J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website https://jem.elmerpub.com

Original Article

Volume 15, Number 4, October 2025, pages 161-180

Link Between Immune Dysregulation in COVID-19 and Beta-Cell Dysfunction

↓ Figure 1. Distribution of the patients from group 2 (post-COVID-19 group) according to the type of carbohydrate disorder. T1DM: type 1 diabetes mellitus; T2DM: type 2 diabetes mellitus; IFG: impaired fasting glucose; IGT: impaired glucose tolerance; IR: insulin resistance; COVID-19: coronavirus disease 2019.

↓ Figure 2. Immunological parameters (mean values) in patients with DM (DM+) and without DM (DM -) in patients from group 1 (active COVID-19) and group 2 (post-COVID-19 with new-onset carbohydrate disorders). The blue star indicates a statistically significant difference (P < 0.05) between the two subgroups (DM+ and DM-). CD: cluster of differentiation; IL: interleukin; IFN-γ: interferon-gamma; TNF-α: tumor-necrosis factor - alpha; HCFD: human complement factor D; DM: diabetes mellitus; COVID-19: coronavirus disease 2019.

↓ Figure 3. Oxidative stress, antioxidant defense and hypoxia indicators (mean values) in patients with DM (DM+) and without DM (DM-) in patients from group 1 (active COVID-19) and group 2 (post-COVID-19 with new-onset carbohydrate disorders). The blue star indicates a statistically significant difference (P < 0.05) between the two subgroups (DM+ and DM-). 8-epi-PGF2α: 8-epi-prostaglandyn F2 alpha; NFE2L2: nuclear factor erythroid 2-related factor 2; HIF-1α: hypoxia inducible factor-1 alpha; DM: diabetes mellitus; COVID-19: coronavirus disease 2019.

↓ Figure 4. Distribution of the patients according to the diagnosis of DM and its duration among the three groups. DM: diabetes mellitus.

↓ **Table 1.** General Clinical Characteristics of the Study Population
Variable	Group 1 (n = 32)	Group 2 (n = 35)	Group 3 (n = 33)	All (n = 100)
DM: diabetes mellitus.
Age (mean)	66.71 ± 4.87	45.35 ± 4.98	48.21 ± 4.51	53.07 ± 3.27
Gender
Male	N = 18 (56.25%)	N = 13 (37.15%)	N = 3 (9.1%)	N = 34 (34%)
Female	N = 14 (43.75%)	N = 22 (62.85%)	N = 30 (90.90%)	N = 66 (66%)
Family history of DM
Yes	N = 7 (21.88%)	N = 14 (40%)	N = 15 (45.45%)	N = 36 (36%)
No	N = 25 (78.12%)	N = 21 (60%)	N = 18 (54.55%)	N = 64 (64%)
Residence
Urban	N = 22 (68.75%)	N = 25 (71.43%)	N = 23 (69.70%)	N = 70 (70%)
Rural	N = 10 (31.25%)	N = 10 (28.57%)	N = 10 (30.30%)	N = 30 (30%)
Smoking
Yes	N = 7 (21.88%)	N = 8 (22.86%)	N = 10 (30.30%)	N = 25 (25%)
No	N = 25 (78.12%)	N = 27 (77.14%)	N = 23 (69.70%)	N = 75 (75%)
Sedentary lifestyle
Yes	N = 22 (68.75%)	N = 13 (37.15%)	N = 20 (60.60%)	N = 55 (55%)
No	N = 10 (31.25%)	N = 22 (62.85%)	N = 13 (39.40%)	N = 45 (45%)

↓ Table 1. General Clinical Characteristics of the Study Population

Variable

Group 1 (n = 32)

Group 2 (n = 35)

Group 3 (n = 33)

All (n = 100)

DM: diabetes mellitus.

