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Meta-analysis: Diabetes but not overweight nor smoking linked to worse COVID-19 outcomes

A large meta-analysis of patients with COVID-19 and diabetes "provides the best current evidence" to identify the risk for severe COVID-19 or death from it, based on patients' and diabetes-related characteristics and laboratory values, researchers report.

Male sex, older age, pre-existing comorbidities (cardiovascular disease, chronic kidney disease, and chronic obstructive pulmonary disease [COPD]), use of insulin, and high blood glucose on hospital admission were associated with increased risk for COVID-19-related death, whereas metformin use was associated with lower risk, based on moderate-to-strong evidence.

The same characteristics were linked with similar risks of having (or not having) severe COVID-19, based on weaker evidence.

"Taken together, the risk group we identified for the population with diabetes and COVID-19 – older individuals with comorbid conditions and using insulin, might simply reflect severity of diabetes or poor health conditions per se," the researchers caution.

"Nevertheless, considering these phenotypes can be helpful for identifying people with diabetes and COVID-19 at high risk for poor outcomes and, therefore, those most likely to require early intensified treatment," they conclude.

The meta-analysis of 22 studies and 17,687 individuals with diabetes and COVID-19 was undertaken by Dr Sabrina Schlesinger, Heinrich Heine University, Düsseldorf, Germany, and colleagues.

Diabetes increases the risk of dying from COVID-19, but the patient characteristics and diabetes-related factors associated with the increased risk for COVID-19 severity or death have not been totally clear.

To investigate this, the researchers identified studies published until October 10, 2020, of patients with type 2, and less often type 1, diabetes and COVID-19.

Compared with women, men had a 28% increased risk of dying from COVID-19 and a 36% increased risk for severe COVID-19, in 10 studies and 11 studies with high-quality evidence.

Compared with younger patients, patients older than 65 had a 3.5-fold higher risk for death from COVID-19 and a 67% higher risk for severe disease, in 6 studies with moderate-level evidence.

However, there were no clear associations between smoking or being overweight or having obesity and COVID-19-related death or severity.

In general, few studies looked at the associations between diabetes-specific risk factors or laboratory markers and outcomes.

Having blood glucose >11 mmol/L versus < 6 mmol/L on admission was linked with an 8.6-fold increased risk for death from COVID-19.

Compared with other patients, those who used insulin (and likely had more advanced type 2 diabetes) were 75% more likely to die from COVID-19.

Conversely, patients receiving metformin (likely mostly for first-line therapy for type 2 diabetes) were 50% less likely to die with COVID-19 than other patients.

As in the general population, comorbidities predicted worse outcomes. Having COPD was associated with a 21% increased risk for death from COVID-19 and a 36% increased risk for severe COVID-19.

Having cardiovascular disease or chronic kidney disease was associated with a 56% and 93% increased risk of dying from COVID-19, respectively, based on weaker evidence.

Patients with diabetes had similar risk factors for worse outcomes as people in the general population, "with some exceptions."

"Older age, male sex, obesity, hypertension, chronic pulmonary diseases, [cardiovascular disease], active cancer, laboratory parameters (low lymphocyte count, and elevations in [C-reactive protein (CRP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]) have been linked to a poor prognosis of COVID-19 in the general population infected with SARS-CoV-2," Schlesinger and colleagues write.

Study details
Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis

Sabrina Schlesinger, Manuela Neuenschwander, Alexander Lang, Kalliopi Pafili, Oliver Kuss, Christian Herder, Michael Roden

Published in Diabetologia on 28 April 2021

Diabetes has been identified as a risk factor for poor prognosis of coronavirus disease-2019 (COVID-19). The aim of this study is to identify high-risk phenotypes of diabetes associated with COVID-19 severity and death.
This is the first edition of a living systematic review and meta-analysis on observational studies investigating phenotypes in individuals with diabetes and COVID-19-related death and severity. Four different databases were searched up to 10 October 2020. We used a random effects meta-analysis to calculate summary relative risks (SRR) with 95% CI. The certainty of evidence was evaluated by the GRADE tool.
A total of 22 articles, including 17,687 individuals, met our inclusion criteria. For COVID-19-related death among individuals with diabetes and COVID-19, there was high to moderate certainty of evidence for associations (SRR [95% CI]) between male sex (1.28 [1.02, 1.61], n = 10 studies), older age (>65 years: 3.49 [1.82, 6.69], n = 6 studies), pre-existing comorbidities (cardiovascular disease: 1.56 [1.09, 2.24], n = 8 studies; chronic kidney disease: 1.93 [1.28, 2.90], n = 6 studies; chronic obstructive pulmonary disease: 1.40 [1.21, 1.62], n = 5 studies), diabetes treatment (insulin use: 1.75 [1.01, 3.03], n = 5 studies; metformin use: 0.50 [0.28, 0.90], n = 4 studies) and blood glucose at admission (≥11 mmol/l: 8.60 [2.25, 32.83], n = 2 studies). Similar, but generally weaker and less precise associations were observed between risk phenotypes of diabetes and severity of COVID-19.
Individuals with a more severe course of diabetes have a poorer prognosis of COVID-19 compared with individuals with a milder course of disease. To further strengthen the evidence, more studies on this topic that account for potential confounders are warranted.


Full Medscape report (Restricted access)

Diabetologia study (Open access)


See also MedicalBrief archives:

More evidence that diabetes/overweight tied to severe COVID-19 — Hospital meta-analysis

Global database for research to examine link between COVID-19 and diabetes

20% of hospitalised COVID-19 patients with diabetes died within 28 days — CORONADO

Diabetes and hypertension most common comorbidities in Gauteng COVID-19 deaths

Mortality risk exceeds 40% for COVID-19 patients with diabetes — Western Cape Health data

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