Restoration of Euglycemia and Normal Acute Insulin Response to Glucose in Obese Subjects With Type 2 Diabetes Following Bariatric Surgery

Abstract

Insulin resistance and loss of glucose-stimulated acute insulin response (AIR) are the two major and earliest defects in the course of type 2 diabetes. We investigated whether weight loss after bariatric surgery in patients with morbid obesity and type 2 diabetes could restore euglycemia and normal AIR to an intravenous glucose tolerance test (IVGTT). We studied 25 morbidly obese patients-12 with type 2 diabetes, 5 with impaired glucose tolerance, and 8 with normal glucose tolerance (NGT)-before and after a biliopancreatic diversion (BPD) with Roux-en-Y gastric bypass (RYGBP). Twelve individuals with normal BMI served as control subjects. Twelve months after surgery, in the diabetes group, BMI decreased from 53.2 ؎ 2.0 to 29.2 ؎ 1.7 kg/m 2 , fasting glucose decreased from 9.5 ؎ 0.83 to 4.5 ؎ 0.13 mmol/l, and fasting insulin decreased from 168.4 ؎ 25.9 to 37.7 ؎ 4.4 pmol/l (mean ؎ SE; P < 0.001). AIR, the mean of insulin concentration at 2, 3, and 5 min over basal in the IVGTT, increased by 770 and 935% at 3 and 12 months after surgery, respectively (from 24.0 ؎ 22.7 to 209 ؎ 43.4 and 248 ؎ 33.1 pmol/l, respectively; P < 0,001). Conversely, in the NGT group, the AIR decreased by 40.5% (from 660 ؎ 60 to 393 ؎ 93 pmol/l; P ‫؍‬ 0.027) 12 months after surgery. BPD with RYGBP performed in morbidly obese patients with type 2 diabetes leads to significant weight loss, euglycemia, and normal insulin sensitivity; but most importantly, it restores a normal ␤-cell AIR to glucose and a normal relationship of AIR to insulin sensitivity. This is the first study to demonstrate that the lost glucose-induced AIR in patients with type 2 diabetes of mild or moderate severity is a reversible abnormality.

Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function

“…Glucose tolerance and insulin sensitivity were significantly heightened post-surgery, even in patients who were NGT at baseline. Previous studies [4][5][6][7] have shown that bariatric surgery is extremely effective in improving glucose tolerance, insulin sensitivity and, to some extent, insulin secretion (as inferred from homeostasis model assessment estimates or the acute insulin response to i.v. glucose).…”

“…In morbidly obese patients undergoing bariatric surgery, one factor contributing to the restoration of normal glucose tolerance is the surgery-induced increase in insulin sensitivity [4][5][6][7]. Although some data are available [5,[7][8][9], the role of beta cell function, its relationship with insulin sensitivity, and the contribution of either factor to the improvement in glucose tolerance are not clearly established.…”

“…Although some data are available [5,[7][8][9], the role of beta cell function, its relationship with insulin sensitivity, and the contribution of either factor to the improvement in glucose tolerance are not clearly established. Furthermore, while there is evidence that the improvement in circulating glucose levels occurs in days [10], it is not clear how early after surgery the improvement in insulin sensitivity occurs.…”

Bariatric surgery for pediatric extreme obesity: now or later?

“…26,36 Improvements in insulin resistance and b-cell function have been documented following surgical weight loss. 36,[106][107][108][109] Interestingly, although significant improvements in carbohydrate metabolism occur after surgical weight loss in adults, studies also demonstrate that in response to a glucose challenge there is only incomplete normalization of parameters of insulin secretion and insulin resistance. [106][107][108][109][110][111] Adolescents undergoing bariatric surgery also demonstrate significant fasting hyperinsulinemia and insulin resistance as estimated by homeostasis model assessment (HOMA-IR) was abnormal in 64% of patients preoperatively.…”

Model of Diabetes Mellitus Type 2, T2DM

“…Food intake restriction is achieved by reducing the size of stomach (gastric band, sleeve gastrectomy) and/ or by resecting the small intestines (biliopancreatic diversion, gastric bypass). Bariatric surgery can achieve full remission of the T2DM syndrome [31,32] (Figure 17). …”