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

Abstract

Roux-en-Y gastric bypass (RYGB) improves glycemic control within days after surgery, and changes in insulin sensitivity and β-cell function are likely to be involved. We studied 10 obese patients with type 2 diabetes (T2D) and 10 obese glucose-tolerant subjects before and 1 week, 3 months, and 1 year after RYGB. Participants were included after a preoperative diet-induced total weight loss of −9.2 ± 1.2%. Hepatic and peripheral insulin sensitivity were assessed using the hyperinsulinemic- euglycemic clamp combined with the glucose tracer technique, and β-cell function was evaluated in response to an intravenous glucose-glucagon challenge as well as an oral glucose load. Within 1 week, RYGB reduced basal glucose production, improved basal hepatic insulin sensitivity, and increased insulin clearance, highlighting the liver as an important organ responsible for early effects on glucose metabolism after surgery. Insulin-mediated glucose disposal and suppression of fatty acids did not improve immediately after surgery but increased at 3 months and 1 year; this increase likely was related to the reduction in body weight. Insulin secretion increased after RYGB only in patients with T2D and only in response to oral glucose, underscoring the importance of the changed gut anatomy.

Incidence and remission of type 2 diabetes in relation to degree of obesity at baseline and 2 year weight change: the Swedish Obese Subjects (SOS) study

“…Furthermore, in line with other reports [18], GBP patients lost more weight than banding or VBG patients [3]. Several studies suggest that GBP may affect glucose metabolism by mechanisms other than weight loss and that early remission of type 2 diabetes after bariatric surgery is independent of weight loss and caused by mechanisms related to the surgery itself [19][20][21][22][23]. For long-term effects on glycaemic control, weight loss is probably a major determinant [18].…”

Hyperglucagonaemia analysed by glucagon sandwich ELISA: nonspecific interference or truly elevated levels?

“…However, hyperglucagonaemia is also observed in renal disease and obesity, and after operations that alter the gastrointestinal delivery of nutrients, such as RYGB and vagotomy plus pyloroplasty [7][8][9]. The immunoreactive glucagon seen in these hyperglucagonaemic states has hitherto been poorly characterised, but the elevated levels may result from increased levels of authentic pancreatic glucagon (arising from increased secretion and/or reduced clearance) and/or the accumulation of other moieties containing the antigenic determinant of glucagon (e.g.…”

“…Elevated plasma glucagon levels have also been reported after Roux-en-Y gastric bypass (RYGB) or vagotomy (plus pyloroplasty), or in patients with end-stage renal disease (ESRD) [7][8][9]. Paradoxically, glucagon levels are generally elevated at elevated glucose levels that should suppress glucagon secretion.…”

“…Plasma samples from type 2 diabetes patients and individuals with normal glucose tolerance (NGT) before and 1 year after RYGB were obtained from Bojsen-Møller et al (trial registration number NCT 01202526) [7]; plasma samples from vagotomised and control individuals were obtained from Plamboeck et al (NCT01176890) [8]; and plasma samples from ESRD patients were obtained from Idorn et al (NCT01327378) [9].…”

Hormonal Signaling in the Gut

“…Despite this, both vertical sleeve gastrectomy and RYGB are effective in normalizing glycemia in several models of models of GLP-1R deficiency (48,49), whereas duodenal-jejunal bypass (DJB) improves glucose levels despite nonelevated postsurgical GLP-1 levels in nonobese type 1 diabetic rats (50). Thus, the role of GLP-1 in mediating the antidiabetic effects of bariatric surgery still remains highly controversial (44,45,(51)(52)(53)(54)(55).…”