Very Low–Calorie Diet Mimics the Early Beneficial Effect of Roux-en-Y Gastric Bypass on Insulin Sensitivity and β-Cell Function in Type 2 Diabetic Patients

Jackness, Clifton; Karmally, Wahida; Febres, Gerardo; Conwell, Irene M.; Ahmed, Leaque; Bessler, Marc; McMahon, Donald J.; Körner, Judith

doi:10.2337/db12-1762

Cited by 240 publications

(217 citation statements)

References 41 publications

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“…After RYGB, a 2.6-fold increase of insulin secretion assessed by the intravenous glucose tolerance test disposition index has been reported (34). A very lowcalorie diet or RYGB results in similarly increased insulin secretion in both groups despite a marked increase in GLP-1 after RYGB only (35). A specific GLP-1 receptor antagonist does not affect insulin secretion after RYGB (36,37).…”

Section: Discussionmentioning

confidence: 99%

Weight Loss Decreases Excess Pancreatic Triacylglycerol Specifically in Type 2 Diabetes

et al. 2015

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OBJECTIVEThis study determined whether the decrease in pancreatic triacylglycerol during weight loss in type 2 diabetes mellitus (T2DM) is simply reflective of whole-body fat or specific to diabetes and associated with the simultaneous recovery of insulin secretory function. RESEARCH DESIGN AND METHODSIndividuals listed for gastric bypass surgery who had T2DM or normal glucose tolerance (NGT) matched for age, weight, and sex were studied before and 8 weeks after surgery. Pancreas and liver triacylglycerol were quantified using inphase, out-of-phase MRI. Also measured were the first-phase insulin response to a stepped intravenous glucose infusion, hepatic insulin sensitivity, and glycemic and incretin responses to a semisolid test meal. RESULTSWeight loss after surgery was similar (NGT: 12.8 6 0.8% and T2DM: 13.6 6 0.7%) as was the change in fat mass (56.7 6 3.3 to 45.4 6 2.3 vs. 56.6 6 2.4 to 43.0 6 2.4 kg). Pancreatic triacylglycerol did not change in NGT (5.1 6 0.2 to 5.5 6 0.4%) but decreased in the group with T2DM (6.6 6 0.5 to 5.4 6 0.4%; P = 0.007). Firstphase insulin response to a stepped intravenous glucose infusion did not change in (P = 0.005). No differential effect of incretin secretion was observed after gastric bypass, with more rapid glucose absorption bringing about equivalently enhanced glucagon-like peptide 1 secretion in the two groups. CONCLUSIONSThe fall in intrapancreatic triacylglycerol in T2DM, which occurs during weight loss, is associated with the condition itself rather than decreased total body fat.Type 2 diabetes mellitus (T2DM) has reached epidemic proportions, affecting 9.2% of the U.S. population and costing the country $322 billion in 2012 (1). The condition is widely recognized to be caused by a combination of insulin resistance and insulin secretory failure. However, insulin resistance alone does not cause blood glucose to rise (2), and T2DM occurs only when the acute insulin response of pancreatic b-cells becomes inadequate to control blood glucose (3,4). The etiologic process underlying this is still uncertain. Inhibition by excess intracellular fatty acids or their metabolites is a potential mechanism (5-7). We have previously demonstrated in people with T2DM that weight loss over 8 weeks can normalize the acute insulin response and

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Section: Discussionmentioning

confidence: 99%

Weight Loss Decreases Excess Pancreatic Triacylglycerol Specifically in Type 2 Diabetes

et al. 2015

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“…4 Obese patients with T2D who underwent RYGB or 500 kcal/day diet lost equivalent weight over three weeks and showed similar improvements in acute insulin secretion and beta-cell function in an IV GTT. 65 Postprandial GLP-1 secretion is substantially and durably increased early after RYGB, before significant weight loss has occurred, due to increased delivery of nutrients to the distal small intestine. 127 The importance of the incretin effect is unclear, with some studies showing that GLP-1 receptor blockade abolishes the RYGB-related improvement in beta-cell glucose sensitivity and insulin secretion 127 while another study found only minimal impairment in glucose tolerance following GLP-1 blockade after RYGB.…”

