World Diabetes Congress

VANCOUVER, B.C. – When patients with poorly controlled type 1 diabetes all receive good training in self-management, pump therapy is not superior to insulin injections in terms of glycemic control, according to findings from the REPOSE trial.

But the two differ somewhat on other outcomes.

A total of 317 adult patients in the United Kingdom were studied. Among the majority with a hemoglobin A_1c level at baseline indicating poor control, the reduction at 24 months did not differ significantly between those assigned to insulin pumps and those assigned to multiple daily injection (MDI) therapy, investigators reported at the World Diabetes Congress.

However, pump therapy was associated with a greater improvement in certain measures of diabetes-specific quality of life, and MDI therapy was associated with a lower rate of diabetic ketoacidosis.

“We believe that these results support a care pathway for adults with type 1 diabetes that starts with structured training using MDI but with pumps offered later to those in whom the limitations of MDI interfere with effective self-management,” commented lead investigator Dr. Simon Heller, professor of clinical diabetes at the University of Sheffield (England).

“Structured training reduces the risk of severe hypoglycemia and leads to modest but importantly long-lasting benefits in HbA_1c, and should be delivered much more widely, even in the U.K.,” he added. “But there is also no doubt that further work is needed … to develop effective approaches to support people in achieving tighter glucose targets while we wait for the artificial pancreas to become generally available.”

In an interview, session moderator Dr. Remi Rabasa-Lhoret, an endocrinologist with the Montreal Diabetes Research Center, commented, “I am overall disappointed. I would say my internal bias was that there would be a larger benefit with the pump.”

The fact that the trial enrolled a relatively unselected population may have played a role, he suggested. In particular, the patients studied had very high HbA_1c levels at baseline, with a mean exceeding 9%, which in some countries would be a contraindication to getting a pump. Thus, they may have been unlikely to benefit even with good training.

“Another message is that maybe you need CGM [continuous glucose monitoring],” Dr. Rabasa-Lhoret added. “But then you are having huge cost issues and access issues to really benefit from the pump.”

Dr. Heller, in introducing the trial, noted that meta-analyses have suggested that pumps may have an edge over MDI when it comes to glycemic control. But “one of the limitations in the existing evidence is that people allocated to pumps have received more training and attention, compared to MDI, and very few trials have compared pumps to MDI with comparable training and insulin adjustment,” he noted.

To be eligible for the REPOSE (Relative Effectiveness of Pumps Over MDI and Structured Education) trial, patients had to have had type 1 diabetes for at least 1 year. Also, they had to be willing to undertake flexible intensive insulin therapy with self-monitoring of blood glucose and carbohydrate counting, and had to have no clinical indication or strong preference for a pump.

The patients were randomized to MDI (using rapid and twice-daily long-acting insulin analogues) or to pumps that provided continuous subcutaneous infusion of insulin. All were given 38 hours of high-quality structured education through the Dose Adjustment for Normal Eating (DAFNE) program, a skills-based program in flexible intensive insulin therapy and self-management.

The results for the entire trial population showed that among the large majority with baseline HbA_1c levels of at least 7.5%, the mean change at 24 months was –0.64%.

In an intent-to-treat analysis, the mean change was –0.84% in the pump group and –0.42% in the MDI group. After adjustment, the difference between groups was not significant (–0.23%; P = .121).

In a per-protocol analysis, however, there was a difference between groups in favor of the pump (–0.84% vs. –0.32%; difference, –0.34%; P = .018).

“Importantly, HbA_1c remained well above recommended national and international targets,” Dr. Heller said, with only about a fifth of patients in each group achieving an HbA_1c of less than 7.5%.

The trial population as a whole had a reduction in the annual number of episodes of severe hypoglycemia per patient from 0.17 before baseline to 0.10 during the trial (incidence rate ratio, 0.46; P = .021). Again, there was no difference between groups.

The groups were also statistically indistinguishable with respect to diabetes-specific quality of life, general measures of well-being, anxiety and depression, and fear of hypoglycemia. But the pump group had greater improvements than the MDI group in scores for diabetes-specific diet restrictions (P = .004), daily hassles and function (P = .006), and treatment satisfaction (P less than .001).

The rates of serious adverse events were generally similar across the two groups, except for a higher rate of diabetic ketoacidosis with the pump (12.9% vs. 3.7%). “The difference was confined to the first year,” Dr. Heller noted. Most of the episodes were due to general infections (for example, urinary tract and upper respiratory tract infections), and the number was small among patients who adhered to sick day rules that had been covered in training.

He offered a parting message to physicians considering putting their patients on pumps: “Make sure they are up to self-managing their diabetes really actively, and if they are, absolutely. … I’m a passionate proponent of using technology for people who are up for it.”

Session attendee Dr. Irl B. Hirsch of the University of Washington, Seattle, said, “I’m very curious … about the frequency of home blood glucose monitoring, because that’s the key in my opinion for any insulin delivery – are they checking their blood sugars enough to make the appropriate adjustments? Was there more testing in one group than the other?”

Those data were obtained from patients who reported them, but were otherwise not systematically collected, Dr. Heller said.

Dr. Heller disclosed that he receives consulting fees/honoraria from Eli Lilly, Novo Nordisk, Sanofi-Aventis, Takeda, MSD, AstraZeneca, Johnson and Johnson, and Boehringer Ingelheim, and that he has clinical trial affiliations with Medtronic, UK.

VANCOUVER, B.C. – When patients with poorly controlled type 1 diabetes all receive good training in self-management, pump therapy is not superior to insulin injections in terms of glycemic control, according to findings from the REPOSE trial.

But the two differ somewhat on other outcomes.

A total of 317 adult patients in the United Kingdom were studied. Among the majority with a hemoglobin A_1c level at baseline indicating poor control, the reduction at 24 months did not differ significantly between those assigned to insulin pumps and those assigned to multiple daily injection (MDI) therapy, investigators reported at the World Diabetes Congress.

However, pump therapy was associated with a greater improvement in certain measures of diabetes-specific quality of life, and MDI therapy was associated with a lower rate of diabetic ketoacidosis.

“We believe that these results support a care pathway for adults with type 1 diabetes that starts with structured training using MDI but with pumps offered later to those in whom the limitations of MDI interfere with effective self-management,” commented lead investigator Dr. Simon Heller, professor of clinical diabetes at the University of Sheffield (England).

“Structured training reduces the risk of severe hypoglycemia and leads to modest but importantly long-lasting benefits in HbA_1c, and should be delivered much more widely, even in the U.K.,” he added. “But there is also no doubt that further work is needed … to develop effective approaches to support people in achieving tighter glucose targets while we wait for the artificial pancreas to become generally available.”

In an interview, session moderator Dr. Remi Rabasa-Lhoret, an endocrinologist with the Montreal Diabetes Research Center, commented, “I am overall disappointed. I would say my internal bias was that there would be a larger benefit with the pump.”

The fact that the trial enrolled a relatively unselected population may have played a role, he suggested. In particular, the patients studied had very high HbA_1c levels at baseline, with a mean exceeding 9%, which in some countries would be a contraindication to getting a pump. Thus, they may have been unlikely to benefit even with good training.

“Another message is that maybe you need CGM [continuous glucose monitoring],” Dr. Rabasa-Lhoret added. “But then you are having huge cost issues and access issues to really benefit from the pump.”

Dr. Heller, in introducing the trial, noted that meta-analyses have suggested that pumps may have an edge over MDI when it comes to glycemic control. But “one of the limitations in the existing evidence is that people allocated to pumps have received more training and attention, compared to MDI, and very few trials have compared pumps to MDI with comparable training and insulin adjustment,” he noted.

To be eligible for the REPOSE (Relative Effectiveness of Pumps Over MDI and Structured Education) trial, patients had to have had type 1 diabetes for at least 1 year. Also, they had to be willing to undertake flexible intensive insulin therapy with self-monitoring of blood glucose and carbohydrate counting, and had to have no clinical indication or strong preference for a pump.

The patients were randomized to MDI (using rapid and twice-daily long-acting insulin analogues) or to pumps that provided continuous subcutaneous infusion of insulin. All were given 38 hours of high-quality structured education through the Dose Adjustment for Normal Eating (DAFNE) program, a skills-based program in flexible intensive insulin therapy and self-management.

The results for the entire trial population showed that among the large majority with baseline HbA_1c levels of at least 7.5%, the mean change at 24 months was –0.64%.

In an intent-to-treat analysis, the mean change was –0.84% in the pump group and –0.42% in the MDI group. After adjustment, the difference between groups was not significant (–0.23%; P = .121).

In a per-protocol analysis, however, there was a difference between groups in favor of the pump (–0.84% vs. –0.32%; difference, –0.34%; P = .018).

“Importantly, HbA_1c remained well above recommended national and international targets,” Dr. Heller said, with only about a fifth of patients in each group achieving an HbA_1c of less than 7.5%.

The trial population as a whole had a reduction in the annual number of episodes of severe hypoglycemia per patient from 0.17 before baseline to 0.10 during the trial (incidence rate ratio, 0.46; P = .021). Again, there was no difference between groups.

The groups were also statistically indistinguishable with respect to diabetes-specific quality of life, general measures of well-being, anxiety and depression, and fear of hypoglycemia. But the pump group had greater improvements than the MDI group in scores for diabetes-specific diet restrictions (P = .004), daily hassles and function (P = .006), and treatment satisfaction (P less than .001).

The rates of serious adverse events were generally similar across the two groups, except for a higher rate of diabetic ketoacidosis with the pump (12.9% vs. 3.7%). “The difference was confined to the first year,” Dr. Heller noted. Most of the episodes were due to general infections (for example, urinary tract and upper respiratory tract infections), and the number was small among patients who adhered to sick day rules that had been covered in training.

He offered a parting message to physicians considering putting their patients on pumps: “Make sure they are up to self-managing their diabetes really actively, and if they are, absolutely. … I’m a passionate proponent of using technology for people who are up for it.”

Session attendee Dr. Irl B. Hirsch of the University of Washington, Seattle, said, “I’m very curious … about the frequency of home blood glucose monitoring, because that’s the key in my opinion for any insulin delivery – are they checking their blood sugars enough to make the appropriate adjustments? Was there more testing in one group than the other?”

Those data were obtained from patients who reported them, but were otherwise not systematically collected, Dr. Heller said.

Dr. Heller disclosed that he receives consulting fees/honoraria from Eli Lilly, Novo Nordisk, Sanofi-Aventis, Takeda, MSD, AstraZeneca, Johnson and Johnson, and Boehringer Ingelheim, and that he has clinical trial affiliations with Medtronic, UK.

VANCOUVER, B.C. – When patients with poorly controlled type 1 diabetes all receive good training in self-management, pump therapy is not superior to insulin injections in terms of glycemic control, according to findings from the REPOSE trial.

But the two differ somewhat on other outcomes.

A total of 317 adult patients in the United Kingdom were studied. Among the majority with a hemoglobin A_1c level at baseline indicating poor control, the reduction at 24 months did not differ significantly between those assigned to insulin pumps and those assigned to multiple daily injection (MDI) therapy, investigators reported at the World Diabetes Congress.

However, pump therapy was associated with a greater improvement in certain measures of diabetes-specific quality of life, and MDI therapy was associated with a lower rate of diabetic ketoacidosis.

“We believe that these results support a care pathway for adults with type 1 diabetes that starts with structured training using MDI but with pumps offered later to those in whom the limitations of MDI interfere with effective self-management,” commented lead investigator Dr. Simon Heller, professor of clinical diabetes at the University of Sheffield (England).

“Structured training reduces the risk of severe hypoglycemia and leads to modest but importantly long-lasting benefits in HbA_1c, and should be delivered much more widely, even in the U.K.,” he added. “But there is also no doubt that further work is needed … to develop effective approaches to support people in achieving tighter glucose targets while we wait for the artificial pancreas to become generally available.”

In an interview, session moderator Dr. Remi Rabasa-Lhoret, an endocrinologist with the Montreal Diabetes Research Center, commented, “I am overall disappointed. I would say my internal bias was that there would be a larger benefit with the pump.”

The fact that the trial enrolled a relatively unselected population may have played a role, he suggested. In particular, the patients studied had very high HbA_1c levels at baseline, with a mean exceeding 9%, which in some countries would be a contraindication to getting a pump. Thus, they may have been unlikely to benefit even with good training.

“Another message is that maybe you need CGM [continuous glucose monitoring],” Dr. Rabasa-Lhoret added. “But then you are having huge cost issues and access issues to really benefit from the pump.”

