Diabetes Management during the Pandemic

The management of diabetes during the pandemic should follow the general principles with focus on patient-centered care.12 It is important to ensure diabetes-specific medical education (DSME) and empower women with skills for self-care. This includes education and motivation about balanced nutrition and physical activity, self-monitoring of blood glucose (SMBG), and adherence to treatment.13

The pandemic is likely to impact routine clinic visits; telemedicine and remote consultation platforms provide an opportunity to ensure continuity of care. The impact of telemedicine services on diabetes care is already well-established.14 15 However, telemedicine may not always be feasible; it is important for diabetes care providers to ensure distancing and appropriate safety measures in clinics.

Optimal glycemic control may reduce the risk of severe disease in people afflicted with diabetes.16 While the factors determining the choice of medications or insulin for diabetes management remain the same, it is important to emphasize the need for optimal cardiometabolic control. The access to medications and the direct cost of treatment are likely to emerge as important variables, as the pandemic continues to have widespread economic impact.

Metformin may have gender-specific immunomodulatory effects. A recent observational study suggested that women but not men with diabetes who had been taking metformin regularly had lower mortality.17 Antidiabetic medications should therefore be continued and insulin should be considered in those with inadequate glycemic control. Patients should be counseled about the need for regular SMBG, especially if they are taking insulin. They should also be educated about sick day guidelines.

In addition, there is a need to provide psychological support to women, as women are more prone toward psychological distress. Women with diabetes are already coping with the demands of diabetes self-care, and diabetes distress puts them at greater risk of suboptimal control and worse outcomes.18

Management of Hyperglycemia in COVID-19 Infected Patients

People afflicted with diabetes constitute a large proportion of patients hospitalized for severe COVID-19, and appropriate inpatient management of hyperglycemia is important for improved outcomes.19 20 Uncontrolled hyperglycemia has been linked to increased morbidity and worse outcomes in recent studies.21

Severe COVID-19 infection may result in significant hyperglycemia not only in those with pre-existing diabetes but also in patients who have prediabetes, obesity or no previous risk factors. This is due to multiple mechanisms: increased secretion of counter-regulatory hormones, increased inflammatory response, medications such as glucocorticoids, inotropes and dextrose-containing fluids, inadequate and unpredictable oral intake, and a direct effect of SARS-CoV-2 on pancreatic islets.21

The management of hyperglycemia in infected individuals follows the general principles of hyperglycemia management during acute illness.22 23 24 Regular point-of-care blood glucose monitoring is recommended in all sick patients including those with pre-existing diabetes. Care should be taken to ensure adequate hydration and optimal nutrition. Titration of antidiabetic medications and insulin takes into account blood glucose levels, nutritional status, age, severity of infection, complications, and underlying comorbidities.

Noninsulin therapies can be continued in mild-to-moderate infection for patients who are at home or in quarantine.23 24 However, they should be instructed about regular SMBG, hypoglycemia prevention and care and sick day guidelines. Correction doses of rapid acting insulin can be used in addition to ongoing antidiabetic medications, but in case of any worsening of symptoms or persistent hyperglycemia, they should contact the medical team immediately.

Small studies have reported that DPP4 inhibitors are safe for use in hospitalized patients with type 2 diabetes and can be considered for mild hyperglycemia.19 Drugs such as sitagliptin or linagliptin, which do not increase the risk of hospitalization for heart failure, are preferred. Sulfonylureas may increase the risk of hypoglycemia while metformin may increase the risk of lactic acidosis, especially in unstable patients who have hypoxia or renal impairment. GLP1-RAs can result in significant nausea and vomiting during acute illness if patients are not taking regular meals. SGLT2 inhibitors may increase the risk of DKA and volume depletion and are best discontinued in sick patients. Pioglitazone may result in fluid retention and increase the risk of heart failure.23 24 Careful monitoring of blood glucose is required in patients on hydroxychloroquine, as it can have glucose-lowering effect.25

Insulin forms the mainstay of treatment for patients who have severe symptoms, significant hyperglycemia, complications and severe infection.23 24 Standard guidance on inpatient management of hyperglycemia using IV and basal-bolus insulin regimens is available.22 Intensive glycemic control with IV insulin infusion is associated with better outcome and reduced inflammatory and procoagulant state.

Targets for glycemic control include blood glucose of 140 to 180 mg/dl in critically ill patients and 100–180 mg/dl in noncritically ill patients.22 Intravenous insulin infusion is recommended in those who are critically ill, while other patients can be optimally managed with basal-bolus insulin regimen.

Vasopressors and glucocorticoids may significantly increase the requirement of insulin. Most patients on glucocorticoids will require insulin for management of hyperglycemia.23 Basal-bolus regimens are optimal but most of these patients require a higher bolus dose than basal insulin. NPH insulin has been used as its pharmacokinetic profile parallels the hyperglycemic effect of prednisolone or methylprednisolone.26 Tapering of glucocorticoids and acute kidney injury can increase risk of hypoglycemia. This may require frequent adjustment in insulin plan.

However, there are several challenges in care posed by shortage of resources such as personal protective equipment (PPE), ICU beds, and healthcare staff. Remote monitoring and guidance by diabetes care specialists can improve care and inpatient glycemic management.

Early reports suggest that severe COVID-19 infection may be associated with increased risk of diabetic ketoacidosis, which is associated with a grave prognosis.27 This calls for greater vigilance with regard to acute hyperglycemic emergencies in patients with COVID-19 infection and their prompt diagnosis and aggressive management. In resource-limited settings, where use of IV insulin infusion is not feasible, frequent subcutaneous injections of rapid-acting insulin analogs can be considered along with IV fluids in mild-moderate DKA.27

Pregnancy with Diabetes

The pandemic has significantly impacted healthcare services, including antenatal care delivery.28 Pregnant women with pre-existing diabetes and gestational diabetes mellitus (GDM) are a vulnerable group at increased risk of adverse maternal and fetal outcomes and require close vigilance. However, there is a need to minimize the risk of inadvertent transmission of infection from frequent visits.

