New-onset diabetes in COVID-19 and clinical outcomes: A systematic review and meta-analysis

Table 4 Qualitative analysis of included studies

Ref.	Type of study	Country	Population	Outcome
Smith et al[19], 2021	Retrospective study, spanning over 7 wk	New Jersey, United States	n = 184, M/F = 98/86. Avg age = 64.4 yr (21-100). Below or equal to 60 yr = 75, Above 60 yr = 109. Mean BMI = 29.8 (17.5-61.4). COVID-19 diagnosis based on: 177 patients: Confirmed positive lab test for SARS-CoV-2. Remaining (7 patients): Clinical diagnosis. Case definitions used by the study: New-onset DM: Persistently elevated FBG > 125 mg/dL and requiring insulin therapy; Pre-DM: HbA1C of 5.7% to 6.4%; Non-diabetic patients: HbA1C < 5.7% and FBG ≤ 125 mg/dL	DM = 114/184 (New-onset DM= 29/184). Pre-DM = 44/184. Non-DM = 26/184. HbA1C levels: (1) ≥ 6.5% = 82/171; and (2) 5.7% to 6.4% = 64/171. Among intubated patients (44/184): (1) DM = 35/44 (Newly diagnosed DM = 7/44; New onset DM = 5/44); (2) Pre-DM with high FBG levels = 7/44; and (3) Non-DM = 1/44 (normal HbA1C and FBG levels at admission, but was clinically obese with a BMI > 30). Among intubated patients (44/184): (1) Mean BMI = 32.2 (vs 29.3 in non-intubated); (2) Mean HbA1C (%) = 8.0 (vs 7.2 in non-intubated); and (3) Mean FBG (mg/dL) = 238.0 (vs 163.7 in non-intubated). Death before intubation: 24/184: (1) DM = 17/24; (2) Pre-DM = 4/24; and (3) Non-DM = 3/24
Zhou et al[16], 2020	Retrospective study	Hefei, China	n = 80. Euglycemia group: (1) 44 (21 males and 23 females); and (2) Age range was 27-52 yr. Secondary hyperglycemia group: (1) 22 (17 males and 5 females); (2) Conditions of no past histories of diabetes, HbA1c < 6.5%, random blood glucose > 11.1 mmol/L during hospitalization, and normal blood glucose after discharge from the hospital; (3) Age range was 40-70 yr; and (4) 5 patients among them had elevated blood sugar after glucocorticoid therapy. Diabetes group: (1) 14 patients (10 males and 4 females); (2) All were T2DM patients; (3) Treated with oral antidiabetics or insulin before hospitalization and without glucocorticoid therapy during hospitalization; and (4) Ages ranged from 43 to 67 yr	Euglycemia group: 44/80. Secondary hyperglycemia group: 22/80. Diabetes group: 14/80. Non-severe COVID: (1) Euglycemia (n = 44): 34 (77.27); (2) Secondary hyperglycemia (n = 22): 15 (68.18); and (3) Diabetes (n = 14): 6 (42.86). Severe COVID: (1) Euglycemia (n = 44): 10 (22.73); (2) Secondary hyperglycemia (n = 22): 7 (31.82); and (3) Diabetes (n = 14): 8 (57.14). Evidence of pneumonia on CT = 78/80: (1) Euglycemia group = 42/44; (2) Secondary hyperglycemia group = 22/22; and (3) Diabetes group = 14/14
Wang et al[20], 2020	Retrospective study	Beijing, China	n = 132. Exclusion criteria: (1) If not tested positive for COVID-19; (2) Receiving glucocorticoids; (3) Hemolytic anemia; (4) Myelosuppression after leukemia chemotherapy; and (5) Median time from onset to admission was 14 (IQR 10.0–17.8) d. Three groups: A, B, and C-(1) Group A had no diabetes and their HbA1c level was 6.0; (2) Group B had no diabetes and their HbA1c level was > 6.0; (3) Group C were diabetic	41/132 patients in group A. 44/132 patients in group B. 47/132 patients in group C: (1) 31/47 = History of type 2 diabetes; and (2) 16/47 = Newly diagnosed with diabetes. Death = 22/132: (1) Deaths in group A = 4/41; (2) Deaths in group B = 5/44; and (3) Deaths in group C = 13/47
Suwanwongse and Shabarek[22], 2021	Case series	United States	n = 3 (18/M, 51/M , 64/F)	New-onset diabetes was diagnosed after infection with COVID-19. 2 out of 3 cases were diagnosed as Diabetic Ketoacidosis. All were discharged home after successful management of blood glucose levels. None of the cases developed any pulmonary, renal, hepatic or cardiac complications due to COVID-19. Invasive Mechanical Ventilation, ICU Admission, or Death did not occur in any of the three cases
Marchand et al[25], 2020	Short communication	France	n = 1	New-onset type-I DM after COVID-19. No information on severity or outcome of COVID-19