Dr. Heller, in introducing the trial, noted that meta-analyses have suggested that pumps may have an edge over MDI when it comes to glycemic control. But “one of the limitations in the existing evidence is that people allocated to pumps have received more training and attention, compared to MDI, and very few trials have compared pumps to MDI with comparable training and insulin adjustment,” he noted.

To be eligible for the REPOSE (Relative Effectiveness of Pumps Over MDI and Structured Education) trial, patients had to have had type 1 diabetes for at least 1 year. Also, they had to be willing to undertake flexible intensive insulin therapy with self-monitoring of blood glucose and carbohydrate counting, and had to have no clinical indication or strong preference for a pump.

The patients were randomized to MDI (using rapid and twice-daily long-acting insulin analogues) or to pumps that provided continuous subcutaneous infusion of insulin. All were given 38 hours of high-quality structured education through the Dose Adjustment for Normal Eating (DAFNE) program, a skills-based program in flexible intensive insulin therapy and self-management.

The results for the entire trial population showed that among the large majority with baseline HbA_1c levels of at least 7.5%, the mean change at 24 months was –0.64%.

In an intent-to-treat analysis, the mean change was –0.84% in the pump group and –0.42% in the MDI group. After adjustment, the difference between groups was not significant (–0.23%; P = .121).

In a per-protocol analysis, however, there was a difference between groups in favor of the pump (–0.84% vs. –0.32%; difference, –0.34%; P = .018).

“Importantly, HbA_1c remained well above recommended national and international targets,” Dr. Heller said, with only about a fifth of patients in each group achieving an HbA_1c of less than 7.5%.

The trial population as a whole had a reduction in the annual number of episodes of severe hypoglycemia per patient from 0.17 before baseline to 0.10 during the trial (incidence rate ratio, 0.46; P = .021). Again, there was no difference between groups.

The groups were also statistically indistinguishable with respect to diabetes-specific quality of life, general measures of well-being, anxiety and depression, and fear of hypoglycemia. But the pump group had greater improvements than the MDI group in scores for diabetes-specific diet restrictions (P = .004), daily hassles and function (P = .006), and treatment satisfaction (P less than .001).

The rates of serious adverse events were generally similar across the two groups, except for a higher rate of diabetic ketoacidosis with the pump (12.9% vs. 3.7%). “The difference was confined to the first year,” Dr. Heller noted. Most of the episodes were due to general infections (for example, urinary tract and upper respiratory tract infections), and the number was small among patients who adhered to sick day rules that had been covered in training.

He offered a parting message to physicians considering putting their patients on pumps: “Make sure they are up to self-managing their diabetes really actively, and if they are, absolutely. … I’m a passionate proponent of using technology for people who are up for it.”

Session attendee Dr. Irl B. Hirsch of the University of Washington, Seattle, said, “I’m very curious … about the frequency of home blood glucose monitoring, because that’s the key in my opinion for any insulin delivery – are they checking their blood sugars enough to make the appropriate adjustments? Was there more testing in one group than the other?”

Those data were obtained from patients who reported them, but were otherwise not systematically collected, Dr. Heller said.

Dr. Heller disclosed that he receives consulting fees/honoraria from Eli Lilly, Novo Nordisk, Sanofi-Aventis, Takeda, MSD, AstraZeneca, Johnson and Johnson, and Boehringer Ingelheim, and that he has clinical trial affiliations with Medtronic, UK.

VANCOUVER, B.C. – When patients with poorly controlled type 1 diabetes all receive good training in self-management, pump therapy is not superior to insulin injections in terms of glycemic control, according to findings from the REPOSE trial.

But the two differ somewhat on other outcomes.

A total of 317 adult patients in the United Kingdom were studied. Among the majority with a hemoglobin A_1c level at baseline indicating poor control, the reduction at 24 months did not differ significantly between those assigned to insulin pumps and those assigned to multiple daily injection (MDI) therapy, investigators reported at the World Diabetes Congress.

However, pump therapy was associated with a greater improvement in certain measures of diabetes-specific quality of life, and MDI therapy was associated with a lower rate of diabetic ketoacidosis.

“We believe that these results support a care pathway for adults with type 1 diabetes that starts with structured training using MDI but with pumps offered later to those in whom the limitations of MDI interfere with effective self-management,” commented lead investigator Dr. Simon Heller, professor of clinical diabetes at the University of Sheffield (England).

“Structured training reduces the risk of severe hypoglycemia and leads to modest but importantly long-lasting benefits in HbA_1c, and should be delivered much more widely, even in the U.K.,” he added. “But there is also no doubt that further work is needed … to develop effective approaches to support people in achieving tighter glucose targets while we wait for the artificial pancreas to become generally available.”

In an interview, session moderator Dr. Remi Rabasa-Lhoret, an endocrinologist with the Montreal Diabetes Research Center, commented, “I am overall disappointed. I would say my internal bias was that there would be a larger benefit with the pump.”

The fact that the trial enrolled a relatively unselected population may have played a role, he suggested. In particular, the patients studied had very high HbA_1c levels at baseline, with a mean exceeding 9%, which in some countries would be a contraindication to getting a pump. Thus, they may have been unlikely to benefit even with good training.

“Another message is that maybe you need CGM [continuous glucose monitoring],” Dr. Rabasa-Lhoret added. “But then you are having huge cost issues and access issues to really benefit from the pump.”

Dr. Heller, in introducing the trial, noted that meta-analyses have suggested that pumps may have an edge over MDI when it comes to glycemic control. But “one of the limitations in the existing evidence is that people allocated to pumps have received more training and attention, compared to MDI, and very few trials have compared pumps to MDI with comparable training and insulin adjustment,” he noted.

To be eligible for the REPOSE (Relative Effectiveness of Pumps Over MDI and Structured Education) trial, patients had to have had type 1 diabetes for at least 1 year. Also, they had to be willing to undertake flexible intensive insulin therapy with self-monitoring of blood glucose and carbohydrate counting, and had to have no clinical indication or strong preference for a pump.

The patients were randomized to MDI (using rapid and twice-daily long-acting insulin analogues) or to pumps that provided continuous subcutaneous infusion of insulin. All were given 38 hours of high-quality structured education through the Dose Adjustment for Normal Eating (DAFNE) program, a skills-based program in flexible intensive insulin therapy and self-management.

The results for the entire trial population showed that among the large majority with baseline HbA_1c levels of at least 7.5%, the mean change at 24 months was –0.64%.

In an intent-to-treat analysis, the mean change was –0.84% in the pump group and –0.42% in the MDI group. After adjustment, the difference between groups was not significant (–0.23%; P = .121).

In a per-protocol analysis, however, there was a difference between groups in favor of the pump (–0.84% vs. –0.32%; difference, –0.34%; P = .018).

“Importantly, HbA_1c remained well above recommended national and international targets,” Dr. Heller said, with only about a fifth of patients in each group achieving an HbA_1c of less than 7.5%.

The trial population as a whole had a reduction in the annual number of episodes of severe hypoglycemia per patient from 0.17 before baseline to 0.10 during the trial (incidence rate ratio, 0.46; P = .021). Again, there was no difference between groups.

The groups were also statistically indistinguishable with respect to diabetes-specific quality of life, general measures of well-being, anxiety and depression, and fear of hypoglycemia. But the pump group had greater improvements than the MDI group in scores for diabetes-specific diet restrictions (P = .004), daily hassles and function (P = .006), and treatment satisfaction (P less than .001).

The rates of serious adverse events were generally similar across the two groups, except for a higher rate of diabetic ketoacidosis with the pump (12.9% vs. 3.7%). “The difference was confined to the first year,” Dr. Heller noted. Most of the episodes were due to general infections (for example, urinary tract and upper respiratory tract infections), and the number was small among patients who adhered to sick day rules that had been covered in training.

He offered a parting message to physicians considering putting their patients on pumps: “Make sure they are up to self-managing their diabetes really actively, and if they are, absolutely. … I’m a passionate proponent of using technology for people who are up for it.”

Session attendee Dr. Irl B. Hirsch of the University of Washington, Seattle, said, “I’m very curious … about the frequency of home blood glucose monitoring, because that’s the key in my opinion for any insulin delivery – are they checking their blood sugars enough to make the appropriate adjustments? Was there more testing in one group than the other?”

Those data were obtained from patients who reported them, but were otherwise not systematically collected, Dr. Heller said.

Dr. Heller disclosed that he receives consulting fees/honoraria from Eli Lilly, Novo Nordisk, Sanofi-Aventis, Takeda, MSD, AstraZeneca, Johnson and Johnson, and Boehringer Ingelheim, and that he has clinical trial affiliations with Medtronic, UK.

VANCOUVER, B.C. – When patients with poorly controlled type 1 diabetes all receive good training in self-management, pump therapy is not superior to insulin injections in terms of glycemic control, according to findings from the REPOSE trial.

But the two differ somewhat on other outcomes.

A total of 317 adult patients in the United Kingdom were studied. Among the majority with a hemoglobin A_1c level at baseline indicating poor control, the reduction at 24 months did not differ significantly between those assigned to insulin pumps and those assigned to multiple daily injection (MDI) therapy, investigators reported at the World Diabetes Congress.

However, pump therapy was associated with a greater improvement in certain measures of diabetes-specific quality of life, and MDI therapy was associated with a lower rate of diabetic ketoacidosis.

“We believe that these results support a care pathway for adults with type 1 diabetes that starts with structured training using MDI but with pumps offered later to those in whom the limitations of MDI interfere with effective self-management,” commented lead investigator Dr. Simon Heller, professor of clinical diabetes at the University of Sheffield (England).

“Structured training reduces the risk of severe hypoglycemia and leads to modest but importantly long-lasting benefits in HbA_1c, and should be delivered much more widely, even in the U.K.,” he added. “But there is also no doubt that further work is needed … to develop effective approaches to support people in achieving tighter glucose targets while we wait for the artificial pancreas to become generally available.”

In an interview, session moderator Dr. Remi Rabasa-Lhoret, an endocrinologist with the Montreal Diabetes Research Center, commented, “I am overall disappointed. I would say my internal bias was that there would be a larger benefit with the pump.”

The fact that the trial enrolled a relatively unselected population may have played a role, he suggested. In particular, the patients studied had very high HbA_1c levels at baseline, with a mean exceeding 9%, which in some countries would be a contraindication to getting a pump. Thus, they may have been unlikely to benefit even with good training.

“Another message is that maybe you need CGM [continuous glucose monitoring],” Dr. Rabasa-Lhoret added. “But then you are having huge cost issues and access issues to really benefit from the pump.”

Dr. Heller, in introducing the trial, noted that meta-analyses have suggested that pumps may have an edge over MDI when it comes to glycemic control. But “one of the limitations in the existing evidence is that people allocated to pumps have received more training and attention, compared to MDI, and very few trials have compared pumps to MDI with comparable training and insulin adjustment,” he noted.

To be eligible for the REPOSE (Relative Effectiveness of Pumps Over MDI and Structured Education) trial, patients had to have had type 1 diabetes for at least 1 year. Also, they had to be willing to undertake flexible intensive insulin therapy with self-monitoring of blood glucose and carbohydrate counting, and had to have no clinical indication or strong preference for a pump.

The patients were randomized to MDI (using rapid and twice-daily long-acting insulin analogues) or to pumps that provided continuous subcutaneous infusion of insulin. All were given 38 hours of high-quality structured education through the Dose Adjustment for Normal Eating (DAFNE) program, a skills-based program in flexible intensive insulin therapy and self-management.

The results for the entire trial population showed that among the large majority with baseline HbA_1c levels of at least 7.5%, the mean change at 24 months was –0.64%.

In an intent-to-treat analysis, the mean change was –0.84% in the pump group and –0.42% in the MDI group. After adjustment, the difference between groups was not significant (–0.23%; P = .121).

In a per-protocol analysis, however, there was a difference between groups in favor of the pump (–0.84% vs. –0.32%; difference, –0.34%; P = .018).

“Importantly, HbA_1c remained well above recommended national and international targets,” Dr. Heller said, with only about a fifth of patients in each group achieving an HbA_1c of less than 7.5%.

The trial population as a whole had a reduction in the annual number of episodes of severe hypoglycemia per patient from 0.17 before baseline to 0.10 during the trial (incidence rate ratio, 0.46; P = .021). Again, there was no difference between groups.

The groups were also statistically indistinguishable with respect to diabetes-specific quality of life, general measures of well-being, anxiety and depression, and fear of hypoglycemia. But the pump group had greater improvements than the MDI group in scores for diabetes-specific diet restrictions (P = .004), daily hassles and function (P = .006), and treatment satisfaction (P less than .001).

