Quantifying and predicting real-world iatrogenic severe hypoglycemia in adults with type 1 or 2 diabetes mellitus (the iNPHORM study, United States)
Abstract
Clinical outpatient strategies to accurately predict diabetes-related iatrogenic severe hypoglycemia (SH) are lacking. To redress this gap, we conducted the first-ever prognosis investigation of guideline-defined (Level 3) SH in the United States (US) (iNPHORM).
Chapter 4 details the design and implementation of iNPHORM: a prospective 12-wave panel survey (2020–2021). N=1206 adults with type 1 or insulin- and/or secretagogue-treated type 2 diabetes mellitus (T1DM or T2DM) were recruited from a US-wide, probability-based internet panel. For one-year, we collected monthly data on SH occurrence (frequencies, detection methods, symptoms, causes, and treatments) and related factors (anthropometric, sociodemographic, clinical, environmental/situational, behavioural, and psychosocial).
iNPHORM data were analyzed in Chapter 5 to characterize and quantify Level 3 SH (N=978). Overall, 60% of events were treated outside the healthcare system; <5% required hospitalization (T1DM: 1.6%; T2DM: 4.9%, p-value=0.0014, α=0.0083). About one-third of participants experienced ≥1 event(s) over prospective follow-up (T1DM: 44.2% [95% CI: 36.8% to 51.8%]; T2DM: 30.8% [95% CI: 28.7% to 35.1%], p-value=0.0404, α=0.0007). The incidence rate was 5.01 (95% CI: 4.15 to 6.05) events per person-year (EPPY) (T1DM: 3.57 [95% CI: 2.49 to 5.11] EPPY; 5.29 [95% CI: 4.26 to 6.57] EPPY).
Chapter 6 describes the development and internal validation of the iNPHORM prognostic model. We modelled one-year recurrent Level 3 SH using Andersen-Gill Cox proportional hazards and penalized regression with multiple imputation (N=986). A range of anthropometric; sociodemographic; and clinical (diabetes-, hypoglycemia-, and general health-related) candidate variables were selected for their relevance and feasibility. The final model demonstrated strong discriminative validity and parsimony (optimism corrected c-statistic: 0.77).
The results of this dissertation promise to enhance real-world SH screening; evidence-based, risk-tailored prevention; and ultimately cost containment.