EASD 2012

BERLIN -- A pancreas-only transplant improved cardiac function and morphology in a group of patients with type 1 diabetes.

After 5 years, the patients showed significantly improved posterior wall and interventricular septal thickness, as well as a significantly increased left ventricular ejection fraction, Dr. Margherita Occhipinti said at the annual meeting of the European Societies for the Study of Diabetes.

She reported 5-year follow-up data on 35 patients with type 1 diabetes who underwent the procedure. The patients were a mean of 38 years old and had a mean disease duration of 25 years. Their mean insulin requirement was 43 U/day.

Most of the transplants (74%) were performed with a portal-enteric drain technique; the remainder had systemic-enteric drainage, said Dr. Occhipinti of the University of Pisa (Italy). The majority (77%) had induction therapy with basiliximab; the rest had antithymocyte globulin (rabbit) induction. The maintenance immunosuppressant regimen was a combination of mycophenolate mofetil, tacrolimus, and steroids.

At last follow-up, fasting plasma glucose level had normalized, hemoglobin A_1c level had fallen from 9% to just under 6%, and C-peptide level had increased from under 1 ng/mL to almost 3 ng/mL.

There were no significant changes in either systolic or diastolic blood pressure. However, the number of patients taking ACE inhibitors or angiotensin receptor blockers decreased from 59% to 43%. Total and LDL cholesterol levels decreased significantly, although there were no significant changes in HDL cholesterol or triglycerides.

Cardiac morphology changed significantly, Dr. Occhipinti said, including a significant decrease in posterior wall thickness during diastole, from 8.1 mm to 7.0 mm, and interventricular septum thickness during diastole, from 9.3 mm to 8.7 mm. The left ventricular mass index decreased significantly, from 82 mg/m² to 73 mg/m²; and the left ventricular ejection fraction increased significantly, from 55.3% to 57.9%.

Dr. Occhipinti compared these changes to 2-year findings in a group of 11 control patients who were on a transplant waiting list or who had a failed pancreatic transplant.

In this group, there were no significant changes in HbA_1c, left ventricular ejection fraction, or any of the measures of cardiac morphology.

Dr. Occhipinti said she had no relevant financial disclosures.

BERLIN -- A pancreas-only transplant improved cardiac function and morphology in a group of patients with type 1 diabetes.

After 5 years, the patients showed significantly improved posterior wall and interventricular septal thickness, as well as a significantly increased left ventricular ejection fraction, Dr. Margherita Occhipinti said at the annual meeting of the European Societies for the Study of Diabetes.

She reported 5-year follow-up data on 35 patients with type 1 diabetes who underwent the procedure. The patients were a mean of 38 years old and had a mean disease duration of 25 years. Their mean insulin requirement was 43 U/day.

Most of the transplants (74%) were performed with a portal-enteric drain technique; the remainder had systemic-enteric drainage, said Dr. Occhipinti of the University of Pisa (Italy). The majority (77%) had induction therapy with basiliximab; the rest had antithymocyte globulin (rabbit) induction. The maintenance immunosuppressant regimen was a combination of mycophenolate mofetil, tacrolimus, and steroids.

At last follow-up, fasting plasma glucose level had normalized, hemoglobin A_1c level had fallen from 9% to just under 6%, and C-peptide level had increased from under 1 ng/mL to almost 3 ng/mL.

There were no significant changes in either systolic or diastolic blood pressure. However, the number of patients taking ACE inhibitors or angiotensin receptor blockers decreased from 59% to 43%. Total and LDL cholesterol levels decreased significantly, although there were no significant changes in HDL cholesterol or triglycerides.

Cardiac morphology changed significantly, Dr. Occhipinti said, including a significant decrease in posterior wall thickness during diastole, from 8.1 mm to 7.0 mm, and interventricular septum thickness during diastole, from 9.3 mm to 8.7 mm. The left ventricular mass index decreased significantly, from 82 mg/m² to 73 mg/m²; and the left ventricular ejection fraction increased significantly, from 55.3% to 57.9%.

Dr. Occhipinti compared these changes to 2-year findings in a group of 11 control patients who were on a transplant waiting list or who had a failed pancreatic transplant.

In this group, there were no significant changes in HbA_1c, left ventricular ejection fraction, or any of the measures of cardiac morphology.

Dr. Occhipinti said she had no relevant financial disclosures.

BERLIN -- A pancreas-only transplant improved cardiac function and morphology in a group of patients with type 1 diabetes.

After 5 years, the patients showed significantly improved posterior wall and interventricular septal thickness, as well as a significantly increased left ventricular ejection fraction, Dr. Margherita Occhipinti said at the annual meeting of the European Societies for the Study of Diabetes.

She reported 5-year follow-up data on 35 patients with type 1 diabetes who underwent the procedure. The patients were a mean of 38 years old and had a mean disease duration of 25 years. Their mean insulin requirement was 43 U/day.

Most of the transplants (74%) were performed with a portal-enteric drain technique; the remainder had systemic-enteric drainage, said Dr. Occhipinti of the University of Pisa (Italy). The majority (77%) had induction therapy with basiliximab; the rest had antithymocyte globulin (rabbit) induction. The maintenance immunosuppressant regimen was a combination of mycophenolate mofetil, tacrolimus, and steroids.

At last follow-up, fasting plasma glucose level had normalized, hemoglobin A_1c level had fallen from 9% to just under 6%, and C-peptide level had increased from under 1 ng/mL to almost 3 ng/mL.

There were no significant changes in either systolic or diastolic blood pressure. However, the number of patients taking ACE inhibitors or angiotensin receptor blockers decreased from 59% to 43%. Total and LDL cholesterol levels decreased significantly, although there were no significant changes in HDL cholesterol or triglycerides.

Cardiac morphology changed significantly, Dr. Occhipinti said, including a significant decrease in posterior wall thickness during diastole, from 8.1 mm to 7.0 mm, and interventricular septum thickness during diastole, from 9.3 mm to 8.7 mm. The left ventricular mass index decreased significantly, from 82 mg/m² to 73 mg/m²; and the left ventricular ejection fraction increased significantly, from 55.3% to 57.9%.

Dr. Occhipinti compared these changes to 2-year findings in a group of 11 control patients who were on a transplant waiting list or who had a failed pancreatic transplant.

In this group, there were no significant changes in HbA_1c, left ventricular ejection fraction, or any of the measures of cardiac morphology.

Dr. Occhipinti said she had no relevant financial disclosures.

BERLIN – Adults who gained weight during the first year following their initial diagnosis with type 2 diabetes had a significantly increased risk for cardiovascular-disease death and for all-cause death, in an analysis of nearly 8,500 patients in Swedish primary care practices.

"Weight gain in patients with newly diagnosed type 2 diabetes may be more hazardous than previously recognized," Dr. Johan Bodegard and his associates reported in a poster at the annual meeting of the European Association for the Study of Diabetes. Steps should be taken to limit weight gain in this patient group, said Dr. Bodegard, a researcher with AstraZeneca in Södertälje, Sweden, and his associates.

Courtesy Bill Branson/National Cancer Institute

The analysis showed that among 1,238 patients who gained at least one body mass index unit (1 kg/m²) during the first year following incident diagnosis with type 2 diabetes had a cardiovascular mortality rate 63% above that of 4,523 patients whose BMI didn’t change, and they had an all-cause mortality 34% above the unchanged group, both statistically significant differences. The analysis was adjusted for baseline differences in age, sex, BMI, prior angina, education, marital status, and glucose-lowering drugs.

The researchers examined records from 8,486 people who were patients in 84 primary-care centers in Sweden during 1999-2008. Patients included in the analysis had newly diagnosed type 2 diabetes who had their BMI measured at the time of initial diagnosis and also 1 year later, and also had no newly diagnosed cardiovascular disease or cancer during the first year following their diabetes diagnosis.

During that first year, 14% of the patients gained at least 1 kg/m², 32% lost at least 1 kg/m², and 53% had no change (percentages total 99% because of rounding). At baseline, the patients’ average age was 58 years, slightly more than half were men, and average BMI was 31 kg/m². About a third of the patients received at least one antidiabetes drug. During a median follow-up of 4.6 years, 197 patients died from cardiovascular disease and 423 patients died overall.

The patients who added at least 1 kg/m² during the first year of follow-up remained at an elevated BMI throughout the study. The weight gainers also had higher levels of hemoglobin A_1c and higher rates of treatment with insulin and sulfonylurea drugs during follow-up, compared with the patients who didn’t change or those who lost weight. But all three subgroups showed similar patterns for blood pressure and cholesterol levels throughout follow-up.

The study was sponsored by AstraZeneca. Dr. Bodegard is an employee of AstraZeneca.

BERLIN – Adults who gained weight during the first year following their initial diagnosis with type 2 diabetes had a significantly increased risk for cardiovascular-disease death and for all-cause death, in an analysis of nearly 8,500 patients in Swedish primary care practices.

"Weight gain in patients with newly diagnosed type 2 diabetes may be more hazardous than previously recognized," Dr. Johan Bodegard and his associates reported in a poster at the annual meeting of the European Association for the Study of Diabetes. Steps should be taken to limit weight gain in this patient group, said Dr. Bodegard, a researcher with AstraZeneca in Södertälje, Sweden, and his associates.

Courtesy Bill Branson/National Cancer Institute

The analysis showed that among 1,238 patients who gained at least one body mass index unit (1 kg/m²) during the first year following incident diagnosis with type 2 diabetes had a cardiovascular mortality rate 63% above that of 4,523 patients whose BMI didn’t change, and they had an all-cause mortality 34% above the unchanged group, both statistically significant differences. The analysis was adjusted for baseline differences in age, sex, BMI, prior angina, education, marital status, and glucose-lowering drugs.

