AACE 2012

PHILADELPHIA – The investigational ultralong-acting insulin, degludec, improved glycemic control while incurring lower risks of hypoglycemia in several studies of diabetes patients, many of them obese with high insulin requirements.

Novo Nordisk’s insulin degludec (IDeg), which is under consideration for approval by the Food and Drug Administration, is a basal insulin that forms soluble multihexamers after subcutaneous injection, extending its half-life significantly longer than 24 hours. The resulting steady blood levels of insulin confer a significantly lower risk of hypoglycemia in type 1 and type 2 patients taking degludec, compared with those taking insulin glargine, the comparator in many clinical trials, according to Dr. Helena W. Rodbard, an endocrinologist who practices in Rockville, Md.

About a third of patients with type 2 diabetes in the United States require more than 60 U just as the basal component, with quite a few requiring 80 or 100 U of insulin, noted Dr. Richard M. Bergenstal, executive director of the International Diabetes Center at Park Nicollet, Minneapolis. This demand for ever-increasing units has led to the development of new basal insulins that are even longer-acting, smoother, and flatter in terms of their pharmacokinetic and pharmacodynamic profiles, he said.

Dr. Rodbard presented the results of a meta-analysis of five phase IIIA, open-label, randomized, treat-to-target, confirmatory, 26- or 52-week trials in which a total of 2,262 type 2 diabetes patients received degludec and 1,110 received glargine, both injected once daily. Among those, 35% of the degludec group and 34% of the glargine group required more than 60 U of basal insulin per day by the end of the trials.

At study completion, hemoglobin A_1c values were similar in both groups, with an insignificant estimated treatment difference (ETD) of just 0.05% (P = .44). The mean fasting plasma glucose values at the end of the trials were lower with degludec than with glargine, with an ETD of –5.9 mg/dL, Dr. Rodbard reported.

Overall confirmed and nocturnal hypoglycemia rates were lower in patients requiring more than 60 U of insulin on degludec than on glargine, with confirmed hypoglycemia defined as self-measured blood glucose less than 56 mg/dL (plasma calibrated) or any episode requiring assistance. Nocturnal confirmed hypoglycemia was defined as any confirmed episode with onset between midnight and 6:00 a.m.

Compared with glargine, there was a 21% lower rate of overall confirmed hypoglycemic episodes with degludec (P = .02) and a 52% lower rate of nocturnal confirmed hypoglycemic episodes (P less than.0001).

The reduction of risk of hypoglycemia with degludec was particularly significant for nocturnal hypoglycemia, the "important area of concern," Dr. Rodbard said in an interview.

Novo Nordisk is also developing a 200 U/mL formulation of insulin degludec specifically for patients with high insulin requirements. This formulation, known as IDeg U200, contains equal units of insulin in half the volume of the 100-U/mL formulation, thus allowing larger insulin doses (up to 160 U) to be administered in a single injection with a prefilled pen device.

Dr. Bergenstal presented data from a 26-week, open-label, treat-to-target trial that compared the efficacy and safety of once-daily IDeg U200 vs. 100 U/mL of insulin glargine, both in combination with oral antidiabetic drugs, in a total of 457 insulin-naive type 2 diabetes patients who qualified for insulin treatment. They were randomized to either IDeg U200 or glargine, both in combination with metformin and some also using other medications.

By 26 weeks, IDeg U200 reduced HbA_1c by 1.30 percentage points (from a baseline of 8.3%) and was noninferior to glargine, with an estimated treatment difference of 0.04 percentage points.

Fasting glucose levels were similarly equally reduced. Rates of overall confirmed hypoglycemia (defined as less than 56 mg/dL, or having an episode requiring assistance) were lower with IDeg U200, at 1.22 episodes per patient per year, compared with 1.42 for glargine.

Rates of nocturnal confirmed hypoglycemia (defined as occurring between midnight and 6:00 a.m.) also were lower with IDeg U200 (0.18 vs. 0.28 episodes per patient-year, respectively). There were no severe hypoglycemic reactions in either group.

Mean daily basal insulin dose was similar after 26 weeks (0.62 U/kg for IDeg U200; 0.66 U/Kg for glargine). Weight gain occurred with a reduction in HbA_1c in both groups, by 1.9 kg with IDeg U200 and 1.5 kg with glargine. Adverse events were similar and infrequent in both groups, said Dr. Bergenstal, who is the president of medicine and science at the American Diabetes Association.

"Insulin degludec 200 U/mL allows patients who require larger daily doses of basal insulin [to] use prefilled pen devices to administer up to 160 U in a single injection," he concluded.

All of the reported studies were funded by Novo Nordisk.

PHILADELPHIA – The investigational ultralong-acting insulin, degludec, improved glycemic control while incurring lower risks of hypoglycemia in several studies of diabetes patients, many of them obese with high insulin requirements.

Novo Nordisk’s insulin degludec (IDeg), which is under consideration for approval by the Food and Drug Administration, is a basal insulin that forms soluble multihexamers after subcutaneous injection, extending its half-life significantly longer than 24 hours. The resulting steady blood levels of insulin confer a significantly lower risk of hypoglycemia in type 1 and type 2 patients taking degludec, compared with those taking insulin glargine, the comparator in many clinical trials, according to Dr. Helena W. Rodbard, an endocrinologist who practices in Rockville, Md.

About a third of patients with type 2 diabetes in the United States require more than 60 U just as the basal component, with quite a few requiring 80 or 100 U of insulin, noted Dr. Richard M. Bergenstal, executive director of the International Diabetes Center at Park Nicollet, Minneapolis. This demand for ever-increasing units has led to the development of new basal insulins that are even longer-acting, smoother, and flatter in terms of their pharmacokinetic and pharmacodynamic profiles, he said.

Dr. Rodbard presented the results of a meta-analysis of five phase IIIA, open-label, randomized, treat-to-target, confirmatory, 26- or 52-week trials in which a total of 2,262 type 2 diabetes patients received degludec and 1,110 received glargine, both injected once daily. Among those, 35% of the degludec group and 34% of the glargine group required more than 60 U of basal insulin per day by the end of the trials.

At study completion, hemoglobin A_1c values were similar in both groups, with an insignificant estimated treatment difference (ETD) of just 0.05% (P = .44). The mean fasting plasma glucose values at the end of the trials were lower with degludec than with glargine, with an ETD of –5.9 mg/dL, Dr. Rodbard reported.

Overall confirmed and nocturnal hypoglycemia rates were lower in patients requiring more than 60 U of insulin on degludec than on glargine, with confirmed hypoglycemia defined as self-measured blood glucose less than 56 mg/dL (plasma calibrated) or any episode requiring assistance. Nocturnal confirmed hypoglycemia was defined as any confirmed episode with onset between midnight and 6:00 a.m.

Compared with glargine, there was a 21% lower rate of overall confirmed hypoglycemic episodes with degludec (P = .02) and a 52% lower rate of nocturnal confirmed hypoglycemic episodes (P less than.0001).

The reduction of risk of hypoglycemia with degludec was particularly significant for nocturnal hypoglycemia, the "important area of concern," Dr. Rodbard said in an interview.

Novo Nordisk is also developing a 200 U/mL formulation of insulin degludec specifically for patients with high insulin requirements. This formulation, known as IDeg U200, contains equal units of insulin in half the volume of the 100-U/mL formulation, thus allowing larger insulin doses (up to 160 U) to be administered in a single injection with a prefilled pen device.

Dr. Bergenstal presented data from a 26-week, open-label, treat-to-target trial that compared the efficacy and safety of once-daily IDeg U200 vs. 100 U/mL of insulin glargine, both in combination with oral antidiabetic drugs, in a total of 457 insulin-naive type 2 diabetes patients who qualified for insulin treatment. They were randomized to either IDeg U200 or glargine, both in combination with metformin and some also using other medications.

By 26 weeks, IDeg U200 reduced HbA_1c by 1.30 percentage points (from a baseline of 8.3%) and was noninferior to glargine, with an estimated treatment difference of 0.04 percentage points.

Fasting glucose levels were similarly equally reduced. Rates of overall confirmed hypoglycemia (defined as less than 56 mg/dL, or having an episode requiring assistance) were lower with IDeg U200, at 1.22 episodes per patient per year, compared with 1.42 for glargine.

Rates of nocturnal confirmed hypoglycemia (defined as occurring between midnight and 6:00 a.m.) also were lower with IDeg U200 (0.18 vs. 0.28 episodes per patient-year, respectively). There were no severe hypoglycemic reactions in either group.

Mean daily basal insulin dose was similar after 26 weeks (0.62 U/kg for IDeg U200; 0.66 U/Kg for glargine). Weight gain occurred with a reduction in HbA_1c in both groups, by 1.9 kg with IDeg U200 and 1.5 kg with glargine. Adverse events were similar and infrequent in both groups, said Dr. Bergenstal, who is the president of medicine and science at the American Diabetes Association.

