Five-year follow-up of waist circumference, insulin and ALT levels in familial combined hyperlipidaemia

FCHL (familial combined hyperlipidaemia), an entity with many features of the metabolic syndrome, is characterized by changes in cholesterol and triacylglycerol (triglyceride) phenotype over time. The present study was conducted to investigate the relationship of ALT (alanine aminotransferase) levels, used as a surrogate marker for the amount of hepatic fat, with the switch in triacylglycerol phenotype and the increased susceptibility to develop hypertriglyceridaemia in FCHL. BMI (body mass index), waist circumference and plasma triacylglycerols, insulin and ALT levels were measured in 145 FCHL family members and 54 spouses at baseline and after a 5-year follow-up. A switch from normotriglyceridaemia to hypertriglyceridaemia or vice versa, as observed in 22 of 145 FCHL family members, was associated with changes in plasma ALT levels (P=0.001), but not with insulin levels or waist circumference. At 5 years of follow-up, an intra-individual relationship was observed between waist circumference and plasma triacylglycerols, insulin and ALT levels. For each waist circumference, FCHL patients, but not their NL (normolipidaemic) relatives, exhibited higher triacylglycerol and insulin levels than spouses (P<0.001). Remarkably, both FCHL patients and the NL relatives had higher ALT levels for each waist circumference compared with spouses (P<0.001 for FCHL patients, and P=0.035 for NL relatives). In conclusion, the present study shows that the longitudinal relationship of abdominal obesity–ALT is more specific for all FCHL family members, i.e. patients and their NL relatives, than the relationship of abdominal obesity–triacylglycerols. Additionally, the association of ALT with the switch in triacylglycerol phenotype suggests a central role of the liver in the pathogenesis of FCHL.