact that they were able to do that is very exciting.
Dr. Elizabeth R. Seaquist is a professor of medicine and the Pennock Family Chair in Diabetes Research at the University of Minnesota, Minneapolis. She gave these comments in an interview at the meeting. Dr. Seaquist is a colleague of Dr. Hering at the university. She reported financial associations with multiple companies but said none are relevant to this topic.
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This is another of the government-funded trials looking at clinical islet-cell transplantation, which are critically important because they have some success in some patients. This does offer promise for people who have hypoglycemia unawareness to the point where they are unable to function in their lives, but we need to find that out from the primary outcome results, which have not been presented. I would not use this treatment at this time.
The indication for islet-cell transplantation was severe hypoglycemia in someone with type 1 diabetes. This identifies a group that may have particular risks with standard therapy, in whom there may be justification for exposing them to the potential side effects of the transplant. That approach changes the risk-benefit ratio – that’s the way I interpret it.
The other exciting piece from this particular study is that it was a multisite project, and they had to do islet isolation at each site under standardized conditions, which is new. If we’re ever going to bring islet transplantation forward as a therapy and have it be approved by the Food and Drug Administration, there must be tremendous standardization in how islets are harvested and prepared for use. The fact that they were able to do that is very exciting.
Dr. Elizabeth R. Seaquist is a professor of medicine and the Pennock Family Chair in Diabetes Research at the University of Minnesota, Minneapolis. She gave these comments in an interview at the meeting. Dr. Seaquist is a colleague of Dr. Hering at the university. She reported financial associations with multiple companies but said none are relevant to this topic.
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This is another of the government-funded trials looking at clinical islet-cell transplantation, which are critically important because they have some success in some patients. This does offer promise for people who have hypoglycemia unawareness to the point where they are unable to function in their lives, but we need to find that out from the primary outcome results, which have not been presented. I would not use this treatment at this time.
The indication for islet-cell transplantation was severe hypoglycemia in someone with type 1 diabetes. This identifies a group that may have particular risks with standard therapy, in whom there may be justification for exposing them to the potential side effects of the transplant. That approach changes the risk-benefit ratio – that’s the way I interpret it.
The other exciting piece from this particular study is that it was a multisite project, and they had to do islet isolation at each site under standardized conditions, which is new. If we’re ever going to bring islet transplantation forward as a therapy and have it be approved by the Food and Drug Administration, there must be tremendous standardization in how islets are harvested and prepared for use. The fact that they were able to do that is very exciting.
Dr. Elizabeth R. Seaquist is a professor of medicine and the Pennock Family Chair in Diabetes Research at the University of Minnesota, Minneapolis. She gave these comments in an interview at the meeting. Dr. Seaquist is a colleague of Dr. Hering at the university. She reported financial associations with multiple companies but said none are relevant to this topic.
SAN FRANCISCO – Half of 48 adults with type 1 diabetes, impaired awareness of hypoglycemia, and a history of severe hypoglycemia were able to stop insulin therapy after experimental transplantation of human pancreatic islet cells in a prospective, phase III trial.
The National Institute of Health’s Clinical Islet Transplantation Consortium reported partial, initial results from 365 days of follow-up after islet-cell transplantation in the eight-center study. Speaking for the consortium at the annual scientific sessions of the American Diabetes Association, Dr. Bernhard J. Hering withheld results for the primary outcome measure (the proportion of patients who had a hemoglobin A1c of less than 7% at day 365 and no severe hypoglycemia in days 28 through 365 after the first islet transplant) pending its publication, he said.
Still, results for secondary measures of effectiveness and safety were good enough that "islet transplantation should be considered in this subgroup of patients when other treatment options have failed," said Dr. Hering, a professor of surgery and director of the Islet Cell Transplantation Program at the University of Minnesota, Minneapolis.
The study included patients who had had type 1 diabetes for at least 5 years, with stimulated C-peptide levels below 0.3 ng/mL (considered "absent") and at least one episode of severe hypoglycemia in the prior year with documentation of reduced hypoglycemia awareness and/or marked glycemic lability, if they didn’t meet any of 32 exclusion criteria. All patients underwent immunosuppression as part of the transplantation protocol.
Of the 48 patients, 26 received a second islet cell transplantation, and 1 received a third transplantation. Islet grafts were functioning in more than 90% of patients at day 365 of follow-up, he and his associates reported.
At day 365, roughly 50% of patients were insulin free. Insulin use decreased significantly to a median of 0 unit/kg per day at day 365.
Serum glucose levels and C-peptide secretion during mixed-meal tolerance tests improved over time after transplantation. Clarke scores and Ryan scores to assess patient awareness of hypoglycemia both improved significantly by day 365, as did measures of the glycemic lability index and the mean amplitude of glycemic excursions.
The median percentage of time spent within the desired glucose range increased from about 50% at baseline to nearly 95% at day 365, Dr. Hering reported.
The 19 serious adverse events included 5 that were procedure related (bleeding after percutaneous cannulation of a portal vein), 13 transient events related to immunosuppression (neutropenia, cytokine release, or elevated liver function test results), and 1 episode of hypoglycemia in a patient on insulin. None of these events caused death, disability, or permanent sequelae. Among other adverse events, a small but statistically significant drop in glomerular function test results was associated with the start of immunosuppression, six patients had calculated panel reactive antibodies above zero, and one patient developed acute kidney injury for unclear reasons.
The investigators plan further long-term follow-up.
Registry data suggest that approximately 35% of U.S. patients with type 1 diabetes each year report severe hypoglycemia requiring assistance, Dr. Hering said.
Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
On Twitter @sherryboschert
SAN FRANCISCO – Half of 48 adults with type 1 diabetes, impaired awareness of hypoglycemia, and a history of severe hypoglycemia were able to stop insulin therapy after experimental transplantation of human pancreatic islet cells in a prospective, phase III trial.
The National Institute of Health’s Clinical Islet Transplantation Consortium reported partial, initial results from 365 days of follow-up after islet-cell transplantation in the eight-center study. Speaking for the consortium at the annual scientific sessions of the American Diabetes Association, Dr. Bernhard J. Hering withheld results for the primary outcome measure (the proportion of patients who had a hemoglobin A1c of less than 7% at day 365 and no severe hypoglycemia in days 28 through 365 after the first islet transplant) pending its publication, he said.
Still, results for secondary measures of effectiveness and safety were good enough that "islet transplantation should be considered in this subgroup of patients when other treatment options have failed," said Dr. Hering, a professor of surgery and director of the Islet Cell Transplantation Program at the University of Minnesota, Minneapolis.
The study included patients who had had type 1 diabetes for at least 5 years, with stimulated C-peptide levels below 0.3 ng/mL (considered "absent") and at least one episode of severe hypoglycemia in the prior year with documentation of reduced hypoglycemia awareness and/or marked glycemic lability, if they didn’t meet any of 32 exclusion criteria. All patients underwent immunosuppression as part of the transplantation protocol.
Of the 48 patients, 26 received a second islet cell transplantation, and 1 received a third transplantation. Islet grafts were functioning in more than 90% of patients at day 365 of follow-up, he and his associates reported.
At day 365, roughly 50% of patients were insulin free. Insulin use decreased significantly to a median of 0 unit/kg per day at day 365.
Serum glucose levels and C-peptide secretion during mixed-meal tolerance tests improved over time after transplantation. Clarke scores and Ryan scores to assess patient awareness of hypoglycemia both improved significantly by day 365, as did measures of the glycemic lability index and the mean amplitude of glycemic excursions.
The median percentage of time spent within the desired glucose range increased from about 50% at baseline to nearly 95% at day 365, Dr. Hering reported.
The 19 serious adverse events included 5 that were procedure related (bleeding after percutaneous cannulation of a portal vein), 13 transient events related to immunosuppression (neutropenia, cytokine release, or elevated liver function test results), and 1 episode of hypoglycemia in a patient on insulin. None of these events caused death, disability, or permanent sequelae. Among other adverse events, a small but statistically significant drop in glomerular function test results was associated with the start of immunosuppression, six patients had calculated panel reactive antibodies above zero, and one patient developed acute kidney injury for unclear reasons.
The investigators plan further long-term follow-up.
Registry data suggest that approximately 35% of U.S. patients with type 1 diabetes each year report severe hypoglycemia requiring assistance, Dr. Hering said.
Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
On Twitter @sherryboschert
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: You’ll have to wait for the primary results, but secondary outcomes suggest success with islet-cell transplantation in a subset of patients with type 1 diabetes.