"Insulin degludec 200 U/mL allows patients who require larger daily doses of basal insulin [to] use prefilled pen devices to administer up to 160 U in a single injection," he concluded.

All of the reported studies were funded by Novo Nordisk.

PHILADELPHIA – The investigational ultralong-acting insulin, degludec, improved glycemic control while incurring lower risks of hypoglycemia in several studies of diabetes patients, many of them obese with high insulin requirements.

Novo Nordisk’s insulin degludec (IDeg), which is under consideration for approval by the Food and Drug Administration, is a basal insulin that forms soluble multihexamers after subcutaneous injection, extending its half-life significantly longer than 24 hours. The resulting steady blood levels of insulin confer a significantly lower risk of hypoglycemia in type 1 and type 2 patients taking degludec, compared with those taking insulin glargine, the comparator in many clinical trials, according to Dr. Helena W. Rodbard, an endocrinologist who practices in Rockville, Md.

About a third of patients with type 2 diabetes in the United States require more than 60 U just as the basal component, with quite a few requiring 80 or 100 U of insulin, noted Dr. Richard M. Bergenstal, executive director of the International Diabetes Center at Park Nicollet, Minneapolis. This demand for ever-increasing units has led to the development of new basal insulins that are even longer-acting, smoother, and flatter in terms of their pharmacokinetic and pharmacodynamic profiles, he said.

Dr. Rodbard presented the results of a meta-analysis of five phase IIIA, open-label, randomized, treat-to-target, confirmatory, 26- or 52-week trials in which a total of 2,262 type 2 diabetes patients received degludec and 1,110 received glargine, both injected once daily. Among those, 35% of the degludec group and 34% of the glargine group required more than 60 U of basal insulin per day by the end of the trials.

At study completion, hemoglobin A_1c values were similar in both groups, with an insignificant estimated treatment difference (ETD) of just 0.05% (P = .44). The mean fasting plasma glucose values at the end of the trials were lower with degludec than with glargine, with an ETD of –5.9 mg/dL, Dr. Rodbard reported.

Overall confirmed and nocturnal hypoglycemia rates were lower in patients requiring more than 60 U of insulin on degludec than on glargine, with confirmed hypoglycemia defined as self-measured blood glucose less than 56 mg/dL (plasma calibrated) or any episode requiring assistance. Nocturnal confirmed hypoglycemia was defined as any confirmed episode with onset between midnight and 6:00 a.m.

Compared with glargine, there was a 21% lower rate of overall confirmed hypoglycemic episodes with degludec (P = .02) and a 52% lower rate of nocturnal confirmed hypoglycemic episodes (P less than.0001).

The reduction of risk of hypoglycemia with degludec was particularly significant for nocturnal hypoglycemia, the "important area of concern," Dr. Rodbard said in an interview.

Novo Nordisk is also developing a 200 U/mL formulation of insulin degludec specifically for patients with high insulin requirements. This formulation, known as IDeg U200, contains equal units of insulin in half the volume of the 100-U/mL formulation, thus allowing larger insulin doses (up to 160 U) to be administered in a single injection with a prefilled pen device.

Dr. Bergenstal presented data from a 26-week, open-label, treat-to-target trial that compared the efficacy and safety of once-daily IDeg U200 vs. 100 U/mL of insulin glargine, both in combination with oral antidiabetic drugs, in a total of 457 insulin-naive type 2 diabetes patients who qualified for insulin treatment. They were randomized to either IDeg U200 or glargine, both in combination with metformin and some also using other medications.

By 26 weeks, IDeg U200 reduced HbA_1c by 1.30 percentage points (from a baseline of 8.3%) and was noninferior to glargine, with an estimated treatment difference of 0.04 percentage points.

Fasting glucose levels were similarly equally reduced. Rates of overall confirmed hypoglycemia (defined as less than 56 mg/dL, or having an episode requiring assistance) were lower with IDeg U200, at 1.22 episodes per patient per year, compared with 1.42 for glargine.

Rates of nocturnal confirmed hypoglycemia (defined as occurring between midnight and 6:00 a.m.) also were lower with IDeg U200 (0.18 vs. 0.28 episodes per patient-year, respectively). There were no severe hypoglycemic reactions in either group.

Mean daily basal insulin dose was similar after 26 weeks (0.62 U/kg for IDeg U200; 0.66 U/Kg for glargine). Weight gain occurred with a reduction in HbA_1c in both groups, by 1.9 kg with IDeg U200 and 1.5 kg with glargine. Adverse events were similar and infrequent in both groups, said Dr. Bergenstal, who is the president of medicine and science at the American Diabetes Association.

"Insulin degludec 200 U/mL allows patients who require larger daily doses of basal insulin [to] use prefilled pen devices to administer up to 160 U in a single injection," he concluded.

All of the reported studies were funded by Novo Nordisk.

PHILADELPHIA – Colesevelam significantly reduced hemoglobin A_1c and LDL cholesterol levels in adults with type 2 diabetes regardless of statin use, according to the results of a post hoc analysis of data from a 26-week study.

The bile acid sequestrant colesevelam HCl (Welchol, Daiichi Sankyo) is the only lipid-lowering agent that is also approved by the Food and Drug Administration for glucose lowering. In February 2012, the FDA issued statin labeling changes that included a notation about increases in HbA_1c and fasting serum glucose levels that have been reported with statin use. In fact, however, in this post hoc analysis of data from a Daiichi Sankyo trial, the reduction in HbA_1c with colesevelam was numerically greater among statin users than in non–statin users, said Dr. Harold E. Bays at the annual meeting of the American Association of Clinical Endocrinologists.

The original study involved a total of 316 adults with type 2 diabetes who had HbA_1c values of 7.5%-9.5% despite metformin therapy. They were randomized to receive 3.75 g/day colesevelam (159) or matching placebo (157). At 26 weeks, colesevelam lowered the mean HbA_1c level by 0.54% and the mean LDL cholesterol by 15.9%, compared with placebo (Arch. Intern. Med. 2008;168:1975-83).

The post hoc study evaluated the 62 in the colesevelam group and 75 in the placebo group who were receiving prestudy statin therapy, which continued throughout the trial. Their baseline demographic characteristics and mean HbA_1c (8.1%) were not different from those of the overall study population. At 26 weeks, HbA_1c had dropped by 0.63% among the statin users and 0.49% in the non–statin users, both statistically significant differences.

"So, there certainly wasn’t any diminished effectiveness of this antidiabetes drug in those patients who had been treated with statins," said Dr. Bays, who is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center in Louisville, Ky.

Colesevelam also reduced LDL cholesterol more than did placebo in both the statin and nonstatin groups (by 16.4% and 15.8%, respectively). "Whatever effect there may be of statins on glucose didn’t seem to adversely affect the cholesterol-lowering effect of colesevelam," he noted.

Total cholesterol, non-HDL cholesterol, apolipoprotein A1, and apolipoprotein B were also reduced with colesevelam in both groups, while HDL cholesterol did not change significantly. Triglycerides also did not change significantly from baseline in either group. Typically, bile acid resins increase triglycerides, but statins blunt that effect, so the result is no overall change, Dr. Bays commented.

"At minimum, there’s nothing in these data to suggest that being on a statin impairs the effectiveness of colesevelam. Thus, to whatever extent statins may affect glycemic parameters, this post hoc analysis did not support any attenuation of colesevelam efficacy based upon statin use or lack of statin use," he concluded.

In response to an audience member’s question about whether it might make sense to prescribe a lower dose of statins to patients who are on colesevelam, Dr. Bays showed additional data from a previous study suggesting that there were no differences in glucose levels by statin dose in patients taking fenofibric acid (Diabetes Care 2010;33:2113-6).

This study was funded by Daiichi Sankyo, for whom Dr. Bays has served as a clinical investigator, consultant, and speaker.

PHILADELPHIA – Colesevelam significantly reduced hemoglobin A_1c and LDL cholesterol levels in adults with type 2 diabetes regardless of statin use, according to the results of a post hoc analysis of data from a 26-week study.

The bile acid sequestrant colesevelam HCl (Welchol, Daiichi Sankyo) is the only lipid-lowering agent that is also approved by the Food and Drug Administration for glucose lowering. In February 2012, the FDA issued statin labeling changes that included a notation about increases in HbA_1c and fasting serum glucose levels that have been reported with statin use. In fact, however, in this post hoc analysis of data from a Daiichi Sankyo trial, the reduction in HbA_1c with colesevelam was numerically greater among statin users than in non–statin users, said Dr. Harold E. Bays at the annual meeting of the American Association of Clinical Endocrinologists.

