Type 2 diabetes mellitus and endothelial lipase.
OBJECTIVE
Endothelial lipase (EL), a new member of the triacylglycerol lipase family, modulates the metabolism of high-density lipoproteins and is upregulated by inflammatory cytokines. Since type 2 diabetes is associated with chronic subclinical inflammation, we have determined whether serum EL concentration is increased in type 2 diabetes and investigated the effect of insulin on EL.


METHODS
237 type 2 diabetic patients on oral anti-diabetic agents, 111 type 2 diabetic patients on insulin therapy and 226 non-diabetic controls were recruited. Serum EL was measured by ELISA. To investigate the effect of insulin on EL production by endothelial cells, human aortic endothelial cells were incubated with insulin and EL mRNA and protein in cell medium was measured. Serum EL was also measured in 16 diabetic subjects before and after starting insulin therapy.


RESULTS
Serum EL level was highest in patients on oral anti-diabetic agents whereas those on insulin had similar EL level as controls (oral: 26.7+/-16.1ng/ml; insulin: 23.3+/-11.6, controls: 23.9+/-12.0; ANOVA p=0.04). In both controls and patients on oral anti-diabetic agents, EL correlated with log(CRP) (r=0.20, p=0.003; r=0.23, p<0.001, respectively) but no correlation was seen in patients on insulin. In vitro experiments showed that insulin significantly reduced EL mRNA and protein in human aortic endothelial cells in a dose-dependent manner. Serum EL concentration also significantly decreased in diabetic patients after starting insulin therapy (p<0.03).


CONCLUSIONS
Serum EL concentration was increased in type 2 diabetic patients and was associated with the degree of subclinical inflammation and exogenous insulin therapy lowered serum EL concentration.
Shiu
Sammy W M
SW
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong.
Tan
Kathryn C B
KC
Huang
Ying
Y
Wong
Ying
Y
D000328:Adult; D001011:Aorta / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D008049:Lipase / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; C410382:LIPG protein, human; D008049:Lipase