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COVID-19 associated CKM syndrome progression in diabetic patients is linked to pancreatic beta cell dysfunction,
Yongcheng Zhang1,2, Ziqi Wang3, Yizhe Wang1,2
1School of Health Science and Engineering,University of Shanghai for Science and Technology, Shanghai, China.
Background And Aims:
SARS-CoV-2 primarily has tissue tropism for the respiratory epithelium; however, it may cause multiple organ dysfunction due to the widespread expression of its entry receptor, ACE2. Specifically, SARS-CoV-2 may enter pancreatic β-cells by exploiting ACE2, disrupting cellular and hormonal activity, and thereby worsening Cardiovascular-Kidney-Metabolic (CKM) syndrome prognosis in diabetic patients. Furthermore, treatment with renin-angiotensin system inhibitors (RASi) may arguably increase ACE2 expression and facilitate viral entry, making its independent impact highly debated. Accordingly, we sought to elucidate the genuine impact of RASi usage on CKM progression via Propensity Score Matching (PSM) and concurrently investigate the specific contribution of pancreatic β-cell secretory dysfunction.
Methods:
We conducted a retrospective investigation involving 682 diabetic patients across CKM stages 2 to 4 with confirmed SARS-CoV-2 infection utilizing multivariate logistic regression coupled with 1:1 PSM to rectify selection bias concerning RASi administration and identifying predictors.
Results:
Post-infection CKM progression was observed in 25.2% of the cohort and while initial multivariate models implicated RASi (OR = 1.56, 95% CI: 1.06-2.28; p=0.02) as a risk factor this association lost statistical significance after rigorously balancing baseline characteristics through PSM (OR = 1.56, 95% CI: 0.91-2.67; p = 0.156). A paradoxical finding emerged wherein the progression group exhibited low HOMA-IR scores accompanied by reduced fasting C-peptide and elevated glucose thereby indicating severe viral-induced β-cell secretory dysfunction rather than enhanced insulin sensitivity while High-Density Lipoprotein Cholesterol (HDL-C) persisted as a protective factor.
Conclusions:
COVID-19 exacerbates CKM progression in diabetic patients, but this is not driven by RASi therapy itself. RASi use should be interpreted as a "marker of severity" for baseline comorbidities, rather than a pathogenic factor. Mechanistically, viral infection may cause the failure of compensatory mechanisms in pancreatic β-cell function (manifested as low C-peptide and spurious low HOMA-IR).
Insights
COVID-19 worsens cardiovascular-kidney-metabolic syndrome in diabetics, not due to renin-angiotensin system inhibitors (RASi). Viral infection impairs pancreatic beta-cell function, leading to disease progression.
Area of Science:
- Endocrinology
- Virology
- Cardiovascular Medicine
Background:
- SARS-CoV-2 infection can affect multiple organs due to ACE2 receptor expression.
- Diabetic patients with Cardiovascular-Kidney-Metabolic (CKM) syndrome are at risk for worsened prognosis following SARS-CoV-2 infection.
- The role of renin-angiotensin system inhibitors (RASi) in SARS-CoV-2 infection and CKM progression is debated due to potential effects on ACE2 expression.
Purpose of the Study:
- To investigate the impact of RASi on CKM progression in diabetic patients post-SARS-CoV-2 infection.
- To determine the specific contribution of pancreatic beta-cell secretory dysfunction to CKM progression after COVID-19.
- To clarify the association between RASi use and CKM progression using Propensity Score Matching (PSM).
Main Methods:
- Retrospective study of 682 diabetic patients (CKM stages 2-4) with confirmed SARS-CoV-2 infection.
- Multivariate logistic regression and 1:1 Propensity Score Matching (PSM) to control for confounding factors related to RASi use.
- Analysis of CKM progression, beta-cell function markers (HOMA-IR, fasting C-peptide), glucose levels, and HDL-C.
Main Results:
- 25.2% of patients experienced CKM progression post-infection.
- Initial analysis suggested RASi as a risk factor, but this association lost significance after PSM.
- Patients with CKM progression showed low HOMA-IR, reduced fasting C-peptide, and elevated glucose, indicating severe beta-cell dysfunction, while HDL-C was protective.
Conclusions:
- COVID-19 exacerbates CKM progression in diabetic patients, primarily through viral-induced pancreatic beta-cell dysfunction.
- RASi therapy is not a direct cause of CKM progression but rather a marker of baseline comorbidities.
- Viral infection disrupts pancreatic beta-cell compensatory mechanisms, leading to impaired function and disease progression.
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