Associations between biomarkers of nonalcoholic fatty liver disease (NAFLD) alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), with 3 separate measures of glucose homeostasis: fasting glucose, fasting insulin and glycated hemoglobin (HbA1c) were studied and compared between women with and without diabetes in order to gain insight into the documented associations between NAFLD, insulin resistance and diabetes. Data from the British Women's Health and Heart Study, a random sample of British women aged 60-79 years (N = 3394; 3086 without diabetes and 308 with diabetes) was used. Associations of ALT and GGT with fasting glucose and HbA1c and of ALT with fasting insulin (and homeostasis model assessment of insulin resistance [HOMA]) are stronger in women with diabetes compared to women without diabetes (P for interaction < 0.001). GGT is associated with fasting insulin (and HOMA) to the same extent in all women, irrespective of diabetes status. Results excluding hyperinsulinemic women, i.e., in the highest fourth of the fasting insulin distribution, were similar to those obtained for all non-diabetic women as were results excluding women in the highest quartile of the alcohol consumption distribution and for women with ALT and GGT levels within the normal range. Associations did not differ substantially between obese and non-obese non-diabetic women.
Conclusion: elevation of liver enzymes and hepatic insulin resistance as reflected by fasting insulin occur in the early stages of insulin resistance and highlight the central role of the liver in insulin resistance in the general population.