Serum alpha-1-microglobulin as a predictor of multiple complications in type 2 diabetes mellitus patients

Table 1 Baseline characteristics of participants by quartiles, n (%)

Characteristic	Overall (n = 5045)	Q1 (n = 1262)	Q2 (n = 1265)	Q3 (n = 1258)	Q4 (n = 1260)	P value
Sex (male)	2855 (56.59)	602 (47.70)	751 (59.37)	720 (57.23)	782 (62.06)	< 0.001
Age (year)	55.00 (46.00, 64.00)	52.00 (42.25, 61.00)	54.00 (45.00, 63.00)	55.00 (46.25, 64.00)	57.00 (50.00, 67.00)	< 0.001
Smoking	1861 (36.89)	368 (29.16)	491 (38.81)	477 (37.92)	525 (41.67)	< 0.001
Alcohol consumption	1763 (34.95)	372 (29.48)	466 (36.84)	448 (35.61)	477 (37.86)	< 0.001
SBP (mmHg)	129.00 (117.00, 141.00)	125.00 (113.00, 137.00)	128.00 (116.00, 138.00)	130.00 (118.00, 142.00)	134.00 (120.00, 149.00)	< 0.001
DBP (mmHg)	80.00 (72.00, 89.00)	79.00 (71.00, 87.00)	80.00 (72.00, 88.00)	80.00 (72.00, 89.75)	81.00 (73.00, 90.00)	< 0.001
Hypertension	3368 (66.76)	663 (52.54)	802 (63.40)	874 (69.48)	1029 (81.67)	< 0.001
Hyperlipidaemia	3173 (62.89)	709 (56.18)	837 (66.17)	825 (65.58)	802 (63.65)	< 0.001
CHD	1538 (30.49)	322 (25.52)	370 (29.25)	387 (30.76)	459 (36.43)	< 0.001
BMI (kg/m2)	24.39 (22.04, 26.67)	23.76 (21.30, 26.05)	24.46 (22.21, 26.70)	24.65 (22.34, 27.05)	24.56 (22.48, 26.95)	< 0.001
FBG (mmol/L)	7.77 (6.12, 10.04)	7.22 (5.61, 9.50)	7.75 (6.13, 9.83)	7.94 (6.24, 10.40)	8.15 (6.47, 10.39)	< 0.001
HbA1c (%)	7.65 (6.40, 9.35)	7.15 (6.10, 9.00)	7.50 (6.40, 9.10)	7.75 (6.50, 9.40)	8.15 (6.85, 9.70)	< 0.001
TC (mmol/L)	4.53 (3.83, 5.28)	4.50 (3.79, 5.22)	4.54 (3.83, 5.28)	4.55 (3.88, 5.25)	4.52 (3.81, 5.38)	0.247
LDL-C (mmol/L)	2.79 (2.32, 3.31)	2.74 (2.27, 3.24)	2.81 (2.34, 3.35)	2.82 (2.36, 3.30)	2.81 (2.30, 3.37)	0.052
TG (mmol/L)	1.55 (1.10, 2.29)	1.27 (0.91, 1.89)	1.54 (1.11, 2.26)	1.62 (1.18, 2.41)	1.81 (1.29, 2.59)	< 0.001
HDL-C (mmol/L)	1.12 (0.95, 1.32)	1.19 (1.00, 1.41)	1.12 (0.95, 1.31)	1.10 (0.95, 1.27)	1.08 (0.92, 1.27)	< 0.001
WBC (109/L)	6.32 (5.29, 7.54)	5.86 (4.85, 7.13)	6.22 (5.23, 7.37)	6.37 (5.40, 7.54)	6.80 (5.71, 8.08)	< 0.001
CRP (mg/L)	2.92 (1.19, 9.94)	2.35 (0.99, 6.94)	2.35 (1.07, 7.21)	2.97 (1.20, 9.56)	4.38 (1.68, 18.99)	< 0.001
AST (IU/L)	21.40 (17.95, 26.60)	22.00 (18.20, 27.15)	21.80 (18.20, 26.85)	21.40 (18.00, 27.09)	20.55 (17.20, 25.06)	< 0.001
ALT (IU/L)	20.30 (15.00, 29.25)	20.85 (15.22, 30.70)	21.50 (16.00, 30.20)	20.70 (15.40, 30.58)	18.40 (13.70, 26.33)	< 0.001
UA (μmol/L)	332.50 (275.00, 399.50)	297.00 (248.39, 353.08)	324.00 (268.00, 379.50)	335.00 (282.00, 393.00)	386.00 (320.75, 455.25)	< 0.001
eGFR (mL/minute/1.73 m2)	96.31 (78.33, 109.40)	105.94 (95.44, 117.22)	101.10 (91.13, 112.08)	95.30 (81.28, 107.61)	65.27 (41.86, 89.28)	< 0.001
LVEF (%)	64.00 (60.00, 67.00)	64.00 (61.00, 68.00)	64.00 (60.00, 67.00)	64.00 (60.00, 67.00)	63.00 (59.00, 67.00)	< 0.001
Antihypertensive drugs	1040 (20.61)	196 (15.53)	245 (19.37)	282 (22.42)	317 (25.16)	< 0.001
Lipid-lowering drugs	1264 (25.05)	285 (22.58)	304 (24.03)	345 (27.42)	330 (26.19)	0.024
Antidiabetic drugs	1389 (27.53)	321 (25.44)	332 (26.25)	374 (29.73)	362 (28.73)	0.051
DN	1997 (39.58)	282 (22.35)	362 (28.62)	478 (38.00)	875 (69.44)	< 0.001
DR	1772 (35.12)	331 (26.23)	391 (30.91)	447 (35.53)	603 (47.86)	< 0.001
DPN	3351 (66.42)	727 (57.61)	808 (63.87)	839 (66.69)	977 (77.54)	< 0.001
LVH	1685 (33.40)	355 (28.13)	359 (28.38)	416 (33.07)	555 (44.05)	< 0.001
α1-MG (mg/L)	26.10 (21.61, 33.10)	19.02 (17.10, 20.49)	23.80 (22.70, 25.00)	29.13 (27.50, 30.86)	40.87 (36.26, 50.80)	-

