Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Original Article

Volume 15, Number 4, August 2024, pages 253-261

Usefulness of Serum Testosterone Concentration and Skin Autofluorescence as Coronary Risk Markers in Male Patients With 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.

**Table 1.** Clinical Characteristics of the Studied Groups
	Overall (n = 162)	Non-CAD (n = 127)	CAD (n = 35)	P value
Continuous values are presented as mean ± SD or median (25th - 75th percentile). CAD: coronary artery disease; SBP: systolic blood pressure; DBP: diastolic blood pressure; FBG; fasting blood glucose; HbA1c: hemoglobin A1c; TyG: triglyceride-glucose; LDL: low-density lipoprotein; HDL: high-density lipoprotein; hs-CRP: high-sensitivity C-reactive protein; eGFR: estimated glomerular filtration rate; CAVI: cardio-ankle vascular index; T-T: total testosterone; SAF: skin autofluorescence; DPP: dipeptidyl peptidase; SGLT2: sodium glucose cotransporter 2; SD: standard deviation.
Age (years)	69 ± 11	67 ± 10	73 ± 13	0.005
Smoker, n (%)	47 (29)	38 (30)	9 (26)	0.129
SBP (mm Hg)	131 ± 19	131 ± 19	131 ± 21	0.853
DBP (mm Hg)	81 ± 11	81 ± 11	82 ± 11	0.783
FBG (mg/dL)	131 ± 20	130 ± 15	133 ± 28	0.385
HbA1c (%)	7.1 ± 1.2	7.0 ± 1.2	7.3 ± 1.1	0.264
TyG index	9.0 ± 0.6	8.9 ± 0.6	9.3 ± 0.5	< 0.001
Total cholesterol (mg/dL)	186 ± 39	191 ± 38	167 ± 37	0.002
LDL cholesterol (mg/dL)	113 ± 37	120 ± 34	89 ± 34	< 0.001
Triglyceride (mg/dL)	142 ± 68	131 ± 60	183 ± 78	< 0.001
HDL cholesterol (mg/dL)	44 ± 13	44 ± 13	42 ± 10	0.310
hs-CRP (mg/L)	0.7 (0.3 - 1.7)	0.6 (0.2 - 1.6)	1.1 (0.5 - 2.7)	0.023
eGFR (mL/min/1.73 m²)	66 ± 21	69 ± 21	57 ± 21	0.004
CAVI	9.1 ± 1.3	8.8 ± 1.1	10.1 ± 1.6	< 0.001
T-T (ng/dL)	481.9 ± 169.0	520.5 ± 149.9	341.8 ± 161.1	< 0.001
SAF (arbitrary unit)	2.8 ± 0.5	2.7 ± 0.5	3.4 ± 0.5	< 0.001
Medication
Biguanide, n (%)	74 (46)	62 (49)	12 (34)	0.128
DPP-4 inhibitor, n (%)	106 (65)	79 (62)	27 (77)	0.101
Sulfonylurea, n (%)	47 (29)	33 (26)	14 (40)	0.107
Thiazolidinedione, n (%)	17 (10)	13 (10)	4 (11)	0.927
SGLT2 inhibitor, n (%)	37 (23)	29 (23)	8 (23)	0.998
Insulin, n (%)	24 (15)	20 (16)	4 (11)	0.527
Statin, n (%)	93 (57)	64 (50)	29 (83)	< 0.001

Table 1. Clinical Characteristics of the Studied Groups

Overall (n = 162)

Non-CAD (n = 127)

CAD (n = 35)

P value

Continuous values are presented as mean ± SD or median (25th - 75th percentile). CAD: coronary artery disease; SBP: systolic blood pressure; DBP: diastolic blood pressure; FBG; fasting blood glucose; HbA1c: hemoglobin A1c; TyG: triglyceride-glucose; LDL: low-density lipoprotein; HDL: high-density lipoprotein; hs-CRP: high-sensitivity C-reactive protein; eGFR: estimated glomerular filtration rate; CAVI: cardio-ankle vascular index; T-T: total testosterone; SAF: skin autofluorescence; DPP: dipeptidyl peptidase; SGLT2: sodium glucose cotransporter 2; SD: standard deviation.

