Sex differences in lipid profiles in relation to the progression of glucose abnormalities

Background:  In the present study, we investigated the role of changes in blood lipids in the abolition of the lower cardiovascular risk associated with the female gender in individuals with type 2 diabetes mellitus (T2DM). Methods:  An oral glucose tolerance test (OGTT) was performed in 1091 consecutive patients (478 men and 613 women) and patients were divided into groups as follows: (i) those with normal glucose tolerance (NGT; n  =   589); (ii) those with pre‐diabetes (pre‐T2DM), who were further divided into those with impaired fasting glucose (IFG; n  =   212), impaired glucose tolerance (IGT; n  =   84), and both IFG and IGT (IFG/IGT; n  =   102); and (iii) those with T2DM ( n  =   104). Total cholesterol, triglycerides, high‐density lipoprotein–cholesterol (HDL‐C), low‐density lipoprotein–cholesterol (LDL‐C), apolipoprotein (apo) A‐I, apoB, and the apoB:apoA‐I ratio were determined in each patient. Differences in lipids between the different groups were assessed using Student’s t ‐test. Results:  Significantly higher triglyceride levels and an apoB:apoA‐I ratio were found in NGT men ( P  <   0.0001), along with lower HDL‐C and apoA‐I ( P  <   0.0001). Men in the pre‐T2DM group maintained a higher apoB:apoA‐I ratio ( P  <   0.05) and lower HDL‐C ( P  <   0.0001) compared with women. In the T2DM group, only HDL‐C was lower in men compared with women ( P  <   0.05). Conclusions:  The progression of glucose intolerance from NGT to pre‐T2DM and T2DM exhibits striking sex differences regarding the lipid profile. The data demonstrate a worsening of plasma lipid composition in women who become diabetic. This could explain, at least in part, the loss of the more favorable cardiovascular risk normally associated with NGT women.