Diabetes 'cure' holds up 6 years after bariatric surgery

INDIANAPOLIS – At 6 years of follow-up data, bariatric surgical cures of type 2 diabetes are holding steady in a single-center series of 217 patients.

"We see sustained weight loss, particularly in Roux-en-Y gastric bypass patients, 5-9 years after surgery." Diabetes remitted in 50% of patients, according to Dr. Stacy A. Brethauer of the Cleveland Clinic. "Bariatric surgery also achieved excellent long-term control of other cardiovascular risk factors; and diabetic nephropathy improved or stabilized."

Of 217 obese type 2 diabetic patients followed for a median of 6 years after bariatric surgery, 24% have been "cured." They have maintained a hemoglobin A_1c level below 6% and fasting blood glucose values below 100 mg/dL for more than 5 years while off all antidiabetic medications, Dr. Brethauer reported at the annual meeting of the American Surgical Association.

Another 26% of patients have had partial remissions, meaning they maintained target HbA_1c and fasting blood glucose levels off antidiabetic medications for more than 1 year but less than 5 years. In addition, 34% of patients were classified as "improved" based upon an absolute 1% or more reduction in HbA_1c, a drop in fasting blood glucose in excess of 25 mg/dL, and a halving in the dose of antidiabetic medication for at least 1 year.

Diabetes recurred in 19% of subjects. Recurrence was defined as a return to an HbA_1c of 6.5% or more or a fasting blood glucose level of at least 126 mg/dL.

The overall study population improved from a mean body mass index of 49 kg/m² before surgery to 37 kg/m² at 6 years after surgery. The mean HbA_1c was 7.5% at baseline and 6.5% at 6 years. Fasting blood glucose at 6 years was a mean of 41.6 mg/dL lower than it was before surgery. LDL cholesterol levels were down by a mean of 10.1 mg/dL and HDL levels were up by 9.8 mg/dL. Systolic blood pressure was reduced by a mean of 10.9 mm Hg, with diastolic blood pressure was down by 3.2 mm Hg at 6 years after surgery.

Preoperatively, all but 5% of patients were on any antidiabetes medications; at 6 years after bariatric surgery, 54% were not on any antidiabetes drugs.

At baseline, 3% of subjects met all three key metabolic goals for diabetic patients as defined by the American Diabetes Association: an HbA_1c below 7%, blood pressure below 130/80 mm Hg, and an LDL level below 100 mg/dL. At 6 years after surgery, 28% of patients met these goals. That result is particularly impressive in light of other studies that indicate 13% of the U.S. diabetic population as a whole meet all three goals.

The bariatric surgery group had a mean Framingham 10-year cardiovascular risk score of 28% preoperatively and of 22% at long-term followup.

The incidence of diabetic nephropathy among patients with type 2 diabetes is typically 2%-4% per year. Yet of 40 gastric bypass recipients known to have a normal urinary albumin-to-creatinine ratio preoperatively, only 1 developed macroalbuminuria and 1 microalbuminuria during a mean of 6 years postsurgical follow-up.

Also impressive, albuminuria regressed in 10 of the 19 gastric bypass recipients known to have the disorder at baseline. Albuminuria remained stable in the other 9 patients over the course of 6 years.

Mean excess weight loss at 1-2 years of follow-up was 61% in the 162 patients who underwent gastric bypass, 50% in the 23 with sleeve gastrectomy, and 30% in patients who had a gastric banding procedure.

In a multivariate analysis adjusted for baseline clinical characteristics, the significant predictors of diabetes remission following bariatric surgery were greater excess weight loss, preoperative diabetes duration of less than 5 years, and having a gastric bypass operation rather than sleeve gastrectomy or a gastric banding procedure.

Dr. Brethauer said this study, taken together with the findings of an earlier randomized clinical trial by the same investigators (N. Engl. J. Med. 2012;366:1567-76), conveys a clear message : "Bariatric surgery can induce a significant and sustainable remission of type 2 diabetes and other metabolic risk factors in obese patients and should be considered early in the course of the disease."

Discussant Dr. Walter J. Pories called Dr. Brethauer’s study "a really important contribution." He added that it’s high time for nonsurgeons to get on board.