The original study involved a total of 316 adults with type 2 diabetes who had HbA_1c values of 7.5%-9.5% despite metformin therapy. They were randomized to receive 3.75 g/day colesevelam (159) or matching placebo (157). At 26 weeks, colesevelam lowered the mean HbA_1c level by 0.54% and the mean LDL cholesterol by 15.9%, compared with placebo (Arch. Intern. Med. 2008;168:1975-83).

The post hoc study evaluated the 62 in the colesevelam group and 75 in the placebo group who were receiving prestudy statin therapy, which continued throughout the trial. Their baseline demographic characteristics and mean HbA_1c (8.1%) were not different from those of the overall study population. At 26 weeks, HbA_1c had dropped by 0.63% among the statin users and 0.49% in the non–statin users, both statistically significant differences.

"So, there certainly wasn’t any diminished effectiveness of this antidiabetes drug in those patients who had been treated with statins," said Dr. Bays, who is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center in Louisville, Ky.

Colesevelam also reduced LDL cholesterol more than did placebo in both the statin and nonstatin groups (by 16.4% and 15.8%, respectively). "Whatever effect there may be of statins on glucose didn’t seem to adversely affect the cholesterol-lowering effect of colesevelam," he noted.

Total cholesterol, non-HDL cholesterol, apolipoprotein A1, and apolipoprotein B were also reduced with colesevelam in both groups, while HDL cholesterol did not change significantly. Triglycerides also did not change significantly from baseline in either group. Typically, bile acid resins increase triglycerides, but statins blunt that effect, so the result is no overall change, Dr. Bays commented.

"At minimum, there’s nothing in these data to suggest that being on a statin impairs the effectiveness of colesevelam. Thus, to whatever extent statins may affect glycemic parameters, this post hoc analysis did not support any attenuation of colesevelam efficacy based upon statin use or lack of statin use," he concluded.

In response to an audience member’s question about whether it might make sense to prescribe a lower dose of statins to patients who are on colesevelam, Dr. Bays showed additional data from a previous study suggesting that there were no differences in glucose levels by statin dose in patients taking fenofibric acid (Diabetes Care 2010;33:2113-6).

This study was funded by Daiichi Sankyo, for whom Dr. Bays has served as a clinical investigator, consultant, and speaker.

PHILADELPHIA – Colesevelam significantly reduced hemoglobin A_1c and LDL cholesterol levels in adults with type 2 diabetes regardless of statin use, according to the results of a post hoc analysis of data from a 26-week study.

The bile acid sequestrant colesevelam HCl (Welchol, Daiichi Sankyo) is the only lipid-lowering agent that is also approved by the Food and Drug Administration for glucose lowering. In February 2012, the FDA issued statin labeling changes that included a notation about increases in HbA_1c and fasting serum glucose levels that have been reported with statin use. In fact, however, in this post hoc analysis of data from a Daiichi Sankyo trial, the reduction in HbA_1c with colesevelam was numerically greater among statin users than in non–statin users, said Dr. Harold E. Bays at the annual meeting of the American Association of Clinical Endocrinologists.

The original study involved a total of 316 adults with type 2 diabetes who had HbA_1c values of 7.5%-9.5% despite metformin therapy. They were randomized to receive 3.75 g/day colesevelam (159) or matching placebo (157). At 26 weeks, colesevelam lowered the mean HbA_1c level by 0.54% and the mean LDL cholesterol by 15.9%, compared with placebo (Arch. Intern. Med. 2008;168:1975-83).

The post hoc study evaluated the 62 in the colesevelam group and 75 in the placebo group who were receiving prestudy statin therapy, which continued throughout the trial. Their baseline demographic characteristics and mean HbA_1c (8.1%) were not different from those of the overall study population. At 26 weeks, HbA_1c had dropped by 0.63% among the statin users and 0.49% in the non–statin users, both statistically significant differences.

"So, there certainly wasn’t any diminished effectiveness of this antidiabetes drug in those patients who had been treated with statins," said Dr. Bays, who is medical director and president of the Louisville Metabolic and Atherosclerosis Research Center in Louisville, Ky.

Colesevelam also reduced LDL cholesterol more than did placebo in both the statin and nonstatin groups (by 16.4% and 15.8%, respectively). "Whatever effect there may be of statins on glucose didn’t seem to adversely affect the cholesterol-lowering effect of colesevelam," he noted.

Total cholesterol, non-HDL cholesterol, apolipoprotein A1, and apolipoprotein B were also reduced with colesevelam in both groups, while HDL cholesterol did not change significantly. Triglycerides also did not change significantly from baseline in either group. Typically, bile acid resins increase triglycerides, but statins blunt that effect, so the result is no overall change, Dr. Bays commented.

"At minimum, there’s nothing in these data to suggest that being on a statin impairs the effectiveness of colesevelam. Thus, to whatever extent statins may affect glycemic parameters, this post hoc analysis did not support any attenuation of colesevelam efficacy based upon statin use or lack of statin use," he concluded.

In response to an audience member’s question about whether it might make sense to prescribe a lower dose of statins to patients who are on colesevelam, Dr. Bays showed additional data from a previous study suggesting that there were no differences in glucose levels by statin dose in patients taking fenofibric acid (Diabetes Care 2010;33:2113-6).

This study was funded by Daiichi Sankyo, for whom Dr. Bays has served as a clinical investigator, consultant, and speaker.

PHILADELPHIA – Diabetic lower-extremity wound response to hyperbaric oxygen treatment was unaffected by pretreatment glycemic control in a multicenter, prospective cohort study of 22 adults with lower-extremity ulcers.

The finding suggests that hyperbaric oxygen treatment should not be delayed in patients whose glycemic control is suboptimal at the time that the therapy is prescribed, said Dr. Owaise Mansuri, an endocrinology fellow at Southern Illinois University, Springfield.

Hyperbaric oxygen is increasingly used as an adjunct to antibiotics, debridement, and revascularization for therapy of chronic nonhealing wounds associated with diabetes mellitus. The treatment enhances wound healing pathways including phagocyte function, collagen synthesis, and angiogenesis. Results have been mixed, but studies show increased rates of ulcer healing (Diabetes Care 2003;26:2378-82) and decreased amputation rates (Wound Rep. Regen. 2008;16:513-9). The impact of glycemic control at time of treatment has not been studied, Dr. Mansuri said.

There were 12 patients with hemoglobin A_1c values less than 7.5% ("controlled") and 10 with values of 7.5% or above ("uncontrolled"). Other than mean HbA_1c (6.5% vs. 8.8%), there were no significant demographic or disease characteristic differences between the two groups.

Patients received 20 hyperbaric oxygen sessions and routine wound care over a 1-month period. No ulcers were superficial; all were Wagner grade 2-4.

Wound volume was reduced by 65% in the controlled group and 71% in the uncontrolled group, a nonsignificant difference. Wound healing also was unaffected by presence or absence of peripheral artery disease, hypertension, tobacco use, weight, duration of diabetes, or ulcer duration, Dr. Mansuri said.

Ulcer area and depth were similarly unaffected by glycemic status, with both groups experiencing an area reduction of 46% and a depth reduction of 47% for the "controlled" group and 48% for the "uncontrolled" patients. Similar numbers of patients from both groups experienced a 50% or greater reduction in ulcer size (4 and 3, respectively).

Asked how to reconcile these findings with those from numerous previous studies suggesting that hyperglycemia delays wound healing, Dr. Mansuri said "We suspect that the effect of hyperbaric oxygen therapy was potent enough to overcome the negative effect of hyperglycemia."

This study was funded by Nevada Idea Network of Biomedical Research Excellence. Dr. Mansuri had no other disclosures.

PHILADELPHIA – Diabetic lower-extremity wound response to hyperbaric oxygen treatment was unaffected by pretreatment glycemic control in a multicenter, prospective cohort study of 22 adults with lower-extremity ulcers.

The finding suggests that hyperbaric oxygen treatment should not be delayed in patients whose glycemic control is suboptimal at the time that the therapy is prescribed, said Dr. Owaise Mansuri, an endocrinology fellow at Southern Illinois University, Springfield.

Hyperbaric oxygen is increasingly used as an adjunct to antibiotics, debridement, and revascularization for therapy of chronic nonhealing wounds associated with diabetes mellitus. The treatment enhances wound healing pathways including phagocyte function, collagen synthesis, and angiogenesis. Results have been mixed, but studies show increased rates of ulcer healing (Diabetes Care 2003;26:2378-82) and decreased amputation rates (Wound Rep. Regen. 2008;16:513-9). The impact of glycemic control at time of treatment has not been studied, Dr. Mansuri said.

There were 12 patients with hemoglobin A_1c values less than 7.5% ("controlled") and 10 with values of 7.5% or above ("uncontrolled"). Other than mean HbA_1c (6.5% vs. 8.8%), there were no significant demographic or disease characteristic differences between the two groups.

