Characteristics of hospitalized patients with COVID-19
A total of 1277 COVID-19-associated hospitalized adults from Wuhan city were included. Among the 1277 hospitalized adults, the median age was 63 years, (interquartile range [IQR], 51–70) (Table 1). 9.4% of COVID-19 patients were diagnosed with severe pneumonia and 48% were males. There were 675 patients with T2DM and 602 patients with no T2DM. 8.5% and 10.2% severe pneumonia were diagnosed in non-T2DM and T2DM patients respectively (Table 1).
Table 1
characteristics of patients grouped by T2DM
Variables
|
Total
(n = 1277)
|
Non-T2DM
(n = 602)
|
T2DM
(n = 675)
|
p
|
Age
|
63 (51, 70)
|
66 (55, 72)
|
61 (47.5, 68)
|
< 0.001
|
Males
|
609 (48)
|
281 (47)
|
328 (49)
|
0.53
|
Severe pneumonia, n (%)
|
120 (9.4)
|
51 (8.5)
|
69 (10.2)
|
0.285
|
CysC baseline, mg/L
|
0.93 (0.77, 1.14)
|
0.96 (0.79, 1.19)
|
0.9 (0.74, 1.12)
|
< 0.001
|
LgBNP, pg/mL
|
1.29 (0.53, 1.71)
|
1.4 (0.77, 1.8)
|
1.21 (0.38, 1.66)
|
< 0.001
|
Lymph_baseline, 109/L
|
1.15 (0.82, 1.6)
|
1.19 (0.86, 1.62)
|
1.1 (0.8, 1.57)
|
0.044
|
Neutrop_baseline, 109/L
|
3.24 (2.39, 4.51)
|
3.37 (2.54, 4.64)
|
3.1 (2.25, 4.41)
|
0.001
|
NLR baseline
|
2.75 (1.80, 4.43)
|
2.50 (1.69,3.69)
|
3.60 (2.34, 6.05)
|
< 0.001
|
PCT_baseline, ug/L
|
0.03 (0.03, 0.05)
|
0.03 (0.03, 0.04)
|
0.03 (0.03, 0.05)
|
0.884
|
ALT_baseline, units/L
|
24 (16, 37)
|
22 (15, 35)
|
26 (16, 39)
|
0.003
|
AST baseline, units/L
|
26 (20, 37)
|
25 (19, 34)
|
27 (21, 39)
|
0.034
|
ALB_baseline, g/L
|
37.42 ± 5.07
|
37.47 ± 5.13
|
37.38 ± 5.02
|
0.765
|
Glu_baseline, mmol/L
|
5.47 (4.73, 6.92)
|
5.25 (4.65, 6.58)
|
5.68 (4.86, 7.2)
|
< 0.001
|
Cre_baseline, umol/L
|
63 (51.3, 78.2)
|
60.7 (50, 78.4)
|
64.7 (52.42, 78.05)
|
0.09
|
ALP_baseline, units/L
|
60 (49, 75)
|
63 (51, 78)
|
59 (48, 73)
|
0.004
|
CK_baseline, units/L
|
67 (45, 116)
|
65 (44, 107)
|
71 (46, 124.25)
|
0.021
|
CK-MB_baseline, ng/mL
|
10 (7, 14)
|
10 (7, 13)
|
10 (8, 14)
|
0.061
|
cTnI_baseline, ug/L
|
0 (0, 0.01)
|
0 (0, 0.01)
|
0 (0, 0.01)
|
0.369
|
hsCRP_baseline, mg/L
|
12.5 (2.2, 20)
|
7.1 (1.9, 20)
|
20 (2.89, 20)
|
< 0.001
|
DD_baseline, mg/L
|
0.63 (0.35, 1.37)
|
0.69 (0.39, 2.15)
|
0.57 (0.33, 1.1)
|
< 0.001
|
Peak Lymph, 109/L
|
1.52 (1.19, 1.92)
|
1.47 (1.11, 1.91)
|
1.54 (1.25, 1.93)
|
0.152
|
Peak Neutrop, 109/L
|
4.75 (3.29, 7.54)
|
4.73 (3.40–7.01)
|
4.76 (3.19, 7.87)
|
0.065
|
Peak NLR
|
1.00 (0.78, 3.75)
|
2.06 (1.57, 5.77)
|
1.00 (0.87, 2.55)
|
0.001
|
Peak CRP, mg/L
|
32.85 (6.76, 99.93)
|
15.48 (3.56, 71.52)
|
56.58 (10.96, 150.96)
|
< 0.001
|
Peak PCT, ug/L
|
0.38 (0.13, 2.5)
|
0.26 (0.1, 2.46)
|
0.48 (0.15, 2.58)
|
0.374
|
Peak ALT, units/L
|
46 (27, 82)
|
42 (24, 69.25)
|
48 (28, 91)
|
0.053
|
Peak AST, units/L
|
35 (24, 64)
|
33 (24, 56)
|
39 (25,68.75)
|
0.062
|
Peak ALB, g/L
|
38.64 ± 4.05
|
38.59 ± 4.19
|
38.69 ± 3.93
|
0.791
|
Peak Cre, umol/L
|
67.1 (54.5, 84.35)
|
65.2 (53.65, 80.3)
|
69 (55.65, 94.85)
|
0.053
|
Peak ALP, units/L
|
74 (60, 93)
|
76 (63, 94)
|
73 (59, 91)
|
0.108
|
Peak CK, units/L
|
71 (47.5, 210.5)
|
63 (44.5, 173)
|
85 (53.75, 246.5)
|
0.116
|
Peak CK-MB, ng/mL
|
14 (10, 23)
|
13 (10, 21)
|
14 (10, 26.25)
|
0.386
|
Peak cTnl, ug/L
|
0.08 (0.02, 0.48)
|
0.05 (0.02, 0.7)
|
0.09 (0.02, 0.42)
|
0.644
|
Peak CysC, mg/L
|
1.19 (0.99, 1.54)
|
1.21 (0.98, 1.57)
|
1.17 (0.99, 1.51)
|
0.755