"One in four adults over age 65 in this country has diabetes. One would have thought our medical colleagues would be ecstatic at the news that an operation on the gut – a safe procedure that can be done in about an hour – could produce full and durable remission of diabetes with complete prevention of amputations, blindness, and kidney failure. But that hasn’t been the case. All we’ve heard are cries for more and more evidence," said Dr. Pories, professor of surgery at East Carolina University, Greenville, N.C.

He added that in his view, Dr. Brethauer and his colleagues set the bar too high in requiring a sustained HbA_1c below 6% as the definition of disease cure when the American Diabetes Association uses a figure of 7%. He noted that if the investigators had accepted the ADA metric, their combined cure/partial remission rate would have been considerably greater than the 50% figure they reported.

Dr. Brethauer replied that he and his coinvestigators chose a cutoff of 6% in order to make a point.

"When we raise this issue of ‘cure,’ which is still quite controversial and somewhat provocative, particularly with our endocrinology colleagues, I think we have to find the strictest and most conservative criteria that we can," he explained. "We continue to provide data in support of the concept that this is a surgically treated disease. It’s a major paradigm shift for our endocrinology colleagues to accept. I think it’s going to take a generation of endocrinologists before it’s embraced."

He reported that he serves as a consultant to Ethicon Endosurgery and Apollo Endosurgery.

bjancin@frontlinemedcom.com

INDIANAPOLIS – At 6 years of follow-up data, bariatric surgical cures of type 2 diabetes are holding steady in a single-center series of 217 patients.

"We see sustained weight loss, particularly in Roux-en-Y gastric bypass patients, 5-9 years after surgery." Diabetes remitted in 50% of patients, according to Dr. Stacy A. Brethauer of the Cleveland Clinic. "Bariatric surgery also achieved excellent long-term control of other cardiovascular risk factors; and diabetic nephropathy improved or stabilized."

Of 217 obese type 2 diabetic patients followed for a median of 6 years after bariatric surgery, 24% have been "cured." They have maintained a hemoglobin A_1c level below 6% and fasting blood glucose values below 100 mg/dL for more than 5 years while off all antidiabetic medications, Dr. Brethauer reported at the annual meeting of the American Surgical Association.

Another 26% of patients have had partial remissions, meaning they maintained target HbA_1c and fasting blood glucose levels off antidiabetic medications for more than 1 year but less than 5 years. In addition, 34% of patients were classified as "improved" based upon an absolute 1% or more reduction in HbA_1c, a drop in fasting blood glucose in excess of 25 mg/dL, and a halving in the dose of antidiabetic medication for at least 1 year.

Diabetes recurred in 19% of subjects. Recurrence was defined as a return to an HbA_1c of 6.5% or more or a fasting blood glucose level of at least 126 mg/dL.

The overall study population improved from a mean body mass index of 49 kg/m² before surgery to 37 kg/m² at 6 years after surgery. The mean HbA_1c was 7.5% at baseline and 6.5% at 6 years. Fasting blood glucose at 6 years was a mean of 41.6 mg/dL lower than it was before surgery. LDL cholesterol levels were down by a mean of 10.1 mg/dL and HDL levels were up by 9.8 mg/dL. Systolic blood pressure was reduced by a mean of 10.9 mm Hg, with diastolic blood pressure was down by 3.2 mm Hg at 6 years after surgery.

Preoperatively, all but 5% of patients were on any antidiabetes medications; at 6 years after bariatric surgery, 54% were not on any antidiabetes drugs.

At baseline, 3% of subjects met all three key metabolic goals for diabetic patients as defined by the American Diabetes Association: an HbA_1c below 7%, blood pressure below 130/80 mm Hg, and an LDL level below 100 mg/dL. At 6 years after surgery, 28% of patients met these goals. That result is particularly impressive in light of other studies that indicate 13% of the U.S. diabetic population as a whole meet all three goals.

The bariatric surgery group had a mean Framingham 10-year cardiovascular risk score of 28% preoperatively and of 22% at long-term followup.

