Comparison of type 1, type 2, and atypical ketosis-prone diabetes at 4 years of diabetes duration

Abstract

Context: Atypical ketosis-prone diabetes (KPD) is frequently detected in obese individuals at diagnosis of diabetes, yet its precise pathophysiology is not understood.

Aim: The hypothesis tested in this study states that while individuals with atypical KPD are phenotypically similar to those with type 2 diabetes, metabolically, they behave more like individuals with autoimmune type 1 diabetes.

Methods: Thirty-seven individuals of Black, Hispanic, or White background and a diagnosis of diabetes mellitus for an average duration of 4 years participated in this cross-sectional study. Ten, 12, and 15 subjects had type 1, atypical, and type 2 diabetes, respectively. Insulin secretion was evaluated by a mixed-meal test. Insulin sensitivity and fuel oxidation were assessed by simultaneous euglycemic hyperinsulinemic clamp and indirect calorimetry. Lastly, a 12-h insulin withdrawal test was performed.

Results: Insulin secretion, insulin sensitivity, and the insulin withdrawal tests yielded significant differences for type 1 vs. atypical diabetes and type 1 vs. type 2 diabetes, while there were no significant differences between atypical vs. type 2 diabetes. The indirect calorimetry showed higher-than-normal basal nonprotein respiratory quotients (RQs) and lower-than-normal insulin-stimulated nonprotein RQs across the three study groups.

Conclusions: After 4 years from diabetes diagnosis and while far from optimal glycemic control, atypical KPD resembles type 2 diabetes phenotypically and metabolically as well. Therefore, this study supports the classification of atypical KPD as ketosis-prone type 2 diabetes, and the concept that metabolic inflexibility occurs in the presence of insulin resistance in type 1 and type 2 diabetes.