The rates of serious adverse events were generally similar across the two groups, except for a higher rate of diabetic ketoacidosis with the pump (12.9% vs. 3.7%). “The difference was confined to the first year,” Dr. Heller noted. Most of the episodes were due to general infections (for example, urinary tract and upper respiratory tract infections), and the number was small among patients who adhered to sick day rules that had been covered in training.

He offered a parting message to physicians considering putting their patients on pumps: “Make sure they are up to self-managing their diabetes really actively, and if they are, absolutely. … I’m a passionate proponent of using technology for people who are up for it.”

Session attendee Dr. Irl B. Hirsch of the University of Washington, Seattle, said, “I’m very curious … about the frequency of home blood glucose monitoring, because that’s the key in my opinion for any insulin delivery – are they checking their blood sugars enough to make the appropriate adjustments? Was there more testing in one group than the other?”

Those data were obtained from patients who reported them, but were otherwise not systematically collected, Dr. Heller said.

Dr. Heller disclosed that he receives consulting fees/honoraria from Eli Lilly, Novo Nordisk, Sanofi-Aventis, Takeda, MSD, AstraZeneca, Johnson and Johnson, and Boehringer Ingelheim, and that he has clinical trial affiliations with Medtronic, UK.

VANCOUVER, B.C. – When patients with poorly controlled type 1 diabetes all receive good training in self-management, pump therapy is not superior to insulin injections in terms of glycemic control, according to findings from the REPOSE trial.

But the two differ somewhat on other outcomes.

A total of 317 adult patients in the United Kingdom were studied. Among the majority with a hemoglobin A_1c level at baseline indicating poor control, the reduction at 24 months did not differ significantly between those assigned to insulin pumps and those assigned to multiple daily injection (MDI) therapy, investigators reported at the World Diabetes Congress.

However, pump therapy was associated with a greater improvement in certain measures of diabetes-specific quality of life, and MDI therapy was associated with a lower rate of diabetic ketoacidosis.

“We believe that these results support a care pathway for adults with type 1 diabetes that starts with structured training using MDI but with pumps offered later to those in whom the limitations of MDI interfere with effective self-management,” commented lead investigator Dr. Simon Heller, professor of clinical diabetes at the University of Sheffield (England).

“Structured training reduces the risk of severe hypoglycemia and leads to modest but importantly long-lasting benefits in HbA_1c, and should be delivered much more widely, even in the U.K.,” he added. “But there is also no doubt that further work is needed … to develop effective approaches to support people in achieving tighter glucose targets while we wait for the artificial pancreas to become generally available.”

In an interview, session moderator Dr. Remi Rabasa-Lhoret, an endocrinologist with the Montreal Diabetes Research Center, commented, “I am overall disappointed. I would say my internal bias was that there would be a larger benefit with the pump.”

The fact that the trial enrolled a relatively unselected population may have played a role, he suggested. In particular, the patients studied had very high HbA_1c levels at baseline, with a mean exceeding 9%, which in some countries would be a contraindication to getting a pump. Thus, they may have been unlikely to benefit even with good training.

“Another message is that maybe you need CGM [continuous glucose monitoring],” Dr. Rabasa-Lhoret added. “But then you are having huge cost issues and access issues to really benefit from the pump.”

Dr. Heller, in introducing the trial, noted that meta-analyses have suggested that pumps may have an edge over MDI when it comes to glycemic control. But “one of the limitations in the existing evidence is that people allocated to pumps have received more training and attention, compared to MDI, and very few trials have compared pumps to MDI with comparable training and insulin adjustment,” he noted.

To be eligible for the REPOSE (Relative Effectiveness of Pumps Over MDI and Structured Education) trial, patients had to have had type 1 diabetes for at least 1 year. Also, they had to be willing to undertake flexible intensive insulin therapy with self-monitoring of blood glucose and carbohydrate counting, and had to have no clinical indication or strong preference for a pump.

The patients were randomized to MDI (using rapid and twice-daily long-acting insulin analogues) or to pumps that provided continuous subcutaneous infusion of insulin. All were given 38 hours of high-quality structured education through the Dose Adjustment for Normal Eating (DAFNE) program, a skills-based program in flexible intensive insulin therapy and self-management.

The results for the entire trial population showed that among the large majority with baseline HbA_1c levels of at least 7.5%, the mean change at 24 months was –0.64%.

In an intent-to-treat analysis, the mean change was –0.84% in the pump group and –0.42% in the MDI group. After adjustment, the difference between groups was not significant (–0.23%; P = .121).

In a per-protocol analysis, however, there was a difference between groups in favor of the pump (–0.84% vs. –0.32%; difference, –0.34%; P = .018).

“Importantly, HbA_1c remained well above recommended national and international targets,” Dr. Heller said, with only about a fifth of patients in each group achieving an HbA_1c of less than 7.5%.

The trial population as a whole had a reduction in the annual number of episodes of severe hypoglycemia per patient from 0.17 before baseline to 0.10 during the trial (incidence rate ratio, 0.46; P = .021). Again, there was no difference between groups.

The groups were also statistically indistinguishable with respect to diabetes-specific quality of life, general measures of well-being, anxiety and depression, and fear of hypoglycemia. But the pump group had greater improvements than the MDI group in scores for diabetes-specific diet restrictions (P = .004), daily hassles and function (P = .006), and treatment satisfaction (P less than .001).

The rates of serious adverse events were generally similar across the two groups, except for a higher rate of diabetic ketoacidosis with the pump (12.9% vs. 3.7%). “The difference was confined to the first year,” Dr. Heller noted. Most of the episodes were due to general infections (for example, urinary tract and upper respiratory tract infections), and the number was small among patients who adhered to sick day rules that had been covered in training.

He offered a parting message to physicians considering putting their patients on pumps: “Make sure they are up to self-managing their diabetes really actively, and if they are, absolutely. … I’m a passionate proponent of using technology for people who are up for it.”

Session attendee Dr. Irl B. Hirsch of the University of Washington, Seattle, said, “I’m very curious … about the frequency of home blood glucose monitoring, because that’s the key in my opinion for any insulin delivery – are they checking their blood sugars enough to make the appropriate adjustments? Was there more testing in one group than the other?”

Those data were obtained from patients who reported them, but were otherwise not systematically collected, Dr. Heller said.

Dr. Heller disclosed that he receives consulting fees/honoraria from Eli Lilly, Novo Nordisk, Sanofi-Aventis, Takeda, MSD, AstraZeneca, Johnson and Johnson, and Boehringer Ingelheim, and that he has clinical trial affiliations with Medtronic, UK.

VANCOUVER, B.C. – So far, just one of the newer diabetes drugs has been shown to cut cardiovascular risk in type 2 diabetes.

Dr. Bernard Zinman, chairman of the meeting’s program committee, explained which one it is, and also shared other highlights from this year’s World Diabetes Congress.

In an interview at the meeting, Dr. Zinman offered new insights on beta-cell preservation, diabetes prevention, pancreas imaging, the microbiome, and the best combination therapies for early intervention.

“Diabetes is a very complex disease,” said Dr. Zinman, also the director of the diabetes center at Mount Sinai Hospital in Toronto and a professor of medicine at the University of Toronto. “To imagine that there’s one therapy or one magic bullet” that’s going to take care of all the problems in diabetes, “is very naive.”

[email protected]

VANCOUVER, B.C. – So far, just one of the newer diabetes drugs has been shown to cut cardiovascular risk in type 2 diabetes.

Dr. Bernard Zinman, chairman of the meeting’s program committee, explained which one it is, and also shared other highlights from this year’s World Diabetes Congress.

In an interview at the meeting, Dr. Zinman offered new insights on beta-cell preservation, diabetes prevention, pancreas imaging, the microbiome, and the best combination therapies for early intervention.

“Diabetes is a very complex disease,” said Dr. Zinman, also the director of the diabetes center at Mount Sinai Hospital in Toronto and a professor of medicine at the University of Toronto. “To imagine that there’s one therapy or one magic bullet” that’s going to take care of all the problems in diabetes, “is very naive.”

[email protected]

VANCOUVER, B.C. – So far, just one of the newer diabetes drugs has been shown to cut cardiovascular risk in type 2 diabetes.

Dr. Bernard Zinman, chairman of the meeting’s program committee, explained which one it is, and also shared other highlights from this year’s World Diabetes Congress.

In an interview at the meeting, Dr. Zinman offered new insights on beta-cell preservation, diabetes prevention, pancreas imaging, the microbiome, and the best combination therapies for early intervention.

“Diabetes is a very complex disease,” said Dr. Zinman, also the director of the diabetes center at Mount Sinai Hospital in Toronto and a professor of medicine at the University of Toronto. “To imagine that there’s one therapy or one magic bullet” that’s going to take care of all the problems in diabetes, “is very naive.”

[email protected]

VANCOUVER, B.C. – Despite agreeing to use birth control and receiving frequent counseling about pregnancy avoidance, a sizable share of teens with type 2 diabetes mellitus become pregnant, and these pregnancies often have poor outcomes, researchers reported at the World Diabetes Congress.

The analysis was based on 452 female participants in the national Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, the largest trial in youth with this form of diabetes to date and one designed to have good representation of various racial/ethnic groups.

Overall, 10% of the girls became pregnant during a period of up to 6.5 years. The majority were not using contraception and did not recall the counseling. More than one-fourth of the pregnancies ended in fetal loss or stillbirth. And one-fifth of live-born infants had major congenital anomalies.

“We need to better understand the reasons for pregnancy in youth with type 2 diabetes and why, despite counseling, they become pregnant,” commented first author Dr. Kristen J. Nadeau of the division of pediatric endocrinology, department of pediatrics, University of Colorado, Aurora.

“Best practices for metabolically unhealthy pregnancy prevention in type 2 diabetic teens also requires further study,” she added. “Long-acting contraception, we think, currently is the best method and likely the way to go in these girls who are not retaining the education and [adhering to] the behaviors that we are hoping for.”

“This study is critically important and horribly depressing,” commented session comoderator Dr. Robert E. Ratner, professor of medicine at Georgetown University and senior research scientist at the MedStar Health Research Institute, Washington, as well as chief scientific and medical officer of the American Diabetes Association, Alexandria, Va.

“It points out the difficulties of being a teenager and the even greater difficulties of being a teenager with a chronic disease,” he said in an interview, adding that there are no easy solutions.

“The combination of a teen pregnancy in someone with type 2 diabetes creates the perfect storm,” Dr. Nadeau noted. “Diabetes control is worse in adolescence than in any other time in the lifespan, and with increasing rates of type 2 diabetes in youth, increases in a teen pregnancy that are complicated by diabetes are anticipated,” she added.

At baseline, participants in TODAY were 10-17 years old, were overweight or obese, and had a diabetes duration of less than 2 years and a hemoglobin A_1c level of less than 8%. They were randomized to three treatment arms (metformin alone, metformin plus rosiglitazone, or metformin plus an intensive lifestyle program).

Consent for the trial required the use of a birth control method, including abstinence; in addition, every 2-3 months, the girls received diabetes education and counseling to defer pregnancy until their HbA_1c level fell below 6%. They also had regular pregnancy testing, and those with a positive result were taken off their trial medication and referred to a maternal-fetal medicine specialist.

The results reported at the meeting and simultaneously published in Diabetes Care (doi: 10.2337/dc15-1206) showed that 46 (10.2%) of the girls had 63 pregnancies. On average, they were 18 years old at the time of a first pregnancy.

Despite the counseling, only about 5% of those teens who became pregnant reported that they had been using contraception. Moreover, just 13% recalled the counseling.

The median body mass index closest to conception was 35.2 kg/m², and the median HbA_1c level was 7%. “Because of the fact that we were so heavily monitoring these girls, we had their HbA_1c under better control than is typical. In our typical clinic, the mean is more like 8.5%-9%,” Dr. Nadeau noted.

Relative to peers who did not become pregnant, those who did were significantly older, were less likely to be living with both parents or their mother, and had a lower household income.

Seven of the 63 pregnancies were electively terminated. Of the 53 remaining pregnancies with data, 12 ended in pregnancy loss and 2 ended in a stillbirth.

Among the 39 live-born infants, 6 were preterm and 8 had major congenital anomalies. And among the 37 with known birth weight, 10 were either small or large for gestational age.

Girls randomized to metformin plus rosiglitazone had a higher rate of term normal births than peers in the other arms (P = .027). “Of note, none of the participants reported taking the rosiglitazone after the pregnancy was discovered, as was per the study protocol,” Dr. Nadeau commented. In contrast, neither maternal body mass index nor – surprisingly – HbA_1c level was significantly associated with pregnancy outcome.

The rate of preterm birth observed in the teens studied was similar to what has been seen in adult women with diabetes, she noted. But the rate of major congenital anomalies was about four times higher.