Major finding: Half of patients were able to stop insulin within a year of transplantation.
Data source: A prospective, open-label, single-arm study of islet-cell transplantation in 48 adults with type 1 diabetes and a history of severe hypoglycemia and hypoglycemia unawareness.
Disclosures: Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
DPPOS: Metformin showed no effect on cognition
SAN FRANCISCO – There appear to be no effects on cognition from participating in the lifestyle and metformin arms of the Diabetes Prevention Program Outcomes Study, results from a large long-term analysis showed.
Diabetes was not related to cognition, but a worse hemoglobin A1c level was associated with a worse cognitive performance, Dr. José A. Luchsinger said at the annual scientific sessions of the American Diabetes Association. "Importantly, metformin is safe from a cognitive standpoint, contrary to some recent reports."
The Diabetes Prevention Program Outcomes Study (DPPOS) is a follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial that compared intensive lifestyle and metformin with placebo for the prevention of diabetes. On behalf of the DPP Research Group, Dr. Luchsinger presented findings from a study that set out to determine if the delay in or prevention of diabetes translated into cognitive benefits 12 years after randomization into the DPP.
"Diabetes in middle age and old age is related to cognitive impairment, both in amnestic and nonamnestic domains, and also in a range of severity from mild cognitive impairment to dementia," said Dr. Luchsinger of the department of medicine at Columbia University Medical Center, New York. "This association extends to the continuum of dysglycemia."
He and his associates hypothesized that diabetes prevention with metformin and lifestyle changes would be associated with better cognitive performance in the DPPOS. Their secondary hypotheses were that diabetes and dysglycemia are associated with worse cognitive function, and that metformin exposure is not associated with cognitive impairment. The researchers conducted cognitive assessments 12 and 14 years after DPP randomization. Global cognition was assessed with the six-item screener of the Mini-Mental State Exam, memory with the Spanish English Verbal Learning Test (SEVLT), and frontal executive function with an animal fluency (AF) and a letter fluency (LF) test and the Digit Symbol Substitution Test (DSST). They also calculated a composite of the SEVLT, AF, LF, and DSST results.
In all, 2,331 participated in the cognitive assessments. Their mean age was 64 years and 68% were women. There were no significant baseline differences in demographic and clinical characteristics by randomization group, but HbA1c level, diabetes prevalence, and diabetes duration were lower in the lifestyle and metformin groups.
Dr. Luchsinger reported that cognition was similar across all DPP treatment arms in year 8, while SEVLT improved from year 8 to year 10 in all arms (P = .0001). Changes in cognition were similar across DPP arms, but a worse HbA1c level was associated with a worse cognition composite score in models adjusted for age at randomization and assessment year (P = .0002). Exposure to metformin was not related to worse cognition.
"It’s important to consider that all DPP participants had impaired glucose tolerance at baseline," Dr. Luchsinger noted. "We had no people with normal glucose tolerance to compare them to; all had a high risk for developing diabetes. Also, the cohort is just entering the age of susceptibility of cognitive impairment. It may be that following them in older ages may show differences that we’re not seeing right now. A legacy effect is possible. By that I mean that there may be a long lag time from the intervention to cognitive effects."
The researchers plan to conduct a longer follow-up of the cohort with an assessment of brain structure function and amyloid load.
The study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Indian Health Service, Bristol-Myers Squibb, Parke Davis, Lipha, and Lifescan. Dr. Luchsinger said he had no relevant financial conflicts.
On Twitter @dougbrunk
SAN FRANCISCO – There appear to be no effects on cognition from participating in the lifestyle and metformin arms of the Diabetes Prevention Program Outcomes Study, results from a large long-term analysis showed.
Diabetes was not related to cognition, but a worse hemoglobin A1c level was associated with a worse cognitive performance, Dr. José A. Luchsinger said at the annual scientific sessions of the American Diabetes Association. "Importantly, metformin is safe from a cognitive standpoint, contrary to some recent reports."
The Diabetes Prevention Program Outcomes Study (DPPOS) is a follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial that compared intensive lifestyle and metformin with placebo for the prevention of diabetes. On behalf of the DPP Research Group, Dr. Luchsinger presented findings from a study that set out to determine if the delay in or prevention of diabetes translated into cognitive benefits 12 years after randomization into the DPP.
"Diabetes in middle age and old age is related to cognitive impairment, both in amnestic and nonamnestic domains, and also in a range of severity from mild cognitive impairment to dementia," said Dr. Luchsinger of the department of medicine at Columbia University Medical Center, New York. "This association extends to the continuum of dysglycemia."
He and his associates hypothesized that diabetes prevention with metformin and lifestyle changes would be associated with better cognitive performance in the DPPOS. Their secondary hypotheses were that diabetes and dysglycemia are associated with worse cognitive function, and that metformin exposure is not associated with cognitive impairment. The researchers conducted cognitive assessments 12 and 14 years after DPP randomization. Global cognition was assessed with the six-item screener of the Mini-Mental State Exam, memory with the Spanish English Verbal Learning Test (SEVLT), and frontal executive function with an animal fluency (AF) and a letter fluency (LF) test and the Digit Symbol Substitution Test (DSST). They also calculated a composite of the SEVLT, AF, LF, and DSST results.
In all, 2,331 participated in the cognitive assessments. Their mean age was 64 years and 68% were women. There were no significant baseline differences in demographic and clinical characteristics by randomization group, but HbA1c level, diabetes prevalence, and diabetes duration were lower in the lifestyle and metformin groups.
Dr. Luchsinger reported that cognition was similar across all DPP treatment arms in year 8, while SEVLT improved from year 8 to year 10 in all arms (P = .0001). Changes in cognition were similar across DPP arms, but a worse HbA1c level was associated with a worse cognition composite score in models adjusted for age at randomization and assessment year (P = .0002). Exposure to metformin was not related to worse cognition.
"It’s important to consider that all DPP participants had impaired glucose tolerance at baseline," Dr. Luchsinger noted. "We had no people with normal glucose tolerance to compare them to; all had a high risk for developing diabetes. Also, the cohort is just entering the age of susceptibility of cognitive impairment. It may be that following them in older ages may show differences that we’re not seeing right now. A legacy effect is possible. By that I mean that there may be a long lag time from the intervention to cognitive effects."
The researchers plan to conduct a longer follow-up of the cohort with an assessment of brain structure function and amyloid load.
The study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Indian Health Service, Bristol-Myers Squibb, Parke Davis, Lipha, and Lifescan. Dr. Luchsinger said he had no relevant financial conflicts.
On Twitter @dougbrunk
SAN FRANCISCO – There appear to be no effects on cognition from participating in the lifestyle and metformin arms of the Diabetes Prevention Program Outcomes Study, results from a large long-term analysis showed.
Diabetes was not related to cognition, but a worse hemoglobin A1c level was associated with a worse cognitive performance, Dr. José A. Luchsinger said at the annual scientific sessions of the American Diabetes Association. "Importantly, metformin is safe from a cognitive standpoint, contrary to some recent reports."
The Diabetes Prevention Program Outcomes Study (DPPOS) is a follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial that compared intensive lifestyle and metformin with placebo for the prevention of diabetes. On behalf of the DPP Research Group, Dr. Luchsinger presented findings from a study that set out to determine if the delay in or prevention of diabetes translated into cognitive benefits 12 years after randomization into the DPP.
"Diabetes in middle age and old age is related to cognitive impairment, both in amnestic and nonamnestic domains, and also in a range of severity from mild cognitive impairment to dementia," said Dr. Luchsinger of the department of medicine at Columbia University Medical Center, New York. "This association extends to the continuum of dysglycemia."
He and his associates hypothesized that diabetes prevention with metformin and lifestyle changes would be associated with better cognitive performance in the DPPOS. Their secondary hypotheses were that diabetes and dysglycemia are associated with worse cognitive function, and that metformin exposure is not associated with cognitive impairment. The researchers conducted cognitive assessments 12 and 14 years after DPP randomization. Global cognition was assessed with the six-item screener of the Mini-Mental State Exam, memory with the Spanish English Verbal Learning Test (SEVLT), and frontal executive function with an animal fluency (AF) and a letter fluency (LF) test and the Digit Symbol Substitution Test (DSST). They also calculated a composite of the SEVLT, AF, LF, and DSST results.
