Abstract
BackgroundNon alcoholic fatty liver disease (NAFLD) is an independent cardiovascular (CV) risk factor which is closely associated with insulin resistance measured by both direct or indirect methods. Gender specific findings in the relationship between alanine aminotransferase (ALT) and CV disease, the prevalence of NAFLD and type 2 diabetes (T2DM) have been published recently.The aim of the present study was to explore the gender aspects of the association between insulin sensitivity, liver markers and other metabolic biomarkers in order to elucidate the background behind the sex influenced difference in both NAFLD, T2DM and their association with CV risk.Patients and methods158 female (47 normal and 111 impaired glucose intolerant) and 148 male (74 normal and 74 impaired glucose tolerant) subjects were included (mean age: 46.5 ± 8.31 vs. 41.6 ± 11.3, average Hba1c < 6.1 %, i.e. prediabetic population, drug naive at the time of the study). Subjects underwent a hyperinsulinemic normoglycemic clamp to determine muscle glucose uptake (M3), besides liver function tests and other fasting metabolic and anthropometric parameters were determined.ResultsSignificant bivariate correlations were found between clamp measured M3 and all three liver enzymes (ALT, aspartate aminotransferase and gamma-glutamyl transferase) in both sexes. When data were adjusted for possible metabolic confounding factors correlations ceased in the male population but stayed significant in the female group. Feature selection analysis showed that ALT is an important attribute for M3 in the female but not in male group (mean Z: 3.85 vs. 0.107). Multiple regression analysis confirmed that BMI (p < 0.0001) and ALT (p = 0.00991) significantly and independently predicted clamp measured muscle glucose uptake in women (R2 = 0.5259), while in men serum fasting insulin (p = 0.0210) and leptin levels (p = 0.0294) but none of the liver enzymes were confirmed as significant independent predictors of M3 (R2 = 0.4989).ConclusionThere is a gender specific association between insulin sensitivity, metabolic risk factors and liver transaminase levels. This might explain the sex difference in the predictive role of ALT elevation for CV disease. Moreover, ALT may be used as a simple diagnostic tool to identify insulin resistant subjects only in the female population according to our results.
Highlights
Non alcoholic fatty liver disease (NAFLD) is an independent cardiovascular (CV) risk factor which is closely associated with insulin resistance measured by both direct or indirect methods
Multiple regression analysis confirmed that body mass index (BMI) (p < 0.0001) and Alanine aminotransferase (ALT) (p = 0.00991) significantly and independently predicted clamp measured muscle glucose uptake in women (R2 = 0.5259), while in men serum fasting insulin (p = 0.0210) and leptin levels (p = 0.0294) but none of the liver enzymes were confirmed as significant independent predictors of M3 (R2 = 0.4989)
Mean Glycated hemoglobin A1c (HbA1c) values were under 6.1 % in all groups, i.e. the population consisted of either normal glucose tolerant or mostly prediabetic (IGT/impaired fasting glucose (IFG) or fresh Type 2 diabetes (T2DM)) subjects, both slightly overweight and obese
Summary
Non alcoholic fatty liver disease (NAFLD) is an independent cardiovascular (CV) risk factor which is closely associated with insulin resistance measured by both direct or indirect methods. Studies have shown that adult men have a higher risk of type 2 diabetes (T2DM) [1] and higher prevalence rates for non-alcoholic fatty acid liver disease (NAFLD) [2], while they seem to have to gain less weight to develop T2DM than do women [3]. It is proposed that women have to undergo greater metabolic deterioration than men to develop type 2 diabetes and as such many insulin resistance risk factors must change to a greater extent [1]. This can be explained by the notion that adult men are more insulin resistant than women [6], since women appear to have better ability to expand safer subcutaneous fat stores; they can remain highly insulin sensitive despite considerable weight gain [7]. This capacity is lower in men, where ectopic fat appears to accumulate more in the intra-abdominal and perivascular cells, skeletal muscle, liver and possibly pancreas
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