“This potentially might be due to lower overall socioeconomic status of the girls in the TODAY study. Other reasons for the anomalies are uncertain, but might include metabolic control, smoking, or extreme obesity,” she said.

Dr. Nadeau disclosed that she had no relevant conflicts of interest.

VANCOUVER, B.C. – Despite agreeing to use birth control and receiving frequent counseling about pregnancy avoidance, a sizable share of teens with type 2 diabetes mellitus become pregnant, and these pregnancies often have poor outcomes, researchers reported at the World Diabetes Congress.

The analysis was based on 452 female participants in the national Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, the largest trial in youth with this form of diabetes to date and one designed to have good representation of various racial/ethnic groups.

Overall, 10% of the girls became pregnant during a period of up to 6.5 years. The majority were not using contraception and did not recall the counseling. More than one-fourth of the pregnancies ended in fetal loss or stillbirth. And one-fifth of live-born infants had major congenital anomalies.

“We need to better understand the reasons for pregnancy in youth with type 2 diabetes and why, despite counseling, they become pregnant,” commented first author Dr. Kristen J. Nadeau of the division of pediatric endocrinology, department of pediatrics, University of Colorado, Aurora.

“Best practices for metabolically unhealthy pregnancy prevention in type 2 diabetic teens also requires further study,” she added. “Long-acting contraception, we think, currently is the best method and likely the way to go in these girls who are not retaining the education and [adhering to] the behaviors that we are hoping for.”

“This study is critically important and horribly depressing,” commented session comoderator Dr. Robert E. Ratner, professor of medicine at Georgetown University and senior research scientist at the MedStar Health Research Institute, Washington, as well as chief scientific and medical officer of the American Diabetes Association, Alexandria, Va.

“It points out the difficulties of being a teenager and the even greater difficulties of being a teenager with a chronic disease,” he said in an interview, adding that there are no easy solutions.

“The combination of a teen pregnancy in someone with type 2 diabetes creates the perfect storm,” Dr. Nadeau noted. “Diabetes control is worse in adolescence than in any other time in the lifespan, and with increasing rates of type 2 diabetes in youth, increases in a teen pregnancy that are complicated by diabetes are anticipated,” she added.

At baseline, participants in TODAY were 10-17 years old, were overweight or obese, and had a diabetes duration of less than 2 years and a hemoglobin A_1c level of less than 8%. They were randomized to three treatment arms (metformin alone, metformin plus rosiglitazone, or metformin plus an intensive lifestyle program).

Consent for the trial required the use of a birth control method, including abstinence; in addition, every 2-3 months, the girls received diabetes education and counseling to defer pregnancy until their HbA_1c level fell below 6%. They also had regular pregnancy testing, and those with a positive result were taken off their trial medication and referred to a maternal-fetal medicine specialist.

The results reported at the meeting and simultaneously published in Diabetes Care (doi: 10.2337/dc15-1206) showed that 46 (10.2%) of the girls had 63 pregnancies. On average, they were 18 years old at the time of a first pregnancy.

Despite the counseling, only about 5% of those teens who became pregnant reported that they had been using contraception. Moreover, just 13% recalled the counseling.

The median body mass index closest to conception was 35.2 kg/m², and the median HbA_1c level was 7%. “Because of the fact that we were so heavily monitoring these girls, we had their HbA_1c under better control than is typical. In our typical clinic, the mean is more like 8.5%-9%,” Dr. Nadeau noted.

Relative to peers who did not become pregnant, those who did were significantly older, were less likely to be living with both parents or their mother, and had a lower household income.

Seven of the 63 pregnancies were electively terminated. Of the 53 remaining pregnancies with data, 12 ended in pregnancy loss and 2 ended in a stillbirth.

Among the 39 live-born infants, 6 were preterm and 8 had major congenital anomalies. And among the 37 with known birth weight, 10 were either small or large for gestational age.

Girls randomized to metformin plus rosiglitazone had a higher rate of term normal births than peers in the other arms (P = .027). “Of note, none of the participants reported taking the rosiglitazone after the pregnancy was discovered, as was per the study protocol,” Dr. Nadeau commented. In contrast, neither maternal body mass index nor – surprisingly – HbA_1c level was significantly associated with pregnancy outcome.

The rate of preterm birth observed in the teens studied was similar to what has been seen in adult women with diabetes, she noted. But the rate of major congenital anomalies was about four times higher.

“This potentially might be due to lower overall socioeconomic status of the girls in the TODAY study. Other reasons for the anomalies are uncertain, but might include metabolic control, smoking, or extreme obesity,” she said.

Dr. Nadeau disclosed that she had no relevant conflicts of interest.

VANCOUVER, B.C. – Despite agreeing to use birth control and receiving frequent counseling about pregnancy avoidance, a sizable share of teens with type 2 diabetes mellitus become pregnant, and these pregnancies often have poor outcomes, researchers reported at the World Diabetes Congress.

The analysis was based on 452 female participants in the national Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, the largest trial in youth with this form of diabetes to date and one designed to have good representation of various racial/ethnic groups.

Overall, 10% of the girls became pregnant during a period of up to 6.5 years. The majority were not using contraception and did not recall the counseling. More than one-fourth of the pregnancies ended in fetal loss or stillbirth. And one-fifth of live-born infants had major congenital anomalies.

“We need to better understand the reasons for pregnancy in youth with type 2 diabetes and why, despite counseling, they become pregnant,” commented first author Dr. Kristen J. Nadeau of the division of pediatric endocrinology, department of pediatrics, University of Colorado, Aurora.

“Best practices for metabolically unhealthy pregnancy prevention in type 2 diabetic teens also requires further study,” she added. “Long-acting contraception, we think, currently is the best method and likely the way to go in these girls who are not retaining the education and [adhering to] the behaviors that we are hoping for.”

“This study is critically important and horribly depressing,” commented session comoderator Dr. Robert E. Ratner, professor of medicine at Georgetown University and senior research scientist at the MedStar Health Research Institute, Washington, as well as chief scientific and medical officer of the American Diabetes Association, Alexandria, Va.

“It points out the difficulties of being a teenager and the even greater difficulties of being a teenager with a chronic disease,” he said in an interview, adding that there are no easy solutions.

“The combination of a teen pregnancy in someone with type 2 diabetes creates the perfect storm,” Dr. Nadeau noted. “Diabetes control is worse in adolescence than in any other time in the lifespan, and with increasing rates of type 2 diabetes in youth, increases in a teen pregnancy that are complicated by diabetes are anticipated,” she added.

At baseline, participants in TODAY were 10-17 years old, were overweight or obese, and had a diabetes duration of less than 2 years and a hemoglobin A_1c level of less than 8%. They were randomized to three treatment arms (metformin alone, metformin plus rosiglitazone, or metformin plus an intensive lifestyle program).

Consent for the trial required the use of a birth control method, including abstinence; in addition, every 2-3 months, the girls received diabetes education and counseling to defer pregnancy until their HbA_1c level fell below 6%. They also had regular pregnancy testing, and those with a positive result were taken off their trial medication and referred to a maternal-fetal medicine specialist.

The results reported at the meeting and simultaneously published in Diabetes Care (doi: 10.2337/dc15-1206) showed that 46 (10.2%) of the girls had 63 pregnancies. On average, they were 18 years old at the time of a first pregnancy.

Despite the counseling, only about 5% of those teens who became pregnant reported that they had been using contraception. Moreover, just 13% recalled the counseling.

The median body mass index closest to conception was 35.2 kg/m², and the median HbA_1c level was 7%. “Because of the fact that we were so heavily monitoring these girls, we had their HbA_1c under better control than is typical. In our typical clinic, the mean is more like 8.5%-9%,” Dr. Nadeau noted.

Relative to peers who did not become pregnant, those who did were significantly older, were less likely to be living with both parents or their mother, and had a lower household income.

Seven of the 63 pregnancies were electively terminated. Of the 53 remaining pregnancies with data, 12 ended in pregnancy loss and 2 ended in a stillbirth.

Among the 39 live-born infants, 6 were preterm and 8 had major congenital anomalies. And among the 37 with known birth weight, 10 were either small or large for gestational age.

Girls randomized to metformin plus rosiglitazone had a higher rate of term normal births than peers in the other arms (P = .027). “Of note, none of the participants reported taking the rosiglitazone after the pregnancy was discovered, as was per the study protocol,” Dr. Nadeau commented. In contrast, neither maternal body mass index nor – surprisingly – HbA_1c level was significantly associated with pregnancy outcome.

The rate of preterm birth observed in the teens studied was similar to what has been seen in adult women with diabetes, she noted. But the rate of major congenital anomalies was about four times higher.

“This potentially might be due to lower overall socioeconomic status of the girls in the TODAY study. Other reasons for the anomalies are uncertain, but might include metabolic control, smoking, or extreme obesity,” she said.

Dr. Nadeau disclosed that she had no relevant conflicts of interest.

VANCOUVER, B.C. – If patients haven’t lost 5% or more of their body weight after 16 weeks on liraglutide at a daily dose of 3 mg, the drug’s not going to work for weight loss and should be stopped, according to findings from a study by Novo Nordisk, the maker of liraglutide, that was presented at the World Diabetes Congress.

The 3-mg dose is marketed for weight loss as Saxenda; the drug is also sold as Victoza for type 2 diabetes at a dose of up to 1.8 mg.

The findings come from a new analysis of Novo Nordisk’s SCALE study, which included diet and exercise along with liraglutide 3 mg. About two-thirds of obese and prediabetic patients, versus about a third of patients on placebo, responded early to the 3-mg dose, losing 5% or more of their weight by week 16. By week 56, they had a mean weight loss of 11.5%. About half of patients with type 2 diabetes were early responders; they lost a mean of 9.3% at week 56. Nonresponders lost about 3.7% of their body weight after 56 weeks. Rates of hepatobiliary disorders with liraglutide were highest in nondiabetic subjects, at 3.5% (N Engl J Med. 2015 Jul 2;373[1]:11-22).

In an interview at the meeting, investigator Dr. Matthias Blüher, an endocrinology professor at the University of Leipzig (Germany), explained how to make use of the findings.

[email protected]

VANCOUVER, B.C. – If patients haven’t lost 5% or more of their body weight after 16 weeks on liraglutide at a daily dose of 3 mg, the drug’s not going to work for weight loss and should be stopped, according to findings from a study by Novo Nordisk, the maker of liraglutide, that was presented at the World Diabetes Congress.

The 3-mg dose is marketed for weight loss as Saxenda; the drug is also sold as Victoza for type 2 diabetes at a dose of up to 1.8 mg.

The findings come from a new analysis of Novo Nordisk’s SCALE study, which included diet and exercise along with liraglutide 3 mg. About two-thirds of obese and prediabetic patients, versus about a third of patients on placebo, responded early to the 3-mg dose, losing 5% or more of their weight by week 16. By week 56, they had a mean weight loss of 11.5%. About half of patients with type 2 diabetes were early responders; they lost a mean of 9.3% at week 56. Nonresponders lost about 3.7% of their body weight after 56 weeks. Rates of hepatobiliary disorders with liraglutide were highest in nondiabetic subjects, at 3.5% (N Engl J Med. 2015 Jul 2;373[1]:11-22).

In an interview at the meeting, investigator Dr. Matthias Blüher, an endocrinology professor at the University of Leipzig (Germany), explained how to make use of the findings.

[email protected]

VANCOUVER, B.C. – If patients haven’t lost 5% or more of their body weight after 16 weeks on liraglutide at a daily dose of 3 mg, the drug’s not going to work for weight loss and should be stopped, according to findings from a study by Novo Nordisk, the maker of liraglutide, that was presented at the World Diabetes Congress.

The 3-mg dose is marketed for weight loss as Saxenda; the drug is also sold as Victoza for type 2 diabetes at a dose of up to 1.8 mg.

The findings come from a new analysis of Novo Nordisk’s SCALE study, which included diet and exercise along with liraglutide 3 mg. About two-thirds of obese and prediabetic patients, versus about a third of patients on placebo, responded early to the 3-mg dose, losing 5% or more of their weight by week 16. By week 56, they had a mean weight loss of 11.5%. About half of patients with type 2 diabetes were early responders; they lost a mean of 9.3% at week 56. Nonresponders lost about 3.7% of their body weight after 56 weeks. Rates of hepatobiliary disorders with liraglutide were highest in nondiabetic subjects, at 3.5% (N Engl J Med. 2015 Jul 2;373[1]:11-22).

In an interview at the meeting, investigator Dr. Matthias Blüher, an endocrinology professor at the University of Leipzig (Germany), explained how to make use of the findings.

[email protected]

VANCOUVER – Intensive glucose control needs to begin early in the course of kidney disease to have its greatest renal protective effect in patients with type 2 diabetes, suggests a study reported at the World Diabetes Congress.