In all, 2,331 participated in the cognitive assessments. Their mean age was 64 years and 68% were women. There were no significant baseline differences in demographic and clinical characteristics by randomization group, but HbA1c level, diabetes prevalence, and diabetes duration were lower in the lifestyle and metformin groups.
Dr. Luchsinger reported that cognition was similar across all DPP treatment arms in year 8, while SEVLT improved from year 8 to year 10 in all arms (P = .0001). Changes in cognition were similar across DPP arms, but a worse HbA1c level was associated with a worse cognition composite score in models adjusted for age at randomization and assessment year (P = .0002). Exposure to metformin was not related to worse cognition.
"It’s important to consider that all DPP participants had impaired glucose tolerance at baseline," Dr. Luchsinger noted. "We had no people with normal glucose tolerance to compare them to; all had a high risk for developing diabetes. Also, the cohort is just entering the age of susceptibility of cognitive impairment. It may be that following them in older ages may show differences that we’re not seeing right now. A legacy effect is possible. By that I mean that there may be a long lag time from the intervention to cognitive effects."
The researchers plan to conduct a longer follow-up of the cohort with an assessment of brain structure function and amyloid load.
The study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Indian Health Service, Bristol-Myers Squibb, Parke Davis, Lipha, and Lifescan. Dr. Luchsinger said he had no relevant financial conflicts.
On Twitter @dougbrunk
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: On long-term follow-up, there appear to be no cognitive differences among the treatment arms of the DPPOS.
Major finding: At year 8 of follow-up, cognition was similar among participants in the lifestyle and metformin arms of DPPOS.
Data source: A total of 2,331 cognitive assessments in the lifestyle and metformin arms of DPPOS.
Disclosures: The study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Indian Health Service, Bristol-Myers Squibb, Parke Davis, Lipha, and Lifescan. Dr. Luchsinger said he had no relevant financial conflicts.
Long-term benefits shown after gastric banding
SAN FRANCISCO – The greater benefits of laparoscopic gastric banding surgery compared with medical treatment for obese patients were maintained for up to 17 years in a study of data on 1,490 patients.
The 527 obese patients (with or without diabetes) who underwent laparoscopic banding were significantly less likely to die of cardiovascular or noncardiovascular causes and were less likely to develop new cases of type 2 diabetes or cardiovascular disease, compared with the 963 nonsurgery patients, Dr. Antonio E. Pontiroli and his associates reported at the annual scientific sessions of the American Diabetes Association.
Patients underwent laparoscopic banding surgery or were seen for a first visit for medical therapy in 1995-2001, and were followed for 11-17 years, through September 2012.
Three percent of the surgery group and 10% of the nonsurgery group died during follow-up, reported Dr. Pontiroli, chair of internal medicine at Università Degli Studi de Milano and San Paolo Hospital, Milan.
To track morbidity, the investigators analyzed records to see which patients got "exemptions" for specific diseases, an Italian government system in which development of a chronic disease exempts someone from having to pay for exams or treatments for that disease. Any exemption obtained after the first surgical or medical visit was considered a proxy of new disease.
New exemptions were granted to 25% in the surgery group and 42% in the nonsurgery group.
Subset analyses divided 385 surgery patients based on the presence or absence of diabetes, and matched the subgroups separately with 681 nonsurgery patients by sex, age, blood pressure, and body mass index.
In the matched comparisons, 3% of the surgery group and 10% of the nonsurgery group died, and exemptions were granted to 22% of the surgery group and 28% of the nonsurgery group, which were statistically significant differences in the intention-to-treat analyses.
Patients in the surgery group were 66% less likely to die than the nonsurgery patients. Patients without diabetes at the first visit were 67% less likely to die than matched nonsurgery patients, and those with diabetes at the first visit were 56% less likely to die compared with matched nonsurgery patients.
Cardiovascular disease, noncardiovascular disease, or neoplasia were significantly less likely to be the causes of death in the surgery group compared with the nonsurgery group. The surgery group recorded significantly fewer hospitalizations during follow-up (120) than the nonsurgery group (273).
New cases of cardiovascular disease (defined by exemptions) appeared in 13% of the surgery group and 22% of the nonsurgery group. In the matched subgroups, 13% who underwent surgery and 18% in the nonsurgery group developed cardiovascular disease.
Among patients without diabetes at baseline, 5% of 454 in the surgery group and 10% of 724 in the nonsurgery group developed diabetes during follow-up. In the subset analysis of matched patients without diabetes at baseline, 4% of 333 in the surgery group and 9% in the nonsurgery group developed diabetes.
The investigators plan another data assessment in 2017 to confirm these long-term findings. Similar studies are needed for other bariatric surgery techniques, he suggested.
Dr. Pontiroli reported financial associations with Sanofi, Eli Lilly, and other companies.
On Twitter @sherryboschert
This is a very interesting study. It was a long-term study, over 17 years, of patients who’d had gastric banding in Milan, looking at development of cardiovascular disease, type 2 diabetes, and death. It is reassuring that there did appear to be favorable outcomes.
There clearly are limitations to the study. The researchers only looked at banding; they didn’t look at sleeve gastrectomies or gastric bypass. The study is specifically related to banding. The comparisons with medical therapies didn’t really define the medical therapies. We’d obviously need details on what they were comparing and whether there are subgroup analyses that could be done.
Nonetheless, they did show that there’s a significant improvement in death rates, cardiovascular death, all-cause death, development of type 2 diabetes, and new cases of cardiovascular disease both in the whole population and in the matched groups. I think these are useful data that are kind of reassuring.
The other thing I would mention: Although bariatric surgery has been done for many years now, it’s really only over the last 10-15 years that the numbers of surgeries have increased hugely. It will be interesting to see the outcomes of the most current cohort over the next 10-15 years.
Dr. Thomas Barber is an associate professor and honorary consultant endocrinologist at the Warwick Medical School, Coventry, England. He gave these comments in an interview at the meeting. Dr. Barber reported having no financial disclosures.
This is a very interesting study. It was a long-term study, over 17 years, of patients who’d had gastric banding in Milan, looking at development of cardiovascular disease, type 2 diabetes, and death. It is reassuring that there did appear to be favorable outcomes.
There clearly are limitations to the study. The researchers only looked at banding; they didn’t look at sleeve gastrectomies or gastric bypass. The study is specifically related to banding. The comparisons with medical therapies didn’t really define the medical therapies. We’d obviously need details on what they were comparing and whether there are subgroup analyses that could be done.
Nonetheless, they did show that there’s a significant improvement in death rates, cardiovascular death, all-cause death, development of type 2 diabetes, and new cases of cardiovascular disease both in the whole population and in the matched groups. I think these are useful data that are kind of reassuring.
The other thing I would mention: Although bariatric surgery has been done for many years now, it’s really only over the last 10-15 years that the numbers of surgeries have increased hugely. It will be interesting to see the outcomes of the most current cohort over the next 10-15 years.
Dr. Thomas Barber is an associate professor and honorary consultant endocrinologist at the Warwick Medical School, Coventry, England. He gave these comments in an interview at the meeting. Dr. Barber reported having no financial disclosures.
This is a very interesting study. It was a long-term study, over 17 years, of patients who’d had gastric banding in Milan, looking at development of cardiovascular disease, type 2 diabetes, and death. It is reassuring that there did appear to be favorable outcomes.
There clearly are limitations to the study. The researchers only looked at banding; they didn’t look at sleeve gastrectomies or gastric bypass. The study is specifically related to banding. The comparisons with medical therapies didn’t really define the medical therapies. We’d obviously need details on what they were comparing and whether there are subgroup analyses that could be done.
Nonetheless, they did show that there’s a significant improvement in death rates, cardiovascular death, all-cause death, development of type 2 diabetes, and new cases of cardiovascular disease both in the whole population and in the matched groups. I think these are useful data that are kind of reassuring.
The other thing I would mention: Although bariatric surgery has been done for many years now, it’s really only over the last 10-15 years that the numbers of surgeries have increased hugely. It will be interesting to see the outcomes of the most current cohort over the next 10-15 years.
Dr. Thomas Barber is an associate professor and honorary consultant endocrinologist at the Warwick Medical School, Coventry, England. He gave these comments in an interview at the meeting. Dr. Barber reported having no financial disclosures.
SAN FRANCISCO – The greater benefits of laparoscopic gastric banding surgery compared with medical treatment for obese patients were maintained for up to 17 years in a study of data on 1,490 patients.
