Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes

Abstract

Background: Some studies have suggested that in people with type 2 diabetes, Roux-en-Y gastric bypass has therapeutic effects on metabolic function that are independent of weight loss.

Methods: We evaluated metabolic regulators of glucose homeostasis before and after matched (approximately 18%) weight loss induced by gastric bypass (surgery group) or diet alone (diet group) in 22 patients with obesity and diabetes. The primary outcome was the change in hepatic insulin sensitivity, assessed by infusion of insulin at low rates (stages 1 and 2 of a 3-stage hyperinsulinemic euglycemic pancreatic clamp). Secondary outcomes were changes in muscle insulin sensitivity, beta-cell function, and 24-hour plasma glucose and insulin profiles.

Results: Weight loss was associated with increases in mean suppression of glucose production from baseline, by 7.04 μmol per kilogram of fat-free mass per minute (95% confidence interval [CI], 4.74 to 9.33) in the diet group and by 7.02 μmol per kilogram of fat-free mass per minute (95% CI, 3.21 to 10.84) in the surgery group during clamp stage 1, and by 5.39 (95% CI, 2.44 to 8.34) and 5.37 (95% CI, 2.41 to 8.33) μmol per kilogram of fat-free mass per minute in the two groups, respectively, during clamp stage 2; there were no significant differences between the groups. Weight loss was associated with increased insulin-stimulated glucose disposal, from 30.5±15.9 to 61.6±13.0 μmol per kilogram of fat-free mass per minute in the diet group and from 29.4±12.6 to 54.5±10.4 μmol per kilogram of fat-free mass per minute in the surgery group; there was no significant difference between the groups. Weight loss increased beta-cell function (insulin secretion relative to insulin sensitivity) by 1.83 units (95% CI, 1.22 to 2.44) in the diet group and by 1.11 units (95% CI, 0.08 to 2.15) in the surgery group, with no significant difference between the groups, and it decreased the areas under the curve for 24-hour plasma glucose and insulin levels in both groups, with no significant difference between the groups. No major complications occurred in either group.

Conclusions: In this study involving patients with obesity and type 2 diabetes, the metabolic benefits of gastric bypass surgery and diet were similar and were apparently related to weight loss itself, with no evident clinically important effects independent of weight loss. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT02207777.).

Figure 1.. Effects of Weight Loss Induced by Diet and Gastric Bypass on Postprandial Glucose Kinetics.

Shown are mean levels of plasma glucose (Panel A), total glucose rate of appearance in the systemic circulation (Panel B), ingested glucose rate of appearance (Panel C), and endogenous glucose production rate (Panel D) after ingestion of an identical mixed meal (consumed from time 0 to 30 minutes) before (white circles) and after (black circles) weight loss induced by low-calorie diet therapy (Diet, 11 participants) or gastric bypass (Surgery, 9 participants). Decreases in postprandial areas under the curve after weight loss for plasma glucose concentration, total glucose rate of appearance, and endogenous glucose production rate were not significantly different between the two groups. To convert the values for glucose to millimoles per liter, multiply by 0.05551. I bars indicate standard errors. FFM denotes fat-free mass.

Figure 2.. Effects of Weight Loss Induced by Diet and Gastric Bypass on 24-hour Plasma Glucose, Free Fatty Acid, C-Peptide, and Insulin Concentrations.

Shown are mean levels of concentrations of plasma glucose (Panel A), free fatty acid (Panel B), C-peptide (Panel C), and insulin (Panel D) from serial samples obtained for 24 hours before (white circles) and after (black circles) weight loss induced by low-calorie diet therapy (Diet, 11 participants) or gastric bypass (Surgery, 8 participants). Gray bars represent the time of mixed-meal consumption. Average 24-hour plasma glucose, free fatty acid, and insulin concentrations were lower after treatment than before treatment in both the diet and surgery groups, with no significant difference between the groups. To convert the values for free fatty acids to grams per liter, multiply by 0.01; to convert the values for C-peptide to nanograms per milliliter, multiply by 0.331. I bars indicate standard errors.