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. 2022 Jun 27:13:890029.
doi: 10.3389/fendo.2022.890029. eCollection 2022.

Low Serum Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate Are Associated With Coronary Heart Disease in Men With Type 2 Diabetes Mellitus

Xinxin Zhang  1 , Jinfeng Xiao  1 , Tong Liu  1 , Qing He  1 , Jingqiu Cui  1 , Shaofang Tang  1 , Xin Li  1 , Ming Liu  1
Affiliations

Low Serum Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate Are Associated With Coronary Heart Disease in Men With Type 2 Diabetes Mellitus

Xinxin Zhang et al. Front Endocrinol (Lausanne). .

Abstract

Aims: Sex hormones play an important role in the pathogenesis of cardiovascular disease (CVD). This cross-sectional study aimed to explore the associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with coronary heart disease (CHD) and stroke in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).

Materials and methods: A total of 995 patients with T2DM were included in the study analysis. Serum levels of DHEA and DHEAS were quantified using liquid chromatography-tandem mass spectrometry. Binary logistic regression analyses were performed to assess the associations of DHEA and DHEAS with CHD and stroke. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal DHEA and DHEAS cutoff values for the detection of CHD in men with T2DM.

Results: In men with T2DM, after adjustment for potential confounders in model 3, the risk of CHD decreased with an increasing serum DHEA level [odds ratio (OR) = 0.38, quartile 4 vs. quartile 1; 95% confidence interval (CI) = 0.16-0.90; p = 0.037 for trend). Consistently, when considered as a continuous variable, this association remained significant in the fully adjusted model (OR = 0.59, 95% CI = 0.40-0.87, p < 0.05). When taken as a continuous variable in model 3, serum DHEAS level was also inversely related to the risk of CHD among men (OR = 0.56, 95% CI = 0.38-0.82, p < 0.05). Similarly, this relationship remained statistically significant when DHEAS was categorized into quartiles (OR = 0.27, quartile 4 vs. quartile 1; 95% CI = 0.11-0.67; p = 0.018 for trend). ROC curve analyses revealed that the optimal cutoff values to detect CHD in men with T2DM were 6.43 nmol/L for DHEA and 3.54 μmol/L for DHEAS. In contrast, no significant associations were found between DHEA and DHEAS on the one hand and stroke on the other in men and women with T2DM (all p > 0.05).

Conclusions: Serum DHEA and DHEAS were significantly and negatively associated with CHD in middle-aged and elderly men with T2DM. This study suggests potential roles of DHEA and DHEAS in CHD pathogenesis.

Keywords: coronary heart disease; dehydroepiandrosterone; dehydroepiandrosterone sulfate; stroke; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of the identification of the study population. Based on the exclusion criteria, 995 patients with type 2 diabetes mellitus were included in the final analysis.
Figure 2
Figure 2
Correlation between serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) among the men and women included in this study evaluated by Spearman’s correlations. The figure indicates that the serum levels of DHEA and DHEAS were highly collinear (among men: r = 0.648, 95% CI = 0.593–0.697, p < 0.001; among women: r = 0.657, 95% CI = 0.602–0.706, p < 0.001).
Figure 3
Figure 3
Prevalence of coronary heart disease (CHD) and stroke by quartiles of serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) in men and women. (A, B) Prevalence of CHD by DHEA (A) and by DHEAS (B). (C, D) Prevalence of stroke by DHEA (C) and by DHEAS (D). The figure shows that the percentages of men with CHD significantly decreased in accordance with increasing quartiles of serum DHEA and DHEAS (all p < 0.001). The prevalence of stroke significantly decreased in line with increasing quartiles of serum DHEA in women (p = 0.003) and DHEAS in men (p = 0.011).
Figure 4
Figure 4
Associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with coronary heart disease (CHD) in men with type 2 diabetes mellitus. Restricted cubic splines were used to assess the dose–response associations of DHEA (A) and DHEAS (B) with CHD after adjusting for age, current smoking, current drinking, insurance type, body mass index (BMI), duration of diabetes, systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and the use of glucagon-like peptide 1 (GLP-1) receptor agonists or sodium–glucose cotransporter 2 (SGLT-2) inhibitors. The p-values for nonlinear associations were 0.969 and 0.942 for DHEA and DHEAS, respectively.
Figure 5
Figure 5
Receiver operating characteristic (ROC) curve analysis of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) to recognize coronary heart disease (CHD) in men with type 2 diabetes mellitus. ROC curve analysis revealed that the areas under the curve (AUCs) for DHEA (A) and DHEAS (B) were 0.66 (95% CI = 0.60–0.72) and 0.64 (95% CI = 0.58–0.69), respectively. The optimal cutoff values, with the best trade-off between sensitivity and specificity, were 6.43 nmol/L for DHEA and 3.54 μmol/L for DHEAS.
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