Patients received 20 hyperbaric oxygen sessions and routine wound care over a 1-month period. No ulcers were superficial; all were Wagner grade 2-4.

Wound volume was reduced by 65% in the controlled group and 71% in the uncontrolled group, a nonsignificant difference. Wound healing also was unaffected by presence or absence of peripheral artery disease, hypertension, tobacco use, weight, duration of diabetes, or ulcer duration, Dr. Mansuri said.

Ulcer area and depth were similarly unaffected by glycemic status, with both groups experiencing an area reduction of 46% and a depth reduction of 47% for the "controlled" group and 48% for the "uncontrolled" patients. Similar numbers of patients from both groups experienced a 50% or greater reduction in ulcer size (4 and 3, respectively).

Asked how to reconcile these findings with those from numerous previous studies suggesting that hyperglycemia delays wound healing, Dr. Mansuri said "We suspect that the effect of hyperbaric oxygen therapy was potent enough to overcome the negative effect of hyperglycemia."

This study was funded by Nevada Idea Network of Biomedical Research Excellence. Dr. Mansuri had no other disclosures.

PHILADELPHIA – Diabetic lower-extremity wound response to hyperbaric oxygen treatment was unaffected by pretreatment glycemic control in a multicenter, prospective cohort study of 22 adults with lower-extremity ulcers.

The finding suggests that hyperbaric oxygen treatment should not be delayed in patients whose glycemic control is suboptimal at the time that the therapy is prescribed, said Dr. Owaise Mansuri, an endocrinology fellow at Southern Illinois University, Springfield.

Hyperbaric oxygen is increasingly used as an adjunct to antibiotics, debridement, and revascularization for therapy of chronic nonhealing wounds associated with diabetes mellitus. The treatment enhances wound healing pathways including phagocyte function, collagen synthesis, and angiogenesis. Results have been mixed, but studies show increased rates of ulcer healing (Diabetes Care 2003;26:2378-82) and decreased amputation rates (Wound Rep. Regen. 2008;16:513-9). The impact of glycemic control at time of treatment has not been studied, Dr. Mansuri said.

There were 12 patients with hemoglobin A_1c values less than 7.5% ("controlled") and 10 with values of 7.5% or above ("uncontrolled"). Other than mean HbA_1c (6.5% vs. 8.8%), there were no significant demographic or disease characteristic differences between the two groups.

Patients received 20 hyperbaric oxygen sessions and routine wound care over a 1-month period. No ulcers were superficial; all were Wagner grade 2-4.

Wound volume was reduced by 65% in the controlled group and 71% in the uncontrolled group, a nonsignificant difference. Wound healing also was unaffected by presence or absence of peripheral artery disease, hypertension, tobacco use, weight, duration of diabetes, or ulcer duration, Dr. Mansuri said.

Ulcer area and depth were similarly unaffected by glycemic status, with both groups experiencing an area reduction of 46% and a depth reduction of 47% for the "controlled" group and 48% for the "uncontrolled" patients. Similar numbers of patients from both groups experienced a 50% or greater reduction in ulcer size (4 and 3, respectively).

Asked how to reconcile these findings with those from numerous previous studies suggesting that hyperglycemia delays wound healing, Dr. Mansuri said "We suspect that the effect of hyperbaric oxygen therapy was potent enough to overcome the negative effect of hyperglycemia."

This study was funded by Nevada Idea Network of Biomedical Research Excellence. Dr. Mansuri had no other disclosures.

PHILADELPHIA – A novel gene expression classifier was successful in determining which "indeterminate" thyroid nodules are benign and which were "suspicious" in a prospective, multicenter trial.

Following fine-needle aspiration (FNA) analysis, 15%-30% of thyroid nodules are not clearly benign or malignant. These cytologically indeterminate nodules (including atypia or follicular lesions of undetermined significance [FLUS] and lesions suspicious for follicular/Hurthle cell neoplasm) are often referred for diagnostic surgery, which proves three-fourths to be benign, Dr. Richard Lanman, chief medical officer at Veracyte Inc., said at the annual meeting of the American Association of Clinical Endocrinologists.

Two previous validation studies – one published (J. Clin. Endocrinol. Metab. 2010;95:5296-304) and one presented at the 2010 International Thyroid Congress – showed high sensitivity and a negative predictive value of about 95%, similar to that of a benign cytology diagnosis. The test, Veracyte’s Afirma Thyroid FNA analysis, became commercially available in April of this year.

The test includes 142 genes, which were identified through whole-genome analyses of hundreds of thyroid samples to differentiate benignity from malignancy in indeterminate thyroid FNA samples. "Unlike the candidate malignancy marker approach to look for markers of cancer, our goal is to look for a pattern of benignity across multiple genes. The results are expressed either as benign or suspicious, so it doesn’t make the malignant call," he explained.

Development of the test has been an iterative process, with retraining for each new set of samples that presumably includes additional rare neoplasms. A prospective analysis of the diagnostic performance of the current iteration was conducted at 49 study sites – about one third academic and two-thirds community based – in 26 states. A variety of FNA collection techniques were used but 99% were ultrasound-guided, noted Dr. Lanman, who is co–principal investigator for the study.

Patients, physicians, surgeons, and endocrine pathologists were all blinded to the molecular results. Interestingly, the two endocrine pathologists, whose diagnosis was defined as "truth" for the purposes of the study, changed the surgical pathology diagnosis from malignant to benign, or vice versa, 14% of the time. "This shows the broad multicenter nature of the trial," Dr. Lanman commented.

Of the total 4,812 nodules of 1 cm or greater evaluated, 12% (577) from 532 patients were indeterminate. Of those, 72% (413) were surgically removed, thereby allowing for the endocrine pathologists’ assessment. Following exclusions for prespecified criteria (including inadequate or degraded RNA, excessive study site storage time, and unavailable reference standard), 265 indeterminate nodules remained.

Among the entire group of 265 indeterminate FNAs, 180 were benign and 85 malignant by cytology. The gene expression classifier correctly identified 78 of those 85 as "suspicious," for a sensitivity of 92%. Specificity was 52% and negative predictive value was 93%. There were seven false negatives, Dr. Lanman noted.

Sensitivity was high for each subcategory of cytology diagnosis of atypia/FLUS, follicular neoplasm, and suspicious for malignancy at 90%, 90%, and 94%, respectively. Negative predictive values were 95%, 94%, and 85% for each subcategory, respectively.

Dr. Lanman said that these data support consideration of a conservative observation approach for many patients with indeterminate FNA cytology and a benign gene expression classifier result. However, he noted, "no test is perfect. All of these patients with a gene expression classifier benign result need close follow-up sonographically and clinically."

In an interview, Dr. Rhoda Cobin said that her endocrinology practice has been using the Afirma assay for the last several months. So far they have had one suspicious nodule, but it was borderline in size (9 mm) and turned out benign at surgery, making it a possibly false-positive result. All other samples sent gave benign results and therefore are being followed conservatively.

"The assay is useful in helping to make clinical decisions, but I believe its true value will be determined when it is in wider use," said Dr. Cobin, clinical professor of endocrinology, diabetes, and bone disease at Mount Sinai School of Medicine, New York.

Dr. Lanman is an employee of Veracyte, which funded the study. Dr. Cobin has no disclosures.

PHILADELPHIA – A novel gene expression classifier was successful in determining which "indeterminate" thyroid nodules are benign and which were "suspicious" in a prospective, multicenter trial.

Following fine-needle aspiration (FNA) analysis, 15%-30% of thyroid nodules are not clearly benign or malignant. These cytologically indeterminate nodules (including atypia or follicular lesions of undetermined significance [FLUS] and lesions suspicious for follicular/Hurthle cell neoplasm) are often referred for diagnostic surgery, which proves three-fourths to be benign, Dr. Richard Lanman, chief medical officer at Veracyte Inc., said at the annual meeting of the American Association of Clinical Endocrinologists.

Two previous validation studies – one published (J. Clin. Endocrinol. Metab. 2010;95:5296-304) and one presented at the 2010 International Thyroid Congress – showed high sensitivity and a negative predictive value of about 95%, similar to that of a benign cytology diagnosis. The test, Veracyte’s Afirma Thyroid FNA analysis, became commercially available in April of this year.

The test includes 142 genes, which were identified through whole-genome analyses of hundreds of thyroid samples to differentiate benignity from malignancy in indeterminate thyroid FNA samples. "Unlike the candidate malignancy marker approach to look for markers of cancer, our goal is to look for a pattern of benignity across multiple genes. The results are expressed either as benign or suspicious, so it doesn’t make the malignant call," he explained.

