Introduction: Ketosis prone diabetes (KPD) comprises heterogeneous syndromes characterized by presentation with DKA. “ß+” subgroups of KPD have substantial beta cell functional reserve measured ≥ 1 month after the index DKA episode, and can discontinue insulin therapy. Either acute beta cell dysfunction leading to DKA is reversible in these patients, or DKA is due to factors other than severe beta cell dysfunction. In a longitudinal study, we measured serum C-peptide, insulin and counter-regulatory hormones in patients with hyperglycemic crises upon admission to the emergency department (ED) to determine beta cell function during the acute DKA episode.

Methods: Among 57 adult patients assessed so far, 32 had DKA (anion-gap acidosis with elevated beta-hydroxybutyrate) and 25 had non-ketotic hyperglycemia. Blood was sampled prior to insulin administration in 24 patients (50% with DKA), and ≤9 h after starting the insulin infusion in 33.

Results: There was no significant difference in C-peptide, glucose, insulin, or cortisol levels in DKA vs. non-ketotic hyperglycemia groups. Mean C-peptide was 1.4 ± 0.5 ng/mL in the DKA group and 2.1 ± 0.4 ng/mL in the non-DKA group (p = 0.29). Among the 24 patients whose blood was sampled prior to administering insulin, there was no group difference in C-peptide levels (2.3 ± 1.2 vs. 2.6 ± 0.7 ng/mL, p = 0.83). C-peptide was >1.5 ng/mL in 22% of the DKA group.

Conclusions: Many adults with KPD have substantial beta cell function at the time of the index DKA episode, a finding that defies the concept that near-complete absence of endogenous insulin secretion is required to develop DKA. Longitudinal follow-up testing will determine whether these patients populate KPD subgroups that are formally defined as “ß+”; such an outcome would indicate that their proclivity to develop ketoacidosis may be due to factors other than absence of endogenous insulin, such as defective amino acid metabolism (Patel et al, Diabetes 62:912-922, 2013) or dysregulation of counter-regulatory hormones.


P.B. Mehta: None. S.N. Mulukutla: None. J.W. Hsu: None. K.R. Keene: None. N. Ram: None. A. Balasubramanyam: None.

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