Effects of bariatric surgery on glucose homeostasis and type 2 diabetes

Abstract

Obesity is an important risk factor for type 2 diabetes mellitus (T2DM). Weight loss improves the major factors involved in the pathogenesis of T2DM, namely insulin action and beta cell function, and is considered a primary therapy for obese patients who have T2DM. Unfortunately, most patients with T2DM fail to achieve successful weight loss and adequate glycemic control from medical therapy. In contrast, bariatric surgery causes marked weight loss and complete remission of T2DM in most patients. Moreover, bariatric surgical procedures that divert nutrients away from the upper gastrointestinal tract are more successful in producing weight loss and remission of T2DM than those that simply restrict stomach capacity. Although upper gastrointestinal tract bypass procedures alter the metabolic response to meal ingestion, by increasing early postprandial plasma concentrations of glucagon-like peptide 1 and insulin, it is not clear whether these effects make an important contribution to long-term control of glycemia and T2DM once substantial surgery-induced weight loss has occurred. Nonetheless, the effects of surgery on body weight and metabolic function indicate that bariatric surgery should be part of the standard therapy for T2DM. More research is needed to advance our understanding of the physiological effects of different bariatric surgical procedures and possible weight loss-independent factors that improve metabolic function and contribute to the resolution of T2DM.

Figure 1

Standard bariatric surgery procedures. (A) roux-en-Y gastric bypass, (B) laparoscopic adjustable gastric banding, (C) sleeve gastrectomy, (D) biliopancreatic diversion, (E) biliopancreatic diversion with duodenal switch. Roux-en-Y gastric bypass involves the creation of a small gastric pouch (<30 mL) that is connected to a segment of jejunum, which has been transected at 30–75 cm from the Ligament of Treitz, to form a Roux-en-Y limb. Bowel continuity is restored via an anastomosis between the “Roux” limb and the excluded biliopancreatic limb approximately 75–150 cm distal to the gastro-jejunostomy. Therefore, ingested food bypasses most of the stomach, the entire duodenum and a short segment of the jejunum. Laparoscopic adjustable gastric banding involves placing a silicone ring with an inflatable inner tube is placed around the upper stomach, just distal to the gastroesophageal junction. The inner tube is connected to a subcutaneous port, which is used to inject or withdraw saline to adjust the band diameter. Typically, six adjustments are made in the first year after band placement, as needed to enhance weight loss. Sleeve gastrectomy was originally intended as a first-stage procedure of BPD in high-risk patients, but has now become a stand-alone operation and is increasing in popularity. This procedure involves dividing the stomach along its vertical length in order to create a slender banana-shaped sleeve, and removing ~75% of the stomach. Biliopancreatic diversion involves a horizontal gastrectomy, leaving behind 200–500 mL of stomach, which is anastomosed to the small intestine, 250 cm from the ileocecal valve. The excluded biliopancreatic limb is anastomosed to the ileum, 50 cm from the ileocecal valve. The distal 50-cm common channel is where digestive secretions from the biliopancreatic limb mix with the ingested food delivered by the alimentary limb. Biliopancreatic diversion with duodenal switch involves constructing a 150–200 mL volume vertical sleeve gastrectomy with preservation of the pylorous and formation of a duodenal-ileal anastomosis. The excluded biliopancreatic limb is anastomosed to the ileum, 100 cm from the ileocecal valve, where digestive secretions and nutrients mix. These latter two procedures cause considerable malabsorption.

Figure 2

Changes in insulin sensitivity evaluated by using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score at various time points after bariatric surgery (LAGB, RYGB, BPD and LSG). Data are weighed means±SE and dashed lines represent upper and lower 95% confidence intervals. Changes in HOMA-IR versus baseline (before surgery) are significant at all time points, P <0.0001. Data adapted from Rao et al.

Figure 3

Relationship between percent weight loss and the change in insulin sensitivity, assessed as the relative increase in insulin-mediated glucose disposal (% change in glucose infusion rate [GIR] in µmol/kg fat-free mass per min) during a hyperinsulinemic-euglycemic clamp procedure (insulin infusion rate of 40–50 mU/m² body surface area per minute) in subjects who had RYGB (white triangles), LAGB/gastroplasty (grey circles) or BPD (black squares) surgeries. Each data point represents the average change insulin sensitivity at a specific average percent weight loss within a study, calculated by using group mean values from published studies that reported adequate data to make these calculations.^,,,,,– The linear regression lines for RYGB (dashed black) and BPD (continuous black) are shown.

Figure 4

(A) Relationship between body mass index and insulin sensitivity, assessed as insulin-mediated glucose infusion rate (GIR) during a hyperinsulinemic-euglycemic clamp procedure (insulin infused at a rate of 40–50 mU/m² body surface area per minute) in 220 nondiabetic lean, overweight and obese subjects (171 women and 49 men, age 46 ± 12 years, BMI 34 ± 8 kg/m² [means ± SD]) studied during the last 5 years in our laboratory. The logarithmic fit is shown with upper and lower 95% confidence limits (GIR = 282 − 66 × ln BMI; R² = 43%; P = 2.6E-28). (B) Relationship between body mass index and insulin sensitivity, assessed as insulin-mediated glucose infusion rate (GIR) during a hyperinsulinemic-euglycemic clamp procedure (insulin infusion rate of 40–50 mU/m² body surface area per minute). Data points represent group mean values and SDs before and after weight loss induced by RYGB (white triangles), LAGB/Gastroplasty (grey circles), and BPD (black squares), from studies that reported adequate data to make these calculations.^,,,,,– Each study is represented by before and after surgery data points. Data points that do not have error bars were calculated by using group mean values when data were not reported in the desirable units but enough data were reported to allow for unit conversions. The upper and lower 95% confidence limits obtained in nondiabetic, non weight-reduced subjects (shown in Figure 4A) are shown (dashed lines) to provide a reference range of insulin sensitivity values at any given body mass index value.

Figure 5

The disposition index (DI) is the product of insulin sensitivity (Si) and the insulin response to glucose (IRG). In subjects with normal fasting plasma glucose concentration and normal glucose tolerance, Si is related to IRG in a hyperbolic fashion. In obese subjects with normal glucose tolerance, an increase in the β-cell response to a glucose challenge compensates for decreased insulin sensitivity and maintains normal glucose homeostasis (a → b; no change in DI). However, an inadequate β-cell response to a decrease in insulin sensitivity results in impaired glucose homeostasis and eventually type 2 diabetes (a → c; reduction in DI).