Diabetes patients with comorbidities had unfavorable outcomes following COVID-19: A retrospective study

doi:10.4239/wjd.v12.i10.1789

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World Journal of Diabetes

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Study

World J Diabetes. Oct 15, 2021; 12(10): 1789-1808
Published online Oct 15, 2021. doi: 10.4239/wjd.v12.i10.1789

Table 1 Baseline characteristics of 1331 coronavirus disease 2019 patients divided into different groups

	Total (n = 1331)	Non-diabetes (n = 1140)	Diabetes (n = 191)	P¹value	Non-comorbidity (n = 779)	Diabetes only (n = 65)	Diabetes with comorbidities (n = 126)	P²value
Demographic
Male	673 (50.6)	565 (49.6)	108 (56.5)	0.074	369 (47.4)	40 (61.5)	68 (54.0)	0.046
Age, yr	56.0 (42.0-65.0)	54.0 (39.0-64.0)	64.0 (56.0-70.0)	< 0.001	48.0^c(36.0-60.0)	57.0 (50.0-64.0)	67.0^c(59.0-72.0)	< 0.001
18-49	500(37.6)	477 (41.8)	23 (12.0)	<0.001	415 (53.3)^c	16 (24.6)	7 (5.6)^c	< 0.001^d
50-64	458 (34.4)	382 (33.5)	76 (39.8)		253 (32.5)	34 (52.3)	42 (33.3)
≥ 65	373 (28.0)	281 (24.6)	92 (48.2)		111 (14.2)	15 (23.1)	77 (61.1)
Wuhan exposure	1190 (89.4)	1008 (88.4)	182 (95.3)	0.004	686 (88.3)	61 (95.3)	120 (95.2)	0.018
Current smoking	107 (8.1)	93 (8.2)	14 (7.4)	0.736	55 (7.2)	3 (4.7)	11 (8.9)	0.149
Onset of symptom, d	8.0 (5.0-14.0)	8.0 (5.0-14.0)	10.0 (6.0-13.0)	0.217	8.0 (4.8-14.0)	10.0 (6.5-16.5)	10.0 (5.8-12.0)	0.109
Symptoms
Fever	955 (71.8)	823 (72.2)	132 (69.1)	0.381	570 (73.2)	46 (70.8)	86 (68.3)	0.496
Dyspnea	270 (20.3)	227 (19.9)	43 (22.5)	0.408	135 (17.3)	9 (13.8)	34 (27.0)	0.021
Cough	777 (58.4)	660 (57.9)	117 (61.3)	0.383	433 (55.6)	46 (70.8)	71 (56.7)	0.060
Sputum production	138 (10.4)	126 (11.1)	12 (6.3)	0.045	84 (10.8)	4 (6.2)	8 (6.3)	0.175
Hemoptysis	3 (0.2)	3 (0.3)	0 (0.0)	1.000	1 (0.1)	0 (0.0)	0 (0.0)	0.885
Fatigue	362 (27.2)	306 (26.8)	56 (29.3)	0.476	212 (27.2)	16 (24.6)	40 (31.7)	0.489
Headache	47 (3.5)	44 (3.9)	3 (1.6)	0.169	29 (3.7)	3 (4.6)	0 (0.0)	0.010
Nausea or vomiting	44 (3.3)	39 (3.4)	5 (2.6)	0.566	25 (3.2)	2 (3.1)	3 (2.4)	0.939
Diarrhea	112 (8.4)	97 (8.5)	15 (7.9)	0.763	63 (8.1)	9 (13.8)	6 (4.8)	0.091
Temperature, ℃	36.8 (36.5-37.5)	36.8 (36.5-37.5)	36.7 (36.4-37.4)	0.018	36.8 (36.5-37.5)	36.8 (36.5-37.6)	36.6 (36.4-37.3)	0.018
≥ 39	30 (2.4)	25 (2.3)	5 (2.7)	0.980	16 (2.2)	2 (3.1)	3 (2.4)	0.889
Pulse ≥ 100 beats per min	244 (18.5)	209 (18.5)	35 (18.3)	0.955	125 (16.1)	12 (18.5)	23 (18.30)	0.761
Blood oxygen saturation < 93%	124 (11.1)	92 (9.6)	32 (19.8)	< 0.001	43 (6.5)	7 (12.5)	25 (23.6)	< 0.001
Respiratory rate > 24 breaths/min	71 (5.4)	56 (5.0)	15 (7.9)	0.105	27 (3.5)	2 (3.1)	13 (10.3)	0.002
Mean systolic blood pressure, mmHg	125 (120-135)	124 (119-135)	128 (120-140)	0.001	121 (118-131)	127 (120-133)	130 (120-140)	< 0.001
Mean diastolic blood pressure, mmHg	80.0 (74.0-85.0)	80.0 (74.0-85.0)	80.0 (74.0-85.0)	0.777	80.0 (73.0-83.0)	80.0 (72.5-85.0)	80.0 (74.0-84.3)	0.550
Radiological findings
Ground glass opacity	294 (22.1)	265 (23.2)	29 (15.2)	0.013	195 (25.0)	9 (13.8)	20 (15.9)	0.014
Bilateral patchy shadowing	813 (61.1)	687 (60.3)	126 (66.0)	0.134	62 (8.0)	5 (7.7)	4 (3.2)	0.107
Bilateral lesions	962 (82.1)	805 (80.1)	157 (94.0)	< 0.001	524 (76.2)^a	53 (91.4)	104 (95.4)	< 0.001
Comorbidity
Hypertension	350 (26.3)	244 (21.4)	106 (55.5)	< 0.001	-	-	-	-
CHD	59 (4.4)	40 (3.5)	19 (9.9)	< 0.001	-	-	-	-
Chronic liver disease	20 (1.5)	18 (1.6)	2 (1.0)	0.812	-	-	-	-
CVD	39 (2.9)	25 (2.2)	14 (7.3)	< 0.001	-	-	-	-
CKD	26 (2.0)	17 (1.5)	9 (4.7)	0.007	-	-	-	-
COPD	10 (0.8)	10 (0.9)	0 (0.0)	0.397	-	-	-	-