Development of the test has been an iterative process, with retraining for each new set of samples that presumably includes additional rare neoplasms. A prospective analysis of the diagnostic performance of the current iteration was conducted at 49 study sites – about one third academic and two-thirds community based – in 26 states. A variety of FNA collection techniques were used but 99% were ultrasound-guided, noted Dr. Lanman, who is co–principal investigator for the study.

Patients, physicians, surgeons, and endocrine pathologists were all blinded to the molecular results. Interestingly, the two endocrine pathologists, whose diagnosis was defined as "truth" for the purposes of the study, changed the surgical pathology diagnosis from malignant to benign, or vice versa, 14% of the time. "This shows the broad multicenter nature of the trial," Dr. Lanman commented.

Of the total 4,812 nodules of 1 cm or greater evaluated, 12% (577) from 532 patients were indeterminate. Of those, 72% (413) were surgically removed, thereby allowing for the endocrine pathologists’ assessment. Following exclusions for prespecified criteria (including inadequate or degraded RNA, excessive study site storage time, and unavailable reference standard), 265 indeterminate nodules remained.

Among the entire group of 265 indeterminate FNAs, 180 were benign and 85 malignant by cytology. The gene expression classifier correctly identified 78 of those 85 as "suspicious," for a sensitivity of 92%. Specificity was 52% and negative predictive value was 93%. There were seven false negatives, Dr. Lanman noted.

Sensitivity was high for each subcategory of cytology diagnosis of atypia/FLUS, follicular neoplasm, and suspicious for malignancy at 90%, 90%, and 94%, respectively. Negative predictive values were 95%, 94%, and 85% for each subcategory, respectively.

Dr. Lanman said that these data support consideration of a conservative observation approach for many patients with indeterminate FNA cytology and a benign gene expression classifier result. However, he noted, "no test is perfect. All of these patients with a gene expression classifier benign result need close follow-up sonographically and clinically."

In an interview, Dr. Rhoda Cobin said that her endocrinology practice has been using the Afirma assay for the last several months. So far they have had one suspicious nodule, but it was borderline in size (9 mm) and turned out benign at surgery, making it a possibly false-positive result. All other samples sent gave benign results and therefore are being followed conservatively.

"The assay is useful in helping to make clinical decisions, but I believe its true value will be determined when it is in wider use," said Dr. Cobin, clinical professor of endocrinology, diabetes, and bone disease at Mount Sinai School of Medicine, New York.

Dr. Lanman is an employee of Veracyte, which funded the study. Dr. Cobin has no disclosures.

PHILADELPHIA – A novel gene expression classifier was successful in determining which "indeterminate" thyroid nodules are benign and which were "suspicious" in a prospective, multicenter trial.

Following fine-needle aspiration (FNA) analysis, 15%-30% of thyroid nodules are not clearly benign or malignant. These cytologically indeterminate nodules (including atypia or follicular lesions of undetermined significance [FLUS] and lesions suspicious for follicular/Hurthle cell neoplasm) are often referred for diagnostic surgery, which proves three-fourths to be benign, Dr. Richard Lanman, chief medical officer at Veracyte Inc., said at the annual meeting of the American Association of Clinical Endocrinologists.

Two previous validation studies – one published (J. Clin. Endocrinol. Metab. 2010;95:5296-304) and one presented at the 2010 International Thyroid Congress – showed high sensitivity and a negative predictive value of about 95%, similar to that of a benign cytology diagnosis. The test, Veracyte’s Afirma Thyroid FNA analysis, became commercially available in April of this year.

The test includes 142 genes, which were identified through whole-genome analyses of hundreds of thyroid samples to differentiate benignity from malignancy in indeterminate thyroid FNA samples. "Unlike the candidate malignancy marker approach to look for markers of cancer, our goal is to look for a pattern of benignity across multiple genes. The results are expressed either as benign or suspicious, so it doesn’t make the malignant call," he explained.

Development of the test has been an iterative process, with retraining for each new set of samples that presumably includes additional rare neoplasms. A prospective analysis of the diagnostic performance of the current iteration was conducted at 49 study sites – about one third academic and two-thirds community based – in 26 states. A variety of FNA collection techniques were used but 99% were ultrasound-guided, noted Dr. Lanman, who is co–principal investigator for the study.

Patients, physicians, surgeons, and endocrine pathologists were all blinded to the molecular results. Interestingly, the two endocrine pathologists, whose diagnosis was defined as "truth" for the purposes of the study, changed the surgical pathology diagnosis from malignant to benign, or vice versa, 14% of the time. "This shows the broad multicenter nature of the trial," Dr. Lanman commented.

Of the total 4,812 nodules of 1 cm or greater evaluated, 12% (577) from 532 patients were indeterminate. Of those, 72% (413) were surgically removed, thereby allowing for the endocrine pathologists’ assessment. Following exclusions for prespecified criteria (including inadequate or degraded RNA, excessive study site storage time, and unavailable reference standard), 265 indeterminate nodules remained.

Among the entire group of 265 indeterminate FNAs, 180 were benign and 85 malignant by cytology. The gene expression classifier correctly identified 78 of those 85 as "suspicious," for a sensitivity of 92%. Specificity was 52% and negative predictive value was 93%. There were seven false negatives, Dr. Lanman noted.

Sensitivity was high for each subcategory of cytology diagnosis of atypia/FLUS, follicular neoplasm, and suspicious for malignancy at 90%, 90%, and 94%, respectively. Negative predictive values were 95%, 94%, and 85% for each subcategory, respectively.

Dr. Lanman said that these data support consideration of a conservative observation approach for many patients with indeterminate FNA cytology and a benign gene expression classifier result. However, he noted, "no test is perfect. All of these patients with a gene expression classifier benign result need close follow-up sonographically and clinically."

In an interview, Dr. Rhoda Cobin said that her endocrinology practice has been using the Afirma assay for the last several months. So far they have had one suspicious nodule, but it was borderline in size (9 mm) and turned out benign at surgery, making it a possibly false-positive result. All other samples sent gave benign results and therefore are being followed conservatively.

"The assay is useful in helping to make clinical decisions, but I believe its true value will be determined when it is in wider use," said Dr. Cobin, clinical professor of endocrinology, diabetes, and bone disease at Mount Sinai School of Medicine, New York.

Dr. Lanman is an employee of Veracyte, which funded the study. Dr. Cobin has no disclosures.

PHILADELPHIA – At 2 years post surgery, safety and efficacy outcomes for the Resolute zotarolimus-eluting coronary stent were similar between non–insulin-requiring patients with diabetes and those without diabetes.

Moreover, even the outcomes for the insulin-requiring patients were superior to results seen with other drug-eluting stents (DES) that have been published in the literature, said Dr. Scott W. Lee, of the department of medicine at Loma Linda (Calif.) University and medical director of global clinical research for Medtronic Diabetes, Northridge, Calif.

Patients with diabetes and coronary artery disease have significantly higher event rates because of endothelial dysfunction, impaired platelet function, altered coagulation/fibrinolysis, and increased smooth muscle proliferation. "From a surgery point of view, many patients with diabetes and heart disease were not even candidates for stent placement 20 years ago. They immediately went on to bypass surgery because of the complexity of their coronary artery disease," Dr. Lee commented.

Since then, current revascularization guidelines support the use of drug-eluting stents for the treatment of obstructive coronary artery disease in patients with diabetes. In March of this year, the Food and Drug Administration approved the Resolute stent for patients with symptomatic ischemic heart disease, including those with diabetes.

In a previous pooled analysis of data on 5,130 patients from five of Medtronic’s clinical trials on the Resolute DES, 878 of the total 1,535 patients with diabetes were compared with 1,302 diabetes patients with DES from the literature in order to define a performance standard. The rate of target vessel failure for the 878 Resolute patients at 12 months was found to be 7.8%, significantly less than the 14.5% seen in the literature among diabetes patients who received other drug-eluting stents. At 24 months, target vessel failure was still lower, at 12.1%, Dr. Lee noted.

Now, new 2-year data come from a post hoc descriptive analysis of the 878 from the Medtronic trials who were matched with 1,903 Resolute stent recipients without diabetes. Even with the same extent of vessel disease, the patients with diabetes had higher metabolic risk. They were slightly older (65.2 vs. 63.6 years) and were more likely to have hypertension (88% vs. 73%) and hyperlipidemia (86% vs. 76%). Males made up a smaller proportion of the diabetic group, 66% vs. 74%.

Target lesion failure – defined as cardiac death, target vessel myocardial infarction, or target lesion revascularization – was higher among those with diabetes at 2 years, 9.6% vs. 7.1%. However, that 9.6% is still "far lower" than the 14.5% published rate in the literature for DES in patients with diabetes, Dr. Lee noted.

