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Papers by John Bantle

Research paper thumbnail of Postgastric bypass hyperinsulinemic hypoglycemia syndrome: characterization and response to a modified diet

Surgery for Obesity and Related Diseases, Jul 1, 2008

Some alarming cases of hypoglycemic episodes in patients who have undergone Roux-en-Y gastric byp... more Some alarming cases of hypoglycemic episodes in patients who have undergone Roux-en-Y gastric bypass have been reported. The syndrome of hyperinsulinemic hypoglycemia with nesidioblastosis after Roux-en-Y gastric bypass has been previously reported and is controversial. It has been suggested that subtotal or total pancreatectomy might be needed to control the symptoms in these patients. We have identified a similar cohort of patients with hyperinsulinemic hypoglycemia for whom we have reviewed patient characteristics and measured the glucose and insulin response to mixed meals. We reviewed the charts of 14 patients identified by clinic follow-up who reported episodes consistent with hyperinsulinemic hypoglycemia (lightheadedness or loss of consciousness after a high-carbohydrate meal). All patients were given a mixed meal consisting of high carbohydrates on day 1 and a low-carbohydrate meal on day 2. The plasma glucose and serum insulin levels were measured before (fasting) and 30, 60, 90, 120, 150, and 180 minutes after the meal. After a high-carbohydrate meal, 12 of 14 patients demonstrated hyperglycemia associated with hyperinsulinemia at 30 minutes. These patients subsequently became hypoglycemic while the serum insulin was rapidly declining. After reaching a nadir at 120 minutes, the plasma glucose level corrected spontaneously. After a low-carbohydrate mixed meal, the patients demonstrated very little change in plasma glucose and only a modest increase in serum insulin. Of the 12 patients treated with a low-carbohydrate diet, 6 had substantive symptom improvement, and 10 exhibited at least some improvement. The hyperinsulinemic hypoglycemia noted in some patients after Roux-en-Y gastric bypass has many similarities to the dumping syndrome. A low-carbohydrate diet successfully improved symptoms in most of our patients. Approaches to treatment should involve a low-carbohydrate diet and alpha-glucosidase inhibitors rather than pancreatectomy.

Research paper thumbnail of Suppression of plasma renin activity by cyclosporine

The American Journal of Medicine, Jul 1, 1987

Research paper thumbnail of Effects of Cyclosporine on the Renin-Angiotensin-Aldosterone System and Potassium Excretion in Renal Transplant Recipients

Archives of internal medicine, Mar 1, 1985

Research paper thumbnail of Post-Gastric Bypass Hyperinsulinemic Hypoglycemia: Fructose is a Carbohydrate Which Can Be Safely Consumed

The Journal of Clinical Endocrinology and Metabolism, Aug 1, 2015

Postprandial hypoglycemia after gastric bypass surgery is a serious problem. Available treatments... more Postprandial hypoglycemia after gastric bypass surgery is a serious problem. Available treatments are often ineffective. Objective: The objective was to test the hypotheses that injection of rapid-acting insulin before a high-carbohydrate meal or replacement of other carbohydrates with fructose in the meal would prevent hypoglycemia. Design: This was a randomized, crossover trial comparing a high-carbohydrate meal with premeal saline injection (control), a high-carbohydrate meal with premeal insulin injection, and a highfructose meal with total carbohydrate content similar to the control meal. The setting was an academic medical center. Patients: Ten patients with post-gastric bypass hyperinsulinemic hypoglycemia participated. Interventions included lispro insulin injected before test meals and replacement of other carbohydrates with fructose in test meals. The main outcome measure was plasma glucose Ͻ 60 mg/dL after test meals. Results: After the control meal, mean peak glucose and insulin were 173 Ϯ 47 mg/dL and 134 Ϯ 55 mU/L, respectively; mean glucose nadir was 44 Ϯ 15 mg/dL; and eight of 10 subjects demonstrated glucose Ͻ 60 mg/dL. Five subjects demonstrated a glucose nadir Ͻ 40 mg/dL. There were no significant differences in the corresponding values after premeal insulin treatment, except that the mean glucose nadir of 34 Ϯ 10 mg/dL was lower (P Ͻ .05). After the fructose meal, mean peak postprandial glucose and insulin were 117 Ϯ 20 mg/dL and 45 Ϯ 31 mU/L, respectively (both P Ͻ .001 for comparison with control), mean glucose nadir was 67 Ϯ 10 mg/dL (P Ͻ .001), and two of 10 subjects demonstrated glucose Ͻ 60 mg/dL (P Ͻ .05). People with post-gastric bypass hypoglycemia can consume a meal sweetened with fructose with little risk of hypoglycemia. Treatment with rapid-acting insulin before a carbohydrate-containing meal did not prevent hypoglycemia. (J Clin Endocrinol Metab 100: 3097-3102, 2015) I n 2005, Service et al (1) first described postprandial hy- poglycemia causing neuroglycopenia after Roux-en-Y gastric bypass surgery. Several of their patients experi-enced confusion and loss of consciousness during episodes. Subsequently, additional patients with this disorder have been described in small series and case reports (2-8).

