Association Between Serum Albumin Level and Microvascular Complications of Type 2 Diabetes Mellitus

Figures & data

Table 1 Baseline Patient Characteristics Based on sALB Tertiles

	Overall (n=951)	Q1 (n=325)	Q2 (n=320)	Q3 (n=306)	P
Age (years)	57.00(48.00–66.00)	61.00(52.00–68.00)	57.00(48.00–66.00)	53.00(44.75–60.00)	<0.001
Sex [male, n (%)]	566(59.52)	157(48.31)	191(59.69)	218(71.24)	<0.001
Duration of diabetes (years)	6.00(1.00–11.00)	10.00(2.00–15.00)	5.00(1.00–10.00)	4.00(1.00–9.25)	<0.001
BMI (kg/m^2)	24.17(21.83–26.70)	23.33(20.31–25.72)	24.40(21.63–27.11)	24.84(22.67–27.43)	<0.001
SBP (mmHg)	132.00(120.00–145.00)	136.00(122.00–149.50)	130.00(118.00–142.00)	129.00(118.00–142.00)	<0.001
DBP (mmHg)	76.00(68.00–84.00)	74.00(67.00–82.50)	75.00(67.00–83.00)	78.00(71.00–86.25)	<0.001
FPG (mmol/L)	7.66(5.88–10.41)	7.64(5.82–10.13)	7.69 (5.92–10.55)	7.66(5.90–10.62)	0.741
HbA1c (%)	8.30(6.80–10.40)	8.60(7.00–10.60)	8.30(7.00–10.50)	8.10(6.50–9.95)	0.006
TC (mmol/L)	4.59(3.88–5.34)	4.51(3.73–5.28)	4.51(3.86–5.32)	4.72(4.04–5.54)	0.017
TG (mmol/L)	1.47(1.02–2.33)	1.24(0.92–1.91)	1.59(1.05–2.35)	1.73(1.11–2.84)	<0.001
LDL-C (mmol/L)	2.57(1.97–3.18)	2.49(1.88–3.19)	2.54 (1.97–3.13)	2.68(2.05–3.26)	0.241
HDL-C (mmol/L)	1.07(0.91–1.31)	1.10(0.92–1.36)	1.05(0.89–1.26)	1.08(0.91–1.29)	0.090
ALT (U/L)	18.60(13.00–26.30)	15.80(11.05–22.85)	18.00(13.38–26.08)	21.00(15.00–30.00)	<0.001
AST (U/L)	19.00(15.00–24.70)	18.30(14.50–23.30)	18.40(15.00–25.00)	20.00(16.00–25.05)	0.006
SUA (μmol/L)	323.10(264.00–390.73)	326.20(253.60–391.10)	314.30(256.15–382.45)	330.00(276.05–398.00)	0.225
UACR [≥30 mg/g, n (%)]	306(32.18)	158(48.62)	84(26.25)	64(20.92)	<0.001
Microalbuminuria [30≤ UACR ≤300 mg/g, n (%)]	204(21.45)	84(25.85)	66(20.63)	54(17.65)	0.039
Macroalbuminuria [UACR >300 mg/g, n (%)]	102(10.73)	74(22.77)	18(5.63)	10(3.27)	<0.001
eGFR (mL/min/1.73 m^2)	97.17(77.05–112.06)	91.22(61.56–106.72)	99.29(82.66–112.46)	102.89(87.14–116.38)	<0.001
DR, n (%)	442(46.48)	174(53.54)	146(45.63)	122 (39.87)	0.003
DKD, n (%)	334(35.12)	171(52.62)	95(29.69)	68(22.22)	<0.001
Treatment of diabetes
Oral drugs, n (%)	881(92.64)	291(89.54)	302(94.38)	288(94.12)	0.031
Insulin, n (%)	344(36.17)	162(49.85)	107(33.44)	75(24.51)	<0.001

Notes: Data for continuous variables are presented as median and interquartile range, categorical variables are presented as percentages. Tertiles of serum albumin were ≤39.3 g/L, 39.4–42.4 g/L and >42.4 g/L.

Abbreviations: sALB, serum albumin; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; TC, total cholesterol; TG, triglyceride; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; ALT, alanine transaminase; AST, aspartate aminotransferase; SUA, serum uric acid; UACR, urine albumin-creatinine ratio; eGFR, estimated glomerular filtration rate; DR, diabetic retinopathy; DKD, diabetic kidney disease.

Figure 1 Relationships of sALB level with the prevalences of DR, DKD and macroalbuminuria. (A): Prevalences of DR, DKD and macroalbuminuria. Using the chi-square test. *P < 0.05 compared with Q1, ^#P < 0.05 compared with Q2. (B): sALB levels in patients with diabetes, with or without DR or DKD. Using the Kruskal–Wallis test, data are presented as medians with interquartile range. *P < 0.05 compared with G1, ^†P < 0.05 compared with G2, ^‡P < 0.05 compared with G3.

Abbreviations: DR, diabetic retinopathy; DKD, diabetic kidney disease; G1, patients without DR or DKD; G2, patients with DR alone; G3, patients with DKD alone; G4, patients with both DR and DKD; sALB, serum albumin.

