Glucose metabolism disorders associated with COVID-19: clinical and morphological study

BACKGROUND. Glucose metabolism disorders (GMD) were detected both in acute and in post-COVID, however, its pathogenic aspects remain unclear.AIM. To analyze the occurrence of GMD in post-COVID patients who have had moderate and severe COVID-19 without previously known GMD disorders, and evaluate exp...

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Main Authors: T. L. Karonova, A. A. Mikhailova, D. I. Lagutina, O. M. Vorobeva, D. O. Grigoreva, K. A. Sterkhova, V. A. Malko, A. G. Mikheeva, A. T. Chernikova, L. B. Mitrofanova, E. V. Shlyakhto
Format: Article
Language:English
Published: Endocrinology Research Centre 2023-12-01
Series:Сахарный диабет
Subjects:
Online Access:https://www.dia-endojournals.ru/jour/article/view/13041
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author T. L. Karonova
A. A. Mikhailova
D. I. Lagutina
O. M. Vorobeva
D. O. Grigoreva
K. A. Sterkhova
V. A. Malko
A. G. Mikheeva
A. T. Chernikova
L. B. Mitrofanova
E. V. Shlyakhto
author_facet T. L. Karonova
A. A. Mikhailova
D. I. Lagutina
O. M. Vorobeva
D. O. Grigoreva
K. A. Sterkhova
V. A. Malko
A. G. Mikheeva
A. T. Chernikova
L. B. Mitrofanova
E. V. Shlyakhto
author_sort T. L. Karonova
collection DOAJ
description BACKGROUND. Glucose metabolism disorders (GMD) were detected both in acute and in post-COVID, however, its pathogenic aspects remain unclear.AIM. To analyze the occurrence of GMD in post-COVID patients who have had moderate and severe COVID-19 without previously known GMD disorders, and evaluate expression of SARS-CoV-2 proteins and its entry factors in pancreas in acute COVID-19.METHODS. Among 187 hospitalized patients with confirmed COVID-19 141 patients without previously diagnosed GMD underwent follow-up post-COVID visits. The examination for all patients included anthropometric measurement with calculation of BMI, level of HbA1c and fasting plasma glucose, for 106 patients level of insulin and HOMA-IR index was analyzed. For histological examination, pancreas fragments of 20 patients with fatal outcome were selected. Immunohistochemical study was performed with antibodies to SARS-CoV-2, ACE2, DPP4, as well as double-labeled immunofluorescence microscopy (insulin-SARS-CoV-2, insulin-ACE2, insulin-DPP4).RESULTS. Among 141 patients in post-COVID period, 9 (6.3%) had HbA1c or fasting plasma glucose levels that met criteria for diabetes mellitus, 38 (26.9%) — exceeded normal values (WHO), and 84 (59.6%) had GMD according to criteria of the ADA. In post-COVID, patients with GMD had a higher BMI and HOMA-IR index (p=0.001) compared to patients with normal glycemic levels. Only 40.4% of people had HOMA-IR index above 2.7. Patients with GMD had higher level of CRP (p=0.007) and a maximum glucose level (p=0.019) in the acute period. Positive relationship was found between BMI and HOMA index both in acute (p<0.001; r=0.389) and post-COVID (p<0.001; r=0.412) periods, as well as the level of HbA1c in acute period (p=0.019, r=0.202) and in post-COVID (p=0.004, r=0.242).Histological and immunohistochemical studies showed the expression of SARS-CoV-2 proteins in 1.85% [0–15.4] and 11.1% [5.3–14.8] cells of the Langerhans islets in patients who died on the second and third waves, respectively. The expression of ACE2 and DPP4 in the islets of Langerhans did not exceed 0.4% [0–1.7] and 0.5% [0–0.8] of cells, respectively. Double-labeled immunofluorescence microscopy showed co-localization of SARS-CoV-2, ACE2, DPP4 with insulin.CONCLUSION. Post-COVID Glucose metabolism disorders may be explained by direct cytotoxic effect of SARS-COV-2, increased glucose toxicity and insulin resistance because of the acute infection and its complex therapy.
