Metabolomics, Stable Isotopes, and A−β+ Ketosis-Prone Diabetes
- 1Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas
- 2Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas
- 3Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, Texas
- Corresponding author: Jeffrey D. Browning, .
First described in 1987 by Winter et al. as “atypical diabetes” (1), A−β+ ketosis-prone diabetes (KPD) describes a group of primarily middle-aged individuals brought to medical attention by an episode of spontaneous ketoacidosis (i.e., without evidence of infection, alcohol abuse, etc.) and subsequently diagnosed with diabetes (2,3). Although not exclusive to a particular ethnic group, KPD has primarily been described in individuals of African descent, Hispanics, and groups traditionally classified as ethnic minorities. Experience from our county hospital in Dallas, Texas, suggests that among those who present with new-onset diabetes and ketoacidosis, 60% meet criteria for the diagnosis of KPD (4). These patients generally lack evidence of endocrine pancreas autoimmunity (A−) and experience improved insulin secretory capacity (β+) and sensitivity after near-normalization of glycemia (5). Patients with KPD tend to be male and obese, and they typically have a family history of diabetes (3). Over time, this condition is characterized by a period of near-normoglycemia followed by sustained deterioration in glucose control and episodes of ketoacidosis. The metabolic perturbations that lead to transient β-cell dysfunction and spontaneous ketoacidosis in individuals with KPD remain unclear. Insights on the extreme metabolic phenotype of KPD have the potential to improve our understanding of more subtle metabolic derangements of type 2 diabetes.
The fluctuating β-cell function that is characteristic of KPD suggests that acute glucose and fatty acid toxicity may play a role in its pathogenesis. However, recent studies of KPD patients during near-normoglycemic remission demonstrated that a 48-h exposure to excess fatty acids …