Age (mean)

66.71 ± 4.87

45.35 ± 4.98

48.21 ± 4.51

53.07 ± 3.27

Gender

Male

N = 18 (56.25%)

N = 13 (37.15%)

N = 3 (9.1%)

N = 34 (34%)

Female

N = 14 (43.75%)

N = 22 (62.85%)

N = 30 (90.90%)

N = 66 (66%)

Family history of DM

Yes

N = 7 (21.88%)

N = 14 (40%)

N = 15 (45.45%)

N = 36 (36%)

N = 25 (78.12%)

N = 21 (60%)

N = 18 (54.55%)

N = 64 (64%)

Residence

Urban

N = 22 (68.75%)

N = 25 (71.43%)

N = 23 (69.70%)

N = 70 (70%)

Rural

N = 10 (31.25%)

N = 10 (28.57%)

N = 10 (30.30%)

N = 30 (30%)

Smoking

Yes

N = 7 (21.88%)

N = 8 (22.86%)

N = 10 (30.30%)

N = 25 (25%)

N = 25 (78.12%)

N = 27 (77.14%)

N = 23 (69.70%)

N = 75 (75%)

Sedentary lifestyle

Yes

N = 22 (68.75%)

N = 13 (37.15%)

N = 20 (60.60%)

N = 55 (55%)

N = 10 (31.25%)

N = 22 (62.85%)

N = 13 (39.40%)

N = 45 (45%)

↓ **Table 2.** Metabolic Characteristics of the Study Population
Variable	Group 1 (n = 32)	Group 2 (n = 35)	Group 3 (n = 33)	All (n = 100)
BMI: body mass index; T1DM: type 1 diabetes mellitus; T2DM: type 2 diabetes mellitus; IFG: impaired fasting glucose; IGT: impaired glucose tolerance; IR: insulin resistance; DM: diabetes mellitus.
BMI
Mean	-	31.91 ± 2.57	35.67 ± 2.8
< 18.5 kg/m²	-	N = 0 (0%)	N = 0 (0%)
18.5 - 24.99 kg/m²	-	N = 7 (20%)	N = 4 (12.12%)
25 - 29.99 kg/m²	-	N = 9 (25.72%)	N = 4 (12.12%)
30 - 34.99 kg/m²	-	N = 6 (17.15%)	N = 8 (24.24%)
35 - 39.99 kg/m²	-	N = 8 (22.85%)	N = 6 (18.18%)
> 40 kg/m²	-	N = 5 (14.28%)	N = 11 (33.33%)
DM
Yes	N = 16 (50%)	N = 19 (54.28%)	N = 11 (33.33%)	N = 46 (46%)
No	N = 16 (50%)	N = 16 (45.72%)	N = 22 (76.76%)	N =54 (54%)
New-diagnosed DM
Yes	N = 7 (21.88%)	N = 19 (54.28%)	N = 2 (6.06%)	N =28 (28%)
No	N =25 (78.12%)	N = 16 (45.72%)	N = 31 (93.94%)	N =72 (72%)
Type of carbohydrate disorder
T1DM		N = 8 (22.85%)	N = 0 (0%)
T2DM		N = 11 (31.43%)	N = 11 (33.33%)
IFG		N = 4 (11.43%)	N = 4 (12.12%)
IGT		N = 3 (8.57%)	N = 2 (6.06%)
IR/hyper-insulinemia		N = 9 (25.72%)	N = 16 (48.48%)

↓ Table 2. Metabolic Characteristics of the Study Population

Variable

Group 1 (n = 32)

Group 2 (n = 35)

Group 3 (n = 33)

All (n = 100)

BMI: body mass index; T1DM: type 1 diabetes mellitus; T2DM: type 2 diabetes mellitus; IFG: impaired fasting glucose; IGT: impaired glucose tolerance; IR: insulin resistance; DM: diabetes mellitus.