Data are expressed as n (%), mean ± SD or median (IQR). P values were calculated by t Test, Mann-Whitney U test, χ²test, Fisher's exact test, One-Way ANOVA or Kruskal-Wallis H test as appropriate.

¹Comparing groups of diabetes and non-diabetes patients.

²Comparing groups of non-comorbidity, only diabetes and diabetes with comorbidities.

^dMann-Whitney U test comparing all subcategories. Compared with diabetes only group.

^aP < 0.05.

^bP < 0.05.

^cP < 0.001.

CHD: Coronary heart disease; CKD: Chronic kidney disease; COPD: Chronic obstructive pulmonary diseas; CVD: Cerebrovascular diseasee.

Table 2 Laboratory results of 1331 coronavirus disease 2019 patients divided into different groups

	Total (n = 1331)	Non-diabetes (n = 1140)	Diabetes (n = 191)	P¹value	Non-comorbidity (n = 779)	Diabetes only (n = 65)	Diabetes with comorbidities (n = 126)	P²value
WBC, × 10⁹/L	5.42 (4.18-7.10)	5.35 (4.10-6.95)	5.93 (4.49-7.53)	0.003	5.28 (4.00-6.77)	6.11 (4.27-7.68)	5.85 (4.57-7.32)	0.001
NEUT, × 10⁹/L	3.58 (2.53-5.12)	3.45 (2.46-5.07)	4.25 (3.13-5.37)	< 0.001	3.29 (2.33-4.64)	4.16 (2.67-5.40)	4.37 (3.20-5.29)	< 0.001
LY, × 10⁹/L	1.15 (0.78-1.59)	1.17 (0.80-1.61)	1.04 (0.72-1.43)	0.015	1.25 (0.86-1.65)	1.27 (0.84-1.73)	0.93 (0.68-1.33)^b	< 0.001
NLR	2.95 (1.97-5.26)	2.79 (1.88-4.93)	3.84 (2.45-6.37)	< 0.001	2.54 (1.79-4.36)	3.15 (2.08-5.06)	4.29 (2.62-7.30)^a	< 0.001
Hb, g/L	130 (118-140)	130 (118-140)	120 (117-140)	0.195	131 ± 16.3	132 ± 14.4	125 ± 17.6^b	< 0.001
PLT, × 10⁹/L	196 (150-251)	196 (151-251)	196 (147-255)	0.714	196 (152-242)	197 (147-265)	196 (146-255)	0.974
PCT, ng/mL
< 0.5	981 (94.4)	838 (94.4)	143 (94.7)	0.869	585 (97.3)	53 (100)	90 (91.8)	0.006
≥ 0.5	58 (5.6)	50 (5.6)	8 (5.3)		16 (2.7)	0 (0.0)	8 (8.2)
CRP	10.9 (1.7-46.7)	9.1 (1.4-39.0)	29.8 (5.3-75.7)	< 0.001	6.11 (1.0-27.7)^a	13.2 (3.0-61.5)	39.9 (6.6-77.7)^a	< 0.001
IL-6, pg/mL	2.77 (1.5-14.09)	2.73 (1.5-13.5)	3.09 (1.5-20.4)	0.471	1.80 (1.50-6.27)	2.32 (1.50-5.06)	4.01 (2.72-28.56)	0.008
PT, s	13.0 (11.3-14.9)	12.9 (11.3-14.6)	14.3 (11.9-15.5)	< 0.001	12.80 (11.20-14.30)	13.70 (10.80-15.05)	14.50 (12.35-16.03)	< 0.001
< 16	830 (85.7)	712 (87.1)	118 (78.1)	0.004	493 (87.7)	41 (83.7)	75 (73.5)	0.001
≥ 16	138 (14.3)	105 (12.9)	33 (21.9)		69 (12.3)	8 (16.3)	27 (26.5)
D-dimer, mg/L	0.49 (0.26-1.14)	0.46 (0.25-1.10)	0.69 (0.35-1.35)	< 0.001	0.38 (0.23-0.80)	0.46 (0.26-0.91)	0.83 (0.46-1.94)^b	< 0.001
≤ 0.5	555 (52.5)	497 (55.0)	58 (37.9)	< 0.001	386 (63.4)	27 (50.9)	31 (31.0)^b	< 0.001³
> 0.5 to ≤ 1.0	209 (19.8)	163 (18.0)	46 (30.1)		100 (16.4)	18 (34.0)	28 (28.0)
> 1.0	293 (27.7)	244 (27.0)	49 (32.0)		123 (20.2)	8 (15.1)	41 (41.0)
ALB, g/L	38.1 ± 5.8	38.5 ± 5.7	35.7 ± 5.5	< 0.001	39.3 ± 5.9^c	36.5 ± 6.4	35.3 ± 5.0	< 0.001
