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. 2010 Jul;59(7):1771-9.
doi: 10.2337/db09-1626. Epub 2010 Apr 14.

Lipoprotein subfraction cholesterol distribution is proatherogenic in women with type 1 diabetes and insulin resistance

Affiliations

Lipoprotein subfraction cholesterol distribution is proatherogenic in women with type 1 diabetes and insulin resistance

David M Maahs et al. Diabetes. 2010 Jul.

Abstract

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.

Research design and 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.

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Figures

FIG. 1.
FIG. 1.
FPLC lipoprotein cholesterol distribution in a 49-year-old nondiabetic woman with a fasting lipid panel total cholesterol of 152 μmol/l, LDL cholesterol of 84 μmol/l, HDL cholesterol of 53, and triglycerides of 74 μmol/l and not on statin therapy.
FIG. 2.
FIG. 2.
A: Means of FPLC lipoprotein cholesterol distribution in subjects with type 1 diabetes (hatched line) and nondiabetic control subjects (solid line). B: Differences in FPLC lipoprotein distribution by type 1 diabetes status (type 1 − nondiabetic, so that a mean above the zero indicates more cholesterol in type 1 diabetic subjects and a mean below the zero line indicates less). Arrows indicate fractions in which statistically significant differences exist.
FIG. 3.
FIG. 3.
A: Differences in FPLC lipoprotein distribution by sex in type 1 diabetic subjects (male type 1 diabetic − female type 1 diabetic). B: Differences in FPLC lipoprotein distribution by sex in nondiabetic subjects (male nondiabetic − female nondiabetic).
FIG. 4.
FIG. 4.
A: Differences in FPLC lipoprotein distribution by type 1 diabetes in male subjects (male type 1 diabetic − male nondiabetic). B: Differences in FPLC lipoprotein distribution by type 1 diabetes in female subjects (female type 1 diabetic − female nondiabetic).
FIG. 5.
FIG. 5.
A: Differences in FPLC lipoprotein distribution by insulin resistance (highest vs. lowest tertiles) in male type 1 diabetic subjects. B: Differences in FPLC lipoprotein distribution by insulin resistance (highest vs. lowest tertiles) in male nondiabetic subjects. C: Differences in FPLC lipoprotein distribution by insulin resistance (highest vs. lowest tertiles) in female type 1 diabetic subjects. D: Differences in FPLC lipoprotein distribution by insulin resistance (highest vs. lowest tertiles) in female nondiabetic subjects.
FIG. 6.
FIG. 6.
A: Differences in FPLC lipoprotein distribution by visceral fat (highest vs. lowest tertiles) in male type 1 diabetic subjects. B: Differences in FPLC lipoprotein distribution by visceral fat (highest vs. lowest tertiles) in male nondiabetic subjects. C: Differences in FPLC lipoprotein distribution by visceral fat (highest vs. lowest tertiles) in female type 1 diabetic subjects. D: Differences in FPLC lipoprotein distribution by visceral fat (highest vs. lowest tertiles) in female nondiabetic subjects.

References

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