New evidence for an association between liver enzymes and pancreatic islet β-cell dysfunction in young obese patients

Abstract

To explore the relationship between serum liver enzymes and both the glucose tolerance status and insulin secretion in young obese patients. A total of 734 young obese patients (BMI ≥ 25 kg m(-2)) and 231 lean healthy volunteers matched in age (BMI < 23 kg m(-2)) were enrolled in this cross-sectional observational study. The 734 obese patients were subdivided to three groups (OB-NGR, OB-IGR, and OB-DM) according to their glucose tolerance status. FSIVGTT was performed to assess the degree of insulin sensitivity (SI) and islet secretion function (AIRg). The disposition index (DI; product of SI and AIRg) was calculated as an integrated measurement of insulin secretion and insulin action after compensating for insulin resistance. The extent and distribution of hepatic fat infiltration was assessed using the liver/spleen ratio (L/S ratio) with CT scan. ALT and GGT levels in OB-NGR, OB-IGR, and OB-DM groups were significantly increased compared to the normal controls, and were incrementally increased in turn in the three groups, whereas DI decreased at the same time. One standard deviation increment in ALT and GGT increased the risk of β-cell dysfunction after controlling for potential confounders such as sex, age, BMI, waist-hip ratio, and blood pressure. Even after the adjustment of the serum lipid profile and L/S ratio, the odds ratio of ALT remained statistically significant (OR, 1.603; 95 % CI, 1.225-2.096). Serum levels of liver enzymes showed an independent close relationship with insulin secretion capacity. Excluding the impact of a fatty liver, increased ALT and GGT levels indicated a significant association with the attenuation of pancreatic β-cell function. This study provides the possibility that elevated liver enzymes might be treated as simple biomarkers of early insulin secretion deficit in type 2 diabetes, especially in young obese patients.