Characterizing progressive beta-cell recovery after new-onset DKA in COVID-19 provoked A-β+ KPD (ketosis-prone diabetes): A prospective study from Eastern India

Abstract

Background: Recent literature suggests a bi-directional relationship between COVID-19 infection and diabetes mellitus, with an increasing number of previously normoglycemic adults with COVID-19 being admitted with new-onset diabetic ketoacidosis (DKA). However, the possibility of COVID-19 being a potential trigger for A-β + ketosis-prone diabetes (KPD) in these patients needs elucidation. Our study aimed at analyzing such a cohort of patients and determining their natural course of β-cell recovery on serial follow-up.

Methods: After initial screening, n = 42 previously non-diabetic patients with new-onset DKA and RT-PCR positive COVID-19, were included in our ten-month follow-up study. Of these, n = 22 were negative (suspected A-β + KPD) and n = 20 were positive (Type 1A DM) for autoantibodies (GAD/IA-2/ZnT8). Subsequently, n = 19 suspected KPD and n = 18 Type 1A DM patients were followed-up over ten months with serial assessments of clinical, biochemical and β-cell secretion. Amongst the former, n = 15 (79%) patients achieved insulin independence, while n = 4 (21%) continued to require insulin at ten-months follow-up.

Results: On comparison, the suspected KPD patients showed significantly greater BMI, age, Hba1c, IL-6 and worse DKA parameters at presentation. Serial C-peptide estimations demonstrated significant β-cell recovery in KPD group, with complete recovery seen in the 15 patients who became insulin independent on follow-up. Younger age, lower BMI, initial severity of DKA and inflammation (IL-6 levels), along-with reduced 25-hydroxy-Vitamin-D levels were associated with poorer recovery of β-cell secretion at ten-month follow-up amongst the KPD patients, CONCLUSIONS: This is the first prospective study to demonstrate progressive recovery of β-cell secretion in new-onset A-β + KPD provoked by COVID-19 infection in Indian adults, with a distinctly different profile from Type 1A DM. Given their significant potential for β-cell recovery, meticulous follow-up involving C-peptide estimations can help guide treatment and avoid injudicious use of insulin.

Keywords: C-peptide; COVID-19 infection; Diabetic ketoacidosis (DKA); Ketosis prone diabetes (KPD).

Fig. 1

Flow diagram depicting the study outline. DKA-diabetic ketoacidosis; DM-diabetes mellitus; KPD-ketosis prone diabetes; GC-glucocorticoids.