The incidence of diabetic nephropathy among patients with type 2 diabetes is typically 2%-4% per year. Yet of 40 gastric bypass recipients known to have a normal urinary albumin-to-creatinine ratio preoperatively, only 1 developed macroalbuminuria and 1 microalbuminuria during a mean of 6 years postsurgical follow-up.

Also impressive, albuminuria regressed in 10 of the 19 gastric bypass recipients known to have the disorder at baseline. Albuminuria remained stable in the other 9 patients over the course of 6 years.

Mean excess weight loss at 1-2 years of follow-up was 61% in the 162 patients who underwent gastric bypass, 50% in the 23 with sleeve gastrectomy, and 30% in patients who had a gastric banding procedure.

In a multivariate analysis adjusted for baseline clinical characteristics, the significant predictors of diabetes remission following bariatric surgery were greater excess weight loss, preoperative diabetes duration of less than 5 years, and having a gastric bypass operation rather than sleeve gastrectomy or a gastric banding procedure.

Dr. Brethauer said this study, taken together with the findings of an earlier randomized clinical trial by the same investigators (N. Engl. J. Med. 2012;366:1567-76), conveys a clear message : "Bariatric surgery can induce a significant and sustainable remission of type 2 diabetes and other metabolic risk factors in obese patients and should be considered early in the course of the disease."

Discussant Dr. Walter J. Pories called Dr. Brethauer’s study "a really important contribution." He added that it’s high time for nonsurgeons to get on board.

"One in four adults over age 65 in this country has diabetes. One would have thought our medical colleagues would be ecstatic at the news that an operation on the gut – a safe procedure that can be done in about an hour – could produce full and durable remission of diabetes with complete prevention of amputations, blindness, and kidney failure. But that hasn’t been the case. All we’ve heard are cries for more and more evidence," said Dr. Pories, professor of surgery at East Carolina University, Greenville, N.C.

He added that in his view, Dr. Brethauer and his colleagues set the bar too high in requiring a sustained HbA_1c below 6% as the definition of disease cure when the American Diabetes Association uses a figure of 7%. He noted that if the investigators had accepted the ADA metric, their combined cure/partial remission rate would have been considerably greater than the 50% figure they reported.

Dr. Brethauer replied that he and his coinvestigators chose a cutoff of 6% in order to make a point.

"When we raise this issue of ‘cure,’ which is still quite controversial and somewhat provocative, particularly with our endocrinology colleagues, I think we have to find the strictest and most conservative criteria that we can," he explained. "We continue to provide data in support of the concept that this is a surgically treated disease. It’s a major paradigm shift for our endocrinology colleagues to accept. I think it’s going to take a generation of endocrinologists before it’s embraced."

He reported that he serves as a consultant to Ethicon Endosurgery and Apollo Endosurgery.

bjancin@frontlinemedcom.com

INDIANAPOLIS – At 6 years of follow-up data, bariatric surgical cures of type 2 diabetes are holding steady in a single-center series of 217 patients.

"We see sustained weight loss, particularly in Roux-en-Y gastric bypass patients, 5-9 years after surgery." Diabetes remitted in 50% of patients, according to Dr. Stacy A. Brethauer of the Cleveland Clinic. "Bariatric surgery also achieved excellent long-term control of other cardiovascular risk factors; and diabetic nephropathy improved or stabilized."

Of 217 obese type 2 diabetic patients followed for a median of 6 years after bariatric surgery, 24% have been "cured." They have maintained a hemoglobin A_1c level below 6% and fasting blood glucose values below 100 mg/dL for more than 5 years while off all antidiabetic medications, Dr. Brethauer reported at the annual meeting of the American Surgical Association.

Another 26% of patients have had partial remissions, meaning they maintained target HbA_1c and fasting blood glucose levels off antidiabetic medications for more than 1 year but less than 5 years. In addition, 34% of patients were classified as "improved" based upon an absolute 1% or more reduction in HbA_1c, a drop in fasting blood glucose in excess of 25 mg/dL, and a halving in the dose of antidiabetic medication for at least 1 year.

Diabetes recurred in 19% of subjects. Recurrence was defined as a return to an HbA_1c of 6.5% or more or a fasting blood glucose level of at least 126 mg/dL.