The conclusions are based on long-term follow-up of patients with type 2 diabetes and high vascular risk who were treated on an international randomized trial for about 5 years with either intensive or standard glucose control.

Results for the 8,494 patients at a median total follow-up of nearly a decade showed that patients with lesser stages of chronic kidney disease (CKD) at the start of the study benefited more from intensive over standard glucose control in reducing the risk of onset of dialysis or renal transplantation, reported Dr. Sophia Zoungas.

Reassuringly, intensive glucose lowering was not associated with an increase in the risk of death or cardiovascular death, regardless of patients’ CKD stage at baseline. And the higher relative risk of severe hypoglycemia with the intensive strategy was likewise similar across baseline CKD stages.

“We think that the commencement of intensive glucose control is particularly important early in the disease process, and hopefully we can get in before the development of significant kidney disease,” said Dr. Zoungas, an endocrinologist with the Monash University School of Public Health and Preventive Medicine in Clayton, Australia.

“The lesser benefit in those with moderately reduced kidney function (CKD stage 3 or greater) may indicate that the glucose-independent mechanisms of renal progression may predominate in the later stages of the disease,” she speculated.

These new data are helpful for real-world clinical care, according to session co-moderator Dr. David A. D’Alessio, a professor of medicine and director of the division of endocrinology, metabolism, and nutrition at Duke University, Durham, N.C.

“I think this study was really important. It shows the strength of doing a good trial and then not stopping at 5 years, but continuing to collect data,” he said in an interview. “These studies end up being really useful to practitioners because we oftentimes see patients whom we’ve followed for up to 10 years.”

The patients studied had participated in the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), which tested both intensive glucose control and blood pressure–lowering therapy. After the 5-year trial, patients returned to their usual practitioners’ care but had continued collection of data. The ADVANCE post-trial observational study (ADVANCE-ON) analyses were conducted after a median total follow-up of 9.9 years. Main findings were previously published (N Engl J Med. 2014;371:1392-406).

The greater reduction in hemoglobin A1c levels seen with intensive glucose control versus standard control on the trial was lost after the trial ended, Dr. Zoungas noted. “So if there was any effect in ADVANCE-ON, it would be attributable to the difference achieved during the in-trial period,” she said.

Compared with peers in the standard control group, patients in the intensive control group had a reduction in the risk of end-stage kidney disease during the entire follow-up (hazard ratio, 0.54) similar to that seen while they were on the trial (hazard ratio, 0.35).

In subgroup analyses, the lower the baseline stage of CKD, the greater the edge of intensive glucose control over standard glucose control for reducing the risk of end-stage kidney disease. The hazard ratio was 0.16 for patients with no CKD at baseline, 0.34 for those with stage 1 or 2, and 0.89 for patients with stage 3 or higher (P = .04). The number needed to treat for 5 years to prevent one case of end-stage kidney disease during the entire follow-up was 259, 109, and 393, respectively.

“What’s interesting to note here is that during the overall 9.9 years of follow-up, we have smaller numbers needed to treat for those with no evidence of CKD or early-stage CKD,” Dr. Zoungas said.

The investigators explored treatment impact on all-cause mortality and cardiovascular mortality according to baseline CKD stage, prompted by findings from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showing increased risks of these outcomes in patients with mild to moderate CKD at baseline who received intensive glucose control (Kidney Int. 2015;87:649-59).

ADVANCE-ON results, in contrast, showed no significant elevation in risk with intensive control, either while patients were on the trial or for the total 9.9 years of follow-up even in those at the more advanced stages of CKD, Dr. Zoungas said.

The relative risk of severe hypoglycemia was similarly elevated with intensive control, compared with standard control across CKD subgroups, although the absolute risk was higher for those with stage 3 or higher disease.

Dr. Zoungas disclosed that she receives honoraria from Servier for speaking about ADVANCE and ADVANCE-ON at scientific meetings, and that she is on the speakers bureau and advisory boards for and receives travel support from Merck Sharp & Dohme and AstraZeneca/Bristol-Myers Squibb. The study was funded in part by Servier.

VANCOUVER – Intensive glucose control needs to begin early in the course of kidney disease to have its greatest renal protective effect in patients with type 2 diabetes, suggests a study reported at the World Diabetes Congress.

The conclusions are based on long-term follow-up of patients with type 2 diabetes and high vascular risk who were treated on an international randomized trial for about 5 years with either intensive or standard glucose control.

Results for the 8,494 patients at a median total follow-up of nearly a decade showed that patients with lesser stages of chronic kidney disease (CKD) at the start of the study benefited more from intensive over standard glucose control in reducing the risk of onset of dialysis or renal transplantation, reported Dr. Sophia Zoungas.

Reassuringly, intensive glucose lowering was not associated with an increase in the risk of death or cardiovascular death, regardless of patients’ CKD stage at baseline. And the higher relative risk of severe hypoglycemia with the intensive strategy was likewise similar across baseline CKD stages.

“We think that the commencement of intensive glucose control is particularly important early in the disease process, and hopefully we can get in before the development of significant kidney disease,” said Dr. Zoungas, an endocrinologist with the Monash University School of Public Health and Preventive Medicine in Clayton, Australia.

“The lesser benefit in those with moderately reduced kidney function (CKD stage 3 or greater) may indicate that the glucose-independent mechanisms of renal progression may predominate in the later stages of the disease,” she speculated.

These new data are helpful for real-world clinical care, according to session co-moderator Dr. David A. D’Alessio, a professor of medicine and director of the division of endocrinology, metabolism, and nutrition at Duke University, Durham, N.C.

“I think this study was really important. It shows the strength of doing a good trial and then not stopping at 5 years, but continuing to collect data,” he said in an interview. “These studies end up being really useful to practitioners because we oftentimes see patients whom we’ve followed for up to 10 years.”

The patients studied had participated in the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), which tested both intensive glucose control and blood pressure–lowering therapy. After the 5-year trial, patients returned to their usual practitioners’ care but had continued collection of data. The ADVANCE post-trial observational study (ADVANCE-ON) analyses were conducted after a median total follow-up of 9.9 years. Main findings were previously published (N Engl J Med. 2014;371:1392-406).

The greater reduction in hemoglobin A1c levels seen with intensive glucose control versus standard control on the trial was lost after the trial ended, Dr. Zoungas noted. “So if there was any effect in ADVANCE-ON, it would be attributable to the difference achieved during the in-trial period,” she said.

Compared with peers in the standard control group, patients in the intensive control group had a reduction in the risk of end-stage kidney disease during the entire follow-up (hazard ratio, 0.54) similar to that seen while they were on the trial (hazard ratio, 0.35).

In subgroup analyses, the lower the baseline stage of CKD, the greater the edge of intensive glucose control over standard glucose control for reducing the risk of end-stage kidney disease. The hazard ratio was 0.16 for patients with no CKD at baseline, 0.34 for those with stage 1 or 2, and 0.89 for patients with stage 3 or higher (P = .04). The number needed to treat for 5 years to prevent one case of end-stage kidney disease during the entire follow-up was 259, 109, and 393, respectively.

“What’s interesting to note here is that during the overall 9.9 years of follow-up, we have smaller numbers needed to treat for those with no evidence of CKD or early-stage CKD,” Dr. Zoungas said.

The investigators explored treatment impact on all-cause mortality and cardiovascular mortality according to baseline CKD stage, prompted by findings from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showing increased risks of these outcomes in patients with mild to moderate CKD at baseline who received intensive glucose control (Kidney Int. 2015;87:649-59).

ADVANCE-ON results, in contrast, showed no significant elevation in risk with intensive control, either while patients were on the trial or for the total 9.9 years of follow-up even in those at the more advanced stages of CKD, Dr. Zoungas said.

The relative risk of severe hypoglycemia was similarly elevated with intensive control, compared with standard control across CKD subgroups, although the absolute risk was higher for those with stage 3 or higher disease.

Dr. Zoungas disclosed that she receives honoraria from Servier for speaking about ADVANCE and ADVANCE-ON at scientific meetings, and that she is on the speakers bureau and advisory boards for and receives travel support from Merck Sharp & Dohme and AstraZeneca/Bristol-Myers Squibb. The study was funded in part by Servier.

VANCOUVER – Intensive glucose control needs to begin early in the course of kidney disease to have its greatest renal protective effect in patients with type 2 diabetes, suggests a study reported at the World Diabetes Congress.

The conclusions are based on long-term follow-up of patients with type 2 diabetes and high vascular risk who were treated on an international randomized trial for about 5 years with either intensive or standard glucose control.

Results for the 8,494 patients at a median total follow-up of nearly a decade showed that patients with lesser stages of chronic kidney disease (CKD) at the start of the study benefited more from intensive over standard glucose control in reducing the risk of onset of dialysis or renal transplantation, reported Dr. Sophia Zoungas.

Reassuringly, intensive glucose lowering was not associated with an increase in the risk of death or cardiovascular death, regardless of patients’ CKD stage at baseline. And the higher relative risk of severe hypoglycemia with the intensive strategy was likewise similar across baseline CKD stages.

“We think that the commencement of intensive glucose control is particularly important early in the disease process, and hopefully we can get in before the development of significant kidney disease,” said Dr. Zoungas, an endocrinologist with the Monash University School of Public Health and Preventive Medicine in Clayton, Australia.

“The lesser benefit in those with moderately reduced kidney function (CKD stage 3 or greater) may indicate that the glucose-independent mechanisms of renal progression may predominate in the later stages of the disease,” she speculated.

These new data are helpful for real-world clinical care, according to session co-moderator Dr. David A. D’Alessio, a professor of medicine and director of the division of endocrinology, metabolism, and nutrition at Duke University, Durham, N.C.

“I think this study was really important. It shows the strength of doing a good trial and then not stopping at 5 years, but continuing to collect data,” he said in an interview. “These studies end up being really useful to practitioners because we oftentimes see patients whom we’ve followed for up to 10 years.”

The patients studied had participated in the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), which tested both intensive glucose control and blood pressure–lowering therapy. After the 5-year trial, patients returned to their usual practitioners’ care but had continued collection of data. The ADVANCE post-trial observational study (ADVANCE-ON) analyses were conducted after a median total follow-up of 9.9 years. Main findings were previously published (N Engl J Med. 2014;371:1392-406).

The greater reduction in hemoglobin A1c levels seen with intensive glucose control versus standard control on the trial was lost after the trial ended, Dr. Zoungas noted. “So if there was any effect in ADVANCE-ON, it would be attributable to the difference achieved during the in-trial period,” she said.

Compared with peers in the standard control group, patients in the intensive control group had a reduction in the risk of end-stage kidney disease during the entire follow-up (hazard ratio, 0.54) similar to that seen while they were on the trial (hazard ratio, 0.35).

In subgroup analyses, the lower the baseline stage of CKD, the greater the edge of intensive glucose control over standard glucose control for reducing the risk of end-stage kidney disease. The hazard ratio was 0.16 for patients with no CKD at baseline, 0.34 for those with stage 1 or 2, and 0.89 for patients with stage 3 or higher (P = .04). The number needed to treat for 5 years to prevent one case of end-stage kidney disease during the entire follow-up was 259, 109, and 393, respectively.

“What’s interesting to note here is that during the overall 9.9 years of follow-up, we have smaller numbers needed to treat for those with no evidence of CKD or early-stage CKD,” Dr. Zoungas said.

The investigators explored treatment impact on all-cause mortality and cardiovascular mortality according to baseline CKD stage, prompted by findings from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showing increased risks of these outcomes in patients with mild to moderate CKD at baseline who received intensive glucose control (Kidney Int. 2015;87:649-59).

ADVANCE-ON results, in contrast, showed no significant elevation in risk with intensive control, either while patients were on the trial or for the total 9.9 years of follow-up even in those at the more advanced stages of CKD, Dr. Zoungas said.

The relative risk of severe hypoglycemia was similarly elevated with intensive control, compared with standard control across CKD subgroups, although the absolute risk was higher for those with stage 3 or higher disease.

Dr. Zoungas disclosed that she receives honoraria from Servier for speaking about ADVANCE and ADVANCE-ON at scientific meetings, and that she is on the speakers bureau and advisory boards for and receives travel support from Merck Sharp & Dohme and AstraZeneca/Bristol-Myers Squibb. The study was funded in part by Servier.

VANCOUVER – At least one of the commercially available energy drinks plays havoc with blood sugar and insulin levels in teen users, according to research from the University of Calgary (Alta.).

Ten teenage boys and ten girls were randomized to one regular “5-hour energy” drink, or, as a control, the decaffeinated version of the product, and then given an oral glucose tolerance test 40 minutes later.