|
Peak hs-CRP, mg/L
|
7.61 (2.03, 20)
|
6.28 (2.02, 20)
|
20 (2.35, 27)
|
0.243
|
Peak DD, mg/L
|
3.14 (0.97, 6.02)
|
2.96 (0.9, 6.32)
|
3.43 (0.98, 5.88)
|
0.631
|
Hospital stays (days)
|
15 (11, 17)
|
16 (14, 17)
|
14 (11, 17)
|
0.003
|
Liver injury, n (%)
|
|
|
|
0.005
|
0 (no)
|
1144 (90)
|
555 (92)
|
589 (87)
|
|
1(yes)
|
133 (10)
|
47 (8)
|
86 (13)
|
|
Heart failure, n (%)
|
|
|
|
0.318
|
0 (no)
|
1232 (96)
|
577 (96)
|
655 (97)
|
|
1(yes)
|
45 (4)
|
25 (4)
|
20 (3)
|
|
Severe inflammatory, n (%)
|
|
|
|
< 0.001
|
0 (no)
|
1162 (91)
|
521 (87)
|
641 (95)
|
|
1(yes)
|
115 (9)
|
81 (13)
|
34 (5)
|
|
All-cause death, n (%)
|
|
|
|
< 0.001
|
0 (no)
|
1221 (96)
|
602 (100)
|
619 (92)
|
|
1(yes)
|
56 (4)
|
0 (0)
|
56 (8)
|
|
Data are reported as mean ± SD, median (IQR) or number and percentage. T2DM, Type 2 diabetes mellitus; BNP, Brain Natriuretic Peptide; NLR, Neutrophil-to-Lymphocyte Ratio; PCT, procalcitonin; ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; ALB, albumin; Glu, glucose; Cre, creatinine; ALP, alkaline phosphatase; CK, choline kinase; CK-MB, creatine kinase isoenzymes; cTnI, hypersensitive troponin I; hsCRP, high-sensitivity C-reactive protein; DD, D-Dimer; Lymph, lymphocyte; Neutrop, Neutrophil; CRP, C-reactive protein; PCT, procalcitonin; ALT, alanine transaminase; CysC, Cystatin C. |
The total population was divided into 2 groups by T2DM or not. Compared with non-T2DM patients, the value of age, hospital stay, the percentage of heart failure, severe inflammatory, liver injury in the hospital are higher in T2DM patients; The difference between the number of males and severe pneumonia are not significant. Refer to blood index, the value of CysC, lgBNP, lymphocyte, neutrophile, NLR, ALT, AST, blood glucose (Glu), alkaline phosphatase (ALP), choline kinase (CK), high-sensitivity C-reactive protein (hsCRP), D-Dimer on the baseline, the peak of NLR, CRP (C-reactive protein) are higher in T2DM group. Other than, the value of procalcitonin (PCT), albumin (ALB), creatinine, cardiac Troponin I (cTnI), creatine kinase isoenzymes (CK-MB) on the baseline, the peak of lymphocyte, neutrophile, PCT, ALT, AST, ALB, creatinine, ALP, CK, CK-MB, cTnI, CysC, hs-CRP, D-Dimer are not different between those 2 groups. It was worth mentioned mentioning that T2DM contributed to all-cause death. (Table 1).
Characteristics of T2DM or not patients grouped by CysC level
T2DM and non-T2DM patients were divided into 2 groups by CysC level, respectively. Among the T2DM patients, the CysC high group has a higher percentage of severe pneumonia, heart failure, death, a higher value of age than the CysC low group. The difference between males, severe inflammatory, and hospital stay are not significant. Refer to blood index, the value of CysC, lgBNP, PCT, ALB, Glu, cTnI, hs-CRP, D-Dimer on the baseline, the peak of ALB is higher in T2DM group. The value of lymphocyte, neutrophile, ALT, AST, Cre, CK, CK-MB on the baseline, the peak of lymphocyte, neutrophile, NLR, CRP, PCT, ALT, AST, Cre, CK, CK-MB, c TnI, CysC, hs-CRP, D-Dimer is not different between those 2 groups.(Table 2)
Table 2
characteristics of patients with or without DM classified by cystatin-C level
Variables
|
Total
|
CysC low
|
CysC high
|
p
|
T2DM
|
N = 675
|
N = 344
|
N = 331
|
|
Age, y
|
61 (47.5, 68)
|
56 (41, 65)
