Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report

Abstract

Here we report a case where the manifestations of insulin-dependent diabetes occurred following SARS-CoV-2 infection in a young individual in the absence of autoantibodies typical for type 1 diabetes mellitus. Specifically, a 19-year-old white male presented at our emergency department with diabetic ketoacidosis, C-peptide level of 0.62 µg l-1 , blood glucose concentration of 30.6 mmol l-1 (552 mg dl-1) and haemoglobin A1c of 16.8%. The patient´s case history revealed probable COVID-19 infection 5-7 weeks before admission, based on a positive test for antibodies against SARS-CoV-2 proteins as determined by enzyme-linked immunosorbent assay. Interestingly, the patient carried a human leukocyte antigen genotype (HLA DR1-DR3-DQ2) considered to provide only a slightly elevated risk of developing autoimmune type 1 diabetes mellitus. However, as noted, no serum autoantibodies were observed against islet cells, glutamic acid decarboxylase, tyrosine phosphatase, insulin and zinc-transporter 8. Although our report cannot fully establish causality between COVID-19 and the development of diabetes in this patient, considering that SARS-CoV-2 entry receptors, including angiotensin-converting enzyme 2, are expressed on pancreatic β-cells and, given the circumstances of this case, we suggest that SARS-CoV-2 infection, or COVID-19, might negatively affect pancreatic function, perhaps through direct cytolytic effects of the virus on β-cells. The recent COVID-19 pandemic caused by the SARS-CoV-2 virus represents a worldwide health crisis causing severe illness and death, especially in people with cardiovascular and metabolic abnormalities 1,2. SARS-CoV-2 enters human cells via angiotensinconverting enzyme 2 (ACE2) 3 , a transmembrane glycoprotein with proteolytic activity also found in human pancreatic β-cells 4 , suggesting that SARS-CoV-2 might alter pancreatic β-cell function and impair insulin secretion. Several recently published studies indicate a link between COVID-19 and diabetes: for example, acute hyper glycaemia has been observed in a large number of individuals infected with SARS-CoV-2, regardless of any past medical history of diabetes 5-8. In another study in Asia, patients were reported

SARS-CoV-2 receptor Angiotensin I-Converting Enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature

“…A recently published case report described autoantibody-negative insulin-dependent diabetes onset in a young patient who was infected by SARS-CoV-2 seven weeks before diabetes symptoms occurrence (20). Additional previous studies further support such observation(21,22).…”

SARS-CoV-2 infects cells of the human exocrine and endocrine pancreas and interferes with beta-cell function

“…Second, severe exacerbations of a preexisting diabetes as well as new-onset diabetes have been reported [13][14][15][16] and cases of non-immune mediated diabetes in previously healthy individuals become increasingly evident 17 . So far, it is unclear whether SARS-CoV-2 triggers immune-mediated β-cell ablation as in type 1 diabetes (T1D) or directly perturbs β-cell function leading to non-autoimmune-mediated diabetes.…”

Beta-cells from patients with COVID-19 and from isolated human islets exhibit ACE2, DPP4, and TMPRSS2 expression, viral infiltration and necroptotic cell death

“…4B). This suggests that SARS-CoV-2 viral infiltration leads to pMLKL positivity, most likely associated with the necroptosis signaling pathway 24 , and might explain why type 1 diabetes has been reported after infection with SARS-CoV-2 5,6 .…”

“…In addition to its known role on the respiratory system, the human coronavirus SARS-CoV-2 has been shown to affect the endocrine system including the pancreas [1][2][3][4] . It has been suggested that the virus can induce type 1 diabetes [5][6][7][8] . Therefore, we isolated human pancreatic islets and examined the expression of angiotensin-converting enzyme 2 (ACE2) and the protease TMPRSS2, known to be important for SARS-CoV-2 entry 9 .…”

“…Furthermore, obesity, hypertension and cardiovascular disorders as common comorbidities of diabetes are all linked with adverse outcomes of COVID-19 3 . Conversely, new-onset diabetes and severe metabolic complications of preexisting diabetes have been observed in patients suffering from COVID-19 [5][6][7][8] . It has been shown that human pancreatic alpha and beta-cells are permissive to SARS-CoV-2 infection 11 .…”