COVID-19 associated CKM syndrome progression in diabetic patients is linked to pancreatic beta cell dysfunction, rather than RASi use: a retrospective cohort study.

Post-infection CKM syndrome progression was observed in 25.2% of the diabetic cohort with confirmed SARS-CoV-2 infection.

• The retrospective cohort included 682 diabetic patients across CKM stages 2 to 4 with confirmed SARS-CoV-2 infection.
• CKM progression occurred in 25.2% of the total cohort.
• Multivariate logistic regression coupled with 1:1 Propensity Score Matching (PSM) was used to identify predictors and rectify selection bias.

RASi use was initially associated with CKM progression in multivariate logistic regression, but this association lost statistical significance after PSM balancing of baseline characteristics.

• Initial multivariate model: OR = 1.56, 95% CI: 1.06–2.28; p = 0.02, implicating RASi as a risk factor.
• After 1:1 PSM to balance baseline comorbidities: OR = 1.56, 95% CI: 0.91–2.67; p = 0.156, no longer statistically significant.
• The authors conclude RASi use should be interpreted as a 'marker of severity' for baseline comorbidities rather than a pathogenic factor.
• The independent impact of RASi on CKM progression is described as 'highly debated' in the context of potential ACE2 upregulation facilitating viral entry.

The CKM progression group exhibited a paradoxical pattern of low HOMA-IR scores accompanied by reduced fasting C-peptide and elevated glucose, indicating severe viral-induced pancreatic β-cell secretory dysfunction.

• Low HOMA-IR in the progression group was accompanied by reduced fasting C-peptide and elevated glucose levels.
• This pattern was interpreted as indicating severe viral-induced β-cell secretory dysfunction rather than enhanced insulin sensitivity.
• The authors describe this as 'failure of compensatory mechanisms in pancreatic β-cell function.'
• SARS-CoV-2 is proposed to enter pancreatic β-cells by exploiting ACE2, disrupting cellular and hormonal activity.

High-Density Lipoprotein Cholesterol (HDL-C) persisted as a protective factor against CKM progression in diabetic patients with COVID-19.

• HDL-C was identified as a protective factor in the analysis of predictors of CKM progression.
• This finding was consistent across the analytical models employed, including multivariate logistic regression and PSM analyses.
• HDL-C's protective role was observed within a cohort of 682 diabetic patients across CKM stages 2 to 4.

SARS-CoV-2 may cause multiple organ dysfunction, including pancreatic β-cell disruption, due to widespread expression of its entry receptor ACE2.

• SARS-CoV-2 primarily has tissue tropism for the respiratory epithelium but may cause multiple organ dysfunction due to widespread ACE2 expression.
• The virus may enter pancreatic β-cells by exploiting ACE2, disrupting cellular and hormonal activity.
• This mechanism is proposed to worsen CKM syndrome prognosis specifically in diabetic patients.
• Treatment with RASi may arguably increase ACE2 expression and potentially facilitate viral entry, making its independent impact debated.