EASD 2011

LISBON – Patients with type 2 diabetes who required insulin therapy were 19% more likely to die following a percutaneous coronary intervention than were patients who managed their disease with diet or oral antiglycemic medications, according to a registry analysis.

The higher mortality rate among insulin users remained after researchers controlled for the severity of diabetes, Dr. Anna Norhammar reported at the annual meeting of the European Association for the Study of Diabetes.

"Patients with type 2 diabetes who are taking insulin are at a very high risk after cardiac angiography, especially if they have a history of previous myocardial infarction or renal complications. We need to give these patients special attention and intensive handling," after the procedure, said Dr. Norhammar of the Karolinska Institute, Stockholm.

She and her colleagues extracted data from a combination of two large Swedish patient registries: the Swedish Coronary Angiography and Angioplasty Register (SCARR), which includes all patients who have undergone the procedures, and the National Diabetes Registry, which contains information on about 70% of Swedish citizens with the disease. They identified 14,079 patients who were included in both registries from 2001 to 2009. These patients formed the basis of the analysis.

Patients were divided into four groups: those on dietary therapy alone (2,936), those on oral agents alone (5,713), those taking both oral medications and insulin (3,008), and those taking insulin only (2,422).

The patients’ mean age was 69 years. Disease duration was shorter for those on the less intensive therapies compared with those taking insulin only (6 years vs. 15 years).

As expected, mean hemoglobin A1c rose along with treatment intensity, from 6.5% in those in the diet-only group to 7% in the oral-only group, and 7.8% in each of the combo and insulin-only groups. Retinopathy was present in 13% of the diet-managed group compared with 54% of the insulin-only group, a significant difference.

Heart failure also was significantly more common in the insulin-only group (24%) compared with the diet-only (14%), oral medications-only (12%) and combination therapy (17%) groups. Heart attacks had occurred in 39% of the insulin-only group, compared with 29% of the diet-only group, again a significant difference.

About 70% of all patients were hypertensive. Renal insufficiency was present in about 2% of the less-intensively-treated groups, 1% of those on combination therapy, and 8% of those taking only insulin, but this difference was not statistically significant. The insulin-only group also had more peripheral artery disease, but that difference also was not significant.

Angiographic results varied by treatment intensity. Those with diet-only therapy were most likely to have normal results (22%); results were normal in 17% of the insulin-only group. There also was a significant difference in the prevalence of three-vessel disease, which occurred in 23% of the diet-only group and 30% of the insulin-only group.

Diabetes treatment did not impact subsequent cardiovascular therapy, however.

By 6 months, the mortality curves were significantly different. Those on diet or oral therapy alone each had a mortality of about 5%, compared with 7% of those on combination therapy and 9% of those taking insulin-only therapy.

By 4 years – the mean follow-up time – mortality was still significantly higher among the insulin-only group (22%) compared with the diet-only and oral therapy-only groups (both 15%). This pattern continued as follow-up proceeded. By 8 years, more than 50% of the insulin-only group had died, compared with about 38% of the oral-only and diet-only groups.

Adjustment for baseline cardiovascular risk factors and diabetes complications (including more severe coronary artery disease, micro- and macrovascular disease, and renal complications) attenuated the risk of death for the most-intensively-treated patients, Dr. Norhammar said. "The risk of death for these patients fell from 1.22 to 1.19, but there was still a significant overall risk of excess mortality for those on insulin."

Whether insulin plays some mechanistic role in poorer outcomes, or whether it is simply a marker of more advanced disease, remains unclear, Dr. Norhammar said.

"We know that when patients start on insulin after [PCI], there can be some adverse reactions, including more occlusion and restenosis after stenting, and poorer response to antiplatelet drugs."

"I think this whole issue will be a lot clearer when we have the results of the ORIGIN study," she added.

The Outcome Reduction With Initial Glargine Intervention (ORIGIN) study is investigating the prevention of cardiovascular morbidity and mortality in people with type 2 diabetes or impaired glucose tolerance. The treatment variables are insulin glargine (variable dose vs. standard care), and different doses of omega-3 fatty acid, and placebo. Participants are being randomized to one of four possible treatment combinations.

Dr. Norhammar reported having no financial conflicts of interest.

LISBON – Patients with type 2 diabetes who required insulin therapy were 19% more likely to die following a percutaneous coronary intervention than were patients who managed their disease with diet or oral antiglycemic medications, according to a registry analysis.

The higher mortality rate among insulin users remained after researchers controlled for the severity of diabetes, Dr. Anna Norhammar reported at the annual meeting of the European Association for the Study of Diabetes.

"Patients with type 2 diabetes who are taking insulin are at a very high risk after cardiac angiography, especially if they have a history of previous myocardial infarction or renal complications. We need to give these patients special attention and intensive handling," after the procedure, said Dr. Norhammar of the Karolinska Institute, Stockholm.

She and her colleagues extracted data from a combination of two large Swedish patient registries: the Swedish Coronary Angiography and Angioplasty Register (SCARR), which includes all patients who have undergone the procedures, and the National Diabetes Registry, which contains information on about 70% of Swedish citizens with the disease. They identified 14,079 patients who were included in both registries from 2001 to 2009. These patients formed the basis of the analysis.

Patients were divided into four groups: those on dietary therapy alone (2,936), those on oral agents alone (5,713), those taking both oral medications and insulin (3,008), and those taking insulin only (2,422).

The patients’ mean age was 69 years. Disease duration was shorter for those on the less intensive therapies compared with those taking insulin only (6 years vs. 15 years).

As expected, mean hemoglobin A1c rose along with treatment intensity, from 6.5% in those in the diet-only group to 7% in the oral-only group, and 7.8% in each of the combo and insulin-only groups. Retinopathy was present in 13% of the diet-managed group compared with 54% of the insulin-only group, a significant difference.

Heart failure also was significantly more common in the insulin-only group (24%) compared with the diet-only (14%), oral medications-only (12%) and combination therapy (17%) groups. Heart attacks had occurred in 39% of the insulin-only group, compared with 29% of the diet-only group, again a significant difference.

About 70% of all patients were hypertensive. Renal insufficiency was present in about 2% of the less-intensively-treated groups, 1% of those on combination therapy, and 8% of those taking only insulin, but this difference was not statistically significant. The insulin-only group also had more peripheral artery disease, but that difference also was not significant.

Angiographic results varied by treatment intensity. Those with diet-only therapy were most likely to have normal results (22%); results were normal in 17% of the insulin-only group. There also was a significant difference in the prevalence of three-vessel disease, which occurred in 23% of the diet-only group and 30% of the insulin-only group.

Diabetes treatment did not impact subsequent cardiovascular therapy, however.

By 6 months, the mortality curves were significantly different. Those on diet or oral therapy alone each had a mortality of about 5%, compared with 7% of those on combination therapy and 9% of those taking insulin-only therapy.

By 4 years – the mean follow-up time – mortality was still significantly higher among the insulin-only group (22%) compared with the diet-only and oral therapy-only groups (both 15%). This pattern continued as follow-up proceeded. By 8 years, more than 50% of the insulin-only group had died, compared with about 38% of the oral-only and diet-only groups.

Adjustment for baseline cardiovascular risk factors and diabetes complications (including more severe coronary artery disease, micro- and macrovascular disease, and renal complications) attenuated the risk of death for the most-intensively-treated patients, Dr. Norhammar said. "The risk of death for these patients fell from 1.22 to 1.19, but there was still a significant overall risk of excess mortality for those on insulin."

Whether insulin plays some mechanistic role in poorer outcomes, or whether it is simply a marker of more advanced disease, remains unclear, Dr. Norhammar said.

"We know that when patients start on insulin after [PCI], there can be some adverse reactions, including more occlusion and restenosis after stenting, and poorer response to antiplatelet drugs."

"I think this whole issue will be a lot clearer when we have the results of the ORIGIN study," she added.

