Retinal Microvascular Diameters are Associated with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Figures & data

Figure 1 Flow chart of patient selection.

Abbreviation: T2DM, type 2 diabetes mellitus.

Table 1 Clinical and Laboratory Characteristics of Participants Between Non-DKD Group and DKD Group

Variable	Total (n=690)	Non-DKD Group (n=424)	DKD Group (n=266)	P value
Age, median (IQR), year	57 (47, 67)	57 (47, 66)	57 (46, 67)	0.401
Sex (male), n (%)	435 (63.0)	264 (62.3)	171 (64.3)	0.592
Hypertension, n (%)	332 (48.1)	168 (39.6)	164 (61.7)	<0.001*
SBP, median (IQR), mmHg	138 (123, 158)	130 (119, 142)	158 (138.75, 170)	<0.001*
DBP, median (IQR), mmHg	80 (72, 88)	81 (74, 88)	80 (70, 87)	0.075
Duration of T2DM, median (IQR), year	7 (1, 13)	5 (1, 10.8)	10 (2, 16)	<0.001*
Body mass index, median (IQR), kg/m^Citation2	26.22 (23.73, 28.82)	25.90 (23.50, 28.40)	27.00 (24.20, 29.20)	0.022*
HbA1c, median (IQR), %	9.20 (7.60, 10.90)	9.10 (7.43, 10.90)	9.30 (7.90, 10.70)	0.411
FPG, median (IQR), mmol/L	8.51 (6.52, 11.70)	8.18 (6.60, 11.62)	8.83 (6.37, 11.89)	0.878
BUN, median (IQR), mmol/L	5.30 (4.40, 6.60)	5.20 (4.30, 6.30)	5.40 (4.60, 7.13)	0.001*
Scr, median (IQR), μmol/L	61.9 (53.28, 72.33)	61.00 (52.95, 68.30)	65.15 (54.53, 80.00)	<0.001*
UA, median (IQR), μmol/L	314.85 (254.38, 383.63)	306.10 (250.68, 375.53)	331.40 (270.40, 399.73)	0.003*
TC, median (IQR), mmol/L	4.73 (3.83, 5.63)	4.77 (3.85, 5.60)	4.60 (3.75, 5.67)	0.480
TG, median (IQR), mmol/L	1.58 (1.03. 2.45)	1.49 (0.98, 2.32)	1.67 (1.11, 2.63)	0.007*
LDL-C, median (IQR), mmol/L	3.10 (2.39, 3.76)	3.14 (2.41, 3.76)	2.97 (2.36, 3.75)	0.368
HDL-C, median (IQR), mmol/L	1.07 (0.91, 1.28)	1.10 (0.94, 1.28)	1.05 (0.89, 1.24)	0.031*

Note: *Denotes significance at a P value of <0.05.

Abbreviations: DKD, diabetic kidney disease; IQR, interquartile range; SBP, systolic blood pressure; DBP, diastolic blood pressure; T2DM, type 2 diabetes mellitus; HbA_1c, glycosylated hemoglobin; FPG, fasting plasma glucose; BUN, blood urea nitrogen; Scr, serum creatinine; UA, uric acid; TC, total cholesterol; TG, triglyceride; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol.

Table 2 Comparison of the Retinal Microvascular Diameters Between Non-DKD Group and DKD Group

