Beta cell function after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention

Abstract

Objective: The effects of various weight loss strategies on pancreatic beta cell function remain unclear. We aimed to compare the effect of intensive lifestyle intervention (ILI) and Roux-en-Y gastric bypass surgery (RYGB) on beta cell function.

Design: One year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104).

Methods: One hundred and nineteen morbidly obese participants without known diabetes from the MOBIL study (mean (s.d.) age 43.6 (10.8) years, body mass index (BMI) 45.5 (5.6) kg/m², 84 women) were allocated to RYGB (n = 64) or ILI (n = 55). The patients underwent repeated oral glucose tolerance tests (OGTTs) and were categorised as having either normal (NGT) or abnormal glucose tolerance (AGT). Twenty-nine normal-weight subjects with NGT (age 42.6 (8.7) years, BMI 22.6 (1.5) kg/m², 19 women) served as controls. OGTT-based indices of beta cell function were calculated.

Results: One year weight reduction was 30% (8) after RYGB and 9% (10) after ILI (P < 0.001). Disposition index (DI) increased in all treatment groups (all P<0.05), although more in the surgery groups (both P < 0.001). Stimulated proinsulin-to-insulin (PI/I) ratio decreased in both surgery groups (both P < 0.001), but to a greater extent in the surgery group with AGT at baseline (P < 0.001). Post surgery, patients with NGT at baseline had higher DI and lower stimulated PI/I ratio than controls (both P < 0.027).

Conclusions: Gastric bypass surgery improved beta cell function to a significantly greater extent than ILI. Supra-physiological insulin secretion and proinsulin processing may indicate excessive beta cell function after gastric bypass surgery.

Figure 1

Mean glucose, insulin and C-peptide during the OGTT in controls and in morbidly obese subjects at baseline and 1 year after gastric bypass surgery and intensive lifestyle intervention according to glucose tolerance status at baseline. Error bars represent 95% CIs. Independent samples t-tests were used for the comparison of means. *P<0.05, controls versus intervention groups. ^†P<0.05, surgery versus lifestyle group.

Figure 2

Mean HOMA-S plotted against first phase_est in controls and morbidly obese subjects with normal glucose tolerance (A) and abnormal glucose tolerance (B) before and 1 year after gastric bypass and lifestyle intervention. The curve represents the regression line of the natural logarithm of estimated insulin secretion as a linear function of the natural logarithm of estimated insulin sensitivity for all participants with normal glucose tolerance at baseline. The bar graph (C) represents mean value of the corresponding disposition indices. Error bars represent 95% CIs. *P value for the effect of treatment choice and glucose tolerance status at baseline on change in disposition index, two-way ANOVA. ^†P<0.05, ^††P<0.001, 1 year versus baseline, paired samples t-test. ^‡P<0.001, between group (surgery versus lifestyle), changes in disposition index within the same glucose tolerance group, ANCOVA with adjusting for gender, age and BMI at baseline and baseline value. ^§P<0.001, normal glucose tolerance versus abnormal glucose tolerance within the same intervention group at baseline, independent samples t-test.

Figure 3

Mean stimulated (A) and fasting (B) proinsulin-to-insulin ratios in controls and morbidly obese subjects with normal and abnormal glucose tolerance before and 1 year after gastric bypass and lifestyle intervention. Error bars represent 95% CIs. *P value for the effect of treatment choice and glucose tolerance status at baseline on change in disposition index, two-way ANOVA. ^††P<0.001, 1 year versus baseline, paired samples t-test. ^‡P<0.001, between groups (surgery versus lifestyle), changes in disposition index within the same glucose tolerance group, ANCOVA with adjusting for gender, age and BMI at baseline and baseline value. ^§P<0.001, normal glucose tolerance versus abnormal glucose tolerance within the same intervention group at baseline, independent samples t-test.