Research paper thumbnail of Clinical Aspects of Sucrose and Fructose Metabolism

Research paper thumbnail of Partial ileal bypass affords protection from onset of type 2 diabetes

Surgery for Obesity and Related Diseases, 2017

Partial ileal bypass (PIB) in the National Institutes of Health-sponsored Program on the Surgical... more Partial ileal bypass (PIB) in the National Institutes of Health-sponsored Program on the Surgical Control of the Hyperlipidemias (POSCH) randomized controlled trial was found to reduce plasma cholesterol, in particular low density lipoprotein cholesterol, with concomitant retardation of atherosclerotic cardiovascular disease and increased life expectancy. Glucagon-like peptide-1, related to amelioration of type 2 diabetes, is increased over 5-fold after PIB. We hypothesized that PIB, in addition to its action on cholesterol metabolism, may also prevent type 2 diabetes. We surveyed by telephone inquiry of former POSCH patients the 30+year posttrial incidence of type 2 diabetes or prediabetes, the presence of which was a trial exclusion criteria. We were able to contact 17.4% (n = 838) of the original POSCH population. Of 66 control responders, 17 contracted type 2 diabetes (25.8%); of 80 PIB responders, 8 contracted type 2 diabetes (10%). The difference between groups was significant (P = .015 by Fisher exact test) with an odds ratio of .320 for the PIB group and an over 2-fold (2.6) increase in the incidence of type 2 diabetes in the controls. Including borderline type 2 diabetes (prediabetic) patients, these values were 22 of 66 controls (33.3%) and 10 of 80 PIB patients (12.5%), with an odds ratio of .286 and a P<.004, and again an over 2-fold (2.7) increase in the incidence of type 2 diabetes in the control patients. PIB appears to afford partial protection from the onset of type 2 diabetes for over 30 years.

Research paper thumbnail of Evidence-Based Nutrition Principles and Recommendations for the Treatment and Prevention of Diabetes and Related Complications

Research paper thumbnail of Effects of dietary fructose on plasma lipids in healthy subjects

The American Journal of Clinical Nutrition, 2000

Research paper thumbnail of Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood Pressure at 5 Years in the Diabetes Surgery Study

JAMA, Jan 16, 2018

The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, bu... more The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. To compare durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical management in achieving diabetes control targets. Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. The American Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic bloo...

Research paper thumbnail of Durability of Addition of Roux-en-Y Gastric Bypass to Lifestyle Intervention and Medical Management in Achieving Primary Treatment Goals for Uncontrolled Type 2 Diabetes in Mild-to-Moderate Obesity: A Randomized Control Trial

Diabetes care, Sep 16, 2016

We compared 3-year achievement of an American Diabetes Association composite treatment goal (HbA1... more We compared 3-year achievement of an American Diabetes Association composite treatment goal (HbA1c <7.0%, LDL cholesterol <100 mg/dL, and systolic blood pressure <130 mmHg) after 2 years of intensive lifestyle-medical management intervention, with and without Roux-en-Y gastric bypass, with one additional year of usual care. A total of 120 adult participants, with BMI 30.0-39.9 kg/m(2) and HbA1c ≥8.0%, were randomized 1:1 to two treatment arms at three clinical sites in the U.S. and one in Taiwan. All patients received the lifestyle-medical management intervention for 24 months; half were randomized to also receive gastric bypass. At 36 months, the triple end point goal was met in 9% of lifestyle-medical management patients and 28% of gastric bypass patients (P = 0.01): 10% and 19% lower than at 12 months. Mean (SD) HbA1c values at 3 years were 8.6% (3.5) and 6.7% (2.0) (P < 0.001). No lifestyle-medical management patient had remission of diabetes at 36 months, whereas 17...