Age (years)

69 ± 11

67 ± 10

73 ± 13

0.005

Smoker, n (%)

47 (29)

38 (30)

9 (26)

0.129

SBP (mm Hg)

131 ± 19

131 ± 21

0.853

DBP (mm Hg)

81 ± 11

82 ± 11

0.783

FBG (mg/dL)

131 ± 20

130 ± 15

133 ± 28

0.385

HbA1c (%)

7.1 ± 1.2

7.0 ± 1.2

7.3 ± 1.1

0.264

TyG index

9.0 ± 0.6

8.9 ± 0.6

9.3 ± 0.5

< 0.001

Total cholesterol (mg/dL)

186 ± 39

191 ± 38

167 ± 37

0.002

LDL cholesterol (mg/dL)

113 ± 37

120 ± 34

89 ± 34

< 0.001

Triglyceride (mg/dL)

142 ± 68

131 ± 60

183 ± 78

< 0.001

HDL cholesterol (mg/dL)

44 ± 13

42 ± 10

0.310

hs-CRP (mg/L)

0.7 (0.3 - 1.7)

0.6 (0.2 - 1.6)

1.1 (0.5 - 2.7)

0.023

eGFR (mL/min/1.73 m²)

66 ± 21

69 ± 21

57 ± 21

0.004

CAVI

9.1 ± 1.3

8.8 ± 1.1

10.1 ± 1.6

< 0.001

T-T (ng/dL)

481.9 ± 169.0

520.5 ± 149.9

341.8 ± 161.1

< 0.001

SAF (arbitrary unit)

2.8 ± 0.5

2.7 ± 0.5

3.4 ± 0.5

< 0.001

Medication

Biguanide, n (%)

74 (46)

62 (49)

12 (34)

0.128

DPP-4 inhibitor, n (%)

106 (65)

79 (62)

27 (77)

0.101

Sulfonylurea, n (%)

47 (29)

33 (26)

14 (40)

0.107

Thiazolidinedione, n (%)

17 (10)

13 (10)

4 (11)

0.927

SGLT2 inhibitor, n (%)

37 (23)

29 (23)

8 (23)

0.998

Insulin, n (%)

24 (15)

20 (16)

4 (11)

0.527

Statin, n (%)

93 (57)

64 (50)

29 (83)

< 0.001

**Table 2.** Correlation Between T-T, SAF and Various Clinical Parameters
	r
r expressed correlation coefficient. P < 0.05, P < 0.01, **P < 0.001. T-T: total testosterone; SAF: skin autofluorescence; SBP: systolic blood pressure; DBP: diastolic blood pressure; FBG; fasting blood glucose; HbA1c: hemoglobin A1c; TyG: triglyceride-glucose; eGFR: estimated glomerular filtration rate; LDL: low-density lipoprotein; HDL: high-density lipoprotein; hs-CRP: high-sensitivity C-reactive protein; CAVI: cardio-ankle vascular index; DPP: dipeptidyl peptidase; SGLT2: sodium glucose cotransporter 2.
Age (actual value)	-0.22**	0.21**
Smoker (no = 0, yes = 1)	0.09	0.23**
SBP (actual value)	-0.09	0.04
DBP (actual value)	-0.10	0.07
FBG (actual value)	-0.18*	0.19*
HbA1c (actual value)	-0.22**	0.23**
TyG index (actual value)	-0.29***	0.20**
Total cholesterol (actual value)	0.15	0.12
LDL cholesterol (actual value)	0.14	0.11
Triglyceride (actual value)	-0.30***	0.20**
HDL cholesterol (actual value)	0.16	-0.13
hs-CRP (actual value)	-0.35***	0.38***
eGFR (actual value)	0.17*	-0.25**
CAVI (actual value)	-0.48***	0.44***
Biguanide (no = 0, yes = 1)	0.02	-0.03
DPP-4 inhibitor (no = 0, yes = 1)	-0.13	-0.07
Sulfonylurea (no = 0, yes = 1)	-0.11	-0.03
Thiazolidinedione (no = 0, yes = 1)	0.11	-0.10
SGLT2 inhibitor (no = 0, yes = 1)	0.15	-0.20**
Insulin (no = 0, yes = 1)	-0.14	0.07
Statin (no = 0, yes = 1)	-0.16	0.17