ALT, U/L	23.1 (14.2-39.0)	23.3 (14.0-40.0)	23.0 (16.0-34.0)	0.844	22.0 (13.8-39.0)	21.0 (16.3-33.5)	24.0 (15.9-34.0)	0.801
AST, U/L	28.8 (22.0-40.4)	28.8 (22.0-40.0)	29.0 (20.0-41.0)	0.583	27.0 (21.0-38.0)	26.0 (18.2-36.5)	31.0 (22.0-43.0)^a	0.034
ALP, U/L	58.0 (46.0-73.0)	58.0 (46.0-73.0)	55.0 (43.5-74.0)	0.171	58.0 (45.0-72.0)	53.0 (38.0-68.5)	58.0 (45.0-77.0)	0.086
TBIL, mmol/L	10.9 (8.2-14.7)	10.8 (8.2-14.5)	11.4 (8.3-15.7)	0.196	10.8 (8.2-14.7)	11.4 (9.5-14.8)	11.3 (8.0-15.8)	0.429
Potassium, mmol/L	3.90 (3.59-4.20)	3.90 (3.60-4.20)	3.88 (3.52-4.21)	0.325	3.94 ± 0.51	3.94 ± 0.49	3.86 ± 0.62	0.279
Sodium, mmol/L	139 (137-141)	140 (137-141)	138 (136-141)	0.001	140 (138-141)^a	138 (136-141)	139 (136-142)	0.002
Chlorine ion, mmol/L	104 (102-107)	105 (102-107)	103 (100-106)	0.002	104.2 ± 5.3	103.1 ± 4.5	103.7 ± 5.1	0.218
Calcium, mmol/L	2.11 (2.00-2.21)	2.12 (2.01-2.21)	2.09 (1.95-2.17)	0.005	2.13 ± 0.22	2.11 ± 0.22	2.07 ± 0.18	0.011
Phosphorus, mmol/L	1.03 (0.89-1.19)	1.03 (0.89-1.19)	1.01 (0.73-1.18)	0.359	1.04 (0.90-1.19)	1.03 (0.92-1.17)	1.00 (0.85-1.19)	0.300
BUN, mmol/L	3.96 (3.10-5.25)	3.90 (3.10-5.13)	4.68 (3.60-6.20)	< 0.001	3.70 (2.96-4.66)^a	4.30 (3.51-5.07)	4.93 (3.60-7.01)	< 0.001
Creatinine, μmol/L	63.6 (53.3-78.0)	63.0 (53.0-77.4)	66.3 (54.0-83.8)	0.088	62.00 (52.70-73.00)	60.00 (52.00-76.60)	67.75 (55.25-90.23)^a	< 0.001
UA, μmol/L	258 (204-336)	257 (205-336)	258 (193-332)	0.725	253 (203-327)	248 (194-306)	264 (191-352)	0.499
CK, U/L	65.0 (43.0-110)	64.5 (44.0-109)	66.5 (40.3-118)	0.830	62.0 (44.0-98.0)	58.5 (36.8-108)	70.0 (43.8-122)	0.233
LDH, U/L	205 (162-272)	201 (160-261)	229 (180-341)	< 0.001	186 (155-239)	198 (164-282)	251 (195-362)^a	< 0.001
Hs-cTnI > ULN, pg/mL	130 (22.1)	117 (23.4)	13 (14.90)	0.080	71 (23.5)	3 (12.5)	6 (9.5)	0.027
TG, mmol/L	1.22 (0.92-1.78)	1.20 (0.89-1.77)	1.39 (1.04-1.83)	0.002	1.18 (0.86-1.77)	1.50 (1.05-2.08)	1.36 (1.03-1.79)^a	0.004
TCH, mmol/L	4.00 (3.40-4.80)	4.01 (3.42-4.80)	4.00 (3.22-4.78)	0.180	4.25 ± 1.09	4.34 ± 1.07	3.88 ± 1.08^a	0.004
LDL-C, mmol/L	2.50 (3.00-3.12)	2.51 (2.02-3.10)	2.48 (1.87-3.15)	0.368	2.65 ± 0.89	2.76 ± 0.91	2.41 ± 0.87^a	0.020
HDL-C, mmol/L	1.01 (0.82-1.21)	1.03 (0.84-1.24)	0.91 (0.76-1.08)	< 0.001	1.11 ± 0.42^a	0.97 ± 0.26	0.92 ± 0.27	< 0.001
FPG, mmol/L	5.80 (5.00-7.46)	5.57 (4.92-6.89)	9.10 (6.50-11.63)	< 0.001	5.37 (4.83-6.50)^c	9.40 (6.48-11.59)	8.80 (6.50-12.03)	< 0.001
3.9-6.9	693 (69.0)	650 (76.7)	43 (27.6)	< 0.001	475 (80.2)^c	17 (29.8))	26 (26.3)	< 0.001³
7.0-11.1	241 (24.0)	179 (21.1)	62 (39.7)		108 (18.2)	22 (38.6)	40 (40.4)
≥ 11.1	70 (7.0)	19 (2.2)	51 (32.7)		9 (1.5)	18 (31.6)	33 (33.3)
HbA1C	6.20 (5.55-7.30)	5.90 (5.40-6.30)	7.87 (6.27-9.03)	< 0.001	5.9 (5.44-6.20)^b	7.60 (5.64-8.98)	7.89 (6.75-9.21)	< 0.001