A small case series of pregnant women with COVID-19 suggested that the presence of gestational diabetes or gestational hypertension did not increase the risk of life-threatening infection in the mother.29 The risk of fetal transmission is another factor to consider.

Some recent guidelines suggest that the standard 2-hour oral glucose tolerance test (OGTT) may be avoided during the pandemic and instead recommend use of fasting plasma glucose, random plasma glucose and HbA1c.30 31 Underdiagnosis of GDM remains a major concern, as these criteria have not been validated but may be useful alternatives during the pandemic.32

As per the recent guidelines from the International Federation of Gynecologists and Obstetricians, the management of diabetes during pregnancy should follow established standards of care using lifestyle modification, medical nutrition therapy, SMBG and insulin.33 Video consultations for management of diabetes during pregnancy may improve care while limiting the need for hospital visits, with clinic visits limited to ultrasound and retinal scans, laboratory monitoring and emergency evaluation.34

Some antenatal women with diabetes may be administered glucocorticoids to promote fetal lung maturation if there is a risk of preterm delivery. This may result in hyperglycemia requiring insulin dose adjustment.34

Adrenal Insufficiency

There is no evidence at present to suggest that patients with adrenal insufficiency who are on glucocorticoid replacement or patients being treated with glucocorticoids for other systemic diseases are at an increased risk from COVID-19 infection or that glucocorticoids protect them.5 15 42 However, people on glucocorticoids (such as those with inflammatory diseases, malignancy, transplant recipients, etc.) represent a group with greater risk of comorbidities and immune disorders which makes them vulnerable.

The Endocrine Society have provided guidance for patients with primary or secondary adrenal insufficiency and for patients on long-term glucocorticoids.16 Patients who are on long-term glucocorticoids as replacement (adrenal insufficiency) or immunosuppressive agents are at risk of adrenal crisis during acute illness and must be instructed on “sick day rules” and stress doses of glucocorticoids.5

In case of fever, cough, diarrhea or any acute illness, they should be advised to double the dose of oral glucocorticoids till symptoms resolve or take oral hydrocortisone 20 mg every 6 to 8 hours.13 16 If there is inadequate supply of oral hydrocortisone, patients should be instructed to use equivalent doses of oral prednisolone. Intravenous or intramuscular hydrocortisone (100 mg bolus followed by infusion or 50 mg every 6–8 hours) should be used in case of any worsening of symptoms or occurrence hypotension, altered sensorium or recurrent vomiting. Timely diagnosis and management of adrenal failure with parenteral glucocorticoids is required.

Critically ill COVID-19 infected patients may develop critical illness-related corticosteroid insufficiency (CIRCI) due to impaired activation of the hypothalamic–pituitary–adrenal (HPA) axis in response to stress.37 CIRCI has been associated with increased inflammatory and procoagulant markers, greater morbidity and ICU stay. Patients with altered sensorium, refractory hypotension and dyselectrolytemia (hyponatremia, hyperkalemia and normal anion gap metabolic acidosis) should be considered for short-term intravenous glucocorticoids (hydrocortisone 100 mg 8 hourly). Such HPA axis suppression was documented in SARS patients, and it would be prudent to assess if patients who continue to complain of significant malaise and fatigue following recovery from COVID-19 have altered cortisol dynamics.43

Recent studies have demonstrated that dexamethasone reduces mortality in critically ill COVID-19 infected patients by preventing cytokine storm and multiorgan failure.42 44 Low-dose dexamethasone reduced the risk of mortality by 35% in ventilated patients and by 20% in those on supplemental oxygen in the RECOVERY trial. No benefit was seen in mild cases.42 This needs to be balanced against the risk of delayed viral clearance, superadded infections and hyperglycemia due to glucocorticoids. Dexamethasone has shown benefits in severe COVID-19 infection. However, there is potential concern of its abuse, as it is a nonexpensive medication that is easily available, even over-the-counter in some countries. For COVID-19 patients who are being treated with glucocorticoids, glucocorticoid therapy may be discontinued if the use has been short-term (less than 3 weeks). However, among patients in whom glucocorticoids are used for longer duration of time, a gradual tapering down of the dose is advisable, as these patients may have adrenal suppression due to exogenous glucocorticoid therapy.45

Cushing’s Syndrome (CS)

Patients with CS, both exogenous and endogenous, are at an increased risk of morbidity and mortality from COVID-19 infection due to immunocompromised state along with occurrence of comorbidities such as diabetes, hypertension, central obesity, cardiovascular disease, endothelial dysfunction, and procoagulant state. Therefore, they constitute a highly vulnerable group.37 Specific data on COVID-19 infection in patients with CS is currently unavailable, but these patients should be instructed to follow strict preventive measures. Treatment should focus on optimal cardiometabolic control as well as rapid normalization of cortisol levels.13

Trans-sphenoidal surgery (TSS) can result in aerosol formation; therefore, presurgical testing for COVID-19 and use of PPE by surgical team should be considered. In cases where surgery is deferred, inhibitors of steroidogenesis such as ketoconazole or metyrapone should be considered to tide over the waiting period.13

Primary Hyperaldosteronism and Pheochromocytoma

There is no data related to risk of COVID-19 infection in patients with primary hyperaldosteronism or pheochromocytoma, but the underlying hypertension and dysglycemia increases the risk in these individuals. Evaluation and treatment of these endocrine disorders should not be delayed or compromised.