|
63 (55, 71)
|
< 0.001
|
Males, n (%)
|
328 (49)
|
165 (48)
|
163 (49)
|
0.798
|
Severe pneumonia, n (%)
|
69 (10.2)
|
14 (4.1)
|
55 (16.6)
|
< 0.001
|
CysC baseline, mg/L
|
0.9 (0.74, 1.12)
|
0.84 (0.71, 1)
|
0.99 (0.78, 1.18)
|
< 0.001
|
LgBNP baseline, pg/mL
|
1.21 (0.38, 1.66)
|
1.09 (0, 1.57)
|
1.32 (0.65, 1.75)
|
< 0.001
|
Lymph baseline, 109/L
|
1.1 (0.8, 1.57)
|
1.16 (0.8, 1.63)
|
1.05 (0.79, 1.52)
|
0.057
|
Neutrop baseline, 109/L
|
3.1 (2.25, 4.41)
|
3.05 (2.24, 4.32)
|
3.14 (2.33, 4.62)
|
0.219
|
NLR baseline
|
2.75 (1.77, 4.27)
|
2.49 (1.66, 3.63)
|
3.11 (1.93, 5.39)
|
0.002
|
PCT baseline, ug/L
|
0.03 (0.03, 0.05)
|
0.03 (0.03, 0.03)
|
0.03 (0.03, 0.05)
|
0.048
|
ALT baseline, units/L
|
26 (16, 39)
|
26 (17, 37)
|
26 (16, 39)
|
0.838
|
AST baseline, units/L
|
27 (21, 39)
|
27 (20, 39)
|
28 (21, 38)
|
0.566
|
ALB baseline, g/L
|
37.38 ± 5.02
|
38.25 ± 4.89
|
36.48 ± 5.01
|
< 0.001
|
Glu baseline, mmol/L
|
5.68 (4.86, 7.2)
|
5.51 (4.74, 7.19)
|
5.87 (4.98, 7.23)
|
0.034
|
Cre baseline, umol/L
|
64.7 (52.42, 78.05)
|
63.5 (52.15, 76.07)
|
65.85 (53.48, 81.62)
|
0.146
|
ALP baseline, units/L
|
59 (48, 73)
|
58 (47.25, 72)
|
59 (49, 73)
|
0.165
|
CK baseline, units/L
|
71 (46, 124.25)
|
70 (47, 119)
|
72 (46, 130.5)
|
0.716
|
CK-MB_baseline, ng/mL
|
10 (8, 14)
|
10 (7, 14)
|
11 (8, 14)
|
0.069
|
cTnI baseline, ug/L
|
0 (0, 0.01)
|
0 (0, 0.01)
|
0 (0, 0.01)
|
< 0.001
|
hsCRP baseline, mg/L
|
20 (2.89, 20)
|
20 (1.9, 20)
|
20 (4.03, 20)
|
0.015
|
DD baseline, mg/L
|
0.57 (0.33, 1.1)
|
0.51 (0.29, 0.84)
|
0.66 (0.37, 1.49)
|
< 0.001
|
Peak Lymph, 109/L
|
1.54 (1.25, 1.93)
|
1.52 (1.27, 1.88)
|
1.55 (1.21, 1.94)
|
0.988
|
Peak Neutrop, 109/L
|
4.76 (3.19, 7.88)
|
5.03 (3.14, 7.72)
|
4.59 (3.21, 8.51)
|
0.216
|
Peak NLR
|
1.00 (0.87, 2.51)
|
1.00 (1.00, 2.31)
|
1.00 (0.57, 2.74)
|
0.985
|
Peak CRP, mg/L
|
56.58 (10.96, 150.96)
|
52.42 (7.98, 156.88)
|
65.06 (13.83, 138.53)
|
0.336
|
Peak PCT, ug/L
|
0.48 (0.15, 2.58)
|
0.54 (0.18, 2.72)
|
0.36 (0.12, 2.58)
|
0.372
|
Peak ALT, units/L
|
48 (28, 91)
|
48 (31, 107)
|
48 (25, 84.5)
|
0.204
|
Peak AST, units/L
|
39 (25, 68.75)
|
37 (25, 70)
|
40 (25.75, 66)
|
0.568
|
Peak ALB, g/L
|
38.69 ± 3.93
|
39.42 ± 3.91
|
38.09 ± 3.85
|
0.011
|
Peak Cre, umol/L
|
69 (55.65, 94.85)
|
66.8 (55, 89.38)
|
72.1 (56, 98.2)
|
0.428
|
Peak ALP, units/L
|
73 (59, 91)
|
70 (55.25, 95.25)
|
74 (61.5, 89.5)
|
0.301
|
Peak CK, units/L
|
85 (53.75, 246.5)
|
73 (51, 244)
|
108 (54, 263.5)
|
0.917
|
Peak CK-MB, ng/mL
|
14 (10, 26.25)
|
14.5 (9, 27.25)
|
13.5 (11, 24.5)
|
0.989
|
Peak cTnl, ug/L
|
0.09 (0.02, 0.42)
|
0.1 (0.01, 0.42)
|
0.08 (0.02, 0.48)
|
0.86
|
Peak CysC, mg/L
|
1.17 (0.99, 1.51)
|
1.12 (0.97, 1.4)
|
1.21 (1.02, 1.64)
|
0.052
|
Peak hs-CRP, mg/L
|
20 (2.35, 27)
|
8.02 (1.52, 27.85)
|
20 (4.19, 20)
|
0.346
|
Peak DD, mg/L
|
3.43 (0.98, 5.88)
|
3.96 (0.98, 7.24)
|
2.88 (1.01, 5.64)
|
0.292
|
Hospital stays (days)
|
14 (11, 17)
|
14 (11, 17)
|
14 (10.5, 18)
|
0.842
|
Liver_injury, n (%)
|
|
|
|
0.699
|
0 (no)
|
589 (87)
|
298 (87)
|
291 (88)
|
|
1(yes)
|
86 (13)
|
46 (13)
|
40 (12)
|
|
Heart failure, n (%)
|
|
|
|
0.033
|
0 (no)
|
655 (97)
|
339 (99)
|
316 (95)
|
|
1(yes)
|
20 (3)
|
5 (1)
|
15 (5)
|
|
Severe inflammatory, n (%)
|
|
|
|
0.952
|
0 (no)
|
641 (95)
|
326 (95)
|
315 (95)
|
|
1(yes)
|
34 (5)
|
18 (5)
|
16 (5)
|
|
