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

Abstract

AimsSex 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 MethodsA 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.ResultsIn 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).ConclusionsSerum 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.

Low serum dehydroepiandrosterone levels are associated with diabetic retinopathy in patients with type 2 diabetes mellitus

“…Moreover, low DHEA levels correlated with cardiovascular disease, including coronary heart disease, myocardial infarction, and stroke, in participants with type 2 diabetes mellitus from 10 communities in Shanghai, China 9 . Similarly, our previous study identified a relationship between low DHEA levels and coronary heart disease in men with type 2 diabetes mellitus 15 . Conversely, a significant relationship was not identified between DHEA and the incidence of cardiovascular disease in studies of women in the general population or those with type 2 diabetes mellitus 9,15,23 .…”

“…Similarly, our previous study identified a relationship between low DHEA levels and coronary heart disease in men with type 2 diabetes mellitus 15 . Conversely, a significant relationship was not identified between DHEA and the incidence of cardiovascular disease in studies of women in the general population or those with type 2 diabetes mellitus 9,15,23 . Sex‐specific differences regarding these associations remain unclear and require further investigation.…”

“…The serum DHEA concentration was quantified using liquid chromatography-tandem mass spectrometry as described previously 10,15 . Briefly, fasting blood samples were collected in the morning after admission and immediately sent to the Laboratory of Endocrinology and Metabolism at the Tianjin Medical University General Hospital.…”

Effects of steroid hormones on lipid metabolism in sexual dimorphism: A Mendelian randomization study

“…In addition, the conclusions drawn from the MR analysis were in accordance with the findings of several epidemiological studies. Lower levels of DHEAS were associated with a higher incidence of cardiovascular disease and cardiovascular disease-related mortality in males and females ( 35 – 38 ) which might result from low DHEAS-associated hyperlipidemia. However, the exact mechanism underlying this regulatory effect remains unclear and requires further research.…”

Opioid-induced adrenal insufficiency: diagnostic and management considerations

“…Accordingly, it may reflect ACTH deficiency and has been studied as a potential additive biomarker to ACTH 1-24 stimulation in the diagnosis of adrenal insufficiency ( 24 , 25 ). However, DHEAS levels decrease with age ( 26 ) and with chronic diseases such as diabetes mellitus ( 27 ), autoimmune disease ( 28 ), and cancer ( 29 ), and the lack of OAI-specific, age-specific reference ranges all may limit its use. Nevertheless, as access to an endocrinologist and ACTH 1-24 stimulation testing may not be readily available to all clinicians, the combination of low/low-normal morning cortisol, DHEAS, and ACTH levels several hours after the last dose of opioids may be used as a preliminary screening tool for OAI.…”