Diabetes, Abdominal Adiposity, and Atherogenic Dyslipoproteinemia in Women Compared With Men

Ken Williams; Andre Tchernof; Kelly J. Hunt; Lynne E. Wagenknecht; Steven M. Haffner; Allan D. Sniderman


Diabetes. 2008;57(12):3289-3296. 

In This Article

Abstract and Introduction


Objective: To understand why atherogenic risk differs more between diabetic and nondiabetic women than between diabetic and nondiabetic men.
Research Design and Methods and Results: Measures of cardiovascular risk, body composition, and serum hormones from the baseline examinations of the Insulin Resistance Atherosclerosis Study on 524 nondiabetic women, 258 diabetic women, 421 nondiabetic men, and 220 diabetic men were compared to detect greater adverse differences in women than in men. Systolic blood pressure; apolipoprotein B (apoB); total cholesterol; apoB-to-apoA-I ratio; non-HDL cholesterol; LDL particle count, small LDL, and intermediate-density lipoprotein by nuclear magnetic resonance; and C-reactive protein exhibited significant diabetes-sex interaction (P < 0.05). ApoB exhibited the most significant interaction (P = 0.0005). Age- and ethnicity-adjusted apoB means were lower in nondiabetic women than nondiabetic men (102.4 vs. 106.8 mg/dl, P < 0.05) but higher in diabetes (115.7 vs. 110.2 mg/dl, P < 0.01). Plotted against BMI, waist circumference was 6% higher and hip circumference 10% lower in diabetic than nondiabetic women (both P < 0.05), whereas the circumference measures did not differ conspicuously between diabetic and nondiabetic men.
Conclusions: In diabetic women, an elevated level of atherogenic particles, as manifested by apoB and LDL particle count, which may result from abdominal adiposity, represents a major treatable cardiovascular risk factor.


Although the gap narrows after menopause, generally the risk of vascular disease is greater in men than in women. In diabetes, by contrast, risk is similar in men and women.[1] The equalization of risk is due to the disproportionately greater increase in risk in women who develop diabetes compared with men who develop diabetes.[2,3,4] Identifying the reasons for this alarming increase in vascular disease in diabetic women is critical. Previous work has established that both sexes have higher plasma triglycerides and lower HDL cholesterol levels in diabetes[5] and that these differences are more pronounced between nondiabetic and diabetic women than between nondiabetic and diabetic men.[6,7,8] However, the differences, if any, in LDL cholesterol are much less pronounced and range from slight decreases to slight increases in diabetes.[5] Thus, the differences in the conventional lipid profile appear inadequate to explain the differences in clinical risk that have been recorded.[2,9]

Because the evidence that apolipoprotein B (apoB) is superior to LDL cholesterol as a marker of atherogenic risk is sufficiently clear,[10,11,12,13,14] the American Diabetes Association and the American College of Cardiology have issued a joint consensus statement[15] that apoB should be the final test of the adequacy of LDL-lowering therapy.[15,16] Nevertheless, only limited information is available on apoB in diabetic subjects compared with nondiabetic subjects. Two studies have noted that apoB was significantly higher in diabetic compared with nondiabetic women with no significant differences between diabetic and nondiabetic men.[17,18] No explanation was offered for this sex difference. Equally important, no mechanism has been suggested that might explain why diabetes in women induces more cardiovascular risk than in men.

The purpose of this study, therefore, was to characterize the lipoprotein profile in greater detail in larger groups of diabetic and nondiabetic men and women than previously examined. We also examined whether the data suggest possible mechanisms that could account for the greater differences in atherogenic risk profile between diabetic and nondiabetic women than between diabetic and nondiabetic men.


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