All-cause death, n (%)
|
|
|
|
0.049
|
0 (no)
|
619 (92)
|
323 (94)
|
296 (89)
|
|
1(yes)
|
56 (8)
|
21 (6)
|
35 (11)
|
|
Non-T2DM
|
N = 602
|
N = 301
|
N = 301
|
|
Age
|
66 (55, 72)
|
60 (48, 67)
|
70 (62, 77)
|
< 0.001
|
Males, n (%)
|
281 (47)
|
125 (42)
|
156 (52)
|
|
Severe pneumonia, n (%)
|
51 (8.5)
|
18 (6.0)
|
33 (11.0)
|
0.108
|
CysC baseline, mg/L
|
0.96 (0.79, 1.19)
|
0.9 (0.76, 1.06)
|
1.02 (0.84, 1.28)
|
< 0.001
|
LgBNP baseline, pg/mL
|
1.4 (0.77, 1.8)
|
1.23 (0.08, 1.68)
|
1.5 (0.98, 1.94)
|
< 0.001
|
Lymph baseline, 109/L
|
1.19 (0.86, 1.62)
|
1.28 (0.88, 1.68)
|
1.11 (0.82, 1.54)
|
0.008
|
Neutrop baseline, 109/L
|
3.37 (2.54, 4.64)
|
3.29 (2.5, 4.49)
|
3.46 (2.57, 4.81)
|
0.287
|
NLR baseline
|
2.50 (1.70, 3.68)
|
2.40 (1.69, 3.37)
|
2.62 (1.69, 4.49)
|
0.206
|
PCT baseline, ug/L
|
0.03 (0.03, 0.04)
|
0.03 (0.03, 0.03)
|
0.03 (0.03, 0.06)
|
0.163
|
ALT baseline, units/L
|
22 (15, 35)
|
20 (14, 32)
|
24 (16, 40)
|
0.002
|
AST baseline, units/L
|
25 (19, 34)
|
23 (18, 30)
|
28 (21, 37)
|
0.000
|
ALB baseline, g/L
|
37.47 ± 5.13
|
38.33 ± 5.07
|
36.6 ± 5.06
|
< 0.001
|
Glu_baseline, mmol/L
|
5.25 (4.65, 6.58)
|
5.2 (4.63, 6.38)
|
5.33 (4.68, 6.69)
|
0.135
|
Cre baseline, umol/L
|
60.7 (50, 78.4)
|
57.65 (48.12, 74.4)
|
64.4 (53.2, 83.15)
|
< 0.001
|
ALP baseline, units/L
|
63 (51, 78)
|
60 (50.75, 77.25)
|
65 (53, 79)
|
0.101
|
CK baseline, units/L
|
65 (44, 107)
|
60 (43, 96)
|
67.5 (48, 116)
|
0.023
|
CK-MB_baseline, ng/mL
|
10 (7, 13)
|
9 (7, 12)
|
10 (7, 14)
|
0.01
|
cTnI baseline, ug/L
|
0 (0, 0.01)
|
0 (0, 0.01)
|
0.01 (0, 0.01)
|
< 0.001
|
hsCRP baseline, mg/L
|
7.1 (1.9, 20)
|
4.9 (1.51, 20)
|
9.94 (2.45, 20)
|
< 0.001
|
DD baseline, mg/L
|
0.69 (0.39, 2.15)
|
0.6 (0.35, 1.18)
|
0.92 (0.45, 3.12)
|
< 0.001
|
Peak Lymph, 109/L
|
1.47 (1.11, 1.91)
|
1.55 (1.16, 2.03)
|
1.43 (1.08, 1.85)
|
0.326
|
Peak Neutrop, 109/L
|
4.72 (3.40, 7.01)
|
4.68 (3.26, 6.45)
|
4.88 (3.53, 7.88)
|
0.800
|
Peak NLR
|
2.06 (0.32, 5.77)
|
1.83 (0.44, 7.57)
|
2.45 (1.00, 5.09)
|
0.403
|
Peak CRP, mg/L
|
15.48 (3.56, 71.52)
|
9.37 (3.04, 40.81)
|
25.89 (5.03, 78.56)
|
0.058
|
Peak PCT, ug/L
|
0.26 (0.1, 2.46)
|
0.35 (0.17, 2.67)
|
0.2 (0.1, 1.16)
|
0.396
|
Peak ALT, units/L
|
42 (24, 69.25)
|
36 (23, 68)
|
48 (27.5, 74)
|
0.073
|
Peak AST, units/L
|
33 (24, 56)
|
29.5 (21.0, 53.0)
|
38.0 (28.0, 68.0)
|
0.004
|
Peak ALB, g/L
|
38.59 ± 4.19
|
39.1 ± 4.28
|
38.16 ± 4.08
|
0.107
|
Peak Cre, umol/L
|
65.2 (53.65, 80.3)
|
61 (50.55, 73.15)
|
69.9 (56.4, 83.4)
|
0.01
|
Peak ALP, units/L
|
76 (63, 94)
|
76.5 (63.25, 91)
|
75 (61, 99)
|
0.603
|
Peak CK, units/L
|
63 (44.5, 173)
|
53 (43.75, 75.5)
|
75 (47, 218)
|
0.128
|
Peak CK-MB, ng/mL
|
13 (10, 21)
|
11 (9, 18.75)
|
14 (10.5, 22)
|
0.025
|
Peak cTnl, ug/L
|
0.05 (0.02, 0.7)
|
0.02 (0.01, 0.11)
|
0.09 (0.03, 0.95)
|
0.132
|
Peak CysC, mg/L
|
1.21 (0.98, 1.57)
|
1.09 (0.91, 1.36)
|
1.3 (1.04, 1.74)
|
< 0.001
|
Peak hs-CRP, mg/L
|
6.28 (2.02, 20)
|
2.42 (1.7, 6.28)
|
20 (3.73, 20)
|
0.005
|
Peak DD, mg/L
|
2.96 (0.9, 6.32)
|
1.65 (0.77, 4.94)
|
4.4 (1.35, 7.15)
|
0.001
|
Hospital stays (days)
|
16 (14, 17)
|
16 (14, 17)
|
16 (13, 18)
|
0.317
|
Liver injury, n (%)
|
|
|
|
0.761
|
0
|
555 (92)
|
279 (93)
|
276 (92)
|
|
1
|
47 (8)
|
22 (7)
|
25 (8)
|
|
Heart failure, n (%)
|
|
|
|
0.004
|
0
|
577 (96)
|
296 (98)
|
281 (93)
|
|
1
|
25 (4)
|
