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. 2023 Nov 2;45(2):281–308. doi: 10.1210/endrev/bnad032

Table 3.

Studies that assessed indexes of glucose metabolism (insulin sensitivity/resistance and/or β-cell function) in adults with COVID-19

Author Design Timing Outcome measure(s) Main findings
Alshammari et al 2023 (275) D: longitudinal
P: COVID-19 (n = 65)
DM: yes (100%)
C: N/A
M: 46.2%
S: N/A		 Before, during, and after complete remission of COVID-19 (timing not specified)

  • HbA1c

  • TyG

  • TyG-BMI

  • TG/HDL

  • METS-IR

Comparisons: before, during, and after COVID-19

  • HbA1c: 7.9 ± 0.2 vs 10.1 ± 0.4 vs 8.4 ± 0.3%,

  • TyG: 9.5 ± 0.04 vs 10.0 ± 0.05 vs 9.7 ± 0.05,

  • TyG-BMI: 312.7 ± 7.7 vs 326.8 ± 8.0 vs 318.1 ± 7.9

  • TG/HDL: 3.9 ± 0.1 vs 4.8 ± 0.1 vs 4.4 ± 0.1

  • METS-IR: 54.9 ± 1.3 vs 58.0 ± 1.4 vs 55.9 ± 1.3
Barreto et al 2023 (206) D: cross-sectional
P: COVID-19, hospitalized (n = 647)
DM: no
C: COVID-19 negative, hospitalized (n = 203)
M: 55.3%
S: moderate (14.2%) or severe (85.8%)		 Acute phase

  • C peptide

  • Glucagon

Comparisons: COVID-19 neg. (n = 17) vs normoglycemic COVID-19 positive (n = 39) vs COVID-19 positive with high BG (n = 63)

All without DM

 > C peptide and glucagon in COVID-19 with hyperglycemia vs non-COVID-19
> C peptide in COVID-19 with hyperglycemia vs COVID-19 with normoglycemia
Chen 2021 et al (276) D: longitudinal
P: COVID-19, hospitalized (n = 64)
DM: no
C: N/A
M: 54.7%
S: 84.4% mild/moderate, 15.6% severe/critical		 Acute phase, 3 and 6 mo. after

  • C peptide (fasting)

  • HOMA-CP

  • TyG

  • HOMA-IR

  • FBG

  • C-peptide: ↑ (0.35 ± 0.24 vs 2.36 ± 0.98 vs 2.52 ± 1.11 μg/L)

  • HOMA-CP: ↑ (median [IQR] 0.42 [0.36-0.62] vs 2.54 [1.95-3.42] vs 2.90 [2.02-4.23])

  • TyG: ↑ (8.57 ± 0.47 vs 8.73 ± 0.60 vs 8.82 ± 0.62)

  • HOMA-IR: ⇌

  • FBG: ↓ (105.1 ± 21.8 vs 89.1 ± 13.7 vs 97.2 ± 12.2 mg/dL)
Gojda et al 2023 (193) D: longitudinal
P: COVID-19, hospitalized
DM: N/A
C: N/A
M: 65%
S: Severe		 Acute phase, 3 and 6 mo after

  • C peptide

  • II

  • ISI

  • DI

  • HOMA-B

  • HOMA-IR

Comparisons:

  • baseline vs 6 mo.

  • normoglycemic vs hyperglycemic

 Baseline vs 6 mo (all)

  • C peptide, DI: ⇌

  • ISI: 3.23 ± 1.41 vs 4.53 ± 2.30

  • HOMA-B: 1.59 [1.14-2.50] vs 1.01[0.81-1.53]

Normoglycemic vs hyperglycemic (baseline)

  • II: 2.78 ± 1.77 vs 1.01 ± 0.51

  • DI: 8.40 ± 5.42 vs 3.05 ± 1.79

  • ISI, HOMA-B, HOMA-IR: =

Normoglycemic vs hyperglycemic (6 mo.)

  • II, ISI, SI, HOMA-B, HOMA-IR: =
Goyal et al 2021 (277) D: longitudinal
P: SARS-CoV-2 infection (n = 159)
DM: no
C: noninfected people (n = 193)
M: 46.9%
S: asymptomatic/mild (76.7%)		 Pre-COVID period (years 2016-2019) and peri-COVID period (years 2020-2021). Mean FU 21.5 ± 7.1 mo (regardless of the timing of COVID-19 diagnosis)

  • HOMA-IR

  • Matsuda index

  • DI

Comparisons: changes from baseline to FU in noninfected vs infected

  • HOMA-IR: ⇌

  • Matsuda index: ⇌

  • DI: ⇌
He et al 2021 (191) D: longitudinal
P: COVID-19, hospitalized (n = 92)
DM: no
C: HC (n = 30)
M: 41.3%
S: 87.0% nonsevere, 13% severe		 Acute and recovery phase (timing not specified)

  • FBG

  • Insulin (fasting)

  • HOMA-IR

  • HDL-C

  • > FBG, insulin and HOMA-IR, and < HDL-C in people with COVID-19 vs HC during the acute phase (values not reported)

  • > FBG and < HDL-C in people with COVID-19 vs HC during the recovery phase (values not reported)
Ilias et al 2021 (278) D: cross-sectional
P: COVID-19, hospitalized (n = 157)
DM: yes (14.0%)
C: N/A
M: 71.3%
S: 53.5% nonsevere (ward), 46.5% severe (ICU)		 Acute phase

  • aBG

  • HbA1c

  • Insulin (admission)

  • C peptide (admission)

