Insulin resistance, but not insulin response, during oral glucose tolerance test (OGTT) is associated to worse histological outcome in obese NAFLD

Abstract Background Obese subjects are at high risk of nonalcoholic fatty liver disease (NAFLD) and diabetes (T2D) due to insulin resistance (IR). Since high glucose levels are as toxic as lipids for hepatic metabolism, we hypothesize that altered response to oral glucose tolerance test (OGTT) is associated to more severe NAFLD with significant/advanced liver damage. Methods and Results We studied 90 subjects with morbid obesity (73F/17M, BMI=43.2±5,9Kg/m2) undergoing bariatric surgery and intraoperative liver biopsy, and measured HbA1c, HOMA-IR (fasting Glucose x Insulin/22.5), OGTT glucose and insulin profile, and calculated OGIS (muscle insulin sensitivity), hepatic-IR (glucose[AUC0-30] x insulin[AUC0-30]) during OGTT, insulin response as (insulin[dAUC0-120]/glucose[dAUC0-120] or Insulinogenic Index (IGI= (I30-I0)/(G30-G0)). Patients were divided in 3 groups according to liver biopsy: A (no-NAFLD, 23%), B (simple steatosis (SS), 53%) and C (NASH, 24%) with similar age, gender and BMI. Diabetes was 0% in no-NAFLD, 13% in SS, 35% in NASH. During OGTT, OGIS decreased from A to C (422 vs 360 vs 338, p Conclusions in morbid obesity OGTT-indexes of IR, and not of insulin response, are markers of histological severity of liver disease.