The 527 obese patients (with or without diabetes) who underwent laparoscopic banding were significantly less likely to die of cardiovascular or noncardiovascular causes and were less likely to develop new cases of type 2 diabetes or cardiovascular disease, compared with the 963 nonsurgery patients, Dr. Antonio E. Pontiroli and his associates reported at the annual scientific sessions of the American Diabetes Association.
Patients underwent laparoscopic banding surgery or were seen for a first visit for medical therapy in 1995-2001, and were followed for 11-17 years, through September 2012.
Three percent of the surgery group and 10% of the nonsurgery group died during follow-up, reported Dr. Pontiroli, chair of internal medicine at Università Degli Studi de Milano and San Paolo Hospital, Milan.
To track morbidity, the investigators analyzed records to see which patients got "exemptions" for specific diseases, an Italian government system in which development of a chronic disease exempts someone from having to pay for exams or treatments for that disease. Any exemption obtained after the first surgical or medical visit was considered a proxy of new disease.
New exemptions were granted to 25% in the surgery group and 42% in the nonsurgery group.
Subset analyses divided 385 surgery patients based on the presence or absence of diabetes, and matched the subgroups separately with 681 nonsurgery patients by sex, age, blood pressure, and body mass index.
In the matched comparisons, 3% of the surgery group and 10% of the nonsurgery group died, and exemptions were granted to 22% of the surgery group and 28% of the nonsurgery group, which were statistically significant differences in the intention-to-treat analyses.
Patients in the surgery group were 66% less likely to die than the nonsurgery patients. Patients without diabetes at the first visit were 67% less likely to die than matched nonsurgery patients, and those with diabetes at the first visit were 56% less likely to die compared with matched nonsurgery patients.
Cardiovascular disease, noncardiovascular disease, or neoplasia were significantly less likely to be the causes of death in the surgery group compared with the nonsurgery group. The surgery group recorded significantly fewer hospitalizations during follow-up (120) than the nonsurgery group (273).
New cases of cardiovascular disease (defined by exemptions) appeared in 13% of the surgery group and 22% of the nonsurgery group. In the matched subgroups, 13% who underwent surgery and 18% in the nonsurgery group developed cardiovascular disease.
Among patients without diabetes at baseline, 5% of 454 in the surgery group and 10% of 724 in the nonsurgery group developed diabetes during follow-up. In the subset analysis of matched patients without diabetes at baseline, 4% of 333 in the surgery group and 9% in the nonsurgery group developed diabetes.
The investigators plan another data assessment in 2017 to confirm these long-term findings. Similar studies are needed for other bariatric surgery techniques, he suggested.
Dr. Pontiroli reported financial associations with Sanofi, Eli Lilly, and other companies.
On Twitter @sherryboschert
SAN FRANCISCO – The greater benefits of laparoscopic gastric banding surgery compared with medical treatment for obese patients were maintained for up to 17 years in a study of data on 1,490 patients.
The 527 obese patients (with or without diabetes) who underwent laparoscopic banding were significantly less likely to die of cardiovascular or noncardiovascular causes and were less likely to develop new cases of type 2 diabetes or cardiovascular disease, compared with the 963 nonsurgery patients, Dr. Antonio E. Pontiroli and his associates reported at the annual scientific sessions of the American Diabetes Association.
Patients underwent laparoscopic banding surgery or were seen for a first visit for medical therapy in 1995-2001, and were followed for 11-17 years, through September 2012.
Three percent of the surgery group and 10% of the nonsurgery group died during follow-up, reported Dr. Pontiroli, chair of internal medicine at Università Degli Studi de Milano and San Paolo Hospital, Milan.
To track morbidity, the investigators analyzed records to see which patients got "exemptions" for specific diseases, an Italian government system in which development of a chronic disease exempts someone from having to pay for exams or treatments for that disease. Any exemption obtained after the first surgical or medical visit was considered a proxy of new disease.
New exemptions were granted to 25% in the surgery group and 42% in the nonsurgery group.
Subset analyses divided 385 surgery patients based on the presence or absence of diabetes, and matched the subgroups separately with 681 nonsurgery patients by sex, age, blood pressure, and body mass index.
In the matched comparisons, 3% of the surgery group and 10% of the nonsurgery group died, and exemptions were granted to 22% of the surgery group and 28% of the nonsurgery group, which were statistically significant differences in the intention-to-treat analyses.
Patients in the surgery group were 66% less likely to die than the nonsurgery patients. Patients without diabetes at the first visit were 67% less likely to die than matched nonsurgery patients, and those with diabetes at the first visit were 56% less likely to die compared with matched nonsurgery patients.
Cardiovascular disease, noncardiovascular disease, or neoplasia were significantly less likely to be the causes of death in the surgery group compared with the nonsurgery group. The surgery group recorded significantly fewer hospitalizations during follow-up (120) than the nonsurgery group (273).
New cases of cardiovascular disease (defined by exemptions) appeared in 13% of the surgery group and 22% of the nonsurgery group. In the matched subgroups, 13% who underwent surgery and 18% in the nonsurgery group developed cardiovascular disease.
Among patients without diabetes at baseline, 5% of 454 in the surgery group and 10% of 724 in the nonsurgery group developed diabetes during follow-up. In the subset analysis of matched patients without diabetes at baseline, 4% of 333 in the surgery group and 9% in the nonsurgery group developed diabetes.
The investigators plan another data assessment in 2017 to confirm these long-term findings. Similar studies are needed for other bariatric surgery techniques, he suggested.
Dr. Pontiroli reported financial associations with Sanofi, Eli Lilly, and other companies.
On Twitter @sherryboschert
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: Gastric banding produced significant benefits in 17 years of follow-up.
Major finding: Obese patients treated with gastric banding were 66% less likely to die, compared with those who received medical therapy.
Data source: An intent-to-treat analysis of data on 1,490 obese patients treated at four Italian centers.
Disclosures: Dr. Pontiroli reported financial associations with Sanofi, Eli Lilly, and other companies.
Intensive blood glucose control: No effect in hyperglycemic patients having CABG
SAN FRANCISCO – Intensive glucose control targeting a blood glucose of 100-140 mg/dL did not significantly reduce perioperative complications or mortality, compared with a less strict glucose target of 141-180 mg/dL in hyperglycemic patients undergoing coronary artery bypass graft surgery, a randomized trial showed.
"Inpatient hyperglycemia is associated with increased hospital complications and mortality," Dr. Guillermo E. Umpierrez said at the annual scientific sessions of the American Diabetes Association. "There have been a lot of controversies regarding what is the best target for glucose targeting in these patients in the perioperative period. There are studies suggesting that improved glycemic control improves outcomes, but others have failed to reproduce this data."
In an effort to address this question, Dr. Umpierrez and his associates at three hospitals in Atlanta conducted the open-label, randomized GLUCO-CABG trial to determine whether intensive glucose control (defined as a blood glucose target of 100-140 mg/dL) reduces perioperative complications, compared with conservative glucose control (defined as a glucose target of 141-180 mg/dL) in hyperglycemic patients undergoing CABG. Their hypothesis was that intensive therapy in the ICU would reduce perioperative complications, compared with a conservative insulin therapy, said Dr. Umpierrez, professor of medicine at Emory University in Atlanta.
The study population included 302 men and women aged 18-80 years with and without a history of diabetes who underwent CABG with or without valve surgery, and who had perioperative hyperglycemia greater than 140 mg/dL during their surgery or ICU stay. Half received intensive insulin therapy, and the other half received conservative insulin therapy. A computerized insulin infusion algorithm (Glytec’s Glucommander) was used to guide continuous IV infusion, which was given in the ICU until the patients were able to eat and/or be transferred to non-ICU services.
The mean age of the patients was 64 years, 72% were male, and their mean body mass index was 30.5 kg/m2. The mean ICU daily blood glucose levels were similar, at 132 mg/dL in the intensive group, compared with 154 mg/dL in the conservative group, and the hospital length of stay was similar between the two groups (11.4 vs. 9.5 days, respectively). In the ICU, a blood glucose level of less than 70 mg/dL occurred in 8% and 2% of the intensive and conservative groups, respectively, a significant difference, while no levels reached less than 40 mg/dL.
After ICU care, there were no differences between the intensive and conservative groups in mean daily blood glucose levels (143 vs. 141 mg/dL, respectively), percentage of patients with hypoglycemia (1% vs. 3%), or hospital readmissions (18% vs. 20%). There were also no differences between groups in rates of mortality, pneumonia, acute kidney injury, respiratory failure, or wound infection.