5 (2)
|
20 (7)
|
|
Severe inflammatory, n (%)
|
|
|
|
0.811
|
0
|
521 (87)
|
262 (87)
|
259 (86)
|
|
1
|
81 (13)
|
39 (13)
|
42 (14)
|
|
All-cause death, n (%)
|
|
|
|
1
|
0
|
602 (100)
|
301 (100)
|
301 (100)
|
|
Data are reported as mean ± SD, median (IQR) or number and percentage. T2DM, Type 2 diabetes mellitus; BNP, Brain Natriuretic Peptide; NLR, Neutrophil-to-Lymphocyte Ratio; PCT, procalcitonin; ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; ALB, albumin; Glu, glucose; Cre, creatinine; ALP, alkaline phosphatase; CK, choline kinase; CK-MB, creatine kinase isoenzymes; cTnI, hypersensitive troponin I; hsCRP, high-sensitivity C-reactive protein; DD, D-Dimer; Lymph, lymphocyte; Neutrop, Neutrophil; CRP, C-reactive protein; PCT, procalcitonin; ALT, alanine transaminase; CysC, Cystatin C. |
As for the non-T2DM patients, the CysC high group has a higher percentage of males, heart failure, higher value of age than the CysC low group. The difference in severe pneumonia and hospital stay, liver injury, severe inflammatory are not significant. Refer to blood index, the value of CysC, lgBNP, lymphocyte, ALT, AST, ALB, Glu, Cre, cTnI, hs-CRP, D-Dimer on the baseline, the peak of cre, CysC, and hs-CRP are higher in the T2DM group. The value of neutrophile, PCT, CK, CK-MB on the baseline, the peak of lymphocyte, neutrophile, CRP, PCT, ALT, AST, Cre, CK, CK-MB, c TnI, D-Dimer are not different between those 2 groups.(Table 2)
Characteristics of patients with T2DM or not grouped by CysC rangeability
T2DM and non-T2DM patients were divided into 2 groups by CysC rangeability, respectively. Among the T2DM patients, the CysC rangeability>0 group has a higher percentage of severe pneumonia, severe inflammatory, liver injury, a higher value of age than the CysC rangeability ≤ 0 group. The difference between the males, hospital stay, heart failure, and death is not significant. Refer to blood index, the value of CysC, lgBNP, lymphocyte, ALT, AST, ALB, cTnI, hs-CRP, D-Dimer on the baseline, the peak of CRP are higher in CysC rangeability>0 groups. The value of neutrophile, creatinine (Cre), PCT, ALP, CK, CK-MB on the baseline, the peak of ALB, lymphocyte, neutrophile, NLR, PCT, ALT, AST, Cre, ALP, CK, CK-MB, c TnI, CysC, hs-CRP, D-Dimer are not different between those 2 groups. (Table 3)
Table 3
characteristics of patients with or without T2DM classified by CysC rangeability
Variables
|
Total
|
CysC rangeability ≤ 0
|
CysC rangeability>0
|
p
|
T2DM
|
N = 675
|
N = 407
|
N = 268
|
|
Age, years
|
61 (47.5, 68)
|
56 (41, 65)
|
63 (55, 71)
|
< 0.001
|
Males, n (%)
|
328 (49)
|
193 (47.4)
|
135 (50.4)
|
|
Severe pneumonia, n (%)
|
69 (10.2)
|
12 (2.9)
|
57 (21.3)
|
< 0.001
|
CysC baseline, mg/L
|
0.96 (0.79, 1.19)
|
0.9 (0.76, 1.06)
|
1.02 (0.84, 1.28)
|
< 0.001
|
LgBNP baseline, pg/mL
|
1.4 (0.77, 1.8)
|
1.23 (0.08, 1.68)
|
1.5 (0.98, 1.94)
|
< 0.001
|
Lymph_baseline, 109/L
|
1.19 (0.86, 1.62)
|
1.28 (0.88, 1.68)
|
1.11 (0.82, 1.54)
|
0.008
|
Neutrop_baseline, 109/L
|
3.37 (2.54, 4.64)
|
3.29 (2.5, 4.49)
|
3.46 (2.57, 4.81)
|
0.287
|
NLR baseline
|
2.50 (1.70, 3.68)
|
2.24 (1.62, 3.09)
|
3.34 (2.42, 5.93)
|
0.206
|
PCT baseline, ug/L
|
0.25 (0.25, 0.25)
|
0.25 (0.25, 0.25)
|
0.25 (0.25, 0.58)
|
0.163
|
ALT baseline, units/L
|
26 (16, 39)
|
24 (16, 38)
|
26 (18, 40)
|
0.002
|
AST baseline, units/L
