Elevation of liver enzymes and hepatic insulin resistance occur in the early stages of insulin resistance
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Data from the British Women’s Health and Heart Study, a random sample of British women aged 60-79 years, was used to examine the associations between alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) as biomarkers of non-alcoholic fatty liver disease (NAFLD) with three separate determinants of glucose homeostasis: fasting glucose, fasting insulin and glycated haemoglobin (HbA1c). As the function of insulin in the fasting state is to suppress hepatic glucose output, fasting insulin is a surrogate of hepatic insulin sensitivity. These associations were compared in women with and without diabetes to gain insight into the documented associations between NAFLD, insulin resistance and diabetes. Compared to women without diabetes, women with diabetes showed stronger associations of ALT and GGT with fasting glucose and HbA1c and of ALT with fasting insulin (P for interaction <0.001). GGT was associated with fasting insulin to the same extent in all women, irrespective of the diabetic status. When excluding women in the highest fourth of the fasting insulin distribution, results were similar to those obtained for non-diabetic women as were results when excluding women in the highest quartile of alcohol consumption distribution. According to the authors, elevation of liver enzyme and hepatic insulin resistance in women, as reflected by fasting insulin, appear to occur in the early stages of insulin resistance, which highlights the central role of the liver in the development of insulin resistance.
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