Sex Differences in Cardiovascular Risk Profile From Childhood to Midlife Between Individuals Who Did and Did Not Develop Diabetes at Follow-up: The Bogalusa Heart Study

Abstract

Childhood and young adulthood may represent time periods in which cardiovascular risk factors (CVRFs) and their cumulative exposure lay the foundation for future risk of chronic diseases. We examined the longitudinal burden of CVRFs since childhood in men and women in whom diabetes did and did not develop at follow-up. RESEARCH DESIGN AND METHODS We included 1,530 participants (mean [SD] follow-up time 33.1 [8.2] years), who participated in the Bogalusa Heart Study and had been examined at least four times starting in childhood (mean age [SD] at first examination 9.4 [3.1] years). The area under the growth curve was used as a measure of cumulative exposure to CVRFs since childhood. RESULTS In childhood, boys and girls in whom diabetes did and did not develop at follow-up had similar CVRFs. Yet, over time, women during the transition from normoglycemia to diabetes experienced greater adverse changes in total cholesterol (TC), LDL cholesterol, and fasting plasma glucose (FPG) (noted as early as 23.5 years old and persisting across adulthood up to the age of the diagnosis of diabetes); a higher burden of exposure to BMI, TC, LDL cholesterol, and FPG from childhood to midlife; and a greater change in rates of BMI, TC, LDL cholesterol, and FPG since childhood than men during the same transition (interaction P values <0.05). CONCLUSIONS The greater exposure of women to and burden of CVRFs associated with diagnosis of diabetes may help to explain the stronger impact of diabetes as a major risk factor for cardiovascular events in women compared with men. The burden of cardiovascular disease (CVD) related to diabetes is a major public health challenge (1). There is a well-recognized CVD risk disparity by sex among individuals with diabetes (2-5). Women with diabetes are at markedly increased risk of CVD events compared with women without diabetes, whereas men with diabetes

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

“…Type 2 diabetes has been shown to be associated with adverse differences in cardiovascular risk factor levels, which in line with our findings, are more pronounced in women than in men 4–7 26. Correspondingly, BMI and waist circumference differ more between women with and without diabetes than between men with and without diabetes 7 26.…”

“…To our knowledge, sex differences associated with oral glucose tolerance test (OGTT) based pre-diabetes and continuous HbA1c among individuals without type 2 diabetes have not been reported previously. However, longitudinal studies did focus on sex differences related to the conversion to diabetes or dysglycemia 24–26. These studies found that women who eventually developed diabetes experienced a greater deterioration in fasting plasma glucose, lipid levels, and BMI during their non-diabetic state.…”

“…These studies found that women who eventually developed diabetes experienced a greater deterioration in fasting plasma glucose, lipid levels, and BMI during their non-diabetic state. Furthermore, women had a relatively greater endothelial dysfunction, more hypertension and a greater degree of dysregulated fibrinolysis and coagulation than their male counterparts 24–26…”

Sex differences in the burden of type 2 diabetes and cardiovascular risk across the life course

“…As such, women may experience a prolonged state of insulin resistance and metabolic dysfunction prior to diagnosis with type 2 diabetes [15,81]. This theory is supported by the Bogalusa Heart Study's findings that women diagnosed with type 2 diabetes as adults have a greater cumulative exposure to cardiovascular risk factors over their lifetime, starting in youth [82]. For instance, sex CV, cardiovascular; IR, insulin resistance; IUGR, intrauterine growth restriction; T2D, type 2 diabetes differences in endothelial dysfunction are a potential biological mediator of the excess vascular risk observed in women with diabetes [83,84].…”

Risk and management of pre-diabetes

“…Only four studies investigated the effect of treatment with metformin to prevent T2DM, and these studies showed a RR of 0.74 (95% CI, 0.6-0.8), resulting in a number needed to treat of 14 (95% CI, [10][11][12][13][14][15][16][17][18][19][20][21][22]. Although effective, the two studies providing a direct comparison between lifestyle intervention and metformin showed that lifestyle intervention was more effective than metformin, albeit with a small difference in the Indian Diabetes Prevention Program (DPP).…”