In the second phase, the kids switched over to the drink they didn’t get in the first go-round, and the tolerance testing was repeated. Blood testing was done at baseline and throughout the study.

Investigator Jane Shearer, Ph.D., of the university’s department of biochemistry and molecular biology, explained the results, and why she’s worried about them, in an interview at the World Diabetes Congress.

Five-hour energy is a sugar-free 2-ounce drink containing about 200 mg of caffeine in its regular-strength formulation.

The findings raise another red flag about energy drinks in kids, especially if they are prone to diabetes. Dr. Shearer also shared her thoughts on what to do to address the issue.

[email protected]

VANCOUVER – At least one of the commercially available energy drinks plays havoc with blood sugar and insulin levels in teen users, according to research from the University of Calgary (Alta.).

Ten teenage boys and ten girls were randomized to one regular “5-hour energy” drink, or, as a control, the decaffeinated version of the product, and then given an oral glucose tolerance test 40 minutes later.

In the second phase, the kids switched over to the drink they didn’t get in the first go-round, and the tolerance testing was repeated. Blood testing was done at baseline and throughout the study.

Investigator Jane Shearer, Ph.D., of the university’s department of biochemistry and molecular biology, explained the results, and why she’s worried about them, in an interview at the World Diabetes Congress.

Five-hour energy is a sugar-free 2-ounce drink containing about 200 mg of caffeine in its regular-strength formulation.

The findings raise another red flag about energy drinks in kids, especially if they are prone to diabetes. Dr. Shearer also shared her thoughts on what to do to address the issue.

[email protected]

VANCOUVER – At least one of the commercially available energy drinks plays havoc with blood sugar and insulin levels in teen users, according to research from the University of Calgary (Alta.).

Ten teenage boys and ten girls were randomized to one regular “5-hour energy” drink, or, as a control, the decaffeinated version of the product, and then given an oral glucose tolerance test 40 minutes later.

In the second phase, the kids switched over to the drink they didn’t get in the first go-round, and the tolerance testing was repeated. Blood testing was done at baseline and throughout the study.

Investigator Jane Shearer, Ph.D., of the university’s department of biochemistry and molecular biology, explained the results, and why she’s worried about them, in an interview at the World Diabetes Congress.

Five-hour energy is a sugar-free 2-ounce drink containing about 200 mg of caffeine in its regular-strength formulation.

The findings raise another red flag about energy drinks in kids, especially if they are prone to diabetes. Dr. Shearer also shared her thoughts on what to do to address the issue.

[email protected]

VANCOUVER, B.C. – Transitioning to adult diabetes care tripled hospital admissions for diabetic ketoacidosis in a Canadian study of 147 patients at Western University in London, Ont.

The number of diabetic ketoacidosis (DKA) admissions and emergency department visits for hypoglycemia or hyperglycemia increased from 65 during the 3 years before the subjects turned 18 to 101 during the 3 years afterward.

There were other problems, too. Mean hemoglobin A_1c increased from 8.66 % to 8.89% after transition to adult care, and urine albumin creatinine ratio (ACR) testing decreased, with 47 patients (32%) tested at least once before transition, but 29 (20%) afterward.

“Some would say that these are teenagers, and they’ll are grow out of” it as they learn how to care for themselves as adults, “but I don’t think that’s good enough” because there’s an increased risk of acute complications. “The transition period is associated with worsening glycemic control and an increased risk of DKA admission. There is room for improved screening, as well. I think there is certainly a role for intervention,” said Dr. Jennifer Huynh, chief resident in internal medicine at Western University.

The differences in HbA_1care big enough to worry about. “We know when A_1c is high, even small increases or decreases” make a difference. Meanwhile, the increased risk of DKA (odds ratio, 3; 95% confidence interval, 1.19-7.5) is “very concerning,” she said at the World Diabetes Congress.

It’s been reported before that children with diabetes run into trouble when they move into adult care; the findings are a reminder of the issue, and help firm up the extent of the problem. The investigators were able to do a robust comparison of pre- and posttransition patients because the database at Western University links patients’ pediatric and adult records.

What often happens is that diabetes takes a backseat to school, work, relationships, and other pressures of emerging adulthood, and parents are no longer around to make sure kids take care of themselves. Given all that’s going on, it’s not surprising that the researchers also found there were 1,149 office visits in the 3 years before the subjects turned 18, but only 750 in the 3 years afterward.

All but three of the young adults in the study had type 1 diabetes, and just over half were women. At the baseline visit at 15 years of age, the median duration of diabetes was 5 years, mean weight was 66.4 kg, and the mean body mass index was 23.5 kg/m^2. Forty-five subjects (31%) were on an insulin pump, 96 (65%) were on multiple daily injections, 3 (2%) were on premixed insulin, and 3 (2%) took oral agents.

Researchers at Western University and elsewhere are putting a lot of effort into figuring out how to improve the situation. Special transition clinics, support groups, and social media campaigns are just some of what’s being tried.

Investigators from Western University are finishing up a randomized trial to see if a transition coordinator helps. Patients were randomized to usual care or care overseen by the coordinator, a certified diabetes educator.

The coordinator stays in touch with the teenagers, sends them test results, reminds them of appointments for lab work and office visits, and, in general, serves as a sounding board, guide, and friend to help them manage the transition into adult care.

The hope is that the efforts will improves clinic attendance and glycemic control, among other things.

Western University is considering a survey of transition programs in Canada, to find out what works so “we can make some recommendations in terms of policy,” Dr. Huynh said.

The investigators have no conflicts of interest, and there was no industry funding for the work.

[email protected]

VANCOUVER, B.C. – Transitioning to adult diabetes care tripled hospital admissions for diabetic ketoacidosis in a Canadian study of 147 patients at Western University in London, Ont.

The number of diabetic ketoacidosis (DKA) admissions and emergency department visits for hypoglycemia or hyperglycemia increased from 65 during the 3 years before the subjects turned 18 to 101 during the 3 years afterward.

There were other problems, too. Mean hemoglobin A_1c increased from 8.66 % to 8.89% after transition to adult care, and urine albumin creatinine ratio (ACR) testing decreased, with 47 patients (32%) tested at least once before transition, but 29 (20%) afterward.

“Some would say that these are teenagers, and they’ll are grow out of” it as they learn how to care for themselves as adults, “but I don’t think that’s good enough” because there’s an increased risk of acute complications. “The transition period is associated with worsening glycemic control and an increased risk of DKA admission. There is room for improved screening, as well. I think there is certainly a role for intervention,” said Dr. Jennifer Huynh, chief resident in internal medicine at Western University.

The differences in HbA_1care big enough to worry about. “We know when A_1c is high, even small increases or decreases” make a difference. Meanwhile, the increased risk of DKA (odds ratio, 3; 95% confidence interval, 1.19-7.5) is “very concerning,” she said at the World Diabetes Congress.

It’s been reported before that children with diabetes run into trouble when they move into adult care; the findings are a reminder of the issue, and help firm up the extent of the problem. The investigators were able to do a robust comparison of pre- and posttransition patients because the database at Western University links patients’ pediatric and adult records.

What often happens is that diabetes takes a backseat to school, work, relationships, and other pressures of emerging adulthood, and parents are no longer around to make sure kids take care of themselves. Given all that’s going on, it’s not surprising that the researchers also found there were 1,149 office visits in the 3 years before the subjects turned 18, but only 750 in the 3 years afterward.

All but three of the young adults in the study had type 1 diabetes, and just over half were women. At the baseline visit at 15 years of age, the median duration of diabetes was 5 years, mean weight was 66.4 kg, and the mean body mass index was 23.5 kg/m^2. Forty-five subjects (31%) were on an insulin pump, 96 (65%) were on multiple daily injections, 3 (2%) were on premixed insulin, and 3 (2%) took oral agents.

Researchers at Western University and elsewhere are putting a lot of effort into figuring out how to improve the situation. Special transition clinics, support groups, and social media campaigns are just some of what’s being tried.

Investigators from Western University are finishing up a randomized trial to see if a transition coordinator helps. Patients were randomized to usual care or care overseen by the coordinator, a certified diabetes educator.

The coordinator stays in touch with the teenagers, sends them test results, reminds them of appointments for lab work and office visits, and, in general, serves as a sounding board, guide, and friend to help them manage the transition into adult care.

The hope is that the efforts will improves clinic attendance and glycemic control, among other things.

Western University is considering a survey of transition programs in Canada, to find out what works so “we can make some recommendations in terms of policy,” Dr. Huynh said.

The investigators have no conflicts of interest, and there was no industry funding for the work.

[email protected]

VANCOUVER, B.C. – Transitioning to adult diabetes care tripled hospital admissions for diabetic ketoacidosis in a Canadian study of 147 patients at Western University in London, Ont.

The number of diabetic ketoacidosis (DKA) admissions and emergency department visits for hypoglycemia or hyperglycemia increased from 65 during the 3 years before the subjects turned 18 to 101 during the 3 years afterward.

There were other problems, too. Mean hemoglobin A_1c increased from 8.66 % to 8.89% after transition to adult care, and urine albumin creatinine ratio (ACR) testing decreased, with 47 patients (32%) tested at least once before transition, but 29 (20%) afterward.

“Some would say that these are teenagers, and they’ll are grow out of” it as they learn how to care for themselves as adults, “but I don’t think that’s good enough” because there’s an increased risk of acute complications. “The transition period is associated with worsening glycemic control and an increased risk of DKA admission. There is room for improved screening, as well. I think there is certainly a role for intervention,” said Dr. Jennifer Huynh, chief resident in internal medicine at Western University.

The differences in HbA_1care big enough to worry about. “We know when A_1c is high, even small increases or decreases” make a difference. Meanwhile, the increased risk of DKA (odds ratio, 3; 95% confidence interval, 1.19-7.5) is “very concerning,” she said at the World Diabetes Congress.

It’s been reported before that children with diabetes run into trouble when they move into adult care; the findings are a reminder of the issue, and help firm up the extent of the problem. The investigators were able to do a robust comparison of pre- and posttransition patients because the database at Western University links patients’ pediatric and adult records.

What often happens is that diabetes takes a backseat to school, work, relationships, and other pressures of emerging adulthood, and parents are no longer around to make sure kids take care of themselves. Given all that’s going on, it’s not surprising that the researchers also found there were 1,149 office visits in the 3 years before the subjects turned 18, but only 750 in the 3 years afterward.

All but three of the young adults in the study had type 1 diabetes, and just over half were women. At the baseline visit at 15 years of age, the median duration of diabetes was 5 years, mean weight was 66.4 kg, and the mean body mass index was 23.5 kg/m^2. Forty-five subjects (31%) were on an insulin pump, 96 (65%) were on multiple daily injections, 3 (2%) were on premixed insulin, and 3 (2%) took oral agents.

Researchers at Western University and elsewhere are putting a lot of effort into figuring out how to improve the situation. Special transition clinics, support groups, and social media campaigns are just some of what’s being tried.

Investigators from Western University are finishing up a randomized trial to see if a transition coordinator helps. Patients were randomized to usual care or care overseen by the coordinator, a certified diabetes educator.

The coordinator stays in touch with the teenagers, sends them test results, reminds them of appointments for lab work and office visits, and, in general, serves as a sounding board, guide, and friend to help them manage the transition into adult care.

The hope is that the efforts will improves clinic attendance and glycemic control, among other things.

Western University is considering a survey of transition programs in Canada, to find out what works so “we can make some recommendations in terms of policy,” Dr. Huynh said.

The investigators have no conflicts of interest, and there was no industry funding for the work.

[email protected]

VANCOUVER, B.C. – Alogliptin, an oral inhibitor of dipeptidyl peptidase 4 (DPP-4) having hypoglycemic activity, promoted regression of preclinical carotid atherosclerosis in patients with type 2 diabetes, judging from the findings of the randomized Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A).

Among the 341 patients studied, all of whom were free of known cardiovascular disease at baseline, those in the alogliptin group had significant reductions in echocardiographic carotid intima-media thickness (IMT) at 2 years when compared with peers in a usual care group, according to data reported at the World Diabetes Congress.

“Our data may suggest … efficacy and benefit of alogliptin when used at an early stage of disease in preventing the progression of atherosclerosis,” commented first author Dr. Tomoya Mita, assistant professor in the department of metabolism and endocrinology at Juntendo University Graduate School of Medicine, Tokyo.

Three other trials – SAVOR TIMI 53, EXAMINE, and TECOS – have not found changes in cardiovascular outcomes with DPP-4 inhibitors among diabetic patients, he noted. Patients in those trials, however, had established cardiovascular disease or were at high risk.

