Continuous glucose monitoring defined time-in-range is associated with sudomotor dysfunction in type 2 diabetes

Table 1 Comparison of clinical variables between sudomotor dysfunction (-) and sudomotor dysfunction (+) groups

	Sudomotor dysfunction (-)	Sudomotor dysfunction (+)	χ2/t/z	P value
n	331	135	-	-
Male, n (%)	234 (70.69)	92 (68.15)	0.296	0.586
Age (yr)	53.30 ± 11.91	57.45 ± 13.03	-3.318	0.001
Diabetes duration (yr)	7 (2, 11)	10 (6, 15)	-4.266	< 0.001
Smoking, n (%)	84 (25.38)	65 (48.15)	22.86	< 0.001
SBP (mmHg)	132.12 ± 15.82	135.30 ± 20.02	-1.646	0.101
DBP (mmHg)	79.46 ± 9.69	79.13 ± 10.57	0.322	0.748
BUN (mmol/L)	5.40 (4.50, 6.63)	5.90 (4.80, 7.40)	-2.845	0.004
SCr (µmol/L)	56.00 (48.00, 67.00)	60.00 (48.00, 79.00)	-1.703	0.089
UA (µmol/L)	328.18 ± 88.92	324.04 ± 88.30	0.456	0.648
TC (mmol/L)	4.35 (3.77, 5.11)	4.30 (3.55, 5.31)	-0.567	0.571
TG (mmol/L)	1.51 (1.04, 2.40)	1.67 (1.12, 2.52)	-0.856	0.392
HDL (mmol/L)	1.03 (0.90, 1.24)	1.09 (0.91, 1.27)	-1.067	0.286
LDL (mmol/L)	2.56 (2.10, 3.25)	2.48 (1.82, 3.19)	-1.297	0.195
HbA1c (%)	8.60 ± 2.01	8.94 ± 2.28	-1.564	0.118
BMI (kg/m2)	25.61 ± 3.53	25.27 ± 3.82	0.899	0.369
FBG (mmol/L)	7.23 ± 2.35	7.74 ± 2.71	-1.770	0.079
PBG (mmol/L)	15.62 ± 3.63	15.92 ± 3.68	-0.710	0.478
SD (mmol/L)	2.25 (1.80, 2.85)	2.46 (1.89, 3.06)	-2.234	0.025
MAGE (mmol/L)	4.38 (3.47, 5.50)	4.08 (3.62, 5.56)	-0.168	0.866
MODD (mmol/L)	1.95 (1.40, 2.67)	2.28 (1.63, 3.08)	-2.562	0.010
ADDR (mmol/L)	21.46 (14.55, 28.02)	27.37 (15.11, 34.82)	-2.411	0.016
M value (mmol/L)	5.99 (3.01, 11.25)	11.30 (3.85, 24.67)	-4.096	< 0.001
TBR (%)	0.00 (0.00, 0.00)	0.00 (0.00, 0.00)	-1.093	0.274
TIR (%)	72.82 (53.06, 86.79)	53.12 (28.36, 79.69)	-4.446	< 0.001
TAR (%)	26.38 (12.65, 42.97)	44.73 (19.28, 71.20)	-4.602	< 0.001
Microvascular complications
DN, n (%)	51 (15.41)	53 (39.26)	31.465	< 0.001
DR, n (%)	69 (20.85)	62 (45.93)	29.846	< 0.001
Treatment, n (%)
No treatment	27 (8.16)	7 (5.19)	7.107	0.069
OHA	104 (31.42)	29 (21.48)
Insulin	44 (13.29)	20 (14.81)
OHA and insulin	156 (47.13)	79 (58.52)

Normally distributed variables in the table are presented as the means ± SD, non-normally distributed values are presented as medians (25% and 75% interquartiles), and categorical variables are presented as frequencies (percentages). Student’s t-test was used for comparison of data with a normal distribution, Wilcoxon rank-sum test for those with abnormal distributions, and χ²-test for categorical variables. SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BUN: Blood urea nitrogen; SCr: Serum creatinine; UA: Uric acid; TC: Total cholesterol; TG: Triglyceride; HDL: High density lipoprotein; LDL: Low density lipoprotein; HbA1c: Hemoglobin A₁c; BMI: Body mass index; FBG: Fasting blood glucose; PBG: Postprandial blood glucose; SD: Standard deviation; MAGE: Mean amplitude of glucose excursions; MODD: Means of daily differences; ADDR: Average daily risk range; TBR: Time below range; TIR: Time in range; TAR: Time above range; DN: Diabetic nephropathy; DR: Diabetic retinopathy; OHA: Oral hypoglycemic agents.

