Gender differences in aging rates among patients with non-alcoholic fatty liver disease

Abstract

Objective — evaluate gender differences in aging rates among patients with non‑alcoholic fatty liver disease (NAFLD) and their relationship with cardiometabolic disorders. Materials and methods. Examinations involved 94 patients with NAFLD with the mean age of 49.5 [41.5;57.9] years. All patients were divided into groups depending on gender: group 1 consisted of men (n=35, 37.2%), group 2 consisted of women (n=59, 62.8%). Groups 1 and 2 were comparable in age (p >0.05) — 45.8 [39.4; 54.5] years versus 52.9 [43.0; 59.0] years, respectively. Anthropometric indicators, calculated indices and body composition were determined for all patients using the OMRON BF511 Body Composition Monitor. Biological age (BA), aging rates, total mortality risk over the next 10 years (MR) and level of global methylation of DNA (GMD) were determined as indicators of aging. Assessment of BA, rates of aging and MR was carried out according to the DNAm PhenoAge calculation method (M. E. Levine, 2018). The level of GMD was assessed in the DNA of blood mononuclear cells by the immunoenzymatic method. Results. Women had significantly higher levels of body mass index (BMI) (p=0.034), hip circumference (HC) (p=0.016), percentage of total body fat (TBF) (p=0.0001), weight‑adjusted‑waist index (WWI) (p=0.003), high‑density lipoprotein cholesterol (HDL‑C) levels (p=0.0001) and significantly lower levels of waist‑to‑hip ratio (WtHR) (p=0.030), percent skeletal muscles (SM) (p=0.0001), creatinine (p=0.0001), glomerular filtration rate (GFR) (p=0.011), uric acid (p=0.001). Women were more likely to have abdominal obesity (p=0.0001), while men were more likely to have a decrease in the percentage of SM (p=0.003). A significant difference between groups was also observed in MR (p=0.045). Significant differences between the groups of men and women younger than 50 years were observed in the percentage of TBF (p=0.0001), SM (p=0.0001), HDL‑C levels (p=0.003), creatinine (p=0.0001) and uric acid (p=0.004), the same indicators differed significantly among patients of the older age category — ≥ 50 years (p=0.0001, p=0.0001, p=0.003, p=0.0001, p=0.004, respectively). Correlation analysis revealed in men a direct relationship between calendar age (CA) and the level of alanine aminotransferase, and between CA and insulin resistance, which was also directly related to BA, aging rates, MR, GMD. The vast majority of anthropometric indices in men were associated with BA, aging rates, MR and GMD. In women, only WtHR was associated with aging speed. The percentage of SM was inversely related to GMD in women. A decrease in GFR in women against the background of an increase in CA was also accompanied by an increase in MR. Among the studied patients with NAFLD, accelerated rates of aging were less often observed in men (24%) than in women (40%), although the differences were not significant. Comparing patients with normal rates of aging depending on gender, we found that women had a significantly worse percentage of TBF (p=0.0001), SM (p=0.041), WWI value (p=0.048), GFR (p=0.011), while men had worse levels of alkaline phosphatase (ALP) (p=0.026), triglycerides (TG) (p=0.049), HDL‑C (p=0.0001), uric acid (p=0.002) and higher WtHR ratio (p=0.0001). Among patients with NAFLD with normal aging rates, an increase in WC above the normal range was more common in women compared to men (80.8% vs. 47.4%, respectively, p=0.019), and a decrease in the percentage of SM was more often among men (68.4% versus 26.9%, respectively, p=0.006). Conclusions. Among the men with NAFLD, insulin resistance is directly related to the CA, BA, rates of aging, MR and GMD. Anthropometric indicators and body composition of men with NAFLD, especially WtHR and WWI index, may be useful for assessing changes in the course of aging processes, because these indicators are related to aging markers. In order to prevent premature aging in men, disorders of lipid profile, especially increased TG levels and decreased HDL‑C levels, liver tests, mainly ALP, and uric acid levels should be detected and corrected in time. In women, for this purpose, it is necessary to pay more attention to the correction of the composition of the body, especially the percentage of SM and TBF, as well as to timely detecting and improving the filtration capacity of the kidneys.