The researchers examined records from 8,486 people who were patients in 84 primary-care centers in Sweden during 1999-2008. Patients included in the analysis had newly diagnosed type 2 diabetes who had their BMI measured at the time of initial diagnosis and also 1 year later, and also had no newly diagnosed cardiovascular disease or cancer during the first year following their diabetes diagnosis.

During that first year, 14% of the patients gained at least 1 kg/m², 32% lost at least 1 kg/m², and 53% had no change (percentages total 99% because of rounding). At baseline, the patients’ average age was 58 years, slightly more than half were men, and average BMI was 31 kg/m². About a third of the patients received at least one antidiabetes drug. During a median follow-up of 4.6 years, 197 patients died from cardiovascular disease and 423 patients died overall.

The patients who added at least 1 kg/m² during the first year of follow-up remained at an elevated BMI throughout the study. The weight gainers also had higher levels of hemoglobin A_1c and higher rates of treatment with insulin and sulfonylurea drugs during follow-up, compared with the patients who didn’t change or those who lost weight. But all three subgroups showed similar patterns for blood pressure and cholesterol levels throughout follow-up.

The study was sponsored by AstraZeneca. Dr. Bodegard is an employee of AstraZeneca.

BERLIN – Adults who gained weight during the first year following their initial diagnosis with type 2 diabetes had a significantly increased risk for cardiovascular-disease death and for all-cause death, in an analysis of nearly 8,500 patients in Swedish primary care practices.

"Weight gain in patients with newly diagnosed type 2 diabetes may be more hazardous than previously recognized," Dr. Johan Bodegard and his associates reported in a poster at the annual meeting of the European Association for the Study of Diabetes. Steps should be taken to limit weight gain in this patient group, said Dr. Bodegard, a researcher with AstraZeneca in Södertälje, Sweden, and his associates.

Courtesy Bill Branson/National Cancer Institute

The analysis showed that among 1,238 patients who gained at least one body mass index unit (1 kg/m²) during the first year following incident diagnosis with type 2 diabetes had a cardiovascular mortality rate 63% above that of 4,523 patients whose BMI didn’t change, and they had an all-cause mortality 34% above the unchanged group, both statistically significant differences. The analysis was adjusted for baseline differences in age, sex, BMI, prior angina, education, marital status, and glucose-lowering drugs.

The researchers examined records from 8,486 people who were patients in 84 primary-care centers in Sweden during 1999-2008. Patients included in the analysis had newly diagnosed type 2 diabetes who had their BMI measured at the time of initial diagnosis and also 1 year later, and also had no newly diagnosed cardiovascular disease or cancer during the first year following their diabetes diagnosis.

During that first year, 14% of the patients gained at least 1 kg/m², 32% lost at least 1 kg/m², and 53% had no change (percentages total 99% because of rounding). At baseline, the patients’ average age was 58 years, slightly more than half were men, and average BMI was 31 kg/m². About a third of the patients received at least one antidiabetes drug. During a median follow-up of 4.6 years, 197 patients died from cardiovascular disease and 423 patients died overall.

The patients who added at least 1 kg/m² during the first year of follow-up remained at an elevated BMI throughout the study. The weight gainers also had higher levels of hemoglobin A_1c and higher rates of treatment with insulin and sulfonylurea drugs during follow-up, compared with the patients who didn’t change or those who lost weight. But all three subgroups showed similar patterns for blood pressure and cholesterol levels throughout follow-up.

The study was sponsored by AstraZeneca. Dr. Bodegard is an employee of AstraZeneca.

BERLIN – Bolus, mealtime dosages of a new formulation of insulin paired with recombinant human hyaluronidase to speed insulin’s absorption and action led to significantly reduced postprandial, glycemic excursions in a randomized study of 113 patients with type 1 diabetes.

The hyaluronidase plus insulin formulation also resulted in a "flatter" daytime glucose profile, and led to a statistically significant reduction in hypoglycemic events, Dr. Jay S. Skyler said at the annual meeting of the European Association for the Study of Diabetes. In addition to these improvements in insulin management, the study results also showed that the hyaluronidase formulation was noninferior to insulin alone for reducing hemoglobin A_1c levels, and also had a similar safety and tolerability profile in type 1 patients, said Dr. Skyler, professor and deputy director of the diabetes research institute of the University of Miami.

Mitchel L. Zoler/IMNG Medical Media

"This is not the first report on hyaluronidase, but it’s very exciting. The results are pretty amazing," commented Dr. John L. Leahy, professor and codirector of the division of endocrinology, diabetes, and metabolism at the University of Vermont in Colchester. "Postprandial control really improved, and safety didn’t seem to change. There are different approaches that companies are taking to try to create superfast insulin; hyaluronidase is one approach. The main limitation is that these are studies of modest duration," 12 weeks in this study, Dr. Leahy noted in an interview. "You don’t know what it means when patients are shooting hyaluronidase over the course of 2 years, so we need more experience with longer duration. But I thought these were powerful data."

The study, done at 18 sites, enrolled patients with type 1 diabetes (average age, 43) who had an average hemoglobin A_1c of 7.43 and were maintained on a basal/bolus regimen.

After a 4- to 6-week run-in period on an open-label bolus with insulin glulisine and a twice-daily basal insulin dosage with glargine, Dr. Skyler and his associates randomized 117 patients to bolus treatment with either of two forms of 100 U/mL insulin – either insulin aspart or lispro – plus 5 g/mL recombinant human hyaluronidase, or to treatment with insulin lispro 100 U/mL alone for 12 weeks. Following the first 12-week period, patients were crossed either off of or onto the hyaluronidase-containing formulation for a second 12-week treatment period. Throughout the study, patients remained on their twice-daily glargine basal regimen. Four patients failed to complete the study, which left 113 patients available for outcomes analysis.

"When you use a very rapidly acting insulin, you need to be sure that the basal insulin level is correct. The protocol was written to treat all patients with glargine insulin twice daily so that patients would have a constant, steady basal insulinemia," Dr. Skyler said.

The average hemoglobin A_1c was about 6.8% in both treatment arms after 12 weeks, which met the study’s prespecified end point for noninferiority for the hyaluronidase formulations.

The incidence of postprandial glycemic excursions throughout the day was 82% lower in patients treated with hyaluronidase formulations than in those who received insulin-only bolus injections, a statistically significant difference. The incidence of total hypoglycemic events was also significantly lower in the hyaluronidase-treated patients; severe hypoglycemic episodes occurred in one patient who received hyaluronidase plus insulin aspart or lispro, and in five who received bolus insulin lispro only.

Commenting on the apparent disconnect between the reduced number of glycemic excursions in the hyaluronidase-treated patients without an improvement in hemoglobin A_1c levels, Dr. Skyler noted that the time on the hyaluronidase formulation was brief, just 12 weeks. "This may not have been enough time" to see an effect on A_1c, he said.

The two treatment arms also showed no differences in the incidence of adverse events, serious adverse events, immunogenicity of the drugs, or injection-site pain.

Now that these results have documented the superior efficacy of hyaluronidase formulations, the next step is to better optimize the dosing algorithms for hyaluronidase-containing insulin formulations, Dr. Skyler said.

The study was sponsored by Halozyme Therapeutics, the company that is developing the hyaluronidase and insulin formulation. Dr. Skyler said his university has received grant support from Halozyme. He said that he has had relationships with several drug companies, as an adviser, consultant, a member of the board of directors, or a shareholder. Dr. Leahy said he has been an adviser to Novo Nordisk, Merck, and Sanofi-Aventis.

BERLIN – Bolus, mealtime dosages of a new formulation of insulin paired with recombinant human hyaluronidase to speed insulin’s absorption and action led to significantly reduced postprandial, glycemic excursions in a randomized study of 113 patients with type 1 diabetes.

The hyaluronidase plus insulin formulation also resulted in a "flatter" daytime glucose profile, and led to a statistically significant reduction in hypoglycemic events, Dr. Jay S. Skyler said at the annual meeting of the European Association for the Study of Diabetes. In addition to these improvements in insulin management, the study results also showed that the hyaluronidase formulation was noninferior to insulin alone for reducing hemoglobin A_1c levels, and also had a similar safety and tolerability profile in type 1 patients, said Dr. Skyler, professor and deputy director of the diabetes research institute of the University of Miami.

Mitchel L. Zoler/IMNG Medical Media

"This is not the first report on hyaluronidase, but it’s very exciting. The results are pretty amazing," commented Dr. John L. Leahy, professor and codirector of the division of endocrinology, diabetes, and metabolism at the University of Vermont in Colchester. "Postprandial control really improved, and safety didn’t seem to change. There are different approaches that companies are taking to try to create superfast insulin; hyaluronidase is one approach. The main limitation is that these are studies of modest duration," 12 weeks in this study, Dr. Leahy noted in an interview. "You don’t know what it means when patients are shooting hyaluronidase over the course of 2 years, so we need more experience with longer duration. But I thought these were powerful data."

The study, done at 18 sites, enrolled patients with type 1 diabetes (average age, 43) who had an average hemoglobin A_1c of 7.43 and were maintained on a basal/bolus regimen.

After a 4- to 6-week run-in period on an open-label bolus with insulin glulisine and a twice-daily basal insulin dosage with glargine, Dr. Skyler and his associates randomized 117 patients to bolus treatment with either of two forms of 100 U/mL insulin – either insulin aspart or lispro – plus 5 g/mL recombinant human hyaluronidase, or to treatment with insulin lispro 100 U/mL alone for 12 weeks. Following the first 12-week period, patients were crossed either off of or onto the hyaluronidase-containing formulation for a second 12-week treatment period. Throughout the study, patients remained on their twice-daily glargine basal regimen. Four patients failed to complete the study, which left 113 patients available for outcomes analysis.

