Study finds BMI, not long-term glycaemic control, tied to COVID-19 severity in diabetic inpatients
An observational study published in Diabetologia looking into the phenotypic characteristics of diabetic patients hospitalised for coronavirus disease 2019 (COVID-19) suggests body mass index (BMI) is an independent prognostic factor for disease severity in this population, whereas chronic glycaemic control and routine therapies, such as RAAS blockers and DPP-4 inhibitors, did not impact the immediate severity of COVID-19.
The CORONADO study focused on 1317 patients with diabetes hospitalised for COVID-19 at 53 sites in France in the period from March 10 to March 31, 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission.
Participants had a mean age of 69.8 years and 64.9% were men. Median BMI was 28.4 kg/m2, while the mean HbA1c value was 65 mmol/mol (8.1%). Histories of hypertension and dyslipidaemia were found in 77.2% and 51% of participants, respectively, while microvascular and macrovascular complications were reported in 46.8% and 40.8% of individuals.
Diabetes classification was mainly type 2 (88.5%), and less frequently type 1 (3%) or other aetiologies (5.4%). In addition, 3.1% of participants were newly diagnosed with diabetes on admission. Regarding routine glucose-lowering medications, 38.3% of patients were on insulin therapy, while 56.6% received metformin and 21.6% took DPP-4 inhibitors. Moreover, treatment with RAAS blockers (ACE inhibitors and/or ARBs and/or mineralocorticoid-receptor antagonists [MRAs]) and statins was used by 57.1% and 47.6% of the participants, respectively.
On admission, diabetes-related disorders were reported in 11.1% of cases, with 132 episodes of severe hyperglycaemia, including 40 of ketosis, of which 19 were ketoacidosis, as well as 14 hypoglycaemic events, while severe anorexia was reported in 83 participants (6.3%).
The primary outcome was encountered in 29% of participants, while 10.6% died and 18% were discharged on day 7. In a univariate analysis, male sex was more frequent (69.1% vs 63.2%, p = 0.0420) and BMI was significantly higher (median 29.1 kg/m2 vs 28.1 kg/m2, p = 0.0009) in patients who met the primary outcome compared to the others, as was the use of RAAS blockers (61.5% vs 55.3%, p = 0.0386), but other factors prior to admission such as age, diabetes type, HbA1c, diabetic complications or glucose-lowering therapies were not significantly associated.
In addition, several characteristics prior to admission were associated with mortality risk on day 7, including age, hypertension, micro- and macrovascular diabetic complications and comorbidities such as heart failure or treated obstructive sleep apnoea (OSA). In terms of medications, metformin use was lower in patients who died, but insulin therapy, RAAS blockers, β-blockers, loop diuretics and MRAs were found to be associated with death on day 7.
Researchers also performed multivariable analyses, and found that only BMI remained positively associated with the primary outcome in a model where sex and age were forced into models. When comorbidities and routine treatment were entered in an adjusted model with stepwise selection, BMI was the only independent factor associated with the primary outcome. Finally, age, history of micro or macrovascular complications, and treated OSA were found to be independently associated with the risk of death on day 7.
"To our knowledge, CORONADO is the first study that provides precise information regarding the characteristics of diabetes in the severe forms of COVID-19," wrote Bertrand Cariou MD, Hôpital Guillaume et René Laennec, Nantes, France, and colleagues. Regarding clinical characteristics of COVID-19 in study participants, they said "there was a high prevalence of fever and respiratory symptoms (cough, dyspnoea) and, to a lesser extent, digestive disorders. In addition to symptoms directly related to COVID-19, people with diabetes can also require management of acute metabolic disorders. In particular, physicians should be warned not only of the risk of ketoacidosis, but also of hypoglycaemia, probably favoured by COVID-19-induced anorexia without concomitant adaptation of glucose-lowering drugs."
The authors highlighted the association of BMI with study outcomes, pointing to a recent report on COVID-19 patients in the ICU showing a link between BMI and the requirement for mechanical ventilation, irrespective of diabetic status. "However, such an association with BMI was no longer statistically significant when considering death on day 7. It should also be noted that the increased risk for the primary outcome appears to be less pronounced in patients with morbid obesity (grade 3, BMI ≥40 kg/m2) compared with those who were overweight or with grade 1–2 obesity," a phenomenon referred to as the so-called "obesity paradox" in ICUs, they noted.
"Additional studies are clearly warranted to decipher the link between obesity, metabolic complications and COVID-19 severity with specific attention to fat mass distribution, insulin resistance and inflammatory/immune profiles," the authors said.