Diabetes and COVID-19

Kacey Chae, M.D., Jordan Perlman, M.D., Rita Rastogi Kalyani, M.D., M.H.S.

DEFINITION

  • SARS-COV-2 is a novel, positive-sense, single-stranded RNA virus belonging to the Coronaviridae family.[31]
  • The virus was first isolated from throat swabs of patients in Wuhan, Hubei Province, China in late-2019.
  • The disease caused by SARS-COV-2 was named COVID-19 by the World Health Organization in January 2020.
  • COVID-19 causes symptoms ranging from mild, flu-like illness to acute respiratory distress syndrome (ARDS) and severe end-organ damage.[7]
  • For more information regarding microbiology, please refer to the Johns Hopkins Antibiotic Guide

EPIDEMIOLOGY

  • There are more than 20 million confirmed cases of COVID-19 worldwide.[48]
  • The U.S. alone has 5 million confirmed cases.
  • The CDC cites multiple risk factors for severe COVID-19 infection, including:
    • T2DM
    • Serious cardiovascular disease
    • COPD
    • CKD
    • Active malignancy
    • Obesity
    • History of solid organ transplant
  • There are also several factors associated with possible increased risk for severe COVID-19 infection, including:
    • T1DM
    • Asthma
    • CVA or other neurological condition
    • Cystic fibrosis
    • Pulmonary fibrosis
    • Current tobacco use
    • Hypertension
    • Immunocompromised state
    • Liver disease
    • Pregnancy
  • The mechanism by which diabetes increases risk for severe COVID-19 infection may be a dysregulated inflammatory response caused by chronic, low-grade inflammation.[49]
  • COVID-19 admission rates are higher among patients with diabetes.
    • In an American study, the COVID-19 admission rate for patients with diabetes was 34.7% compared to 9.7% in those without.[4]
  • DKA occurs frequently among individuals with diabetes and COVID-19 infection.
    • In an English study, 1.5% of all patients admitted for COVID-19 infection developed DKA[12].

DIAGNOSIS

  • COVID-19 infection should be considered in all patients with concerning symptoms, labs or imaging findings or who have had close contact with a suspected or confirmed case.
  • For coronavirus COVID-19 (SARS-CoV-2) testing information, see the Johns Hopkins Antibiotic Guide

SIGNS AND SYMPTOMS

COVID-19 infection in the adult population

  • A large percentage of patients with positive COVID-19 throat swabs are asymptomatic.
  • The most common symptoms of COVID-19 include:[22]
    • Fever (44-98%)
    • Cough (69-82%)
    • Dyspnea (19-64%)
    • Sputum production (14-34%)
    • Myalgias (11-15%)
  • Less common symptoms of COVID-19 include:
    • Rhinorrhea (4-24%)
    • Sore throat (5-14%)
    • Headache (5-14%)
    • Diarrhea (2-5%)
    • Nausea/vomiting (1-10%)
    • Loss of taste/smell
  • Characteristic laboratory findings in COVID-19 infection:
    • CBC: Lymphopenia, leukopenia, thrombocytopenia
    • Chemistry: Elevated AST/ALT
    • Inflammatory markers: Elevated CRP, elevated ESR, elevated D-dimer, elevated LDH, elevated serum ferritin, elevated IL-6
  • Characteristic imaging findings in COVID-19 infection:
    • CT chest: ground-glass opacities, bilateral patchy shadows, subsegmental areas of consolidation

COVID-19 infection in the pediatric population

  • Symptoms are similar to those reported in adults.
  • A small subset of the pediatric population develops multisystem inflammatory syndrome (MIS-C), leading to multiple organ system dysfunction.[3]
  • In a limited cohort study conducted at a New York hospital, 30% of children with MIS-C developed cardiomegaly, 69% developed decreased EF and 18% developed bilateral pulmonary opacities. One patient was sick enough to require ECMO, and another needed an intra-aortic balloon pump.

Concerning symptoms in patients with preexisting diabetes

  • Any infection can increase the risk for severe hyperglycemia, DKA and HHS in patients with preexisting diabetes.[47]
  • Patients with preexisting diabetes who contract the novel coronavirus need be educated about possible symptoms of severe hyperglycemia, DKA and HHS, and may need to monitor glucose levels at home more frequently.
    • Concerning symptoms: polyuria/polydipsia, nausea/vomiting, abdominal pain, fruity odor on the breath, difficulty breathing or rapid breathing, altered level of consciousness

CLINICAL TREATMENT

Outpatient diabetes management in patients with COVID-19

  • Previous oral regimen can be continued provided patient is tolerating PO and completes more frequent blood glucose checks.
  • Consider holding SGLT-2 inhibitors as these may precipitate euglycemic DKA in acute illness.[29][35][33]
    • Any patient prescribed insulin should be counseled about inappropriate dose reduction and omission.
    • Potential symptoms of DKA (including impaired consciousness, nausea/vomiting and abdominal pain) should prompt further evaluation for blood ketones (even if the blood glucose is normal).
    • It is still possible for SGLT-2 inhibitors to precipitate DKA in patients not prescribed insulin. We are most concerned about individuals who are insulin-deficient and/or have severe elevated HbA1c. There is also increased risk to persons who follow ketogenic (carbohydrate-restricted) diets or drink alcohol to excess. Most other patients treated with oral diabetes medications can be considered very low risk for DKA.
  • CGM users can review the effects of the virus on blood glucose values in real-time.
  • It may be necessary to adjust home insulin dosing based on sick-day protocols.
  • Empiric dexamethasone may not be appropriate in all inpatients with diabetes.
    • The risk of severe hyperglycemia likely outweighs the COVID-19 treatment benefit in the outpatient setting.[13][16][6][32][1]
  • Oral diabetes medications may interact with those used to treat COVID-19.[18]
    • Hydroxychloroquine interacts with sulfonylureas and causes hypoglycemia.
    • Protease inhibitors interact with most classes of non-insulin diabetes medication and may cause hyperglycemia.
  • Some oral diabetes medications have antiviral properties and decrease lung inflammation in animal models.[29][5][44][34][36][30][38]
  • There was no evidence of clinical improvement starting a DPP-4 inhibitor in patients with SARS or MERS.