"When you use a very rapidly acting insulin, you need to be sure that the basal insulin level is correct. The protocol was written to treat all patients with glargine insulin twice daily so that patients would have a constant, steady basal insulinemia," Dr. Skyler said.

The average hemoglobin A_1c was about 6.8% in both treatment arms after 12 weeks, which met the study’s prespecified end point for noninferiority for the hyaluronidase formulations.

The incidence of postprandial glycemic excursions throughout the day was 82% lower in patients treated with hyaluronidase formulations than in those who received insulin-only bolus injections, a statistically significant difference. The incidence of total hypoglycemic events was also significantly lower in the hyaluronidase-treated patients; severe hypoglycemic episodes occurred in one patient who received hyaluronidase plus insulin aspart or lispro, and in five who received bolus insulin lispro only.

Commenting on the apparent disconnect between the reduced number of glycemic excursions in the hyaluronidase-treated patients without an improvement in hemoglobin A_1c levels, Dr. Skyler noted that the time on the hyaluronidase formulation was brief, just 12 weeks. "This may not have been enough time" to see an effect on A_1c, he said.

The two treatment arms also showed no differences in the incidence of adverse events, serious adverse events, immunogenicity of the drugs, or injection-site pain.

Now that these results have documented the superior efficacy of hyaluronidase formulations, the next step is to better optimize the dosing algorithms for hyaluronidase-containing insulin formulations, Dr. Skyler said.

The study was sponsored by Halozyme Therapeutics, the company that is developing the hyaluronidase and insulin formulation. Dr. Skyler said his university has received grant support from Halozyme. He said that he has had relationships with several drug companies, as an adviser, consultant, a member of the board of directors, or a shareholder. Dr. Leahy said he has been an adviser to Novo Nordisk, Merck, and Sanofi-Aventis.

BERLIN – Bolus, mealtime dosages of a new formulation of insulin paired with recombinant human hyaluronidase to speed insulin’s absorption and action led to significantly reduced postprandial, glycemic excursions in a randomized study of 113 patients with type 1 diabetes.

The hyaluronidase plus insulin formulation also resulted in a "flatter" daytime glucose profile, and led to a statistically significant reduction in hypoglycemic events, Dr. Jay S. Skyler said at the annual meeting of the European Association for the Study of Diabetes. In addition to these improvements in insulin management, the study results also showed that the hyaluronidase formulation was noninferior to insulin alone for reducing hemoglobin A_1c levels, and also had a similar safety and tolerability profile in type 1 patients, said Dr. Skyler, professor and deputy director of the diabetes research institute of the University of Miami.

Mitchel L. Zoler/IMNG Medical Media

"This is not the first report on hyaluronidase, but it’s very exciting. The results are pretty amazing," commented Dr. John L. Leahy, professor and codirector of the division of endocrinology, diabetes, and metabolism at the University of Vermont in Colchester. "Postprandial control really improved, and safety didn’t seem to change. There are different approaches that companies are taking to try to create superfast insulin; hyaluronidase is one approach. The main limitation is that these are studies of modest duration," 12 weeks in this study, Dr. Leahy noted in an interview. "You don’t know what it means when patients are shooting hyaluronidase over the course of 2 years, so we need more experience with longer duration. But I thought these were powerful data."

The study, done at 18 sites, enrolled patients with type 1 diabetes (average age, 43) who had an average hemoglobin A_1c of 7.43 and were maintained on a basal/bolus regimen.

After a 4- to 6-week run-in period on an open-label bolus with insulin glulisine and a twice-daily basal insulin dosage with glargine, Dr. Skyler and his associates randomized 117 patients to bolus treatment with either of two forms of 100 U/mL insulin – either insulin aspart or lispro – plus 5 g/mL recombinant human hyaluronidase, or to treatment with insulin lispro 100 U/mL alone for 12 weeks. Following the first 12-week period, patients were crossed either off of or onto the hyaluronidase-containing formulation for a second 12-week treatment period. Throughout the study, patients remained on their twice-daily glargine basal regimen. Four patients failed to complete the study, which left 113 patients available for outcomes analysis.

"When you use a very rapidly acting insulin, you need to be sure that the basal insulin level is correct. The protocol was written to treat all patients with glargine insulin twice daily so that patients would have a constant, steady basal insulinemia," Dr. Skyler said.

The average hemoglobin A_1c was about 6.8% in both treatment arms after 12 weeks, which met the study’s prespecified end point for noninferiority for the hyaluronidase formulations.

The incidence of postprandial glycemic excursions throughout the day was 82% lower in patients treated with hyaluronidase formulations than in those who received insulin-only bolus injections, a statistically significant difference. The incidence of total hypoglycemic events was also significantly lower in the hyaluronidase-treated patients; severe hypoglycemic episodes occurred in one patient who received hyaluronidase plus insulin aspart or lispro, and in five who received bolus insulin lispro only.

Commenting on the apparent disconnect between the reduced number of glycemic excursions in the hyaluronidase-treated patients without an improvement in hemoglobin A_1c levels, Dr. Skyler noted that the time on the hyaluronidase formulation was brief, just 12 weeks. "This may not have been enough time" to see an effect on A_1c, he said.

The two treatment arms also showed no differences in the incidence of adverse events, serious adverse events, immunogenicity of the drugs, or injection-site pain.

Now that these results have documented the superior efficacy of hyaluronidase formulations, the next step is to better optimize the dosing algorithms for hyaluronidase-containing insulin formulations, Dr. Skyler said.

The study was sponsored by Halozyme Therapeutics, the company that is developing the hyaluronidase and insulin formulation. Dr. Skyler said his university has received grant support from Halozyme. He said that he has had relationships with several drug companies, as an adviser, consultant, a member of the board of directors, or a shareholder. Dr. Leahy said he has been an adviser to Novo Nordisk, Merck, and Sanofi-Aventis.

BERLIN – A hypoglycemic event and a high rate of glucose excursions were associated with an increased rate of ventricular tachycardia, in a study of 30 patients with type 2 diabetes and a history of cardiovascular disease.

The findings highlight the potentially important role that glycemic excursions and hypoglycemic events play in patient health. "We have underestimated the risk from hypoglycemia as a cause of death," Dr. Markolf Hanefeld said in an interview at the annual meeting of the European Association for the Study of Diabetes.

"Hypoglycemia is very dangerous, and is also under-recognized and under-reported. Our results are another reason to avid glycemic excursions and hypoglycemia," he said.

Patients who may be especially at danger for arrhythmias triggered by poor glycemic control are those with a history of cardiovascular disease and on treatment that can produce hypoglycemia, such as a complex insulin regimen or a regimen that includes a sulfonylurea, said Dr. Hanefeld, professor and director of the Centre for Clinical Studies at Dresden (Germany) Technical University.

Dr. Hanefeld recommended that in addition to performing 1-day glucose monitoring on all patients who meet similar criteria, physicians should perform 24-hour ECG monitoring on patients with a prior major cardiovascular event, patients on a complex insulin regimen, and patients treated with a long-acting sulfonylurea.

"If you record their ECG [for a day or more,] that’s even better, but also very expensive," he said. "The three most dangerous complications of hypoglycemia are ventricular tachycardia, atrial fibrillation, and ischemic reactions. Ventricular tachycardia was our focus because it can lead to ventricular fibrillation and sudden death."

The patient’s treatment should then be tailored to improve their glycemic profile, and patients at higher risk for arrhythmias should be identified.

In addition to improved glycemic control with additional or alternative antidiabetic drugs, many patients like the ones studied could benefit from treatment with a beta-blocker to minimize the potential impact of a ventricular arrhythmia. But beta-blockers cannot be given to all patients with type 2 diabetes and a history of atherosclerotic cardiovascular disease, because some patients have bradycardia and would not tolerate a beta-blocker.

Dr. Hanefeld enrolled 30 consecutive patients with type 2 diabetes and documented atherosclerotic cardiovascular disease. Patients had a hemoglobin A_1c of less than 9% and were on stable treatment with insulin, a sulfonylurea-like glyburide, or both. The investigators excluded patients on any other antidiabetic treatment, patients with preexisting arrhythmias, and patients on any antiarrhythmic drug except for a beta-blocker. Enrolled patients averaged 68 years old, their average hemoglobin A_1c was 7.3%, and all but one was a man.

Each patient underwent 5 consecutive days of simultaneous continuous glucose monitoring and ECG recording. During this period, severe hypoglycemic events – defined as a blood glucose level less than 3.1 mmol/L – occurred in 23 patients, with a total of 35 episodes. The average time of each severe episode was 40 minutes.

Twenty-eight of 30 patients had ventricular extrasystoles (VESs), with an average of more than 3,600 during 5 days of ECG recording. Seventeen patients had couplets, 10 had triplets, and 5 had ventricular tachycardia.

Analysis showed a statistically significant increase in the rate of severe VESs in patients who had a mean amplitude of glycemic excursions of at least 4.02 mmol/L, Dr. Hanefeld and his colleagues reported. The highest rate by far of VES occurred in patients who had at least one severe hypoglycemic event and a mean amplitude of glycemic excursions of greater than 5.61 mmol/L.

Dr. Hanefeld said that he and his associates on the study had no disclosures.

BERLIN – A hypoglycemic event and a high rate of glucose excursions were associated with an increased rate of ventricular tachycardia, in a study of 30 patients with type 2 diabetes and a history of cardiovascular disease.

The findings highlight the potentially important role that glycemic excursions and hypoglycemic events play in patient health. "We have underestimated the risk from hypoglycemia as a cause of death," Dr. Markolf Hanefeld said in an interview at the annual meeting of the European Association for the Study of Diabetes.

"Hypoglycemia is very dangerous, and is also under-recognized and under-reported. Our results are another reason to avid glycemic excursions and hypoglycemia," he said.