Table 2. Correlation Between T-T, SAF and Various Clinical Parameters

T-T

SAF

r expressed correlation coefficient. *P < 0.05, **P < 0.01, ***P < 0.001. T-T: total testosterone; SAF: skin autofluorescence; SBP: systolic blood pressure; DBP: diastolic blood pressure; FBG; fasting blood glucose; HbA1c: hemoglobin A1c; TyG: triglyceride-glucose; eGFR: estimated glomerular filtration rate; LDL: low-density lipoprotein; HDL: high-density lipoprotein; hs-CRP: high-sensitivity C-reactive protein; CAVI: cardio-ankle vascular index; DPP: dipeptidyl peptidase; SGLT2: sodium glucose cotransporter 2.

Age (actual value)

-0.22**

0.21**

Smoker (no = 0, yes = 1)

0.09

0.23**

SBP (actual value)

-0.09

0.04

DBP (actual value)

-0.10

0.07

FBG (actual value)

-0.18*

0.19*

HbA1c (actual value)

-0.22**

0.23**

TyG index (actual value)

-0.29***

0.20**

Total cholesterol (actual value)

0.15

0.12

LDL cholesterol (actual value)

0.14

0.11

Triglyceride (actual value)

-0.30***

0.20**

HDL cholesterol (actual value)

0.16

-0.13

hs-CRP (actual value)

-0.35***

0.38***

eGFR (actual value)

0.17*

-0.25**

CAVI (actual value)

-0.48***

0.44***

Biguanide (no = 0, yes = 1)

0.02

-0.03

DPP-4 inhibitor (no = 0, yes = 1)

-0.13

-0.07

Sulfonylurea (no = 0, yes = 1)

-0.11

-0.03

Thiazolidinedione (no = 0, yes = 1)

0.11

-0.10

SGLT2 inhibitor (no = 0, yes = 1)

0.15

-0.20**

Insulin (no = 0, yes = 1)

-0.14

0.07

Statin (no = 0, yes = 1)

-0.16

0.17

**Table 3.** Multiple Regression Analysis for CAD
Explanatory factor	β	P value
R² = 0.34, P < 0.001. CAD: coronary artery disease; LDL: low-density lipoprotein; CAVI: cardio-ankle vascular index; SAF: skin autofluorescence; T-T: total testosterone; TyG: triglyceride-glucose; eGFR: estimated glomerular filtration rate; hs-CRP: high-sensitivity C-reactive protein; HbA1c: hemoglobin A1c; β: standardized regression coefficient; R²: coefficient of determination.
LDL cholesterol	-0.27	< 0.001
CAVI	0.26	< 0.001
SAF	0.22	0.014
T-T	-0.18	0.029
TyG index	0.15	0.047
Statin	0.13	0.101
eGFR	-0.12	0.089
hs-CRP	0.04	0.580
Age	0.02	0.729
HbA1C	0.01	0.929

Table 3. Multiple Regression Analysis for CAD

Explanatory factor

P value

R² = 0.34, P < 0.001. CAD: coronary artery disease; LDL: low-density lipoprotein; CAVI: cardio-ankle vascular index; SAF: skin autofluorescence; T-T: total testosterone; TyG: triglyceride-glucose; eGFR: estimated glomerular filtration rate; hs-CRP: high-sensitivity C-reactive protein; HbA1c: hemoglobin A1c; β: standardized regression coefficient; R²: coefficient of determination.

LDL cholesterol

-0.27

< 0.001

CAVI

0.26

< 0.001

SAF

0.22

0.014

T-T

-0.18

0.029

TyG index

0.15

0.047

Statin

0.13

0.101

eGFR

-0.12

0.089

hs-CRP

0.04

0.580

Age

0.02

0.729

HbA1C

0.01

0.929