Section: Bariatric Surgerymentioning

confidence: 99%

“…4,64 VLCD leads to a reduction in fasting plasma glucose within the first days -when weight loss is minimal -largely attributable to reduced hepatic glucose output. 4,65 This is associated with reduced basal insulin secretion, suggesting improved hepatic insulin sensitivity. 4,65 It would be predicted that reduction in FPG would improve beta-cell function by amelioration of glucotoxicity and, in overweight patients with T2D, eight weeks of VLCD can lead to a gradual restoration of first-phase insulin response.…”

Section: Very Low Calorie Diet (Vlcd)mentioning

confidence: 99%

“…4,65 This is associated with reduced basal insulin secretion, suggesting improved hepatic insulin sensitivity. 4,65 It would be predicted that reduction in FPG would improve beta-cell function by amelioration of glucotoxicity and, in overweight patients with T2D, eight weeks of VLCD can lead to a gradual restoration of first-phase insulin response. 4,66 Reduced lipotoxicity following VLCD may also improve beta-cell function.…”

Section: Very Low Calorie Diet (Vlcd)mentioning

confidence: 99%

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Targeting beta-cell preservation in the management of type 2 diabetes

2017

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Type 2 diabetes (T2D) is widely considered a chronic and progressive disease without cure. As beta-cell function progressively declines over time, blood glucose rises. Current management of T2D involves incremental introduction of dietary and drug therapies to achieve normoglycaemia. However, recent studies have demonstrated remission of T2D following bariatric surgery, very low calorie diet or intensive insulin therapy, raising the possibility that the declining beta-cell function in T2D may be arrested or even reversed. The point at which such interventions are introduced in the course of T2D is key for clinical benefit. Future treatment strategies should be revised to target early betacell preservation and thus disease remission. This article reviews the pathogenesis of beta-cell dysfunction and evidence for the clinical benefit of preserving beta-cell function in T2D, and discusses the evidence for beta-cell preservation of current glucose-lowering therapies with particular reference to their effect when initiated at the time of diagnosis of T2D. Br J Diabetes 2017;17:134-144

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“…In studies with bariatric surgery patients, it is standard procedure to provide a very low calorie diet for a week or two after gastric bypass surgery [19][20][21] and caloric intake is often also restricted before surgery. In addition, patients typically receive heavy dietary counseling before and after surgery, making it difficult to analyze quantity and pattern of voluntarily ingested food, particularly during the early post-surgical period.…”

Section: Behavioral Evidence For Rygb-induced Change In Defended Bodymentioning

confidence: 99%

Does gastric bypass surgery change body weight set point?

et al. 2016

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The relatively stable body weight during adulthood is attributed to a homeostatic regulatory mechanism residing in the brain which uses feedback from the body to control energy intake and expenditure. This mechanism guarantees that if perturbed up or down by design, body weight will return to pre-perturbation levels, defined as the defended level or set point. The fact that weight re-gain is common after dieting suggests that obese subjects defend a higher level of body weight. Thus, the set point for body weight is flexible and likely determined by the complex interaction of genetic, epigenetic and environmental factors. Unlike dieting, bariatric surgery does a much better job in producing sustained suppression of food intake and body weight, and an intensive search for the underlying mechanisms has started. Although one explanation for this lasting effect of particularly Roux-en-Y gastric bypass surgery (RYGB) is simple physical restriction due to the invasive surgery, a more exciting explanation is that the surgery physiologically reprograms the body weight defense mechanism. In this non-systematic review, we present behavioral evidence from our own and other studies that defended body weight is lowered after RYGB and sleeve gastrectomy. After these surgeries, rodents return to their preferred lower body weight if over-or underfed for a period of time, and the ability to drastically increase food intake during the anabolic phase strongly argues against the physical restriction hypothesis. However, the underlying mechanisms remain obscure. Although the mechanism involves central leptin and melanocortin signaling pathways, other peripheral signals such as gut hormones and their neural effector pathways likely contribute. Future research using both targeted and non-targeted 'omics' techniques in both humans and rodents as well as modern, genetically targeted, neuronal manipulation techniques in rodents will be necessary.

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Very Low–Calorie Diet Mimics the Early Beneficial Effect of Roux-en-Y Gastric Bypass on Insulin Sensitivity and β-Cell Function in Type 2 Diabetic Patients

Cited by 240 publications

References 41 publications

Weight Loss Decreases Excess Pancreatic Triacylglycerol Specifically in Type 2 Diabetes

Weight Loss Decreases Excess Pancreatic Triacylglycerol Specifically in Type 2 Diabetes

Targeting beta-cell preservation in the management of type 2 diabetes

Does gastric bypass surgery change body weight set point?

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