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Metabolic Signatures of Type 2 Diabetes Mellitus and Hypertension in COVID-19 Patients With Different Disease Severity.

ABSTRACT: Introduction: Increased COVID-19 disease severity is higher among patients with type 2 diabetes mellitus and hypertension. However, the metabolic pathways underlying this association are not fully characterized. This study aims to identify the metabolic signature associated with increased COVID-19 severity in patients with diabetes mellitus and hypertension. Methods: One hundred and fifteen COVID-19 patients were divided based on disease severity, diabetes status, and hypertension status. Targeted metabolomics of serum samples from all patients was performed using tandem mass spectrometry followed by multivariate and univariate models. Results: Reduced levels of various triacylglycerols were observed with increased disease severity in the diabetic patients, including those containing palmitic (C16:0), docosapentaenoic (C22:5, DPA), and docosahexaenoic (C22:6, DHA) acids (FDR < 0.01). Functional enrichment analysis revealed triacylglycerols as the pathway exhibiting the most significant changes in severe COVID-19 in diabetic patients (FDR = 7.1 × 10^-27). Similarly, reduced levels of various triacylglycerols were also observed in hypertensive patients corresponding with increased disease severity, including those containing palmitic, oleic (C18:1), and docosahexaenoic acids. Functional enrichment analysis revealed long-chain polyunsaturated fatty acids (n-3 and n-6) as the pathway exhibiting the most significant changes with increased disease severity in hypertensive patients (FDR = 0.07). Conclusions: Reduced levels of triacylglycerols containing specific long-chain unsaturated, monounsaturated, and polyunsaturated fatty acids are associated with increased COVID-19 severity in diabetic and hypertensive patients, offering potential novel diagnostic and therapeutic targets.

SUBMITTER: Elrayess MA

PROVIDER: S-EPMC8784560 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT04365634.ContextDiabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear.ObjectiveWe aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients.Design and methodsIn this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups.ResultsCompared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8+ T cells and NK cells than survivors.ConclusionThe elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8+ T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.

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Metabolic Signatures of Type 2 Diabetes Mellitus and Hypertension in COVID-19 Patients With Different Disease Severity.

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