Metabolic heterogeneity associated with high plasma triglyceride or low HDL cholesterol levels in men

Abstract

To further understand the factors involved in the regulation of high plasma triglyceride (TG) or low plasma high density lipoprotein cholesterol (HDL-C) levels, three groups of male subjects (normal TG with low HDL-C levels, high TG with normal HDL-C levels, and high TG with low HDL-C levels) were compared with a sample of normolipemic men with normal TG and HDL-C plasma levels. Mean age was 34 years (range, 20-42 years), and none of the subjects had plasma TG levels >4.0 nimol/l or familial hypercholesterolemia. Both groups of subjects with high TG levels had a higher body mass index, waist circumference, waist-to-hip circumferences ratio, and a higher ratio of abdominal to femoral adipose tissue areas as measured by computed tomography when compared with normolipemic control subjects. However, during an oral glucose tolerance test only high TG-low HDL-C men had fasting hyperinsulinemia and higher plasma insulin levels compared with normolipemic subjects. In addition, the high TG-low HDL-C group showed reduced HDL apoprotein (apo) A-I levels and a low HDL2-C/HDL3-C ratio. These changes were observed along with a nonsignificant trend for a lower plasma postheparin lipoprotein lipase activity. However, among subjects with high TG and normal HDL-C levels, no evidence of insulin resistance or of a reduction in postheparin lipoprotein lipase activity was observed, suggesting that the high plasma TG levels could be attributed to an increased production of apo B-containing lipoproteins, as high plasma apo B and low density lipoprotein (LDL)-apo B levels were observed in this group. In addition, HDL-apo A-I levels measured in the high TG-normal HDL-C group were similar to normolipemic control subjects. Finally, in men with normal plasma TG and low HDL-C levels, no evidence of insulin resistance was noted, nor was there any sign of reduction in plasma postheparin lipoprotein lipase activity. However, HDL2-C, HDL3-C, and HDL-apo A-I levels were reduced, suggesting altered synthesis or catabolism of apo A-I. A nonsignificant trend for increased hepatic TG lipase activity was also observed in both groups with low HDL-C levels. These results provide further support for the presence of metabolic heterogeneity underlying high plasma TG or low HDL-C concentrations in men.