Patients who may be especially at danger for arrhythmias triggered by poor glycemic control are those with a history of cardiovascular disease and on treatment that can produce hypoglycemia, such as a complex insulin regimen or a regimen that includes a sulfonylurea, said Dr. Hanefeld, professor and director of the Centre for Clinical Studies at Dresden (Germany) Technical University.

Dr. Hanefeld recommended that in addition to performing 1-day glucose monitoring on all patients who meet similar criteria, physicians should perform 24-hour ECG monitoring on patients with a prior major cardiovascular event, patients on a complex insulin regimen, and patients treated with a long-acting sulfonylurea.

"If you record their ECG [for a day or more,] that’s even better, but also very expensive," he said. "The three most dangerous complications of hypoglycemia are ventricular tachycardia, atrial fibrillation, and ischemic reactions. Ventricular tachycardia was our focus because it can lead to ventricular fibrillation and sudden death."

The patient’s treatment should then be tailored to improve their glycemic profile, and patients at higher risk for arrhythmias should be identified.

In addition to improved glycemic control with additional or alternative antidiabetic drugs, many patients like the ones studied could benefit from treatment with a beta-blocker to minimize the potential impact of a ventricular arrhythmia. But beta-blockers cannot be given to all patients with type 2 diabetes and a history of atherosclerotic cardiovascular disease, because some patients have bradycardia and would not tolerate a beta-blocker.

Dr. Hanefeld enrolled 30 consecutive patients with type 2 diabetes and documented atherosclerotic cardiovascular disease. Patients had a hemoglobin A_1c of less than 9% and were on stable treatment with insulin, a sulfonylurea-like glyburide, or both. The investigators excluded patients on any other antidiabetic treatment, patients with preexisting arrhythmias, and patients on any antiarrhythmic drug except for a beta-blocker. Enrolled patients averaged 68 years old, their average hemoglobin A_1c was 7.3%, and all but one was a man.

Each patient underwent 5 consecutive days of simultaneous continuous glucose monitoring and ECG recording. During this period, severe hypoglycemic events – defined as a blood glucose level less than 3.1 mmol/L – occurred in 23 patients, with a total of 35 episodes. The average time of each severe episode was 40 minutes.

Twenty-eight of 30 patients had ventricular extrasystoles (VESs), with an average of more than 3,600 during 5 days of ECG recording. Seventeen patients had couplets, 10 had triplets, and 5 had ventricular tachycardia.

Analysis showed a statistically significant increase in the rate of severe VESs in patients who had a mean amplitude of glycemic excursions of at least 4.02 mmol/L, Dr. Hanefeld and his colleagues reported. The highest rate by far of VES occurred in patients who had at least one severe hypoglycemic event and a mean amplitude of glycemic excursions of greater than 5.61 mmol/L.

Dr. Hanefeld said that he and his associates on the study had no disclosures.

BERLIN – A hypoglycemic event and a high rate of glucose excursions were associated with an increased rate of ventricular tachycardia, in a study of 30 patients with type 2 diabetes and a history of cardiovascular disease.

The findings highlight the potentially important role that glycemic excursions and hypoglycemic events play in patient health. "We have underestimated the risk from hypoglycemia as a cause of death," Dr. Markolf Hanefeld said in an interview at the annual meeting of the European Association for the Study of Diabetes.

"Hypoglycemia is very dangerous, and is also under-recognized and under-reported. Our results are another reason to avid glycemic excursions and hypoglycemia," he said.

Patients who may be especially at danger for arrhythmias triggered by poor glycemic control are those with a history of cardiovascular disease and on treatment that can produce hypoglycemia, such as a complex insulin regimen or a regimen that includes a sulfonylurea, said Dr. Hanefeld, professor and director of the Centre for Clinical Studies at Dresden (Germany) Technical University.

Dr. Hanefeld recommended that in addition to performing 1-day glucose monitoring on all patients who meet similar criteria, physicians should perform 24-hour ECG monitoring on patients with a prior major cardiovascular event, patients on a complex insulin regimen, and patients treated with a long-acting sulfonylurea.

"If you record their ECG [for a day or more,] that’s even better, but also very expensive," he said. "The three most dangerous complications of hypoglycemia are ventricular tachycardia, atrial fibrillation, and ischemic reactions. Ventricular tachycardia was our focus because it can lead to ventricular fibrillation and sudden death."

The patient’s treatment should then be tailored to improve their glycemic profile, and patients at higher risk for arrhythmias should be identified.

In addition to improved glycemic control with additional or alternative antidiabetic drugs, many patients like the ones studied could benefit from treatment with a beta-blocker to minimize the potential impact of a ventricular arrhythmia. But beta-blockers cannot be given to all patients with type 2 diabetes and a history of atherosclerotic cardiovascular disease, because some patients have bradycardia and would not tolerate a beta-blocker.

Dr. Hanefeld enrolled 30 consecutive patients with type 2 diabetes and documented atherosclerotic cardiovascular disease. Patients had a hemoglobin A_1c of less than 9% and were on stable treatment with insulin, a sulfonylurea-like glyburide, or both. The investigators excluded patients on any other antidiabetic treatment, patients with preexisting arrhythmias, and patients on any antiarrhythmic drug except for a beta-blocker. Enrolled patients averaged 68 years old, their average hemoglobin A_1c was 7.3%, and all but one was a man.

Each patient underwent 5 consecutive days of simultaneous continuous glucose monitoring and ECG recording. During this period, severe hypoglycemic events – defined as a blood glucose level less than 3.1 mmol/L – occurred in 23 patients, with a total of 35 episodes. The average time of each severe episode was 40 minutes.

Twenty-eight of 30 patients had ventricular extrasystoles (VESs), with an average of more than 3,600 during 5 days of ECG recording. Seventeen patients had couplets, 10 had triplets, and 5 had ventricular tachycardia.

Analysis showed a statistically significant increase in the rate of severe VESs in patients who had a mean amplitude of glycemic excursions of at least 4.02 mmol/L, Dr. Hanefeld and his colleagues reported. The highest rate by far of VES occurred in patients who had at least one severe hypoglycemic event and a mean amplitude of glycemic excursions of greater than 5.61 mmol/L.

Dr. Hanefeld said that he and his associates on the study had no disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age.

The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%.

All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed.

After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study.

At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline.

More than half of the subjects (62%) reached a level of 7%.

Fasting glucose and acute glucose response improved significantly.

Insulin sensitivity improved early and that was maintained.

Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age.

The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%.

All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed.

After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study.

At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline.

More than half of the subjects (62%) reached a level of 7%.

Fasting glucose and acute glucose response improved significantly.

Insulin sensitivity improved early and that was maintained.

Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age.

The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%.

All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed.

After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study.

At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline.

More than half of the subjects (62%) reached a level of 7%.

Fasting glucose and acute glucose response improved significantly.

Insulin sensitivity improved early and that was maintained.

Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

BERLIN – In patients with type 1 diabetes and end-stage renal disease, a combined pancreas/kidney transplant was associated with significantly better 15-year survival than a single kidney graft alone.

Patients who got the simultaneous transplant were 30% more likely to survive to 15 years than were those who received a living donor kidney. Those patients who got a single kidney from a deceased donor, however, were 30% less likely to survive for 15 years after the operation, Dr. Trond Jenssen said at the annual meeting of the European Associations for the Study of Diabetes.

The combined graft is the preferred method of treating end-stage renal disease (ESRD) caused by diabetic nephropathy, said Dr. Jenssen of Oslo University. Not all patients are suited for it, however.

"According to the algorithm at our center, if you are older than 55 or too sick, you have to decide between the living and deceased donor single kidney graft. Patients who are younger and have less comorbidity are the ones considered for a combined transplant," he said.

Since those who have the dual-organ operation almost always normalize their glycemic values afterward, Dr. Jenssen said, it’s assumed that they will live longer than those who get only a kidney, but studies are divided on the finding.

"The literature over the past 10 years has differed," he said. Comparing studies among institutions is impossible because of the differences in surgical technique and immunosuppressive regimens; the patient populations can also vary widely.

Oslo University is in a unique place to study the issue, Dr. Jenssen suggested. The facility is the national transplant center, with nearly 30 years of full follow-up data on 630 type 1 diabetes patients who were transplanted for ESRD. All of the patients are followed at least annually and their information is entered into the Norwegian Renal Registry.

"Because patients in Norway tend to be very faithful to their doctors, we have not lost a single one of these to follow-up," he said.

Of the entire group, 222 received the simultaneous transplants, 171 received a living donor single kidney, and 237 got a deceased donor kidney. Patients who received the simultaneous transplant were younger than the living or deceased single graft groups (41 years vs. 45 and 55 years, respectively).

The study controlled for the evolution of surgical techniques and immunosuppressant regimens. Before 1989, all pancreases were transplanted with occluded ducts. From 1989 to 1999, the exocrine duct drained into the bladder, and since 2000, into the intestine. The pancreas has always been connected to the systemic circulation by the iliac artery and vein.

Before 2000, the immunosuppressive regiment consisted of cyclosporine and azathioprine; afterward, tacrolimus and mycophenolate. All patients from both eras take a daily dose of prednisone as well. There was no induction therapy before 2000, Dr. Jenssen said. After that time, patients receiving a single kidney began to receive basiliximab, and the dual-transplant patients got thymoglobulin.

The overall 15-year survival rate was 50% in the simultaneous-graft group, 30% in the living donor kidney group, and 12% in the deceased donor kidney group.

Dr. Jenssen presented two regression models. In the first, which controlled for recipient age, time on dialysis, and the transplant era, patients who got the dual graft were significantly more likely to survive to 15 years than were those who got the single live donor kidney (hazard ratio, 0.70). Patients who received a single deceased donor kidney were 31% less likely to survive (HR, 1.29). These differences were no longer significant in a second model, which also controlled for donor age, but Dr. Jenssen said the difference was not clinically meaningful.

