Diabesity and COVID-19: A critical combination

The concurrent occurrence of diabesity and COVID-19 may lead to more severe disease due to the latter, according to a presentation at the Opening Session of ENDO Online.

“It is certainly the perfect storm – the collision of two public health epidemics in mostly, but not just, developed countries,” noted Professor Manuel Puig-Domingo from the Germans Trias i Pujol University Hospital in Barcelona, Spain.

“Diabetes confers a higher risk of severe disease and mortality,” he continued. “Diabesity prevalence is increased in hospitalized vs non-hospitalized patients [and] is present in one out of three patients requiring intensive care unit (ICU), mechanical ventilation, or in those dying from COVID-19.”

To illustrate the diabesity–COVID-19 connection, Puig-Domingo cited a study of 4,103 patients (median age 52 years, 50.5 percent male) with COVID-19 treated in New York City, New York, US. Of these, 15 percent had diabetes, 26.8 percent had obesity, and 30.1 percent had cardiovascular disease (CVD). [medRxiv 2020;doi:10.1101/2020.04.08.20057794]

A total of 1,999 patients were hospitalized, with certain comorbidities increasing the likelihood of hospitalization including CVD (44.6 percent vs 16.4 percent in hospitalized vs non-hospitalized patients), obesity (39.8 percent vs 14.5 percent), and diabetes (31.8 percent vs 5.4 percent). Of the hospitalized patients, 31 percent required ICU admission, 28.1 percent mechanical ventilation, and 18.5 percent died.

Predictors for COVID-19-related hospitalization included advanced age (odds ratio [OR], 10.91 and 66.79 for age 65–74 and ≥75 years, respectively), male sex (OR, 2.8), chronic kidney disease (OR, 3.07), diabetes (OR, 2.81), obesity (OR, 4.26 and 6.2 for BMI 30–40 and ≥40 kg/m², respectively; p<0.001 for all), and heart failure (OR, 4.29; p=0.001).

The increased COVID-19 mortality risk in patients with diabetes was also demonstrated in a study of 72,314 cases in China where the case-fatality rate (CFR) among patients with diabetes was 7.3 percent compared with the overall CFR of 2.3 percent. [JAMA 2020;323:1239-1242]

Another study of 174 patients with COVID-19 suggested an increased severity of pneumonia in patients with diabetes compared with non-diabetics. [Diabetes Metab Res Rev 2020;e3319]

Moreover, almost all biomarkers assessed in this study (eg, lactate dehydrogenase, alanine aminotransferase, γ-glutamyltransferase, albumin, and total protein) suggested a higher level of organ injury in patients with diabetes compared with non-diabetics, said Puig-Domingo.

In a study of 7,337 individuals in China, 952 of whom had pre-existing diabetes, mortality risk was higher in patients with diabetes than non-diabetics (7.8 percent vs 2.7 percent; adjusted hazard ratio [adjHR], 1.49; p=0.005). Additionally, in-hospital mortality rate was lower among patients with well-controlled compared with poorly controlled glucose levels (1.1 percent vs 11.0 percent; adjHR, 0.13; p<0.001). [Cell Metab 2020;31:1068-1077.e3]

“Mortality in COVID-19 is mostly age-dependent but also comorbidity-dependent, and in particular, glucose-dependent [with diabesity accounting] for a three- to fivefold increased risk of mortality,” said Puig-Domingo.

He proposed a variety of mechanisms that may contribute to the pathophysiology of systemic failure in patients with diabetes and COVID-19. These included diabetes- or obesity-related impaired pulmonary function, exaggerated inflammasome response and renin-angiotensin system dysregulation, aberrant protein glycation, increased coagulation, potential bacterial superinfection, increased mortality risk with hyperglycaemia, and direct pancreatic damage. 

Managing diabetes during COVID-19

According to Dr Daniel Drucker from Mount Sinai Hospital in Toronto, Ontario, Canada, prevention remains a fundamental method of diabetes management during the COVID-19 pandemic. This includes handwashing, mask wearing, personal hygiene, and physical distancing. Patients should have an adequate supply of medications and test strips, maintain a good diet, exercise regimen, and blood glucose and blood pressure levels, and use telemedicine to communicate with their physicians.

In patients with diabetes who are hospitalized for COVID-19, key considerations include hydration levels, nutrition, renal and liver function, ketosis, and insulin deficiency, and other medications or procedures such as steroids, immunomodulators, and contrast agents.

Among patients hospitalized with COVID-19 who are on glucose-lowering agents, consideration of effects differs by medication.

“We need to think about [lactic] acidosis and declining renal function with metformin,” said Drucker. Use of sodium-glucose contransporter-2 (SGLT-2) inhibitors needs careful monitoring for ketoacidosis, renal function, and volume status, with potential discontinuation if close monitoring is not feasible. There is no major concern regarding adverse effects with dipeptidyl peptidase 4 (DPP-4) inhibitors, while sulfonylureas and thiazolidinediones are best discontinued. Nausea and vomiting may be concerns with glucagon-like peptide 1 (GLP-1) receptor agonists. Exenatide-based agents, specifically, should be discontinued if estimated glomerular filtration rate declines, he added.

While caveats exist for all glucose-lowering drugs, metformin and GLP-1 receptor agonists are likely to be safe. However, we have 99 years of experience with insulin and only 10–15 years with GLP-1 receptor agonists, less in the hospitalized ill patient, said Drucker.

“[As such,] insulin is the preferred glucose-lowering drug in acutely ill hospitalized patients with diabetes,” he said. We have the most experience with insulin in the hospitalized, critically ill, or ICU-admitted patient. However, potential insulin resistance and dynamic changes in insulin requirements warrant careful monitoring of these patients, he continued.

There is insufficient evidence defining the optimal glycaemic range for patients hospitalized with severe critical illness. Hypoglycaemia in the ICU needs to be avoided, he said, proposing a blood glucose target of 6.0–10.0 mmol/L, as per the Diabetes Canada guidelines.