Table 2 Association between time below range, time in range, or time above range and SUDOSCAN indicators

	TBR		TIR		TAR
	r	P value	r	P value	r	P value
HESC	-0.032	0.497	0.195	< 0.001	-0.207	< 0.001
FESC	-0.035	0.452	0.164	< 0.001	-0.164	< 0.001
HASYM	-0.014	0.766	-0.175	< 0.001	0.183	< 0.001
FASYM	0.046	0.320	-0.180	< 0.001	0.169	< 0.001

TBR: Time below range; TIR: Time in range; TAR: Time above range; HESC: Electrochemical skin conductance in hands; FESC: Electrochemical skin conductance in feet; HASYM: Asymmetry ratio in hands; FASYM: Asymmetry ratio in feet.

Table 3 Binary logistic regression analysis with presence or absence of sudomotor dysfunction as dependent variable

		OR	95%CI	P value
Model 1
TIR	-0.021	0.979	0.971-0.987	< 0.001
Age	0.023	1.024	1.003-1.045	0.027
Smoking	0.632	1.881	1.115-3.174	0.018
Model 2
TIR	-0.024	0.976	0.967-0.986	< 0.001
Age	0.024	1.024	1.003-1.045	0.027
Smoking	0.632	1.881	1.113-3.177	0.018
Model 3
TIR	-0.025	0.975	0.957-0.994	0.010
Age	0.031	1.031	1.008-1.055	0.008
Smoking	0.717	2.047	1.146-3.659	0.016
M value	0.093	1.097	1.040-1.158	0.001

Model 1 was adjusted for age, diabetes duration, sex, body mass index, systolic blood pressure, diastolic blood pressure, smoking, triglyceride, and total cholesterol. Model 2 was adjusted for variables as in model 1 and for HbA1c. Model 3 was adjusted for variables as in model 2 and for glycemic variability values like standard deviation, mean amplitude of glucose excursions, means of daily differences, average daily risk range, and M value. TIR: Time in range; CI: Confidence interval.

Table 4 Association between tertiles of time in range and sudomotor dysfunction

		OR	95%CI	P value
Model 1
TIR T1	-	-	-	-
TIR T2	-1.175	0.309	0.183-0.521	< 0.001
TIR T3	-0.961	0.383	0.225-0.649	< 0.001
Age	0.022	1.022	1.002-1.044	0.035
Smoking	0.600	1.823	1.085-3.063	0.023
Model 2
TIR T1	-	-	-	-
TIR T2	-1.241	0.289	0.164-0.509	< 0.001
TIR T3	-1.032	0.356	0.189-0.673	0.001
Age	0.022	1.022	1.001-1.044	0.036
Smoking	0.608	1.837	1.092-3.091	0.022
Model 3
TIR T1	-	-	-	-
TIR T2	-0.809	0.445	0.209-0.948	0.036
TIR T3	-1.141	0.320	0.123-0.831	0.019
Age	0.029	1.030	1.007-1.053	0.011
Smoking	0.670	1.953	1.100-3.468	0.022
M value	0.111	1.117	1.057-1.180	< 0.001

Time in range T1: < 55.69%; T2: 55.69%-79.86%; T3: > 79.86%. Model 1 was adjusted for age, diabetes duration, sex, body mass index, systolic blood pressure, diastolic blood pressure, smoking, triglyceride, and total cholesterol. Model 2 was adjusted for variables as in model 1 and for HbA1c. Model 3 was adjusted for variables as in model 2 and for glycemic variability metrics like standard deviation, mean amplitude of glucose excursions, means of daily differences, average daily risk range, and M value. TIR: Time in range; CI: Confidence interval.