Association between cardiorespiratory fitness and impaired vascular function in type 2 diabetes

Table 1 Characteristics of participants stratified by vascular function, n (%)

Variables	Total	Normal vascular function	Impaired vascular function	P value
Sample size	343	255	88
Age (years)	54 (48, 59)	52 (45, 57)	59 (55, 65)	< 0.001
Gender				0.45
Male	218 (63.6)	165 (64.7)	53 (60.2)
Female	125 (36.4)	90 (35.3)	35 (39.8)
Smoking				0.64
Yes	128 (37.3)	97 (38.0)	31 (35.2)
No	215 (62.7)	158 (62.0)	57 (64.8)
Drinking				0.42
Yes	89 (25.9)	69 (27.1)	20 (22.7)
No	254 (74.1)	186 (72.9)	68 (77.3)
Hypertension				< 0.001
Yes	186 (54.2)	123 (48.2)	63 (71.6)
No	157 (45.8)	132 (51.8)	25 (28.4)
SBP (mmHg)	120 (120, 130)	120 (115, 126)	120 (112, 124)	< 0.001
DBP (mmHg)	80 (70, 80)	80 (70, 80)	80 (70, 80)	0.83
BMI (kg/m2)	25.0 (22.8, 30.1)	24.9 (22.5, 27.1)	25.9 (24.0, 28.6)	0.02
HbAlc (%)1	9.4 (7.8, 11.2)	9.4 (7.8, 11.3)	9.0 (7.5, 11.0)	0.25
TG (mmol/L)1	1.71 (1.06, 2.59)	1.79 (1.07, 2.68)	1.57 (1.05, 2.25)	0.23
TC (mmol/L)1	4.9 (4.2, 5.7)	5.0 (4.2, 5.7)	4.8 (4.3, 5.8)	0.54
HDL (mmol/L)1	1.2 (1.0, 1.4)	1.2 (1.0, 1.4)	1.2 (1.0, 1.4)	0.37
LDL (mmol/L)1	3.0 (2.5, 3.6)	3.0 (2.5, 3.5)	3.0 (2.6, 3.9)	0.49
eGFR (mL/minute/1.73 m2)1	90.9 (79.6, 104.0)	92.6 (81.3, 105.3)	87.9 (77.0, 98.7)	0.02
CRF (MET)	5.7 (4.8, 6.6)	5.9 (5.0, 6.7)	5.2 (4.5, 6.0)	< 0.001

¹There were 28 participants without information on estimated glomerular filtration rate, triglycerides and total cholesterol, 29 without high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol, and 24 without hemoglobin A1c.

SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BMI: Body mass index; HbA1c: Hemoglobin A1c; TG: Triglycerides; TC: Total cholesterol; HDL: High-density lipoprotein-cholesterol; LDL: Low-density lipoprotein-cholesterol; eGFR: Estimated glomerular filtration rate; CRF: Cardiorespiratory fitness; MET: Metabolic equivalent.

Table 2 Association between cardiorespiratory fitness and vascular function

Variables	Model 1		Model 2		Model 3
	Sβ	P value	Sβ	P value	Sβ	P value
VHI	0.20	< 0.001	0.10	0.045	0.10	0.047
ABI	0.07	0.20	0.04	0.53	0.08	0.18
TcPO2	0.16	0.004	0.16	0.01	0.13	0.03
PWV	-0.24	< 0.001	-0.08	0.02	-0.11	< 0.001
cIMT	-0.07	0.21	-0.04	0.53	-0.03	0.58

Model 1 was a crude model. Model 2 was adjusted for age and gender. Model 3 was adjusted for age, gender, history of smoking and drinking, systolic blood pressure, body mass index, estimated glomerular filtration rate, high-density lipoprotein-cholesterol, triglycerides, and hemoglobin A1c. VHI: Vascular health index; ABI: Ankle brachial index; TcPO₂: Transcutaneous oxygen pressure; PWV: Pulse wave velocity; cIMT: Carotid intima media thickness; Sβ: Standardized regression coefficient.

