More on the Importance of Glycemic Control and COVID-19 Outcomes

May 26, 2020

More on the importance of good glycemic control…

Outcomes in Patients With Hyperglycemia Affected by Covid-19: Can We Do More on Glycemic Control?

Retrospective review.  Peer reviewed and published in Diabetes Care.

This was a single-site study from Italy examining the impact of hyperglycemia and insulin infusion on outcomes. 34 patients had normoglycemia on admission and 25 patients had hyperglycemia (defined as 7.7mmol/L or 139mg/dL). The hyperglycemia patients were further divided into insulin infusion versus no insulin infusion treatment in the hospital.  Patients who had a previous diagnosis of diabetes and were on other antiglycemic medications had those held while in the hospital. All patients were treated with the same COVID-19 protocol. Composite end points were admission to the ICU, need for mechanical ventilation, and death. All patients had a definite outcome.

Eight patients with normoglycemia and 18 patients with hyperglycemia had a diagnosis of diabetes prior to admission. Beta-blocker use was significantly greater in patients with hyperglycemia and ARB use was slightly greater. Diuretics, statins, calcium channel blockers and ACEI were the same between groups. There were no significant differences in glycemic control medications between the groups for patients with a pre admission diagnosis of diabetes. At admission IL-6 and d-dimer were higher in patients with hyperglycemia and were correlated with admission blood sugar. 

The composite end point occurred in 13 (52%) patients with hyperglycemia and 5 (14.7%) with normoglycemia (P , 0.01). The mean glycemia during hospitalization was 10.65 6 0.84 mmol/L in the no insulin infusion group and 7.69 6 1.85 mmol/L in the insulin infusion group (P , 0.001).

Overall, this study reiterates the importance of admission glycemic status along with the significant improvement in outcomes with good in-patient glycemic control.  Insulin infusion in the hospital produced superior glucose control and outcomes than subcutaneous insulin. Interestingly, the triglycerides, although elevated in all groups at admission were not significantly different between any group. 

Are we in for a “surge” of T1D?

Yet another study highlights the importance of glycemic control in COVID-19 outcomes. This is not only a concern for patients with preexisting diabetes. COVID-19 patients without diabetes presenting with acute onset of hyperglycemia (often without exposure to steroids) have been reported not only in the study above, but in several case reports and previous studies.  

Type 1 Diabetes Triggered by COVID-19 Pandemic: A Potential Outbreak?

Peer reviewed and published in Diabetes Research and Clinical Practice

This very informative article discusses the possibility of an impending T1D outbreak following the COVID-19 pandemic. This is not new for coronaviruses, as hyperglycemia was found in patients without diabetes in the SARS and MERS epidemics as well.  

In a large pre-COVID study that included almost 90,000 participants, a significant rate of T1D was found in patients who had both severe and mild respiratory viral infections.  In fact, 5.8% of enrolled patients developed persistent pancreatic islet autoimmunity, with single or multiple T1DM autoantibodies at seroconversion after 9 months from the infection.

Potential causes for the insulitis and pancreatic beta cell destruction include:

  • The loss of β-cells may directly result from virus amplification cycle and/or viral antigens diffusion through the circulation. 
  • β-cell damage may determine the release of sequestered islet antigens which consequently are expressed by antigen-presenting cells in the regional lymph nodes. 
  • Overexpression of the major histocompatibility complex class I proteins could be responsible for a prolonged presentation of β-cell epitopes to the immune system, increasing the risk of autoantibodies generation
  • Viral epitopes sharing homologies with amino acid sequences of autoantigens could lead to the production of cross-reactive antibodies’ against β-cells, even after the viral infection is cleared (molecular mimicry hypothesis). 
  • Viral infection can contribute to a faster development of T1DM through cytokines release and T cells activation in individuals genetically predisposed to autoimmunity 

Type 1 and Type 2 diabetes and COVID-19 related mortality in England: a whole population study

Preprint. This has not yet been peer reviewed.

This study is the first to break down risk by type of diabetes.  Additionally, this study looked at almost the entire population of England. 

Here is a population cohort study that examined the risk of in-hospital death separately for patients with T1D and T2D and included almost the entire country of England.  The study period was March 1st 2020 - May 11th 2020. Of the almost 65 million people in the NHS database, 0.4% had a diagnosis of T1d, 4.7% had a diagnosis of T2D, and 0.1% had a diagnosis of “other” diabetes. **Much lower rate of T2D compared to US.

There were almost 24,000 hospital deaths with COVID-19 in England before the May 11th data extraction date.  A third of the deaths were recorded in patients with diabetes.

  • T2D - 7,466 (31.7% of total COVID deaths )
  • T1D - 365 (1.5%)
  • “Other” diabetes - 69 (0.3%)

Deaths were also considered by deprivation quintile. According to the NHS website - What defines whether an area is a deprived area is based on a number of characteristics included in the index of Multiple Deprivation – Income Deprivation, Employment Deprivation; Education, Skills and Training Deprivation; Health Deprivation and Disability; Crime; Barriers to Housing and Services; Living Environment Deprivation.

  • Most deprived quintile - 23.8%
  • Least deprived quintile - 15.8%

Other results to highlight:

  • There were no T1D deaths below the age of 50.
  • 61.5% of deaths overall were male
  • Mean age of those who died was 78.6
  • In overall deaths, 30.8% had a history coronary artery disease, 19.8% had cerebrovascular disease, and 17.7% had heart failure
  • Age was the most significant factor in death
  • Risk of death was significantly higher in the Asian and black population
  • After adjustments, T1D patients were 3.5 times more likely to die than the general population without diabetes, and for T2D it was 2.03 times.  After adding cardiovascular disease to adjustments the OR decreased to 2.86 for T1D and 1.81 for T2D. 
  • The risk of diabetes (T1D being the greatest) predicting death is independent of age, ethnicity, deprivation status and history of vascular disease.