Variable	Total (n=690)	Non-DKD Group (n=424)	DKD Group (n=266)	P value
Venule
Temporal superior, median (IQR), μm	154.16 (138.58, 167.28)	149.24 (134.48, 164.82)	160.72 (148.42, 169.74)	<0.001*
Temporal inferior, median (IQR), μm	159.90 (141.04, 170.56)	151.70 (136.12,166.46)	165.64 (157.24, 175.69)	<0.001*
Nasal superior, median (IQR), μm	112.75 (102.50, 123.82)	108.24 (99.22, 118.90)	119.72 (111.52, 127.10)	<0.001*
Nasal inferior, median (IQR), μm	113.16 (103.12, 122.18)	108.24 (100.04, 119.72)	118.08 (111.52, 123.82)	<0.001*
CRVE, median (IQR), μm	187.25 (170.65, 199.03)	180.78 (165.25, 193.67)	195.35 (186.03, 202.45)	<0.001*
Arteriole
Temporal superior, median (IQR), μm	104.96 (96.76, 114.19)	109.06 (100.04, 116.44)	99.22 (94.30, 105.78)	<0.001*
Temporal inferior, median (IQR), μm	105.37 (96.76, 114.80)	108.24 (100.86, 117.26)	100.04 (92.66, 107.42)	<0.001*
Nasal superior, median (IQR), μm	86.10 (77.85, 95.12)	89.38 (82.00, 97.58)	81.68 (74.87, 88.77)	<0.001*
Nasal inferior, median (IQR), μm	85.28 (77.24, 95.12)	89.38 (82.00, 97.58)	80.98 (74.84, 86.31)	<0.001*
CRAE, median (IQR), μm	120.49 (111.47, 129.46)	124.65 (117.40, 131.00)	112.32 (108.26, 121.11)	<0.001*

Note: *Denotes significance at a P value of <0.05.

Abbreviations: CRVE, central retinal venular equivalent; CRAE, central retinal arteriolar equivalent.

Table 3 The Logistic Regression Analyses Between Retinal Venular Diameters and DKD

Variable	Model 1		Model 2		Model 3
	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
Temporal superior	1.023 (1.015 to 1.031)	<0.001	1.025 (1.016 to 1.033)	<0.001	1.026 (1.016 to 1.036)	<0.001
Temporal inferior	1.037 (1.028 to 1.046)	<0.001	1.038 (1.029 to 1.048)	<0.001	1.034 (1.023 to 1.045)	<0.001
Nasal superior	1.038 (1.027 to 1.050)	<0.001	1.039 (1.028 to 1.051)	<0.001	1.029 (1.016 to 1.042)	<0.001
Nasal inferior	1.030 (1.019 to 1.041)	<0.001	1.030 (1.019 to 1.042)	<0.001	1.024 (1.012 to 1.038)	<0.001
CRVE	1.041 (1.032 to 1.051)	<0.001	1.044 (1.033 to 1.054)	<0.001	1.038 (1.026 to 1.050)	<0.001

Notes: Model 1: Unadjusted. Model 2: Adjusted for duration of T2DM and hypertension. Model 3: Model 2 plus additional adjustments for SBP, DBP, BMI, TG, HDL-C, BUN, Scr and UA.

Table 4 ORs (and 95% CIs) of DKD According to Quartiles of Retinal Venular Diameter Levels^a

Variable	Quartiles of Retinal Venular Diameters, μm				P value for Trend^b
	Quartile 1	Quartile 2	Quartile 3	Quartile 4
Temporal superior	1.00 (reference)	1.772 (0.984 to 3.190)	4.465 (2.504 to 7.961)	3.831 (2.131 to 6.884)	<0.001
Temporal inferior	1.00 (reference)	4.300 (2.342 to 7.894)	5.038 (2.727 to 9.308)	6.936 (3.704 to 12.987)	<0.001
Nasal superior	1.00 (reference)	0.763 (0.416 to 1.399)	3.049 (1.717 to 5.413)	3.240 (1.836 to 5.718)	<0.001
Nasal inferior	1.00 (reference)	1.079 (0.600 to 1.941)	4.200 (2.357 to 7.484)	2.976 (1.690 to 5.242)	<0.001
CRVE	1.00 (reference)	4.031 (2.139 to 7.597)	7.525 (3.960 to 14.299)	8.367 (4.379 to 15.988)	<0.001

Notes: ^aORs and 95% CIs were calculated with the use of binary logistic regression model adjusted for duration of T2DM, hypertension, SBP, DBP, BMI, TG, HDL-C, BUN, Scr and UA. ^bTests for trend were conducted by treating the quartiles as a continuous variable and assigning the median for each quartile.