When the diabetes patients were further divided into the 250 who were insulin requiring (including both type 1 and type 2 patients) and the 628 who were not, there was a continuum of risk: Target lesion revascularization rates by 2 years were similar between the non–insulin-requiring patients, 4.3%, and the nondiabetics, 3.4%. Among the insulin-requiring diabetes patients, 6.5% had target lesion revascularization.

Cardiac death/myocardial infarction rates were also similar between the non–insulin-requiring diabetic group and the nondiabetics, at 3.9% and 4.1% respectively, and were higher among the insulin-requiring diabetes patients, at 8.6%. "Again, this event rate is still lower than what is in the published literature," Dr. Lee noted.

Stent thrombosis rates were low – less than 1% – across all three groups, he said.

"I think it’s reassuring that there are other options available with regard to acute disease management that are specifically outcome driven," Dr. Lee concluded.

There are plans to study the Resolute DES in diabetes patients in a randomized, prospective study, he said in response to an audience member’s question.

In an interview, session moderator Dr. Alan Garber commented, "This study is very interesting. ... Restenosis has really plagued the patients with diabetes. Thus far, drug-eluting stents have not produced the relief [that] we would like to see in patients with diabetes. Things are better, to be sure, but they haven’t normalized restenosis rates in diabetes patients, compared to nondiabetic patients. This looks to be a substantial advancement in improving rates of restenosis that, although not normal, are closer to normal," said Dr. Garber, professor of medicine, biochemistry and molecular biology and molecular and cellular biology at Baylor College, Houston.

But, he added, "It’s not a head-to-head study. It’s a retrospective post-hoc analysis, but it looks to be better and therefore would justify doing a head-to-head prospective trial. I think cardiologists should consider [using Resolute in patients with diabetes], but a definitive randomized prospective head-to-head trial would be required to be sure."

The post hoc analysis was funded by Medtronic, and Dr. Lee is an employee of the company. Dr. Garber is a consultant/advisory board member and/or on the speakers bureaus for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

PHILADELPHIA – At 2 years post surgery, safety and efficacy outcomes for the Resolute zotarolimus-eluting coronary stent were similar between non–insulin-requiring patients with diabetes and those without diabetes.

Moreover, even the outcomes for the insulin-requiring patients were superior to results seen with other drug-eluting stents (DES) that have been published in the literature, said Dr. Scott W. Lee, of the department of medicine at Loma Linda (Calif.) University and medical director of global clinical research for Medtronic Diabetes, Northridge, Calif.

Patients with diabetes and coronary artery disease have significantly higher event rates because of endothelial dysfunction, impaired platelet function, altered coagulation/fibrinolysis, and increased smooth muscle proliferation. "From a surgery point of view, many patients with diabetes and heart disease were not even candidates for stent placement 20 years ago. They immediately went on to bypass surgery because of the complexity of their coronary artery disease," Dr. Lee commented.

Since then, current revascularization guidelines support the use of drug-eluting stents for the treatment of obstructive coronary artery disease in patients with diabetes. In March of this year, the Food and Drug Administration approved the Resolute stent for patients with symptomatic ischemic heart disease, including those with diabetes.

In a previous pooled analysis of data on 5,130 patients from five of Medtronic’s clinical trials on the Resolute DES, 878 of the total 1,535 patients with diabetes were compared with 1,302 diabetes patients with DES from the literature in order to define a performance standard. The rate of target vessel failure for the 878 Resolute patients at 12 months was found to be 7.8%, significantly less than the 14.5% seen in the literature among diabetes patients who received other drug-eluting stents. At 24 months, target vessel failure was still lower, at 12.1%, Dr. Lee noted.

Now, new 2-year data come from a post hoc descriptive analysis of the 878 from the Medtronic trials who were matched with 1,903 Resolute stent recipients without diabetes. Even with the same extent of vessel disease, the patients with diabetes had higher metabolic risk. They were slightly older (65.2 vs. 63.6 years) and were more likely to have hypertension (88% vs. 73%) and hyperlipidemia (86% vs. 76%). Males made up a smaller proportion of the diabetic group, 66% vs. 74%.

Target lesion failure – defined as cardiac death, target vessel myocardial infarction, or target lesion revascularization – was higher among those with diabetes at 2 years, 9.6% vs. 7.1%. However, that 9.6% is still "far lower" than the 14.5% published rate in the literature for DES in patients with diabetes, Dr. Lee noted.

When the diabetes patients were further divided into the 250 who were insulin requiring (including both type 1 and type 2 patients) and the 628 who were not, there was a continuum of risk: Target lesion revascularization rates by 2 years were similar between the non–insulin-requiring patients, 4.3%, and the nondiabetics, 3.4%. Among the insulin-requiring diabetes patients, 6.5% had target lesion revascularization.

Cardiac death/myocardial infarction rates were also similar between the non–insulin-requiring diabetic group and the nondiabetics, at 3.9% and 4.1% respectively, and were higher among the insulin-requiring diabetes patients, at 8.6%. "Again, this event rate is still lower than what is in the published literature," Dr. Lee noted.

Stent thrombosis rates were low – less than 1% – across all three groups, he said.

"I think it’s reassuring that there are other options available with regard to acute disease management that are specifically outcome driven," Dr. Lee concluded.

There are plans to study the Resolute DES in diabetes patients in a randomized, prospective study, he said in response to an audience member’s question.

In an interview, session moderator Dr. Alan Garber commented, "This study is very interesting. ... Restenosis has really plagued the patients with diabetes. Thus far, drug-eluting stents have not produced the relief [that] we would like to see in patients with diabetes. Things are better, to be sure, but they haven’t normalized restenosis rates in diabetes patients, compared to nondiabetic patients. This looks to be a substantial advancement in improving rates of restenosis that, although not normal, are closer to normal," said Dr. Garber, professor of medicine, biochemistry and molecular biology and molecular and cellular biology at Baylor College, Houston.

But, he added, "It’s not a head-to-head study. It’s a retrospective post-hoc analysis, but it looks to be better and therefore would justify doing a head-to-head prospective trial. I think cardiologists should consider [using Resolute in patients with diabetes], but a definitive randomized prospective head-to-head trial would be required to be sure."

The post hoc analysis was funded by Medtronic, and Dr. Lee is an employee of the company. Dr. Garber is a consultant/advisory board member and/or on the speakers bureaus for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

PHILADELPHIA – At 2 years post surgery, safety and efficacy outcomes for the Resolute zotarolimus-eluting coronary stent were similar between non–insulin-requiring patients with diabetes and those without diabetes.

Moreover, even the outcomes for the insulin-requiring patients were superior to results seen with other drug-eluting stents (DES) that have been published in the literature, said Dr. Scott W. Lee, of the department of medicine at Loma Linda (Calif.) University and medical director of global clinical research for Medtronic Diabetes, Northridge, Calif.

Patients with diabetes and coronary artery disease have significantly higher event rates because of endothelial dysfunction, impaired platelet function, altered coagulation/fibrinolysis, and increased smooth muscle proliferation. "From a surgery point of view, many patients with diabetes and heart disease were not even candidates for stent placement 20 years ago. They immediately went on to bypass surgery because of the complexity of their coronary artery disease," Dr. Lee commented.

Since then, current revascularization guidelines support the use of drug-eluting stents for the treatment of obstructive coronary artery disease in patients with diabetes. In March of this year, the Food and Drug Administration approved the Resolute stent for patients with symptomatic ischemic heart disease, including those with diabetes.

In a previous pooled analysis of data on 5,130 patients from five of Medtronic’s clinical trials on the Resolute DES, 878 of the total 1,535 patients with diabetes were compared with 1,302 diabetes patients with DES from the literature in order to define a performance standard. The rate of target vessel failure for the 878 Resolute patients at 12 months was found to be 7.8%, significantly less than the 14.5% seen in the literature among diabetes patients who received other drug-eluting stents. At 24 months, target vessel failure was still lower, at 12.1%, Dr. Lee noted.

Now, new 2-year data come from a post hoc descriptive analysis of the 878 from the Medtronic trials who were matched with 1,903 Resolute stent recipients without diabetes. Even with the same extent of vessel disease, the patients with diabetes had higher metabolic risk. They were slightly older (65.2 vs. 63.6 years) and were more likely to have hypertension (88% vs. 73%) and hyperlipidemia (86% vs. 76%). Males made up a smaller proportion of the diabetic group, 66% vs. 74%.

Target lesion failure – defined as cardiac death, target vessel myocardial infarction, or target lesion revascularization – was higher among those with diabetes at 2 years, 9.6% vs. 7.1%. However, that 9.6% is still "far lower" than the 14.5% published rate in the literature for DES in patients with diabetes, Dr. Lee noted.

When the diabetes patients were further divided into the 250 who were insulin requiring (including both type 1 and type 2 patients) and the 628 who were not, there was a continuum of risk: Target lesion revascularization rates by 2 years were similar between the non–insulin-requiring patients, 4.3%, and the nondiabetics, 3.4%. Among the insulin-requiring diabetes patients, 6.5% had target lesion revascularization.

