Factors associated with early relapse to insulin dependence in unprovoked A-β+ ketosis-prone diabetes

Abstract

Objective: Unprovoked "A-β+" Ketosis-Prone Diabetes (KPD), a unique diabetic syndrome of adult-onset, obesity and proneness to ketoacidosis, is associated with rapid recovery of β cell function and insulin-independence. Whereas most patients experience prolonged remission, a subset relapses early to insulin dependence. We sought to define factors associated with early relapse.

Methods: We utilized a prospective, longitudinal database to analyze 50 unprovoked A-β+ KPD patients with >2 measurements of β cell function and glycemia following baseline assessment.

Results: 19 patients (38%) relapsed to insulin dependence <1 year after the index DKA episode, while 31 (62%) remained insulin-independent for >1 year (median 4.2 years). Younger age at baseline (OR=0.947, P=0.033), and lower HOMA2-%β (OR=0.982, P=0.001), lower HOMA2-IR (OR=0.582, P=0.046) and higher HbA1c at 1 year (OR=1.71, P=0.002) were associated with early relapse. A multivariate model with these variables and the interaction of HOMA2-%β and HbA1c at 1 year provided a good fit (P<0.05).

Conclusions: Relapse to insulin dependence in unprovoked A-β+ KPD patients is associated with younger age and, after 1 year, lack of robust increase in β cell functional reserve, and suboptimal glycemic control. Measurements of these parameters 1 year after the index DKA episode can be used to assess the need for insulin therapy.

Keywords: Beta-cell; HLA; Insulin-dependence; Ketoacidosis; Multivariate.