Research paper thumbnail of Partial Ileal Bypass Affords Protection from Onset of Type 2 Diabetes

Surgery for Obesity and Related Diseases, 2017

Partial ileal bypass (PIB) in the National Institutes of Health-sponsored Program on the Surgical... more Partial ileal bypass (PIB) in the National Institutes of Health-sponsored Program on the Surgical Control of the Hyperlipidemias (POSCH) randomized controlled trial was found to reduce plasma cholesterol, in particular low density lipoprotein cholesterol, with concomitant retardation of atherosclerotic cardiovascular disease and increased life expectancy. Glucagon-like peptide-1, related to amelioration of type 2 diabetes, is increased over 5-fold after PIB. We hypothesized that PIB, in addition to its action on cholesterol metabolism, may also prevent type 2 diabetes. We surveyed by telephone inquiry of former POSCH patients the 30+year posttrial incidence of type 2 diabetes or prediabetes, the presence of which was a trial exclusion criteria. We were able to contact 17.4% (n = 838) of the original POSCH population. Of 66 control responders, 17 contracted type 2 diabetes (25.8%); of 80 PIB responders, 8 contracted type 2 diabetes (10%). The difference between groups was significant (P = .015 by Fisher exact test) with an odds ratio of .320 for the PIB group and an over 2-fold (2.6) increase in the incidence of type 2 diabetes in the controls. Including borderline type 2 diabetes (prediabetic) patients, these values were 22 of 66 controls (33.3%) and 10 of 80 PIB patients (12.5%), with an odds ratio of .286 and a P&lt;.004, and again an over 2-fold (2.7) increase in the incidence of type 2 diabetes in the control patients. PIB appears to afford partial protection from the onset of type 2 diabetes for over 30 years.

Research paper thumbnail of Roux-en-Y gastric bypass for diabetes (the Diabetes Surgery Study): 2-year outcomes of a 5-year, randomised, controlled trial

The lancet. Diabetes & endocrinology, 2015

Conventional treatments for patients with type 2 diabetes are often inadequate. We aimed to asses... more Conventional treatments for patients with type 2 diabetes are often inadequate. We aimed to assess outcomes of diabetes control and treatment risks 2 years after adding Roux-en-Y gastric bypass to intensive lifestyle and medical management. We report 2-year outcomes of a 5-year randomised trial (the Diabetes Surgery Study) at four teaching hospitals (three in the USA and one in Taiwan). At baseline, eligible participants had to have HbA1c of at least 8·0% (64 mmol/mol), BMI between 30·0 and 39·9 kg/m(2), and type 2 diabetes for at least 6 months, and be aged 30-67 years. We randomly assigned participants to receive either intensive lifestyle and medical management alone (lifestyle and medical management), or lifestyle and medical management plus standard Roux-en-Y gastric bypass surgery (gastric bypass). Staff from the clinical centres had access to data from individual patients, but were masked to other patients' data and aggregated data until the 2-year follow-up. Drugs for hy...

Research paper thumbnail of Clinical research strategies for fructose metabolism

Advances in nutrition (Bethesda, Md.), 2014

Fructose and simple sugars are a substantial part of the western diet, and their influence on hum... more Fructose and simple sugars are a substantial part of the western diet, and their influence on human health remains controversial. Clinical studies in fructose nutrition have proven very difficult to conduct and interpret. NIH and USDA sponsored a workshop on 13-14 November 2012, "Research Strategies for Fructose Metabolism," to identify important scientific questions and parameters to be considered while designing clinical studies. Research is needed to ascertain whether there is an obesogenic role for fructose-containing sugars via effects on eating behavior and energy balance and whether there is a dose threshold beyond which these sugars promote progression toward diabetes and liver and cardiovascular disease, especially in susceptible populations. Studies tend to fall into 2 categories, and design criteria for each are described. Mechanistic studies are meant to validate observations made in animals or to elucidate the pathways of fructose metabolism in humans. These h...

Research paper thumbnail of Dietary Fructose and Metabolic Syndrome and Diabetes

The Journal of Nutrition, 2009

Studies in both healthy and diabetic subjects demonstrated that fructose produced a smaller postp... more Studies in both healthy and diabetic subjects demonstrated that fructose produced a smaller postprandial rise in plasma glucose and serum insulin than other common carbohydrates. Substitution of dietary fructose for other carbohydrates produced a 13% reduction in mean plasma glucose in a study of type 1 and type 2 diabetic subjects. However, there is concern that fructose may aggravate lipemia. In 1 study, day-long plasma triglycerides in healthy men were 32% greater while they consumed a high-fructose diet than while they consumed a high-glucose diet. There is also concern that fructose may be a factor contributing to the growing worldwide prevalence of obesity. Fructose stimulates insulin secretion less than does glucose and glucose-containing carbohydrates. Because insulin increases leptin release, lower circulating insulin and leptin after fructose ingestion might inhibit appetite less than consumption of other carbohydrates and lead to increased energy intake. However, there is no convincing experimental evidence that dietary fructose actually does increase energy intake. There is also no evidence that fructose accelerates protein glycation. High fructose intake has been associated with increased risk of gout in men and increased risk of kidney stones. Dietary fructose appears to have adverse effects on postprandial serum triglycerides, so adding fructose in large amounts to the diet is undesirable. Glucose may be a suitable replacement sugar. The fructose that occurs naturally in fruits and vegetables provides only a modest amount of dietary fructose and should not be of concern.