BMI

Mean

31.91 ± 2.57

35.67 ± 2.8

< 18.5 kg/m²

N = 0 (0%)

18.5 - 24.99 kg/m²

N = 7 (20%)

N = 4 (12.12%)

25 - 29.99 kg/m²

N = 9 (25.72%)

N = 4 (12.12%)

30 - 34.99 kg/m²

N = 6 (17.15%)

N = 8 (24.24%)

35 - 39.99 kg/m²

N = 8 (22.85%)

N = 6 (18.18%)

> 40 kg/m²

N = 5 (14.28%)

N = 11 (33.33%)

Yes

N = 16 (50%)

N = 19 (54.28%)

N = 11 (33.33%)

N = 46 (46%)

N = 16 (50%)

N = 16 (45.72%)

N = 22 (76.76%)

N =54 (54%)

New-diagnosed DM

Yes

N = 7 (21.88%)

N = 19 (54.28%)

N = 2 (6.06%)

N =28 (28%)

N =25 (78.12%)

N = 16 (45.72%)

N = 31 (93.94%)

N =72 (72%)

Type of carbohydrate disorder

T1DM

N = 8 (22.85%)

N = 0 (0%)

T2DM

N = 11 (31.43%)

N = 11 (33.33%)

IFG

N = 4 (11.43%)

N = 4 (12.12%)

IGT

N = 3 (8.57%)

N = 2 (6.06%)

IR/hyper-insulinemia

N = 9 (25.72%)

N = 16 (48.48%)

↓ **Table 3.** Standard Biochemical Parameters (Lipid Profile, UA and Liver Function Test) of the Study Population
Variable (mean ± SD)	Group 1 (n = 32)	Group 2 (n = 35)	Group 3 (n = 33)	P value
NS: no significance; P < 0.05 indicates a statistically significance difference. P < 0.05: statistically significant difference between group 1 and group 2; P < 0.05: statistically significant difference between group 2 and group 3. **P < 0.05: statistically significant difference between group 1 and group 3. SD: standard deviation; TC: total cholesterol; TG: triglycerides; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; UA: uric acid; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: gamma-glutamyl transferase.
Lipid profile parameters
TC (mmol/L)	4.00 ± 1.11	4.87 ± 1.46	4.89 ± 1.14	< 0.05*
				< 0.05***
TG (mmol/L)	2.05 ± 0.86	1.88 ± 0.84	1.90 ± 0.82	NS
LDL-C (mmol/L)	3.23 ± 0.93	3.10 ± 1.37	3.19 ± 0.96	NS
HDL-C (mmol/L)	0.72 ± 0.24	0.96 ± 0.38	0.87 ± 0.23	< 0.05*
UA (µmol/mL)	367.79 ± 159.0	398.23 ± 101.58	416.31 ± 101.37	< 0.05***
Liver function test
AST (IU/L)	32.72 ± 30.52	20.13 ± 13.73	24.50 ± 19.35	NS
ALT (IU/L)	34.77 ± 26.54	34.34 ± 45.74	26.09 ± 20.81	NS
GGT (IU/L)	106.78 ± 199.04

↓ Table 3. Standard Biochemical Parameters (Lipid Profile, UA and Liver Function Test) of the Study Population

Variable (mean ± SD)

Group 1 (n = 32)

Group 2 (n = 35)

Group 3 (n = 33)

P value

NS: no significance; P < 0.05 indicates a statistically significance difference. *P < 0.05: statistically significant difference between group 1 and group 2; **P < 0.05: statistically significant difference between group 2 and group 3. ***P < 0.05: statistically significant difference between group 1 and group 3. SD: standard deviation; TC: total cholesterol; TG: triglycerides; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; UA: uric acid; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: gamma-glutamyl transferase.

