Association between the preoperative fasting and postprandial C-peptide AUC with resolution of type 2 diabetes 6 months following bariatric surgery.

BACKGROUND AND AIMS: Bariatric surgery results in the remission of type 2 diabetes mellitus (T2DM) in morbidly obese subjects. The aim of the study was to investigate the predictive value of both static and dynamic measures of C-peptide in relation to T2DM resolution 6 months after bariatric surgery regardless of the operation type. METHODS AND RESULTS: A non-randomized prospective study of 24 participants with T2DM undergoing bariatric surgery. Measurements of fasting and 2-hour plasma glucose, insulin, C-peptide and measures of insulin sensitivity were recorded temporally during an oral glucose tolerance test pre-operatively and 6 months post-operatively. A responder was defined with a fasting glucose <5.6 mmol/L and HbA1c <6.0% postoperatively. Within the sample there were 11 responders and 13 non-responders at 6 months. There was a significant difference in the duration of diabetes between the groups. Fasting C-peptide (P≤0.05) and 2-hour C-peptide (P≤0.05) were higher in responders compared to non-responders. Significantly higher C-peptide levels were observed preoperatively at all time points for responders, with significantly higher area under the curve (AUC0-60 and AUC0-120). Using the lower quartiles for C-peptide levels, both fasting C-peptide (>2.5 ng/mL [0.83 nmol/L]) and 2-hour C-peptide (>5.2 ng/mL [1.73 nmol/L]) had a sensitivity and negative predictive value of 100% to predict T2DM remission. Logistic regression showed that C-peptide, duration of diabetes and BMI were associated with response. The area under the ROC curve was 0.94 and a regression model predicted diabetes remission with a sensitivity of 85.7% and a specificity of 88.9%. CONCLUSIONS: This study demonstrated that static (fasting) and dynamic (AUC, 2-hour) C-peptide measurements predict T2DM resolution 6 months following bariatric surgery. This work provides insight into C-peptide dynamics as a predictor of response to bariatric surgery.

Changes in plasma levels of N-arachidonoyl ethanolamine and N-palmitoylethanolamine following bariatric surgery in morbidly obese females with impaired glucose homeostasis.

AIM: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. METHODS: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). RESULTS: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = -0.59, P = 0.04). CONCLUSION: Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis.

Impending hyperglycemia in normoglycemic renal transplant recipients--an experimental predictive surrogate.

BACKGROUND: beta-Cell dysfunction and insulin resistance combine to cause new-onset diabetes after transplantation. The product of these two parameters, quantitatively measured as disposition index (DI), is a mathematical constant in normoglycemia and declines in advance of impending hyperglycemia. The aim of this study was to derive a simple surrogate for the DI to expose predysglycemic abnormalities posttransplantation. METHODS: First-phase insulin secretion and sensitivity were determined by mathematical minimal model analysis of 58 frequently sampled, intravenous glucose tolerance tests in 58 non-diabetic renal transplant recipients and correlated against surrogate indexes based on fasting blood samples. Products of insulin secretion/resistance indexes were correlated against calculated DI, regression analysis performed for hyperbolic compatibility, autocorrelation studies conducted, and surrogates tested in various subgroups of renal transplant recipients to ensure robustness in a heterogeneous group. RESULTS: The best correlation was achieved with "HOMA(sec) (first-phase insulin secretion)xMcAuley's index (insulin resistance)" (r=0.594, P<0.001). Regression analysis was consistent with a mathematical hyperbola (ln HOMA(sec) vs. ln McAuley's index, r=-0.639 [95% confidence interval, -1.772 to -0.950]), statistical autocorrelation was excluded (in a subset of 20 patients with repeat metabolic investigations), and the surrogate remained valid in different subgroups of transplant recipients. CONCLUSIONS: Our surrogate "HOMA(sec)xMcAuley's index," requiring only fasting glucose, insulin, and triglycerides, is a simple and noninvasive surrogate for the DI. Its predictive utility for identifying impending hyperglycemia posttransplantation should be investigated further to ascertain whether its experimental nature can translate to clinical validity.

Insulin hyposecretion in nondiabetic, tacrolimus-treated renal transplant recipients more than 6 months posttransplantation.

BACKGROUND: New-onset diabetes after transplantation is an important complication of renal transplantation. Few studies have examined nondiabetic renal transplant recipients for occult defects in insulin sensitivity or secretion. The aims of this study were to identify abnormalities of glucose metabolism in nondiabetic, tacrolimus-treated renal transplant recipients more than 6 months posttransplantation and characterize determinants. METHODS: Eighteen nondiabetic renal transplant recipients and 20 healthy control subjects were examined with a frequently sampled intravenous glucose tolerance test and meal tolerance test to derive first-phase insulin secretion (FPIR), insulin sensitivity, and second-phase insulin secretion. RESULTS: FPIR was higher in controls compared with transplant recipients (2225 vs. 1173 pmol/L; P=0.003). In transplant subjects, there was a strong positive linear correlation between glomerular filtration rate (GFR) and FPIR (Pearson correlation r=0.7; P=0.002). There were strong negative correlations between trough tacrolimus concentration at study entry (r=-0.56; P=0.01) and 3-month tacrolimus exposure (r=-0.49; P=0.02) with GFR, but not with FPIR. CONCLUSIONS: Nondiabetic renal transplant recipients had lower FPIR than controls with normal renal function. Declining FPIR predicts type 2 diabetes in the general population. Interpreting the relationship between FPIR and GFR requires exploration of dual tacrolimus toxicity on both renal and pancreatic beta-islet cell function.