The Outcome Reduction With Initial Glargine Intervention (ORIGIN) study is investigating the prevention of cardiovascular morbidity and mortality in people with type 2 diabetes or impaired glucose tolerance. The treatment variables are insulin glargine (variable dose vs. standard care), and different doses of omega-3 fatty acid, and placebo. Participants are being randomized to one of four possible treatment combinations.

Dr. Norhammar reported having no financial conflicts of interest.

LISBON – Patients with type 2 diabetes who required insulin therapy were 19% more likely to die following a percutaneous coronary intervention than were patients who managed their disease with diet or oral antiglycemic medications, according to a registry analysis.

The higher mortality rate among insulin users remained after researchers controlled for the severity of diabetes, Dr. Anna Norhammar reported at the annual meeting of the European Association for the Study of Diabetes.

"Patients with type 2 diabetes who are taking insulin are at a very high risk after cardiac angiography, especially if they have a history of previous myocardial infarction or renal complications. We need to give these patients special attention and intensive handling," after the procedure, said Dr. Norhammar of the Karolinska Institute, Stockholm.

She and her colleagues extracted data from a combination of two large Swedish patient registries: the Swedish Coronary Angiography and Angioplasty Register (SCARR), which includes all patients who have undergone the procedures, and the National Diabetes Registry, which contains information on about 70% of Swedish citizens with the disease. They identified 14,079 patients who were included in both registries from 2001 to 2009. These patients formed the basis of the analysis.

Patients were divided into four groups: those on dietary therapy alone (2,936), those on oral agents alone (5,713), those taking both oral medications and insulin (3,008), and those taking insulin only (2,422).

The patients’ mean age was 69 years. Disease duration was shorter for those on the less intensive therapies compared with those taking insulin only (6 years vs. 15 years).

As expected, mean hemoglobin A1c rose along with treatment intensity, from 6.5% in those in the diet-only group to 7% in the oral-only group, and 7.8% in each of the combo and insulin-only groups. Retinopathy was present in 13% of the diet-managed group compared with 54% of the insulin-only group, a significant difference.

Heart failure also was significantly more common in the insulin-only group (24%) compared with the diet-only (14%), oral medications-only (12%) and combination therapy (17%) groups. Heart attacks had occurred in 39% of the insulin-only group, compared with 29% of the diet-only group, again a significant difference.

About 70% of all patients were hypertensive. Renal insufficiency was present in about 2% of the less-intensively-treated groups, 1% of those on combination therapy, and 8% of those taking only insulin, but this difference was not statistically significant. The insulin-only group also had more peripheral artery disease, but that difference also was not significant.

Angiographic results varied by treatment intensity. Those with diet-only therapy were most likely to have normal results (22%); results were normal in 17% of the insulin-only group. There also was a significant difference in the prevalence of three-vessel disease, which occurred in 23% of the diet-only group and 30% of the insulin-only group.

Diabetes treatment did not impact subsequent cardiovascular therapy, however.

By 6 months, the mortality curves were significantly different. Those on diet or oral therapy alone each had a mortality of about 5%, compared with 7% of those on combination therapy and 9% of those taking insulin-only therapy.

By 4 years – the mean follow-up time – mortality was still significantly higher among the insulin-only group (22%) compared with the diet-only and oral therapy-only groups (both 15%). This pattern continued as follow-up proceeded. By 8 years, more than 50% of the insulin-only group had died, compared with about 38% of the oral-only and diet-only groups.

Adjustment for baseline cardiovascular risk factors and diabetes complications (including more severe coronary artery disease, micro- and macrovascular disease, and renal complications) attenuated the risk of death for the most-intensively-treated patients, Dr. Norhammar said. "The risk of death for these patients fell from 1.22 to 1.19, but there was still a significant overall risk of excess mortality for those on insulin."

Whether insulin plays some mechanistic role in poorer outcomes, or whether it is simply a marker of more advanced disease, remains unclear, Dr. Norhammar said.

"We know that when patients start on insulin after [PCI], there can be some adverse reactions, including more occlusion and restenosis after stenting, and poorer response to antiplatelet drugs."

"I think this whole issue will be a lot clearer when we have the results of the ORIGIN study," she added.

The Outcome Reduction With Initial Glargine Intervention (ORIGIN) study is investigating the prevention of cardiovascular morbidity and mortality in people with type 2 diabetes or impaired glucose tolerance. The treatment variables are insulin glargine (variable dose vs. standard care), and different doses of omega-3 fatty acid, and placebo. Participants are being randomized to one of four possible treatment combinations.

Dr. Norhammar reported having no financial conflicts of interest.

LISBON – Reasonably similar glucose-lowering effects and modest weight loss can be achieved in patients with type 2 diabetes who are treated with a once-weekly, extended-release formulation of exenatide or once-daily liraglutide, the DURATION-6 study results show.

Liraglutide resulted in a mean change in hemoglobin A_1c of –1.48%, compared with baseline. This was slightly (but not significantly) lower than the result for exenatide, which produced a mean drop in HbA_1c of –1.28%. Change in HbA_1c was the primary end point of the trial, but once-weekly exenatide did not demonstrate noninferiority to once-daily liraglutide.

In addition, significantly more patients who took liraglutide rather than exenatide achieved an HbA_1c lower than 7% (60% and 52% of patients, respectively).

These results, from the first head-to-head study comparing the two injected regimens, were discussed in full Sept. 14 at the annual meeting of the European Society for the Study of Diabetes, although they had been previously mentioned in a brief press release from Eli Lilly, which manufactures the once-weekly exenatide formulation (Bydureon) in collaboration with Amylin Pharmaceuticals and Alkermes.

"Both exenatide once-weekly and liraglutide once-daily provided effective glucose control with substantial lowering of HbA_1c," commented study investigator Dr. John Buse of the University of North Carolina at Chapel Hill, as he presented these data.

DURATION-6 was a 26-week, multicenter, open-label, trial in which 911 patients with suboptimal control of type 2 diabetes were randomized to treatment with 2 mg once-weekly exenatide, or 1.8 mg once-daily liraglutide. The mean age of participants was 57 years and the mean duration of diabetes was 8-9 years.

Dr. Buse noted that "modest weight loss" could be achieved with both agents, although results reached statistical significance with liraglutide. The mean change in weight from baseline to posttreatment assessment was –2.68 kg for exenatide and –3.58 kg for liraglutide, with a mean difference of 0.9 kg overall.

However, liraglutide was associated with more gastrointestinal side effects than was exenatide, which may be an influencing factor when clinicians and patients decide which of the glucagonlike peptide–1 (GLP-1) receptor agonist regimens to use.

When liraglutide and exenatide were compared, the incidence of GI adverse events was 20.4% vs. 9.4% for nausea, 13.1% vs. 6.1% for diarrhea, and 10.7% vs. 3.7% for vomiting.

Patients taking liraglutide were more likely than those taking exenatide to discontinue treatment as a result of non-GI treatment-emergent adverse effects (5.3% vs. 2.6%).

No major hypoglycemic episodes were reported during the trial, and Dr. Buse reported no significant difference in minor hypoglycemia between the groups (10.8% of patients treated with liraglutide vs. 8.9% for exenatide). Hypoglycemia was more likely if patients were also receiving sulfonylurea therapy.

Bydureon has been approved for use in Europe since June, and is available in the United Kingdom. In the United States, however, the Food and Drug Administration bounced the application back to Amylin and Alkermes last October because of concerns of potential QT prolongation with high circulating levels of the drug. The two companies have since submitted new tQT studies, the results of DURATION-5 (comparing Bydureon with Byetta), and updated safety data from previous studies. The agency is expected to respond in January 2012.

In an interview, Dr. Michaela Diamant, who chaired the session in which the DURATION-6 results were revealed, commented that although there appear to be subtle differences between the regimens studied, the findings could still help clinical decision making, particularly if they are considered alongside the other DURATION trial findings.

"If you have two or three studies, then you can say, ‘As a physician, I’ve seen this evidence and, well, I’m going to discuss [this] with my patients,’ " said Dr. Diamant, professor of diabetology and director of the diabetes center at the Free University Medical Center in Amsterdam.

