Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes

Abstract

Gastric bypass surgery causes resolution of type 2 diabetes (T2DM), which has led to the hypothesis that upper gastrointestinal (UGI) tract diversion, itself, improves glycemic control. The purpose of this study was to determine whether UGI tract bypass without gastric exclusion has therapeutic effects in patients with T2DM. We performed a prospective trial to assess glucose and β-cell response to an oral glucose load before and at 6, 9, and 12 months after duodenal-jejunal bypass (DJB) surgery. Thirty-five overweight or obese adults (BMI: 27.0 ± 4.0 kg/m(2)) with T2DM and 35 sex-, age-, race-, and BMI-matched subjects with normal glucose tolerance (NGT) were studied. Subjects lost weight after surgery, which was greatest at 3 months (6.9 ± 4.9%) with subsequent regain to 4.2 ± 5.3% weight loss at 12 months after surgery. Glycated hemoglobin (HbA(1c)) decreased from 9.3 ± 1.6% before to 7.7 ± 2.0% at 12 months after surgery (P < 0.001), in conjunction with a 20% decrease in the use of diabetes medications (P < 0.05); 7 (20%) subjects achieved remission of diabetes (no medications and HbA(1c) <6.5%). The area under the curve after glucose ingestion was ~20% lower for glucose but doubled for insulin and C-peptide at 12 months, compared with pre-surgery values (all P < 0.01). However, the β-cell response was still 70% lower than subjects with NGT (P < 0.001). DJB surgery improves glycemic control and increases, but does not normalize the β-cell response to glucose ingestion. These findings suggest that altering the intestinal site of delivery of ingested nutrients has moderate therapeutic effects by improving β-cell function and glycemic control.

Figures

Figure 1

Schematic representation of duodenal-jejunal bypass surgery

Figure 2

Glucose (A), insulin (B) and c-peptide (C) concentrations during a 75 g oral glucose load. Values from the three postoperative studies, obtained at 6, 9 and 12 months after surgery, are averaged together. Results are mean ± SEM. Value significantly different from correspondent pre-operative time point, * P‡P<0.05

Figure 3

Pancreatic β-cell function was assessed by the response to a 75 g oral glucose load, determined as the c-peptide secretory response [c-peptide iAUC (μg/mL × 120 min) ÷ glucose iAUC (mg/dL × 120 min)] (A), the total insulinogenic index over 120 min [IGI120: insulin iAUC (μU/mL × 120 min) ÷ glucose iAUC (mg/dL × 120 min)] (B), and the acute insulinogenic index at 30 min [IGI30: Δ insulin30–0 (μU/mL) ÷ Δ glucose30–0 (mg/dL)] (C) before and at 6, 9 and 12 months after duodenal-jejunal bypass surgery. Values at 12 months are also expressed as a percent of the value obtained in subjects with normal glucose tolerance (NGT), matched on age, sex, race and body mass index (white bar, right axis). Results are mean ± SEM. Value significantly different from basal pre-operative value, * P<0.001, ‡P<0.05