Impaired Vascular Endothelial Function is Associated with Peripheral Neuropathy in Patients with Type 2 Diabetes

Figures & data

Table 1 Comparison of Clinical and Biochemical Features of Patients with T2DM

	FMD>7% (n, 90)	4%≤FMD≤7% (n, 91)	FMD<4% (n, 91)	p value
Age (y)	53.4±9.6	53.4±10.7	53.4±8.9	0.91
Gender (male/female)	51/39	43/48	54/37	0.37
BMI (kg/m^2)	22.9±1.8	24.8±4.0	24.3±3.1	0.17
Duration (y)	9.1±6.5	9.3±7.1	10.3±7.6	0.64
FPG (mmol/L)	9.5±3.6	9.9±4.0	9.9±4.2	0.76
HbA1c (%)	8.4±2.1	8.5±1.8	8.4±1.8	0.99
TC (mmol/L)	3.8±1.0	4.2±1.3	3.8±1.0	0.48
TG (mmol/L)	1.6±0.8	1.6±2.1	1.6±1.1	0.10
HDL (mmol/L)	1.0±0.2	1.0±0.3	0.9±0.2	0.18
LDL (mmol/L)	2.5±0.8	2.7±0.9	2.5±0.8	0.70
SBP (mmHg)	121.5±24.1	129.5±17.9	131.7±18.7	0.36
DBP (mmHg)	76.2±8.7	80.0±11.3	76.7±8.3	0.43
HR (bpm)	83.6±11.6	88.6±11.4	83.1±12.5	0.22
Smoking (%)	20(22.2%)	26(28.6%)	23(25.3%)	0.16
Drinking (%)	14(15.6%)	18(19.8%)	12(13.2%)	0.16
25(OH)D(ng/mL)	24.6±9.1	17.9±6.1	17.5±6.8	0.11
HCY (µmol/L)	13.1±3.4	13.4±3.6	16.8±13.5	0.23
baPWV (cm/s)	1627.1±377.3	1623.1±263.7	1630.1±595.2	0.57
ABI	1.2±0.1	1.2±0.1	1.2±0.1	0.87

Note: Univariate ANOVA and Chi-square test are used in this table.

Abbreviations: FMD, flow-mediated dilation; F, female; M, male; BMI, body mass index; FPG, fasting blood glucose; HbA1C, glycosylated hemoglobin; TC, total cholesterol; TG, triglyceride; HDL, High density lipoprotein; LDL, low density lipoprotein; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; HCY, homocysteine; baPWV, brachial ankle pulse wave velocity; ABI, ankle-brachial index.

Figure 1 Flow diagram. The chart shows patient inclusion and exclusion in the study.

Table 2 Proportion of Peripheral Neuropathy Severity in Three Groups

	FMD>7% (n, 90)	4%≤FMD≤7% (n, 91)	FMD<4% (n, 91)
No nerve injury (n; %)	56(62%)	30(33%)	3(3%)
Mild nerve injury (n; %)	22(25%)	24(26%)	9(10%)
Moderate nerve injury (n; %)	10(11%)	19(21%)	16(17%)
Severe nerve injury (n; %)	2(2%)	18(20%)	63(70%)

Notes: Kruskal-Wallis H-test is used in this table X², 11.114; p, 0.004; the severity of peripheral neuropathy can be considered different among the three groups.

Figure 2 Scatter diagram of FMD and TCSS (0–19 points).

Table 3 Abnormal Ratio of TCSS Indicators of Three Groups

	Total (n, 272)	FMD>7% (n, 90)	4%≤FMD≤7% (n, 91)	FMD<4% (n, 91)	X^2	p
Nerve symptoms^a					44.249	<0.001
Lower limb pain	141(52%)	40(44%)	50(55%)	51(56%)
Numbness	60(22%)	5(5%)	10(11%)	45(49%)
Picotement	44(16%)	5(5%)	3(3%)	36(40%)
Fatigue	137(50%)	45(50%)	54(59%)	68(75%)
Walking imbalance	33(12%)	5(5%)	9(10%)	19(21%)
Upper-limb symptoms	35(13%)	0	9(10%)	26(29%)
Sensory examinations^b					26.758	0.003
Acmesthesia	25(9%)	5(5%)	7(8%)	13(14%)
Temperature sensation	198(73%)	50(55%)	65(71%)	83(91%)
Light touch sensation	54(20%)	0	18(20%)	36(40%)
Vibration sensation	138(51%)	10(11%)	57(63%)	71(78%)
Joint-position sensation	0	0	0	0
Nerve reflexes^c					76.631	<0.001
Ankle reflex	127(47%)	9(10%)	36(40%)	82(90%)
Knee reflex	119(44%)	9(10%)	30(33%)	80(88%)

Notes: Chi-square test is used in this table TCSS, Toronto clinical scoring system. a is for nerve symptoms; ^aX², 44.249; p<0.001; b is for sensory examinations; ^bX², 26.758; p, 0.003; c is for nerve reflexes; ^cX², 76.631; p<0.001. Nerve symptoms; sensory examinations; and nerve reflexes can be considered different among the three groups.

Table 4 Correlation Between Components of TCSS and FMD

	FMD (%)
	r	p
TCSS total points (0–19)	−0.756	<0.001
Nerve symptoms (0–6)	−0.328	<0.001
Sensory examination (0–5)	−0.081	<0.05
Nerve reflexes (0–8)	−0.714	<0.001

Note: Pearson correlation analysis is used in this table.

