Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgery

Abstract

Background: The aim of the present study was to determine the mechanisms underlying Type 2 diabetes remission after gastric bypass (GBP) surgery by characterizing the short- and long-term changes in hormonal determinants of blood glucose.

Methods: Eleven morbidly obese women with diabetes were studied before and 1, 6, and 12 months after GBP; eight non-diabetic morbidly obese women were used as controls. The incretin effect was measured as the difference in insulin levels in response to oral glucose and to an isoglycemic intravenous challenge. Outcome measures were glucose, insulin, C-peptide, proinsulin, amylin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) levels and the incretin effect on insulin secretion.

Results: The decrease in fasting glucose (r = 0.724) and insulin (r = 0.576) was associated with weight loss up to 12 months after GBP. In contrast, the blunted incretin effect (calculated at 22%) that improved at 1 month remained unchanged with further weight loss at 6 (52%) and 12 (52%) months. The blunted incretin (GLP-1 and GIP) levels, early phase insulin secretion, and other parameters of β-cell function (amylin, proinsulin/insulin) followed the same pattern, with rapid improvement at 1 month that remained unchanged at 1 year.

Conclusions: The data suggest that weight loss and incretins may contribute independently to improved glucose levels in the first year after GBP surgery.

Keywords: gastric bypass; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; incretins.

Figure 1

Glucose, insulin, proinsulin, C-peptide, glucagon and amylin concentrations during a 3-h oral glucose tolerance test (50 g glucose) before (◆) and 1 (□), 6 (▲) and 12 months (●) after gastric bypass in obese women with Type 2 diabetes. Data are the mean ± SEM.

Figure 2

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) concentrations during a 3-h oral glucose tolerance test (50 g glucose) before (◆) and 1 (□), 6 (▲) and 12 months (●) after gastric bypass in obese women with Type 2 diabetes. Data are the mean ± SEM.

Figure 3

Correlations between weight loss and fasting glucose, fasting insulin, fasting proinsulin and fasting glucagon at 1, 6 and 12 months after gastric bypass (GBP). There was no correlation between weight loss and the early phase insulin secretion (INSAUC_0–30′), the incretin effect, peak glucagon-like peptide-1 (GLP-1) and peak glucose-dependent insulinotropic polypeptide (GIP) at 1, 6 and 12 months after GBP. HOMA-IR, homeostasis model assessment of insulin resistance.