The COVID-19 pandemic has raged for more than two and a half years now. For eye care providers, its presence has meant keeping a keen eye out for its ocular manifestations (e.g., conjunctivitis) and, most recently, its consequences on established patients who have diabetes and those who may develop diabetes post-virus.

Here, I review the consequences on patients who have diabetes, and the action steps optometrists can take to continue to be vigilant in protecting these patients, other patients, and themselves.

ESTABLISHED DIABETIC PATIENTS

Although patients who have diabetes appear to be no more likely to develop COVID-19 than patients who don’t have diabetes, the presence of diabetes is now a well-established risk factor for poor outcomes.¹ These poor outcomes include higher risk of intensive care unit (ICU) admission, need to be placed on a ventilator, and death.² In fact, those patients who have diabetes have experienced disproportionately higher morbidity and mortality to COVID-19 than those without diabetes.

The reasons for this:

• A higher propensity for immunocompromised status.¹
• Increased COVID-19 entry into cells as a function of hyperglycemia.¹
• Higher rates of poorly controlled blood glucose as a function of both direct infection³ and increased sedentary behaviors, coupled with excess consumption of refined carbohydrates during lockdowns, and self-imposed isolation.⁴
• Older age of many diabetes patients, a known risk factor for more severe COVID infection and poorer outcomes.⁵

The result of these intermingled factors has been higher rates of vascular diabetes complications, including diabetic retinopathy (DR),⁶ reduced follow-up visits with health care providers, including eye doctors for both routine surveillance and necessary treatment, and higher rates of death.

Meta-analysis suggests that in type 2 diabetes (T2DM), the most common form of diabetes mellitus, glycated hemoglobin (HbA1c), fasting glucose and body mass index significantly increased during the pandemic.⁴

Of note: Obesity and hypertension are conditions that frequently commingle with diabetes, and these three conditions together are those most associated with COVID-19 hospitalization and mortality.^7,8 The reasons for this increased risk are not entirely clear. That said, diabetes in general, and hyperglycemia and insulin resistance, in particular, are linked to excess inflammation, vascular coagulability, and increased risk of secondary infection, including pneumonia.⁹ According to the American Diabetes Association, infections are an important issue for individuals who have diabetes due to the immune system’s failure to fight off invading pathogens.¹⁰

Something else to keep in mind: Diabetic ketoacidosis occurs at higher rates in patients who have diabetes and COVID-19. This is a condition that may cause cerebral edema, acute respiratory distress syndrome (ARDS), myocardial infarction, and death as a consequence of rapid shifts in intracellular fluid volume.¹¹

Interestingly, patients with diabetes who have high blood glucose levels upon hospital admission have worse outcomes. One study shows that patients who had blood sugar levels >196 mg/dl were 3.2 times more likely to experience in-hospital complications, including more than a doubled risk of ARDS and ICU admission, and nearly a 10-fold increased risk of acute cardiac injury. Additionally, these patients were 7.6 times more likely to die vs. patients who had blood glucoses <196 mg/dL.¹²

Another analysis reveals that patients with diabetes and good metabolic control prior to admission (defined as most glucose readings between 70 mg/dL and 180 mg/dL and/or hemoglobin A1c <7.5%) had better outcomes than those who had poorer glucose control.¹³

Regarding the progression of DR, cross-sectional analyses reveal significantly higher rates of nonproliferative DR, proliferative DR (PDR) and diabetic macular edema and worsening VA during the pandemic.^6,14,15 This is predominantly due to worsening blood glucose control and follow-up non-attendance with eye care providers during the COVID-19 lockdown. That said, patients who had acutely symptomatic manifestations of PDR (i.e., vitreous hemorrhage, traction retinal detachment, neovascular glaucoma) did receive timely intervention in another retrospective analysis of patients in the UK.¹⁶

A related concern is the extent to which DR presence and severity is associated with increased hospitalization and death. There is some evidence that the presence of any DR in general, and referable DR in particular, increases the likelihood of ICU admission and death up to 67%.¹⁷