Kuchay et al[23], 2020	Case series	Haryana, India	n = 3 (30/M, 60/M, 34/M). Follow up duration: 14 wk. Three patients with newly diagnosed Diabetes Mellitus and Diabetic Ketoacidosis with positive SARS-CoV-2 laboratory report. Case Definition: Diabetic Ketoacidosis: DKA was defined as plasma glucose > 250 mg/dL, a positive test for urine or serum ketones, and arterial pH < 7.35 and/or a bicarbonate level less than 18 mmol/L	All three patients responded well to intravenous fluids, antibiotics, and insulin and were discharged after the third week. All three patients were given oral antihyperglycemic drugs after their requirement for exogenous insulin diminished after 4-6 wk. No mortality
Fadini et al[17], 2020	Retrospective study	Italy	COVID-19 positive hospitalized patients included: n (Total) = 413. Median observation time of 17 d	No diabetes = 306/413. Diabetes = 107/413 (Pre-existing diabetes = 86/413; Newly-diagnosed diabetes = 21/413). Primary Outcome (composite of ICU admission or death): 62/306 (20.3%); 7/86 (31.4%); 13/21 (61.9%). Death: 33/306 (10.8%); 12/86 (14.0%); 3/21 (14.3%). Discharged alive: 238/306 (77.8%); 51/86 (59.3%); 9/21 (42.9%). Mean time to discharge in alive pts: 10.1 ± 5.7 (n = 306); 11.6 ± 6.6 (n = 74); 17.4 ± 8.5 (n = 18). Mean days of hospitalization in survivors: 11.3 ± 7.1 (n = 306); 13.8 ± 8.0 (n = 74): 19.7 ± 9.3 (n = 18)
Wang et al[21], 2020	Multicenter retrospective study	China	Without previous diagnosis of diabetes. n = 605 among 1258. Non-survivor = 114. Survivor = 491. Median age: 59.0 yr (IQR 47.0, 68.0). M/F = 322/283. Out of total patients included in analysis: (1) FBG < 6.1 mmol/L (n) = 329; (2) FBG 6.1-6.9 mmol/L (n) = 100; and (3) FBG ≥ 7.0 mmol/L (n) = 176	Major outcome studied: 28-d mortality. Admission FBG (Total Non-survivor Survivor): (1) < 6.1 mmol/L = 329/605, 35/114, 294/491; (2) 6.1–6.9 mmol/L = 100/605, 21/114, 79/491; (3) ≥ 7.0 mmol/L = 176/605, 58/114, 118/491; and (4) Complications 237/605, 114/114, 123/491. With complications: (1) < 6.1 mmol/L = 86/605, 35/114, 51/491; (2) 6.1–6.9 mmol/SL = 48/608, 21/114, 27/491; and (3) ≥ 7.0 mmol/L = 103/605, 58/114, 45/489. Without complications: (1) < 6.1 mmol/L = 243/605, 0/114, 243/491; (2) 6.1–6.9 mmol/L = 52/605, 0/114, 52/491; and (3) ≥ 7.0 mmol/L = 73/603, 0/114, 73/490
Yang et al[24], 2020	Retrospective case series	China	n = 69 among 120 evaluated. Exclusion Criteria: (1) Previously diagnosed Diabetes Mellitus; (2) Patients treated with Glucocorticoids; (3) Patients with heart disease (myocardial infarction and heart failure); (4) Patients with kidney disease (maintenance dialysis or renal 20 transplantation); and (5) Patients with liver disease (liver cirrhosis). Median age = 61 (IQR 52-67). M/F = 34/35	FBG ≥ 7.0 mmol/L for two times during hospitalization and without a history of diabetes in COVID-19 patients: 69/120. COVID-19 Severity: (1) Moderate = 23/69; (2) Severe = 20/69; and (3) Critical = 26/69. Mortality = 16/69
Li et al[14], 2020	Retrospective study	China	Inclusion: Laboratory confirmed SARS-CoV-2 Infection. Exclusion: Incomplete data available, cases without clinical results, patients with pneumonia due to other pathogens. n = 453. Non survivor (n) = 39. Recovered (n) = 414. Median age = 61 yr (IQR 49-68). Divided into four groups: (1) Normal glucose: FBG < 5.6 mmol/L, HBA1c: < 5.7% (n = 132); (2) Hyperglycemia: FBG 5.6-6.9 mmol/L HbA1c: 5.7%-6.4% (n = 129); (3) Newly diagnosed Diabetes: No history of previous Diabetes. FBG: ≥ 7 mmol/L and/or HbA1c ≥ 6.5% (n = 94); and (4) Known Diabetes: Previously diagnosed Diabetes Mellitus (n = 98)	Main clinical outcomes: (1) Invasive mechanical ventilation: 3/132; 6/129; 11/94; 9/98; (2) ICU admission: 2/132, 8/129, 11/94, 4/98; and (3) Death: 2/132, 6/129, 20/94, 11/98. Other outcomes: (1) ARDS: 1/132, 4/129, 10/94, 3/98; (2) Acute Cardiac Injury: 27/132, 26/129, 23/94, 32/98; (3) Coagulopathy: 12/132, 12/129, 15/94, 17/98; (4) Hypoalbuminemia: 14/132, 15/129, 37/94, 36/98; and (5) Length of hospital stay (days): 22.5 (1.19), 21.9 (1.16), 26.5 (1.37), 23.6 (1.37)

ARDS: Acute Respiratory Distress Syndrome; BMI: Body mass index; COVID-19: Coronavirus disease 2019; CT: Computed tomography; DKA: Diabetic ketoacidosis; DM: Diabetes mellitus; F: Female; FBG: Fasting blood glucose; HbA1C: Hemoglobin A1C; ICU: Intensive care unit; IQR: Inter quartile range; M: Male; N: Total participants; Non-DM: Non-diabetes mellitus; Pre-DM: Pre-diabetes mellitus; T2DM: Type 2 diabetes mellitus; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.