Cardiac death/myocardial infarction rates were also similar between the non–insulin-requiring diabetic group and the nondiabetics, at 3.9% and 4.1% respectively, and were higher among the insulin-requiring diabetes patients, at 8.6%. "Again, this event rate is still lower than what is in the published literature," Dr. Lee noted.

Stent thrombosis rates were low – less than 1% – across all three groups, he said.

"I think it’s reassuring that there are other options available with regard to acute disease management that are specifically outcome driven," Dr. Lee concluded.

There are plans to study the Resolute DES in diabetes patients in a randomized, prospective study, he said in response to an audience member’s question.

In an interview, session moderator Dr. Alan Garber commented, "This study is very interesting. ... Restenosis has really plagued the patients with diabetes. Thus far, drug-eluting stents have not produced the relief [that] we would like to see in patients with diabetes. Things are better, to be sure, but they haven’t normalized restenosis rates in diabetes patients, compared to nondiabetic patients. This looks to be a substantial advancement in improving rates of restenosis that, although not normal, are closer to normal," said Dr. Garber, professor of medicine, biochemistry and molecular biology and molecular and cellular biology at Baylor College, Houston.

But, he added, "It’s not a head-to-head study. It’s a retrospective post-hoc analysis, but it looks to be better and therefore would justify doing a head-to-head prospective trial. I think cardiologists should consider [using Resolute in patients with diabetes], but a definitive randomized prospective head-to-head trial would be required to be sure."

The post hoc analysis was funded by Medtronic, and Dr. Lee is an employee of the company. Dr. Garber is a consultant/advisory board member and/or on the speakers bureaus for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

PHILADELPHIA – Linagliptin was associated with significant improvements in hyperglycemia in a multicenter, randomized, placebo-controlled, double-blind trial of 226 African-American patients with type 2 diabetes.

"African Americans have a 77% greater likelihood of developing diabetes yet tend to be underrepresented in clinical trials of antidiabetic drugs," said Dr. James R. Thrasher, director of medical investigation at Arkansas Diabetes and Endocrinology Center, Little Rock. "We wanted to look at this group with higher rates of diabetes and higher risk for complications of diabetes."

Linagliptin (Tradjenta) is a once-daily dipeptidyl peptidase-4 inhibitor, licensed for the treatment of type 2 diabetes. Unlike other DPP-4 inhibitors, it does not require dose adjustment for patients with renal or hepatic impairment, Dr. Thrasher noted in an interview at the annual meeting of the American Association of Clinical Endocrinologists.

Patients were randomized to 24 weeks of 5 mg/day linagliptin or placebo. Overall, 54% of the patients were men. The mean age was 54 years and mean body mass index was 32.7 kg/m². Nearly two-thirds (72%) had hypertension. In the efficacy analysis set of 100 linagliptin and 111 placebo patients, mean baseline hemoglobin A_1c was 8.6% for the linagliptin group and 8.7% for the placebo group. Most patients were already taking metformin or a sulfonylurea, which did not change. Twelve percent were treatment naive.

By 24 weeks, mean HbA_1c had dropped by 0.88 percentage points with linagliptin and 0.24 with placebo, a highly significant difference (P = 0.0002). Roughly three times more linagliptin patients achieved an HbA_1c of less than 7.0% (28.0% vs. 8.7%) and almost twice as many had an HbA_1c reduction of 0.5% or more (55.3% vs. 28.3%), Dr. Thrasher reported.

In the safety analysis set comprising 106 linagliptin and 120 placebo patients, most adverse events were mild or moderated and were considered unrelated to the study drug. The most common of these were hyperglycemia (2.8% in the linagliptin group and 9.2% in the placebo group) and nasopharyngitis (3.8% and 5.0%, respectively). Serious adverse events were reported in one linagliptin patient and two placebo patients. Hypoglycemia occurred in three linagliptin patients and one placebo patient. No event required external assistance, he said.

The responses among the African Americans in this study were comparable to those seen in the pivotal trials for linagliptin. "We know from studies of blood pressure medications that African Americans respond differently to different medications. In the area of diabetes, this is kind of landmark. It’s something new for us to look at ethnic groups specifically with a clinical trial for a drug. ... I hope this opens up the door to more [such] research with other drugs," Dr. Thrasher said.

Dr. Thrasher disclosed that he has received research grants and is a speaker for Boehringer Ingelheim, which manufactures linagliptin, and Lilly.

PHILADELPHIA – Linagliptin was associated with significant improvements in hyperglycemia in a multicenter, randomized, placebo-controlled, double-blind trial of 226 African-American patients with type 2 diabetes.

"African Americans have a 77% greater likelihood of developing diabetes yet tend to be underrepresented in clinical trials of antidiabetic drugs," said Dr. James R. Thrasher, director of medical investigation at Arkansas Diabetes and Endocrinology Center, Little Rock. "We wanted to look at this group with higher rates of diabetes and higher risk for complications of diabetes."

Linagliptin (Tradjenta) is a once-daily dipeptidyl peptidase-4 inhibitor, licensed for the treatment of type 2 diabetes. Unlike other DPP-4 inhibitors, it does not require dose adjustment for patients with renal or hepatic impairment, Dr. Thrasher noted in an interview at the annual meeting of the American Association of Clinical Endocrinologists.

Patients were randomized to 24 weeks of 5 mg/day linagliptin or placebo. Overall, 54% of the patients were men. The mean age was 54 years and mean body mass index was 32.7 kg/m². Nearly two-thirds (72%) had hypertension. In the efficacy analysis set of 100 linagliptin and 111 placebo patients, mean baseline hemoglobin A_1c was 8.6% for the linagliptin group and 8.7% for the placebo group. Most patients were already taking metformin or a sulfonylurea, which did not change. Twelve percent were treatment naive.

By 24 weeks, mean HbA_1c had dropped by 0.88 percentage points with linagliptin and 0.24 with placebo, a highly significant difference (P = 0.0002). Roughly three times more linagliptin patients achieved an HbA_1c of less than 7.0% (28.0% vs. 8.7%) and almost twice as many had an HbA_1c reduction of 0.5% or more (55.3% vs. 28.3%), Dr. Thrasher reported.

In the safety analysis set comprising 106 linagliptin and 120 placebo patients, most adverse events were mild or moderated and were considered unrelated to the study drug. The most common of these were hyperglycemia (2.8% in the linagliptin group and 9.2% in the placebo group) and nasopharyngitis (3.8% and 5.0%, respectively). Serious adverse events were reported in one linagliptin patient and two placebo patients. Hypoglycemia occurred in three linagliptin patients and one placebo patient. No event required external assistance, he said.

The responses among the African Americans in this study were comparable to those seen in the pivotal trials for linagliptin. "We know from studies of blood pressure medications that African Americans respond differently to different medications. In the area of diabetes, this is kind of landmark. It’s something new for us to look at ethnic groups specifically with a clinical trial for a drug. ... I hope this opens up the door to more [such] research with other drugs," Dr. Thrasher said.

Dr. Thrasher disclosed that he has received research grants and is a speaker for Boehringer Ingelheim, which manufactures linagliptin, and Lilly.

PHILADELPHIA – Linagliptin was associated with significant improvements in hyperglycemia in a multicenter, randomized, placebo-controlled, double-blind trial of 226 African-American patients with type 2 diabetes.

"African Americans have a 77% greater likelihood of developing diabetes yet tend to be underrepresented in clinical trials of antidiabetic drugs," said Dr. James R. Thrasher, director of medical investigation at Arkansas Diabetes and Endocrinology Center, Little Rock. "We wanted to look at this group with higher rates of diabetes and higher risk for complications of diabetes."

Linagliptin (Tradjenta) is a once-daily dipeptidyl peptidase-4 inhibitor, licensed for the treatment of type 2 diabetes. Unlike other DPP-4 inhibitors, it does not require dose adjustment for patients with renal or hepatic impairment, Dr. Thrasher noted in an interview at the annual meeting of the American Association of Clinical Endocrinologists.

Patients were randomized to 24 weeks of 5 mg/day linagliptin or placebo. Overall, 54% of the patients were men. The mean age was 54 years and mean body mass index was 32.7 kg/m². Nearly two-thirds (72%) had hypertension. In the efficacy analysis set of 100 linagliptin and 111 placebo patients, mean baseline hemoglobin A_1c was 8.6% for the linagliptin group and 8.7% for the placebo group. Most patients were already taking metformin or a sulfonylurea, which did not change. Twelve percent were treatment naive.