"The results of this study have significant clinical implications in the management of patients with hyperglycemia and diabetes in critical care units," Dr. Umpierrez said. "This study indicates that a target glucose of 141-180 mg/dL is as safe and effective and results in a lower rate of hypoglycemic events compared to a more intensive target of 100-140 mg/dL."
The study was funded by the National Institutes of Health and by a clinical research award from the American Diabetes Association. Glytec provided the Glucommander and Sanofi provided medications. Dr. Umpierrez has received research funding from and/or has served as an adviser to several pharmaceutical companies.
On Twitter @dougbrunk
SAN FRANCISCO – Intensive glucose control targeting a blood glucose of 100-140 mg/dL did not significantly reduce perioperative complications or mortality, compared with a less strict glucose target of 141-180 mg/dL in hyperglycemic patients undergoing coronary artery bypass graft surgery, a randomized trial showed.
"Inpatient hyperglycemia is associated with increased hospital complications and mortality," Dr. Guillermo E. Umpierrez said at the annual scientific sessions of the American Diabetes Association. "There have been a lot of controversies regarding what is the best target for glucose targeting in these patients in the perioperative period. There are studies suggesting that improved glycemic control improves outcomes, but others have failed to reproduce this data."
In an effort to address this question, Dr. Umpierrez and his associates at three hospitals in Atlanta conducted the open-label, randomized GLUCO-CABG trial to determine whether intensive glucose control (defined as a blood glucose target of 100-140 mg/dL) reduces perioperative complications, compared with conservative glucose control (defined as a glucose target of 141-180 mg/dL) in hyperglycemic patients undergoing CABG. Their hypothesis was that intensive therapy in the ICU would reduce perioperative complications, compared with a conservative insulin therapy, said Dr. Umpierrez, professor of medicine at Emory University in Atlanta.
The study population included 302 men and women aged 18-80 years with and without a history of diabetes who underwent CABG with or without valve surgery, and who had perioperative hyperglycemia greater than 140 mg/dL during their surgery or ICU stay. Half received intensive insulin therapy, and the other half received conservative insulin therapy. A computerized insulin infusion algorithm (Glytec’s Glucommander) was used to guide continuous IV infusion, which was given in the ICU until the patients were able to eat and/or be transferred to non-ICU services.
The mean age of the patients was 64 years, 72% were male, and their mean body mass index was 30.5 kg/m2. The mean ICU daily blood glucose levels were similar, at 132 mg/dL in the intensive group, compared with 154 mg/dL in the conservative group, and the hospital length of stay was similar between the two groups (11.4 vs. 9.5 days, respectively). In the ICU, a blood glucose level of less than 70 mg/dL occurred in 8% and 2% of the intensive and conservative groups, respectively, a significant difference, while no levels reached less than 40 mg/dL.
After ICU care, there were no differences between the intensive and conservative groups in mean daily blood glucose levels (143 vs. 141 mg/dL, respectively), percentage of patients with hypoglycemia (1% vs. 3%), or hospital readmissions (18% vs. 20%). There were also no differences between groups in rates of mortality, pneumonia, acute kidney injury, respiratory failure, or wound infection.
"The results of this study have significant clinical implications in the management of patients with hyperglycemia and diabetes in critical care units," Dr. Umpierrez said. "This study indicates that a target glucose of 141-180 mg/dL is as safe and effective and results in a lower rate of hypoglycemic events compared to a more intensive target of 100-140 mg/dL."
The study was funded by the National Institutes of Health and by a clinical research award from the American Diabetes Association. Glytec provided the Glucommander and Sanofi provided medications. Dr. Umpierrez has received research funding from and/or has served as an adviser to several pharmaceutical companies.
On Twitter @dougbrunk
SAN FRANCISCO – Intensive glucose control targeting a blood glucose of 100-140 mg/dL did not significantly reduce perioperative complications or mortality, compared with a less strict glucose target of 141-180 mg/dL in hyperglycemic patients undergoing coronary artery bypass graft surgery, a randomized trial showed.
"Inpatient hyperglycemia is associated with increased hospital complications and mortality," Dr. Guillermo E. Umpierrez said at the annual scientific sessions of the American Diabetes Association. "There have been a lot of controversies regarding what is the best target for glucose targeting in these patients in the perioperative period. There are studies suggesting that improved glycemic control improves outcomes, but others have failed to reproduce this data."
In an effort to address this question, Dr. Umpierrez and his associates at three hospitals in Atlanta conducted the open-label, randomized GLUCO-CABG trial to determine whether intensive glucose control (defined as a blood glucose target of 100-140 mg/dL) reduces perioperative complications, compared with conservative glucose control (defined as a glucose target of 141-180 mg/dL) in hyperglycemic patients undergoing CABG. Their hypothesis was that intensive therapy in the ICU would reduce perioperative complications, compared with a conservative insulin therapy, said Dr. Umpierrez, professor of medicine at Emory University in Atlanta.
The study population included 302 men and women aged 18-80 years with and without a history of diabetes who underwent CABG with or without valve surgery, and who had perioperative hyperglycemia greater than 140 mg/dL during their surgery or ICU stay. Half received intensive insulin therapy, and the other half received conservative insulin therapy. A computerized insulin infusion algorithm (Glytec’s Glucommander) was used to guide continuous IV infusion, which was given in the ICU until the patients were able to eat and/or be transferred to non-ICU services.
The mean age of the patients was 64 years, 72% were male, and their mean body mass index was 30.5 kg/m2. The mean ICU daily blood glucose levels were similar, at 132 mg/dL in the intensive group, compared with 154 mg/dL in the conservative group, and the hospital length of stay was similar between the two groups (11.4 vs. 9.5 days, respectively). In the ICU, a blood glucose level of less than 70 mg/dL occurred in 8% and 2% of the intensive and conservative groups, respectively, a significant difference, while no levels reached less than 40 mg/dL.
After ICU care, there were no differences between the intensive and conservative groups in mean daily blood glucose levels (143 vs. 141 mg/dL, respectively), percentage of patients with hypoglycemia (1% vs. 3%), or hospital readmissions (18% vs. 20%). There were also no differences between groups in rates of mortality, pneumonia, acute kidney injury, respiratory failure, or wound infection.
"The results of this study have significant clinical implications in the management of patients with hyperglycemia and diabetes in critical care units," Dr. Umpierrez said. "This study indicates that a target glucose of 141-180 mg/dL is as safe and effective and results in a lower rate of hypoglycemic events compared to a more intensive target of 100-140 mg/dL."
The study was funded by the National Institutes of Health and by a clinical research award from the American Diabetes Association. Glytec provided the Glucommander and Sanofi provided medications. Dr. Umpierrez has received research funding from and/or has served as an adviser to several pharmaceutical companies.
On Twitter @dougbrunk
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: A conservative target glucose of 141-180 mg/dL is as safe and effective as a more intensive target of 100-140 mg/dL, and results in a lower rate of hypoglycemic events.
Major finding: After ICU care, there were no differences between the intensive and conservative groups in mean daily blood glucose levels (143 vs. 141 mg/dL, respectively) or in the percentage of patients with hypoglycemia (1% vs. 3%; P = .68).
Data source: GLUCO-CABG, a randomized trial of 302 men and women aged 18-80 years who underwent CABG with or without valve surgery and who had perioperative hyperglycemia greater than 140 mg/dL during their surgery or ICU stay.
Disclosures: The study was funded by the National Institutes of Health and by a clinical research award from the American Diabetes Association. Glytec provided the Glucommander and Sanofi provided medications. Dr. Umpierrez has received research funding from and/or has served as an adviser to several pharmaceutical companies.
Pharmacist-led clinic helps improve diabetes outcomes
SAN FRANCISCO – Hemoglobin A1c levels fell by 2.4% in veterans with diabetes whose primary care physicians referred them to a 6-month pharmacist-led intense management clinic, compared with a 0.2% drop in similar patients who did not attend the clinic.
That translates to a $9,104 reduction in estimated 3-year medical costs for each patient seen in the clinic and a $1,803 drop in costs in the comparison group, reported Candis M. Morello, Pharm.D. The changes in HbA1c and costs in the intervention group were significant, compared with the nonclinic group.
After factoring in the $61,992 cost of the pharmacist over 3 years, $7.81 would be saved for every $1 spent on the program, said Dr. Morello of the University of California, San Diego, and director of the diabetes intense medical management clinic in the Veterans Affairs San Diego Healthcare System.
