Obesità severa e nafld in pazienti con e senza diabete tipo 2 prima e dopo chirurgia bariatrica: studio degli indici non invasivi di steatosi e fibrosi e dei livelli plasmatici di acidi biliari come predittori di severità dell’istologia epatica

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<0.01). Increased insulin concentrations, HbA1c, HOMA-IR and OGIS, not Hep-IR, were strongly associated to hepatic steatosis (p0.03, p0.0001 and p0.01 respectively) Hepatic fibrosis stage was mild as most of the patients had fibrosis grade-1 (69% vs. 8% no fibrosis) and associated to fasting insulin, HbA1c and HOMA-IR. Total insulin response was similar in the 3 groups, while IGI was strongly associated to steatosis (r=0.48, p<0.0001), but not to fibrosis. Conclusions: in morbid obesity OGTT-indexes of IR, and not of insulin response, are markers of histological severity of liver disease