Data are expressed as n (%), mean ± SD or median (IQR). P values were calculated by t Test, Mann-Whitney U test, χ²test, Fisher’s exact test, One-Way ANOVA or Kruskal-Wallis H test as appropriate.

¹Comparing groups of diabetes and non-diabetes patients.

²Comparing groups of non-comorbidity, only diabetes and diabetes with comorbidities.

³Mann-Whitney U test comparing all subcategories.

Compared with diabetes only group,

^aP < 0.05.

^bP < 0.05.

^cP < 0.001.

ALB: Albumin; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BUN: Urea nitrogen; CK: Creatine kinase; CRP: C reactive protein; FPG: Fasting plasma glucose; Hb: Hemoglobin; HbA1C: Glycosylated hemoglobin; HDL-C: High density lipoprotein cholesterol; Hs-cTnI: Hypersensitive troponin I; LDH: Lactate dehydrogenase; LDL-C: Low density lipoprotein cholesterol; LY: Lymphocyte; NEUT: Neutrophil; NLR: Neutrophil lymphocyte ratio; PCT: Procalcitonin; PLT: Platelet; PT: Prothrombin time; TBIL: Total bilirubin; TCH: Total cholesterol; TG: Triglyceride; UA: Uric acid; WBC: White blood cell.

Table 3 Treatments and outcomes of 1331 coronavirus disease 2019 patients divided into different groups

	Tota (n = 1331)	Non-diabetes (n = 1140)	Diabetes (n = 191)	P¹value	Non- comorbidity (n = 779)	Diabetes only (n = 65)	Diabetes with comorbidities (n = 126)	P² value
Treatments
Antiviral therapy	1227 (92.2)	1057 (92.7)	170 (89.0)	0.077	725 (93.1)	62 (95.4)	108 (85.7)	0.010
Antibiotic therapy	1142 (85.8)	982 (86.1)	160 (83.8)	0.385	665 (85.4)	57 (87.7)	103 (81.7)	0.472
Systemic glucocorticoid	533 (40.0)	458 (40.2)	75 (39.3)	0.813	292 (37.5)	23 (35.4)	52 (41.3)	0.657
Intravenous immunoglobulin	403 (30.3)	342 (30.0)	61 (31.9)	0.590	210 (27.0)	18 (27.7)	43 (34.1)	0.250
Renal replacement therapy	2 (0.2)	1 (0.1)	1 (0.5)	0.267	0 (0.0)	0 (0.0)	1 (0.8)	0.197
Oxygen support
Oxygenation	786 (59.1)	672 (58.9)	114 (59.7)	0.848	426 (54.7)	38 (58.5)	76 (60.3)	0.446
Mechanical ventilation	154 (11.6)	124 (10.9)	30 (15.7)	0.053	68 (8.7)	7 (10.8)	23 (18.3)	0.004
Illness severity
Severe	313 (23.5)	247 (21.7)	66 (34.6)	< 0.001	123 (15.8)	14 (21.5)	52 (41.3)^a	< 0.001
Complications
ARDS	86 (6.5)	65 (5.7)	21 (11.0)	0.006	26 (3.3)	2 (3.1)	19 (15.1)	< 0.001
ACI	148 (11.1)	132 (11.6)	16 (8.4)	0.193	77 (9.9)	3 (4.6)	12 (9.5)	0.379
AKI	18 (1.4)	14 (1.2)	4 (2.1)	0.535	6 (0.8)	1 (1.5)	3 (2.4)	0.122
Secondary infection	161 (12.1)	139 (12.2)	22 (11.5)	0.791	76 (9.8)	4 (6.2)	18 (14.3)	0.162
Shock	25 (1.9)	23 (2.0)	2 (1.0)	0.531	9 (1.2)	0 (0.0)	2 (1.6)^a	0.706
Hypoproteinemia < 30g/l	99 (7.7)	71 (6.5)	28 (15.0)	< 0.001	38 (5.0)^c	11 (16.9)	17 (13.9)	< 0.001
Length of hospital stay, d	17.0 (10.0-24.0)	17.0 (10.0-24.0)	16.0 (10.0-25.0)	0.655	17.0 (11.0-24.0)	19.0 (11.5-27.0)	16.0 (8.0-22.5)	0.109
ICU admission	125 (9.4)	103 (9.0)	22 (11.5)	0.276	57 (7.3)	5 (7.7)	17 (13.5)	0.062
Duration from admission to ICU, d	4.00 (1.00-7.50)	5.00 (1.00-8.00)	3.50 (1.75-5.25)	0.383	4.50 (1.00-8.00)	5.00 (1.50-6.00)	3 (1.50-4.50)	0.733
Prognosis
Death, No	108 (8.1)	82 (7.2)	26 (13.6)	0.003	26 (3.3)	3 (4.6)	23 (18.3)	< 0.001

¹Comparing groups of diabetic and non-diabetic patients.

