Updated analysis of multiple COVID-19-diabetes studies shows the risks associated with diabetes

The latest update to a large and continuing review and meta-analysis of studies of COVID-19 and diabetes confirms that patients with a more advanced course of diabetes have a higher risk of death when infected with SARS-CoV-2. The new data are being presented at this year’s annual meeting of the European Association for the Study of Diabetes (EASD).

The updated analysis includes 60 studies (40 on COVID-19-related death) and 44 509 people from 18 countries and is led by Dr Sabrina Schlesinger, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Germany, and colleagues.

This is the second edition of a ‘living’ systematic review and meta-analysis on observational studies investigating 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 first analysis was published in the journal Diabetologia in July 2021 (see link below).

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 39% more likely to die with COVID-19 than women with diabetes (from 21 studies), and people aged over 65 with diabetes were more than three times more likely to die than those aged under 65 with diabetes (from eight studies). With each 1-year increase in age, the relative risk for COVID-19 related death in people living with diabetes increased by 5% (from 14 studies). People with obesity (a body mass index [BMI] of 30 kg/m²) and diabetes were found to have a 47% increased risk of COVID-19-related death compared with people of normal weight (BMI 18.5 – 24.9kg/m²) with diabetes.

Only a few 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 3.7 times increased risk of death compared to <6 mmol/l), with the strength of evidence deemed moderate as it came from just three of the 40 studies.

Patients using insulin to control their diabetes were found (from 11 studies) to be 79% 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 37% less likely to die with COVID-19 than those not using metformin (from 11 studies).

As with the general population without diabetes, pre-existing conditions were found to increase the risk of COVID-19 related death in people living with diabetes. Cardiovascular disease (by 39%, 18 studies), chronic kidney disease (by 81%, 15 studies) and chronic obstructive pulmonary disease (by 23%, 10 studies) all increased risk of COVID-19-related death in people living with diabetes.

A new finding for this updated analysis was that chronic use of statins (that lower cholesterol) was associated with a 75% increased risk of COVID-19-related death for people with diabetes – the authors suggest this could be because statins are an indicator for underlying cardiovascular disease. The authors also found an association between a person’s level of C-reactive protein (which indicates systemic inflammation) and risk of COVID-19-related death, with each 10mg/L increase in CRP associated with a 15% increased risk of death.

The authors say: “This new update to our systemic review and meta-analysis provides the best current evidence on associations between characteristics of individuals with diabetes and confirmed SARS-CoV-2 and their subsequent risk of COVID-19 related death and severity of COVID-19 disease.”

They add: “Male sex, older age, obesity and some pre-existing conditions, as well as the use of insulin and statins, 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.”

They conclude: “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.”