High Alanine Aminotransferase Is Associated With Decreased Hepatic Insulin Sensitivity and Predicts the Development of Type 2 Diabetes

Abstract

and acute insulin response (AIR) (25-g intravenous glucose challenge). Sixty-three subjects developed diabetes over an average follow-up of 6.9 ؎ 4.9 years. In 224 subjects, who remained nondiabetic, follow-up measurements of M and AIR were available. At baseline, ALT, AST, and GGT were related to percent body fat (r ‫؍‬ 0.16, 0.17, and 0.11, respectively), M (r ‫؍‬ ؊0.32, ؊0.28, and ؊0.24), and HGO (r ‫؍‬ 0.27, 0.12, and 0.14; all P < 0.01). In a proportional hazard analysis with adjustment for age, sex, body fat, M, and AIR, higher ALT [relative hazard 90th vs. 10th centiles (95% CI): 1.9 (1.1-3.3), P ‫؍‬ 0.02], but not AST or GGT, predicted diabetes. Elevated ALT at baseline was associated prospectively with an increase in HGO (r ‫؍‬ 0.21, P ‫؍‬ 0.001) but not with changes in M or AIR (both P ‫؍‬ 0.1). Higher ALT concentrations were cross-sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of type 2 diabetes. Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver in the pathogenesis of type 2 diabetes.

1296 Visceral Adipose Tissue Area as an Independent Risk Factor of Elevated Liver Enzyme in Nonalcoholic Fatty Liver Disease

“…25,26 In addition, higher ALT levels were previously known to be associated with increased insulin resistance and the development of type 2 diabetes. 27,28 In accordance with previous studies, ALT elevations were significantly correlated with metabolic variables and insulin resistance in our study. Adipocytes in the visceral fat promote the increased release of free fatty acids and the subsequent production of cytokines, such as adiponectin, interleukin-6, tumor necrosis factor-a, and leptin, and these adipocytokines flow directly into the liver because abdominal fat has a circulatory communication pathway to the liver via the portal vein.…”

Intake of brown rice lees reduces waist circumference and improves metabolic parameters in type 2 diabetes

“…It has also been proposed that high ALT levels are a risk factor for type 2 diabetes, suggesting a potential role for liver dysfunction in the pathogenesis of type 2 diabetes [36]. In overt type 2 diabetes, elevated ALT levels are related to decreased insulin sensitivity and impaired conduit vessel vascular function [35].…”

A comparison of associations of alanine aminotransferase and gamma-glutamyltransferase with fasting glucose, fasting insulin, and glycated hemoglobin in women with and without diabetes

“…There is evidence that hepatic fat content as determined by magnetic resonance imaging is closely correlated with fasting insulin and is a main determinant of the sensitivity of endogenous glucose production to insulin in both nondiabetics and diabetic patients. 6,30,31 A study conducted in rats has provided evidence for a causal relationship between liver fat content and hepatic insulin resistance as well as a dose-response relationship between the two. 32 Therefore NAFLD may cause hepatic insulin resistance even in the absence of peripheral insulin resistance.…”