Liver enzyme and adipocytokine profiles are synergistically associated with insulin resistance: the J-SHIPP study.

AIM: Alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) are associated with insulin resistance and arteriosclerotic disease. Since adiposity raises liver enzyme levels and causes insulin resistance, adipocytokines are thought to underlie the relationship between liver enzymes and insulin resistance. To clarify this hypothesis, we conducted a cross-sectional epidemiological study in a Japanese general population. METHODS: The study subjects were 903 middle-aged to elderly persons. Plasma levels of adiponectin and leptin were measured, while other clinical parameters were obtained from personal health records of medical check-ups. Insulin resistance was assessed by a homeostasis model assessment index (HOMA-IR). RESULTS: Plasma levels of ALT (r=0.379, p<0.001), GGT (r=0.225, p<0.001), adiponectin (r= -0.346, p<0.001) and leptin (r=0.369, p<0.001) were significantly correlated with insulin resistance even on subgroup analysis by sex. Further, any combination of liver enzymes and adipocytokines was synergistically associated with insulin resistance (p<0.001) after adjustment for possible covariates (ALT*adiponectin: β=-0.098, p<0.001, ALT*leptin: β=0.129, p<0.001, GGT*adiponectin: β=-0.054, p=0.054, GGT*leptin: β=0.126, p<0.001); however, in simple obese subjects with normal adipocytokine levels, liver enzymes were not associated with insulin resistance (mean HOMA-IR: worsened adipocytokine +/visceral obesity +, 2.01±1.14; +/-, 1.39±0.84; -/+, 1.23± 0.55; -/-, 1.03±0.57; p<0.001). CONCLUSION: Plasma levels of ALT and GGT were independent determinants of insulin resistance only in subjects with a worsened adipocytokine profile. Use of liver enzyme levels as a marker of insulin resistance requires stratification by adipocytokine profile.