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Age group, C-Reactive Protein Forecast COVID-19 Death within Diabetes

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Both high C-reactive protein (CRP) and older age predict mortality from COVID-19 in patients with diabetes, new research suggests.

The data, from the retrospective ACCREDIT cohort study, were presented September 28 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting by Daniel Kevin Llanera, MD.

The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index (BMI) did not predict COVID-19 outcomes.

“Both of these variables are easily available upon admission to hospital,” said Llanera, who now works at Imperial College, London, UK, in an EASD press release.

“This means we can easily identify patients early on their hospital stay who will likely require more aggressive interventions to try and improve survival.”

“It makes sense that CRP and age are important,” commented Simon Heller, MB BChir, DM, of the University of Sheffield, UK. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.”

“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”

Kidney Disease in Younger Patients Also Linked to Poorer Outcomes

The study, conducted when Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from January 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the UK government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.

They had a median BMI of 27.6 kg/m2, which is lower than that reported in previous studies and might explain the difference, Llanera noted.

The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly due to greater socioeconomic deprivation and older age of the population, Llanera speculated.

A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.

On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).

In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes as compared with other diabetes types (OR, 2.52).

Similar to previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor were the presence of diabetes-related complications.

In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.

Data for glycemic control during the time of hospitalization weren’t available for this study, Llanera said in response to a question.

“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”

Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.

“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.

Llanera has reported no relevant financial relationships. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.

EASD 2021 Annual Meeting. Presented September 28, 2021.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter @MiriamETucker.

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