Dr. Jenssen had no financial disclosures.

BERLIN – In patients with type 1 diabetes and end-stage renal disease, a combined pancreas/kidney transplant was associated with significantly better 15-year survival than a single kidney graft alone.

Patients who got the simultaneous transplant were 30% more likely to survive to 15 years than were those who received a living donor kidney. Those patients who got a single kidney from a deceased donor, however, were 30% less likely to survive for 15 years after the operation, Dr. Trond Jenssen said at the annual meeting of the European Associations for the Study of Diabetes.

The combined graft is the preferred method of treating end-stage renal disease (ESRD) caused by diabetic nephropathy, said Dr. Jenssen of Oslo University. Not all patients are suited for it, however.

"According to the algorithm at our center, if you are older than 55 or too sick, you have to decide between the living and deceased donor single kidney graft. Patients who are younger and have less comorbidity are the ones considered for a combined transplant," he said.

Since those who have the dual-organ operation almost always normalize their glycemic values afterward, Dr. Jenssen said, it’s assumed that they will live longer than those who get only a kidney, but studies are divided on the finding.

"The literature over the past 10 years has differed," he said. Comparing studies among institutions is impossible because of the differences in surgical technique and immunosuppressive regimens; the patient populations can also vary widely.

Oslo University is in a unique place to study the issue, Dr. Jenssen suggested. The facility is the national transplant center, with nearly 30 years of full follow-up data on 630 type 1 diabetes patients who were transplanted for ESRD. All of the patients are followed at least annually and their information is entered into the Norwegian Renal Registry.

"Because patients in Norway tend to be very faithful to their doctors, we have not lost a single one of these to follow-up," he said.

Of the entire group, 222 received the simultaneous transplants, 171 received a living donor single kidney, and 237 got a deceased donor kidney. Patients who received the simultaneous transplant were younger than the living or deceased single graft groups (41 years vs. 45 and 55 years, respectively).

The study controlled for the evolution of surgical techniques and immunosuppressant regimens. Before 1989, all pancreases were transplanted with occluded ducts. From 1989 to 1999, the exocrine duct drained into the bladder, and since 2000, into the intestine. The pancreas has always been connected to the systemic circulation by the iliac artery and vein.

Before 2000, the immunosuppressive regiment consisted of cyclosporine and azathioprine; afterward, tacrolimus and mycophenolate. All patients from both eras take a daily dose of prednisone as well. There was no induction therapy before 2000, Dr. Jenssen said. After that time, patients receiving a single kidney began to receive basiliximab, and the dual-transplant patients got thymoglobulin.

The overall 15-year survival rate was 50% in the simultaneous-graft group, 30% in the living donor kidney group, and 12% in the deceased donor kidney group.

Dr. Jenssen presented two regression models. In the first, which controlled for recipient age, time on dialysis, and the transplant era, patients who got the dual graft were significantly more likely to survive to 15 years than were those who got the single live donor kidney (hazard ratio, 0.70). Patients who received a single deceased donor kidney were 31% less likely to survive (HR, 1.29). These differences were no longer significant in a second model, which also controlled for donor age, but Dr. Jenssen said the difference was not clinically meaningful.

Dr. Jenssen had no financial disclosures.

BERLIN – In patients with type 1 diabetes and end-stage renal disease, a combined pancreas/kidney transplant was associated with significantly better 15-year survival than a single kidney graft alone.

Patients who got the simultaneous transplant were 30% more likely to survive to 15 years than were those who received a living donor kidney. Those patients who got a single kidney from a deceased donor, however, were 30% less likely to survive for 15 years after the operation, Dr. Trond Jenssen said at the annual meeting of the European Associations for the Study of Diabetes.

The combined graft is the preferred method of treating end-stage renal disease (ESRD) caused by diabetic nephropathy, said Dr. Jenssen of Oslo University. Not all patients are suited for it, however.

"According to the algorithm at our center, if you are older than 55 or too sick, you have to decide between the living and deceased donor single kidney graft. Patients who are younger and have less comorbidity are the ones considered for a combined transplant," he said.

Since those who have the dual-organ operation almost always normalize their glycemic values afterward, Dr. Jenssen said, it’s assumed that they will live longer than those who get only a kidney, but studies are divided on the finding.

"The literature over the past 10 years has differed," he said. Comparing studies among institutions is impossible because of the differences in surgical technique and immunosuppressive regimens; the patient populations can also vary widely.

Oslo University is in a unique place to study the issue, Dr. Jenssen suggested. The facility is the national transplant center, with nearly 30 years of full follow-up data on 630 type 1 diabetes patients who were transplanted for ESRD. All of the patients are followed at least annually and their information is entered into the Norwegian Renal Registry.

"Because patients in Norway tend to be very faithful to their doctors, we have not lost a single one of these to follow-up," he said.

Of the entire group, 222 received the simultaneous transplants, 171 received a living donor single kidney, and 237 got a deceased donor kidney. Patients who received the simultaneous transplant were younger than the living or deceased single graft groups (41 years vs. 45 and 55 years, respectively).

The study controlled for the evolution of surgical techniques and immunosuppressant regimens. Before 1989, all pancreases were transplanted with occluded ducts. From 1989 to 1999, the exocrine duct drained into the bladder, and since 2000, into the intestine. The pancreas has always been connected to the systemic circulation by the iliac artery and vein.

Before 2000, the immunosuppressive regiment consisted of cyclosporine and azathioprine; afterward, tacrolimus and mycophenolate. All patients from both eras take a daily dose of prednisone as well. There was no induction therapy before 2000, Dr. Jenssen said. After that time, patients receiving a single kidney began to receive basiliximab, and the dual-transplant patients got thymoglobulin.

The overall 15-year survival rate was 50% in the simultaneous-graft group, 30% in the living donor kidney group, and 12% in the deceased donor kidney group.

Dr. Jenssen presented two regression models. In the first, which controlled for recipient age, time on dialysis, and the transplant era, patients who got the dual graft were significantly more likely to survive to 15 years than were those who got the single live donor kidney (hazard ratio, 0.70). Patients who received a single deceased donor kidney were 31% less likely to survive (HR, 1.29). These differences were no longer significant in a second model, which also controlled for donor age, but Dr. Jenssen said the difference was not clinically meaningful.

Dr. Jenssen had no financial disclosures.

BERLIN – Roux-en-Y gastric bypass surgery can reverse type 2 diabetes in up to 73% of patients – even in those with long-standing disease.

Disease remission even occurred in 38% of those who had diabetes for longer than 8 years, with all who were taking insulin able to discontinue the medication, Dr. Sarah Steven said at the annual meeting of the European Association for the Study of Diabetes.

Dr. Steven, of Newcastle (England) University, presented a retrospective study of 73 patients with type 2 diabetes who underwent gastric bypass surgery with the Roux-en-Y technique.

Most (46) were women; the group’s median age was 49 years. Their median disease duration was 5 years, although the range was wide, from 1 month to 19 years.

She did not give a median follow-up time, but did say that it was a minimum of 3 months.

Overall, they were obese, with a median body mass index of 50 kg/m². Their median preoperative hemoglobin A_1c was 7.1%. Criteria for reversal was a postoperative HbA_1c of 6%.

At baseline, all of the patients were taking metformin and 12 were also on insulin. Other medications included sulphonylurea, thiazolidinedione, glucagon-like peptide-1 agonist, and dipeptidyl peptidase-4 inhibitor.

Diabetes reversal occurred in 79% of those with short-duration disease (up to 4 years); 73% of the patients were able to discontinue all diabetes medications. *Diabetes reversed in 38% of those who had the disease longer than 8 years; 21% of that group no longer needed any antidiabetic medication.

The amount of weight lost was significantly associated with disease reversal. Reversal occurred in 50% of the group that lost fewer than 10 kg/m²; in 73% of those that lost 10-15 kg/m²; and in 76% of those who lost more than 15 kg/m².

In the group with long disease duration, the mean weight loss in those whose diabetes reversed was 34 kg/m², compared with 21 kg/m² in those whose diabetes did not.

Weight loss also significantly influenced the individual ability to successfully withdraw from diabetes medications. About a quarter (27%) of those who lost fewer than 10 kg no longer needed the drugs. However, 67% of those who lost 10-15 kg/m² and 50% of those who lost more than 15 kg/m² no longer needed any of the medications.

"The reversal of type 2 diabetes seems to depend on the degree of weight loss," Dr. Steven said. "Individuals with long-term diabetes are likely to have gained more weight than those with short-term – this is in part due to the natural history of the disease and is compounded by the use of medications and insulin therapy.

"It’s hypothesized that these individuals may need to lose more weight to reach the target weight that will normalize their glucose levels."

The benefit of weight loss is most likely tied to improved beta cell functioning, Dr. Steven suggested.

"There is good in vitro evidence that saturated fatty acids are particularly detrimental to beta cells, inhibiting acute insulin secretion and inducing apoptosis," she said.

"Autopsy studies have shown that beta cells continue replication and neogenesis [in type 2 diabetes]," Dr. Steven continued. "So it’s at least theoretically possible that beta cell function could be regained at any stage of the disease upon removal of the toxic environment."

*CORRECTION 10/26/12: This article misstated the percentage of long-term diabetes patients (having the disease more than 8 years)who experienced disease reversal. Diabetes reversed in 38% of this population.

BERLIN – Roux-en-Y gastric bypass surgery can reverse type 2 diabetes in up to 73% of patients – even in those with long-standing disease.

Disease remission even occurred in 38% of those who had diabetes for longer than 8 years, with all who were taking insulin able to discontinue the medication, Dr. Sarah Steven said at the annual meeting of the European Association for the Study of Diabetes.