“I’m not sure whether our data will translate into clinical outcome. But the magnitude of IMT reduction was identical to that of pioglitazone, [which] may reduce CV events,” Dr. Mita commented. “We are conducting a follow-up study that focuses on clinical outcome and safety, so we will find more detailed information in that study.”

“The importance of this study is really showing the limitations to cardiovascular outcome trials that have been going on,” commented Dr. Robert E. Ratner, professor of medicine at Georgetown University and senior research scientist at the MedStar Health Research Institute, both in Washington, as well as chief scientific and medical officer of the American Diabetes Association in Alexandria, Va., who was session comoderator.

Those studies have been limited by selection bias, he agreed in an interview. “Taking patients who are so far advanced in their disease really isn’t the practical solution. We need to be thinking earlier, we need to be thinking in terms of prevention.”

Patients were recruited to SPEAD-A from diabetes outpatient clinics at 11 centers in Japan. They had to be 30 years of age or older and to have diabetes inadequately controlled by diet and lifestyle measures, or agents other than DPP-4 inhibitors, but with a glycated hemoglobin level of less than 9.4%.

Trial results, reported at the meeting and simultaneously published (Diabetes Care. 2016;39:18-27. doi: 10.2337/dc15-0781), showed that, relative to peers given usual care, patients given alogliptin (U.S. brand name Nesina) had greater reductions at 2 years in levels of glycated hemoglobin (−0.3% vs. −0.1%, P = .004) without a higher incidence of hypoglycemia.

Echocardiographic data revealed differences between the alogliptin group and the usual-care group in favor of the former with respect to changes in common carotid IMT (−0.026 mm vs. +0.005 mm, P = .022), right carotid maximum IMT (−0.045 mm vs. +0.011 mm, P = .025), and left carotid maximum IMT (−0.079 mm vs. −0.015 mm, P = .013).

Body mass index increased in the alogliptin group but decreased in the usual-care group (+0.3 kg/m2 vs. –0.3 kg/m², P = .003), Dr. Mita reported.

The groups were statistically indistinguishable with respect to insulin and fasting glucose levels, lipid profiles, blood pressure, markers of inflammation, and estimated glomerular filtration rate.

Rates of adverse events and serious adverse events were similar with alogliptin and usual care. There was no significant difference between groups in cardiovascular events, but only five patients experienced these events.

“I’m not sure how the DPP-4 inhibitor reduces the carotid intima-media thickness in this study,” Dr. Mita commented, but other research has suggested that drugs in this class decrease smooth muscle cell proliferation and inflammation and improve endothelial function.

Dr. Mita disclosed that he receives research funds from MSD and Takeda Pharma and that he receives lecture fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Ono Pharmaceutical, and Takeda Pharmaceutical.

Financial support for the study was provided by Astellas Pharma, AstraZeneca, Bayer Holding, Daiichi Sankyo, Sumitomo Dainippon Pharma, Eli Lilly Japan, MSD, Nippon Boehringer Ingelheim, Novartis Pharma, Novo Nordisk Pharma, Pfizer Japan, Sanofi, Sanwa Kagaku Kenkyusho, Shionogi, and Takeda

VANCOUVER, B.C. – Alogliptin, an oral inhibitor of dipeptidyl peptidase 4 (DPP-4) having hypoglycemic activity, promoted regression of preclinical carotid atherosclerosis in patients with type 2 diabetes, judging from the findings of the randomized Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A).

Among the 341 patients studied, all of whom were free of known cardiovascular disease at baseline, those in the alogliptin group had significant reductions in echocardiographic carotid intima-media thickness (IMT) at 2 years when compared with peers in a usual care group, according to data reported at the World Diabetes Congress.

“Our data may suggest … efficacy and benefit of alogliptin when used at an early stage of disease in preventing the progression of atherosclerosis,” commented first author Dr. Tomoya Mita, assistant professor in the department of metabolism and endocrinology at Juntendo University Graduate School of Medicine, Tokyo.

Three other trials – SAVOR TIMI 53, EXAMINE, and TECOS – have not found changes in cardiovascular outcomes with DPP-4 inhibitors among diabetic patients, he noted. Patients in those trials, however, had established cardiovascular disease or were at high risk.

“I’m not sure whether our data will translate into clinical outcome. But the magnitude of IMT reduction was identical to that of pioglitazone, [which] may reduce CV events,” Dr. Mita commented. “We are conducting a follow-up study that focuses on clinical outcome and safety, so we will find more detailed information in that study.”

“The importance of this study is really showing the limitations to cardiovascular outcome trials that have been going on,” commented Dr. Robert E. Ratner, professor of medicine at Georgetown University and senior research scientist at the MedStar Health Research Institute, both in Washington, as well as chief scientific and medical officer of the American Diabetes Association in Alexandria, Va., who was session comoderator.

Those studies have been limited by selection bias, he agreed in an interview. “Taking patients who are so far advanced in their disease really isn’t the practical solution. We need to be thinking earlier, we need to be thinking in terms of prevention.”

Patients were recruited to SPEAD-A from diabetes outpatient clinics at 11 centers in Japan. They had to be 30 years of age or older and to have diabetes inadequately controlled by diet and lifestyle measures, or agents other than DPP-4 inhibitors, but with a glycated hemoglobin level of less than 9.4%.

Trial results, reported at the meeting and simultaneously published (Diabetes Care. 2016;39:18-27. doi: 10.2337/dc15-0781), showed that, relative to peers given usual care, patients given alogliptin (U.S. brand name Nesina) had greater reductions at 2 years in levels of glycated hemoglobin (−0.3% vs. −0.1%, P = .004) without a higher incidence of hypoglycemia.

Echocardiographic data revealed differences between the alogliptin group and the usual-care group in favor of the former with respect to changes in common carotid IMT (−0.026 mm vs. +0.005 mm, P = .022), right carotid maximum IMT (−0.045 mm vs. +0.011 mm, P = .025), and left carotid maximum IMT (−0.079 mm vs. −0.015 mm, P = .013).

Body mass index increased in the alogliptin group but decreased in the usual-care group (+0.3 kg/m2 vs. –0.3 kg/m², P = .003), Dr. Mita reported.

The groups were statistically indistinguishable with respect to insulin and fasting glucose levels, lipid profiles, blood pressure, markers of inflammation, and estimated glomerular filtration rate.

Rates of adverse events and serious adverse events were similar with alogliptin and usual care. There was no significant difference between groups in cardiovascular events, but only five patients experienced these events.

“I’m not sure how the DPP-4 inhibitor reduces the carotid intima-media thickness in this study,” Dr. Mita commented, but other research has suggested that drugs in this class decrease smooth muscle cell proliferation and inflammation and improve endothelial function.

Dr. Mita disclosed that he receives research funds from MSD and Takeda Pharma and that he receives lecture fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Ono Pharmaceutical, and Takeda Pharmaceutical.

Financial support for the study was provided by Astellas Pharma, AstraZeneca, Bayer Holding, Daiichi Sankyo, Sumitomo Dainippon Pharma, Eli Lilly Japan, MSD, Nippon Boehringer Ingelheim, Novartis Pharma, Novo Nordisk Pharma, Pfizer Japan, Sanofi, Sanwa Kagaku Kenkyusho, Shionogi, and Takeda

VANCOUVER, B.C. – Alogliptin, an oral inhibitor of dipeptidyl peptidase 4 (DPP-4) having hypoglycemic activity, promoted regression of preclinical carotid atherosclerosis in patients with type 2 diabetes, judging from the findings of the randomized Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A).

Among the 341 patients studied, all of whom were free of known cardiovascular disease at baseline, those in the alogliptin group had significant reductions in echocardiographic carotid intima-media thickness (IMT) at 2 years when compared with peers in a usual care group, according to data reported at the World Diabetes Congress.

“Our data may suggest … efficacy and benefit of alogliptin when used at an early stage of disease in preventing the progression of atherosclerosis,” commented first author Dr. Tomoya Mita, assistant professor in the department of metabolism and endocrinology at Juntendo University Graduate School of Medicine, Tokyo.

Three other trials – SAVOR TIMI 53, EXAMINE, and TECOS – have not found changes in cardiovascular outcomes with DPP-4 inhibitors among diabetic patients, he noted. Patients in those trials, however, had established cardiovascular disease or were at high risk.

“I’m not sure whether our data will translate into clinical outcome. But the magnitude of IMT reduction was identical to that of pioglitazone, [which] may reduce CV events,” Dr. Mita commented. “We are conducting a follow-up study that focuses on clinical outcome and safety, so we will find more detailed information in that study.”

“The importance of this study is really showing the limitations to cardiovascular outcome trials that have been going on,” commented Dr. Robert E. Ratner, professor of medicine at Georgetown University and senior research scientist at the MedStar Health Research Institute, both in Washington, as well as chief scientific and medical officer of the American Diabetes Association in Alexandria, Va., who was session comoderator.

Those studies have been limited by selection bias, he agreed in an interview. “Taking patients who are so far advanced in their disease really isn’t the practical solution. We need to be thinking earlier, we need to be thinking in terms of prevention.”

Patients were recruited to SPEAD-A from diabetes outpatient clinics at 11 centers in Japan. They had to be 30 years of age or older and to have diabetes inadequately controlled by diet and lifestyle measures, or agents other than DPP-4 inhibitors, but with a glycated hemoglobin level of less than 9.4%.

Trial results, reported at the meeting and simultaneously published (Diabetes Care. 2016;39:18-27. doi: 10.2337/dc15-0781), showed that, relative to peers given usual care, patients given alogliptin (U.S. brand name Nesina) had greater reductions at 2 years in levels of glycated hemoglobin (−0.3% vs. −0.1%, P = .004) without a higher incidence of hypoglycemia.

Echocardiographic data revealed differences between the alogliptin group and the usual-care group in favor of the former with respect to changes in common carotid IMT (−0.026 mm vs. +0.005 mm, P = .022), right carotid maximum IMT (−0.045 mm vs. +0.011 mm, P = .025), and left carotid maximum IMT (−0.079 mm vs. −0.015 mm, P = .013).

Body mass index increased in the alogliptin group but decreased in the usual-care group (+0.3 kg/m2 vs. –0.3 kg/m², P = .003), Dr. Mita reported.

The groups were statistically indistinguishable with respect to insulin and fasting glucose levels, lipid profiles, blood pressure, markers of inflammation, and estimated glomerular filtration rate.

Rates of adverse events and serious adverse events were similar with alogliptin and usual care. There was no significant difference between groups in cardiovascular events, but only five patients experienced these events.

“I’m not sure how the DPP-4 inhibitor reduces the carotid intima-media thickness in this study,” Dr. Mita commented, but other research has suggested that drugs in this class decrease smooth muscle cell proliferation and inflammation and improve endothelial function.

Dr. Mita disclosed that he receives research funds from MSD and Takeda Pharma and that he receives lecture fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Ono Pharmaceutical, and Takeda Pharmaceutical.

Financial support for the study was provided by Astellas Pharma, AstraZeneca, Bayer Holding, Daiichi Sankyo, Sumitomo Dainippon Pharma, Eli Lilly Japan, MSD, Nippon Boehringer Ingelheim, Novartis Pharma, Novo Nordisk Pharma, Pfizer Japan, Sanofi, Sanwa Kagaku Kenkyusho, Shionogi, and Takeda

VANCOUVER – Patients with type 2 diabetes mellitus who lose weight after bariatric surgery experience a reduction in pancreatic triacylglycerol that is not seen in similarly treated nondiabetic individuals, according to a new study that sheds more light on the etiology and reversibility of this disease.

Dr. Roy Taylor and his colleagues performed specialized magnetic resonance imaging in 18 patients with diabetes and 9 matched control patients with normal glucose tolerance, all of whom underwent bariatric surgery.

Despite similar overall weight and fat loss in the diabetic and control groups at 8 weeks after surgery, pancreatic triacylglycerol had fallen by 18% in the former – corresponding to loss of about 0.6 g of fat from the organ – but remained essentially unchanged in the latter, he reported at the World Diabetes Congress.

The findings lend further support to the twin cycle hypothesis of type 2 diabetes, maintained Dr. Taylor, who is a professor with the Institute of Cellular Medicine, Department of Diabetes & Metabolism, Newcastle upon Tyne, England.

According to this hypothesis, positive caloric balance and pre-existing insulin resistance set up dual reinforcing vicious cycles, whereby fat accumulates first in the liver and then in the pancreas, including the islets (Diabetologia. 2008 Oct;51:1781-9). Chronic exposure of beta cells to fat ultimately leads to reduced acute secretion of insulin, contributing to elevated plasma glucose levels.