The overall study population improved from a mean body mass index of 49 kg/m² before surgery to 37 kg/m² at 6 years after surgery. The mean HbA_1c was 7.5% at baseline and 6.5% at 6 years. Fasting blood glucose at 6 years was a mean of 41.6 mg/dL lower than it was before surgery. LDL cholesterol levels were down by a mean of 10.1 mg/dL and HDL levels were up by 9.8 mg/dL. Systolic blood pressure was reduced by a mean of 10.9 mm Hg, with diastolic blood pressure was down by 3.2 mm Hg at 6 years after surgery.

Preoperatively, all but 5% of patients were on any antidiabetes medications; at 6 years after bariatric surgery, 54% were not on any antidiabetes drugs.

At baseline, 3% of subjects met all three key metabolic goals for diabetic patients as defined by the American Diabetes Association: an HbA_1c below 7%, blood pressure below 130/80 mm Hg, and an LDL level below 100 mg/dL. At 6 years after surgery, 28% of patients met these goals. That result is particularly impressive in light of other studies that indicate 13% of the U.S. diabetic population as a whole meet all three goals.

The bariatric surgery group had a mean Framingham 10-year cardiovascular risk score of 28% preoperatively and of 22% at long-term followup.

The incidence of diabetic nephropathy among patients with type 2 diabetes is typically 2%-4% per year. Yet of 40 gastric bypass recipients known to have a normal urinary albumin-to-creatinine ratio preoperatively, only 1 developed macroalbuminuria and 1 microalbuminuria during a mean of 6 years postsurgical follow-up.

Also impressive, albuminuria regressed in 10 of the 19 gastric bypass recipients known to have the disorder at baseline. Albuminuria remained stable in the other 9 patients over the course of 6 years.

Mean excess weight loss at 1-2 years of follow-up was 61% in the 162 patients who underwent gastric bypass, 50% in the 23 with sleeve gastrectomy, and 30% in patients who had a gastric banding procedure.

In a multivariate analysis adjusted for baseline clinical characteristics, the significant predictors of diabetes remission following bariatric surgery were greater excess weight loss, preoperative diabetes duration of less than 5 years, and having a gastric bypass operation rather than sleeve gastrectomy or a gastric banding procedure.

Dr. Brethauer said this study, taken together with the findings of an earlier randomized clinical trial by the same investigators (N. Engl. J. Med. 2012;366:1567-76), conveys a clear message : "Bariatric surgery can induce a significant and sustainable remission of type 2 diabetes and other metabolic risk factors in obese patients and should be considered early in the course of the disease."

Discussant Dr. Walter J. Pories called Dr. Brethauer’s study "a really important contribution." He added that it’s high time for nonsurgeons to get on board.

"One in four adults over age 65 in this country has diabetes. One would have thought our medical colleagues would be ecstatic at the news that an operation on the gut – a safe procedure that can be done in about an hour – could produce full and durable remission of diabetes with complete prevention of amputations, blindness, and kidney failure. But that hasn’t been the case. All we’ve heard are cries for more and more evidence," said Dr. Pories, professor of surgery at East Carolina University, Greenville, N.C.

He added that in his view, Dr. Brethauer and his colleagues set the bar too high in requiring a sustained HbA_1c below 6% as the definition of disease cure when the American Diabetes Association uses a figure of 7%. He noted that if the investigators had accepted the ADA metric, their combined cure/partial remission rate would have been considerably greater than the 50% figure they reported.

Dr. Brethauer replied that he and his coinvestigators chose a cutoff of 6% in order to make a point.

"When we raise this issue of ‘cure,’ which is still quite controversial and somewhat provocative, particularly with our endocrinology colleagues, I think we have to find the strictest and most conservative criteria that we can," he explained. "We continue to provide data in support of the concept that this is a surgically treated disease. It’s a major paradigm shift for our endocrinology colleagues to accept. I think it’s going to take a generation of endocrinologists before it’s embraced."

He reported that he serves as a consultant to Ethicon Endosurgery and Apollo Endosurgery.

bjancin@frontlinemedcom.com