Ketosis-Prone Type 2 Diabetes Mellitus: 3 Decades of Clinical, Pathophysiologic, and Therapeutic Insights

Over 3 decades ago, our group reported that newly diagnosed Black patients with diabetic ketoacidosis (DKA) are obese and that many of them can discontinue insulin after the acute episode, revealing a clinical course consistent with type 2 diabetes. This presentation is now recognized as ketosis-prone type 2 diabetes mellitus (KPDM).

We review observational, prospective, and interventional studies that characterize the epidemiology, clinical features, pathophysiology, and management of KPDM. Patients typically present with severe hyperglycemia, metabolic acidosis, obesity, male predominance, and a strong family history of type 2 diabetes.

KPDM accounts for 20% to 50% of new-onset DKA in Black and Hispanic adults and has been reported globally. Acute management follows standard DKA protocols, but insulin requirements decline rapidly after the crisis, with ∼70% achieving near-normoglycemic remission. Pathophysiologic studies show reversible β-cell dysfunction and transient insulin resistance, resembling type 2 diabetes. Low prevalence of autoantibody positivity distinguishes KPDM from latent autoimmune diabetes. Pharmacologic therapy with metformin, dipeptidyl peptidase-4 inhibitors, or glucagon-like peptide-1 receptor agonists prolongs remission, preserves β-cell function, and reduces hyperglycemic relapse.

KPDM exemplifies diabetes heterogeneity and is a common presentation of DKA, particularly among obese Black and Hispanic adults. Early recognition and individualized therapy optimize β-cell recovery, prolong near-normoglycemic remission, and improve outcomes. Further research is needed to define optimal long-term management and prevention strategies to sustain remission and reduce diabetic complications.