Research paper thumbnail of Efficacy of the Roux-en-Y gastric bypass compared to medically managed controls in meeting the American Diabetes Association composite end point goals for management of type 2 diabetes mellitus

Obesity surgery, 2012

The treatment goals recommended by the American Diabetes Association (ADA) for patients with type... more The treatment goals recommended by the American Diabetes Association (ADA) for patients with type 2 diabetes mellitus include hemoglobin A1c (HbA1C) <7.0%, low-density lipoprotein (LDL) <100 mg/dL, and systolic blood pressure (SBP) <130 mmHg. Only 10% of conventionally treated patients reach these goals as a composite endpoint. The efficacy of the Roux-en-Y gastric bypass (RYGB) in meeting this composite endpoint has not been reported.

Research paper thumbnail of Roux-en-Y Gastric Bypass vs Intensive Medical Management for the Control of Type 2 Diabetes, Hypertension, and Hyperlipidemia

Research paper thumbnail of Pharmacologic induction of weight loss to treat type 2 diabetes

Diabetes Care, 1999

OBJECTIVE: Most individuals with type 2 diabetes are overweight, and weight loss for them is an i... more OBJECTIVE: Most individuals with type 2 diabetes are overweight, and weight loss for them is an important therapeutic objective. However, usual weight-loss strategies have generally not produced sustained weight loss. Pharmacologic agents to assist weight loss might be useful, but no long-term data on their effectiveness and safety in patients with type 2 diabetes are available. We therefore initiated a 2-year placebo-controlled trial of the weight-loss medications fenfluramine and phentermine in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: A total of 44 overweight (> 120% ideal body weight) subjects with type 2 diabetes were enrolled in a randomized, placebo-controlled, double-blind trial of fenfluramine and phentermine. All subjects received intensive nutrition counseling, an exercise prescription, and instruction in behavior modification. Subjects were randomly assigned to 20 mg fenfluramine three times a day and 37.5 mg phentermine daily (n = 23) or dual placebos (n...

Research paper thumbnail of Metabolic Effects of Dietary Sucrose in Type II Diabetic Subjects

Diabetes Care, 1993

Objective— To assess in diabetic subjects the effects of dietary sucrose on glycemia and lipemia.... more Objective— To assess in diabetic subjects the effects of dietary sucrose on glycemia and lipemia. Research Design and Methods— Twelve type II diabetic subjects consumed, in random order, two isocaloric, 55% carbohydrate study diets for 28 days. In one diet, 19% of energy was derived from sucrose. In the other diet, <3% of energy was derived from sucrose, and carbohydrate energy came primarily from starch. Both study diets were composed of common foods. All meals were prepared in a metabolic kitchen where foods were weighed during meal preparation. Results— No significant differences were noted between the study diets at any time point in mean plasma glucose. At day 28, mean plasma glucose values for the sucrose diet were 9.6 ± 0.5 mM and for the starch diet were 9.4 ± 0.6 mM (P = 0.63). Also, no significant differences were observed between the study diets in urine glucose, fasting serum total, HDL, or LDL cholesterol; fasting serum TG; or peak postprandial serum TG. Conclusions—...

Research paper thumbnail of Nutrition Recommendations and Interventions for Diabetes–2006

Research paper thumbnail of Metabolic Effects of Dietary Fructose in Diabetic Subjects

Diabetes Care, 1992

OBJECTIVE To assess the metabolic effects of chronic dietary fructose consumption in diabetic sub... more OBJECTIVE To assess the metabolic effects of chronic dietary fructose consumption in diabetic subjects. RESEARCH DESIGN AND METHODS Six type I and 12 type II diabetic subjects consumed, in random order, two isocaloric study diets for 28 days. In one diet, 20% of energy was derived from fructose. In the other diet, <3% of energy came from fructose, and carbohydrate energy was derived primarily from starch. Both study diets were composed of common foods. All meals were prepared in a metabolic kitchen where all foods were weighed during meal preparation. RESULTS Mean plasma glucose, urine glucose, and serum glycosylated albumin values were lower during the fructose diet than during the starch diet, but the differences achieved only marginal statistical significance. The day-28 value for mean plasma glucose was 12.5% lower (P = 0.03) during the fructose diet than during the starch diet. At days 14, 21, and 28, fasting serum cholesterol and LDL cholesterol were both significantly high...

