Diabetes abrogates sex differences and aggravates cardiometabolic risk in postmenopausal women

Abstract

Background: The aim of this study is to evaluate the effect of gender and menopause in cardiometabolic risk in a type 2 diabetes mellitus (T2DM) population, based on classical and non-traditional markers.

Methods: Seventy four volunteers and 110 T2DM patients were enrolled in the study. Anthropometric data, blood pressure, body mass index (BMI), waist circumference (WC) and the following serum markers were analyzed: glucose, Total-c, TGs, LDL-c, Oxidized-LDL, total HDL-c and large and small HDL-c subpopulations, paraoxonase 1 activity, hsCRP, uric acid, TNF-α, adiponectin and VEGF.

Results: Non-diabetic women, compared to men, presented lower glycemia, WC, small HDL-c, uric acid, TNF-α and increased large HDL-c. Diabetes abrogates the protective effect of female gender, since diabetic women showed increased BMI, WC, small HDL-c, VEGF, uric acid, TNF-α and hsCRP, as well as reduced adiponectin, when compared with non-diabetic. In diabetic females, but not in males, WC is directly and significantly associated with TNF-α, VEGF, hsCRP and uric acid; TNF-α is directly associated with VEGF and hsCRP, and inversely with adiponectin. Postmenopausal females presented a worsen cardiometabolic profile, viewed by the increased WC, small HDL-c, VEGF, uric acid, TNF-α and hsCRP. In this population, WC is directly and significantly associated with TNF-α, VEGF, hsCRP; TNF-α is directly associated with VEGF; and uric acid is inversely associated with large HDL-c and hsCRP with adiponectin, also inversely.

Conclusions: Diabetes abrogates the protective effect of gender on non-diabetic women, and postmenopausal diabetic females presented worsen cardiometabolic risk, including a more atherogenic lipid sketch and a pro-inflammatory and pro-angiogenic profile. The classical cardiovascular risk factors (CVRFs) fail to completely explain these differences, which are better clarified using "non-traditional" factors, such as HDL-c subpopulations, rather than total HDL-c content, and markers of inflammation and angiogenesis, namely TNF-α, hsCRP, uric acid and VEGF. Multi-therapeutic intervention, directed to obesity, atherogenic lipid particles and inflammatory mediators is advisory in order to efficiently prevent the serious diabetic cardiovascular complications.

Figure 1

Gender effect on control and diabetic populations. Serum total HDL-c (A), large HDL-c (B), small HDL-c (C), waist circumference (D), VEGF (E), uric acid (F), adiponectin (G), TNF-α (H) and hsCRP (I), in male and female diabetic patients and controls. Results are presented as mean ± SEM. *p<0.05, **p<0.01 and ***p<0.001.

Figure 2

Menopause effect on control and diabetic populations. Serum total HDL-c (A), large HDL-c (B), small HDL-c (C), waist circumference (D), VEGF (E), uric acid (F), adiponectin (G), TNF-α (H) and hsCRP (I), in pre and postmenopausal diabetic patients and controls. Results are presented as mean ± SEM. *p<0.05, **p<0.01 and ***p<0.001.

Figure 3

Main correlations in male and female diabetic patients. Correlation between waist circumference and TNF-α (A), VEGF (B), hsCRP (C) and uric acid (D); between TNF-α and VEGF (E) and between hsCRP and adiponectin (F).

Figure 4

Main correlations in postmenopausal diabetic patients. Correlation between waist circumference and TNF-α (A), VEGF (B) and hsCRP (C); between uric acid and large HDL-c (D); between TNF-α and VEGF (E) and between hsCRP and adiponectin (F).