²Comparing groups of non-comorbidity, only diabetes and diabetes with comorbidities.

Compared with diabetes only group:

^aP < 0.05.

^bP < 0.05.

^cP < 0.001.

ACI: Acute cardiac injury; AKI: Acute kidney injury; ARDS: Acute respiratory distress syndrome.

Table 4 Laboratory results of diabetic survivors and non-survivors with coronavirus disease 2019

	Total (n = 191)	Survivors (n = 165)	Non-survivors (n = 26)	P value
WBC, × 10⁹per L	5.94 (4.49-7.53)	5.91 (4.42-7.29)	7.26(5.19-13.07)	0.016
NEUT, × 10⁹per L	4.25 (3.13-5.37)	4.09 (3.01-5.13)	6.22 (3.69-11.33)	< 0.001
LY, × 10⁹per L	1.04 (0.72-1.43)	1.08 (0.78-1.48)	0.65 (0.56-1.07)	< 0.001
NLR	3.85 (2.45-6.37)	3.50 (2.33-5.53)	10.43 (5.78-16.84)	< 0.001
Hb, g/L	127.3 ± 16.9	126.8 ± 16.7	131.6 ± 18.3	0.314
PLT, × 10⁹per L	196 (147-255)	201 (152-201)	155 (110-230)	0.033
PCT, ng/mL
< 0.5	143 (94.7)	132 (98.5)	11 (64.7)	< 0.001
≥ 0.5	8 (5.3)	2 (1.5)	6 (35.3)
CRP	29.8 (5.5-75.9)	25.4 (4.4-63.0)	115.3 (66.1-170.6)	< 0.001
IL-6, pg/mL	3.31 (1.64-17.49)	3.09 (1.50-5.25)	83.47 (35.75-243.60)	< 0.001
PT, s	14.30 (11.90-15.50)	14.00 (11.60-15.40)	16.20 (13.52-18.92)	0.002
< 16	116 (76.8)	110 (81.5)	6 (37.5)	< 0.001
≥ 16	35 (23.2)	25 (18.5)	10 (62.5)
D-dimer, mg/L	0.69 (0.35-1.35)	0.62 (0.62-1.09)	5.40 (1.50-21.00)	< 0.001
≤ 0.5	58 (37.9)	57 (41.9)	1 (5.9)	< 0.001
> 0.5 to ≤ 1.0	46 (30.1)	43 (31.6)	3 (17.6)
> 1.0	49 (32.0)	36 (26.5)	13 (76.5)
ALB, g/L	35.7 ± 5.5	36.0 ± 30.5	33.5 ± 23.4	0.031
ALT, U/L	23.0 (16.0-34.0)	21.3 (15.3-32.3)	31.0 (20.9-46.6)	0.008
AST, U/L	29.0 (20.0-41.0)	27.0 (19.0-38.7)	43.0 (31.0-60.5)	< 0.001
ALP, U/L	55.0 (43.5-74.0)	55.0 (41.5-73.0)	57.0 (49.5-89.5)	0.241
TBIL, mmol/L	11.3 (8.3-15.7)	11.4 (9.0-15.1)	11.2 (7.6-28.0)	0.642
Potassium, mmol/L	3.88 (3.52-4.21)	3.90 (3.54-4.21)	3.65 (3.37-4.30)	0.381
Sodium, mmol/L	138.4 ± 4.3	138.2 ± 3.9	139.3 ± 6.4	0.418
Chlorine ion, mmol/L	103.5 ± 4.9	103.2 ± 4.7	105.3 ± 6.0	0.052
Calcium, mmol/L	2.09 (1.95-2.17)	2.10 (1.95-2.20)	2.00 (1.89-2.11)	0.042
Phosphorus, mmol/L	1.01 (0.86-1.18)	1.02 (0.87-1.19)	0.93 (0.76-1.18)	0.268
BUN, mmol/L	4.70 (3.60-6.22)	4.5 (3.59-5.82)	6.51 (4.92-17.45)	< 0.001
Creatinine, μmol/L	66.3 (54.0-83.8)	64.0 (44.6-81.0)	73.0 (64.0-129.6)	0.006
UA, μmol/L	258 (193-332)	258 (147-321)	293 (179-428)	0.286
CK, U/L	66.5 (40.3-117.8)	61.0 (36.5-111.0)	85.0 (71.0-364.0)	0.002
LDH, U/L	229 (180-341)	216 (172-219)	522 (420-611)	< 0.001
Hs-cTnI > ULN, pg/mL	10/88 (11.4)	8/72 (11.1)	2/16 (12.5)	1.000
TG, mmol/L	1.39 (1.04-1.83)	1.41 (1.05-1.98)	1.31 (0.99-1.57)	0.398
TCH, mmol/L	4.04 ± 1.10	4.12 ± 1.06	3.39 ± 1.16	0.009
LDL-C, mmol/L	2.54 ± 0.90	2.59 ± 0.88	2.10 ± 0.93	0.036
HDL-C, mmol/L	0.94 ± 0.26	0.94 ± 0.26	0.89 ± 0.33	0.450
FPG, mmol/L	9.10 (6.50-11.72)	8.70 (6.50-11.36)	12.00 (9.40-16.81)	0.011
3.9-6.9	43 (27.7)	40 (28.6)	3 (20.0)	0.069¹
7.0-11.1	61 (39.4)	58 (41.4)	3 (20.0)
≥ 11.1	51 (32.9)	42 (30.0)	9 (60.0)
HbA1C	7.77 ± 1.97	7.61 ± 1.90	9.53 ± 2.02	0.021