Some patients may prefer the once-daily injections with liraglutide, she suggested, as they then can "see a more direct coupling" with what they are eating and their treatment, whereas others may prefer the less-frequent dosing regimen offered by once-weekly exenatide.

Dr. Diamant noted that even marginally different treatments in terms of efficacy and safety could help tailor diabetes therapy more specifically to the individual. "It’s like with insulin," she said. "We have different insulins for [different] patients."

The study was funded by Amylin and Lilly. Dr. Buse disclosed acting as a consultant or investigator for multiple pharmaceutical companies via his contract with the University of North Carolina at Chapel Hill. Dr. Diamant has acted as a consultant, speaker, or both, for Lilly, Merck, Novo Nordisk, and Sanofi-Aventis. She has also received research support from Amylin, Lilly, Merck, Novartis, Novo Nordisk, and Takeda.

LISBON – Reasonably similar glucose-lowering effects and modest weight loss can be achieved in patients with type 2 diabetes who are treated with a once-weekly, extended-release formulation of exenatide or once-daily liraglutide, the DURATION-6 study results show.

Liraglutide resulted in a mean change in hemoglobin A_1c of –1.48%, compared with baseline. This was slightly (but not significantly) lower than the result for exenatide, which produced a mean drop in HbA_1c of –1.28%. Change in HbA_1c was the primary end point of the trial, but once-weekly exenatide did not demonstrate noninferiority to once-daily liraglutide.

In addition, significantly more patients who took liraglutide rather than exenatide achieved an HbA_1c lower than 7% (60% and 52% of patients, respectively).

These results, from the first head-to-head study comparing the two injected regimens, were discussed in full Sept. 14 at the annual meeting of the European Society for the Study of Diabetes, although they had been previously mentioned in a brief press release from Eli Lilly, which manufactures the once-weekly exenatide formulation (Bydureon) in collaboration with Amylin Pharmaceuticals and Alkermes.

"Both exenatide once-weekly and liraglutide once-daily provided effective glucose control with substantial lowering of HbA_1c," commented study investigator Dr. John Buse of the University of North Carolina at Chapel Hill, as he presented these data.

DURATION-6 was a 26-week, multicenter, open-label, trial in which 911 patients with suboptimal control of type 2 diabetes were randomized to treatment with 2 mg once-weekly exenatide, or 1.8 mg once-daily liraglutide. The mean age of participants was 57 years and the mean duration of diabetes was 8-9 years.

Dr. Buse noted that "modest weight loss" could be achieved with both agents, although results reached statistical significance with liraglutide. The mean change in weight from baseline to posttreatment assessment was –2.68 kg for exenatide and –3.58 kg for liraglutide, with a mean difference of 0.9 kg overall.

However, liraglutide was associated with more gastrointestinal side effects than was exenatide, which may be an influencing factor when clinicians and patients decide which of the glucagonlike peptide–1 (GLP-1) receptor agonist regimens to use.

When liraglutide and exenatide were compared, the incidence of GI adverse events was 20.4% vs. 9.4% for nausea, 13.1% vs. 6.1% for diarrhea, and 10.7% vs. 3.7% for vomiting.

Patients taking liraglutide were more likely than those taking exenatide to discontinue treatment as a result of non-GI treatment-emergent adverse effects (5.3% vs. 2.6%).

No major hypoglycemic episodes were reported during the trial, and Dr. Buse reported no significant difference in minor hypoglycemia between the groups (10.8% of patients treated with liraglutide vs. 8.9% for exenatide). Hypoglycemia was more likely if patients were also receiving sulfonylurea therapy.

Bydureon has been approved for use in Europe since June, and is available in the United Kingdom. In the United States, however, the Food and Drug Administration bounced the application back to Amylin and Alkermes last October because of concerns of potential QT prolongation with high circulating levels of the drug. The two companies have since submitted new tQT studies, the results of DURATION-5 (comparing Bydureon with Byetta), and updated safety data from previous studies. The agency is expected to respond in January 2012.

In an interview, Dr. Michaela Diamant, who chaired the session in which the DURATION-6 results were revealed, commented that although there appear to be subtle differences between the regimens studied, the findings could still help clinical decision making, particularly if they are considered alongside the other DURATION trial findings.

"If you have two or three studies, then you can say, ‘As a physician, I’ve seen this evidence and, well, I’m going to discuss [this] with my patients,’ " said Dr. Diamant, professor of diabetology and director of the diabetes center at the Free University Medical Center in Amsterdam.

Some patients may prefer the once-daily injections with liraglutide, she suggested, as they then can "see a more direct coupling" with what they are eating and their treatment, whereas others may prefer the less-frequent dosing regimen offered by once-weekly exenatide.

Dr. Diamant noted that even marginally different treatments in terms of efficacy and safety could help tailor diabetes therapy more specifically to the individual. "It’s like with insulin," she said. "We have different insulins for [different] patients."

The study was funded by Amylin and Lilly. Dr. Buse disclosed acting as a consultant or investigator for multiple pharmaceutical companies via his contract with the University of North Carolina at Chapel Hill. Dr. Diamant has acted as a consultant, speaker, or both, for Lilly, Merck, Novo Nordisk, and Sanofi-Aventis. She has also received research support from Amylin, Lilly, Merck, Novartis, Novo Nordisk, and Takeda.

LISBON – Reasonably similar glucose-lowering effects and modest weight loss can be achieved in patients with type 2 diabetes who are treated with a once-weekly, extended-release formulation of exenatide or once-daily liraglutide, the DURATION-6 study results show.

Liraglutide resulted in a mean change in hemoglobin A_1c of –1.48%, compared with baseline. This was slightly (but not significantly) lower than the result for exenatide, which produced a mean drop in HbA_1c of –1.28%. Change in HbA_1c was the primary end point of the trial, but once-weekly exenatide did not demonstrate noninferiority to once-daily liraglutide.

In addition, significantly more patients who took liraglutide rather than exenatide achieved an HbA_1c lower than 7% (60% and 52% of patients, respectively).

These results, from the first head-to-head study comparing the two injected regimens, were discussed in full Sept. 14 at the annual meeting of the European Society for the Study of Diabetes, although they had been previously mentioned in a brief press release from Eli Lilly, which manufactures the once-weekly exenatide formulation (Bydureon) in collaboration with Amylin Pharmaceuticals and Alkermes.

"Both exenatide once-weekly and liraglutide once-daily provided effective glucose control with substantial lowering of HbA_1c," commented study investigator Dr. John Buse of the University of North Carolina at Chapel Hill, as he presented these data.

DURATION-6 was a 26-week, multicenter, open-label, trial in which 911 patients with suboptimal control of type 2 diabetes were randomized to treatment with 2 mg once-weekly exenatide, or 1.8 mg once-daily liraglutide. The mean age of participants was 57 years and the mean duration of diabetes was 8-9 years.

Dr. Buse noted that "modest weight loss" could be achieved with both agents, although results reached statistical significance with liraglutide. The mean change in weight from baseline to posttreatment assessment was –2.68 kg for exenatide and –3.58 kg for liraglutide, with a mean difference of 0.9 kg overall.

However, liraglutide was associated with more gastrointestinal side effects than was exenatide, which may be an influencing factor when clinicians and patients decide which of the glucagonlike peptide–1 (GLP-1) receptor agonist regimens to use.

When liraglutide and exenatide were compared, the incidence of GI adverse events was 20.4% vs. 9.4% for nausea, 13.1% vs. 6.1% for diarrhea, and 10.7% vs. 3.7% for vomiting.

Patients taking liraglutide were more likely than those taking exenatide to discontinue treatment as a result of non-GI treatment-emergent adverse effects (5.3% vs. 2.6%).

No major hypoglycemic episodes were reported during the trial, and Dr. Buse reported no significant difference in minor hypoglycemia between the groups (10.8% of patients treated with liraglutide vs. 8.9% for exenatide). Hypoglycemia was more likely if patients were also receiving sulfonylurea therapy.

