Usefulness of Serum Testosterone Concentration and Skin Autofluorescence as Coronary Risk Markers in Male Patients With Type 2 Diabetes Mellitus

Abstract

Background: No studies have reported simultaneous evaluation of the two coronary risk markers of testosterone and skin autofluorescence (SAF) as a marker of advanced glycation end products in patients with type 2 diabetes mellitus (T2DM) at present. This study aimed to clarify the clinical significance of both indicators as risk markers of coronary artery disease (CAD), including the association and background factors between testosterone and SAF in male patients with T2DM.

Methods: This study enrolled 162 male patients with T2DM (CAD: n = 35). Testosterone was evaluated by serum total testosterone concentration (T-T). Various analyses related to T-T and SAF as coronary risk markers were performed.

Results: T-T was significantly lower, and SAF was significantly higher in patients with CAD than in patients with non-CAD. A significant negative correlation was found between T-T and SAF (r = -0.45, P < 0.001), and the correlation was stronger in patients with CAD than in patients with non-CAD (non-CAD, r = -0.27, P = 0.003; CAD, r = -0.51, P < 0.001). However, both T-T and SAF had significant associations with triglyceride-glucose index as an insulin resistance marker and cardio-ankle vascular index as an arterial function marker. Multiple regression analysis revealed that both T-T and SAF were selected as independent variables to the presence of CAD as a dependent variable. However, the odds ratio increased due to the merger of two coronary risk markers, low T-T and high SAF (odds ratio: one risk marker: 3.24, 95% confidence interval: 1.01 - 10.50, P = 0.045; two risk markers: 13.22, 95% confidence interval: 3.41 - 39.92, P < 0.001).

Conclusions: The results of this cross-sectional study indicate that T-T and SAF are closely related in CAD patients with T2DM. It also shows that insulin resistance and arterial dysfunction are in the background of both indicators. Additionally, not only are both indicators independent coronary risk markers, but the overlap of both indicators increases their weight as coronary risk markers.

Keywords: Cardio-ankle vascular index; Coronary artery disease; Male; Skin autofluorescence; Testosterone; Triglyceride-glucose index; Type 2 diabetes mellitus.

Figure 1

Correlation between T-T and SAF. (a) All patients. (b) Non-CAD patients. (c) CAD patients. There was a significant negative correlation between T-T and SAF in all study groups ((a) r = -0.45, P < 0.001). However, as a result of examining the correlation with the presence or absence of CAD, the correlation was stronger in CAD patients than in non-CAD patients ((b) non-CAD: r = -0.27, P = 0.003; (c) CAD: r = -0.51, P < 0.001). T-T: total testosterone; SAF: skin autofluorescence; CAD: coronary artery disease; AU: arbitrary unit.

Figure 2

CAD risks due to the combination of T-T and SAF. The optimal cut-off values for detecting CAD based on receiver operating characteristic curve analysis were 474.5 ng/dL for T-T (a), and 3.0 AU for SAF (b). However, the OR significantly increased by combining the low T-T with the high SAF (c) (OR: one risk marker: 3.24, 95% CI: 1.01 - 10.50, P = 0.045; two risk markers: 13.22, 95% CI: 3.41 - 39.92, P < 0.001) The analysis was corrected by the LDL-C, CAVI, TyG index, and age, and the bar expressed 95% CI. *P = 0.039, **P < 0.001. CAD: coronary artery disease; T-T: total testosterone; SAF: skin autofluorescence; OR: odds ratio; CI: confidence interval; AU: arbitrary unit; AUC: area under the curve; LDL-C: low-density lipoprotein cholesterol; CAVI: cardio-ankle vascular index; TyG: triglyceride-glucose.