Lipid profile parameters

TC (mmol/L)

4.00 ± 1.11

4.87 ± 1.46

4.89 ± 1.14

< 0.05*

< 0.05***

TG (mmol/L)

2.05 ± 0.86

1.88 ± 0.84

1.90 ± 0.82

LDL-C (mmol/L)

3.23 ± 0.93

3.10 ± 1.37

3.19 ± 0.96

HDL-C (mmol/L)

0.72 ± 0.24

0.96 ± 0.38

0.87 ± 0.23

< 0.05*

UA (µmol/mL)

367.79 ± 159.0

398.23 ± 101.58

416.31 ± 101.37

< 0.05***

Liver function test

AST (IU/L)

32.72 ± 30.52

20.13 ± 13.73

24.50 ± 19.35

ALT (IU/L)

34.77 ± 26.54

34.34 ± 45.74

26.09 ± 20.81

GGT (IU/L)

106.78 ± 199.04

↓ **Table 4.** Immunological and Other Parameters Evaluated Among the Study Population
Variable (mean ± SD)	Group 1 (n = 32)	Group 2 (n = 35)	Group 3 (n = 33)	P value
NS: no significance; P < 0.05 indicates statistically significance difference. P < 0.05: statistically significant difference between group 1 and group 2; P < 0.05: statistically significant difference between group 2 and group 3; **P < 0.05: statistically significant difference between group 1 and group 3. SD: standard deviation; CD: cluster of differentiation; IL: interleukin; IFN-γ: interferon-gamma; TNF-α: tumor-necrosis factor-alpha; HCFD: human complement factor D; 8-epi-PGF2α: 8-epi-Prostaglandyn F2 alpha; NFE2L2: nuclear factor erythroid 2-related factor 2; HIF-1α: hypoxia inducible factor - 1 alpha.
CD4 (ng/mL)	8.65 ± 2.07	8.24 ± 3.18	4.41 ± 1.30	P < 0.05***
CD8 (ng/mL)	18.70 ± 4.21	24.45 ± 8.27	31.08 ± 7.73	NS
IL-7 (pg/mL)	36.70 ± 4.2	34.38 ± 11.71	55.22 ± 10.52	P < 0.05**
				P < 0.05***
IL-10 (pg/mL)	4.54 ± 1.84	3.45 ± 1.48	2.99 ± 0.45	NS
IL-17A (pg/mL)	29.44 ± 1.90	30.26 ± 5.23	40.45 ± 12.62	P < 0.05**
IFN-γ (pg/mL)	12.23 ± 1.29	5.90 ± 1.51	14.90 ± 2.09	P < 0.05**
				P < 0.05***
TNF-α (pg/mL)	117.09 ± 30.13	129.09 ± 40.17	86.36 ± 25.82	NS
HCFD (ng/mL)	8,027.77 ± 5,178.25	966.18 ± 700.37	34,611.23 ± 10,086.35	P < 0.05*
				P < 0.05**
				P < 0.05***
8-epi-PGF2α (pg/mL)	46.74 ± 3.91	62.64 ± 8.47	85.81 ± 28.41	P < 0.05*
				P < 0.05**
				P < 0.05***
NFE2L2 (pg/mL)	229.21 ± 26.27	245.91 ± 95.33	220.42 ± 38.32	NS
HIF-1α (pg/mL)	1,321.51 ± 474.21	358.76 ± 164.45	558.87 ± 168.36	P < 0.05*
				P < 0.05**
				P < 0.05***

↓ Table 4. Immunological and Other Parameters Evaluated Among the Study Population

Variable (mean ± SD)

Group 1 (n = 32)

Group 2 (n = 35)

Group 3 (n = 33)

P value

NS: no significance; P < 0.05 indicates statistically significance difference. *P < 0.05: statistically significant difference between group 1 and group 2; **P < 0.05: statistically significant difference between group 2 and group 3; ***P < 0.05: statistically significant difference between group 1 and group 3. SD: standard deviation; CD: cluster of differentiation; IL: interleukin; IFN-γ: interferon-gamma; TNF-α: tumor-necrosis factor-alpha; HCFD: human complement factor D; 8-epi-PGF2α: 8-epi-Prostaglandyn F2 alpha; NFE2L2: nuclear factor erythroid 2-related factor 2; HIF-1α: hypoxia inducible factor - 1 alpha.