Bydureon has been approved for use in Europe since June, and is available in the United Kingdom. In the United States, however, the Food and Drug Administration bounced the application back to Amylin and Alkermes last October because of concerns of potential QT prolongation with high circulating levels of the drug. The two companies have since submitted new tQT studies, the results of DURATION-5 (comparing Bydureon with Byetta), and updated safety data from previous studies. The agency is expected to respond in January 2012.

In an interview, Dr. Michaela Diamant, who chaired the session in which the DURATION-6 results were revealed, commented that although there appear to be subtle differences between the regimens studied, the findings could still help clinical decision making, particularly if they are considered alongside the other DURATION trial findings.

"If you have two or three studies, then you can say, ‘As a physician, I’ve seen this evidence and, well, I’m going to discuss [this] with my patients,’ " said Dr. Diamant, professor of diabetology and director of the diabetes center at the Free University Medical Center in Amsterdam.

Some patients may prefer the once-daily injections with liraglutide, she suggested, as they then can "see a more direct coupling" with what they are eating and their treatment, whereas others may prefer the less-frequent dosing regimen offered by once-weekly exenatide.

Dr. Diamant noted that even marginally different treatments in terms of efficacy and safety could help tailor diabetes therapy more specifically to the individual. "It’s like with insulin," she said. "We have different insulins for [different] patients."

The study was funded by Amylin and Lilly. Dr. Buse disclosed acting as a consultant or investigator for multiple pharmaceutical companies via his contract with the University of North Carolina at Chapel Hill. Dr. Diamant has acted as a consultant, speaker, or both, for Lilly, Merck, Novo Nordisk, and Sanofi-Aventis. She has also received research support from Amylin, Lilly, Merck, Novartis, Novo Nordisk, and Takeda.

LISBON – A single in-home test of urinary C-peptide creatinine ratio appears to differentiate type 1 diabetes from a genetic form of the disease – maturity-onset diabetes of youth.

The in-home test saves children and parents from the stress and inconvenience of a blood test, and discriminates maturity-onset diabetes of youth (MODY) from type 1 diabetes with 100% sensitivity and 85% specificity, Dr. Rachel Besser said at the annual meeting of the European Association for the Study of Diabetes.

"MODY is frequently misdiagnosed as type 1 diabetes in children, and inappropriately treated with insulin," said Dr. Besser of the Peninsula Medical School, Exeter (England). "This test is clinically useful even in patients with a very short duration of disease."

In addition to guiding treatment, the test can pinpoint which children should undergo genetic testing for MODY, she said.

The test is a simple kit designed to be administered after a normal, diabetic-healthy evening meal. "We ask the children to empty their bladders before eating, have a dinner that contains healthy carbohydrates, and then take the test about 2 hours later."

Parents collect the urine at home and mail it to a laboratory, where the C-peptide creatinine ratio (UCPCR) is measured. A boric acid solution preserves the biomarker for up to 72 hours while en route to the lab.

Dr. Besser and her colleagues examined the test’s efficacy in 96 children who had been diagnosed with type 1 diabetes and 29 children who had confirmed MODY (10 with the HNF1A/4A subtype and 19 with the GCK subtype). All of the children had a mean disease duration of about 3 years. The mean age of the type 1 patients was 13 years; the MODY children were slightly older, at a mean of 14 years.

The test differentiated the two disorders quite well, Dr. Besser said. UCPCR was significantly lower in the type 1 samples than in the MODY samples (median 0.05 vs. 3.41 nmol/mmol).

Using a cutoff of at least 1.4 nmol/mmol, the test correctly discriminated MODY from type 1 diabetes with 100% sensitivity and 85% specificity. Fourteen of the patients diagnosed with type 1 diabetes met the cutoff point of at least 1.4 nmol/mmol.

The test is obviously far better than the method of calculation by family history, Dr. Besser added. "That only correctly identifies about 50% of these patients. There are also new, different mutations that we are discovering all the time," which are not familial.

Dr. Besser had no financial disclosures.

LISBON – A single in-home test of urinary C-peptide creatinine ratio appears to differentiate type 1 diabetes from a genetic form of the disease – maturity-onset diabetes of youth.

The in-home test saves children and parents from the stress and inconvenience of a blood test, and discriminates maturity-onset diabetes of youth (MODY) from type 1 diabetes with 100% sensitivity and 85% specificity, Dr. Rachel Besser said at the annual meeting of the European Association for the Study of Diabetes.

"MODY is frequently misdiagnosed as type 1 diabetes in children, and inappropriately treated with insulin," said Dr. Besser of the Peninsula Medical School, Exeter (England). "This test is clinically useful even in patients with a very short duration of disease."

In addition to guiding treatment, the test can pinpoint which children should undergo genetic testing for MODY, she said.

The test is a simple kit designed to be administered after a normal, diabetic-healthy evening meal. "We ask the children to empty their bladders before eating, have a dinner that contains healthy carbohydrates, and then take the test about 2 hours later."

Parents collect the urine at home and mail it to a laboratory, where the C-peptide creatinine ratio (UCPCR) is measured. A boric acid solution preserves the biomarker for up to 72 hours while en route to the lab.

Dr. Besser and her colleagues examined the test’s efficacy in 96 children who had been diagnosed with type 1 diabetes and 29 children who had confirmed MODY (10 with the HNF1A/4A subtype and 19 with the GCK subtype). All of the children had a mean disease duration of about 3 years. The mean age of the type 1 patients was 13 years; the MODY children were slightly older, at a mean of 14 years.

The test differentiated the two disorders quite well, Dr. Besser said. UCPCR was significantly lower in the type 1 samples than in the MODY samples (median 0.05 vs. 3.41 nmol/mmol).

Using a cutoff of at least 1.4 nmol/mmol, the test correctly discriminated MODY from type 1 diabetes with 100% sensitivity and 85% specificity. Fourteen of the patients diagnosed with type 1 diabetes met the cutoff point of at least 1.4 nmol/mmol.

The test is obviously far better than the method of calculation by family history, Dr. Besser added. "That only correctly identifies about 50% of these patients. There are also new, different mutations that we are discovering all the time," which are not familial.

Dr. Besser had no financial disclosures.

LISBON – A single in-home test of urinary C-peptide creatinine ratio appears to differentiate type 1 diabetes from a genetic form of the disease – maturity-onset diabetes of youth.

The in-home test saves children and parents from the stress and inconvenience of a blood test, and discriminates maturity-onset diabetes of youth (MODY) from type 1 diabetes with 100% sensitivity and 85% specificity, Dr. Rachel Besser said at the annual meeting of the European Association for the Study of Diabetes.

"MODY is frequently misdiagnosed as type 1 diabetes in children, and inappropriately treated with insulin," said Dr. Besser of the Peninsula Medical School, Exeter (England). "This test is clinically useful even in patients with a very short duration of disease."

In addition to guiding treatment, the test can pinpoint which children should undergo genetic testing for MODY, she said.

The test is a simple kit designed to be administered after a normal, diabetic-healthy evening meal. "We ask the children to empty their bladders before eating, have a dinner that contains healthy carbohydrates, and then take the test about 2 hours later."

Parents collect the urine at home and mail it to a laboratory, where the C-peptide creatinine ratio (UCPCR) is measured. A boric acid solution preserves the biomarker for up to 72 hours while en route to the lab.

Dr. Besser and her colleagues examined the test’s efficacy in 96 children who had been diagnosed with type 1 diabetes and 29 children who had confirmed MODY (10 with the HNF1A/4A subtype and 19 with the GCK subtype). All of the children had a mean disease duration of about 3 years. The mean age of the type 1 patients was 13 years; the MODY children were slightly older, at a mean of 14 years.

The test differentiated the two disorders quite well, Dr. Besser said. UCPCR was significantly lower in the type 1 samples than in the MODY samples (median 0.05 vs. 3.41 nmol/mmol).