  • HOMA2%B

  • HOMA2%S

Comparisons: ICU (+/− DM) vs ward (+/no DM)

  • aBG: lowest in ward-DM vs ward + DM vs ICU-DM vs ICU-DM (median [IQR] 101 [84-116] vs 136 [113-171] vs138 [110-184] vs 192 [149-275] mg/dL)

  • HOMA2%B > in ward −/+ DM vs ICU −/+ DM (103.2 ± 63.2 and 89.0 ± 84.5 vs 76.9 ± 63.2 and 44.0 ± 19.0%)

  • HbA1c, insulin, C peptide, HOMA2%S: =
Milic et al 2022 (240) D: cross-sectional
P: COVID-19, hospitalized (n = 235)
DM: yes (14.0%)
C: N/A
M: 69%
S: 19.2% severe (IMV or NIV)		 143 (median) [IQR, 130-163.5] days after symptom onset

  • HOMA-IR

  • HOMA-IR (median [IQR]): 2.2 [1.4-3.8]
Montefusco et al 2021 (279) D: retrospective, longitudinal
P: COVID-19, hospitalized (n = 20)
DM: no
C: HC (n = 15)
M: 62%
S: N/A		 Acute phase and 62.0 ± 6.5 days after disease onset

  • CGM

  • Insulin (fasting)

  • C peptide

  • HOMA-B

  • HOMA-IR

  • Arginine stimulation test

 Acute COVID vs HC

  • CGM: longer BG > 140 mg/dL, > BG AUC >140 mg/dL, > mean postprandial BG at 60 minutes, > glycemic variability

  • Insulin (fasting): > vs HC

  • C peptide: > vs HC

  • HOMA-B: > vs HC

  • HOMA-IR: > vs HC

  • Arginine test: > AIRmax, > insulin and C peptideAUC

Post-COVID-19 vs HC

  • CGM: longer duration of BG > 140 mg/dL, > mean postprandial BG at 120 min, > mean blood glucose, > nadir BG

  • Insulin (fasting): > vs HC

  • C peptide: > vs HC

  • HOMA-B: > vs HC

  • HOMA-IR: > vs HC

  • Arginine test: > AIRmax, > insulinAUC
Reiterer et al 2021 (107) D: retrospective, cross-sectional
P: COVID-19, hospitalized (n = 59)
DM: 28.8%
C: ICU, no COVID-19 (n = 42, 42.9% with ARDS)
M: 78%
S: severe (ARDS)		 Acute phase

  • Insulin (fasting)

  • C peptide

  • C-peptide/glucose ratio

  • Insulin resistance (based on C-peptide/glucose ratio)

  • β cell failure (based on C-peptide/glucose ratio)

Comparisons: COVID-19 vs ICU + ARDS vs ICUnoARDS

  • Insulin (fasting, median [IQR]): =

  • C peptide (median [IQR]): highest in COVID-19: 3487 [1552-5756] vs 1436 [851-2819] vs 1437 [916-2014] pg/mL

  • C-peptide/glucose ratio highest in COVID-19

  • Insulin resistance: 57.6% vs 16.7% vs 8.3%

  • β-cell failure: 35.6% vs 55.6% vs 25.0%
Soto et al 2022 (280) D: cross-sectional
P: COVID-19, hospitalized (n = 61)
DM: yes (26%)
C: HC (n = 25)
M: 72%
S: moderate (55.7%) or severe (44.3%)		 Acute phase

  • Insulin (fasting)

  • FBG

  • HOMA-IR

  • > insulin, FBG, HOMA-IR in COVID-19 vs HC
Yazdanpanah et al 2023 (204) D: longitudinal
P: COVID-19, nonhospitalized (n = 221)
DM:
C: non-COVID-19 (n = 220)
M: 56.1%
S: mild to moderate (no hospitalization)		 Before and after COVID-19 (one month since the baseline assessment, regardless of the timing of COVID-19 diagnosis)

  • HOMA-IR

Comparisons:

  • non-COVID-19, pre-post

  • COVID-19, pre-post

 COVID-19

  • HOMA-IR: 0.92 ± 0.3 vs 1.23 ± 0.28

Non-COVID-19

  • HOMA-IR: 0.91 ± 0.3 vs 0.8 ± 0.21

Legend: ↑ increase; ↓ decrease; ⇌ no change; > higher; < lower; = no difference.

Abbreviations: aBG, blood glucose on admission; AIRmax, acute insulin responses to arginine; ARDS, acute respiratory distress syndrome; AUC, area under the curve; C, controls; CGM, continuous glucose monitoring; D, design; DI, disposition index; DM, diabetes mellitus; FBG, fasting blood glucose; FU, follow-up; HC, healthy controls; HDL-C, high-density lipoprotein cholesterol; HOMA, homeostatic model assessment; HOMA2%B, homeostatic model assessment 2 for β-cell function; HOMA2%S, homeostatic model assessment 2 for insulin sensitivity; HOMA-CP, homeostatic model assessment for β-cell function (using C peptide); HOMA-IR, homeostatic model assessment for insulin resistance; ICU, intensive care unit; II, insulinogenic index; IMV, invasive mechanical ventilation; IQR, interquartile range; ISI, insulin sensitivity index; M, males (%); METS-IR, metabolic score for insulin resistance; NIV, noninvasive mechanical ventilation; N/A, not available; P, participants; S, severity; TG/HDL, triglyceride to high-density lipoprotein cholesterol ratio; TyG, triglyceride-glucose index; TyG-BMI, triglyceride glucose-body mass index.