Studies in insulin resistance following very low calorie diet and/or gastric bypass surgery.

The explanation for the rapid improvement in insulin resistance after Roux-en Y gastric bypass (RYGB) may involve mechanisms additional to caloric restriction and improvements in peripheral glucose disposal. 8 severely obese patients underwent a 6-day very low calorie diet (VLCD) (456 kcal/day) followed 1-3 weeks later by RYGB. Insulin resistance was measured by short intravenous insulin tolerance test (IVITT) and by homeostasis model assessment (HOMA) before and again 6 days after the VLCD and after RYGB. In a group of 24 matched patients, HOMA assessments were made before and six days after RYGB. HOMA-IR fell significantly from 6.84.9 to 4.32.9 (p < 0.05) following VLCD, but this was less than the subsequent fall following RYGB (6.8 ± 4.9 to 1.50.4, p < 0.01). Control patients who underwent RYGB alone, reduced their HOMA-IR to 1.50.9 following the operation which was not significantly different from the VLCD then RYGB group. Following VLCD, IVITT showed no significant change. However, 6 days after RYGB, IVITT showed worsened insulin induced glucose uptake (p < 0.05). Patients undergoing VLCD over six days had a reduction in HOMA-IR which was half that of patients undergoing RYGB. Patients who underwent both VLCD and RYGB had a total reduction in HOMA similar to those who underwent the RYGB alone. In contrast, IVITT showed a worsening in insulin induced glucose disposal following RYGB, which suggests worsening peripheral insulin resistance. This study supports the hypothesis that mechanisms other than caloric restriction are involved in the acute improvement in HOMA-IR following RYGB.

Is intestinal gluconeogenesis a key factor in the early changes in glucose homeostasis following gastric bypass?

BACKGROUND: In 2008, Troy et al. hypothesised that under fasting conditions, intestinal gluconeogenesis generates glucose levels in the portal vein which trigger the portal sensor to change insulin resistance and that this mechanism contributes to the effects of Roux-en-Y gastric bypass (RYGB) surgery on type 2 diabetes mellitus (T2DM). In a recent paper, Kashyap et al. (Int J Obes 34(3):426-471, 2010) cited this hypothesis as a potential explanation for the early changes in insulin sensitivity and beta cell function seen after RYGB. We proposed a study to examine this possibility. METHODS: We simultaneously sampled fasting portal venous blood and central venous blood in 28 patients (eight diabetics and 20 non-diabetics) before and again six days after RYGB surgery in morbidly obese patients, for measurement of glucose levels. RESULTS: We found no significant difference in the glucose levels from the two sites either before or after RYGB in diabetic patients and a small, but significant difference in the post-operative glucose levels from non-diabetic patients (4.2 vs 4.0 mM, p < 0.0001). CONCLUSIONS: Direct simultaneous measurement of fasting glucose in portal and central venous blood before and 6 days after RYGB provides no evidence to support the hypothesis that intestinal gluconeogenesis contributes to the resolution of T2DM seen after RYGB.

A model for predicting the resolution of type 2 diabetes in severely obese subjects following Roux-en Y gastric bypass surgery.

BACKGROUND: Severely obese type 2 diabetics who undergo Roux-en Y gastric bypass surgery have significant improvements in glycaemic control. Little work has been undertaken to establish the independent predictors of such resolution or to develop a predictive model. The aim of this study was to develop a mathematical model and establish independent predictors for the resolution of diabetes. METHODS: A consecutive sample of 130 severely obese type 2 diabetics who underwent gastric bypass surgery for weight loss from November 1997 to May 2007 with prospective pre-operative documentation of biochemical and clinical measurements was followed up over 12 months. Logistic discrimination analysis was undertaken to identify those variables with independent predictive value and to develop a predictive model for resolution of type 2 diabetes. Consecutive samples of 130 patients with body mass index (BMI) ≥ 35 with type 2 diabetes were selected. One hundred and twenty-seven patients completed the study with a sufficient data set. Patients were deemed unresolved if (1) diabetic medication was still required after surgery; (2) if fasting plasma glucose (FPG) remained >7 mmol/L; or (3) HbA1c remained >7%. RESULTS: Resolution of diabetes was seen in 84%, while diabetes remained but was improved in 16% of patients. Resolution was rapid and sustained with 74% of those on medication before surgery being able to discontinue this by the time of discharge 6 days following surgery. Five pre-operative variables were found to have independent predictive value for resolution of diabetes, including BMI, HbA1c, FPG, hypertension and requirement for insulin. Two models have been proposed for prediction of diabetes resolution, each with 86% correct classification in this cohort of patients. CONCLUSIONS: Type 2 diabetes resolves in a very high percentage of patients undergoing gastric bypass surgery for severe obesity. The key predictive variables include pre-operative BMI, HbA1c, FPG, the presence of hypertension and diabetic status.