CD4 (ng/mL)

8.65 ± 2.07

8.24 ± 3.18

4.41 ± 1.30

P < 0.05***

CD8 (ng/mL)

18.70 ± 4.21

24.45 ± 8.27

31.08 ± 7.73

IL-7 (pg/mL)

36.70 ± 4.2

34.38 ± 11.71

55.22 ± 10.52

P < 0.05**

P < 0.05***

IL-10 (pg/mL)

4.54 ± 1.84

3.45 ± 1.48

2.99 ± 0.45

IL-17A (pg/mL)

29.44 ± 1.90

30.26 ± 5.23

40.45 ± 12.62

P < 0.05**

IFN-γ (pg/mL)

12.23 ± 1.29

5.90 ± 1.51

14.90 ± 2.09

P < 0.05**

P < 0.05***

TNF-α (pg/mL)

117.09 ± 30.13

129.09 ± 40.17

86.36 ± 25.82

HCFD (ng/mL)

8,027.77 ± 5,178.25

966.18 ± 700.37

34,611.23 ± 10,086.35

P < 0.05*

P < 0.05**

P < 0.05***

8-epi-PGF2α (pg/mL)

46.74 ± 3.91

62.64 ± 8.47

85.81 ± 28.41

P < 0.05*

P < 0.05**

P < 0.05***

NFE2L2 (pg/mL)

229.21 ± 26.27

245.91 ± 95.33

220.42 ± 38.32

HIF-1α (pg/mL)

1,321.51 ± 474.21

358.76 ± 164.45

558.87 ± 168.36

P < 0.05*

P < 0.05**

P < 0.05***

↓ **Table 5.** Evaluated Glycemic and Hormonal Parameters Among the Studied Population
Variable (mean ± SD)	Group 1 (n = 32)	Group 2 (n = 35)	Group 3 (n = 33)	P value
NS: no significance; P < 0.05 indicates statistically significance difference. P < 0.05: statistically significant difference between group 1 and group 2; P < 0.05: statistically significant difference between group 2 and group 3; **P < 0.05: statistically significant difference between group 1 and group 3. SD: standard deviation; HbA1c: glycated hemoglobin; GP-73: golgi protein-73.
Fasting glucose (mmol/L)	7.37 ± 1.81	7.64 ± 3.7	5.69 ± 1.76	P < 0.05**
				P < 0.05***
HbA1c (%)	6.33 ± 0.83	8.00 ± 2.69	7.04 ± 1.4	NS
Insulin (µIU/mL)	26.19 ± 16.52	20.11 ± 19.5	31.86 ± 62.38	NS
C-peptide (ng/mL)	1.21 ± 1.21	1.54 ± 1.29	0.41 ± 0.61	P < 0.05**
				P < 0.05***
Proinsulin (pg/mL)	56.03 ± 34.14	41.55 ± 39.98	54.22 ± 52.37	NS
Glucagon (pg/mL)	6,456.68 ± 2,391.16	5,403.88 ± 1,999.43	8,152.59 ± 1,492.96	P < 0.05**
				P < 0.05***
GP-73 (ng/mL)	20.78 ± 9.7	42.39 ± 20.34	48.91 ± 26.15	P < 0.05*
				P < 0.05***
Leptin (ng/mL)	20.25 ± 26.30	32.14 ± 25.69	52.02 ± 34.59	P < 0.05*
				P < 0.05***
Adiponectin (µg/mL)	23.53 ± 3.92	25.03 ± 1.84	25.87 ± 0.60	NS

↓ Table 5. Evaluated Glycemic and Hormonal Parameters Among the Studied Population

Variable (mean ± SD)

Group 1 (n = 32)

Group 2 (n = 35)

Group 3 (n = 33)

P value

Fasting glucose (mmol/L)