“Weight loss over 8 weeks brings about loss of pancreatic triglyceride specifically in type 2 diabetes,” he concluded of the study. “[I]t is likely that type 2 diabetes is caused by less than 1 g of fat in the pancreas.”

One session attendee wondered about the role of initially elevated insulin levels in the development of type 2 diabetes. “Do you have any data that reducing insulin levels, not through weight loss or hypocaloric diet, can do the same thing?” he asked.

“Yes, the pre-existing raised insulin levels will be a vital part of the genesis of type 2 diabetes,” Dr. Taylor replied. “Are there other ways to reducing that? Well, I have to say that I don’t know any better way of reducing plasma insulin than weight loss. It has a profound effect: the insulin levels come down entirely into the normal range. If there was some other clever way of doing it, we would expect that to help. But in the practical world, I think we are left with weight loss as the most likely way ahead.”

Another attendee wondered whether the change in pancreatic triacylglycerol was an epiphenomenon. “If you looked at some other tissue and measured triglycerides in the kidney or the heart, would you see a similar relationship? Or is there a way to show that this is actually producing a change in insulin secretion independent of the triglyceride change itself?” he asked.

“I think the clearest data come from the in vitro studies where we can manipulate the islets and show that it will produce the effect,” Dr. Taylor replied, additionally pointing to a recent study in mice in which knocking out fatty acid receptors specifically in the pancreas stopped the development of diabetes in response to obesity (Nat Med. 2015 Feb;21:173-7).

“So I think we have a clear biological model that will be difficult to show in humans. But I would suggest that in view of the totality of the evidence, it’s now beyond a reasonable doubt that we are looking at a causal effect,” he said.

Giving more background to his study, Dr. Taylor noted that previous research has shown that as pancreatic fat content declines in diabetic patients, insulin secretion normalizes (Diabetologia. 2011 Oct;54:2506-14).

“But critics pointed out that if people lose substantial weight, well, of course the fat in the organ will go down. It will happen in anyone, won’t it?” he said. “Well, if it happened only in people with diabetes, the causal relationship would be very strong. If on the other hand it happened in anyone, then perhaps it is a coincidence.”

The patients studied had diabetes for about 7 years, on average. They were matched for age, weight, and sex with control patients having normal glucose tolerance. All had Roux-en-Y gastric bypass surgery.

The investigators performed in-phase, out-of-phase magnetic resonance imaging before and 8 weeks after surgery to quantify the amount of triacylglycerol in the patients’ pancreas and liver.

Results reported at the meeting and simultaneously published (Diab Care. 2015 Dec 1. doi: 10.2337/dc15-0750) showed that after surgery, the control and diabetic groups had a similar reduction in weight (12.8% and 13.6%) and fat mass (11.3 and 13.6 kg).

The diabetic group had higher fasting plasma glucose levels, hepatic insulin resistance, and liver fat content at baseline, and experienced significant reductions into the normal range in all of these measures by 8 weeks, whereas values remained unchanged in the control group.

Pancreatic triacylglycerol content changed minimally in the control group (from 5.1% to 5.5%), but it fell significantly in the diabetic patients (from 6.6% to 5.4%, corresponding to loss of about 0.6 g of fat; P less than .005), according to Dr. Taylor, who disclosed that he had no relevant conflicts of interest.

In addition, the diabetic group had a significant increase in the first-phase insulin response to a stepped intravenous glucose infusion to normal levels (P less than .005), whereas the control group had no change.

VANCOUVER – Patients with type 2 diabetes mellitus who lose weight after bariatric surgery experience a reduction in pancreatic triacylglycerol that is not seen in similarly treated nondiabetic individuals, according to a new study that sheds more light on the etiology and reversibility of this disease.

Dr. Roy Taylor and his colleagues performed specialized magnetic resonance imaging in 18 patients with diabetes and 9 matched control patients with normal glucose tolerance, all of whom underwent bariatric surgery.

Despite similar overall weight and fat loss in the diabetic and control groups at 8 weeks after surgery, pancreatic triacylglycerol had fallen by 18% in the former – corresponding to loss of about 0.6 g of fat from the organ – but remained essentially unchanged in the latter, he reported at the World Diabetes Congress.

The findings lend further support to the twin cycle hypothesis of type 2 diabetes, maintained Dr. Taylor, who is a professor with the Institute of Cellular Medicine, Department of Diabetes & Metabolism, Newcastle upon Tyne, England.

According to this hypothesis, positive caloric balance and pre-existing insulin resistance set up dual reinforcing vicious cycles, whereby fat accumulates first in the liver and then in the pancreas, including the islets (Diabetologia. 2008 Oct;51:1781-9). Chronic exposure of beta cells to fat ultimately leads to reduced acute secretion of insulin, contributing to elevated plasma glucose levels.

“Weight loss over 8 weeks brings about loss of pancreatic triglyceride specifically in type 2 diabetes,” he concluded of the study. “[I]t is likely that type 2 diabetes is caused by less than 1 g of fat in the pancreas.”

One session attendee wondered about the role of initially elevated insulin levels in the development of type 2 diabetes. “Do you have any data that reducing insulin levels, not through weight loss or hypocaloric diet, can do the same thing?” he asked.

“Yes, the pre-existing raised insulin levels will be a vital part of the genesis of type 2 diabetes,” Dr. Taylor replied. “Are there other ways to reducing that? Well, I have to say that I don’t know any better way of reducing plasma insulin than weight loss. It has a profound effect: the insulin levels come down entirely into the normal range. If there was some other clever way of doing it, we would expect that to help. But in the practical world, I think we are left with weight loss as the most likely way ahead.”

Another attendee wondered whether the change in pancreatic triacylglycerol was an epiphenomenon. “If you looked at some other tissue and measured triglycerides in the kidney or the heart, would you see a similar relationship? Or is there a way to show that this is actually producing a change in insulin secretion independent of the triglyceride change itself?” he asked.

“I think the clearest data come from the in vitro studies where we can manipulate the islets and show that it will produce the effect,” Dr. Taylor replied, additionally pointing to a recent study in mice in which knocking out fatty acid receptors specifically in the pancreas stopped the development of diabetes in response to obesity (Nat Med. 2015 Feb;21:173-7).

“So I think we have a clear biological model that will be difficult to show in humans. But I would suggest that in view of the totality of the evidence, it’s now beyond a reasonable doubt that we are looking at a causal effect,” he said.

Giving more background to his study, Dr. Taylor noted that previous research has shown that as pancreatic fat content declines in diabetic patients, insulin secretion normalizes (Diabetologia. 2011 Oct;54:2506-14).

“But critics pointed out that if people lose substantial weight, well, of course the fat in the organ will go down. It will happen in anyone, won’t it?” he said. “Well, if it happened only in people with diabetes, the causal relationship would be very strong. If on the other hand it happened in anyone, then perhaps it is a coincidence.”

The patients studied had diabetes for about 7 years, on average. They were matched for age, weight, and sex with control patients having normal glucose tolerance. All had Roux-en-Y gastric bypass surgery.

The investigators performed in-phase, out-of-phase magnetic resonance imaging before and 8 weeks after surgery to quantify the amount of triacylglycerol in the patients’ pancreas and liver.

Results reported at the meeting and simultaneously published (Diab Care. 2015 Dec 1. doi: 10.2337/dc15-0750) showed that after surgery, the control and diabetic groups had a similar reduction in weight (12.8% and 13.6%) and fat mass (11.3 and 13.6 kg).

The diabetic group had higher fasting plasma glucose levels, hepatic insulin resistance, and liver fat content at baseline, and experienced significant reductions into the normal range in all of these measures by 8 weeks, whereas values remained unchanged in the control group.

Pancreatic triacylglycerol content changed minimally in the control group (from 5.1% to 5.5%), but it fell significantly in the diabetic patients (from 6.6% to 5.4%, corresponding to loss of about 0.6 g of fat; P less than .005), according to Dr. Taylor, who disclosed that he had no relevant conflicts of interest.

In addition, the diabetic group had a significant increase in the first-phase insulin response to a stepped intravenous glucose infusion to normal levels (P less than .005), whereas the control group had no change.

VANCOUVER – Patients with type 2 diabetes mellitus who lose weight after bariatric surgery experience a reduction in pancreatic triacylglycerol that is not seen in similarly treated nondiabetic individuals, according to a new study that sheds more light on the etiology and reversibility of this disease.

Dr. Roy Taylor and his colleagues performed specialized magnetic resonance imaging in 18 patients with diabetes and 9 matched control patients with normal glucose tolerance, all of whom underwent bariatric surgery.

Despite similar overall weight and fat loss in the diabetic and control groups at 8 weeks after surgery, pancreatic triacylglycerol had fallen by 18% in the former – corresponding to loss of about 0.6 g of fat from the organ – but remained essentially unchanged in the latter, he reported at the World Diabetes Congress.

The findings lend further support to the twin cycle hypothesis of type 2 diabetes, maintained Dr. Taylor, who is a professor with the Institute of Cellular Medicine, Department of Diabetes & Metabolism, Newcastle upon Tyne, England.

According to this hypothesis, positive caloric balance and pre-existing insulin resistance set up dual reinforcing vicious cycles, whereby fat accumulates first in the liver and then in the pancreas, including the islets (Diabetologia. 2008 Oct;51:1781-9). Chronic exposure of beta cells to fat ultimately leads to reduced acute secretion of insulin, contributing to elevated plasma glucose levels.

“Weight loss over 8 weeks brings about loss of pancreatic triglyceride specifically in type 2 diabetes,” he concluded of the study. “[I]t is likely that type 2 diabetes is caused by less than 1 g of fat in the pancreas.”

One session attendee wondered about the role of initially elevated insulin levels in the development of type 2 diabetes. “Do you have any data that reducing insulin levels, not through weight loss or hypocaloric diet, can do the same thing?” he asked.

“Yes, the pre-existing raised insulin levels will be a vital part of the genesis of type 2 diabetes,” Dr. Taylor replied. “Are there other ways to reducing that? Well, I have to say that I don’t know any better way of reducing plasma insulin than weight loss. It has a profound effect: the insulin levels come down entirely into the normal range. If there was some other clever way of doing it, we would expect that to help. But in the practical world, I think we are left with weight loss as the most likely way ahead.”

Another attendee wondered whether the change in pancreatic triacylglycerol was an epiphenomenon. “If you looked at some other tissue and measured triglycerides in the kidney or the heart, would you see a similar relationship? Or is there a way to show that this is actually producing a change in insulin secretion independent of the triglyceride change itself?” he asked.

“I think the clearest data come from the in vitro studies where we can manipulate the islets and show that it will produce the effect,” Dr. Taylor replied, additionally pointing to a recent study in mice in which knocking out fatty acid receptors specifically in the pancreas stopped the development of diabetes in response to obesity (Nat Med. 2015 Feb;21:173-7).

“So I think we have a clear biological model that will be difficult to show in humans. But I would suggest that in view of the totality of the evidence, it’s now beyond a reasonable doubt that we are looking at a causal effect,” he said.

Giving more background to his study, Dr. Taylor noted that previous research has shown that as pancreatic fat content declines in diabetic patients, insulin secretion normalizes (Diabetologia. 2011 Oct;54:2506-14).

“But critics pointed out that if people lose substantial weight, well, of course the fat in the organ will go down. It will happen in anyone, won’t it?” he said. “Well, if it happened only in people with diabetes, the causal relationship would be very strong. If on the other hand it happened in anyone, then perhaps it is a coincidence.”

The patients studied had diabetes for about 7 years, on average. They were matched for age, weight, and sex with control patients having normal glucose tolerance. All had Roux-en-Y gastric bypass surgery.

The investigators performed in-phase, out-of-phase magnetic resonance imaging before and 8 weeks after surgery to quantify the amount of triacylglycerol in the patients’ pancreas and liver.

Results reported at the meeting and simultaneously published (Diab Care. 2015 Dec 1. doi: 10.2337/dc15-0750) showed that after surgery, the control and diabetic groups had a similar reduction in weight (12.8% and 13.6%) and fat mass (11.3 and 13.6 kg).

The diabetic group had higher fasting plasma glucose levels, hepatic insulin resistance, and liver fat content at baseline, and experienced significant reductions into the normal range in all of these measures by 8 weeks, whereas values remained unchanged in the control group.

Pancreatic triacylglycerol content changed minimally in the control group (from 5.1% to 5.5%), but it fell significantly in the diabetic patients (from 6.6% to 5.4%, corresponding to loss of about 0.6 g of fat; P less than .005), according to Dr. Taylor, who disclosed that he had no relevant conflicts of interest.

In addition, the diabetic group had a significant increase in the first-phase insulin response to a stepped intravenous glucose infusion to normal levels (P less than .005), whereas the control group had no change.