INTRODUCTION: Familial combined hyperlipidemia (FCHL), an entity with many features of the metabolic syndrome, is characterized by changes in cholesterol and triglyceride phenotype over time. This study was conducted to investigate the relation of alanineaminotransferase (ALT) levels, used as a surrogate for the amount of hepatic fat, with the switch in triglyceride phenotype and the increased susceptibility to develop hypertriglyceridemia in FCHL. METHODS: Body mass index, waist circumference, plasma triglycerides, insulin and ALT levels were measured in 145 FCHL family members and 54 spouses at baseline and after a five-year follow-up. RESULTS: A switch from normotriglyceridemia to hypertriglyceridemia 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. In five-year follow-up, an intra-individual relation was observed between waist circumference and both plasma triglycerides, insulin and ALT levels. For each waist circumference FCHLpatients, but not their normolipidemic relatives, exhibited higher triglyceride and insulin levels than spouses (p<0.001). Remarkably, both FCHL patients and the normolipidemic relatives showed higher ALT levels for each waist circumference as compared to spouses(p<0.001 for FCHL patients, p=0.035 for normolipidemic relatives). CONCLUSION: The present study shows that the longitudinal relation abdominal obesity-ALT is more specific for all FCHL family members, i.e. patients and their normolipidemic relatives, than the relation abdominal obesity-triglycerides. Additionally,the association of ALT with the switch in triglyceride phenotype suggests a central role of the liver in the pathogenesis of FCHL.
INTRODUCTION: Familial combined hyperlipidemia (FCHL), an entity with many features of the metabolic syndrome, is characterized by changes in cholesterol and triglyceride phenotype over time. This study was conducted to investigate the relation of alanineaminotransferase (ALT) levels, used as a surrogate for the amount of hepatic fat, with the switch in triglyceride phenotype and the increased susceptibility to develop hypertriglyceridemia in FCHL. METHODS: Body mass index, waist circumference, plasma triglycerides, insulin and ALT levels were measured in 145 FCHL family members and 54 spouses at baseline and after a five-year follow-up. RESULTS: A switch from normotriglyceridemia to hypertriglyceridemia 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. In five-year follow-up, an intra-individual relation was observed between waist circumference and both plasma triglycerides, insulin and ALT levels. For each waist circumference FCHLpatients, but not their normolipidemic relatives, exhibited higher triglyceride and insulin levels than spouses (p<0.001). Remarkably, both FCHL patients and the normolipidemic relatives showed higher ALT levels for each waist circumference as compared to spouses(p<0.001 for FCHL patients, p=0.035 for normolipidemic relatives). CONCLUSION: The present study shows that the longitudinal relation abdominal obesity-ALT is more specific for all FCHL family members, i.e. patients and their normolipidemic relatives, than the relation abdominal obesity-triglycerides. Additionally,the association of ALT with the switch in triglyceride phenotype suggests a central role of the liver in the pathogenesis of FCHL.
Authors: Martijn C G J Brouwers; Jacqueline de Graaf; Nynke Simons; Steven Meex; Sophie Ten Doeschate; Shadana van Heertum; Britt Heidemann; Jim Luijten; Douwe de Boer; Nicolaas Schaper; Coen D A Stehouwer; Marleen M J van Greevenbroek Journal: BMJ Open Diabetes Res Care Date: 2020-03