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Narrative Review: Ketosis-Prone Type 2 Diabetes Mellitus

Guillermo E. Umpierrez, MD; Dawn Smiley, MD; and Abbas E. Kitabchi, PhD, MD
[+] Article, Author, and Disclosure Information

From Emory University School of Medicine, Atlanta, Georgia, and University of Tennessee Health Science Center, Memphis, Tennessee.

Grant Support: In part by research grants from the American Diabetes Association (7-03-CR-35) (Dr. Umpierrez) and National Institutes of Health (R03 DK073190-01 and MO1-RR00039 [Dr. Umpierrez] and RR00211 [Drs. Kitabchi and Umpierrez]).

Potential Financial Conflicts of Interest: Grants received: A.E. Kitabchi (Lilly, Novo, Takeda, Aventis, Abbott).

Requests for Single Reprints: Guillermo E. Umpierrez, MD, Emory University School of Medicine, 49 Jesse Hill Jr. Drive, Atlanta, GA 30303; e-mail, geumpie@emory.edu.

Current Author Addresses: Drs. Umpierrez and Smiley: Emory University School of Medicine, 49 Jesse Hill Jr. Drive, Atlanta, GA 30303.

Dr. Kitabchi: University of Tennessee Health Science Center, Room 334D, 956 Court Avenue, Memphis, TN 38163.

Ann Intern Med. 2006;144(5):350-357. doi:10.7326/0003-4819-144-5-200603070-00011
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Several investigators have reported that more than half of African-American persons with new diagnoses of diabetic ketoacidosis have clinical, metabolic, and immunologic features of type 2 diabetes during follow-up. These patients are usually obese, have a strong family history of diabetes, have a low prevalence of autoimmune markers, and lack a genetic association with HLA. Their initial presentation is acute, with a few days to weeks of polyuria, polydipsia, and weight loss and lack of a precipitating cause of metabolic decompensation. At presentation, they have markedly impaired insulin secretion and insulin action, but intensified diabetic management results in significant improvement in β-cell function and insulin sensitivity sufficient to allow discontinuation of insulin therapy within a few months of follow-up. On discontinuation of insulin therapy, the period of near-normoglycemic remission may last for a few months to several years. The absence of autoimmune markers and the presence of measurable insulin secretion have proven useful in predicting near-normoglycemic remission and long-term insulin dependence in adult patients with a history of diabetic ketoacidosis. This clinical presentation is commonly reported in African and African-American persons but is also observed in Hispanic persons and those from other minority ethnic groups. The underlying mechanisms for β-cell dysfunction in ketosis-prone type 2 diabetes are not known; however, preliminary evidence suggests an increased susceptibility to glucose desensitization.


Grahic Jump Location
Levels of plasma C-peptide before and after glucagon stimulation (1 mg intravenously) in patients with ketosis-prone type 2 diabetes.(2, 3)

Insulin secretion was assessed 1 day after resolution of diabetic ketoacidosis (at presentation) and after 10 weeks of follow-up . Data are expressed as means and SDs. Acute insulin response to glucagon is the incremental change in C-peptide level over the baseline level. To convert values to nmol/L, multiply by 0.333.

Grahic Jump Location




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