Table 3 Association between cardiorespiratory fitness and the odds of impaired vascular function

Variable	No. of cases/total	Model 1		Model 2		Model 3
		OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
CRF tertiles (MET)
Lowest (< 5.2)	42/117	1 (reference)		1 (reference)		1 (reference)
Middle (5.2-6.2)	29/119	0.58 (0.33-1.01)	0.06	0.73 (0.40-1.35)	0.32	0.68 (0.35-1.32)	0.25
Highest (> 6.2)	17/107	0.34 (0.18-0.64)	0.001	0.48 (0.24-0.98)	0.04	0.44 (0.20-0.96)	0.04
Per 1-MET increase	88/343	0.69 (0.57-0.84)	< 0.001	0.75 (0.61-0.94)	0.01	0.73 (0.57-0.93)	0.01

Model 1 was a crude model. Model 2 was adjusted for age and gender. Model 3 was adjusted for age, gender, history of smoking and drinking, systolic blood pressure, body mass index, estimated glomerular filtration rate, high-density lipoprotein-cholesterol, triglycerides, and hemoglobin A1c. CRF: Cardiorespiratory fitness; MET: Metabolic equivalent; OR: Odds ratio; CI: Confidence interval.

Table 4 Subgroup analysis of cardiorespiratory fitness and the odds of impaired vascular function

Variables	Model 1		Model 2		Model 3		Pinteraction1
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Age (years)							0.68
< 60	0.77 (0.60-0.98)	0.04	0.76 (0.59-0.99)	0.04	0.74 (0.54-1.00)	0.05
≥ 60	0.67 (0.47-0.96)	0.03	0.66 (0.45-0.95)	0.03	0.58 (0.36-0.92)	0.02
Gender							0.30
Male	0.62 (0.47-0.82)	0.001	0.66 (0.50-0.88)	0.004	0.62 (0.45-0.87)	0.01
Female	0.79 (0.57-1.09)	0.15	0.84 (0.59-1.19)	0.32	0.80 (0.54-1.20)	0.28
Duration of diabetes (years)2							0.55
< 1	0.96 (0.60-1.55)	0.87	0.74 (0.52-1.04)	0.08	0.66 (0.46-0.95)	0.03
1-10	0.98 (0.58-1.68)	0.95	0.75 (0.51-1.09)	0.13	0.67 (0.45-0.99)	0.04
≥ 10	1.40 (0.54-3.61)	0.48	0.76 (0.46-1.26)	0.29	0.56 (0.36-0.88)	0.01
Smoking							0.82
Yes	0.75 (0.54-1.05)	0.09	0.76 (0.54-1.06)	0.11	0.75 (0.47-1.20)	0.23
No	0.66 (0.51-0.85)	0.001	0.70 (0.53-0.93)	0.01	0.63 (0.46-0.87)	0.003
Drinking							0.73
Yes	0.80 (0.55-1.16)	0.25	0.79 (0.53-1.18)	0.25	0.81 (0.50-1.31)	0.40
No	0.65 (0.51-0.83)	0.001	0.69 (0.53-0.89)	0.01	0.66 (0.50-0.88)	0.01
BMI (kg/m2)							0.19
< 24	0.66 (0.47-0.92)	0.01	0.67 (0.46-0.98)	0.04	0.57 (0.36-0.89)	0.01
24-28	0.85 (0.62-1.17)	0.33	0.91 (0.63-1.31)	0.61	0.86 (0.55-1.35)	0.52
≥ 28	0.56 (0.35-0.89)	0.01	0.67 (0.40-1.10)	0.12	0.61 (0.33-1.14)	0.12
LDL (mmol/L)							0.72
< 2.6	0.64 (0.45-0.93)	0.02	0.57 (0.37-0.89)	0.01	0.51 (0.30-0.85)	0.01
≥ 2.6	0.71 (0.56-0.90)	0.01	0.78 (0.61-1.00)	0.05	0.75 (0.56-1.00)	0.05

¹P_interaction values are derived from Model 3.

²There were 259 data available for analysis.

Model 1 was a crude model. Model 2 was adjusted for age and gender. Model 3 was adjusted for age, gender, history of smoking and drinking, systolic blood pressure, body mass index, estimated glomerular filtration rate, high-density lipoprotein-cholesterol, triglycerides, and hemoglobin A1c (except the variables used for subgrouping). HbA1c: Glycated hemoglobin A1c; OR: Odds ratio; CI: Confidence interval.