Data are expressed as n (%), mean ± SD or median (IQR). P values were calculated by t Test, Mann-Whitney U test, χ²test, Fisher’s exact test as appropriate.

¹Mann-Whitney U test comparing all subcategories.

P: Comparing groups of diabetic survivors and non-survivors; ALB: Albumin; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BUN: Urea nitrogen; CK: Creatine kinase; CRP: C reactive protein; FPG: Fasting plasma glucose; Hb: Hemoglobin; HbA1C: Glycosylated hemoglobin; HDL-C: High density lipoprotein cholesterol; Hs-cTnI: Hypersensitive troponin I; LDH: Lactate dehydrogenase; LDL-C: Low density lipoprotein cholesterol; LY: Lymphocyte; NEUT: Neutrophil; NLR: Neutrophil lymphocyte ratio; PCT: Procalcitonin; PLT: Platelet; PT: Prothrombin time; TBIL: Total bilirubin; TCH: Total cholesterol; TG: Triglyceride; UA: Uric acid; WBC: White blood cell.

Table 5 Treatments and outcomes of diabetic survivors and non-survivors with coronavirus disease 2019

	Total (n = 191)	Survivors (n = 165)	Non-survivors (n = 26)	P value
Treatments
Antiviral therapy	170 (89.0)	149 (90.3)	21 (80.8)	0.268
Antibiotic therapy	160 (83.8)	139 (84.2)	21 (80.8)	0.873
Systemic glucocorticoids	74 (38.7)	55 (33.3)	19 (73.1)	< 0.001
Intravenous immunoglobulin	60 (31.4)	50 (30.3)	10 (38.5)	0.405
Renal replacement therapy	1 (0.5)	0 (0.0)	1 (3.8)	0.136
Insulin	88 (46.1)	75 (45.5)	13 (50.0)	0.666
Metformin	54 (28.3)	51 (30.9)	3 (11.5)	0.041
Sulfonylurea	37 (19.4)	36 (21.8)	1 (3.8)	0.031
DPP-4 inhibitor	11 (5.8)	10 (6.1)	1 (3.8)	1.000
Acarbose	77 (40.3)	75 (45.5)	2 (7.7)	< 0.001
Thiazolidinedione	7 (3.7)	7 (4.2)	0 (0.0)	0.596
Oxygen support
Oxygenation	115 (60.2)	95 (57.6)	20 (76.9)	0.061
Mechanical ventilation	35 (18.3)	15 (9.1)	20 (76.9)	< 0.001
Illness severity
Severe	63 (33.0)	37 (33.7)	26 (100)	< 0.001
Complications
ARDS	21 (11.0)	5 (3.0)	16 (61.5)	< 0.001
ACI	16 (8.4)	9 (5.5)	7 (26.9)	0.001
AKI	3 (1.6)	1 (0.6)	2 (7.7)	0.049
Secondary infection	22 (11.5)	10 (6.1)	12 (46.2)	< 0.001
Shock	3 (1.6)	0 (0.0)	3 (11.5)	0.002
Hypoproteinemia < 30 g/L	28 (14.7)	22 (13.3)	6 (23.1)	0.314
Coagulopathy	36 (18.8)	26 (15.8)	10 (38.5)	0.013
Length of hospital stay, d	16.0 (10.0-25.0)	18.0 (11.5-26.0)	7.0 (3.0-11.0)	< 0.001
ICU admission	22 (11.5)	11 (6.7)	11 (42.3)	< 0.001
Duration from admission to ICU, d	4.00 ± 3.51	3.91 ± 3.11	4.09 ± 4.01	0.907

Data are expressed as n (%), mean ± SD or median (IQR). P values were calculated by t Test, Mann-Whitney U test, χ²test, Fisher’s exact test as appropriate. Comparing groups of diabetic survivors and non-survivors. ACI: Acute cardiac injury; AKI: Acute kidney injury; ARDS: Acute respiratory distress syndrome.

