Adverse differences in cardiometabolic risk factor levels between individuals with pre-diabetes and normal glucose metabolism are more pronounced in women than in men: the Maastricht Study

Abstract

ObjectiveTo investigate whether adverse differences in levels of cardiovascular risk factors in women than men, already established when comparing individuals with and without diabetes, are also present before type 2 diabetes onset.Research design and methodsIn a population-based cohort study of individuals aged 40-75 years (n=3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated associations with cardiometabolic and lifestyle risk factors of (1) pre-diabetes and type 2 diabetes (reference category: normal glucose metabolism) and (2) among non-diabetic individuals, of continuous levels of hemoglobin A1c (HbA1c). Age-adjusted sex differences were analyzed using linear and logistic regression models with sex interaction terms.ResultsIn pre-diabetes, adverse differences in cardiometabolic risk factors were greater in women than men for systolic blood pressure (difference, 3.02 mm Hg; 95% CI:−0.26 to 6.30), high-density lipoprotein (HDL) cholesterol (difference, −0.10 mmol/L; 95% CI: −0.18 to −0.02), total-to-HDL cholesterol ratio (difference, 0.22; 95% CI: −0.01 to 0.44), triglycerides (ratio: 1.11; 95% CI: 1.01 to 1.22), and inflammation markers Z-score (ratio: 1.18; 95% CI: 0.98 to 1.41). In type 2 diabetes, these sex differences were similar in direction, and of greater magnitude. Additionally, HbA1c among non-diabetic individuals was more strongly associated with several cardiometabolic risk factors in women than men: per one per cent point increase, systolic blood pressure (difference, 3.58 mm Hg; 95% CI: −0.03 to 7.19), diastolic blood pressure (difference, 2.10 mm Hg; 95% CI: −0.02 to 4.23), HDL cholesterol (difference, −0.09 mmol/L; 95% CI: −0.19 to 0.00), and low-density lipoprotein cholesterol (difference, 0.26 mmol/L; 95% CI: 0.05 to 0.47). With regard to lifestyle risk factors, no consistent pattern was observed.ConclusionOur results are consistent with the concept that the more adverse changes in cardiometabolic risk factors in women (than men) arise as a continuous process before the onset of type 2 diabetes.

Sex-specific differences in left ventricular mass and myocardial energetic efficiency in non-diabetic, pre-diabetic and newly diagnosed type 2 diabetic subjects

“…However, there are some plausible candidates that may explain this phenomenon. Several prior investigations have demonstrated that the differences in cardiovascular risk factors associated with deterioration of glucose tolerance are greater in women than men [ 9 – 11 , 40 , 41 ]. Accordingly, we found that prediabetic and newly diagnosed T2DM women exhibited greater relative differences in BMI, waist circumference, blood pressure, and HOMA-IR than prediabetic and men with newly diagnosed T2DM when compared with their NGT counterparts with formal tests for glucose tolerance status × sex interaction being statistically significant (Table 1 and Fig.…”

Sex differences in cardiometabolic risk factors, pharmacological treatment and risk factor control in type 2 diabetes: findings from the Dutch Diabetes Pearl cohort

“…40 This time window may offer clinicians the opportunity to identify those at increased risk for diabetes and subsequently offer the opportunity for timely intervention. 31 As cardiovascular risk factor levels seem to deteriorate more strongly in women than in men, before the onset of diabetes, 16 it is of great importance to conduct a thorough cardiovascular risk assessment in women at risk of diabetes and those with overt diabetes, while not neglecting men. 31 Moreover, increasing awareness among physicians about the stronger deterioration of risk factors in women is Epidemiology/Health services research recommended to prevent women with diabetes from being treated less aggressively than men.…”

“… 9 The reasons for these sex differences are likely multifactorial, for example physiological differences between women and men, including the impact of sex hormones, 10–12 female-specific factors such as age of menarche, menopause, and childbearing history, oral contraception, and hormone replacement therapy 13–15 and a more adverse cardiometabolic risk profile among women than men with T2D. 16 17 In addition, healthcare provision for the prevention and delay of cardiovascular complications between men and women with diabetes may differ. 13 15 17–21 …”

Sex differences in the risk of vascular disease associated with diabetes

“…In future studies, it would be useful to investigate possible sex differences in cardiovascular risk factor levels associated with glucose metabolism status and across levels of glycemic control. Previous results from our research group indicated that there are already sex differences in cardiometabolic risk factors to women's disadvantage before the development of type 2 diabetes, albeit weaker than in type 2 diabetes, with greater differences in systolic blood pressure and lipid levels among women than men with prediabetes and across levels of HbA1c [43]. To further understand the effects of sex differences in adiposity, detailed body composition and body fat distribution measurements conducted by DEXA and MRI can be used.…”