Pioglitazone even at low dosage improves NAFLD in type 2 diabetes: clinical and pathophysiological insights from a subgroup of the TOSCA.IT randomised trial. (August 2021)

• Record Type: Journal Article
• Authors: Della Pepa, Giuseppe; Russo, Marco; Vitale, Marilena; Carli, Fabrizia; Vetrani, Claudia; Masulli, Maria; Riccardi, Gabriele; Vaccaro, Olga; Gastaldelli, Amalia; Rivellese, Angela A.; Bozzetto, Lutgarda
• Is Part Of: Diabetes research and clinical practice. Volume 178(2021)
• Publication Date: 2021-08
• Subjects: Non-alcoholic fatty liver disease -- Insulin resistance -- Pioglitazone -- Sulphonylureas -- Type 2 diabetes; ADIPO-IR Adipose tissue insulin resistance -- ALT Alanine aminotransferase -- AST Aspartate aminotransferase -- GGT Gamma-glutamyl-transpeptidase -- HSI hepatic steatosis index -- ION index of non-alcoholic steatohepatitis -- LFE liver fat equation -- NAFLD non-alcoholic fatty liver disease -- NASH non-alcoholic steatohepatitis -- T2D type 2 diabetes -- VAI visceral adiposity index; Diabetes -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462
• DOI: 10.1016/j.diabres.2021.108984
• Languages: English
• ISSNs: 0168-8227

Abstract

Highlights: Pioglitazone at low dose improved NAFLD and insulin resistance indirect indices in type 2 diabetes. Effects of pioglitazone on NAFLD are independent of glucose control. Indirect indices of NAFLD are reliable tools in both clinical and experimental contexts. Low-dose pioglitazone is safe and effective for NAFLD treatment in type 2 diabetes. Abstract: Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) and type 2 diabetes (T2D) share pathophysiological mechanisms and possible therapeutic strategies. We evaluated the effects of 1-year treatment with pioglitazone or sulphonylureas on indirect indices of NAFLD in people with T2D and the role of insulin-resistance and glucotoxicity in determining these effects. Methods: Patients with T2D (n = 195) aged 50–75 years, poorly controlled with metformin 2 g/day, were randomly allocated to add-on pioglitazone (n = 98) or sulphonylureas (n = 97) within the TOSCA.IT trial. Plasma insulin, glucose, and liver enzymes were measured at baseline and after 1-year. Indirect indices of NAFLD (Liver Fat Equation [LFE], Hepatic Steatosis Index [HSI], and Index of NASH [ION]), and insulin resistance (HOMA-IR, Visceral Adiposity Index [VAI] and adipose tissue Insulin Resistance [ADIPO-IR]) were calculated. Results: Indices of NAFLD improved after pioglitazone, but not after sulphonylureas; differences between changes (1-year minus baseline) were respectively: -1.76 ± 3.84 vs. 0.28 ± 3.75 for LFE; -1.35 ± 2.78 vs. -0.27 ± 2.63 for HSI; -9.75 ± 43 vs. 3.24 ± 31 for ION; p < 0.05 for all. Indices of insulin resistance decreased after pioglitazone, but not after sulphonylureas: -0.95 ± 4.57 vs. 0.37 ± 3.34 for HOMA-IR, p = 0.032; -1.25 ± 4.11 vs. 1.36 ± 5.43 for ADIPO-IR, p = 0.001; -0.53 ± 1.88 vs. 0.03 ± 2.36 for VAI, p = 0.074. Changes in NAFLD indices were similar with different doses of pioglitazone (15, 30, or 45 mg/day), and were independent of blood glucose control. Conclusions: One-year treatment with pioglitazone even at low dosage significantly improved liver steatosis and inflammation, systemic and adipose tissue insulin resistance in patients with T2D. The beneficial effects of pioglitazone on NAFLD were independent of blood glucose control.