Dr. Steven, of Newcastle (England) University, presented a retrospective study of 73 patients with type 2 diabetes who underwent gastric bypass surgery with the Roux-en-Y technique.

Most (46) were women; the group’s median age was 49 years. Their median disease duration was 5 years, although the range was wide, from 1 month to 19 years.

She did not give a median follow-up time, but did say that it was a minimum of 3 months.

Overall, they were obese, with a median body mass index of 50 kg/m². Their median preoperative hemoglobin A_1c was 7.1%. Criteria for reversal was a postoperative HbA_1c of 6%.

At baseline, all of the patients were taking metformin and 12 were also on insulin. Other medications included sulphonylurea, thiazolidinedione, glucagon-like peptide-1 agonist, and dipeptidyl peptidase-4 inhibitor.

Diabetes reversal occurred in 79% of those with short-duration disease (up to 4 years); 73% of the patients were able to discontinue all diabetes medications. *Diabetes reversed in 38% of those who had the disease longer than 8 years; 21% of that group no longer needed any antidiabetic medication.

The amount of weight lost was significantly associated with disease reversal. Reversal occurred in 50% of the group that lost fewer than 10 kg/m²; in 73% of those that lost 10-15 kg/m²; and in 76% of those who lost more than 15 kg/m².

In the group with long disease duration, the mean weight loss in those whose diabetes reversed was 34 kg/m², compared with 21 kg/m² in those whose diabetes did not.

Weight loss also significantly influenced the individual ability to successfully withdraw from diabetes medications. About a quarter (27%) of those who lost fewer than 10 kg no longer needed the drugs. However, 67% of those who lost 10-15 kg/m² and 50% of those who lost more than 15 kg/m² no longer needed any of the medications.

"The reversal of type 2 diabetes seems to depend on the degree of weight loss," Dr. Steven said. "Individuals with long-term diabetes are likely to have gained more weight than those with short-term – this is in part due to the natural history of the disease and is compounded by the use of medications and insulin therapy.

"It’s hypothesized that these individuals may need to lose more weight to reach the target weight that will normalize their glucose levels."

The benefit of weight loss is most likely tied to improved beta cell functioning, Dr. Steven suggested.

"There is good in vitro evidence that saturated fatty acids are particularly detrimental to beta cells, inhibiting acute insulin secretion and inducing apoptosis," she said.

"Autopsy studies have shown that beta cells continue replication and neogenesis [in type 2 diabetes]," Dr. Steven continued. "So it’s at least theoretically possible that beta cell function could be regained at any stage of the disease upon removal of the toxic environment."

*CORRECTION 10/26/12: This article misstated the percentage of long-term diabetes patients (having the disease more than 8 years)who experienced disease reversal. Diabetes reversed in 38% of this population.

BERLIN – Roux-en-Y gastric bypass surgery can reverse type 2 diabetes in up to 73% of patients – even in those with long-standing disease.

Disease remission even occurred in 38% of those who had diabetes for longer than 8 years, with all who were taking insulin able to discontinue the medication, Dr. Sarah Steven said at the annual meeting of the European Association for the Study of Diabetes.

Dr. Steven, of Newcastle (England) University, presented a retrospective study of 73 patients with type 2 diabetes who underwent gastric bypass surgery with the Roux-en-Y technique.

Most (46) were women; the group’s median age was 49 years. Their median disease duration was 5 years, although the range was wide, from 1 month to 19 years.

She did not give a median follow-up time, but did say that it was a minimum of 3 months.

Overall, they were obese, with a median body mass index of 50 kg/m². Their median preoperative hemoglobin A_1c was 7.1%. Criteria for reversal was a postoperative HbA_1c of 6%.

At baseline, all of the patients were taking metformin and 12 were also on insulin. Other medications included sulphonylurea, thiazolidinedione, glucagon-like peptide-1 agonist, and dipeptidyl peptidase-4 inhibitor.

Diabetes reversal occurred in 79% of those with short-duration disease (up to 4 years); 73% of the patients were able to discontinue all diabetes medications. *Diabetes reversed in 38% of those who had the disease longer than 8 years; 21% of that group no longer needed any antidiabetic medication.

The amount of weight lost was significantly associated with disease reversal. Reversal occurred in 50% of the group that lost fewer than 10 kg/m²; in 73% of those that lost 10-15 kg/m²; and in 76% of those who lost more than 15 kg/m².

In the group with long disease duration, the mean weight loss in those whose diabetes reversed was 34 kg/m², compared with 21 kg/m² in those whose diabetes did not.

Weight loss also significantly influenced the individual ability to successfully withdraw from diabetes medications. About a quarter (27%) of those who lost fewer than 10 kg no longer needed the drugs. However, 67% of those who lost 10-15 kg/m² and 50% of those who lost more than 15 kg/m² no longer needed any of the medications.

"The reversal of type 2 diabetes seems to depend on the degree of weight loss," Dr. Steven said. "Individuals with long-term diabetes are likely to have gained more weight than those with short-term – this is in part due to the natural history of the disease and is compounded by the use of medications and insulin therapy.

"It’s hypothesized that these individuals may need to lose more weight to reach the target weight that will normalize their glucose levels."

The benefit of weight loss is most likely tied to improved beta cell functioning, Dr. Steven suggested.

"There is good in vitro evidence that saturated fatty acids are particularly detrimental to beta cells, inhibiting acute insulin secretion and inducing apoptosis," she said.

"Autopsy studies have shown that beta cells continue replication and neogenesis [in type 2 diabetes]," Dr. Steven continued. "So it’s at least theoretically possible that beta cell function could be regained at any stage of the disease upon removal of the toxic environment."

*CORRECTION 10/26/12: This article misstated the percentage of long-term diabetes patients (having the disease more than 8 years)who experienced disease reversal. Diabetes reversed in 38% of this population.

BERLIN – Adding insulin degludec to an existing oral antidiabetes regimen produced significantly better glycemic control than did adding sitagliptin in the first head-to-head trial of the two drug classes in patients with type 2 diabetes.

After 26 weeks, patients who received insulin degludec as part of their regimen had an average 0.43% added reduction in their hemoglobin A_1c level, compared with patients on sitagliptin, a dipeptidyl peptidase 4 (DDP-4) inhibitor, in a multicenter, randomized study with 447 patients, Dr. Athena Philis-Tsimikas said at the meeting.

The main downside of the degludec regimen was an increased incidence of hypoglycemic episodes, with a 43% rate of confirmed hypoglycemic events among patients on insulin compared with a 13% rate among those who got sitagliptin. But just one degludec patient had a severe hypoglycemic event (none occurred among patients in the sitagliptin arm), said Dr. Philis-Tsimikas, an endocrinologist and chief medical officer at the Scripps Whittier Diabetes Institute in La Jolla, Calif.

Novo Nordisk, the company developing insulin degludec, currently has an application for approval of the drug pending with the Food and Drug Administration. Earlier this year, the company said that an FDA advisory committee was scheduled to consider the application in November. The data reported by Dr. Philis-Tsimikas forms part of the application.

"The results say that if a patient is failing [antidiabetes treatment] on one or two oral drugs, and their [Hb]A_1c is considerably below 9%, then a DDP-4 inhibitor is reasonable, but for efficacy insulin is probably a better choice," commented Dr. John L. Leahy, a professor and co-director of the division of endocrinology, diabetes, and metabolism at the University of Vermont in Colchester.

"Sitagliptin is a good comparator because when patients fail on one or two oral drugs the decision is often whether to add another oral drug or treat with insulin," Dr. Leahy said in an interview. "Some physicians then use a DPP-4 inhibitor, possibly inappropriately because the patient hemoglobin A_1c level is too high and the DDP-4 is not powerful enough. The message should go out to prescribing physicians that a DPP-4 inhibitor is not going to get your patient to goal unless their [Hb]A_1c is considerably lower than 9%."

The study enrolled patients with type 2 diabetes never previously treated with insulin whose HbA_1c levels remained at or above 7.5% despite treatment with one or two oral antidiabetes drugs for at least 3 months. The patients averaged about 56 years old, their average body mass index was about 30 kg/m², and their average HbA_1c at enrollment was about 9%. The researchers randomized patients to received 100 mg/day sitagliptin, or insulin degludec starting at a daily dosage of 10 U and titrated to achieve a prebreakfast plasma glucose of 4.0-4.9 mmol/L (71-89 mg/dL). Patients received insulin degludec once a day; they could choose the time of day to take their insulin, and although they had to keep to their dosing schedule they had the option to change their time of daily insulin treatment during the study.

After 26 weeks, the average HbA_1c level fell by about 1.6% in the 225 insulin-treated patients and by about 1.15% in the 222 sitagliptin-treated patients, an average difference in the amount of reduction of 0.43% that was statistically significant for the study’s primary end point. Treatment with insulin degludec led to an average reduction of fasting plasma glucose of 2.17 mmol/L compared with the reduction in the sitagliptin arm.

In addition to causing more hypoglycemic events, treatment with insulin degludec also produced an average weight gain of about 2.5 kg, compared with a slight weight loss in the sitagliptin-treated patients. Overall, treatment with insulin degludec produced an average 2.75 kg increase in weight compared with sitagliptin, a statistically significant difference. The incidence of all other adverse events was similar in the two treatment groups.

The study was sponsored by Novo Nordisk, the company that is developing insulin degludec. Dr. Philis-Tsimikas said that she has been an adviser to and speaker for and has received research funding from Novo Nordisk and from several other drug companies. Dr. Leahy said that he has been an adviser to Novo Nordisk and Merck.

BERLIN – Adding insulin degludec to an existing oral antidiabetes regimen produced significantly better glycemic control than did adding sitagliptin in the first head-to-head trial of the two drug classes in patients with type 2 diabetes.