Abbreviations: TCSS, Toronto clinical scoring system; FMD, flow-mediated dilation.

Table 5 Comparison of Peripheral Motor Nerve Measurements in Three Groups

	FMD>7% (n, 90)	4%≤FMD≤7% (n, 91)	FMD<4% (n, 91)
CV (m/s)
Median nerve	51.18±6.56	50.23±5.32	48.75±5.43^ab
Ulnar nerve	50.61±4.85	50.16±5.23	45.05±5.05^ab
Common peroneal nerve	38.43±4.98	37.38±7.50	35.45±7.90^ab
Tibial nerve	38.04±3.51	36.98±5.47	34.3±5.55^ab
Amp (mV)
Median nerve	6.27±2.30	6.16±3.51	4.82±1.99^ab
Ulnar nerve	7.45±2.49	6.93±2.31	6.84±2.80^ab
Common peroneal nerve	1.19±1.39	0.91±1.17	0.80±0.87^a
Tibial nerve	5.25±2.84	5.16±2.50	4.40±3.45^ab
DML (ms)
Median nerve	3.08±0.72	3.50±0.72	4.29±3.07^ab
Ulnar nerve	2.53±0.97	2.56±0.81	2.67±0.52^ab
Common peroneal nerve	6.02±3.41	6.23±1.97	6.62±1.92^ab
Tibial nerve	4.43±1.05	4.89±2.08	5.64±2.27^ab

Notes: Univariate ANOVA and s-N-K test are used in this table Compared with FMD > 7% group; ^ap<0.05; Compared with 4%≤FMD≤7% group; ^bp<0.05.

Abbreviations: CV, conduction velocity; Amp, amplitude; DML, distal motor latency.

Table 6 Correlation Analysis of Motor Nerve CV; Amp; DML and FMD

	FMD>7% (n, 90)		4%≤FMD≤7% (n, 91)		FMD<4% (n, 91)
CV (m/s)	r	p	r	p	r	p
Median nerve	0.002	0.987	0.010	0.677	0.357	0.017
Ulnar nerve	0.194	0.297	0.190	0.267	0.472	<0.001
Common peroneal nerve	0.040	0.779	0.121	0.665	0.650	<0.001
Tibial nerve	0.059	0.681	0.098	0.543	0.798	<0.001
Amp (mV)
Median nerve	0.005	0.972	0.111	0.767	0.340	0.028
Ulnar nerve	0.182	0.201	0.220	0.134	0.431	0.010
Common peroneal nerve	0.222	0.118	0.321	0.101	0.791	<0.001
Tibial nerve	0.121	0.397	0.226	0.267	0.790	<0.001
DML (ms)
Median nerve	−0.274	0.072	−0.254	0.102	−0.359	0.017
Ulnar nerve	−0.095	0.539	−0.143	0.213	−0.576	0.009
Common peroneal nerve	−0.158	0.304	−0.145	0.144	−0.801	<0.001
Tibial nerve	−0.220	0.151	−0.221	0.151	−0.767	<0.001

Note: Pearson correlation analysis is used in this table.

Abbreviations: CV, conduction velocity; Amp, amplitude; DML, distal motor latency.

Table 7 Multiple Linear Regression Analysis of Risk Factors for Endothelial Function Injury in T2DM

	Model1 (R2, 0.262)		Model2 (R2, 0.588)		Model3 (R2, 0.535)
	β	p	β	p	β	p
Age	−0.71	0.395	−0.70	0.395	−0.71	0.395
Duration	−0.68	0.121	−0.67	0.122	−0.69	0.125
FPG	−0.54	0.111	−0.53	0.110	−0.53	0.110
HbA1c	−0.55	0.159	−0.55	0.156	−0.56	0.159
SBP	−0.60	0.002**	−0.60	0.002**	−0.60	0.002**
TG	−0.57	0.017*	−0.57	0.015*	−0.57	0.017*
Smoking	−0.015	0.056	−0.015	0.056	−0.014	0.055
25 (OH)D	0.13	0.067	0.13	0.056	0.12	0.056
TCSS^a			−0.51	<0.001**
CV^1b					0.19	0.052
CV^2b					0.24	0.067
CV^3b					0.13	0.014*
CV^4b					0.27	0.003**
Amp^3b					0.37	0.070
Amp^4b					0.04	0.070
DML^3b					−0.04	0.098
DML^4b					−0.08	0.088

Notes: *p<0.05; **p<0.01. Model1: Age; Duration; FPG; HbA1c; SBP and TG are forced to enter the model; and other indicators are entered by stepwise (p<0.05 entered; p>0.1 removed). Model2: Model1 +TCSS score (Age; Duration; FPG; HbA1c; SBP and TG are forced to enter the model; other indicators are entered stepwise; p<0.05 entered; p>0.1 removed) (a is removed from Model3). Model3: CV; Amp and DML of Model1 + median nerve¹; ulnar nerve²; common peroneal nerve³ and tibial nerve⁴ (Age; Duration; FPG; HbA1c; SBP and TG were forced into the model; and other indicators were entered by stepwise. p<0.05 entered; p>0.1 removed) (b is removed from Model2).