Older, Sicker Diabetes Patients Have Worse COVID-19 Prognosis

Marlene Busko

April 28, 2021

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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, researcher report.

Male sex, older age, preexisting 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, i.e. 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 by Sabrina Schlesinger, PhD, Heinrich Heine University, Düsseldorf, Germany, and colleagues was published April 28 in Diabetologia.

Which Diabetes Patients Are at Higher Risk?

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.

Obesity, High BP Did Not Predict Worse Outcomes in This Analysis

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 (e.g. 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.

However, "interestingly," the meta-analysis did not find that obesity or hypertension were associated with an increased risk for severe COVID-19 or death from COVID-19.

There were no clear associations for CRP (the most frequently measured biomarker of inflammation) or for liver enzymes (ALT, AST) and worse outcomes, but this was based on limited data. 

Call for More Research

"To strengthen the evidence, more primary studies investigating diabetes-specific risk factors, e.g. type and duration of diabetes or additional comorbidities (such as liver disease and neuropathy), and accounting for important confounders, are needed," the researchers urge.

"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," they conclude.

Diabetologia. Published online April 28, 2021. Article

The study was funded by Projekt DEAL and a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD). Schlesinger disclosed no relevant financial relationships. The disclosures of the other authors are listed with the article.

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