Using a cutoff of at least 1.4 nmol/mmol, the test correctly discriminated MODY from type 1 diabetes with 100% sensitivity and 85% specificity. Fourteen of the patients diagnosed with type 1 diabetes met the cutoff point of at least 1.4 nmol/mmol.

The test is obviously far better than the method of calculation by family history, Dr. Besser added. "That only correctly identifies about 50% of these patients. There are also new, different mutations that we are discovering all the time," which are not familial.

Dr. Besser had no financial disclosures.

LISBON – Women with a history of gestational diabetes had an overall 50% elevated risk for cardiovascular events later in life, with a doubled risk among those who were overweight, in a large, case-control, population-based Swedish study.

It is well known that women who have gestational diabetes during pregnancy are at increased risk for type 2 diabetes later in life, but the relationship between gestational diabetes mellitus (GDM) and later cardiovascular disease (CVD) has been less well studied. In this analysis, the first such one to adjust for possible confounders, the increased risk for CVD among women with previous GDM was significant among women with body mass indexes (BMIs) of at least 25 kg/m², but not below.

Moreover, hypertension and smoking during pregnancy were stronger risk factors than GDM for later CVD. "Preventive strategies after pregnancy might need to be individualized depending on each woman’s characteristics and risk profile," said Dr. Erik Schwarcz, an endocrinologist and senior physician at University Hospital Orebro, Sweden.

Cases in the study, which used data from Swedish National Healthcare Quality registers from 1991 through 2008, were 4,590 women diagnoses with cardiovascular death or a first cardiovascular event – ischemic heart disease, ischemic stroke, peripheral arterial disease, or atherosclerosis – and who gave birth to at least one child during the study period. Those women were each matched with about five age-matched controls – total 22,398 – who did not have cardiovascular disease who gave birth to a child during the same year. Complete data on BMI and smoking were available for 2,660 cases and 13,357 controls.

At the time of the CVD event, the cases had a mean age of 41 years (range 19-61), with a mean of 9 years between the pregnancy and the event. There were 130 deaths among the 2,660 cases, compared with just 2 in the 13,357 controls. Ischemic heart disease and stroke were the most common diagnoses, affecting 56% and 35%, respectively.

A history of GDM was present for 2.4% of the cases, compared with 1.2% of the controls, a significant difference. Also significantly increased among the cases were chronic hypertension (2.1% vs. 0.3%), smoking (35.3% vs. 18.1%), non-Nordic ethnicity (14.1% vs. 11.5%), mean BMI (25.4 vs. 23.9), and low education (23.4% vs. 15.1%).

After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, all of the risk factors remained significant except for non-Nordic ethnicity, with odds ratios of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking. Using BMI of 20-25 as the referent, a BMI of 25-29 gave an odds ratio of 1.32, while a BMI of 30 or greater doubled the risk (OR, 2.00).

When divided into normal weight (BMI 20-24) versus overweight (BMI 25 or greater), only the overweight women had an increased risk for CVD events (OR, 2.35), while there was no excess CVD risk among those with normal BMI (0.48). When stratified for smoking, GDM was not a risk factor for CVD. In other words, GDM didn’t add any risk above and beyond that of smoking, Dr. Schwarcz explained, adding that the numbers for hypertension were too small to stratify.

In response to an audience member’s question about how many women developed diabetes after pregnancy, Dr. Schwarcz replied that the only available information on that is for prescribed medications and that he is currently analyzing those data.

Dr. Schwarcz disclosed that he has received lecture fees and has conducted clinical trials for Sanofi-Aventis, Novo-Nordisk, and AstraZeneca.

LISBON – Women with a history of gestational diabetes had an overall 50% elevated risk for cardiovascular events later in life, with a doubled risk among those who were overweight, in a large, case-control, population-based Swedish study.

It is well known that women who have gestational diabetes during pregnancy are at increased risk for type 2 diabetes later in life, but the relationship between gestational diabetes mellitus (GDM) and later cardiovascular disease (CVD) has been less well studied. In this analysis, the first such one to adjust for possible confounders, the increased risk for CVD among women with previous GDM was significant among women with body mass indexes (BMIs) of at least 25 kg/m², but not below.

Moreover, hypertension and smoking during pregnancy were stronger risk factors than GDM for later CVD. "Preventive strategies after pregnancy might need to be individualized depending on each woman’s characteristics and risk profile," said Dr. Erik Schwarcz, an endocrinologist and senior physician at University Hospital Orebro, Sweden.

Cases in the study, which used data from Swedish National Healthcare Quality registers from 1991 through 2008, were 4,590 women diagnoses with cardiovascular death or a first cardiovascular event – ischemic heart disease, ischemic stroke, peripheral arterial disease, or atherosclerosis – and who gave birth to at least one child during the study period. Those women were each matched with about five age-matched controls – total 22,398 – who did not have cardiovascular disease who gave birth to a child during the same year. Complete data on BMI and smoking were available for 2,660 cases and 13,357 controls.

At the time of the CVD event, the cases had a mean age of 41 years (range 19-61), with a mean of 9 years between the pregnancy and the event. There were 130 deaths among the 2,660 cases, compared with just 2 in the 13,357 controls. Ischemic heart disease and stroke were the most common diagnoses, affecting 56% and 35%, respectively.

A history of GDM was present for 2.4% of the cases, compared with 1.2% of the controls, a significant difference. Also significantly increased among the cases were chronic hypertension (2.1% vs. 0.3%), smoking (35.3% vs. 18.1%), non-Nordic ethnicity (14.1% vs. 11.5%), mean BMI (25.4 vs. 23.9), and low education (23.4% vs. 15.1%).

After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, all of the risk factors remained significant except for non-Nordic ethnicity, with odds ratios of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking. Using BMI of 20-25 as the referent, a BMI of 25-29 gave an odds ratio of 1.32, while a BMI of 30 or greater doubled the risk (OR, 2.00).

When divided into normal weight (BMI 20-24) versus overweight (BMI 25 or greater), only the overweight women had an increased risk for CVD events (OR, 2.35), while there was no excess CVD risk among those with normal BMI (0.48). When stratified for smoking, GDM was not a risk factor for CVD. In other words, GDM didn’t add any risk above and beyond that of smoking, Dr. Schwarcz explained, adding that the numbers for hypertension were too small to stratify.

In response to an audience member’s question about how many women developed diabetes after pregnancy, Dr. Schwarcz replied that the only available information on that is for prescribed medications and that he is currently analyzing those data.

Dr. Schwarcz disclosed that he has received lecture fees and has conducted clinical trials for Sanofi-Aventis, Novo-Nordisk, and AstraZeneca.

LISBON – Women with a history of gestational diabetes had an overall 50% elevated risk for cardiovascular events later in life, with a doubled risk among those who were overweight, in a large, case-control, population-based Swedish study.

It is well known that women who have gestational diabetes during pregnancy are at increased risk for type 2 diabetes later in life, but the relationship between gestational diabetes mellitus (GDM) and later cardiovascular disease (CVD) has been less well studied. In this analysis, the first such one to adjust for possible confounders, the increased risk for CVD among women with previous GDM was significant among women with body mass indexes (BMIs) of at least 25 kg/m², but not below.

Moreover, hypertension and smoking during pregnancy were stronger risk factors than GDM for later CVD. "Preventive strategies after pregnancy might need to be individualized depending on each woman’s characteristics and risk profile," said Dr. Erik Schwarcz, an endocrinologist and senior physician at University Hospital Orebro, Sweden.

Cases in the study, which used data from Swedish National Healthcare Quality registers from 1991 through 2008, were 4,590 women diagnoses with cardiovascular death or a first cardiovascular event – ischemic heart disease, ischemic stroke, peripheral arterial disease, or atherosclerosis – and who gave birth to at least one child during the study period. Those women were each matched with about five age-matched controls – total 22,398 – who did not have cardiovascular disease who gave birth to a child during the same year. Complete data on BMI and smoking were available for 2,660 cases and 13,357 controls.