Research paper thumbnail of Postgastric bypass hyperinsulinemic hypoglycemia syndrome: characterization and response to a modified diet

Surgery for Obesity and Related Diseases, Jul 1, 2008

Some alarming cases of hypoglycemic episodes in patients who have undergone Roux-en-Y gastric byp... more Some alarming cases of hypoglycemic episodes in patients who have undergone Roux-en-Y gastric bypass have been reported. The syndrome of hyperinsulinemic hypoglycemia with nesidioblastosis after Roux-en-Y gastric bypass has been previously reported and is controversial. It has been suggested that subtotal or total pancreatectomy might be needed to control the symptoms in these patients. We have identified a similar cohort of patients with hyperinsulinemic hypoglycemia for whom we have reviewed patient characteristics and measured the glucose and insulin response to mixed meals. We reviewed the charts of 14 patients identified by clinic follow-up who reported episodes consistent with hyperinsulinemic hypoglycemia (lightheadedness or loss of consciousness after a high-carbohydrate meal). All patients were given a mixed meal consisting of high carbohydrates on day 1 and a low-carbohydrate meal on day 2. The plasma glucose and serum insulin levels were measured before (fasting) and 30, 60, 90, 120, 150, and 180 minutes after the meal. After a high-carbohydrate meal, 12 of 14 patients demonstrated hyperglycemia associated with hyperinsulinemia at 30 minutes. These patients subsequently became hypoglycemic while the serum insulin was rapidly declining. After reaching a nadir at 120 minutes, the plasma glucose level corrected spontaneously. After a low-carbohydrate mixed meal, the patients demonstrated very little change in plasma glucose and only a modest increase in serum insulin. Of the 12 patients treated with a low-carbohydrate diet, 6 had substantive symptom improvement, and 10 exhibited at least some improvement. The hyperinsulinemic hypoglycemia noted in some patients after Roux-en-Y gastric bypass has many similarities to the dumping syndrome. A low-carbohydrate diet successfully improved symptoms in most of our patients. Approaches to treatment should involve a low-carbohydrate diet and alpha-glucosidase inhibitors rather than pancreatectomy.

Research paper thumbnail of Suppression of plasma renin activity by cyclosporine

The American Journal of Medicine, Jul 1, 1987

Research paper thumbnail of Effects of Cyclosporine on the Renin-Angiotensin-Aldosterone System and Potassium Excretion in Renal Transplant Recipients

Archives of internal medicine, Mar 1, 1985

Research paper thumbnail of Post-Gastric Bypass Hyperinsulinemic Hypoglycemia: Fructose is a Carbohydrate Which Can Be Safely Consumed

The Journal of Clinical Endocrinology and Metabolism, Aug 1, 2015

Postprandial hypoglycemia after gastric bypass surgery is a serious problem. Available treatments... more Postprandial hypoglycemia after gastric bypass surgery is a serious problem. Available treatments are often ineffective. Objective: The objective was to test the hypotheses that injection of rapid-acting insulin before a high-carbohydrate meal or replacement of other carbohydrates with fructose in the meal would prevent hypoglycemia. Design: This was a randomized, crossover trial comparing a high-carbohydrate meal with premeal saline injection (control), a high-carbohydrate meal with premeal insulin injection, and a highfructose meal with total carbohydrate content similar to the control meal. The setting was an academic medical center. Patients: Ten patients with post-gastric bypass hyperinsulinemic hypoglycemia participated. Interventions included lispro insulin injected before test meals and replacement of other carbohydrates with fructose in test meals. The main outcome measure was plasma glucose Ͻ 60 mg/dL after test meals. Results: After the control meal, mean peak glucose and insulin were 173 Ϯ 47 mg/dL and 134 Ϯ 55 mU/L, respectively; mean glucose nadir was 44 Ϯ 15 mg/dL; and eight of 10 subjects demonstrated glucose Ͻ 60 mg/dL. Five subjects demonstrated a glucose nadir Ͻ 40 mg/dL. There were no significant differences in the corresponding values after premeal insulin treatment, except that the mean glucose nadir of 34 Ϯ 10 mg/dL was lower (P Ͻ .05). After the fructose meal, mean peak postprandial glucose and insulin were 117 Ϯ 20 mg/dL and 45 Ϯ 31 mU/L, respectively (both P Ͻ .001 for comparison with control), mean glucose nadir was 67 Ϯ 10 mg/dL (P Ͻ .001), and two of 10 subjects demonstrated glucose Ͻ 60 mg/dL (P Ͻ .05). People with post-gastric bypass hypoglycemia can consume a meal sweetened with fructose with little risk of hypoglycemia. Treatment with rapid-acting insulin before a carbohydrate-containing meal did not prevent hypoglycemia. (J Clin Endocrinol Metab 100: 3097-3102, 2015) I n 2005, Service et al (1) first described postprandial hy- poglycemia causing neuroglycopenia after Roux-en-Y gastric bypass surgery. Several of their patients experi-enced confusion and loss of consciousness during episodes. Subsequently, additional patients with this disorder have been described in small series and case reports (2-8).