Inpatient diabetes management in patients with COVID-19

  • Good outpatient glycemic control is important for survival.[43]
    • T2DM OR for death from COVID-19 at HbA1c > 10% = 1.62
    • T1DM OR for death from COVID-19 at HbA1c > 10% = 2.19
  • Inpatient hyperglycemia in COVID-19 increases the risk of death independent of diabetes.[8]
  • No current COVID-specific inpatient blood glucose targets
  • Italian study published in Lancet showed reduced inflammatory markers at mean inpatient blood glucose 115 mg/dL compared to 135 mg/dL.[18]
    • Increased risk of DKA and HHS in T1DM and T2DM
  • Recent American study showed that 45.5% of T1DM patients admitted with COVID-19 had DKA, and 11% of admitted T2DM patients with COVID-19 had DKA or HHS[20]
  • Some patients may not even have a preexisting diabetes diagnosis, and COVID-19 infection with hyperglycemia and/or DKA could be the initial presentation.[11][26][2]
  • Subcutaneous protocols to treat DKA available from numerous academic centers designed to limit nursing exposure[21][17]
  • Any patient who has a new diagnosis of diabetes or preexisting T2DM and develops DKA/HHS should have islet antibody and c-peptide screening.
  • SARS-COV2 binds to the ACE-2 receptor on beta cells leading to impaired insulin secretion and/or destruction.[8]
  • Previous research on the HHV-8 virus showed increased ketosis in patients with T2DM.[39]
  • Continuous glucose monitoring (CGM) offers promise as an effective tool for monitoring hospitalized patients. During the COVID-19 pandemic, this technology can be implemented to address emergent needs when there is increased demand for both nursing staff and PPE.[9]
    • In April 2020, the FDA allowed use of inpatient CGM to monitor coronavirus patients.[10]
    • Abbott and Dexcom offered to supply hospitals with CGM systems and help clients learn to use these devices effectively.[45][46]
    • The newest generation of CGM devices have alarms that can alert clinicians (and patients) to abnormal blood glucose values.
    • A few of the newer systems are FDA approved for nonadjunctive use to dose insulin (i.e. confirmatory fingerstick not required).
    • CGM accuracy is no longer impacted by use of acetaminophen.
    • More data are needed to assess performance of CGM in mainstream hospital practice:
      • The current EHR must be modified to accept blood glucose data from the sensor.
      • Hospitalist physicians and staff need to be trained to interpret CGM trends.
      • CGM may not be feasible for patients who require frequent imaging (must be removed prior to CT and MRI).

FOLLOW UP

  • There are no published guidelines on appropriate follow-up for patients with diabetes who contract COVID-19.
    • We suggest that patients wait to restart SGLT-2 inhibitors until they are feeling better and able to eat and drink.[35][33]
    • Any new diagnosis of diabetes in the setting of COVID-19 should be referred to primary care at discharge.
  • An elevated HbA1c during hospitalization argues against hyperglycemia due to acute illness..
    • Any new outpatient insulin requirement following COVID-19 infection should be referred to primary care or Endocrinology at discharge.
  • Some patients may require insulin for an extended duration following hospitalization due to insulin resistance (from counter-regulatory hormones) and glucose toxicity.
    • These patients should receive instruction on blood glucose monitoring and nutrition inpatient if possible.
    • These patients must be given a prescription for a glucagon emergency kit if intending to continue insulin.
  • Any patient who develops DKA or HHS in the setting of COVID-19 should be referred to Endocrinology at discharge.
    • There is no literature on what percentage of patients recover previous beta cell function.

EXPERT COMMENTS

  • There is no direct evidence that diabetes increases the risk of contracting COVID-19, but we know that hyperglycemia impairs leukocyte function in vitro.[37][41][40]
    • In a Chinese meta-analysis, the prevalence of diabetes in COVID-19 patients was similar to that in the general population.[28]
    • In an Italian study, the prevalence of diabetes in patients admitted for COVID-19 infection was lower than that in the same region.[27]
    • In an American study, T1DM patients who contracted COVID-19 had similar clinical characteristics and outpatient glycemic control compared to those not infected.[15]
  • It is clear that diabetes increases the risk of complications and death from COVID-19.
    • In an Italian study, 31.1% of hospitalized patients who died from COVID-19 had diabetes.[42]
    • In a French study, 43% of hospitalized patients who died from COVID-19 had diabetes.[19]
    • In an English study, 31.4% of hospitalized patients who died from COVID-19 had T2DM (adjusted OR = 1.8) and 1.5% had T1DM (adjusted OR = 2.86).[14]
  • We use a glycemic target of 140-180 mg/dL for hospitalized COVID-19 patients similar to other patients with diabetes.
  • There is increased incidence of DKA and HHS in COVID-19 infection[12][20], including among patients with no previous known history of diabetes.
    • We do not yet know whether this is due to increased insulin resistance/glucose toxicity, beta cell destruction or induction of autoimmunity.
    • There are no published data on the post-discharge clinical course of patients with new insulin requirement following COVID-19 infection.
  • Where appropriate, some institutions have implemented scheduled subcutaneous insulin protocols adapted from previous studies versus intravenous insulin to help reduce nursing exposure.[17]
  • As diabetes providers, we need to be advocating for influenza vaccination and COVID-19 vaccination once it becomes available.

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Last updated: October 5, 2020