After 26 weeks, patients who received insulin degludec as part of their regimen had an average 0.43% added reduction in their hemoglobin A_1c level, compared with patients on sitagliptin, a dipeptidyl peptidase 4 (DDP-4) inhibitor, in a multicenter, randomized study with 447 patients, Dr. Athena Philis-Tsimikas said at the meeting.

The main downside of the degludec regimen was an increased incidence of hypoglycemic episodes, with a 43% rate of confirmed hypoglycemic events among patients on insulin compared with a 13% rate among those who got sitagliptin. But just one degludec patient had a severe hypoglycemic event (none occurred among patients in the sitagliptin arm), said Dr. Philis-Tsimikas, an endocrinologist and chief medical officer at the Scripps Whittier Diabetes Institute in La Jolla, Calif.

Novo Nordisk, the company developing insulin degludec, currently has an application for approval of the drug pending with the Food and Drug Administration. Earlier this year, the company said that an FDA advisory committee was scheduled to consider the application in November. The data reported by Dr. Philis-Tsimikas forms part of the application.

"The results say that if a patient is failing [antidiabetes treatment] on one or two oral drugs, and their [Hb]A_1c is considerably below 9%, then a DDP-4 inhibitor is reasonable, but for efficacy insulin is probably a better choice," commented Dr. John L. Leahy, a professor and co-director of the division of endocrinology, diabetes, and metabolism at the University of Vermont in Colchester.

"Sitagliptin is a good comparator because when patients fail on one or two oral drugs the decision is often whether to add another oral drug or treat with insulin," Dr. Leahy said in an interview. "Some physicians then use a DPP-4 inhibitor, possibly inappropriately because the patient hemoglobin A_1c level is too high and the DDP-4 is not powerful enough. The message should go out to prescribing physicians that a DPP-4 inhibitor is not going to get your patient to goal unless their [Hb]A_1c is considerably lower than 9%."

The study enrolled patients with type 2 diabetes never previously treated with insulin whose HbA_1c levels remained at or above 7.5% despite treatment with one or two oral antidiabetes drugs for at least 3 months. The patients averaged about 56 years old, their average body mass index was about 30 kg/m², and their average HbA_1c at enrollment was about 9%. The researchers randomized patients to received 100 mg/day sitagliptin, or insulin degludec starting at a daily dosage of 10 U and titrated to achieve a prebreakfast plasma glucose of 4.0-4.9 mmol/L (71-89 mg/dL). Patients received insulin degludec once a day; they could choose the time of day to take their insulin, and although they had to keep to their dosing schedule they had the option to change their time of daily insulin treatment during the study.

After 26 weeks, the average HbA_1c level fell by about 1.6% in the 225 insulin-treated patients and by about 1.15% in the 222 sitagliptin-treated patients, an average difference in the amount of reduction of 0.43% that was statistically significant for the study’s primary end point. Treatment with insulin degludec led to an average reduction of fasting plasma glucose of 2.17 mmol/L compared with the reduction in the sitagliptin arm.

In addition to causing more hypoglycemic events, treatment with insulin degludec also produced an average weight gain of about 2.5 kg, compared with a slight weight loss in the sitagliptin-treated patients. Overall, treatment with insulin degludec produced an average 2.75 kg increase in weight compared with sitagliptin, a statistically significant difference. The incidence of all other adverse events was similar in the two treatment groups.

The study was sponsored by Novo Nordisk, the company that is developing insulin degludec. Dr. Philis-Tsimikas said that she has been an adviser to and speaker for and has received research funding from Novo Nordisk and from several other drug companies. Dr. Leahy said that he has been an adviser to Novo Nordisk and Merck.

BERLIN – Adding insulin degludec to an existing oral antidiabetes regimen produced significantly better glycemic control than did adding sitagliptin in the first head-to-head trial of the two drug classes in patients with type 2 diabetes.

After 26 weeks, patients who received insulin degludec as part of their regimen had an average 0.43% added reduction in their hemoglobin A_1c level, compared with patients on sitagliptin, a dipeptidyl peptidase 4 (DDP-4) inhibitor, in a multicenter, randomized study with 447 patients, Dr. Athena Philis-Tsimikas said at the meeting.

The main downside of the degludec regimen was an increased incidence of hypoglycemic episodes, with a 43% rate of confirmed hypoglycemic events among patients on insulin compared with a 13% rate among those who got sitagliptin. But just one degludec patient had a severe hypoglycemic event (none occurred among patients in the sitagliptin arm), said Dr. Philis-Tsimikas, an endocrinologist and chief medical officer at the Scripps Whittier Diabetes Institute in La Jolla, Calif.

Novo Nordisk, the company developing insulin degludec, currently has an application for approval of the drug pending with the Food and Drug Administration. Earlier this year, the company said that an FDA advisory committee was scheduled to consider the application in November. The data reported by Dr. Philis-Tsimikas forms part of the application.

"The results say that if a patient is failing [antidiabetes treatment] on one or two oral drugs, and their [Hb]A_1c is considerably below 9%, then a DDP-4 inhibitor is reasonable, but for efficacy insulin is probably a better choice," commented Dr. John L. Leahy, a professor and co-director of the division of endocrinology, diabetes, and metabolism at the University of Vermont in Colchester.

"Sitagliptin is a good comparator because when patients fail on one or two oral drugs the decision is often whether to add another oral drug or treat with insulin," Dr. Leahy said in an interview. "Some physicians then use a DPP-4 inhibitor, possibly inappropriately because the patient hemoglobin A_1c level is too high and the DDP-4 is not powerful enough. The message should go out to prescribing physicians that a DPP-4 inhibitor is not going to get your patient to goal unless their [Hb]A_1c is considerably lower than 9%."

The study enrolled patients with type 2 diabetes never previously treated with insulin whose HbA_1c levels remained at or above 7.5% despite treatment with one or two oral antidiabetes drugs for at least 3 months. The patients averaged about 56 years old, their average body mass index was about 30 kg/m², and their average HbA_1c at enrollment was about 9%. The researchers randomized patients to received 100 mg/day sitagliptin, or insulin degludec starting at a daily dosage of 10 U and titrated to achieve a prebreakfast plasma glucose of 4.0-4.9 mmol/L (71-89 mg/dL). Patients received insulin degludec once a day; they could choose the time of day to take their insulin, and although they had to keep to their dosing schedule they had the option to change their time of daily insulin treatment during the study.

After 26 weeks, the average HbA_1c level fell by about 1.6% in the 225 insulin-treated patients and by about 1.15% in the 222 sitagliptin-treated patients, an average difference in the amount of reduction of 0.43% that was statistically significant for the study’s primary end point. Treatment with insulin degludec led to an average reduction of fasting plasma glucose of 2.17 mmol/L compared with the reduction in the sitagliptin arm.

In addition to causing more hypoglycemic events, treatment with insulin degludec also produced an average weight gain of about 2.5 kg, compared with a slight weight loss in the sitagliptin-treated patients. Overall, treatment with insulin degludec produced an average 2.75 kg increase in weight compared with sitagliptin, a statistically significant difference. The incidence of all other adverse events was similar in the two treatment groups.

The study was sponsored by Novo Nordisk, the company that is developing insulin degludec. Dr. Philis-Tsimikas said that she has been an adviser to and speaker for and has received research funding from Novo Nordisk and from several other drug companies. Dr. Leahy said that he has been an adviser to Novo Nordisk and Merck.

BERLIN – Patients who had suboptimal glycemic control and reduced their hemoglobin A_1c value by slightly less than 1% were 50% less likely to die within 5 years than were patients whose HbA_1c did not improve, Dr. Katarina Eeg-Olofsson reported.

At 5 years, all-cause mortality was 15% among the group with no improvement in HbA_1c and 10% in the group with improved HbA_1c in an observational study of 12,359 patients with poorly controlled type 2 diabetes at baseline. The patients were selected from the Swedish National Diabetes Registry and their outcomes were verified by the Swedish Cause of Death and Hospital Registries. None of the patients had any cardiovascular or coronary heart disease at baseline.

After adjusting for baseline risk factors and treatment changes during the study period, patients whose HbA_1c decreased were half as likely to develop cardiovascular or coronary heart disease as were those whose levels increased. They were also 33% less likely to experience fatal cardiovascular disease and 41% less likely to die from any cause than were those in the poorly controlled group. All of these differences were statistically significant, she said at the annual meeting of the European Association for the Study of Diabetes.

"Patients with poorly controlled blood glucose clearly benefit" from gaining and improving glycemic control, said Dr. Eeg-Olofsson of the University of Gothenburg, Sweden. "We must make an effort to identify patients who don’t respond to diabetes medications earlier."

For the study, Dr. Eeg-Olofssson separated the patients into two groups: Those whose HbA_1c decreased by at least 0.1% over the 5 years (6,841) and those whose HbA_1c remained stable or increased by at least 0.1% (5,518).

At baseline, the patients averaged 62 years old, with mean disease duration of 9 years. Their average baseline HbA_1c was 7.8%, and their mean body mass index was 30 kg/m². Their mean blood pressure was 140/78 mmHg; 62% were taking antihypertensives and 46% were on lipid-lowering drugs.

After 5 years, mean HbA_1c was 7% in the improved-control group (-0.8%) and 8.4% in the poorly controlled group (+0.7%), she said.

By then, 12% of the well-controlled group and 20% of the poorly controlled group had developed coronary heart disease. Cardiovascular disease was present in 17% of those in the well-controlled group and 30% of the poorly controlled group. Both these findings were statistically significant.

Dr. Eeg-Olofssson had no financial disclosures.

BERLIN – Patients who had suboptimal glycemic control and reduced their hemoglobin A_1c value by slightly less than 1% were 50% less likely to die within 5 years than were patients whose HbA_1c did not improve, Dr. Katarina Eeg-Olofsson reported.

