Federica Coccia1, Moira Testa2, Gloria Guarisco3, Claudio Di Cristofano4, Gianfranco Silecchia5, Frida Leonetti6, Amalia Gastaldelli7, Danila Capoccia8. 1. Diabetes Unit, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy. Electronic address: f.coccia84@gmail.com. 2. Diabetes Unit, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy. Electronic address: moira2488@gmail.com. 3. Diabetes Unit, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy. Electronic address: gloriaguarisco@gmail.com. 4. Pathology Unit, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy. Electronic address: claudio.dicristofano@uniroma1.it. 5. General Surgery Unit and Bariatric Centre of Excellence, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy. Electronic address: gianfranco.silecchia@gmail.com. 6. Diabetes Unit, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy. Electronic address: frida.leonetti@uniroma1.it. 7. Cardiometabolic Risk Unit, Institute of Clinical Physiology, National Research Council, Pisa, Italy. Electronic address: amalia@ifc.cnr.it. 8. Diabetes Unit, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy. Electronic address: danilacapoccia@yahoo.it.
Abstract
BACKGROUND AND AIM: 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 ± 5,9 kg/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 (p = 0.03, p = 0.0001 and p = 0.01 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. dAUC-I/dAUC-G was similar in the 3 groups, while only AUC-I was strongly associated to steatosis (r = 0.35, p = 0.005), but not to fibrosis. CONCLUSIONS: In morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease.
BACKGROUND AND AIM: 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 ± 5,9 kg/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 (p = 0.03, p = 0.0001 and p = 0.01 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. dAUC-I/dAUC-G was similar in the 3 groups, while only AUC-I was strongly associated to steatosis (r = 0.35, p = 0.005), but not to fibrosis. CONCLUSIONS: In morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease.
Authors: Dieter Furthner; Christian-Heinz Anderwald; Peter Bergsten; Anders Forslund; Joel Kullberg; Håkan Ahlström; Hannes Manell; Iris Ciba; Harald Mangge; Katharina Maruszczak; Pia Koren; Sebastian Schütz; Susanne Maria Brunner; Anna Maria Schneider; Daniel Weghuber; Katharina Mörwald Journal: Front Endocrinol (Lausanne) Date: 2022-02-02 Impact factor: 5.555
Authors: Zaida Zakaria; Zaidatul Akmal Othman; Joseph Bagi Suleiman; Nur Asyilla Che Jalil; Wan Syaheedah Wan Ghazali; Victor Udo Nna; Mahaneem Mohamed Journal: Antioxidants (Basel) Date: 2021-12-20