Table 6 Laboratory results of diabetic coronavirus disease 2019 patients using metformin or acarbose and matched non-metformin or non-acarbose inhibitor user

	Metformin (n = 50)	Matched non-Metformin (n = 50)	Acarbose (n = 46)	Matched non-acarbose (n = 46)
WBC, × 10⁹/L	6.33 ± 2.25	6.27 ± 2.62	4.83 (4.04-6.68)	5.91 (4.42-9.35)^c
NEUT, × 10⁹/L	4.20 (3.02-5.18)	4.17 (3.21-5.87)	3.50 (2.48-4.74)	4.60 (3.14-8.13)
LY, × 10⁹/L	1.20 (0.69-1.74)	1.14 (0.82-1.50)	1.19 ± 0.55	1.04 ± 0.53
NLR	3.69 (2.11-6.05)	3.74 (2.47-5.55)	3.25 (2.05-4.41)	4.88 (2.50-12.32)^d
Hb, g/L	126.0 ± 15.7	126.5 ± 14.9	126.0 ± 16.9	129.3 ± 17.3
PLT, × 10⁹/L	229.5 ± 93.5	208.5 ± 103.8	233.0 ± 93.2	214.2 ± 99.7
PCT, ng/mL
< 0.5	43 (100.0)	34 (91.9)	37 (100.0)	34 (87.2)
≥ 0.5	0 (0.0)	3 (8.1)	0 (0.0)	5 (12.8)
CRP	50.7 (5.0-78.0)	46.5 (6.3-106.8)	26.2 (3.7-52.2)	63.8 (10.8-83.4)^c
IL-6, pg/mL	2.07 (1.50-4.90)	3.20 (1.68-67.28)	2.58 (1.50-5.06)	19.88 (1.95-67.28)
PT, s	13.5 ± 2.7	14.2 ± 2.2	14.1 ± 2.6	14.2 ± 3.2
< 16	37 (86.0)	31 (79.5)	30 (78.9)	27 (73.0)
≥ 16	6 (14.0)	8 (20.5)	8 (21.1)	10 (27.0)
D-dimer, mg/L	0.45 (0.26-1.19)	0.83 (0.33-1.60)	0.59 (0.33-0.98)	0.96 (0.39-5.40)
≤ 0.5	22 (52.4)	13 (33.3)	18 (42.9)	12 (33.3)
> 0.5 to ≤ 1.0	6 (14.3)	11 (28.2)	15 (35.7)	7 (19.4)
> 1.0	14 (33.3)	15 (38.5)	9 (21.4)	17 (47.2)
ALB, g/L	35.7 ± 5.9	35.8 ± 5.5	35.7 ± 6.5	35.1 ± 4.8
ALT, U/L	20.0 (13.5-27.5)	22.0 (17.0-36.0)	20.0 (14.0-31.0)	23.00 (14.00-33.25)
AST, U/L	25.5 (18.5-33.7)	29.0 (20.0-42.0)	23.0 (17.5-36.4)	31.0 (21.5-39.6)
ALP, U/L	51.0 (37.0-71.0)	54.0 (44.0-68.0)	59.5 24.6	61.5 25.5
TBIL, mmol/L	12.2 ± 5.4	13.4 ± 16.2	11.5 ± 4.8	13.5 ± 5.4
Potassium, mmol/L	3.81 ± 0.46	3.77 ± 0.54	3.90 ± 0.50	3.82 ± 0.63
Sodium, mmol/L	137.9 ± 3.9	138.2 ± 4.1	138. 5 ± 3.8	138.1 ± 4.7
Chlorine ion, mmol/L	103.3 ± 4.5	103.4 ± 5.0	103.2 ± 4.6	103.7 ± 5.3
Calcium, mmol/L	2.14 ± 0.22	2.05 ± 0.18^a	2.12 ± 0.22	2.08 ± 0.19
Phosphorus, mmol/L	1.02 (0.83-1.21)	0.99 (0.87-1.17)	1.07( 0.88-1.21)	1.00 (0.77-1.21)
BUN，mmol/L	4.40 (3.67-4.84)	5.20 (3.50-5.75)	4.16 (3.60-5.18)	5.04 (3.80-6.64)
Creatinine, μmol/L	54.0 (49.0-73.7)	60.0 (52.5-90.3)	59.5 (48.8-74.5)	68.0 (55.0-89.3)
UA, μmol/L	266.5 ± 96.6	260.9 ± 98.7	229 (168-263)	258 (179-324)
CK, U/L	64.0 (49.0-84. 0)	82.0 (39.0-135.3)	53.5 (35.5-73.8)	71.0 (40.0-114.0)
LDH, U/L	237 ± 115	304 ± 162^a	229 (185-263)	267 (181-446)
Hs-cTnI > ULN , pg/mL	0/24 (0.0)	3/15 (20.0)	1/21 (4.8)	2/26 (7.7)
TG, mmol/L	1.55 (1.15-1.82)	1.32 (1.08-3.40)	1.36 (1.05-1.83)	1.15 (0.94-1.61)
TCH, mmol/L	3.91 ± 0.87	3.80 ± 0.92	4.40 ± 1.14	4.04 ± 0.96
LDL-C, mmol/L	2.40 ± 0.73	2.43 ± 0.78	2.84 ± 0.87	2.57 ± 0.83
HDL-C, mmol/L	0.93 ± 0.22	0.88 ± 0.28	0.98 ± 0.27	0.93 ± 0.23
FPG, mmol/L	10.57 ± 4.92	8.32 ± 2.47^b	9.92 ± 4.90	10.00 ± 4.26
3.9-6.9	11 (44.0)	13 (38.2)	12 (30.8)	8 (22.2)
7.0-11.1	13 (52.0)	21 (61.8)	13 (33.3)	16 (44.4)
≥ 11.1	1 (4.0)	0 (0.0)	14 (35.9)	12 (33.3)
HbA1C	7.96 ± 1.85	6.71 ± 1.94	7.85 ± 1.78	8.25 ± 2.04

Data are expressed as n (%), mean ± SD or median (IQR). P values were calculated by t Test, Mann-Whitney U test, χ²test, Fisher’s exact test as appropriate.