By 24 weeks, mean HbA_1c had dropped by 0.88 percentage points with linagliptin and 0.24 with placebo, a highly significant difference (P = 0.0002). Roughly three times more linagliptin patients achieved an HbA_1c of less than 7.0% (28.0% vs. 8.7%) and almost twice as many had an HbA_1c reduction of 0.5% or more (55.3% vs. 28.3%), Dr. Thrasher reported.

In the safety analysis set comprising 106 linagliptin and 120 placebo patients, most adverse events were mild or moderated and were considered unrelated to the study drug. The most common of these were hyperglycemia (2.8% in the linagliptin group and 9.2% in the placebo group) and nasopharyngitis (3.8% and 5.0%, respectively). Serious adverse events were reported in one linagliptin patient and two placebo patients. Hypoglycemia occurred in three linagliptin patients and one placebo patient. No event required external assistance, he said.

The responses among the African Americans in this study were comparable to those seen in the pivotal trials for linagliptin. "We know from studies of blood pressure medications that African Americans respond differently to different medications. In the area of diabetes, this is kind of landmark. It’s something new for us to look at ethnic groups specifically with a clinical trial for a drug. ... I hope this opens up the door to more [such] research with other drugs," Dr. Thrasher said.

Dr. Thrasher disclosed that he has received research grants and is a speaker for Boehringer Ingelheim, which manufactures linagliptin, and Lilly.

PHILADELPHIA – Patients who lived in rural areas and received tele-endocrinology consultations saw improvements in endocrine disorders such as diabetes, according to a small pilot study.

There was marked improvement in hemoglobin A_1c in patients with diabetes, marked improvement in some patients’ lipid profiles, "and we had some patients with thyroid disorders and we saw some euthyroid during the course of the study," said Dr. Rabia Rehman, an endocrinology fellow at the University of Tennessee Health Science Center, Memphis.

The study also highlighted the role of primary care providers in rural areas who referred the patients to the telemedicine consultations and helped with the continuity of their care.

Telemedicine is not a new concept and its potential benefits have been established in certain areas such as stroke care.

Dr. Rehman said tele-endocrinology can be beneficial today, when the rates of diabetes and other endocrine disorders are rising. That’s especially true in rural areas where there’s a lack of specialists and patients have to travel far to get to the nearest specialty provider or medical center, she said.

Sixty-six patients from five rural areas in Tennessee received remote consultations at the telemedicine unit of the University of Tennessee in Memphis over a period of 2½ years. The unit and the remote sites were connected by video cameras, television monitors, and Internet.

Recommendations for management of the conditions were faxed to the patients’ primary care providers, and specialists evaluated laboratory results per primary care providers’ requests.

Among the 66 patients, 35 (53%) had type 2 diabetes, 24 (41%) had hypertension, 30 (45%) had dyslipidemia, 20 (30%) had thyroid disease, and 8 (12%) had osteoporosis or hypercalcemia.

In the 20 of the 35 diabetic patients who had a 6-month follow-up, mean HbA_1c decreased by 1.7 percentage points, from 9.1% to 7.5%. The other 15 patients dropped out.

High dropout rate, in fact, was one of the limitations of the study. Dr. Rehman said the attrition could be due to the fact that the patients were comfortable with continuing their care with their primary care providers, and for other unknown reasons.

Follow-up data were available for 4 of the 20 patients with thyroid disease; all 4 became euthyroid, according to the study.

Also, data available on 17 patients with dyslipidemia showed that lipid profiles improved in 12 of them.

Almost all of the patients (97%) said they were comfortable with receiving care through videoconferencing.

Dr. Rehman said that the long-term cost savings due to improved health outcomes far outweighed the upfront cost of setting up the remote sites. She did not provide specific data on the cost of remote sites presented in this study.

These results show that "this is something that should be continued, and bigger, prospective studies should be done on effectiveness of telemedicine and bridging [the health care] gap," said Dr. Rehman, who indicated that she had no disclosures.

PHILADELPHIA – Patients who lived in rural areas and received tele-endocrinology consultations saw improvements in endocrine disorders such as diabetes, according to a small pilot study.

There was marked improvement in hemoglobin A_1c in patients with diabetes, marked improvement in some patients’ lipid profiles, "and we had some patients with thyroid disorders and we saw some euthyroid during the course of the study," said Dr. Rabia Rehman, an endocrinology fellow at the University of Tennessee Health Science Center, Memphis.

The study also highlighted the role of primary care providers in rural areas who referred the patients to the telemedicine consultations and helped with the continuity of their care.

Telemedicine is not a new concept and its potential benefits have been established in certain areas such as stroke care.

Dr. Rehman said tele-endocrinology can be beneficial today, when the rates of diabetes and other endocrine disorders are rising. That’s especially true in rural areas where there’s a lack of specialists and patients have to travel far to get to the nearest specialty provider or medical center, she said.

Sixty-six patients from five rural areas in Tennessee received remote consultations at the telemedicine unit of the University of Tennessee in Memphis over a period of 2½ years. The unit and the remote sites were connected by video cameras, television monitors, and Internet.

Recommendations for management of the conditions were faxed to the patients’ primary care providers, and specialists evaluated laboratory results per primary care providers’ requests.

Among the 66 patients, 35 (53%) had type 2 diabetes, 24 (41%) had hypertension, 30 (45%) had dyslipidemia, 20 (30%) had thyroid disease, and 8 (12%) had osteoporosis or hypercalcemia.

In the 20 of the 35 diabetic patients who had a 6-month follow-up, mean HbA_1c decreased by 1.7 percentage points, from 9.1% to 7.5%. The other 15 patients dropped out.

High dropout rate, in fact, was one of the limitations of the study. Dr. Rehman said the attrition could be due to the fact that the patients were comfortable with continuing their care with their primary care providers, and for other unknown reasons.

Follow-up data were available for 4 of the 20 patients with thyroid disease; all 4 became euthyroid, according to the study.

Also, data available on 17 patients with dyslipidemia showed that lipid profiles improved in 12 of them.

Almost all of the patients (97%) said they were comfortable with receiving care through videoconferencing.

Dr. Rehman said that the long-term cost savings due to improved health outcomes far outweighed the upfront cost of setting up the remote sites. She did not provide specific data on the cost of remote sites presented in this study.

These results show that "this is something that should be continued, and bigger, prospective studies should be done on effectiveness of telemedicine and bridging [the health care] gap," said Dr. Rehman, who indicated that she had no disclosures.

PHILADELPHIA – Patients who lived in rural areas and received tele-endocrinology consultations saw improvements in endocrine disorders such as diabetes, according to a small pilot study.

There was marked improvement in hemoglobin A_1c in patients with diabetes, marked improvement in some patients’ lipid profiles, "and we had some patients with thyroid disorders and we saw some euthyroid during the course of the study," said Dr. Rabia Rehman, an endocrinology fellow at the University of Tennessee Health Science Center, Memphis.

The study also highlighted the role of primary care providers in rural areas who referred the patients to the telemedicine consultations and helped with the continuity of their care.

Telemedicine is not a new concept and its potential benefits have been established in certain areas such as stroke care.

Dr. Rehman said tele-endocrinology can be beneficial today, when the rates of diabetes and other endocrine disorders are rising. That’s especially true in rural areas where there’s a lack of specialists and patients have to travel far to get to the nearest specialty provider or medical center, she said.

Sixty-six patients from five rural areas in Tennessee received remote consultations at the telemedicine unit of the University of Tennessee in Memphis over a period of 2½ years. The unit and the remote sites were connected by video cameras, television monitors, and Internet.

Recommendations for management of the conditions were faxed to the patients’ primary care providers, and specialists evaluated laboratory results per primary care providers’ requests.

Among the 66 patients, 35 (53%) had type 2 diabetes, 24 (41%) had hypertension, 30 (45%) had dyslipidemia, 20 (30%) had thyroid disease, and 8 (12%) had osteoporosis or hypercalcemia.

In the 20 of the 35 diabetic patients who had a 6-month follow-up, mean HbA_1c decreased by 1.7 percentage points, from 9.1% to 7.5%. The other 15 patients dropped out.

High dropout rate, in fact, was one of the limitations of the study. Dr. Rehman said the attrition could be due to the fact that the patients were comfortable with continuing their care with their primary care providers, and for other unknown reasons.

Follow-up data were available for 4 of the 20 patients with thyroid disease; all 4 became euthyroid, according to the study.

Also, data available on 17 patients with dyslipidemia showed that lipid profiles improved in 12 of them.

Almost all of the patients (97%) said they were comfortable with receiving care through videoconferencing.

Dr. Rehman said that the long-term cost savings due to improved health outcomes far outweighed the upfront cost of setting up the remote sites. She did not provide specific data on the cost of remote sites presented in this study.

These results show that "this is something that should be continued, and bigger, prospective studies should be done on effectiveness of telemedicine and bridging [the health care] gap," said Dr. Rehman, who indicated that she had no disclosures.