Type 1 Diabetes, COVID-19 in Navajo and Cherokee Tribes, Inflammation, and Analysis of Hospitalizations

April 20, 2020

Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China

Peer Reviewed to appear in Chest. Retrospective Cohort study

Nationwide study from China which included data from 575 hospitals through January 31st.  A total of 2007 patients were admitted with confirmed COVID-19.  417 patients were excluded due to missing data.  Of the 1590 cases included in this cohort, 50 deaths were reported by Jan 31st. Of those 50 patients, thirty-five (70%) cases reported 1 or more co-existing illness : twenty-eight (56.0%) with hypertension, thirteen(26.0%) with diabetes [**consistent with previous studies], eight(16.0%) with coronary heart disease(CHD), six(12.0%) with cerebrovascular disease(CVD), six (12.0%) with chronic obstructive pulmonary disease (COPD), five (10.0%) with renal disease

The multivariate Cox regression model  demonstrated some independent predictive factors for a fatal outcome. Age≥75 (HR: 7.86, 95% CI: 2.44-25.35), age between 65-74 years (HR:3.43, 95%CI: 1.24- 9.5), CHD (HR:4.28, 95%CI:1.14-16.13), CVD (HR:3.1, 95%CI:1.07-8.94), dyspnea(HR: 3.96, 95%CI:1.42-11), PCT>0.5ng/ml(HR:8.72, 95%CI:3.42-22.28), AST>40U/liter (HR: 2.2, 95% CI: 1.1- 6.73) were independent risk factors associated with fatal outcomes

Kaplan-Meier survival plots for different prognostic factors.

Managing New-Onset Type 1 Diabetes During the COVID-19 Pandemic: Challenges and Opportunities

Peer Reviewed and Published in Diabetes Technology & Therapeutics. Two case studies.

Case 1: 20 year old new diagnosis T1D who presented with DKA and was admitted to the ICU for 2 days and the general medical floor for a 3rd day.  He had in-office appointments on day 1 and day 4 post-hospitalization, otherwise, he was given care virtually.  His insulin was adjusted daily in the first week based on continuous glucose monitoring (CGM) with a Dexcom G6.  In addition to physician virtual visits, he also met with the diabetes educator virtually.  Over a 3-week period of time his glucose control improved significantly and he had no hypoglycemic events.

Case 2: 12-month old was admitted with mild DKA and diagnosed with T1D.  The family lived far from any medical center so she was started on an insulin pump and CGM (Dexcom G6).  During the first 2-weeks, the mother uploaded the insulin pump nightly.  Insulin adjustments were made via phone or email daily based on insulin pump and CGM data.  After 2-weeks the patient had significant post-prandial glucose excursions due to post prandial insulin dosing secondary to unpredictable intake but otherwise care was successfully implemented virtually.

Summary: New diabetes technologies along with decreased regulation are making virtual care for diabetes a reality in the age of COVID-19.  Virtual care has the potential to improve care and provide cost savings. 

Susceptibility of Southwestern American Indian Tribes to Coronavirus Disease 2019 (COVID-19)

Peer Reviewed and published in the Journal of Public Health. Commentary.

The Navajo and Cherokee nations in the southwest United States have been disproportionately affected by COVID-19 compared to rates within their states as a whole. Social distancing is more difficult for American Indians as there are often multiple generations living in the same household.  There are also concerns about inadequate innate immune responses within these populations.  The American Indians had a significantly higher mortality rate than the rest of the country during the 1918 Spanish flu, a regional Hantavirus outbreak and the H1N1 virus. Other concerns revolve around social determinants of health caused by poverty. American Indian populations have demonstrated disproportionately higher prevalence and/or mortality rates of obesity, diabetes mellitus, and cardiovascular disease than the general US population and also have a higher rate of smoking.  All these have been associated with a higher risk of poor outcomes due to COVID-19 infection. One conclusion - increasing telehealth in these populations may help to protect these particularly vulnerable groups. 

Paradigm Shift for COVID-19 Response: Identifying High-risk Individuals and Treating Inflammation

Peer reviewed and published in Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health.  Expert Commentary.

This article discusses that cytokine release syndrome (CRS)/cytokine storm symptoms are a consistent finding in patients with poor outcomes from COVID-19.  Measuring inflammatory markers such as CRP, IL-6 and ferritin may be helpful in predicting which patients are at the highest risk for decompensating.  Traditional anti-inflammatory medications such as steroids and NSAIDS have not proven helpful in treating COVID-19 patients.  Drugs such as biologics that are known to decrease IL-6 levels may be helpful.  The virus is disproportionately targeting older men and post-menopausal women and low testosterone in these groups has been associated with higher levels of IL-6 along with higher rates of diabetes and obesity. Other otc medications that have been shown to decrease IL-6 are noted including Vitamin D3,

Zinc, magnesium, probiotics, aspirin, fish oil/DHA, and resveratrol.  Diabetes, obesity, high blood sugar, high glycemic index or starchy foods have all been associated with high IL-6.  The suggestion is that inflammatory markers could help healthcare providers identify who is at high risk and for patients there may be lifestyle, otc interventions, and possibly testosterone that may help prevent complications from COVID.

**There is evidence regarding cytokine storm and poor outcomes in COVID-19, but the premise of decreasing inflammation prior to infection to improve outcomes is plausible, but only speculative at this time.

Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Hospitalized in the United States

Peer reviewed and published in Journal of Diabetes Science and Technology. Retrospective observational study. 

Diabetes has consistently been found to be a risk factor for poor outcomes from COVID-19 in the United States and other countries. Little evidence exists on if glucose control is a factor in the overall increased risk.  This retrospective observational study gathered data from Glytec (Waltham, MA), an insulin software titration company that maintains a large data warehouse of patient clinical and glycemic data.   COVID-19 inpatients from the Glytec data warehouse that were treated during a 37-day period from March 1-April 6, 2020 had data analyzed from all transmitted BGs during their hospital stay   The focus of the review was on 1) clinical characteristics at hospital presentation, 2) inpatient glycemic control and 3) clinical outcomes. Patients who had diabetes or uncontrolled hyperglycemia were compared against each other and against contemporaneously hospitalized COVID-19 patients who did not have either diabetes or uncontrolled hyperglycemia. 

1122 patients with COVID-19 from 88 U.S. hospitals distributed across 10 states were identified.  Of those patients, 194 patients (17.3% of the total population) had diabetes, and an additional 257 patients had uncontrolled hyperglycemia. The combined group of 451 patients with diabetes by A1C criteria and/or uncontrolled hyperglycemia (194 + 257), compared with 671 patients who did not meet diabetes or uncontrolled hyperglycemia criteria. The group with diabetes or uncontrolled hyperglycemia were significantly older and had a higher percentage of males.  Significant hyper and hypoglycemia were more likely to occur in the cohort with diabetes and uncontrolled hyperglycemia.  

Almost half of the patients were still in the hospital at the time of analysis.  Of the group that was no longer in the hospital,  the death rate was 13.5% overall (77 patients).  Of these 77 patients who died, 53 of them were among the 184 patients in the combined diabetes and uncontrolled hyperglycemia group (28.8%) compared with 24 of them who were among the 386 patients in the comparison unaffected group (6.2%, p < 0.001).

Diabetes patients had a higher admission mean BG at 238.3 mg/dl compared with uncontrolled hyperglycemia patients at 175.3 mg/dl (p < 0.001).  In a within-group subset analysis of 184  patients who were no longer inpatients with diabetes or uncontrolled hyperglycemia patients, 88 patients met criteria for diabetes (47.8%), and 96 met criteria for uncontrolled hyperglycemia (52.2%). Among these 184 non-hospitalized patients, death occurred in 40 of 96 uncontrolled hyperglycemia patients (41.7%) compared with death in 13 of 88 diabetes patients (14.8%, p < 0.001)  

Conclusions: Among hospitalized patients with COVID-19, diabetes, and/or uncontrolled hyperglycemia occurred frequently. These COVID-19 patients with diabetes and/or uncontrolled hyperglycemia had a longer LOS and markedly higher mortality than patients without diabetes and/or uncontrolled hyperglycemia. Patients with uncontrolled hyperglycemia had a particularly high mortality rate. We recommend that health systems ensure inpatient hyperglycemia is safely and effectively treated.

Epidemiology and clinical features of COVID-19: A review of current literature

Peer reviewed and published in the Journal of Virology.  Review.

This paper organizes previously published data into a summary review and the non-clinical care aspects of this paper are reviewed below.

Viral structure and life cycle COVID-19 is a single, positive-stranded RNA virus enveloped in a lipid bilayer.  The virus binds to human protein ACE2 which is found in lung, heart, kidney, and adipose tissue to allow entry into cells.

Transmission and infectivity Modes of transmission appear to be droplet, close contact and fomites.  Little evidence of airborne transmission.  Incubation period is 3-9 days and 18% remain asymptomatic.  People are contagious before they have symptoms and viral shedding can continue for up to 25 days after symptoms appear.

Clinical features Most COVID-19 cases involve people aged 30-79.The most common comorbidity is hypertension (30.7 %). This is followed by diabetes mellitus (14.3 %) and cardiovascular diseases (11.9 %).  The most common symptom associated with COVID-19 is fever, followed by cough. RT-PCR remains the gold standard for diagnosing COVID-19. 

Prognosis Comorbidities associated with severe COVID-19 cases include elderly age, hypertension, cardiovascular disease, cerebrovascular disease, and chronic kidney disease. 

Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome

Peer reviewed and published in the Journal of Clinical Virology. Systematic review. 

This paper searched all English language articles with search terms “COVID” and “mortality” or “ICU” or “Diabetes Mellitus”.  The primary outcome was the risk for patients with diabetes to require ICU admission and the secondary outcome was the mortality risk of those patients.  Eight studies overall met the criteria with four studies for the primary outcome and 4 studies for the secondary outcome. 

Risk of ICU admission

Diabetes was found to be the second most common comorbidity and they had a significantly increased risk of ICU admission (OR: 2.79, 95 % CI 1.85–4.22, p < 0.0001, I2 = 46 %).

Mortality risk

Diabetes was also found to be the second most common comorbidity and those with diabetes were determined to be at a much higher mortality risk (OR 3.21, 95 % CI 1.82–5.64, p < 0.0001, I2 = 16 %). 

**Noted limitation is the lack of ability to account for other cofounding factors based on the data available.  

Conclusions: Our analysis suggests that diabetic patients with COVID-19 infection have a higher risk of being admitted to the ICU and a higher mortality risk during the disease.