Calorie restriction and not glucagon‐like peptide‐1 explains the acute improvement in glucose control after gastric bypass in Type 2 diabetes

Abstract

 The increased weight loss at 7 days following RYGB compared to 7 days of VLCD in T2DM is due to greater loss of lean and water mass  After RYGB, the early and enhanced post-meal rise in glucose and insulin is due to rapid absorption through the gastroenterostomy  The increased post-meal GLP-1 secretion specific to RYGB is not accompanied by an improvement in insulin or glucose AUC when compared to VLCD  The early improvement in glucose control in T2DM after bariatric surgery is not explained by improved beta cell function  The relationship between weight loss and loss of liver fat at 7 days following bariatric surgery and VLCD appears different 2 Abstract AimsIt remains unclear whether the mechanism underlying the early improvement in glucose metabolism in type 2 diabetes following roux-en-Y gastric bypass surgery (RYGB) differs from that seen with a very low calorie diet (VLCD). Specifically, whether the markedly increased GLP-1 secretion following surgery is of primary importance has been controversial. This study compared directly the impact of GLP-1 secretion on glucose metabolism in individuals with type 2 diabetes listed for RYGB, randomised to be studied before and at 7 days following RYGB or VLCD. MethodsA semi-solid meal test was used to investigate glucose, insulin and GLP-1 response. Insulin secretion to intravenous glucose and arginine stimulus was measured. Hepatic and pancreatic fat content was quantified using a magnetic resonance (MR) method. ResultsDecrease in fat mass was almost identical after surgery or VLCD (3.0±0.3 and 3.0±0.7kg). The early plasma glucose rise and acute insulin secretion were greater following surgery than VLCD. However, the early GLP-1 rise was disproportionately greater (7-fold) after surgery than VLCD. This did not translate into a greater improvement in fasting glucose or glucose area under the curve. The reduction in liver fat was greater after surgery (29.8±3.7 vs. 18.6±4.0%) and the relationship between weight loss and reduction in liver fat differed following surgery or VLCD. ConclusionsIn conclusion, this study demonstrates that gastroenterostomy increases the rate of nutrient absorption, bringing about a commensurately rapid rise insulin. However, there was no relationship with the large post-meal rise in GLP-1 and post-meal glucose homeostasis was similar after surgery or VLCD.

Effect of Laparoscopic Sleeve Gastrectomy on Static and Dynamic Measures of Glucose Homeostasis and Incretin Hormone Response 4-Years Post-Operatively

“…Our findings question the role of GLP-1 in the mechanism of longterm diabetes remission. Of note, Steven and colleagues reported that calorie restriction but not GLP-1 explains the acute improvement in glycaemic control following RYGB in subjects with T2DM [31].…”

Time Course of Normalization of Functional β-Cell Capacity in the Diabetes Remission Clinical Trial After Weight Loss in Type 2 Diabetes

“…No comparable observations have been made in previous studies, and the pathophysiologic mechanism underlying this requires investigation. GLP-1 responsiveness was not examined in this study and dietary weight loss has previously been shown not to change this after return to non-diabetic glucose control (28,29).…”

Very low‐energy and low‐energy formula diets: Effects on weight loss, obesity co‐morbidities and type 2 diabetes remission – an update on the evidence for their use in clinical practice

“…), which occurs prior to any changes in bodyweight or alterations in plasma GLP‐1 levels (Steven et al . ). With only a fraction of individuals accessing surgery, there is a need for other treatment options to help achieve clinically relevant weight loss that may bring about T2D remission.…”

“…The exact mechanisms which drive improvements in, and remission of, T2D following bariatric surgery remain to be fully understood, although are hypothesised to include alterations in gut hormones, bile acid changes, adaptions in the microbiome and changes in food preferences and smell (Miras & le Roux 2013;Batterham & Cummings 2016). Recent evidence points towards the acute energy restriction that occurs immediately following bariatric surgery playing a pivotal role in the early glycaemic improvements seen in both biliopancreatic diversion (BPD) and Roux-en-Y gastric bypass (RYGB) (Jackness et al 2013;Lips et al 2014), which occurs prior to any changes in bodyweight or alterations in plasma GLP-1 levels (Steven et al 2016b). With only a fraction of individuals accessing surgery, there is a need for other treatment options to help achieve clinically relevant weight loss that may bring about T2D remission.…”