At the time of the CVD event, the cases had a mean age of 41 years (range 19-61), with a mean of 9 years between the pregnancy and the event. There were 130 deaths among the 2,660 cases, compared with just 2 in the 13,357 controls. Ischemic heart disease and stroke were the most common diagnoses, affecting 56% and 35%, respectively.

A history of GDM was present for 2.4% of the cases, compared with 1.2% of the controls, a significant difference. Also significantly increased among the cases were chronic hypertension (2.1% vs. 0.3%), smoking (35.3% vs. 18.1%), non-Nordic ethnicity (14.1% vs. 11.5%), mean BMI (25.4 vs. 23.9), and low education (23.4% vs. 15.1%).

After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, all of the risk factors remained significant except for non-Nordic ethnicity, with odds ratios of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking. Using BMI of 20-25 as the referent, a BMI of 25-29 gave an odds ratio of 1.32, while a BMI of 30 or greater doubled the risk (OR, 2.00).

When divided into normal weight (BMI 20-24) versus overweight (BMI 25 or greater), only the overweight women had an increased risk for CVD events (OR, 2.35), while there was no excess CVD risk among those with normal BMI (0.48). When stratified for smoking, GDM was not a risk factor for CVD. In other words, GDM didn’t add any risk above and beyond that of smoking, Dr. Schwarcz explained, adding that the numbers for hypertension were too small to stratify.

In response to an audience member’s question about how many women developed diabetes after pregnancy, Dr. Schwarcz replied that the only available information on that is for prescribed medications and that he is currently analyzing those data.

Dr. Schwarcz disclosed that he has received lecture fees and has conducted clinical trials for Sanofi-Aventis, Novo-Nordisk, and AstraZeneca.

LISBON – Early and intensive multifactorial risk factor management in patients with screen-detected type 2 diabetes does not significantly reduce their risk of first, second, or third cardiovascular events, compared with standard diabetes care, according to a subanalysis of ADDITION-Europe.

Although the risk of experiencing a first cardiovascular event was reduced by 17% with an intensive risk management strategy, and the risk of a second, third, or even fourth CV event was lowered by 30%, 70%, and 78%, respectively, none of these differences reached statistical significance.

However, intensive risk management did not increase the risk of CV death or have any other adverse CV outcome, as previously suggested by some trials such as the oft-cited ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, which was conducted in patients with long-standing disease.

These findings are consistent with the main study results, which – although negative – suggested that the early identification and treatment of type 2 diabetes was more important than the intensity of treatment. "If you find people [with type 2 diabetes] early, then they appear to have a lower risk of [subsequent CV] events," said Dr. Simon Griffin, one of the investigators of ADDITION-Europe in an interview at the annual meeting of the European Society for the Study of Diabetes.

Dr. Griffin, who is a primary care practitioner and assistant director of the Medical Research Council (MRC) Epidemiology Unit in Cambridge, England, added that the trial findings show that "if you start intensive treatment early, you can reduce patients’ risk of events without apparently harming them."

ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen Detected Diabetes in Primary Care)–Europe randomized primary care patients with screen-detected diabetes to either routine care or targeted risk factor management.

Of more than 3,000 patients with screen-detected type 2 diabetes, who had a mean age of 60 years and were identified according to World Health Organization criteria, 1,379 were randomized to routine care and 1,678 to intensive risk factor management. The latter included lifestyle interventions (dietary advice, increased physical activity, and smoking cessation) and targeted blood glucose, blood pressure, and cholesterol control, as well as the prescription of daily low-dose aspirin.

As reported recently in the Lancet (2011;378:156-167), the intensive risk management strategy resulted in slight – but significant – improvement in CV risk factors such as HbA_1c, total cholesterol, and blood pressure, but produced a small, nonsignificant decrease in the incidence of a first CV event and death. The aim of the present analysis was to see if there was any greater effect on the incidence of experiencing a subsequent CV event.

After a mean follow-up of 5.3 years, 167 patients experienced a single CV event and 71 had experienced multiple events. Patients who experienced more than one event were more likely to be smokers, male, older, and unemployed.

Revascularization was the most common type of CV event, occurring for the first time in 88 (37%) of patients and for the second or three or more times in 55 (77%) and 15 (60%) of patients.

First, second, and third or more CV death event occurred in 48 (20%), 8 (11%), and 4 (16%) patients, respectively, and first, second, and third or more nonfatal MI occurred in 61 (26%), 5 (7%), and 3 (12%) patients. Respective rates for nonfatal stoke were 17% (41 patients), 3% (2), and 8% (2).

Rebecca Simmons, Ph.D., also of the MRC Epidemiology Unit, presented the data, and noted that the overall hazard ratio for a first CV event was 0.82 (95% confidence interval, 0.65-1.05), which favored intensive over routine diabetes treatment in the patient population studied.

The HR for any further CV event was 0.77 (95% CI, 0.58-1.02), and specifically for a second, third, or fourth event was a respective 0.70 (95% CI, 0.43-1.12), 0.30 (95% CI, 0.10-0.97), and 0.22 (95% CI, 0.02-2.18).

Dr. Simmons said of the findings that "modest but significant increases in intensity of treatment was not associated with significant reduction in first or second CVD events." However, there were clearly differences in the distribution of subsequent CV events, she noted.

Dr. Griffin further commented on the differences between studies such as ACCORD (Action to Control Cardiovascular Risk in Diabetes): "If you take people who have had diabetes for 10 years and they’ve not got very good glucose or blood pressure control and you suddenly try and change that, in terms of the glucose it does not necessarily help people. But if you take people early and you try to keep their glucose as low as possible for as long as possible then it does not appear to harm them and it appears to be beneficial."

The ADDITION-Europe study is financed by multiple organizations based in the United Kingdom, Denmark, and the Netherlands, including national health services and research institutions, and via unrestricted grants from Astra, Bio-Rad, GlaxoSmithKline, HemoCue, Merck, Novo Nordisk, Pfizer, and Servier. Dr. Griffin has previously received lecture fees from GSK, Unilever, Eli Lilly, and MSD. Dr. Simmons reported no personal conflicts of interest.

LISBON – Early and intensive multifactorial risk factor management in patients with screen-detected type 2 diabetes does not significantly reduce their risk of first, second, or third cardiovascular events, compared with standard diabetes care, according to a subanalysis of ADDITION-Europe.

Although the risk of experiencing a first cardiovascular event was reduced by 17% with an intensive risk management strategy, and the risk of a second, third, or even fourth CV event was lowered by 30%, 70%, and 78%, respectively, none of these differences reached statistical significance.

However, intensive risk management did not increase the risk of CV death or have any other adverse CV outcome, as previously suggested by some trials such as the oft-cited ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, which was conducted in patients with long-standing disease.

These findings are consistent with the main study results, which – although negative – suggested that the early identification and treatment of type 2 diabetes was more important than the intensity of treatment. "If you find people [with type 2 diabetes] early, then they appear to have a lower risk of [subsequent CV] events," said Dr. Simon Griffin, one of the investigators of ADDITION-Europe in an interview at the annual meeting of the European Society for the Study of Diabetes.

Dr. Griffin, who is a primary care practitioner and assistant director of the Medical Research Council (MRC) Epidemiology Unit in Cambridge, England, added that the trial findings show that "if you start intensive treatment early, you can reduce patients’ risk of events without apparently harming them."

ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen Detected Diabetes in Primary Care)–Europe randomized primary care patients with screen-detected diabetes to either routine care or targeted risk factor management.

Of more than 3,000 patients with screen-detected type 2 diabetes, who had a mean age of 60 years and were identified according to World Health Organization criteria, 1,379 were randomized to routine care and 1,678 to intensive risk factor management. The latter included lifestyle interventions (dietary advice, increased physical activity, and smoking cessation) and targeted blood glucose, blood pressure, and cholesterol control, as well as the prescription of daily low-dose aspirin.