The CORONADO study, conducted, in France examined hospitalized COVID-19 patients who had preexisting diabetes (n = 2796) to assess factors predicting hospital discharge within 28 days of admission and mortality.¹⁸ Protective factors included a long duration of symptoms prior to hospitalization, metformin use, absence of microvascular complications, and younger age. Conversely, short duration between symptom onset and hospitalization (especially shortness of breath), presence of microvascular complications, (especially DR and diabetic kidney disease), older age, insulin use, elevated C-reactive protein and the liver enzyme aspartate aminotransferase (AST), and decreased platelet count were significantly associated with long hospital stay and death. A recent systematic review concludes that there is an “independent association between DR and poorer COVID-19 prognosis in patients who have diabetes mellitus after controlling for key variables, such as age.”¹⁹

The evidence is clear that diabetes and DR are cumulatively associated with a significantly increased risk of poor COVID-19 outcomes, including death. Additionally, the virus worsens diabetes control and DR severity at a population level.

POST-COVID-19 DIABETIC PATIENTS

The COVID-19 pandemic has been linked to a significant increase in the onset of both type 1 and T2DM diabetes after the acute infectious period that has been demonstrated to persist out to a year.²⁰ The changes discussed in the aforementioned meta-analysis might explain the increased incidence of new-onset T2DM in those who had prediabetes or a history of gestational diabetes, two huge risk factors for developing T2DM.⁴

Something else to consider: A 40% increased risk of new-onset T2DM was found at 12 months in U.S. veterans who survived COVID-19 vs. COVID-19-negative controls in a cohort study of more than 181,000 U.S. veterans who had confirmed COVID-19 vs. more than 8 million control subjects. The highest risk for T2DM diabetes was seen in veterans requiring hospitalization (91% increase) or ICU admission (23% increase).²¹ This has led some researchers to conclude that diabetes should be considered another manifestation of post-acute sequelae of COVID-19 infection, also known as “long COVID.”¹⁹ Of note: New-onset diabetes was most commonly seen within the first three months after acute COVID-19 infection.¹⁹

These findings beg the question, “why is COVID-19 infection thought to increase the risk of diabetes?” Two possible answers:

• Damage to or destruction on the insulin-producing pancreatic beta cells may result from direct infection by COVID-19, as well as an immune-mediated destruction and even pancreatitis.²² Increased excess rates of autoimmune type 1 diabetes have been seen during the pandemic, consistent with this hypothesis.²³
• Stress with accompanying increased levels of endogenous cortisol, cytokine storm and use of corticosteroids in the treatment of acute COVID-19 are all known to increase insulin resistance that directly contributes to T2DM.²²

The bottom line: COVID-19 infection increases the likelihood of developing diabetes in the post-infectious period up to an entire year later.

ACTION STEPS

So how can ODs continue to be vigilant in protecting these patient populations, their other patients, and themselves? The answers are they can:

• Work diligently with established patients who have diabetes toward good metabolic control, particularly when viral illnesses are rampant. Educate about the importance of good glucose control to prevent bad outcomes, stress medication compliance, and discuss the benefits of a low refined carbohydrate diet. As, “The alterations in behavioral patterns, daily life and exercise as well as increased feelings of stress and anxiety are all known to influence diabetes self-management and glycemic control.²⁴
• Take reasonable precautions (use of face masks, room ventilation, social distancing) against COVID-19 transmission when examining high-risk patients, including those who have diabetes.
• Encourage patients who have diabetes to take these precautions in public settings outside offices.
• Encourage patients who have diabetes to receive recommended vaccinations against airborne respiratory illnesses, such as COVID-19.
• Encourage patients who have diabetes to correct a possible vitamin D deficiency linked to respiratory illness and poorer COVID-19 outcomes.²⁵
• Encourage patients who have diabetes to achieve consistently good metabolic control to reduce these risks when COVID-19 infection occurs.
• Be especially vigilant for manifestations of undiagnosed diabetes (e.g., sudden refractive change, but also the classic three Ps: polyuria, polyphagia and polydipsia) during this time period. OM

REFERENCES

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DR. CHOUS practices at Chous Eye Care, in Tacoma, Wash. He has practiced optometry with a special emphasis on diabetic eye disease and diabetes education for 30 years. Dr. Chous is a primary investigator for the Diabetes Visual Function Supplement Study, and adjunct professor of optometry at Western University of Health Sciences, and he lectures and writes frequently on diabetes and diabetic retinopathy. He is on advisory boards for or has lectured on behalf of Bausch & Lomb, Genentech, Notal, Regeneron, VSP, ZeaVision, and Zeiss.