Immunogenetic analysis suggests different pathogenesis for obese and learnAfrican-Americans with diabetic ketoacidosis

OBJECTIVE - When presenting with diabetic ketoacidosis (DKA), lean and obes e patients differ in their subsequent clinical course. Although lean patien ts tend to remain insulin dependent, most obese patients recover endogenous insulin secretion and discontinue insulin therapy. The aim of this study w as to determine whether obese African-American patients with DKA could be d etermined to have type 1 or type 2 diabetes based on insulin secretion or t he presence of immunological and genetic markers. RESEARCH DESIGN AND METHODS - This was a prospective study that analyzed th e clinical characteristics, insulin secretion indices, immunological marker s (islet cell, GAD, ICA512, and insulin autoantibodies), and HLA susceptibi lity genes (DR/DQ) in 131 patients with DKA (77 obese and 54 lean), 51 obes e patients with hyperglycemia but no DKA, and 25 nondiabetic subjects. All subjects were African-American. beta-cell function was evaluated by the C-p eptide response to glucagon (1 mg i.v.) within 48 h of resolution of DKA or hyperglycemia. RESULTS - The acute C-peptide response was lower in obese DKA patients (1.0 +/- 0.1 ng/ml) than in obese patients with hyperglycemia (1.7 +/- 0.2 ng/m l, P < 0.01), but was higher than that in lean DKA patients (0.2 +/- 0.1 ng /ml, both P < 0.01). The overall prevalence of autoantibodies in obese subj ects with DKA (17%) and obese subjects with hyperglycemia (16%) was lower t han that in lean subjects with DKA (65%, P < 0.01). Obese patients with hyp erglycemia and positive autoantibodies had lower rates of insulin secretion than those without antibodies. Regardless of body weight, all DKA patients with GAD autoantibodies carried the DQB1*0201 allele. However, there were no significant differences in HLA distribution between the three patient gr oups. CONCLUSIONS - Our results indicate that most obese African-American patient s with DKA have type 2 diabetes characterized by higher insulin secretion, the absence of autoimmune markers, and a lack of HLA. genetic association. In contrast, most lean African-American patients with DKA have metabolic an d immunological features of type 1 diabetes. At presentation, assessment of beta-cell function and determination of autoimmune markers allow for corre ct classification of diabetes in African-Americans with hyperglycemic crise s.