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COVID-19: large meta-analysis shows people with more advanced diabetes have higher risk of death from SARS-CoV-2

Graphical abstract for Schlesinger

Embargo 2301H UK time Wednesday 28 April

A new systematic review and meta-analysis published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) shows that patients with a more advanced course of diabetes have a higher risk of death when infected with SARS-CoV-2. The analysis includes 22 studies and 17,687 people and is by Dr Sabrina Schlesinger, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Germany, and colleagues.

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, which the authors will update periodically as new studies on diabetes and COVID-19 are published.

The review found that associations with COVID-19 related death in people with diabetes were similar to those found in the general population without diabetes. Men with diabetes were 28% more likely to die with COVID-19 than women with diabetes, and people aged over 65 with diabetes were more than three times more likely to die than those under that age with diabetes. With each 5-year increase in age, the relative risk for COVID-19 related death in people living with diabetes increased by 43%.

Only few of the 22 studies investigated diabetes-specific factors related to COVID-19, and the authors call for more studies into these factors to improve the strength of the evidence. The strongest associations were observed for blood glucose levels ≥11 mmol/l at admission and death, with a 8.6 times increased risk of death compared to <6 mmol/,with the strength of evidence deemed moderate as it came from just two of the 22 studies.

Patients using insulin to control their diabetes were found (from 5 studies) to be 75% more likely to die with COVID-19 than non-insulin users. Use of insulin usually indicates a more advanced course of diabetes. Conversely, people treating their diabetes with metformin (the ‘first line’ therapy used in most cases of type 2 diabetes) were 50% less likely to die with COVID-19 than those not using metformin (from 4 studies).

As with the general population without diabetes, pre-existing conditions were found to increase the risk of COVID-19 related death in those with diabetes. Cardiovascular disease (by 56%, 8 studies), chronic kidney disease (by 93%, 6 studies) and chronic obstructive pulmonary disease (by 40%, 5 studies) all increased risk of COVID-19-related death in people living with diabetes.

The authors say: “In conclusion, our living systemic review and meta-analysis provides the best current evidence on associations between phenotypes of individuals with diabetes and confirmed SARS-CoV-2 and COVID-19 related death and severity of COVID-19.”

“Male sex, older age and some pre-existing conditions, as well as the use of insulin, most of which are potential indicators for a more progressive course of diabetes, were associated with increased risk of COVID-19 related death and severity in individuals with diabetes and SARS-CoV-2 infection, whereas metformin use was associated with a lower risk of death”, according to the authors.

“To strengthen the evidence, more primary studies investigating diabetes-specific risk factors, such type and duration of diabetes or additional pre-existing conditions, and accounting for important variables, are needed. We will continuously update this report to strengthen the evidence of already examined associations and to investigate further outcomes, such as long-term complications due to COVID-19 for individuals with diabetes”, conclude the authors.

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