Comparison of metformin users and non-users:

^aP < 0.05.

^bP < 0.01.

Comparison of acarbose users and non-users:

^cP < 0.05.

^dP < 0.01.

Table 7 Treatments and outcomes of diabetic coronavirus disease 2019 patients using metformin and matched non-metformin, acarbose and matched non-acarbose

	Metformin (n = 50)	Matched non-Metformin (n = 50)	Acarbose (n = 46)	Matched non-acarbose (n = 46)
Treatments
Antiviral therapy	49 (98.0)	42 (84.0)^a	41 (89.1)	43 (93.5)
Antibiotic therapy	45 (90.0)	37 (74.0)^a	40 (87.0)	40 (87.0)
systemic glucocorticoids	17 (34.0)	16 (32.0)	12 (26.1)	22 (47.8)^e
Intravenous immunoglobulin	15 (30.0)	11 (22.0)	11 (23.9)	22 (47.8)^e
Renal replacement therapy	0 (0.0)	1 (2.0)	0 (0.0)	0 (0.0)
Insulin	26 (52.0)	10 (20.0)^b	23 (50.0)	39 (84.8)^g
Metformin	50	0	21 (45.7)	15 (32.6)
Sulfonylurea	18 (36.0)	1 (2.0)^c	17 (37.0)	8 (17.4)^e
DPP-4 inhibitor	3 (6.0)	0 (0.0)	3 (6.5)	3 (6.5)
Acarbose	28 (56.0)	3 (6.0)^c	46 (100.0)	0 (0.0)
thiazolidinedione	6 (12.0)	0 (0.0)^a	4 (8.7)	0 (0.0)
Oxygen support
Oxygenation	32 (64.0)	21 (42.0)	30 (65.2)	30 (65.2)
Mechanical ventilation	6 (12.0)	11 (22.0)	3 (6.5)	10 (21.7)^e
Illness severity
Severe	14 (28.0)	21 (42.0)	12 (26.1)	18 (39.1)
Complications
ARDS	4 (8.0)	8 (16.0)	1 (2.2)	8 (17.4)^e
ACI	1 (2.0)	4 (8.0)	2 (4.3)	6 (13.0)
AKI	0 (0.0)	0 (0.0)	0 (0.0)	2 (4.3)
Secondary infection	8 (16.0)	5 (10.0)	0 (0.0)	2 (4.3)
Shock	1 (2.0)	0 (0.0)	1 (2.2)	10 (21.7)^e
Hypoproteinemia < 30 g/L	9 (18.0)	5 (10.0)	10 (21.7)	6 (13.0)
Coagulopathy	6 (12.0)	9 (18.0)	8 (17.4)	10 (21.7)
Length of hospital stay, d	17.60 ± 8.74	16.80 ± 10.51	18.37 ± 8.15	16.52 ± 9.96
ICU admission	6 (12.0)	6 (12.0)	3 (6.5)	8 (17.4)
Duration from admission to ICU, d	3.83 ± 2.04	2.83 ± 2.14	6.00 (3.50-6.00)	2.50 (2.00-5.00)
Prognosis
Discharged	47 (94)	41 (82)	45 (97.8)	34 (73.9)^f
Death	3 (6.0)	9 (18)	1 (2.2)	12 (26.1)

Data are expressed as n (%), mean ± SD or median (IQR). P values were calculated by t Test, Mann-Whitney U test, χ²test, Fisher’s exact test as appropriate.

Comparison of metformin users and non-users:

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

Comparison of acarbose users and non-users:

^eP < 0.05.

^fP < 0.01.

^gP < 0.001.

ACI: Acute cardiac injury; AKI: Acute kidney injury; ARDS: Acute respiratory distress syndrome.

Table 8 Multivariate COX regression analysis on the risk factors associated with mortality of 1331 coronavirus disease 2019 patients

Factor	Hazard ratio	P value
Sex (male)	2.59 (1.68-3.99)	< 0.001
Age, yr
18-49	1 (ref)
50-64	5.86 (2.27-15.12)	< 0.001
≥ 65	11.8 (4.6- 30.2)	< 0.001
Hypertension	1.75 (1.18-2.60)	0.006
CKD	4.55 (2.52-8.20)	< 0.001
CVD	2.35 (1.27-4.33)	0.006
Diabetes	0.98 (0.62-1.54)	0.918

CKD: Chronic kidney disease; CVD: Cerebrovascular disease.

Citation: Luo SK, Hu WH, Lu ZJ, Li C, Fan YM, Chen QJ, Chen ZS, Ye JF, Chen SY, Tong JL, Wang LL, Mei J, Lu HY. Diabetes patients with comorbidities had unfavorable outcomes following COVID-19: A retrospective study. World J Diabetes 2021; 12(10): 1789-1808
URL: https://www.wjgnet.com/1948-9358/full/v12/i10/1789.htm
DOI: https://dx.doi.org/10.4239/wjd.v12.i10.1789