The clinic is a collaborative practice between an endocrinologist and a doctor of pharmacy who also is a certified diabetes educator and has full prescribing privileges. The pharmacist spends 4 hours/week in the clinic and 3 hours/week on phone follow-up calls to manage 60 patients per year who have HbA1c levels of at least 8%, high comorbidity, and complex medication regimens.
Patients are referred by primary care providers for the 6-month "tune-up" clinic involving three to five hour-long, one-on-one visits between the patient and the pharmacist. After that, patients return to their primary care providers but can make follow-up phone calls to the clinic.
The tune-up focuses on finding the best combination of medications for the individual patient, education on medication adherence, simplifying the drug regimen to fit around the patient’s schedule, and setting personalized goals.
The study compared clinic patients with a random sample of patients treated by primary care providers in the same time period. Initial HbA1c levels were 10.5% in the clinic group and 9.3% in the comparison group, Dr. Morello and her associates reported at the annual scientific session of the American Diabetes Association.
They used a published regression model applied to retrospective chart data to estimate the 3-year costs of medical care (Diabetes Care 1997;20:1847-53). Based on baseline health status (largely driven by HbA1c levels), estimated costs per patient were $42,032 in the clinic group and $37,065 in the comparison group. Assuming that HbA1c changes were maintained 3 years later, estimated costs of care were $32,928 in the clinic group and $35,262 in the comparison group.
For 60 patients seen per year in the clinic, that amounts to a cumulative potential $546,240 savings from reduced costs, for a benefit-to-cost ratio of $8.81 and a return on investment of $7.81, she said.
If mean HbA1c levels rise by 1% over 3 years, the estimated medical cost avoided would be $6,412 per patient in the clinic group, still better than results in the comparison group, a secondary analysis found. That adds up to $384,720 in costs avoided over 3 years, for a benefit-to-cost ratio of $6.21 and a $5.21 return on investment after factoring in the cost of the pharmacist.
"I’m pretty sure that spending a little bit of money on the front end saves money on the back end," Dr. Morello said.
She reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Hemoglobin A1c levels fell by 2.4% in veterans with diabetes whose primary care physicians referred them to a 6-month pharmacist-led intense management clinic, compared with a 0.2% drop in similar patients who did not attend the clinic.
That translates to a $9,104 reduction in estimated 3-year medical costs for each patient seen in the clinic and a $1,803 drop in costs in the comparison group, reported Candis M. Morello, Pharm.D. The changes in HbA1c and costs in the intervention group were significant, compared with the nonclinic group.
After factoring in the $61,992 cost of the pharmacist over 3 years, $7.81 would be saved for every $1 spent on the program, said Dr. Morello of the University of California, San Diego, and director of the diabetes intense medical management clinic in the Veterans Affairs San Diego Healthcare System.
The clinic is a collaborative practice between an endocrinologist and a doctor of pharmacy who also is a certified diabetes educator and has full prescribing privileges. The pharmacist spends 4 hours/week in the clinic and 3 hours/week on phone follow-up calls to manage 60 patients per year who have HbA1c levels of at least 8%, high comorbidity, and complex medication regimens.
Patients are referred by primary care providers for the 6-month "tune-up" clinic involving three to five hour-long, one-on-one visits between the patient and the pharmacist. After that, patients return to their primary care providers but can make follow-up phone calls to the clinic.
The tune-up focuses on finding the best combination of medications for the individual patient, education on medication adherence, simplifying the drug regimen to fit around the patient’s schedule, and setting personalized goals.
The study compared clinic patients with a random sample of patients treated by primary care providers in the same time period. Initial HbA1c levels were 10.5% in the clinic group and 9.3% in the comparison group, Dr. Morello and her associates reported at the annual scientific session of the American Diabetes Association.
They used a published regression model applied to retrospective chart data to estimate the 3-year costs of medical care (Diabetes Care 1997;20:1847-53). Based on baseline health status (largely driven by HbA1c levels), estimated costs per patient were $42,032 in the clinic group and $37,065 in the comparison group. Assuming that HbA1c changes were maintained 3 years later, estimated costs of care were $32,928 in the clinic group and $35,262 in the comparison group.
For 60 patients seen per year in the clinic, that amounts to a cumulative potential $546,240 savings from reduced costs, for a benefit-to-cost ratio of $8.81 and a return on investment of $7.81, she said.
If mean HbA1c levels rise by 1% over 3 years, the estimated medical cost avoided would be $6,412 per patient in the clinic group, still better than results in the comparison group, a secondary analysis found. That adds up to $384,720 in costs avoided over 3 years, for a benefit-to-cost ratio of $6.21 and a $5.21 return on investment after factoring in the cost of the pharmacist.
"I’m pretty sure that spending a little bit of money on the front end saves money on the back end," Dr. Morello said.
She reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Hemoglobin A1c levels fell by 2.4% in veterans with diabetes whose primary care physicians referred them to a 6-month pharmacist-led intense management clinic, compared with a 0.2% drop in similar patients who did not attend the clinic.
That translates to a $9,104 reduction in estimated 3-year medical costs for each patient seen in the clinic and a $1,803 drop in costs in the comparison group, reported Candis M. Morello, Pharm.D. The changes in HbA1c and costs in the intervention group were significant, compared with the nonclinic group.
After factoring in the $61,992 cost of the pharmacist over 3 years, $7.81 would be saved for every $1 spent on the program, said Dr. Morello of the University of California, San Diego, and director of the diabetes intense medical management clinic in the Veterans Affairs San Diego Healthcare System.
The clinic is a collaborative practice between an endocrinologist and a doctor of pharmacy who also is a certified diabetes educator and has full prescribing privileges. The pharmacist spends 4 hours/week in the clinic and 3 hours/week on phone follow-up calls to manage 60 patients per year who have HbA1c levels of at least 8%, high comorbidity, and complex medication regimens.
Patients are referred by primary care providers for the 6-month "tune-up" clinic involving three to five hour-long, one-on-one visits between the patient and the pharmacist. After that, patients return to their primary care providers but can make follow-up phone calls to the clinic.
The tune-up focuses on finding the best combination of medications for the individual patient, education on medication adherence, simplifying the drug regimen to fit around the patient’s schedule, and setting personalized goals.
The study compared clinic patients with a random sample of patients treated by primary care providers in the same time period. Initial HbA1c levels were 10.5% in the clinic group and 9.3% in the comparison group, Dr. Morello and her associates reported at the annual scientific session of the American Diabetes Association.
They used a published regression model applied to retrospective chart data to estimate the 3-year costs of medical care (Diabetes Care 1997;20:1847-53). Based on baseline health status (largely driven by HbA1c levels), estimated costs per patient were $42,032 in the clinic group and $37,065 in the comparison group. Assuming that HbA1c changes were maintained 3 years later, estimated costs of care were $32,928 in the clinic group and $35,262 in the comparison group.
For 60 patients seen per year in the clinic, that amounts to a cumulative potential $546,240 savings from reduced costs, for a benefit-to-cost ratio of $8.81 and a return on investment of $7.81, she said.
If mean HbA1c levels rise by 1% over 3 years, the estimated medical cost avoided would be $6,412 per patient in the clinic group, still better than results in the comparison group, a secondary analysis found. That adds up to $384,720 in costs avoided over 3 years, for a benefit-to-cost ratio of $6.21 and a $5.21 return on investment after factoring in the cost of the pharmacist.
"I’m pretty sure that spending a little bit of money on the front end saves money on the back end," Dr. Morello said.
She reported having no financial disclosures.
On Twitter @sherryboschert
AT THE ADA ANNUAL SCIENTIFIC SESSION
Key clinical point: A 6-month pharmacist-led diabetes clinic lowered HbA1c levels and reduced estimated costs.
Major finding: HbA1c levels fell by 2.4% in the intervention group and 0.2% in the comparison group.
Data source: A retrospective comparison of data on 85 patients in the intervention group and 51 patients seen in primary care clinics.
Disclosures: Dr. Morello reported having no financial disclosures.
‘Walkable’ neighborhoods may be protective against diabetes
SAN FRANCISCO – People who live in "walkable" neighborhoods have a 15% lower rate of diabetes, compared with those who live in areas that require reliance on automobile transportation, a large Canadian study found.
"It’s become clear that the way we build and design our cities has an important impact on our health," Dr. Gillian L. Booth said at the annual scientific sessions of the American Diabetes Association. "Neighborhoods that were designed for pedestrian use are more conducive for walking. They tend to be older areas that are more densely populated, have more street connections, and are zoned in a way that retail and other services are embedded within residential areas. That means that there are more walkable destinations."