7.37 ± 1.81

7.64 ± 3.7

5.69 ± 1.76

P < 0.05**

P < 0.05***

HbA1c (%)

6.33 ± 0.83

8.00 ± 2.69

7.04 ± 1.4

Insulin (µIU/mL)

26.19 ± 16.52

20.11 ± 19.5

31.86 ± 62.38

C-peptide (ng/mL)

1.21 ± 1.21

1.54 ± 1.29

0.41 ± 0.61

P < 0.05**

P < 0.05***

Proinsulin (pg/mL)

56.03 ± 34.14

41.55 ± 39.98

54.22 ± 52.37

Glucagon (pg/mL)

6,456.68 ± 2,391.16

5,403.88 ± 1,999.43

8,152.59 ± 1,492.96

P < 0.05**

P < 0.05***

GP-73 (ng/mL)

20.78 ± 9.7

42.39 ± 20.34

48.91 ± 26.15

P < 0.05*

P < 0.05***

Leptin (ng/mL)

20.25 ± 26.30

32.14 ± 25.69

52.02 ± 34.59

P < 0.05*

P < 0.05***

Adiponectin (µg/mL)

23.53 ± 3.92

25.03 ± 1.84

25.87 ± 0.60

↓ **Table 6.** Estimated Insulin and Non-Insulin Derived Indices Among the Studied Population
Variable (mean ± SD)	Group 1 (n = 32)	Group 2 (n = 35)	Group 3 (n = 33)	P value
NS: no significance; P < 0.05 indicates statistically significance difference. P < 0.05: statistically significant difference between group 1 and group 2; P < 0.05: statistically significant difference between group 2 and group 3; **P < 0.05: statistically significant difference between group 1 and group 3. SD: standard deviation; HOMA-IR: homeostasis model assessment of insulin resistance; HOMA-B: homeostasis model assessment of beta-cell function.
HOMA-IR	8.57 ± 5.59	7.41 ± 11.37	8.4 ± 17.67	NS
HOMA-B	159.33 ± 138.77	183.14 ± 175.85	330.09 ± 441.90	P < 0.05**
				P < 0.05***
C-peptide/glucose ratio	0.89 ± 0.81	1.35 ± 1.26	0.45 ± 0.69	P < 0.05**
				P < 0.05***
Insulin/proinsulin ratio	0.73 ± 0.87	0.71 ± 0.89	0.43 ± 0.26	P < 0.05**
				P < 0.05***
Adiponectin/leptin ratio	5.81 ± 8.35	2.24 ± 3.69	0.89 ± 0.79	P < 0.05**
				P < 0.05***

↓ Table 6. Estimated Insulin and Non-Insulin Derived Indices Among the Studied Population

Variable (mean ± SD)

Group 1 (n = 32)

Group 2 (n = 35)

Group 3 (n = 33)

P value

NS: no significance; P < 0.05 indicates statistically significance difference. *P < 0.05: statistically significant difference between group 1 and group 2; **P < 0.05: statistically significant difference between group 2 and group 3; ***P < 0.05: statistically significant difference between group 1 and group 3. SD: standard deviation; HOMA-IR: homeostasis model assessment of insulin resistance; HOMA-B: homeostasis model assessment of beta-cell function.

HOMA-IR

8.57 ± 5.59

7.41 ± 11.37

8.4 ± 17.67

HOMA-B

159.33 ± 138.77

183.14 ± 175.85

330.09 ± 441.90

P < 0.05**

P < 0.05***

C-peptide/glucose ratio

0.89 ± 0.81

1.35 ± 1.26

0.45 ± 0.69

P < 0.05**

P < 0.05***

Insulin/proinsulin ratio

0.73 ± 0.87

0.71 ± 0.89

0.43 ± 0.26

P < 0.05**

P < 0.05***

Adiponectin/leptin ratio

5.81 ± 8.35

2.24 ± 3.69

0.89 ± 0.79

P < 0.05**

P < 0.05***