Individuals with T1DM exhibited significantly lower mean liver fat content (4.5%) compared with nondiabetic controls (6.6%) and those with T2DM (9.2%) (p < 0.01).
Cross-Sectional (n=405)
Hepatic insulin exposure, rather than obesity alone, appears to be a principal determinant of liver fat accumulation across individuals with and without diabetes.
Absolute Event Rate: 4.5% vs 6.6%
p-value: p=< 0.01
Introduction and Objective: Hepatic steatosis is closely linked to obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). However, the relative contributions of obesity versus portal insulin exposure to liver fat accumulation remain unclear. We examined the relationship between liver fat content, body mass index (BMI), and portal insulin concentration in individuals with type 1 diabetes mellitus (T1DM), T2DM, and nondiabetic controls. Methods: Liver fat content was quantified by magnetic resonance imaging (MRI) in 75 individuals with T1DM, 90 individuals with T2DM, and 240 nondiabetic subjects matched for BMI. Liver fat content was analyzed in relation to BMI and estimated portal insulin concentration. Subjects within each group were stratified by BMI tertiles and by portal insulin concentration. Results: Mean liver fat content was significantly lower in individuals with T1DM compared with nondiabetic controls and highest in individuals with T2DM (4.5 ± 0.6%, 6.6 ± 0.5%, and 9.2 ± 0.7%, respectively; p 0.01). Liver fat content increased progressively across BMI tertiles in all three groups. However, for any given BMI, liver fat content remained lowest in T1DM and highest in T2DM. In contrast, when subjects were stratified according to portal insulin concentration, liver fat content increased in parallel across all groups, with individuals with T1DM, T2DM, and nondiabetes following a common regression line (r = 0.93, p 0.0001) Conclusion: Despite similar degrees of obesity, individuals with T1DM exhibit significantly lower liver fat content compared with those with T2DM and nondiabetic controls. The strong, unified relationship between portal insulin concentration and liver fat across all groups suggests that hepatic insulin exposure, rather than obesity per se, is a principal determinant of liver fat accumulation. These findings provide mechanistic insight into the link between obesity, hepatic steatosis, insulin resistance, and diabetes. Disclosure M. Abu-Farha: None. F. Alajmi: Advisory Panel; Ended; Abbott Diabetes, Novo Nordisk. Research Support; Ended; Novo Nordisk. F. Al-Mulla: None. M. Qaddoumi: None. R.A. DeFronzo: Advisory Panel; Ended; AstraZeneca. Research Support; Current; AstraZeneca. Advisory Panel; Current; Novo Nordisk. Research Support; Current; Eli Lilly and Company. Advisory Panel; Current; Corcept Therapeutics. Speaker's Bureau; Current; Corcept Therapeutics. Consultant; Current; Alnylam Pharmaceuticals, Inc. Advisory Panel; Current; Regeneron Pharmaceuticals Inc., Aardvark. J.A. Abubaker: None. M. Abdul-Ghani: None. T. Alessaa: Advisory Panel; Ended; Sanofi. Speaker's Bureau; Ended; Sanofi. Advisory Panel; Ended; Novo Nordisk. Speaker's Bureau; Ended; Novo Nordisk, Novartis Pharmaceuticals Corporation, Amgen Inc., Lilly. Funding Kuwait Foundation for the Advancement of Sciences (KFAS) (RA AM-2023-027)
ABU-FARHA et al. (Sat,) conducted a cross-sectional in Hepatic steatosis (n=405). Type 1 Diabetes vs. Type 2 Diabetes and nondiabetic controls was evaluated on Mean liver fat content (p=< 0.01). Individuals with T1DM exhibited significantly lower mean liver fat content (4.5%) compared with nondiabetic controls (6.6%) and those with T2DM (9.2%) (p < 0.01).