At 5 years, all-cause mortality was 15% among the group with no improvement in HbA_1c and 10% in the group with improved HbA_1c in an observational study of 12,359 patients with poorly controlled type 2 diabetes at baseline. The patients were selected from the Swedish National Diabetes Registry and their outcomes were verified by the Swedish Cause of Death and Hospital Registries. None of the patients had any cardiovascular or coronary heart disease at baseline.

After adjusting for baseline risk factors and treatment changes during the study period, patients whose HbA_1c decreased were half as likely to develop cardiovascular or coronary heart disease as were those whose levels increased. They were also 33% less likely to experience fatal cardiovascular disease and 41% less likely to die from any cause than were those in the poorly controlled group. All of these differences were statistically significant, she said at the annual meeting of the European Association for the Study of Diabetes.

"Patients with poorly controlled blood glucose clearly benefit" from gaining and improving glycemic control, said Dr. Eeg-Olofsson of the University of Gothenburg, Sweden. "We must make an effort to identify patients who don’t respond to diabetes medications earlier."

For the study, Dr. Eeg-Olofssson separated the patients into two groups: Those whose HbA_1c decreased by at least 0.1% over the 5 years (6,841) and those whose HbA_1c remained stable or increased by at least 0.1% (5,518).

At baseline, the patients averaged 62 years old, with mean disease duration of 9 years. Their average baseline HbA_1c was 7.8%, and their mean body mass index was 30 kg/m². Their mean blood pressure was 140/78 mmHg; 62% were taking antihypertensives and 46% were on lipid-lowering drugs.

After 5 years, mean HbA_1c was 7% in the improved-control group (-0.8%) and 8.4% in the poorly controlled group (+0.7%), she said.

By then, 12% of the well-controlled group and 20% of the poorly controlled group had developed coronary heart disease. Cardiovascular disease was present in 17% of those in the well-controlled group and 30% of the poorly controlled group. Both these findings were statistically significant.

Dr. Eeg-Olofssson had no financial disclosures.

BERLIN – Patients who had suboptimal glycemic control and reduced their hemoglobin A_1c value by slightly less than 1% were 50% less likely to die within 5 years than were patients whose HbA_1c did not improve, Dr. Katarina Eeg-Olofsson reported.

At 5 years, all-cause mortality was 15% among the group with no improvement in HbA_1c and 10% in the group with improved HbA_1c in an observational study of 12,359 patients with poorly controlled type 2 diabetes at baseline. The patients were selected from the Swedish National Diabetes Registry and their outcomes were verified by the Swedish Cause of Death and Hospital Registries. None of the patients had any cardiovascular or coronary heart disease at baseline.

After adjusting for baseline risk factors and treatment changes during the study period, patients whose HbA_1c decreased were half as likely to develop cardiovascular or coronary heart disease as were those whose levels increased. They were also 33% less likely to experience fatal cardiovascular disease and 41% less likely to die from any cause than were those in the poorly controlled group. All of these differences were statistically significant, she said at the annual meeting of the European Association for the Study of Diabetes.

"Patients with poorly controlled blood glucose clearly benefit" from gaining and improving glycemic control, said Dr. Eeg-Olofsson of the University of Gothenburg, Sweden. "We must make an effort to identify patients who don’t respond to diabetes medications earlier."

For the study, Dr. Eeg-Olofssson separated the patients into two groups: Those whose HbA_1c decreased by at least 0.1% over the 5 years (6,841) and those whose HbA_1c remained stable or increased by at least 0.1% (5,518).

At baseline, the patients averaged 62 years old, with mean disease duration of 9 years. Their average baseline HbA_1c was 7.8%, and their mean body mass index was 30 kg/m². Their mean blood pressure was 140/78 mmHg; 62% were taking antihypertensives and 46% were on lipid-lowering drugs.

After 5 years, mean HbA_1c was 7% in the improved-control group (-0.8%) and 8.4% in the poorly controlled group (+0.7%), she said.

By then, 12% of the well-controlled group and 20% of the poorly controlled group had developed coronary heart disease. Cardiovascular disease was present in 17% of those in the well-controlled group and 30% of the poorly controlled group. Both these findings were statistically significant.

Dr. Eeg-Olofssson had no financial disclosures.

BERLIN – Vitamin D deficiency during the first trimester of pregnancy linked with a significantly increased risk for the development of gestational diabetes by the second trimester in a study of 655 pregnant women.

The study results also indicated that increased insulin resistance explained the significant association between vitamin D deficiency and an increased incidence of gestational diabetes, Marilyn Lacroix said at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

The analysis showed that for every standard-deviation decrease in blood levels of 25-hydroxyvitamin D identified during the first trimester, women had a statistically significant 40% increased rate of having gestational diabetes during their second trimester, after adjustment for age, season of blood sampling, use of vitamin D supplements, and degree of adiposity, reported Ms. Lacroix, an endocrinology researcher at Sherbrooke (Que.) University. In the population studied, a standard-deviation reduction in blood levels of vitamin D corresponded to a drop of 19 nmol/L.

The study included 655 pregnant women aged 18 or older at 6-13 weeks’ gestation with a singleton pregnancy and no history of diabetes or gestational diabetes, miscarriage, or alcohol or drug abuse. The researchers measured each woman’s blood level of 25-hydroxyvitamin D at gestational week 6-13, and then assessed each woman for diabetes at week 24-28. During the study, 54 of the women (8%) developed gestational diabetes.

The prevalence of first-trimester vitamin D deficiency – a blood level of less than 50 nmol/L – was 26% among the 601 women who were normoglycemic during the second trimester, and 37% among women who developed gestational diabetes by the second trimester.

The analysis also showed a significantly reduced average Matsuda index (Diabetes Care 1999;22:1462-70), as well as a significantly reduced insulin secretion sensitivity index (Diabetic Medicine 2009;26:1198-1203) among patients who went on to have gestational diabetes. These reductions suggest that insulin resistance forms the link between low vitamin D levels and incident gestational diabetes, Ms. Lacroix said.

Ms. Lacroix reported that she and her associates also had no relevant financial disclosures.

BERLIN – Vitamin D deficiency during the first trimester of pregnancy linked with a significantly increased risk for the development of gestational diabetes by the second trimester in a study of 655 pregnant women.

The study results also indicated that increased insulin resistance explained the significant association between vitamin D deficiency and an increased incidence of gestational diabetes, Marilyn Lacroix said at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

The analysis showed that for every standard-deviation decrease in blood levels of 25-hydroxyvitamin D identified during the first trimester, women had a statistically significant 40% increased rate of having gestational diabetes during their second trimester, after adjustment for age, season of blood sampling, use of vitamin D supplements, and degree of adiposity, reported Ms. Lacroix, an endocrinology researcher at Sherbrooke (Que.) University. In the population studied, a standard-deviation reduction in blood levels of vitamin D corresponded to a drop of 19 nmol/L.

The study included 655 pregnant women aged 18 or older at 6-13 weeks’ gestation with a singleton pregnancy and no history of diabetes or gestational diabetes, miscarriage, or alcohol or drug abuse. The researchers measured each woman’s blood level of 25-hydroxyvitamin D at gestational week 6-13, and then assessed each woman for diabetes at week 24-28. During the study, 54 of the women (8%) developed gestational diabetes.

The prevalence of first-trimester vitamin D deficiency – a blood level of less than 50 nmol/L – was 26% among the 601 women who were normoglycemic during the second trimester, and 37% among women who developed gestational diabetes by the second trimester.

The analysis also showed a significantly reduced average Matsuda index (Diabetes Care 1999;22:1462-70), as well as a significantly reduced insulin secretion sensitivity index (Diabetic Medicine 2009;26:1198-1203) among patients who went on to have gestational diabetes. These reductions suggest that insulin resistance forms the link between low vitamin D levels and incident gestational diabetes, Ms. Lacroix said.

Ms. Lacroix reported that she and her associates also had no relevant financial disclosures.

BERLIN – Vitamin D deficiency during the first trimester of pregnancy linked with a significantly increased risk for the development of gestational diabetes by the second trimester in a study of 655 pregnant women.

The study results also indicated that increased insulin resistance explained the significant association between vitamin D deficiency and an increased incidence of gestational diabetes, Marilyn Lacroix said at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

The analysis showed that for every standard-deviation decrease in blood levels of 25-hydroxyvitamin D identified during the first trimester, women had a statistically significant 40% increased rate of having gestational diabetes during their second trimester, after adjustment for age, season of blood sampling, use of vitamin D supplements, and degree of adiposity, reported Ms. Lacroix, an endocrinology researcher at Sherbrooke (Que.) University. In the population studied, a standard-deviation reduction in blood levels of vitamin D corresponded to a drop of 19 nmol/L.

The study included 655 pregnant women aged 18 or older at 6-13 weeks’ gestation with a singleton pregnancy and no history of diabetes or gestational diabetes, miscarriage, or alcohol or drug abuse. The researchers measured each woman’s blood level of 25-hydroxyvitamin D at gestational week 6-13, and then assessed each woman for diabetes at week 24-28. During the study, 54 of the women (8%) developed gestational diabetes.

The prevalence of first-trimester vitamin D deficiency – a blood level of less than 50 nmol/L – was 26% among the 601 women who were normoglycemic during the second trimester, and 37% among women who developed gestational diabetes by the second trimester.

The analysis also showed a significantly reduced average Matsuda index (Diabetes Care 1999;22:1462-70), as well as a significantly reduced insulin secretion sensitivity index (Diabetic Medicine 2009;26:1198-1203) among patients who went on to have gestational diabetes. These reductions suggest that insulin resistance forms the link between low vitamin D levels and incident gestational diabetes, Ms. Lacroix said.

Ms. Lacroix reported that she and her associates also had no relevant financial disclosures.