Intact cross-talk between insulin secretion and insulin action after postgastroplasty recovery of ideal body weight in severely obese patients.

Most reports investigating the hormonal and metabolic effects of bariatric surgery studied obese subjects after partial weight loss only. Nevertheless, all studies showed significant improvements of insulin secretion, action, clearance and inhibition of its own secretion, although the parallel kinetics of all these changes remained questionable. Using the intravenous glucose tolerance test, we demonstrated a full normalization of insulin secretion, action on glucose metabolism and clearance in eight obese women who recovered and maintained ideal body weight following gastroplasty. Reciprocal changes were observed between postglucose acute insulin secretion and insulin-mediated glucose disposal so that the so-called disposition index (product of these two variables) remained unchanged after vs before gastroplasty in those individuals with normal glucose tolerance. These favourable results should encourage obtaining a drastic and sustained weight loss in patients with severe obesity at risk of developing type II diabetes

Pharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease.

Introduction: Patients with type 2 diabetes have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents may be a cause for concern in the case of hepatic impairment (HI). Areas covered: An extensive literature search was performed to analyze the influence of HI on the pharmacokinetics (PK) of glucose-lowering agents and the potential consequences for clinical practice as far as the efficacy/safety balance of their use in diabetic patients with CLD is concerned. Expert opinion: Almost no PK studies have been published regarding metformin, sulfonylureas, thiazolidinediones and alpha-glucosidase inhibitors in patients with HI. Only mild changes in PK of glinides, dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporters type 2 inhibitors were observed in dedicated PK studies in patients with various degrees of HI, presumably without major clinical relevance although large clinical experience is lacking. Glucagon-like peptide-1 receptor agonists have a renal excretion rather than liver metabolism. Rare anecdotal case reports of hepatotoxicity have been described with various glucose-lowering agents contrasting with numerous reassuring data. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, including with the use of metformin

Insulin Sensitivity and Variability in Hepatitis C Virus Infection Using Direct Measurement

BACKGROUND & AIMS: Studies investigating insulin resistance (IR) in chronic hepatitis C virus (HCV) infection have used surrogate measures of IR that have limited reliability. We aimed to describe the distribution and risk factors associated with IR and its change over time in HCV using direct measurement. METHODS: One hundred and two non-cirrhotic, non-diabetic, HCV-infected subjects underwent clinical, histologic, and metabolic evaluation, and 27 completed repeat evaluation at 6 months. Insulin-mediated glucose uptake was measured by steady-state plasma glucose (SSPG) concentration during the insulin suppression test. RESULTS: Three subjects with diabetes were excluded and 95 completed all testing. SSPG ranged from 39 to 328 mg/dL (mean 135 mg/dL) and was stable over time (mean SSPG change -0.3 mg/dL). SSPG was associated with Latino ethnicity (Coef 67, 95%CI 37-96), BMI (Coef 19 per 5 kg/m(2), 95%CI 5-32), ferritin (Coef 1.4 per 10 ng/ml, 95%CI 0.2-2.5), male gender (Coef -48, 95%CI -80 to -16), and HDL (Coef -16, 95%CI -28 to -5 mg/dL). Current tobacco use (Coef 55, 95%CI 19-90), steatosis (Coef -44, 95%CI -86 to -3), and increases in BMI (Coef 30 per 5 kg/m(2), 95%CI 6-53) and triglyceride (Coef 3.5 per 10 mg/dL, 95%CI 0.3-6.7) predicted change in SSPG. CONCLUSIONS: There was a wide spectrum of insulin resistance in our HCV population. Host factors, rather than viral factors, appeared to more greatly influence insulin action and its change in HCV