Research paper thumbnail of Clinical Aspects of Sucrose and Fructose Metabolism

Research paper thumbnail of Partial ileal bypass affords protection from onset of type 2 diabetes

Surgery for Obesity and Related Diseases, 2017

Partial ileal bypass (PIB) in the National Institutes of Health-sponsored Program on the Surgical... more Partial ileal bypass (PIB) in the National Institutes of Health-sponsored Program on the Surgical Control of the Hyperlipidemias (POSCH) randomized controlled trial was found to reduce plasma cholesterol, in particular low density lipoprotein cholesterol, with concomitant retardation of atherosclerotic cardiovascular disease and increased life expectancy. Glucagon-like peptide-1, related to amelioration of type 2 diabetes, is increased over 5-fold after PIB. We hypothesized that PIB, in addition to its action on cholesterol metabolism, may also prevent type 2 diabetes. We surveyed by telephone inquiry of former POSCH patients the 30+year posttrial incidence of type 2 diabetes or prediabetes, the presence of which was a trial exclusion criteria. We were able to contact 17.4% (n = 838) of the original POSCH population. Of 66 control responders, 17 contracted type 2 diabetes (25.8%); of 80 PIB responders, 8 contracted type 2 diabetes (10%). The difference between groups was significant (P = .015 by Fisher exact test) with an odds ratio of .320 for the PIB group and an over 2-fold (2.6) increase in the incidence of type 2 diabetes in the controls. Including borderline type 2 diabetes (prediabetic) patients, these values were 22 of 66 controls (33.3%) and 10 of 80 PIB patients (12.5%), with an odds ratio of .286 and a P&lt;.004, and again an over 2-fold (2.7) increase in the incidence of type 2 diabetes in the control patients. PIB appears to afford partial protection from the onset of type 2 diabetes for over 30 years.

Research paper thumbnail of Evidence-Based Nutrition Principles and Recommendations for the Treatment and Prevention of Diabetes and Related Complications

Research paper thumbnail of Effects of dietary fructose on plasma lipids in healthy subjects

The American Journal of Clinical Nutrition, 2000

Research paper thumbnail of Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood Pressure at 5 Years in the Diabetes Surgery Study

JAMA, Jan 16, 2018

The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, bu... more The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. To compare durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical management in achieving diabetes control targets. Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. The American Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic bloo...

Research paper thumbnail of Durability of Addition of Roux-en-Y Gastric Bypass to Lifestyle Intervention and Medical Management in Achieving Primary Treatment Goals for Uncontrolled Type 2 Diabetes in Mild-to-Moderate Obesity: A Randomized Control Trial

Diabetes care, Sep 16, 2016

We compared 3-year achievement of an American Diabetes Association composite treatment goal (HbA1... more We compared 3-year achievement of an American Diabetes Association composite treatment goal (HbA1c <7.0%, LDL cholesterol <100 mg/dL, and systolic blood pressure <130 mmHg) after 2 years of intensive lifestyle-medical management intervention, with and without Roux-en-Y gastric bypass, with one additional year of usual care. A total of 120 adult participants, with BMI 30.0-39.9 kg/m(2) and HbA1c ≥8.0%, were randomized 1:1 to two treatment arms at three clinical sites in the U.S. and one in Taiwan. All patients received the lifestyle-medical management intervention for 24 months; half were randomized to also receive gastric bypass. At 36 months, the triple end point goal was met in 9% of lifestyle-medical management patients and 28% of gastric bypass patients (P = 0.01): 10% and 19% lower than at 12 months. Mean (SD) HbA1c values at 3 years were 8.6% (3.5) and 6.7% (2.0) (P < 0.001). No lifestyle-medical management patient had remission of diabetes at 36 months, whereas 17...

