Diabetes mellitus increases the prevalence of anemia in patients with chronic kidney disease: A nested case-control study

Table 1 Demographic, clinical and routine biochemical characteristics of the two study groups (patients with and without diabetes)

Parameter	Diabetic CKD patients	Non-diabetic CKD patients	P
n	184	184	-
Age (yr)	75.91 ± 8.38	76.00 ± 9.54	0.908
Gender n (%)
Female	88 (47.8)	88 (47.8)	1
Male	96 (52.2)	96 (52.2)
Weight (kg)	79.78 ± 14.51	78.51 ± 12.58	0.373
Height (m)	1.67 ± 0.09	1.66 ± 0.08	0.121
BMI (kg/m2)	28.34 ± 4.16	28.33 ± 3.26	0.979
Urea Nitrogen (mmol/L)	10.95 ± 5.06	10.90 ± 4.82	0.927
Creatinine (μmol/L)	136.14 ± 45.97	134.37 ± 46.85	0.826
eGFR (mL/min per 1.73 m2)	43.3 ± 14.8	43.7 ± 14.9	0.778
Glucose (mmol/L)	8.61 ± 2.74	5.46 ± 0.61	< 0.001
24 h urine protein excretion (mg)	527 (59-9, 300)	320 (65-3, 100)	< 0.001
CKD Stages n (%)
Stage 2	26 (14.1)	26 (14.1)	1
Stage 3a	53 (28.8)	53 (28.8)
Stage 3b	74 (40.2)	74 (40.2)
Stage 4	31 (16.8)	31 (16.8)
Hypertension n (%)	171 (92.9)	175 (95.1)	0.379
Dyslipidemia n (%)	103 (56)	86 (46.7)	0.076
Coronary heart disease n (%)	65 (35.3)	60 (32.6)	0.582
Heart failure n (%)	30 (16.3)	34 (18.5)	0.583
Arrhythmia n (%)	20 (10.9)	25 (13.6)	0.426
Stroke history n (%)	16 (8.7)	1 (0.5)	< 0.001
Peripheral vascular disease n (%)	17 (9.2)	13 (7.1)	0.446
Smoking n (%)	73 (39.7)	31 (16.8)	< 0.001

CKD: Chronic kidney disease; eGFR: Estimated glomerular filtration rate.

Table 2 Comparisons between the two study groups for anemia-related parameters in total study population and by chronic kidney disease stages (statistically significant P values are indicated in bold)

Parameter	Total studypopulation	P	Stage 2	P	Stage 3	P	Stage 3a	P	Stage 3b	P	Stage 4	P
Hematocrit (%)
Diabetics	39.02 ± 4.30	0.015	42.27 ± 4.79	0.324	38.69 ± 3.97	0.001	38.92 ± 4.08	< 0.001	38.53 ± 3.91	0.278	37.63 ± 4.02	0.687
Non-diabetics	40.07 ± 4		41.18 ± 2.83		40.34 ± 4.09		41.93 ± 4.10		39.21 ± 3.71		38.04 ± 3.9
Hemoglobin (g/L)
Diabetics	128.7 ± 15.6	0.036	141.8 ± 17.4	0.21	127.4 ± 14.1	0.003	128.2 ± 14.8	0.001	126.9 ± 13.6	0.383	122.7 ± 14.1	0.58
Non-diabetics	131.9 ± 14.0		136.7 ± 10.9		132.7 ± 14.1		138.2 ± 14.0		128.8 ± 13.0		124.7 ± 13.5
MCV (fL)
Diabetics	87.62 ± 6.99	0.739	87.76 ± 74.2	0.536	87.70 ± 7.49	0.633	87.78 ± 5.88	0.81	87.65 ± 8.5	0.457	87.11 ± 6.86	0.527
Non-diabetics	87.9 ± 6.99		86 ± 13.7		88.20 ± 8.83		87.45 ± 8.34		88.73 ± 9.17		88.29 ± 7.68
MCH (pg/cell)
Diabetics	29.91 ± 5.08	0.748	29.53 ± 2.21	0.684	30.28 ± 5.89	0.494	29.52 ± 2.24	0.792	30.82 ± 7.45	0.526	28.76 ± 2.42	0.415
Non-diabetics	29.78 ± 2.64		29.83 ± 3		29.89 ± 2.55		29.4 ± 2.75		30.25 ± 2.35		29.3 ± 2.73
MCHC (g/L)
Diabetics	323.8 ± 17.6	0.523	333.6 ± 12.0	0.03	321.6 ± 19.0	0.362	323.0 ± 21.7	0.982	320.6 ± 16.9	0.174	324.8 ± 11.6	0.282
Non-diabetics	322.6 ± 20.1		319.5 ± 29.5		323.7 ± 18.4		322.9 ± 20.9		324.3 ± 16.4		320.3 ± 19.7
Serum iron (μmol/L)
Diabetics	12.35	0.783	2.75	0.027	12.17	0.351	12.71	0.86	11.01	0.194	10.92	0.559
	(1.61-35.73)		(1.09-4.23)		(1.61-35.73)		(1.61-28.28)		(2.15-35.73)		(3.83-20.23)
Non-diabetics	12.53		2.21		12.53		12.35		12.71		11.99
	(2.69-27.03)		(0.38-4.13)		(2.69-27.03)		(4.47-23.27)		(2.69-27.03)		(3.94-23.81)
Ferritin (ng/mL)
Diabetics	200	< 0.001	230.3	0.01	175.3	0.003	175.3	0.013	175.3	0.061	220.2	0.011
	(17.3-1048.7)		(62.9-570.7)		(17.3-1048.7)		(23.4-1048.7)		(7.7-1015.6)		(25.6-867.3)
Non-diabetics	148.3		155.1		148.3		155.1		143.8		143.8
	(7.2-993.2)		(78.6-435.9)		(22.5-993.2)		(22.5-294.4)		(26.9-993.2)		(7.2-441.4)
24 h urine protein Excretion (mg)
Diabetics	527	< 0.001	283	0.126	530	< 0.001	545	< 0.001	525	< 0.001	670	0.647
	(59-9300)		(68-5100)		(59-9300)		(129-1700)		(59-9300)		(95-3800)
Non-diabetics	320		245		300		250		375		560
	(65-3100)		(110-780)		(65-3100)		(65-1500)		(104-3100)		(117-3100)
Smoking (n, %)
Diabetics	73 (39.7)	< 0.001	10 (38.5)	0.375	57 (44.9)	< 0.001	32 (60.4)	0.011	25 (33.8)	< 0.001	6 (19.4)	0.255
Non-diabetics	31 (16.8)		7 (26.9)		22 (17.3)		19 (35.8)		3 (4.1)		2 (6.5)
Use of erythropoietin (n, %)
Diabetics	15 (8.2)	0.851	0 (0)	n/a	9 (7.1)	0.271	4 (7.5)	0.118	5 (6.8)	1	6 (80.6)	0.155
Non-diabetics	16 (8.7)		0 (0)		5 (3.9)		0 (0)		5 (6.8)		11 (35.5)
Iron supplements therapy (n, %)
Diabetics	27 (14.7)	0.152	1 (3.8)	1	19 (15)	0.076	8 (15.1)	0.111	11 (14.9)	0.314	7 (22.6)	1
Non-diabetics	18 (9.8)		1 (3.8)		10 (7.9)		3 (5.7)		7 (9.5)		7 (22.6)
ACEIs/ARBs (n, %)
Diabetics	121 (65.8)	0.372	22 (84.6)	1	88 (69.3)	0.784	38 (71.7)	0.831	50 (67.6)	0.592	11 (35.5)	0.075
Non-diabetics	129 (70.1)		21 (80.8)		90 (70.9)		37 (69.8)		53 (71.6)		18 (58.1)
Antiplatelet/anticoagulant drugs (n, %)
Diabetics	86 (46.7)	0.034	9 (34.6)	0.199	62 (48.8)	0.165	27 (50.9)	0.171	35 (47.3)	0.508	15 (48.4)	0.303
Non-diabetics	66 (35.9)		4 (15.4)		51 (40.2)		20 (37.7)		31 (41.9)		11 (35.5)

