Comparison of type 1, type 2, and atypical ketosis-prone diabetes at 4 years of diabetes duration.
BACKGROUND
Atypical ketosis-prone diabetes (KPD) is frequently detected in obese individuals at diagnosis of diabetes, yet its precise pathophysiology is not understood.


OBJECTIVE
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.
Ramos-Román
María A
MA
Department of Internal Medicine at the University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8858, USA. maria.ramos-roman@utsouthwestern.edu
Piñero-Piloña
Antonio
A
Adams-Huet
Beverley
B
Raskin
Philip
P
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002245:Carbon Dioxide / Q000378:metabolism; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000145:classification* / Q000175:diagnosis / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007657:Ketone Bodies / Q000097:blood; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D007657:Ketone Bodies; D002245:Carbon Dioxide