Table 2 Association Between sALB and Risk Factors Related to Microvascular Disease in Study Subjects

Variable	r	P-value	Adjusted r	Adjusted P-value
Age	−0.259	<0.001	-	-
Sex	−0.193	<0.001	-	-
Diabetes duration	−0.201	<0.001	-	-
BMI	0.160	<0.001	-	-
SBP	−0.150	<0.001	−0.128	<0.001
DBP	0.104	0.001	−0.008	0.800
FPG	0.037	0.250	−0.002	0.961
HbA1c	−0.083	0.010	−0.102	0.002
TC	0.085	0.009	0.015	0.645
TG	0.190	<0.001	0.076	0.020
LDL-C	0.050	0.130	−0.022	0.502
HDL-C	−0.042	0.202	0.034	0.302
ALT	0.224	<0.001	0.113	0.001
AST	0.098	0.003	0.046	0.160
SUA	0.011	0.732	−0.069	0.035
UACR	−0.323	<0.001	−0.386	<0.001
eGFR	0.259	<0.001	0.275	<0.001
DR	−0.131	<0.001	−0.138	<0.001
DKD	−0.306	<0.001	−0.287	<0.001

Notes: Men were defined as 0 and females were defined as 1. Participants without DKD or DR were defined as 0 and those with DKD or DR as 1.

Abbreviations: sALB, serum albumin; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; TC, total cholesterol; TG, triglyceride; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; ALT, alanine transaminase; AST, aspartate aminotransferase; SUA, serum uric acid; UACR, urine albumin-creatinine ratio; eGFR, estimated glomerular filtration rate; DR, diabetic retinopathy; DKD, diabetic kidney disease.

Table 3 Associations Between sALB Tertiles and Microvascular Disease in Study Subject

	DR Odds Ratio (95% CI)	P	DKD Odds Ratio (95% CI)	P	Macroalbuminuria Odds Ratio (95% CI)	P
Model 1
Q1(≤39.3 g/L)	1.74(1.27–2.38)	0.001	3.89(2.75–5.50)	<0.001	8.73(4.42–17.25)	<0.001
Q2(39.4–42.4 g/L)	1.27(0.92–1.74)	0.146	1.48(1.03–2.12)	0.034	1.76(0.80–3.89)	0.159
Q3(>42.4 g/L)	1.00(Reference)		1.00(Reference)		1.00(Reference)
Model 2
Q1(≤39.3 g/L)	1.80(1.29–2.49)	<0.001	3.43(2.40–4.91)	<0.001	9.55(4.73–19.28)	<0.001
Q2(39.4–42.4 g/L)	1.29(0.93–1.77)	0.124	1.38(0.95–1.98)	0.088	1.83(0.83–4.05)	0.136
Q3(>42.4 g/L)	1.00(Reference)		1.00(Reference)		1.00(Reference)
Model 3
Q1(≤39.3 g/L)	1.59(1.12–2.26)	0.010	3.00(2.04–4.41)	<0.001	9.76(4.62–20.63)	<0.001
Q2(39.4–42.4 g/L)	1.30(0.93–1.82)	0.130	1.29(0.88–1.90)	0.194	2.05(0.90–4.67)	0.086
Q3(>42.4 g/L)	1.00(Reference)		1.00(Reference)		1.00(Reference)

Notes: Data are odds ratio (95% CI) from logistic regression model. Model 1 was no adjustment of covariates. Model 2 was adjusted for age and sex. Model 3 was adjusted for age, sex, diabetes duration, BMI, FPG, HbA1c, TC, TG, and treatment of diabetes.

Abbreviations: sALB, serum albumin; DR, diabetic retinopathy; DKD, diabetic kidney disease; CI, confidence interval.

Table 4 Subgroup Analysis of Association Between sALB Tertiles and Microvascular Complication Stratified by Sex and Age

	Subgroup	sALB	DR Odds Ratio (95% CI)	P	DKD Odds Ratio (95% CI)	P
Sex
	Male	Q1(≤39.3 g/L)	1.60(1.00–2.56)	0.049	3.78(2.26–6.32)	<0.001
	(n=566)	Q2(39.4–42.4 g/L)	1.29(0.85–1.96)	0.227	1.25(0.77–2.03)	0.370
		Q3(>42.4 g/L)	1.00(Reference)		1.00(Reference)
	Female	Q1(≤39.3 g/L)	1.51(0.86–2.68)	0.155	2.35(1.26–4.35)	0.007
	(n=385)	Q2(39.4–42.4 g/L)	1.24(0.69–2.23)	0.473	1.29(0.67–2.48)	0.440
		Q3(>42.4 g/L)	1.00(Reference)		1.00(Reference)
Age
	<65years	Q1(≤39.3 g/L)	1.74(1.14–2.65)	0.010	3.46(2.16–5.53)	<0.001
	(n=691)	Q2(39.4–42.4 g/L)	1.28(0.87–1.88)	0.204	1.45(0.92–2.29)	0.110
		Q3(>42.4 g/L)	1.00(Reference)		1.00(Reference)
	≥65 years	Q1(≤39.3 g/L)	1.25(0.61–2.56)	0.543	1.86(0.90–3.86)	0.094
	(n=260)	Q2(39.4–42.4 g/L)	1.36(0.65–2.89)	0.416	0.81(0.38–1.74)	0.592
		Q3(>42.4 g/L)	1.00(Reference)		1.00(Reference)

Abbreviations: sALB, serum albumin; DR, diabetic retinopathy; DKD, diabetic kidney disease; CI, confidence interval.