ACEI: Angiotensin-converting enzyme inhibitors; ARB: Angiotensin receptor blocker; CKD: Chronic kidney disease; MCH: Mean corpuscular hemoglobin; MCV: Mean corpuscular volume; n/a: Not applicable.

Table 3 Univariate and multivariate regression analysis for occurrence of anemia (defined as serum hemoglobin levels < 130 g/L for men and < 120 g/L for women and/or use of recombinant erythropoietin) in the total studied population

Parameter	Univariate analysis		Multivariate analysis
	Unadjusted odds ratio (95%CI)	P	Adjusted odds ratio (95%CI)	P
ΒΜΙ Groups
Normal (18.5-25)	Reference group
Underweight (< 18.5)	0.545 (0.046-6.443)	0.63
Overweight (25-30)	0.714 (0.377-1.350)	0.3
Obese (> 30)	0.708 (0.348-1.442)	0.342
Age
< 75 yr	Reference group		Reference group
≥ 75 yr	1.623 (1.028-2.564)	0.038	1.198 (0.694-2.069)	0.517
Gender
Male	Reference group		Reference group
Female	0.546 (0.357-0.833)	0.005	0.389 (0.224-0.675)	0.001
CKD Stages
Stage 2	Reference group		Reference group
Stage 3a	7.207 (2.656-19.566)	< 0.001	6.068 (2.112-17.430)	0.001
Stage 3b	7.162 (2.694-19.038)	< 0.001	7.499 (2.604-21.597)	< 0.001
Stage 4	11.414 (3.999-32.582)	< 0.001	12.169 (3.783-39.147)	< 0.001
Diabetes	1.848 (1.212-2.818)	0.004	2.206 (1.196-4.069)	0.011
Hypertension	0.663 (0.280-1.573)	0.351
Dyslipidemia	0.745 (0.491-1.130)	0.166	0.659 (0.404-1.074)	0.094
Coronary heart disease	1.446 (0.934-2.239)	0.098	1.048 (0.506-1.960)	0.883
Heart failure	1.725 (1.003-2.967)	0.049	1.228 (0.628-2.398)	0.548
Arrhythmia	0.788 (0.412-1.509)	0.472
Smoking	1.051 (0.662-1.667)	0.834
Serum glucose levels (per mg/dL increase)	1.006 (1.002 to 1.011)	0.009	0.999 (0.992-1.005)	0.736
Serum iron (per mg/dL increase)	0.978 (0.970-0.986)	< 0.001	0.976 (0.968-0.985)	< 0.001
Ferritin (per ng/mL increase)	0.998 (0.995-1.001)	0.209
24 h urine protein excretion (per mg increase)	1.000 (1.000-1.003)	0.146	1.000 (1.000-1.001)	0.772
ACEIs/ARBs	0.690 (0.443-1.075)	0.101	0.963 (0.565-1.641)	0.888
Antiplatelet/anticoagulant drugs	1.413 (0.927-2.156)	0.108	1.161 (0.669-2.015)	0.595

ACEI: Angiotensin-converting enzyme inhibitors; ARB: Angiotensin receptor blocker; CKD: Chronic kidney disease; BMI: Body mass index.