|
27 (21, 38)
|
26 (20, 37)
|
30 (21, 42)
|
0.000
|
ALB baseline, g/L
|
37.15 ± 4.33
|
37.64 ± 4.21
|
36.25 ± 4.76
|
< 0.001
|
Glu baseline, mmol/L
|
5.67 (4.84, 7.19)
|
5.62 (4.87, 7.13)
|
5.76 (4.80, 7.33)
|
0.135
|
Cre baseline, umol/L
|
65.10 (52.40, 78.70)
|
64.20 (51.60, 78.20)
|
65.5 (54.40, 80.80)
|
< 0.001
|
ALP baseline, units/L
|
59.00 (48.00, 73.00)
|
57.00 (47.00, 72.00)
|
61.00 (49.00, 74.00)
|
0.101
|
CK baseline, units/L
|
72.00 (46.00, 129.00)
|
68.00 (45.00, 123.00)
|
76.50 (48.25, 136.75)
|
0.023
|
CK-MB_baseline, ng/mL
|
10 (8, 14)
|
10 (8, 13)
|
11 (7, 14)
|
0.01
|
cTnI baseline, ug/L
|
0 (0, 0.01)
|
0 (0, 0.01)
|
0.01 (0, 0.01)
|
< 0.001
|
hsCRP baseline, mg/L
|
20.0 (2.8, 20.0)
|
20.0 (2.30, 20.0)
|
20.0 (3.14, 20.0)
|
< 0.001
|
DD baseline, mg/L
|
0.69 (0.39, 2.15)
|
0.6 (0.35, 1.18)
|
0.92 (0.45, 3.12)
|
< 0.001
|
Peak Lymph, 109/L
|
1.53 (1.25, 1.93)
|
1.54 (1.23, 1.93)
|
1.53 (1.25, 1.93)
|
0.245
|
Peak Neutrop, 109/L
|
4.76 (3.19, 7.88)
|
4.81 (3.16, 7.63)
|
4.66 (3.42, 9.38)
|
0.803
|
Peak NLR
|
1.00 (0.87, 2.51)
|
1.00 (1.00, 2.40)
|
1.00 (1.00, 2.92)
|
0.611
|
Peak CRP, mg/L
|
56.58 (10.38, 152.32)
|
58.76 (12.75, 149.93)
|
52.43 (8.65, 138.53)
|
0.027
|
Peak PCT, ug/L
|
0.48 (0.15, 2.69)
|
0.37 (0.10, 4.34)
|
0.51 (0.18, 2.43)
|
0.901
|
Peak ALT, units/L
|
49.5 (28.25, 96.75)
|
43.00 (28.00, 84.50)
|
54.00 (29.00, 107.00)
|
0.058
|
Peak AST, units/L
|
39 (25, 68.75)
|
35 (24, 59)
|
44 (27, 77.5)
|
0.066
|
Peak ALB, g/L
|
38.69 ± 3.93
|
38.60 ± 3.79
|
38.25 ± 4.04
|
0.691
|
Peak Cre, umol/L
|
69 (55.65, 94.85)
|
67.8 (54.1, 100.1)
|
74.5 (59.6, 105.0)
|
0.280
|
Peak ALP, units/L
|
73 (59, 91)
|
70.50 (59.00, 85.25)
|
75.00 (59.00, 101.50)
|
0.021
|
Peak CK, units/L
|
85 (53.75, 246.5)
|
85 (45.00, 398.00)
|
115 (63, 459)
|
0.522
|
Peak CK-MB, ng/mL
|
14.0 (10, 26.25)
|
14.0 (9, 27.25)
|
15.0 (10.0, 31.0)
|
0.338
|
Peak cTnl, ug/L
|
0.09 (0.02, 0.42)
|
0.1 (0.98, 1.52)
|
1.20 (1.00, 1.50)
|
0.909
|
Peak CysC, mg/L
|
1.17 (0.99, 1.51)
|
1.15 (0.97, 1.4)
|
1.21 (1.02, 1.64)
|
0.717
|
Peak hs-CRP, mg/L
|
20 (2.35, 27)
|
8.02 (1.52, 27.85)
|
20 (4.19, 20)
|
0.297
|
Peak DD, mg/L
|
3.43 (0.98, 5.88)
|
3.11 (0.97, 5.48)
|
3.70 (1.04, 7.21)
|
0.936
|
Hospital stays (days)
|
14 (11, 17)
|
14 (10, 17)
|
14 (11, 18)
|
0.071
|
Liver injury, n (%)
|
|
|
|
0.020
|
0 (no)
|
589 (87)
|
365 (89.7)
|
224 (83.6)
|
|
1 (yes)
|
86 (13)
|
42 (10.3)
|
44 (16.4)
|
|
Heart failure, n (%)
|
|
|
|
0.632
|
0 (no)
|
655 (97)
|
396 (97.3)
|
259 (96.6)
|
|
1 (yes)
|
20 (3)
|
11 (2.7)
|
9 (3.4)
|
|
Severe inflammation, n (%)
|
|
|
|
0.048
|
0 (no)
|
641 (95)
|
392 (96.3)
|
249 (92.9)
|
|
1 (yes)
|
34 (5)
|
15 (3.7)
|
19 (7.1)
|
|
All-cause Death, n (%)
|
|
|
|
0.283
|
0 (no)
|
619 (92)
|
377 (92.6)
|
242 (90.3)
|
|
1 (yes)
|
56 (8)
|
30 (7.4)
|
26 (9.7)
|
|
Non-T2DM
|
N = 602
|
N = 386
|
N = 216
|
|
Age
|
66 (55, 72)
|
60 (48, 67)
|
70 (62, 77)
|
< 0.001
|
Males, n (%)
|
281 (47)
|
176 (45.6)
|
105 (48.6)
|
0.477
|
Severe pneumonia, n (%)
|
51 (8.5)
|
15 (3.9)
|
36 (16.7)
|
< 0.001
|
CysC baseline, mg/L
|
0.95 (0.79, 1.19)
|
0.94 (0.78, 1.18)
|
0.96 (0.81, 1.22)
|
< 0.001
|
LgBNP baseline, pg/mL
|
1.39 (0.77, 1.80)
|
1.33 (0.17, 1.78)
|
1.48 (0.98, 1.88)
|
< 0.001
|
Lymph baseline, 109/L
|
1.19 (0.85, 1.62)
|
1.20 (0.86, 1.64)
|
1.17 (0.82, 1.58)
|
0.008
|
