Indirect insulin resistance markers are associated with nonalcoholic fatty liver disease in type 1 diabetes

Abstract

INTRODUCTION: Insulin resistance (IR) in type 1 diabetes mellitus (T1DM) is associated with increased insulin dose requirements, poor glycemic control, and elevated risk of chronic complications. IR increases lipid synthesis and hepatic lipid content. Disruption in hepatic lipid accumulation and export leads to liver steatosis resulting in nonalcoholic liver disease (NAFLD). OBJECTIVES: The aim of the study was to explore the relationship between indirect IR markers and NAFLD in T1DM. PATIENTS AND METHODS: We analyzed 151 patients with T1DM (59 men, 92 women), with a median (interquartile range [IQR]) age of 40 (33-47) years and a median (IQR) diabetes duration of 19 (13-21)years. The median (IQR) value of glycated hemoglobin (HbA1c) was 7.5% (6.8%-8.%; 58 [51-66] mmol/mol). The following indirect IR markers were evaluated: estimated glucose distribution rate (eGDR), visceral adiposity index (VAI), and the triglyceride to high‑density lipoprotein cholesterol ratio (TG/HDL‑C). Fatty infiltration of the liver was quantified using transient elastography. Presence of NAFLD was defined as a controlled attenuation parameter value of 238 dB/m or greater. RESULTS: NAFLD was observed in 65 patients (43%). The participants with NAFLD were less insulin‑sensitive (eGDR, 8.93 [6.39-9.97] vs 9.94 [8.09-11.13] mg/kg/min; P = 0.001; VAI, 1.52 [1.2-2.64] vs 1.34 [0.92-1.74]; P = 0.014; TG/HDL‑C ratio, 1.35 [0.95-2.11] vs 1.11 [0.77-1.6]; P = 0.02) and were characterized by higher HbA1c values (7.75% [7.2%-8.4%] vs 7.3% [6.5%-8.1%]; 61 [55-68] vs 56 [48-65] mmol/mol; P = 0.02) than the patients without the disease. In a multivariable regression analysis adjusted for sex, diabetes duration, and HbA1c level, indirect IR markers were independently associated with NAFLD (eGDR: odds ratio [OR], 0.86; 95% CI, 0.77-0.97; P = 0.01; VAI: OR, 1.61; 95% CI, 1.05-2.49; P = 0.03, TG/HDL‑C ratio: OR, 1.88; 95% CI, 1.11-3.18; P = 0.02). CONCLUSIONS: In T1DM, NAFLD is more likely to be found in individuals with lower insulin sensitivity.