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spelling doaj.art-2e3a712cbd6049b3a5d367722468b4962024-03-20T11:48:05ZengEndocrinology Research CentreСахарный диабет2072-03512072-03782023-12-0126651552510.14341/DM1304111059Glucose metabolism disorders associated with COVID-19: clinical and morphological studyT. L. Karonova0A. A. Mikhailova1D. I. Lagutina2O. M. Vorobeva3D. O. Grigoreva4K. A. Sterkhova5V. A. Malko6A. G. Mikheeva7A. T. Chernikova8L. B. Mitrofanova9E. V. Shlyakhto10Almazov National Medical Research CentreAlmazov National Medical Research CentreAlmazov National Medical Research CentreAlmazov National Medical Research CentreAlmazov National Medical Research CentreAlmazov National Medical Research CentreAlmazov National Medical Research CentreAlmazov National Medical Research CentreAlmazov National Medical Research CentreAlmazov National Medical Research CentreAlmazov National Medical Research CentreBACKGROUND. Glucose metabolism disorders (GMD) were detected both in acute and in post-COVID, however, its pathogenic aspects remain unclear.AIM. To analyze the occurrence of GMD in post-COVID patients who have had moderate and severe COVID-19 without previously known GMD disorders, and evaluate expression of SARS-CoV-2 proteins and its entry factors in pancreas in acute COVID-19.METHODS. Among 187 hospitalized patients with confirmed COVID-19 141 patients without previously diagnosed GMD underwent follow-up post-COVID visits. The examination for all patients included anthropometric measurement with calculation of BMI, level of HbA1c and fasting plasma glucose, for 106 patients level of insulin and HOMA-IR index was analyzed. For histological examination, pancreas fragments of 20 patients with fatal outcome were selected. Immunohistochemical study was performed with antibodies to SARS-CoV-2, ACE2, DPP4, as well as double-labeled immunofluorescence microscopy (insulin-SARS-CoV-2, insulin-ACE2, insulin-DPP4).RESULTS. Among 141 patients in post-COVID period, 9 (6.3%) had HbA1c or fasting plasma glucose levels that met criteria for diabetes mellitus, 38 (26.9%) — exceeded normal values (WHO), and 84 (59.6%) had GMD according to criteria of the ADA. In post-COVID, patients with GMD had a higher BMI and HOMA-IR index (p=0.001) compared to patients with normal glycemic levels. Only 40.4% of people had HOMA-IR index above 2.7. Patients with GMD had higher level of CRP (p=0.007) and a maximum glucose level (p=0.019) in the acute period. Positive relationship was found between BMI and HOMA index both in acute (p<0.001; r=0.389) and post-COVID (p<0.001; r=0.412) periods, as well as the level of HbA1c in acute period (p=0.019, r=0.202) and in post-COVID (p=0.004, r=0.242).Histological and immunohistochemical studies showed the expression of SARS-CoV-2 proteins in 1.85% [0–15.4] and 11.1% [5.3–14.8] cells of the Langerhans islets in patients who died on the second and third waves, respectively. The expression of ACE2 and DPP4 in the islets of Langerhans did not exceed 0.4% [0–1.7] and 0.5% [0–0.8] of cells, respectively. Double-labeled immunofluorescence microscopy showed co-localization of SARS-CoV-2, ACE2, DPP4 with insulin.CONCLUSION. Post-COVID Glucose metabolism disorders may be explained by direct cytotoxic effect of SARS-COV-2, increased glucose toxicity and insulin resistance because of the acute infection and its complex therapy.https://www.dia-endojournals.ru/jour/article/view/13041covid-19sars-cov-2dpp4ace2post-covidglucose metabolism disordershoma-ir
spellingShingle T. L. Karonova
A. A. Mikhailova
D. I. Lagutina
O. M. Vorobeva
D. O. Grigoreva
K. A. Sterkhova
V. A. Malko
A. G. Mikheeva
A. T. Chernikova
L. B. Mitrofanova
E. V. Shlyakhto
Glucose metabolism disorders associated with COVID-19: clinical and morphological study
Сахарный диабет
covid-19
sars-cov-2
dpp4
ace2
post-covid
glucose metabolism disorders
homa-ir
title Glucose metabolism disorders associated with COVID-19: clinical and morphological study
title_full Glucose metabolism disorders associated with COVID-19: clinical and morphological study
title_fullStr Glucose metabolism disorders associated with COVID-19: clinical and morphological study
title_full_unstemmed Glucose metabolism disorders associated with COVID-19: clinical and morphological study
title_short Glucose metabolism disorders associated with COVID-19: clinical and morphological study
title_sort glucose metabolism disorders associated with covid 19 clinical and morphological study
topic covid-19
sars-cov-2
dpp4
ace2
post-covid
glucose metabolism disorders
homa-ir
url https://www.dia-endojournals.ru/jour/article/view/13041
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