Research paper thumbnail of Partial Ileal Bypass Affords Protection from Onset of Type 2 Diabetes

Surgery for Obesity and Related Diseases, 2017

Partial ileal bypass (PIB) in the National Institutes of Health-sponsored Program on the Surgical... more Partial ileal bypass (PIB) in the National Institutes of Health-sponsored Program on the Surgical Control of the Hyperlipidemias (POSCH) randomized controlled trial was found to reduce plasma cholesterol, in particular low density lipoprotein cholesterol, with concomitant retardation of atherosclerotic cardiovascular disease and increased life expectancy. Glucagon-like peptide-1, related to amelioration of type 2 diabetes, is increased over 5-fold after PIB. We hypothesized that PIB, in addition to its action on cholesterol metabolism, may also prevent type 2 diabetes. We surveyed by telephone inquiry of former POSCH patients the 30+year posttrial incidence of type 2 diabetes or prediabetes, the presence of which was a trial exclusion criteria. We were able to contact 17.4% (n = 838) of the original POSCH population. Of 66 control responders, 17 contracted type 2 diabetes (25.8%); of 80 PIB responders, 8 contracted type 2 diabetes (10%). The difference between groups was significant (P = .015 by Fisher exact test) with an odds ratio of .320 for the PIB group and an over 2-fold (2.6) increase in the incidence of type 2 diabetes in the controls. Including borderline type 2 diabetes (prediabetic) patients, these values were 22 of 66 controls (33.3%) and 10 of 80 PIB patients (12.5%), with an odds ratio of .286 and a P&lt;.004, and again an over 2-fold (2.7) increase in the incidence of type 2 diabetes in the control patients. PIB appears to afford partial protection from the onset of type 2 diabetes for over 30 years.

Research paper thumbnail of Roux-en-Y gastric bypass for diabetes (the Diabetes Surgery Study): 2-year outcomes of a 5-year, randomised, controlled trial

The lancet. Diabetes & endocrinology, 2015

Conventional treatments for patients with type 2 diabetes are often inadequate. We aimed to asses... more Conventional treatments for patients with type 2 diabetes are often inadequate. We aimed to assess outcomes of diabetes control and treatment risks 2 years after adding Roux-en-Y gastric bypass to intensive lifestyle and medical management. We report 2-year outcomes of a 5-year randomised trial (the Diabetes Surgery Study) at four teaching hospitals (three in the USA and one in Taiwan). At baseline, eligible participants had to have HbA1c of at least 8·0% (64 mmol/mol), BMI between 30·0 and 39·9 kg/m(2), and type 2 diabetes for at least 6 months, and be aged 30-67 years. We randomly assigned participants to receive either intensive lifestyle and medical management alone (lifestyle and medical management), or lifestyle and medical management plus standard Roux-en-Y gastric bypass surgery (gastric bypass). Staff from the clinical centres had access to data from individual patients, but were masked to other patients' data and aggregated data until the 2-year follow-up. Drugs for hy...

Research paper thumbnail of Clinical research strategies for fructose metabolism

Advances in nutrition (Bethesda, Md.), 2014

Fructose and simple sugars are a substantial part of the western diet, and their influence on hum... more Fructose and simple sugars are a substantial part of the western diet, and their influence on human health remains controversial. Clinical studies in fructose nutrition have proven very difficult to conduct and interpret. NIH and USDA sponsored a workshop on 13-14 November 2012, "Research Strategies for Fructose Metabolism," to identify important scientific questions and parameters to be considered while designing clinical studies. Research is needed to ascertain whether there is an obesogenic role for fructose-containing sugars via effects on eating behavior and energy balance and whether there is a dose threshold beyond which these sugars promote progression toward diabetes and liver and cardiovascular disease, especially in susceptible populations. Studies tend to fall into 2 categories, and design criteria for each are described. Mechanistic studies are meant to validate observations made in animals or to elucidate the pathways of fructose metabolism in humans. These h...

Research paper thumbnail of Dietary Fructose and Metabolic Syndrome and Diabetes

The Journal of Nutrition, 2009

Studies in both healthy and diabetic subjects demonstrated that fructose produced a smaller postp... more Studies in both healthy and diabetic subjects demonstrated that fructose produced a smaller postprandial rise in plasma glucose and serum insulin than other common carbohydrates. Substitution of dietary fructose for other carbohydrates produced a 13% reduction in mean plasma glucose in a study of type 1 and type 2 diabetic subjects. However, there is concern that fructose may aggravate lipemia. In 1 study, day-long plasma triglycerides in healthy men were 32% greater while they consumed a high-fructose diet than while they consumed a high-glucose diet. There is also concern that fructose may be a factor contributing to the growing worldwide prevalence of obesity. Fructose stimulates insulin secretion less than does glucose and glucose-containing carbohydrates. Because insulin increases leptin release, lower circulating insulin and leptin after fructose ingestion might inhibit appetite less than consumption of other carbohydrates and lead to increased energy intake. However, there is no convincing experimental evidence that dietary fructose actually does increase energy intake. There is also no evidence that fructose accelerates protein glycation. High fructose intake has been associated with increased risk of gout in men and increased risk of kidney stones. Dietary fructose appears to have adverse effects on postprandial serum triglycerides, so adding fructose in large amounts to the diet is undesirable. Glucose may be a suitable replacement sugar. The fructose that occurs naturally in fruits and vegetables provides only a modest amount of dietary fructose and should not be of concern.

