Over 50% of obese African-Americans (AA) presenting with newly diagnosed, severe
hyperglycemia and/or unprovoked diabetic ketoacidosis (DKA) display clinical, metabolic, and
immunogenetic features of type 2 diabetes. Prior studies indicate that these patients a) have
markedly decreased insulin secretion and impaired insulin action at presentation, b) absent
or low prevalence of beta-cell autoantibodies and c) are able to discontinue aggressive
insulin therapy in ~70% of cases within 3 months of follow-up. These patients have been
referred to as having ketosis-prone type 2 diabetes (KPDM). Most patients with KPDM, however,
experience a hyperglycemic relapse within a year of insulin discontinuation. Consequently,
patients with "KPDM" are an ideal model to follow throughout their clinical course. The
specific aims of this proposal are to 1) identify clinical, metabolic, and immunogenetic
markers that alone, or in combination, are predictive of short- and long-term
near-normoglycemic remission and 2) determine whether pioglitazone or sitagliptin therapy
will delay an insulin-deficient relapse once insulin is discontinued. The Principal
Investigator hypothesizes that measures of beta-cell function at presentation, alone or in
combination with measures of insulin sensitivity, will correlate with the ability of a
patient to achieve and remain in near-normoglycemic remission. She also hypothesizes that
intervention compared to placebo will preserve beta-cell function, improve insulin
sensitivity, and prevent an insulin-deficient relapse. This prospective, cohort study with a
RCT arm would better characterize the natural history of KPDM, facilitate the direction of
long-term therapy, and likely decrease the recurrence of DKA which is associated with
increased mortality and morbidity.