Values are presented as median and interquartile range [25%, 75%].

SBP: Systolic blood pressure; DBP: Diastolic blood pressure; CHD: Coronary heart disease; BMI: Body mass index; FBG: Fasting blood glucose; HbA1c: Glycated haemoglobin; TC: Total cholesterol; LDL-C: Low-density lipoprotein cholesterol; TG: Triglycerides; HDL-C: High-density lipoprotein cholesterol; WBC: White blood cell; CRP: C-reactive protein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; UA: Uric acid; eGFR: Estimated glomerular filtration rate; LVEF: Left ventricular ejection fraction; DN: Diabetic nephropathy; DR: Diabetic retinopathy; DPN: Diabetic peripheral neuropathy; LVH: Left ventricular hypertrophy; α1-MG: Alpha-1-microglobulin.

Table 2 The associations between serum alpha-1-microglobulin level and the risk of complications occurrence in type 2 diabetes mellitus patients

Complications		Model 1		Model 2		Model 3
		OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
DN	Continuous (per SD)	3.31 (2.99, 3.67)	< 0.001	2.89 (2.60, 3.21)	< 0.001	1.84 (1.62, 2.10)	< 0.001
	Quartiles (Q1-Q4)
	Q1	Reference		Reference		Reference
	Q2	1.39 (1.16, 1.67)	< 0.001	1.17 (0.97, 1.41)	0.108	1.08 (0.88, 1.31)	0.470
	Q3	2.13 (1.79, 2.54)	< 0.001	1.72 (1.43, 2.07)	< 0.001	1.28 (1.05, 1.56)	0.014
	Q4	7.90 (6.61, 9.46)	< 0.001	5.90 (4.88, 7.15)	< 0.001	2.47 (1.96, 3.12)	< 0.001
	P for trend	< 0.001		< 0.001		< 0.001
DR	Continuous (per SD)	1.40 (1.32, 1.49)	< 0.001	1.32 (1.24, 1.41)	< 0.001	1.17 (1.07, 1.28)	< 0.001
	Quartiles (Q1-Q4)
	Q1	Reference		Reference		Reference
	Q2	1.26 (1.06, 1.50)	0.009	1.11 (0.93, 1.33)	0.247	1.11 (0.92, 1.33)	0.287
	Q3	1.55 (1.31, 1.84)	< 0.001	1.33 (1.11, 1.59)	0.002	1.23 (1.02, 1.49)	0.031
	Q4	2.58 (2.19, 3.05)	< 0.001	2.08 (1.74, 2.49)	< 0.001	1.61 (1.29, 2.01)	< 0.001
	P for trend	< 0.001		< 0.001		< 0.001
DPN	Continuous (per SD)	1.41 (1.31, 1.53)	< 0.001	1.21 (1.12, 1.30)	< 0.001	1.14 (1.03, 1.27)	0.014
	Quartiles (Q1-Q4)
	Q1	Reference		Reference		Reference
	Q2	1.30 (1.11, 1.53)	0.001	1.02 (0.85, 1.22)	0.835	1.01 (0.83, 1.22)	0.956
	Q3	1.47 (1.25, 1.73)	< 0.001	1.09 (0.91, 1.31)	0.339	0.98 (0.79, 1.20)	0.812
	Q4	2.54 (2.14, 3.02)	< 0.001	1.64 (1.36, 1.90)	< 0.001	1.44 (1.11, 1.87)	0.005
	P for trend	< 0.001		< 0.001		0.043
LVH	Continuous (per SD)	1.38 (1.30, 1.47)	< 0.001	1.35 (1.26, 1.44)	< 0.001	1.28 (1.18, 1.38)	< 0.001
	Quartiles (Q1-Q4)
	Q1	Reference		Reference		Reference
	Q2	1.01 (0.85, 1.20)	0.889	1.06 (0.88, 1.29)	0.522	0.98 (0.81, 1.19)	0.863
	Q3	1.26 (1.07, 1.50)	0.007	1.21 (1.01, 1.47)	0.043	1.08 (0.89, 1.31)	0.459
	Q4	2.01 (1.71, 2.37)	< 0.001	1.90 (1.58, 2.30)	< 0.001	1.48 (1.18, 1.84)	< 0.001
	P for trend	< 0.001		< 0.001		0.001