Research paper thumbnail of Efficacy of the Roux-en-Y gastric bypass compared to medically managed controls in meeting the American Diabetes Association composite end point goals for management of type 2 diabetes mellitus

Obesity surgery, 2012

The treatment goals recommended by the American Diabetes Association (ADA) for patients with type... more The treatment goals recommended by the American Diabetes Association (ADA) for patients with type 2 diabetes mellitus include hemoglobin A1c (HbA1C) <7.0%, low-density lipoprotein (LDL) <100 mg/dL, and systolic blood pressure (SBP) <130 mmHg. Only 10% of conventionally treated patients reach these goals as a composite endpoint. The efficacy of the Roux-en-Y gastric bypass (RYGB) in meeting this composite endpoint has not been reported.

Research paper thumbnail of Roux-en-Y Gastric Bypass vs Intensive Medical Management for the Control of Type 2 Diabetes, Hypertension, and Hyperlipidemia

Research paper thumbnail of Pharmacologic induction of weight loss to treat type 2 diabetes

Diabetes Care, 1999

OBJECTIVE: Most individuals with type 2 diabetes are overweight, and weight loss for them is an i... more OBJECTIVE: Most individuals with type 2 diabetes are overweight, and weight loss for them is an important therapeutic objective. However, usual weight-loss strategies have generally not produced sustained weight loss. Pharmacologic agents to assist weight loss might be useful, but no long-term data on their effectiveness and safety in patients with type 2 diabetes are available. We therefore initiated a 2-year placebo-controlled trial of the weight-loss medications fenfluramine and phentermine in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: A total of 44 overweight (> 120% ideal body weight) subjects with type 2 diabetes were enrolled in a randomized, placebo-controlled, double-blind trial of fenfluramine and phentermine. All subjects received intensive nutrition counseling, an exercise prescription, and instruction in behavior modification. Subjects were randomly assigned to 20 mg fenfluramine three times a day and 37.5 mg phentermine daily (n = 23) or dual placebos (n...

Research paper thumbnail of Metabolic Effects of Dietary Sucrose in Type II Diabetic Subjects

Diabetes Care, 1993

Objective— To assess in diabetic subjects the effects of dietary sucrose on glycemia and lipemia.... more Objective— To assess in diabetic subjects the effects of dietary sucrose on glycemia and lipemia. Research Design and Methods— Twelve type II diabetic subjects consumed, in random order, two isocaloric, 55% carbohydrate study diets for 28 days. In one diet, 19% of energy was derived from sucrose. In the other diet, <3% of energy was derived from sucrose, and carbohydrate energy came primarily from starch. Both study diets were composed of common foods. All meals were prepared in a metabolic kitchen where foods were weighed during meal preparation. Results— No significant differences were noted between the study diets at any time point in mean plasma glucose. At day 28, mean plasma glucose values for the sucrose diet were 9.6 ± 0.5 mM and for the starch diet were 9.4 ± 0.6 mM (P = 0.63). Also, no significant differences were observed between the study diets in urine glucose, fasting serum total, HDL, or LDL cholesterol; fasting serum TG; or peak postprandial serum TG. Conclusions—...

Research paper thumbnail of Nutrition Recommendations and Interventions for Diabetes–2006

Research paper thumbnail of Metabolic Effects of Dietary Fructose in Diabetic Subjects

Diabetes Care, 1992

OBJECTIVE To assess the metabolic effects of chronic dietary fructose consumption in diabetic sub... more OBJECTIVE To assess the metabolic effects of chronic dietary fructose consumption in diabetic subjects. RESEARCH DESIGN AND METHODS Six type I and 12 type II diabetic subjects consumed, in random order, two isocaloric study diets for 28 days. In one diet, 20% of energy was derived from fructose. In the other diet, <3% of energy came from fructose, and carbohydrate energy was derived primarily from starch. Both study diets were composed of common foods. All meals were prepared in a metabolic kitchen where all foods were weighed during meal preparation. RESULTS Mean plasma glucose, urine glucose, and serum glycosylated albumin values were lower during the fructose diet than during the starch diet, but the differences achieved only marginal statistical significance. The day-28 value for mean plasma glucose was 12.5% lower (P = 0.03) during the fructose diet than during the starch diet. At days 14, 21, and 28, fasting serum cholesterol and LDL cholesterol were both significantly high...