The role of insulin insensitivity and hepatic lipase in the dyslipidaemia of type 2 diabetes.
Fourteen male patients with Type 2 diabetes were studied to identify relationships between insulin-mediated glucose disposal, basal and glucose-stimulated insulin secretion, fasting lipoproteins and apolipoproteins, and the activities of lipoprotein lipase and hepatic lipase. Sensitivity of glucose disposal to exogenous insulin correlated positively with HDL-cholesterol (r = 0.65, p less than 0.05), HDL2-cholesterol (r = 0.59, p less than 0.05), and apolipoprotein A1 (r = 0.57, p less than 0.05) and negatively with apolipoprotein B (r = -0.53, p less than 0.05) and total: HDL-cholesterol ratio (r = -0.68, p less than 0.01). Fasting C-peptide correlated negatively with HDL-cholesterol (r = -0.76, p less than 0.01), HDL2-cholesterol (r = -0.80, p less than 0.001) and apoprotein A1 (r = -0.56, p less than 0.05) and positively with total: HDL-cholesterol ratio (r = 0.64, p less than 0.05). Neither fasting plasma glucose nor the indices of stimulated insulin secretion (glucose-stimulated plasma insulin and C-peptide) were related to any of the lipoprotein measures. Insulin insensitivity and hyperinsulinaemia were both associated with higher levels of hepatic lipase activity but did not influence lipoprotein lipase activity. In multiple linear regression analysis, hepatic lipase activity was related to HDL-cholesterol independent of insulin insensitivity. In addition, fasting C-peptide alone accounted for 70% of the variance in hepatic lipase activity and this was independent of insulin sensitivity and body mass index. We propose that the abnormalities of HDL-cholesterol in Type 2 diabetes are closely related to enhanced hepatic lipase activity brought about by increased insulin secretion which, in turn, is secondary to the defect in insulin action.
Baynes
C
C
Department of Clinical Endocrinology, St Mary's Hospital, London, UK.
Henderson
A D
AD
Anyaoku
V
V
Richmond
W
W
Hughes
C L
CL
Johnston
D G
DG
Elkeles
R S
RS
D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D008049:Lipase / Q000378:metabolism*; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis
D001053:Apolipoproteins; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D008049:Lipase