Effect of SARS-CoV-2 Infection on Incident Diabetes by Viral Variant: Findings From the National COVID Cohort Collaborative (N3C)

Abstract

Objective: The coronavirus 2019 (COVID-19) pandemic has evolved over time by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, disease severity, treatment, and prevention. There is evidence of an elevated risk of incident diabetes after COVID-19; our objective was to evaluate whether this association is consistent across time and with contemporary viral variants.

Research design and methods: We conducted a retrospective cohort study using National COVID Cohort Collaborative (N3C) data to evaluate incident diabetes risk among COVID-positive adults compared with COVID-negative patients or control patients with acute respiratory illness (ARI). Cohorts were weighted on demographics, data site, and Charlson comorbidity index score. The primary outcome was the cumulative incidence ratio (CIR) of incident diabetes for each viral variant era.

Results: Risk of incident diabetes 1 year after COVID-19 was increased for patients with any viral variant compared with COVID-negative control patients (ancestral CIR 1.16 [95% CI 1.12-1.21]; Alpha CIR 1.14 [95% CI 1.11-1.17]; Delta CIR 1.17 [95% CI 1.13-1.21]; Omicron CIR 1.13 [95% CI 1.10-1.17]) and control patients with ARI (ancestral CIR 1.17 [95% CI 1.11-1.22]; Alpha CIR 1.14 [95% CI 1.09-1.19]; Delta CIR 1.18 [95% CI 1.11-1.26]; Omicron CIR 1.20 [95% CI 1.13-1.27]). There was latency in the timing of incident diabetes risk with the Omicron variant; in contrast with other variants, the risk presented after 180 days.

Conclusions: Incident diabetes risk after COVID-19 was similar across different SARS-CoV-2 variants. However, there was greater latency in diabetes onset in the Omicron variant era.

Graphical abstract

Figure 1

Cumulative incidence and CIR of diabetes in adults after COVID-19 compared with COVID-negative and ARI control patients by COVID variant and time period: ancestral (A), Alpha (B), Delta (C), and Omicron (D). NA, not applicable.

Figure 2

Results of studies comparing risk of incident diabetes in adult COVID-positive vs. COVID-negative control groups (12,13,15,17,18,41–43). CIR indicates CIR at 1 year from index date. Pietropaolo et al. (42) reported odds ratios (ORs) as risk of incident diabetes in COVID-negative vs. COVID-positive patients. SHR, sub-HR; T1D, type 1 diabetes; T2D, type 2 diabetes.

Figure 3

Results of studies comparing risk of incident diabetes in adult COVID-positive vs. ARI control groups (15,18–21,41). CIR indicates CIR at 1 year from index date, and mild, moderate (mod), and severe indicate severity of illness. IRR, incidence rate ratio; OR, odds ratio; RR, rate ratio; SHR, sub-HR; T1D, type 1 diabetes; T2D, type 2 diabetes.