Sprawling suburban communities, on the other hand, tend to be more sparsely populated, and have fewer connections between streets, "and the zoning is such that retail and other services are separated and far away from where people live, thus increasing one’s reliance on automobiles for transportation," continued Dr. Booth, an endocrinologist and research scientist at St. Michael’s Hospital and the University of Toronto "There’s mounting literature that these types of neighborhood features are associated with lower rates of walking and physical activity and higher levels of obesity. They also lead to more time spent in cars, which in itself has been linked to a higher risk of becoming obese."
Until recently, there have been few prospective studies looking at neighborhood design and the development of diabetes. Limitations to previous studies include the fact that those who prefer to live in one neighborhood over another may differ systematically from those who choose to live in other neighborhoods. To account for this, Dr. Booth and her associates used Inverse Probability of Treatment Weighting to create balanced groups of adults aged 30-64 years living in high- and low-walkability areas.
"We asked the question, are individuals living in more walkable areas at a lower risk of developing diabetes? If this is true, does that still hold after we account for other confounders?" These confounders included age, sex, presence of comorbidities, previous hypertension, stroke, health care use, socioeconomic status, and ethnicity.
The study area consisted of 15 Canadian municipalities, including Toronto, which have a combined population of more than 7 million people. The researchers used anonymous health data from provincial databases of people who were free of diabetes and living in high- or low-walkability neighborhoods in April 2002, and followed them through March 2012 for the development of diabetes. The investigators excluded people with a prior diagnosis of diabetes.
Dr. Booth and her associates identified new cases of diabetes via the Ontario Diabetes Database, an electronic registry based on hospital and physician service claims. The walkability index was based on four features: population density (number of residents per square kilometer); residential density (number of dwellings per square kilometer); street connectivity (number of intersections per square kilometer), and walkable destinations (the number of stores and services within a 10-minute walk).
The study population consisted of 958,567 Canadian residents; their mean age was 49 years and 49% were male. Over the 10-year follow-up period, 90,922 new cases of diabetes were observed, for an incidence rate of 1.03/100 person-years. The researchers observed a 15% lower diabetes incidence among those living in the highest-walkability areas, compared with the lowest-walkability areas, in all study regions (hazard ratio of 0.85). They observed similar findings when they stratified people by income (HR of 0.86 and 0.82 for lower- and higher-income areas, respectively) and immigration status (HR of 0.85 among long-term residents and 0.87 among those who had been Canadian citizens for fewer than 10 years).
She concluded that high neighborhood walkability appears to be protective against the development of diabetes in young and middle-aged urban populations. "This suggests that changes in zoning, urban planning, and design that promote walking and other forms of active transportation may help to curb the ongoing rise in obesity and diabetes," she said. "Further research is needed to understand the full impact that such interventions will have."
The study was funded by the Canadian Institutes of Health Research. Dr. Booth said that she had no relevant financial conflicts to disclose.
SAN FRANCISCO – People who live in "walkable" neighborhoods have a 15% lower rate of diabetes, compared with those who live in areas that require reliance on automobile transportation, a large Canadian study found.
"It’s become clear that the way we build and design our cities has an important impact on our health," Dr. Gillian L. Booth said at the annual scientific sessions of the American Diabetes Association. "Neighborhoods that were designed for pedestrian use are more conducive for walking. They tend to be older areas that are more densely populated, have more street connections, and are zoned in a way that retail and other services are embedded within residential areas. That means that there are more walkable destinations."
Sprawling suburban communities, on the other hand, tend to be more sparsely populated, and have fewer connections between streets, "and the zoning is such that retail and other services are separated and far away from where people live, thus increasing one’s reliance on automobiles for transportation," continued Dr. Booth, an endocrinologist and research scientist at St. Michael’s Hospital and the University of Toronto "There’s mounting literature that these types of neighborhood features are associated with lower rates of walking and physical activity and higher levels of obesity. They also lead to more time spent in cars, which in itself has been linked to a higher risk of becoming obese."
Until recently, there have been few prospective studies looking at neighborhood design and the development of diabetes. Limitations to previous studies include the fact that those who prefer to live in one neighborhood over another may differ systematically from those who choose to live in other neighborhoods. To account for this, Dr. Booth and her associates used Inverse Probability of Treatment Weighting to create balanced groups of adults aged 30-64 years living in high- and low-walkability areas.
"We asked the question, are individuals living in more walkable areas at a lower risk of developing diabetes? If this is true, does that still hold after we account for other confounders?" These confounders included age, sex, presence of comorbidities, previous hypertension, stroke, health care use, socioeconomic status, and ethnicity.
The study area consisted of 15 Canadian municipalities, including Toronto, which have a combined population of more than 7 million people. The researchers used anonymous health data from provincial databases of people who were free of diabetes and living in high- or low-walkability neighborhoods in April 2002, and followed them through March 2012 for the development of diabetes. The investigators excluded people with a prior diagnosis of diabetes.
Dr. Booth and her associates identified new cases of diabetes via the Ontario Diabetes Database, an electronic registry based on hospital and physician service claims. The walkability index was based on four features: population density (number of residents per square kilometer); residential density (number of dwellings per square kilometer); street connectivity (number of intersections per square kilometer), and walkable destinations (the number of stores and services within a 10-minute walk).
The study population consisted of 958,567 Canadian residents; their mean age was 49 years and 49% were male. Over the 10-year follow-up period, 90,922 new cases of diabetes were observed, for an incidence rate of 1.03/100 person-years. The researchers observed a 15% lower diabetes incidence among those living in the highest-walkability areas, compared with the lowest-walkability areas, in all study regions (hazard ratio of 0.85). They observed similar findings when they stratified people by income (HR of 0.86 and 0.82 for lower- and higher-income areas, respectively) and immigration status (HR of 0.85 among long-term residents and 0.87 among those who had been Canadian citizens for fewer than 10 years).
She concluded that high neighborhood walkability appears to be protective against the development of diabetes in young and middle-aged urban populations. "This suggests that changes in zoning, urban planning, and design that promote walking and other forms of active transportation may help to curb the ongoing rise in obesity and diabetes," she said. "Further research is needed to understand the full impact that such interventions will have."
The study was funded by the Canadian Institutes of Health Research. Dr. Booth said that she had no relevant financial conflicts to disclose.
SAN FRANCISCO – People who live in "walkable" neighborhoods have a 15% lower rate of diabetes, compared with those who live in areas that require reliance on automobile transportation, a large Canadian study found.
"It’s become clear that the way we build and design our cities has an important impact on our health," Dr. Gillian L. Booth said at the annual scientific sessions of the American Diabetes Association. "Neighborhoods that were designed for pedestrian use are more conducive for walking. They tend to be older areas that are more densely populated, have more street connections, and are zoned in a way that retail and other services are embedded within residential areas. That means that there are more walkable destinations."
Sprawling suburban communities, on the other hand, tend to be more sparsely populated, and have fewer connections between streets, "and the zoning is such that retail and other services are separated and far away from where people live, thus increasing one’s reliance on automobiles for transportation," continued Dr. Booth, an endocrinologist and research scientist at St. Michael’s Hospital and the University of Toronto "There’s mounting literature that these types of neighborhood features are associated with lower rates of walking and physical activity and higher levels of obesity. They also lead to more time spent in cars, which in itself has been linked to a higher risk of becoming obese."
Until recently, there have been few prospective studies looking at neighborhood design and the development of diabetes. Limitations to previous studies include the fact that those who prefer to live in one neighborhood over another may differ systematically from those who choose to live in other neighborhoods. To account for this, Dr. Booth and her associates used Inverse Probability of Treatment Weighting to create balanced groups of adults aged 30-64 years living in high- and low-walkability areas.
"We asked the question, are individuals living in more walkable areas at a lower risk of developing diabetes? If this is true, does that still hold after we account for other confounders?" These confounders included age, sex, presence of comorbidities, previous hypertension, stroke, health care use, socioeconomic status, and ethnicity.
The study area consisted of 15 Canadian municipalities, including Toronto, which have a combined population of more than 7 million people. The researchers used anonymous health data from provincial databases of people who were free of diabetes and living in high- or low-walkability neighborhoods in April 2002, and followed them through March 2012 for the development of diabetes. The investigators excluded people with a prior diagnosis of diabetes.