Figure 2 Restricted cubic splines for the association between retinal venular diameters and DKD. OR of DKD by the diameters of superior temporal retinal venula (A), inferior temporal retinal venula (B), superior nasal retinal venula (C), inferior nasal retinal venula (D) and CRVE (E) with the use of restricted cubic splines. The analysis was adjusted for duration of T2DM, hypertension, SBP, DBP, BMI, TG, HDL-C, BUN, Scr and UA.

Abbreviation: CRVE, central retinal venular equivalent.

Table 5 The Logistic Regression Analyses Between Retinal Arteriolar Diameters and DKD

Variable	Model 1		Model 2		Model 3
	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
Temporal superior	0.969 (0.958 to 0.980)	<0.001	0.971 (0.960 to 0.982)	<0.001	0.984 (0.972 to 0.997)	0.015
Temporal inferior	0.970 (0.960 to 0.981)	<0.001	0.973 (0.962 to 0.984)	<0.001	0.986 (0.974 to 0.999)	0.035
Nasal superior	0.964 (0.952 to 0.976)	<0.001	0.966 (0.954 to 0.979)	<0.001	0.978 (0.964 to 0.993)	0.005
Nasal inferior	0.954 (0.942 to 0.967)	<0.001	0.956 (0.944 to 0.969)	<0.001	0.966 (0.951 to 0.981)	<0.001
CRAE	0.946 (0.933 to 0.959)	<0.001	0.949 (0.935 to 0.962)	<0.001	0.971 (0.956 to 0.986)	<0.001

Notes: Model 1: Unadjusted. Model 2: Adjusted for duration of T2DM and hypertension. Model 3: Model 2 plus additional adjustments for SBP, DBP, BMI, TG, HDL-C, BUN, Scr and UA.

Table 6 ORs (and 95% CIs) of DKD According to Quartiles of Retinal Arteriolar Diameter Levels^a

Variable	Quartiles of Retinal Arteriolar Diameters, μm				P value for Trend^b
	Quartile 1	Quartile 2	Quartile 3	Quartile 4
Temporal superior	1.932 (1.116 to 3.345)	2.347 (1.321 to 4.169)	0.480 (0.258 to 0.892)	1.00 (reference)	<0.001
Temporal inferior	2.142 (1.230 to 3.731)	1.212 (0.668 to 2.202)	0.500 (0.276 to 0.905)	1.00 (reference)	<0.001
Nasal superior	2.260 (1.282 to 3.985)	1.515 (0.853 to 2.692)	0.762 (0.425 to 1.368)	1.00 (reference)	0.001
Nasal inferior	3.310 (1.827 to 5.999)	3.348 (1.849 to 6.061)	1.278 (0.695 to 2.350)	1.00 (reference)	<0.001
CRAE	2.758 (1.565 to 4.860)	1.086 (0.620 to 1.902)	0.305 (0.164 to 0.570)	1.00 (reference)	<0.001

Notes: ^aORs and 95% CIs were calculated with the use of binary logistic regression model adjusted for duration of T2DM, hypertension, SBP, DBP, BMI, TG, HDL-C, BUN, Scr and UA. ^bTests for trend were conducted by treating the quartiles as a continuous variable and assigning the median for each quartile.

Figure 3 Restricted cubic splines for the association between retinal arteriolar diameters and DKD. OR of DKD by the diameters of superior temporal retinal arteriole (A), inferior temporal retinal arteriole (B), superior nasal retinal arteriole (C), inferior nasal retinal arteriole (D) and CRAE (E) with the use of restricted cubic splines. The analysis was adjusted for duration of T2DM, hypertension, SBP, DBP, BMI, TG, HDL-C, BUN, Scr and UA.

Abbreviation: CRAE, central retinal arteriolar equivalent.

Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. doi:10.1016/j.diabres.2021.109119

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