Model 1: Unadjusted; Model 2: Adjusted for age, sex, body mass index (BMI), smoking, drinking, systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension, hyperlipidaemia, and coronary heart disease (CHD); Model 3: Adjusted for age, sex, BMI, smoking, alcohol consumption, SBP, DBP, hypertension, hyperlipidaemia, CHD, antihypertensive drugs, lipid-lowering drugs, antidiabetic drugs, fasting blood glucose, glycated haemoglobin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, uric acid, estimated glomerular filtration rate, alanine aminotransferase, aspartate aminotransferase, white blood cell, C-reactive protein, and left ventricular ejection fraction. DN: Diabetic nephropathy; DR: Diabetic retinopathy; DPN: Diabetic peripheral neuropathy; LVH: Left ventricular hypertrophy.

Table 3 Subgroup analysis of the relationship between serum alpha-1-microglobulin level and complications risk in type 2 diabetes mellitus patients

	DN (95%CI)	P value	P for interaction	DR (95%CI)	P value	P for interaction	DPN (95%CI)	P value	P for interaction	LVH (95%CI)	P value	P for interaction
Age			0.017			0.392			0.978			0.887
< 60	1.80 (1.54, 2.12)	< 0.001		1.12 (1.01, 1.25)	0.039		1.04 (0.92, 1.18)	0.524		1.28 (1.16, 1.41)	< 0.001
≥ 60	1.98 (1.58, 2.48)	< 0.001		1.22 (1.04, 1.42)	0.011		1.16 (0.94, 1.43)	0.177		1.28 (1.09, 1.49)	0.002
Sex			0.335			0.059			0.379			0.004
Male	1.76 (1.48, 2.08)	< 0.001		1.09 (0.98, 1.22)	0.114		1.09 (0.95, 1.25)	0.213		1.30 (1.15, 1.47)	< 0.001
Female	1.97 (1.59, 2.44)	< 0.001		1.31 (1.13, 1.53)	< 0.001		1.18 (0.99, 1.40)	0.059		1.11 (0.98, 1.25)	0.102
BMI			0.598			0.867			0.549			0.352
< 25	1.83 (1.54, 2.18)	< 0.001		1.15 (1.02, 1.29)	0.027		1.07 (0.93, 1.23)	0.342		1.20 (1.06, 1.36)	0.004
≥ 25	1.85 (1.51, 2.25)	< 0.001		1.20 (1.05, 1.37)	0.007		1.20 (1.02, 1.42)	0.028		1.29 (1.15, 1.46)	< 0.001
Hypertension			0.003			0.060			0.707			0.464
Yes	2.00 (1.71, 2.35)	< 0.001		1.15 (1.05, 1.27)	0.003		1.15 (1.01, 1.30)	0.033		1.29 (1.19, 1.41)	< 0.001
No	1.48 (1.16, 1.89)	0.001		1.29 (1.02, 1.64)	0.033		1.06 (0.83, 1.34)	0.637		1.10 (0.86, 1.42)	0.433
Hyperlipidaemia			0.564			0.270			0.360			0.575
Yes	1.91 (1.61, 2.25)	< 0.001		1.23 (1.10, 1.38)	< 0.001		1.15 (1.00, 1.32)	0.053		1.25 (1.12, 1.38)	< 0.001
No	1.79 (1.44, 2.22)	< 0.001		1.06 (0.92, 1.23)	0.426		1.13 (0.96, 1.34)	0.149		1.21 (1.05, 1.39)	0.010
CHD			0.169			< 0.001			0.690			0.954
Yes	1.61 (1.24, 2.10)	< 0.001		1.06 (0.92, 1.22)	0.460		1.01 (0.82, 1.24)	0.944		1.23 (1.05, 1.43)	0.008
No	1.91 (1.64, 2.22)	< 0.001		1.26 (1.13, 1.41)	< 0.001		1.19 (1.05, 1.35)	0.007		1.31 (1.19, 1.45)	< 0.001

Stratified by age, sex, body mass index (BMI), hypertension, hyperlipidaemia, and coronary heart disease (CHD). Adjusted for age, sex, BMI, smoking, alcohol consumption, systolic blood pressure, diastolic blood pressure, hypertension, hyperlipidaemia, CHD, antihypertensive drugs, lipid-lowering drugs, antidiabetic drugs, fasting blood glucose, glycated haemoglobin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, uric acid, estimated glomerular filtration rate, alanine aminotransferase, aspartate aminotransferase, white blood cell, C-reactive protein, and left ventricular ejection fraction. DN: Diabetic nephropathy; DR: Diabetic retinopathy; DPN: Diabetic peripheral neuropathy; LVH: Left ventricular hypertrophy; BMI: Body mass index; CHD: Coronary heart disease.