Higher levels of alanine aminotransferase within the reference range predict unhealthy metabolic phenotypes of obesity in normoglycemic first-degree relatives of patients with type 2 diabetes mellitus

Obesity is a heterogeneous disorder with metabolically healthy and unhealthy phenotypes and varying degrees of cardiometabolic complications. To evaluate whether alanine aminotransferase (ALT) could be used for identification of obese phenotypes, the authors measured ALT, adiponectin, leptin, leptin receptor, free leptin index, high-sensitivity C-reactive protein, fasting insulin, glucose, and full lipid profile in 486 (176 men and 310 women) normoglycemic first-degree relatives of patients with type 2 diabetes mellitus with negative medication history and hepatitis screen. Patients were classified into obesity phenotypes on the basis of the degree of adiposity and the International Diabetes Federation criteria for the metabolic syndrome. One hundred and thirty-seven (28%) patients were positive for the metabolic syndrome, 32 (7%) had normal weight but metabolically unhealthy phenotype, and 201 (41%) were obese but metabolically healthy. ALT showed significant positive correlations with body mass index, waist circumference, beta-cell function, insulin, homeostasis model assessment for insulin resistance, high-sensitivity C-reactive protein, total cholesterol, and triglycerides and increased with increasing number of metabolic syndrome components. Binary logistic regression analyses showed that higher ALT levels within the normal range were significantly associated with the metabolic syndrome. ALT could be used for identification of the metabolically obese phenotype. Lowering the ALT upper normal reference limit will facilitate earlier detection of risky phenotypes of obesity.