As reported recently in the Lancet (2011;378:156-167), the intensive risk management strategy resulted in slight – but significant – improvement in CV risk factors such as HbA_1c, total cholesterol, and blood pressure, but produced a small, nonsignificant decrease in the incidence of a first CV event and death. The aim of the present analysis was to see if there was any greater effect on the incidence of experiencing a subsequent CV event.

After a mean follow-up of 5.3 years, 167 patients experienced a single CV event and 71 had experienced multiple events. Patients who experienced more than one event were more likely to be smokers, male, older, and unemployed.

Revascularization was the most common type of CV event, occurring for the first time in 88 (37%) of patients and for the second or three or more times in 55 (77%) and 15 (60%) of patients.

First, second, and third or more CV death event occurred in 48 (20%), 8 (11%), and 4 (16%) patients, respectively, and first, second, and third or more nonfatal MI occurred in 61 (26%), 5 (7%), and 3 (12%) patients. Respective rates for nonfatal stoke were 17% (41 patients), 3% (2), and 8% (2).

Rebecca Simmons, Ph.D., also of the MRC Epidemiology Unit, presented the data, and noted that the overall hazard ratio for a first CV event was 0.82 (95% confidence interval, 0.65-1.05), which favored intensive over routine diabetes treatment in the patient population studied.

The HR for any further CV event was 0.77 (95% CI, 0.58-1.02), and specifically for a second, third, or fourth event was a respective 0.70 (95% CI, 0.43-1.12), 0.30 (95% CI, 0.10-0.97), and 0.22 (95% CI, 0.02-2.18).

Dr. Simmons said of the findings that "modest but significant increases in intensity of treatment was not associated with significant reduction in first or second CVD events." However, there were clearly differences in the distribution of subsequent CV events, she noted.

Dr. Griffin further commented on the differences between studies such as ACCORD (Action to Control Cardiovascular Risk in Diabetes): "If you take people who have had diabetes for 10 years and they’ve not got very good glucose or blood pressure control and you suddenly try and change that, in terms of the glucose it does not necessarily help people. But if you take people early and you try to keep their glucose as low as possible for as long as possible then it does not appear to harm them and it appears to be beneficial."

The ADDITION-Europe study is financed by multiple organizations based in the United Kingdom, Denmark, and the Netherlands, including national health services and research institutions, and via unrestricted grants from Astra, Bio-Rad, GlaxoSmithKline, HemoCue, Merck, Novo Nordisk, Pfizer, and Servier. Dr. Griffin has previously received lecture fees from GSK, Unilever, Eli Lilly, and MSD. Dr. Simmons reported no personal conflicts of interest.

LISBON – Early and intensive multifactorial risk factor management in patients with screen-detected type 2 diabetes does not significantly reduce their risk of first, second, or third cardiovascular events, compared with standard diabetes care, according to a subanalysis of ADDITION-Europe.

Although the risk of experiencing a first cardiovascular event was reduced by 17% with an intensive risk management strategy, and the risk of a second, third, or even fourth CV event was lowered by 30%, 70%, and 78%, respectively, none of these differences reached statistical significance.

However, intensive risk management did not increase the risk of CV death or have any other adverse CV outcome, as previously suggested by some trials such as the oft-cited ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, which was conducted in patients with long-standing disease.

These findings are consistent with the main study results, which – although negative – suggested that the early identification and treatment of type 2 diabetes was more important than the intensity of treatment. "If you find people [with type 2 diabetes] early, then they appear to have a lower risk of [subsequent CV] events," said Dr. Simon Griffin, one of the investigators of ADDITION-Europe in an interview at the annual meeting of the European Society for the Study of Diabetes.

Dr. Griffin, who is a primary care practitioner and assistant director of the Medical Research Council (MRC) Epidemiology Unit in Cambridge, England, added that the trial findings show that "if you start intensive treatment early, you can reduce patients’ risk of events without apparently harming them."

ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen Detected Diabetes in Primary Care)–Europe randomized primary care patients with screen-detected diabetes to either routine care or targeted risk factor management.

Of more than 3,000 patients with screen-detected type 2 diabetes, who had a mean age of 60 years and were identified according to World Health Organization criteria, 1,379 were randomized to routine care and 1,678 to intensive risk factor management. The latter included lifestyle interventions (dietary advice, increased physical activity, and smoking cessation) and targeted blood glucose, blood pressure, and cholesterol control, as well as the prescription of daily low-dose aspirin.

As reported recently in the Lancet (2011;378:156-167), the intensive risk management strategy resulted in slight – but significant – improvement in CV risk factors such as HbA_1c, total cholesterol, and blood pressure, but produced a small, nonsignificant decrease in the incidence of a first CV event and death. The aim of the present analysis was to see if there was any greater effect on the incidence of experiencing a subsequent CV event.

After a mean follow-up of 5.3 years, 167 patients experienced a single CV event and 71 had experienced multiple events. Patients who experienced more than one event were more likely to be smokers, male, older, and unemployed.

Revascularization was the most common type of CV event, occurring for the first time in 88 (37%) of patients and for the second or three or more times in 55 (77%) and 15 (60%) of patients.

First, second, and third or more CV death event occurred in 48 (20%), 8 (11%), and 4 (16%) patients, respectively, and first, second, and third or more nonfatal MI occurred in 61 (26%), 5 (7%), and 3 (12%) patients. Respective rates for nonfatal stoke were 17% (41 patients), 3% (2), and 8% (2).

Rebecca Simmons, Ph.D., also of the MRC Epidemiology Unit, presented the data, and noted that the overall hazard ratio for a first CV event was 0.82 (95% confidence interval, 0.65-1.05), which favored intensive over routine diabetes treatment in the patient population studied.

The HR for any further CV event was 0.77 (95% CI, 0.58-1.02), and specifically for a second, third, or fourth event was a respective 0.70 (95% CI, 0.43-1.12), 0.30 (95% CI, 0.10-0.97), and 0.22 (95% CI, 0.02-2.18).

Dr. Simmons said of the findings that "modest but significant increases in intensity of treatment was not associated with significant reduction in first or second CVD events." However, there were clearly differences in the distribution of subsequent CV events, she noted.

Dr. Griffin further commented on the differences between studies such as ACCORD (Action to Control Cardiovascular Risk in Diabetes): "If you take people who have had diabetes for 10 years and they’ve not got very good glucose or blood pressure control and you suddenly try and change that, in terms of the glucose it does not necessarily help people. But if you take people early and you try to keep their glucose as low as possible for as long as possible then it does not appear to harm them and it appears to be beneficial."

The ADDITION-Europe study is financed by multiple organizations based in the United Kingdom, Denmark, and the Netherlands, including national health services and research institutions, and via unrestricted grants from Astra, Bio-Rad, GlaxoSmithKline, HemoCue, Merck, Novo Nordisk, Pfizer, and Servier. Dr. Griffin has previously received lecture fees from GSK, Unilever, Eli Lilly, and MSD. Dr. Simmons reported no personal conflicts of interest.

LISBON – Snacking throughout the day might not be the best way to help control type 2 diabetes, especially if the snacks contain much fat.

A high-fat meal in people with diabetes and impaired glucose tolerance appears to trigger the passage of bacterial endotoxins through the intestinal wall, adding to the load of inflammatory cytokines that have already been implicated in the disease, Alison Harte, Ph.D., said at the annual meeting of the European Association for the Study of Diabetes.

Because people with diabetes are often counseled to consume food in smaller, but more frequent, meals, this "leaky gut" effect could be compounded by this eating pattern, building up more and more of the lipopolysaccharide endotoxin – the main component of a gram-negative bacterium’s cell membrane – in the blood.

"Our data highlight that these people can be exposed to as much as 126% more circulating lipopolysaccharide after a high-fat meal," said Dr. Harte of the University of Warwick (England). "A continual grazing routine will cumulatively promote their pathogenic condition more rapidly than other individuals’ due to the elevated exposure to endotoxin."