Neutrop baseline, 109/L
|
3.37 (2.51, 4.64)
|
3.31 (2.45, 4.51)
|
3.55 (2.66, 4.83)
|
0.287
|
NLR baseline
|
2.75 (1.77, 4.27)
|
2.35 (1.59, 3.52)
|
3.30 (2.19, 5.99)
|
0.206
|
PCT baseline, ug/L
|
0.25 (0.25, 0.25)
|
0.25 (0.25, 0.25)
|
0.25 (0.25, 0.58)
|
0.163
|
ALT baseline, units/L
|
22 (14.75, 35.00)
|
22.00 (14.00, 35.00)
|
27.00 (20.00, 35.75)
|
0.002
|
AST baseline, units/L
|
25 (19, 34)
|
24 (19, 33.25)
|
27.00 (20.00, 35.75)
|
0.000
|
ALB baseline, g/L
|
37.40 ± 3.37
|
37.58 ± 3.82
|
37.08 ± 3.97
|
< 0.001
|
Glu baseline, mmol/L
|
5.24 (4.63, 6.58)
|
5.21 (4.61, 6.58)
|
5.37 (4.67, 6.63)
|
0.135
|
Cre baseline, umol/L
|
61.25 (50.20, 80.23)
|
60.45 (50.15, 78.18)
|
62.95 (50.32, 85.42)
|
< 0.001
|
ALP baseline, units/L
|
63.00 (51.00, 78.00)
|
64.00 (52.00, 81.00)
|
59.00 (48.00, 73.00)
|
0.101
|
CK baseline, units/L
|
65.00 (44.00, 110.25)
|
63.50 (44.00, 105.50)
|
68.00 (43.25, 115.75)
|
0.023
|
CK-MB_baseline, ng/mL
|
10 (7, 13)
|
9 (7, 14)
|
10 (7, 13)
|
0.01
|
cTnI baseline, ug/L
|
0 (0, 0.01)
|
0 (0, 0.01)
|
0.01 (0, 0.01)
|
< 0.001
|
hsCRP baseline, mg/L
|
7.04 (1.88, 20.00)
|
5.13 (1.60, 20.00)
|
10.1 (2.81, 20.0)
|
< 0.001
|
DD baseline, mg/L
|
0.69 (0.39, 2.15)
|
0.66 (0.38, 1.92)
|
0.81 (0.41, 2.96)
|
0.167
|
Peak Lymph, 109/L
|
1.47 (1.11, 1.91)
|
1.44 (1.10, 1.88)
|
1.58 (1.11, 1.97)
|
0.309
|
Peak Neutrop, 109/L
|
4.72 (3.40, 7.01)
|
4.60 (3.41, 6.37)
|
4.85 (3.36, 7.98)
|
0.698
|
Peak NLR
|
2.06 (0.32, 5.77)
|
1.74 (1.00, 5.09)
|
2.54 (0.52, 8.24)
|
0.052
|
Peak CRP, mg/L
|
15.48 (3.56, 71.52)
|
9.78 (2.53, 63.12)
|
25.36 (5.41, 73.60)
|
0.100
|
Peak PCT, ug/L
|
0.26 (0.1, 2.46)
|
0.23 (0.10, 0.75)
|
0.80 (0.1, 4.15)
|
0.490
|
Peak ALT, units/L
|
42 (24, 69.25)
|
38 (22, 65)
|
50 (27, 77)
|
0.031
|
Peak AST, units/L
|
33 (24, 56)
|
31.0 (22.0, 50.0)
|
35.0 (28.0, 60.3)
|
0.263
|
Peak ALB, g/L
|
38.59 ± 4.19
|
38.3 ± 3.81
|
38.5 ± 4.63
|
0.951
|
Peak Cre, umol/L
|
65.2 (53.65, 80.3)
|
66.85 (54.53, 85.28)
|
64.9 (53.2, 80.0)
|
0.66
|
Peak ALP, units/L
|
76 (63, 94)
|
77.0 (62.0, 91.0)
|
74.0 (63.3, 91.2)
|
0.812
|
Peak CK, units/L
|
63 (44.5, 173)
|
70.00 (49.00, 244.00)
|
71.00 (42.00, 314.75)
|
0.899
|
Peak CK-MB, ng/mL
|
13 (10, 21)
|
13 (10, 21)
|
14 (10, 21.25)
|
0.587
|
Peak cTnl, ug/L
|
0.05 (0.02, 0.7)
|
0.03 (0.01, 0.09)
|
0.12 (0.02, 1.90)
|
0.167
|
Peak CysC, mg/L
|
1.21 (0.98, 1.57)
|
1.22 (0.94, 1.59)
|
1.20 (1.00, 1.55)
|
0.87
|
Peak hs-CRP, mg/L
|
6.28 (2.02, 20)
|
6.74 (1.90, 20.00)
|
5.57 (2.21, 20.00)
|
0.751
|
Peak DD, mg/L
|
2.96 (0.9, 6.32)
|
3.60 (1.09, 6.31)
|
2.36 (0.79, 6.36)
|
0.331
|
Hospital stays (days)
|
16 (14, 17)
|
16 (9, 17)
|
16 (14, 18)
|
0.004
|
Liver injury, n (%)
|
|
|
|
0.104
|
0 (no)
|
555 (92)
|
194 (89.8)
|
361 (93.5)
|
|
1 (yes)
|
47 (8)
|
22 (10.2)
|
25 (6.5)
|
|
Heart failure, n (%)
|
|
|
|
0.400
|
0 (no)
|
577 (96)
|
205 (94.9)
|
372 (96.4)
|
|
1 (yes)
|
25 (4)
|
11 (5.1)
|
14 (3.6)
|
|
Severe inflammation, n (%)
|
|
|
|
0.084
|
0 (no)
|
521 (87)
|
341 (88.3)
|
180 (83.3)
|
|
1 (yes)
|
81 (13)
|
45 (11.7)
|
36 (16.7)
|
|
All-cause death, n (%)
|
|
|
|
1
|
0 (no)
|
602 (100)
|
301 (100)
|
301 (100)
|
|
