Acute effects of gastric bypass versus gastric restrictive surgery on beta-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes

Abstract

Context: Hyperglycemia resolves quickly after bariatric surgery, but the underlying mechanism and the most effective type of surgery remains unclear.

Objective: To examine glucose metabolism and beta-cell function in patients with type 2 diabetes mellitus (T2DM) after two types of bariatric intervention; Roux-en-Y gastric bypass (RYGB) and gastric restrictive (GR) surgery.

Design: Prospective, nonrandomized, repeated-measures, 4-week, longitudinal clinical trial.

Patients: In all, 16 T2DM patients (9 males and 7 females, 52+/-14 years, 47+/-9 kg m(-2), HbA1c 7.2+/-1.1%) undergoing either RYGB (N=9) or GR (N=7) surgery.

Outcome measures: Glucose, insulin secretion, insulin sensitivity at baseline, and 1 and 4 weeks post-surgery, using hyperglycemic clamps and C-peptide modeling kinetics; glucose, insulin secretion and gut-peptide responses to mixed meal tolerance test (MMTT) at baseline and 4 weeks post-surgery.

Results: At 1 week post-surgery, both groups experienced a similar weight loss and reduction in fasting glucose (P<0.01). However, insulin sensitivity increased only after RYGB, (P<0.05). At 4 weeks post-surgery, weight loss remained similar for both groups, but fasting glucose was normalized only after RYGB (95+/-3 mg 100 ml(-1)). Insulin sensitivity improved after RYGB (P<0.01) and did not change with GR, whereas the disposition index remained unchanged after RYGB and increased 30% after GR (P=0.10). The MMTT elicited a robust increase in insulin secretion, glucagon-like peptide-1 (GLP-1) levels and beta-cell sensitivity to glucose only after RYGB (P<0.05).

Conclusion: RYGB provides a more rapid improvement in glucose regulation compared with GR. This improvement is accompanied by enhanced insulin sensitivity and beta-cell responsiveness to glucose, in part because of an incretin effect.

Figure 1

Glucose (a, b), insulin (c, d) and C-peptide (e, f) responses during the hyperglycemic clamp (Δ 125 mg 100 ml⁻¹ glucose) performed before surgery (-●-), 1 week (-○-) and 4 weeks () after surgery. Insulin sensitivity was estimated from the M/I ratio by dividing the average glucose infusion (M value in mg kg⁻¹ min⁻¹) during the last 40 min of the clamp by the average plasma insulin concentration during that same interval (M/I) (g, h). Subgroup analysis of subjects with matched insulin sensitivity values are shown in panels for g, h. Values represent mean±s.e.m. *Significantly lower than the pre-surgery response, P<0.05. ^†Significantly greater than the pre-surgery response P<0.05.

Figure 2

Data are shown for the disposition index determined at pre-surgery and 4 weeks after Roux-en-Y gastric bypass (RYGB) (□) and gastric restrictive surgery (GR) (●) groups respectively. The disposition index is determined as the acute insulin response (AIR) during 0–10 min relative to insulin sensitivity (M/I) multiplied by 100 during the hyperglycemic clamp. The AIR was evaluated as the area under the curve of insulin secretion rate from 0 to 10 min. Values represent mean±s.e.m.

Figure 3

Glucose (a, b), insulin (c, d), c-peptide (e, f), glucagon-like peptide-1 (GLP-1) (g, h), and gastric-inhibitory peptide (GIP) (i, j) responses during the mixed meal tolerance test (MMTT) carried out before surgery and 4 weeks after surgery. Mixed meal consisted of Ensure 4oz with 30 min interval blood sampling for glucose, insulin and C-peptide values. GLP and GIP levels were obtained at fasting, 30 and 60 min during MMTT. Values represent means±s.e.m. *Significantly reduced compared with the corresponding pre-surgery response, P<0.05. ^†Significantly increased compared with the corresponding pre-surgery response, P<0.05.

Figure 4

Beta (β)-cell function in response to the prevailing plasma glucose observed during the mixed meal tolerance test (MMTT) at fasting, 30, 60, 90 and 120 min timepoints. Data represent the average insulin-secretion rate for each timepoint during the MMTT carried out at pre-surgery (●) and 4 weeks after gastric restrictive surgery (GR) and Roux-en-Y gastric bypass (RYGB) (). The values of the slopes are indicated in Table 1. Comparison between slopes for RYGB (pre-surgery versus 4 weeks) was statistically different P<0.05. Comparison between pre-surgery slopes for RYGB versus GR was also statistically different P<0.05.