Lipoprotein subfraction cholesterol distribution is proatherogenic in women with type 1 diabetes and insulin resistance.
OBJECTIVE
Individuals with type 1 diabetes have a less atherogenic fasting lipid profile than those without diabetes but paradoxically have increased rates of cardiovascular disease (CVD). We investigated differences in lipoprotein subfraction cholesterol distribution and insulin resistance between subjects with and without type 1 diabetes to better understand the etiology of increased CVD risk.


METHODS
Fast protein liquid chromatography was used to fractionate lipoprotein cholesterol distribution in a substudy of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study (n = 82, age 46 +/- 8 years, 52% female, 49% with type 1 diabetes for 23 +/- 8 years). Insulin resistance was assessed by a hyperinsulinemic-euglycemic clamp.


RESULTS
Among men, those with type 1 diabetes had less VLDL and more HDL cholesterol than control subjects (P < 0.05), but among women, those with diabetes had a shift in cholesterol to denser LDL, despite more statin use. Among control subjects, men had more cholesterol distributed as VLDL and LDL but less as HDL than women; however, among those with type 1 diabetes, there was no sex difference. Within sex and diabetes strata, a more atherogenic cholesterol distribution by insulin resistance was seen in men with and without diabetes, but only in women with type 1 diabetes.


CONCLUSIONS
The expected sex-based less atherogenic lipoprotein cholesterol distribution was not seen in women with type 1 diabetes. Moreover, insulin resistance was associated with a more atherogenic lipoprotein cholesterol distribution in all men and in women with type 1 diabetes. This lipoprotein cholesterol distribution may contribute to sex-based differences in CVD in type 1 diabetes.
Maahs
David M
DM
Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA. david.maahs@ucdenver.edu
Hokanson
John E
JE
Wang
Hong
H
Kinney
Gregory L
GL
Snell-Bergeon
Janet K
JK
East
Ashley
A
Bergman
Bryan C
BC
Schauer
Irene E
IE
Rewers
Marian
M
Eckel
Robert H
RH
D000328:Adult; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood*; D002853:Chromatography, Liquid; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012737:Sex Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D002784:Cholesterol
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