Data are reported as mean ± SD, median (IQR) or number and percentage. T2DM, Type 2 diabetes mellitus; BNP, Brain Natriuretic Peptide; NLR, Neutrophil-to-Lymphocyte Ratio; PCT, procalcitonin; ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; ALB, albumin; Glu, glucose; Cre, creatinine; ALP, alkaline phosphatase; CK, choline kinase; CK-MB, creatine kinase isoenzymes; cTnI, hypersensitive troponin I; hsCRP, high-sensitivity C-reactive protein; DD, D-Dimer; Lymph, lymphocyte; Neutrop, Neutrophil; CRP, C-reactive protein; PCT, procalcitonin; ALT, alanine transaminase; CysC, Cystatin C. |
In the non-diabetic population, the CysC rangeability>0 group has a higher percentage of severe pneumonia, higher value of age, hospital stay than CysC rangeability ≤ 0. The difference between liver injury, severe inflammatory, heart failure is not significant. Refer to blood index, the value of CysC, lgBNP, lymphocyte, ALT, AST, ALB, creatinine, CK, CK-MB, cTnI, hs-CRP, D-Dimer on the baseline, the peak of cre and ALT is higher in CysC rangeability>0 group. The value of neutrophile, PCT, CK, CK-MB, glucose on the baseline, the peak of lymphocyte, neutrophile, CRP, PCT, ALT, CysC, and hs-CRP CK, CK-MB, cTnI, D-Dimer are not different between those 2 groups. (Table 3)
The association between CysC and Organ dysfunction, all-cause death classified by T2DM
Multivariate logistic analysis for organ dysfunction and all-cause death showed that when CysC ≤ 0.93 mg/dl as a reference, CysC>0.93 mg/dl were significantly associated with the risk of heart failure (OR = 2.401, 95% CI: 1.118–5.156) and all-cause death (OR = 2.734, 95% CI: 1.098–6.811), but the association did not go for severe inflammatory (OR = 0.98, 95% CI: 0.661–1.446) and liver injury (OR = 1.168, 95% CI: 0.789–1.729), (Fig. 1).
Furthermore, classified by T2DM status, using CysC ≤ 0.93 mg/dl as a reference standard, CysC > 0.93 mg/dl had an increased risk of heart failure (OR = 2.962, 95% CI: 1.006–8.724) and all-cause death (OR = 5.585, 95% CI: 2.328–13.397), but not for severe inflammatory (OR = 0.81, 95% CI: 0.402–1.647) and liver injury (OR = 0.986, 95% CI:0.601–1.618) for T2DM patients. Whereas the relationship between CysC>0.93 mg/dl and severe inflammatory, liver injury, or heart failure was not significant in the non-T2DM group (Fig. 1).
When goes for sex subgroup of T2DM patients, adjusted by age, severe pneumonia, serum albumin, blood glucose, Lg BNP, there was a significantly increased contribution of CysC>0.93 mg/dl to all-cause death (OR = 4.059, 95% CI: 1.045–14.340) in females, but showed no significance for males. Whereas referring to CysC ≤ 0.93 mg/dl, CysC>0.93 mg/dl did not show obvious links to severe inflammatory, liver injury, and heart failure both in males and females, (Fig. 2).
The association between CysC rangeability and all-cause death classified by T2DM
Compared with patients with CysC rangeability ≤ 0, those with CysC rangeability>0 were highly correlated with all-cause death (OR = 4.029, 95% CI: 1.864–8.706). For T2DM, there was a significantly increased contribution of CysC rangeability>0 to all-cause death (OR = 5.585, 95% CI: 2.328–13.397), (Fig. 3).
As for the sex subgroup of T2DM patients, adjusted by age, severe pneumonia, serum albumin, blood glucose, LgBNP, there was a significant contribution of CysC rangeability>0 to all-cause death both males (OR = 4.699, 95% CI: 1.604–13.767). Notably, the association increased significantly for female patients (OR = 13.514, 95% CI: 1.398–30.675), (Fig. 4).