Sex differences in hepatic and cardiac lipid accumulation and cardiac function across a cohort with a wide range of glycemic control: A secondary, cross-sectional analysis

Abstract Background: Sex differences in diabetes, obesity, metabolic disorders and cardiovascular disease are well described, however, differences between women and men in intrahepatocellular (HCL) and intramyocardial (MYCL) lipids with increasing impairment of glucose metabolism and different BMI strata are controversial and yet not well investigated. Aim of this analysis is to identify sex differences in patients with different grades of glucometabolic impairment and different BMI strata in intrahepatocellular (HCL) and intramyocardial lipids (MYCL) and cardiac function. Methods: In this cross-sectional study, we analyzed data from 503 individuals from seventeen clinical experimental studies. Patients with metabolic-dysfunction associated steatotic liver disease (MASLD), metabolic syndrome, prediabetes, type 2 diabetes and PCOS were included in the analysis and only baseline measurements were included. HCL and MYCL were assessed at 3T/7T scanners by single voxel magnetic resonance spectroscopy and fat fractions were calculated. Cardiac function was measured at a 3T scanner using retrospective ECG-gated TrueFISP magnetic resonance imaging. Participants were classified into normoglycemia, prediabetes, or type 2 diabetes, based on previous diagnosis of diabetes or either levels of HbA1c, fasting glucose level and/or postprandial glucose level. Three-way-ANCOVAs with post hoc simple effects analyses were used for statistical assessment. Results: We observed sex differences in HCL and MYCL with more pronounced increases in women. Consistent increases of HCL with BMI and deterioration of glucose metabolism, especially in women, were detected. MYCL increased with BMI and glucose impairment in women, but not in men. Sex differences were found in cardiac function loss, with significant effects found among men with worsening glucose metabolism. Myocardial mass and volume of the ventricle were higher in men in all groups. This sex difference narrowed with increasing BMI and with progressing dysglycemia. Conclusions: Sex differences in HCL and MYCL may be associated with a higher CVD risk observed in women progressing to diabetes. Further studies are needed to elucidate possible sex differences with advancing impairment of glucose metabolism and different grades of obesity and their potential impact on cardiovascular outcomes.