Dr. Booth and her associates identified new cases of diabetes via the Ontario Diabetes Database, an electronic registry based on hospital and physician service claims. The walkability index was based on four features: population density (number of residents per square kilometer); residential density (number of dwellings per square kilometer); street connectivity (number of intersections per square kilometer), and walkable destinations (the number of stores and services within a 10-minute walk).
The study population consisted of 958,567 Canadian residents; their mean age was 49 years and 49% were male. Over the 10-year follow-up period, 90,922 new cases of diabetes were observed, for an incidence rate of 1.03/100 person-years. The researchers observed a 15% lower diabetes incidence among those living in the highest-walkability areas, compared with the lowest-walkability areas, in all study regions (hazard ratio of 0.85). They observed similar findings when they stratified people by income (HR of 0.86 and 0.82 for lower- and higher-income areas, respectively) and immigration status (HR of 0.85 among long-term residents and 0.87 among those who had been Canadian citizens for fewer than 10 years).
She concluded that high neighborhood walkability appears to be protective against the development of diabetes in young and middle-aged urban populations. "This suggests that changes in zoning, urban planning, and design that promote walking and other forms of active transportation may help to curb the ongoing rise in obesity and diabetes," she said. "Further research is needed to understand the full impact that such interventions will have."
The study was funded by the Canadian Institutes of Health Research. Dr. Booth said that she had no relevant financial conflicts to disclose.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: People who lived in walkable neighborhoods had a lower rate of diabetes than did those who lived in sprawling suburban areas.
Major finding: A 15% lower diabetes incidence was observed among Canadians living in the highest-walkability areas, compared with those who lived in the lowest-walkability areas (hazard ratio of 0.85).
Data source: A study of 958,567 residents who lived in 1 of 15 Canadian municipalities who did not have diabetes at baseline and were followed for 10 years.
Disclosures: The study was funded by the Canadian Institutes of Health Research. Dr. Booth said that she had no relevant financial conflicts.
TTP399 for type 2 diabetes shows promise
SAN FRANCISCO – The investigative liver-selective glucokinase activator TTP399 lowered glucose and did not increase lipids in subjects with type 2 diabetes, results from a randomized study demonstrated.
"The compound was extremely well tolerated," Carmen Valcarce, Ph.D., said at the annual scientific sessions of the American Diabetes Association.
Results were presented from a phase Ib/IIa double-blind, 6-week, multiple-dose trial studying TTP399 in 120 type 2 diabetes patients on stable doses of metformin. Three doses were tested: 400 mg twice daily, 800 mg once daily, and 800 mg twice daily, plus a placebo group. The major objective was to assess the safety and tolerability of TTP399 and to evaluate its pharmacodynamics and pharmacokinetics.
The mean age of study participants was 57 years, their mean body mass index was 31.4 kg/m2, their mean HbA1c was 8.2%, and their mean duration of diabetes was about 7 years.
Dr. Valcarce, TransTech Pharma’s senior vice president and scientific liaison, reported that the most frequent adverse event was headache, followed by dizziness and diarrhea. There was only one case of symptomatic hypoglycemia, which occurred in the placebo group. There were no increases in fasting triglycerides, cholesterol, lactate, insulin, or C-peptide.
The researchers observed decreases in the mean daily glucose profile in all treatment groups. In well-controlled subjects (defined as those with a baseline hemoglobin A1c of 7.5% or lower), 85% of those in the 800-mg twice-daily arm and 40% of those receiving any dose of TTP399 achieved normalization. None of the placebo-treated subjects reached an HbA1c of 6.5% or less.
"The clinical results to date are completely consistent with preclinical data and with the mechanism of action of liver-selective glucokinase activators," Dr. Valcarce said.
The study was funded and conducted by Forest Laboratories under a license agreement with TransTech Pharma, which is now continuing the development of TTP399 and will soon begin a 6-month phase IIb study. Dr. Valcarce is an employee of TransTech.
On Twitter @dougbrunk
SAN FRANCISCO – The investigative liver-selective glucokinase activator TTP399 lowered glucose and did not increase lipids in subjects with type 2 diabetes, results from a randomized study demonstrated.
"The compound was extremely well tolerated," Carmen Valcarce, Ph.D., said at the annual scientific sessions of the American Diabetes Association.
Results were presented from a phase Ib/IIa double-blind, 6-week, multiple-dose trial studying TTP399 in 120 type 2 diabetes patients on stable doses of metformin. Three doses were tested: 400 mg twice daily, 800 mg once daily, and 800 mg twice daily, plus a placebo group. The major objective was to assess the safety and tolerability of TTP399 and to evaluate its pharmacodynamics and pharmacokinetics.
The mean age of study participants was 57 years, their mean body mass index was 31.4 kg/m2, their mean HbA1c was 8.2%, and their mean duration of diabetes was about 7 years.
Dr. Valcarce, TransTech Pharma’s senior vice president and scientific liaison, reported that the most frequent adverse event was headache, followed by dizziness and diarrhea. There was only one case of symptomatic hypoglycemia, which occurred in the placebo group. There were no increases in fasting triglycerides, cholesterol, lactate, insulin, or C-peptide.
The researchers observed decreases in the mean daily glucose profile in all treatment groups. In well-controlled subjects (defined as those with a baseline hemoglobin A1c of 7.5% or lower), 85% of those in the 800-mg twice-daily arm and 40% of those receiving any dose of TTP399 achieved normalization. None of the placebo-treated subjects reached an HbA1c of 6.5% or less.
"The clinical results to date are completely consistent with preclinical data and with the mechanism of action of liver-selective glucokinase activators," Dr. Valcarce said.
The study was funded and conducted by Forest Laboratories under a license agreement with TransTech Pharma, which is now continuing the development of TTP399 and will soon begin a 6-month phase IIb study. Dr. Valcarce is an employee of TransTech.
On Twitter @dougbrunk
SAN FRANCISCO – The investigative liver-selective glucokinase activator TTP399 lowered glucose and did not increase lipids in subjects with type 2 diabetes, results from a randomized study demonstrated.
"The compound was extremely well tolerated," Carmen Valcarce, Ph.D., said at the annual scientific sessions of the American Diabetes Association.
Results were presented from a phase Ib/IIa double-blind, 6-week, multiple-dose trial studying TTP399 in 120 type 2 diabetes patients on stable doses of metformin. Three doses were tested: 400 mg twice daily, 800 mg once daily, and 800 mg twice daily, plus a placebo group. The major objective was to assess the safety and tolerability of TTP399 and to evaluate its pharmacodynamics and pharmacokinetics.
The mean age of study participants was 57 years, their mean body mass index was 31.4 kg/m2, their mean HbA1c was 8.2%, and their mean duration of diabetes was about 7 years.
Dr. Valcarce, TransTech Pharma’s senior vice president and scientific liaison, reported that the most frequent adverse event was headache, followed by dizziness and diarrhea. There was only one case of symptomatic hypoglycemia, which occurred in the placebo group. There were no increases in fasting triglycerides, cholesterol, lactate, insulin, or C-peptide.
The researchers observed decreases in the mean daily glucose profile in all treatment groups. In well-controlled subjects (defined as those with a baseline hemoglobin A1c of 7.5% or lower), 85% of those in the 800-mg twice-daily arm and 40% of those receiving any dose of TTP399 achieved normalization. None of the placebo-treated subjects reached an HbA1c of 6.5% or less.
"The clinical results to date are completely consistent with preclinical data and with the mechanism of action of liver-selective glucokinase activators," Dr. Valcarce said.
The study was funded and conducted by Forest Laboratories under a license agreement with TransTech Pharma, which is now continuing the development of TTP399 and will soon begin a 6-month phase IIb study. Dr. Valcarce is an employee of TransTech.
On Twitter @dougbrunk
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: An investigative liver-specific glucokinase activator was well tolerated and did not increase lipids in patients with type 2 diabetes.
Major finding: In well-controlled patients with type 2 diabetes (defined as those with a baseline HbA1c of 7.5% or lower), 85% of those in the 800-mg b.i.d. arm and 40% of those receiving any dose of TTP399 achieved normalization.
Data source: A phase Ib/IIa double-blind, 6-week multiple-dose trial studying TTP399 in 120 type 2 diabetes patients on stable doses of metformin.
Disclosures: The study was funded and conducted by Forest Laboratories under a license agreement with TransTech Pharma, which is now continuing the development of TTP399 and will soon begin a 6-month phase IIb study. Dr. Valcarce is an employee of TransTech.