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

J Diabetes Complications. 2015 Sep-Oct;29(7):918-22. doi: 10.1016/j.jdiacomp.2015.04.013. Epub 2015 Apr 30.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Analysis of Variance
  • Blood Glucose / analysis
  • Databases, Factual
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetic Ketoacidosis / drug therapy*
  • Diabetic Ketoacidosis / etiology
  • Diabetic Ketoacidosis / physiopathology
  • Female
  • Follow-Up Studies
  • HLA Antigens / blood
  • Humans
  • Insulin / administration & dosage*
  • Insulin-Secreting Cells / physiology*
  • Logistic Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Prospective Studies
  • Recurrence
  • Risk Assessment
  • Severity of Illness Index
  • Time Factors


  • Blood Glucose
  • HLA Antigens
  • Insulin