Dr. Harte and her colleagues tested this hypothesis in 54 participants: 9 nonobese controls, 15 obese subjects, 12 with impaired glucose tolerance, and 18 with type 2 diabetes. The mean body mass index was 25 kg/m² in the normal controls, 33 kg/m² in the obese subjects, 32 kg/m² in those with impaired glucose tolerance, and 30 kg/m² in those with type 2 diabetes.

Each of the subjects ate a high-fat meal composed of 75 g of fat, 5 g of carbohydrate, and 6 g of protein after an overnight fast. Blood was drawn at baseline and at 1, 2, 3, and 4 hours after eating.

At baseline, lipopolysaccharide was already significantly higher in obese subjects and those with diabetes and impaired glucose tolerance (mean of 5.7 endotoxin units [EU]/mL), compared with the control subjects (mean of 3.5 EU/mL).

The high-fat meal caused a significant jump in lipopolysaccharides among those with diabetes and impaired glucose tolerance. By 4 hours, those with diabetes had a mean lipopolysaccharide load of 17 EU/mL. The load increased to 8 EU/mL in those with impaired glucose tolerance. At 4 hours after the meal, the obese controls had a nonsignificant increase but still had a mean of 22% more circulating lipopolysaccharide than the normal controls. This group had a slight, nonsignificant increase in the endotoxin.

Triglycerides followed a parallel course, she said, increasing over the 4-hour period significantly more in those with type 2 diabetes, impaired glucose tolerance, and obesity, compared with the controls.

"A high-fat diet raises endotoxin and triglycerides over 4 hours, and this increase could be further compounded by subsequent eating during the day, potentially resulting in continually raised levels," Dr. Harte said. "The fasting studies that we do might actually be masking the true impact of these circulating endotoxins and lipids."

Research confirms that obesity, diabetes, and cardiovascular disease all have an element of systemic inflammation. Dr. Harte said that her research suggests this inflammatory insult could arise, in part, from a compromised gut mucosa that allows bacterial endotoxins to enter the circulation and initiate a systemic inflammatory response.

Dr. Harte reported no financial conflicts.

LISBON – Snacking throughout the day might not be the best way to help control type 2 diabetes, especially if the snacks contain much fat.

A high-fat meal in people with diabetes and impaired glucose tolerance appears to trigger the passage of bacterial endotoxins through the intestinal wall, adding to the load of inflammatory cytokines that have already been implicated in the disease, Alison Harte, Ph.D., said at the annual meeting of the European Association for the Study of Diabetes.

Because people with diabetes are often counseled to consume food in smaller, but more frequent, meals, this "leaky gut" effect could be compounded by this eating pattern, building up more and more of the lipopolysaccharide endotoxin – the main component of a gram-negative bacterium’s cell membrane – in the blood.

"Our data highlight that these people can be exposed to as much as 126% more circulating lipopolysaccharide after a high-fat meal," said Dr. Harte of the University of Warwick (England). "A continual grazing routine will cumulatively promote their pathogenic condition more rapidly than other individuals’ due to the elevated exposure to endotoxin."

Dr. Harte and her colleagues tested this hypothesis in 54 participants: 9 nonobese controls, 15 obese subjects, 12 with impaired glucose tolerance, and 18 with type 2 diabetes. The mean body mass index was 25 kg/m² in the normal controls, 33 kg/m² in the obese subjects, 32 kg/m² in those with impaired glucose tolerance, and 30 kg/m² in those with type 2 diabetes.

Each of the subjects ate a high-fat meal composed of 75 g of fat, 5 g of carbohydrate, and 6 g of protein after an overnight fast. Blood was drawn at baseline and at 1, 2, 3, and 4 hours after eating.

At baseline, lipopolysaccharide was already significantly higher in obese subjects and those with diabetes and impaired glucose tolerance (mean of 5.7 endotoxin units [EU]/mL), compared with the control subjects (mean of 3.5 EU/mL).

The high-fat meal caused a significant jump in lipopolysaccharides among those with diabetes and impaired glucose tolerance. By 4 hours, those with diabetes had a mean lipopolysaccharide load of 17 EU/mL. The load increased to 8 EU/mL in those with impaired glucose tolerance. At 4 hours after the meal, the obese controls had a nonsignificant increase but still had a mean of 22% more circulating lipopolysaccharide than the normal controls. This group had a slight, nonsignificant increase in the endotoxin.

Triglycerides followed a parallel course, she said, increasing over the 4-hour period significantly more in those with type 2 diabetes, impaired glucose tolerance, and obesity, compared with the controls.

"A high-fat diet raises endotoxin and triglycerides over 4 hours, and this increase could be further compounded by subsequent eating during the day, potentially resulting in continually raised levels," Dr. Harte said. "The fasting studies that we do might actually be masking the true impact of these circulating endotoxins and lipids."

Research confirms that obesity, diabetes, and cardiovascular disease all have an element of systemic inflammation. Dr. Harte said that her research suggests this inflammatory insult could arise, in part, from a compromised gut mucosa that allows bacterial endotoxins to enter the circulation and initiate a systemic inflammatory response.

Dr. Harte reported no financial conflicts.

LISBON – Snacking throughout the day might not be the best way to help control type 2 diabetes, especially if the snacks contain much fat.

A high-fat meal in people with diabetes and impaired glucose tolerance appears to trigger the passage of bacterial endotoxins through the intestinal wall, adding to the load of inflammatory cytokines that have already been implicated in the disease, Alison Harte, Ph.D., said at the annual meeting of the European Association for the Study of Diabetes.

Because people with diabetes are often counseled to consume food in smaller, but more frequent, meals, this "leaky gut" effect could be compounded by this eating pattern, building up more and more of the lipopolysaccharide endotoxin – the main component of a gram-negative bacterium’s cell membrane – in the blood.

"Our data highlight that these people can be exposed to as much as 126% more circulating lipopolysaccharide after a high-fat meal," said Dr. Harte of the University of Warwick (England). "A continual grazing routine will cumulatively promote their pathogenic condition more rapidly than other individuals’ due to the elevated exposure to endotoxin."

Dr. Harte and her colleagues tested this hypothesis in 54 participants: 9 nonobese controls, 15 obese subjects, 12 with impaired glucose tolerance, and 18 with type 2 diabetes. The mean body mass index was 25 kg/m² in the normal controls, 33 kg/m² in the obese subjects, 32 kg/m² in those with impaired glucose tolerance, and 30 kg/m² in those with type 2 diabetes.

Each of the subjects ate a high-fat meal composed of 75 g of fat, 5 g of carbohydrate, and 6 g of protein after an overnight fast. Blood was drawn at baseline and at 1, 2, 3, and 4 hours after eating.

At baseline, lipopolysaccharide was already significantly higher in obese subjects and those with diabetes and impaired glucose tolerance (mean of 5.7 endotoxin units [EU]/mL), compared with the control subjects (mean of 3.5 EU/mL).

The high-fat meal caused a significant jump in lipopolysaccharides among those with diabetes and impaired glucose tolerance. By 4 hours, those with diabetes had a mean lipopolysaccharide load of 17 EU/mL. The load increased to 8 EU/mL in those with impaired glucose tolerance. At 4 hours after the meal, the obese controls had a nonsignificant increase but still had a mean of 22% more circulating lipopolysaccharide than the normal controls. This group had a slight, nonsignificant increase in the endotoxin.

Triglycerides followed a parallel course, she said, increasing over the 4-hour period significantly more in those with type 2 diabetes, impaired glucose tolerance, and obesity, compared with the controls.

"A high-fat diet raises endotoxin and triglycerides over 4 hours, and this increase could be further compounded by subsequent eating during the day, potentially resulting in continually raised levels," Dr. Harte said. "The fasting studies that we do might actually be masking the true impact of these circulating endotoxins and lipids."

Research confirms that obesity, diabetes, and cardiovascular disease all have an element of systemic inflammation. Dr. Harte said that her research suggests this inflammatory insult could arise, in part, from a compromised gut mucosa that allows bacterial endotoxins to enter the circulation and initiate a systemic inflammatory response.

Dr. Harte reported no financial conflicts.