Mechanisms of action of a carbohydrate-reduced, high-protein diet in reducing the risk of postprandial hypoglycemia after Roux-en-Y gastric bypass surgery.

Background Postprandial hypoglycemia is a risk after Roux-en-Y gastric bypass (RYGB). Objectives We speculated that a carbohydrate-reduced, high-protein (CRHP) diet might reduce the risk of hypoglycemia and therefore compared the acute effects of a conventionally recommended (CR) diet and CRHP diet [55/30 energy percent (E%) carbohydrate and 15/30 E% protein, respectively] in RYGB patients. Methods Ten individuals (2 males, 8 females, mean ± SD age 47 ± 7 y; stable body mass index 31 ± 6 kg/m2; 6 ± 3 y post-RYGB) with recurrent postprandial hypoglycemia documented by plasma glucose (PG) ≤3.4 mmol/L were examined on 2 d with isoenergetic CRHP or CR diets comprising a breakfast and subsequent lunch meal. Results Peak PG was significantly reduced on the CRHP diet after breakfast and lunch by 11% and 31% compared with the CR diet. Nadir PG increased significantly on CRHP (by 13% and 9%). Insulin secretion was reduced, and glucagon secretion increased on the CRHP diet after both meals. Glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide secretion were lower after lunch but unaltered after breakfast on CRHP; β-cell function and insulin clearance were unchanged. Conclusions The CRHP diet lowered glucose excursions and reduced insulin secretion and incretin hormone responses, but enhanced glucagon responses compared with the CR diet. Taken together, the results may explain the decreased glucose variability and lower risk of postprandial hypoglycemia. This study was registered at clinicaltrials.gov as NCT02665715.

[1]  J. Holst,et al.  Critical role for GLP-1 in symptomatic post-bariatric hypoglycaemia , 2017, Diabetologia.

[2]  J. Holst,et al.  Glucagon and Amino Acids Are Linked in a Mutual Feedback Cycle: The Liver–α-Cell Axis , 2017, Diabetes.

[3]  U. Wiklund,et al.  Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia , 2016, Diabetes.

[4]  J. Holst,et al.  No Islet Cell Hyperfunction, but Altered Gut-Islet Regulation and Postprandial Hypoglycemia in Glucose-Tolerant Patients 3 Years After Gastric Bypass Surgery , 2016, Obesity Surgery.

[5]  H. Hanaire,et al.  Hypoglycaemia after gastric bypass: mechanisms and treatment , 2016, Diabetes, obesity & metabolism.

[6]  B. Richelsen,et al.  Continuous Glucose Monitoring After Gastric Bypass to Evaluate the Glucose Variability After a Low-Carbohydrate Diet and to Determine Hypoglycemia , 2016, Obesity Surgery.

[7]  J. Bantle,et al.  Post-Gastric Bypass Hyperinsulinemic Hypoglycemia: Fructose is a Carbohydrate Which Can Be Safely Consumed. , 2015, The Journal of clinical endocrinology and metabolism.

[8]  B. Ludvik,et al.  Hypoglycemia after Roux-En-Y gastric bypass: detection rates of continuous glucose monitoring (CGM) versus mixed meal test. , 2015, Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery.

[9]  M. Patti,et al.  Insulin response to oral stimuli and glucose effectiveness increased in neuroglycopenia following gastric bypass , 2015, Obesity.

[10]  C. L. le Roux,et al.  More symptoms but similar blood glucose curve after oral carbohydrate provocation in patients with a history of hypoglycemia-like symptoms compared to asymptomatic patients after Roux-en-Y gastric bypass. , 2014, Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery.

[11]  I. Janssen,et al.  Effect of Carbohydrate Restriction in Patients with Hyperinsulinemic Hypoglycemia after Roux-en-Y Gastric Bypass , 2014, Obesity Surgery.

[12]  J. Holst,et al.  Early Enhancements of Hepatic and Later of Peripheral Insulin Sensitivity Combined With Increased Postprandial Insulin Secretion Contribute to Improved Glycemic Control After Roux-en-Y Gastric Bypass , 2014, Diabetes.

[13]  A. Gastaldelli,et al.  Altered islet function and insulin clearance cause hyperinsulinemia in gastric bypass patients with symptoms of postprandial hypoglycemia. , 2014, The Journal of clinical endocrinology and metabolism.

[14]  A. Gastaldelli,et al.  Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass. , 2014, Gastroenterology.

[15]  M. Patti,et al.  Hypoglycemia after gastric bypass: the dark side of GLP-1. , 2014, Gastroenterology.

[16]  J. Holst,et al.  Exaggerated Glucagon-Like Peptide 1 Response Is Important for Improved β-Cell Function and Glucose Tolerance After Roux-en-Y Gastric Bypass in Patients With Type 2 Diabetes , 2013, Diabetes.

[17]  J. Holst,et al.  Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals , 2013, Diabetologia.

[18]  L. Sjöström Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery , 2013, Journal of internal medicine.

[19]  J. Holst,et al.  Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance. , 2012, American journal of physiology. Endocrinology and metabolism.

[20]  R. Rector,et al.  The Second Meal Effect and Its Influence on Glycemia , 2012 .

[21]  D. D’Alessio,et al.  Gastric Bypass Surgery Enhances Glucagon-Like Peptide 1–Stimulated Postprandial Insulin Secretion in Humans , 2011, Diabetes.

[22]  M. Patti,et al.  Hypoglycaemia following gastric bypass surgery—diabetes remission in the extreme? , 2010, Diabetologia.

[23]  F. Rasmussen,et al.  Nationwide cohort study of post-gastric bypass hypoglycaemia including 5,040 patients undergoing surgery for obesity in 1986–2006 in Sweden , 2010, Diabetologia.

[24]  C. Lamendola,et al.  Plasma Glucose and Insulin Regulation Is Abnormal Following Gastric Bypass Surgery with or Without Neuroglycopenia , 2009, Obesity surgery.

[25]  S. Ikramuddin,et al.  Postgastric bypass hyperinsulinemic hypoglycemia syndrome: characterization and response to a modified diet. , 2008, Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery.

[26]  Daniel B. Jones,et al.  Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. , 2007, The Journal of clinical endocrinology and metabolism.

[27]  J. Holst,et al.  Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence for inappropriate insulin secretion and pancreatic islet hyperplasia , 2005, Diabetologia.

[28]  R. Lloyd,et al.  Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. , 2005, The New England journal of medicine.

[29]  Stephen Colagiuri,et al.  Low-glycemic index diets in the management of diabetes: a meta-analysis of randomized controlled trials. , 2003, Diabetes care.

[30]  R. Hovorka,et al.  ISEC: a program to calculate insulin secretion. , 1996, Computer methods and programs in biomedicine.

[31]  P. Cryer Hypoglycemia: The Limiting Factor in the Management of IDDM , 1994, Diabetes.

[32]  Jeppe Sturis,et al.  Estimation of Insulin Secretion Rates from C-Peptide Levels: Comparison of Individual and Standard Kinetic Parameters for C-Peptide Clearance , 1992, Diabetes.

[33]  D. M. Rocha,et al.  Glucagon-stimulating activity of 20 amino acids in dogs. , 1972, The Journal of clinical investigation.

[34]  R. Unger,et al.  The role of aminogenic glucagon secretion in blood glucose homeostasis. , 1969, The Journal of clinical investigation.

[35]  M. Ohrvall,et al.  Effects of gastric bypass on the GH/IGF-I axis in severe obesity--and a comparison with GH deficiency. , 2006, European journal of endocrinology.