GAD ANTIBODY NEGATIVE NIDDM IN ADULT BLACK SUBJECTS WITH DIABETIC-KETOACIDOSIS AND INCREASED FREQUENCY OF HUMAN-LEUKOCYTE ANTIGEN DR3 AND DR4 - FLATBUSH DIABETES

The objective of this study is to understand the metabolic and immunol ogic basis of diabetes in adult blacks with diabetic ketoacidosis (DKA ). Twenty-one black adults presenting with DKA ([mean +/- SD] blood pH = 7.18 +/- 0.09, plasma glucose = 693 +/- 208 mg/dl, and positive ser um ketones) had a subsequent clinical course of noninsulin-dependent d iabetes mellitus (NIDDM). Human leukocyte antigens (HLAs) DR and DQ an d antibodies to glutamic acid decarboxylase (GAD) and islet cell cytop lasmic proteins (ICP) were measured to assess autoimmunity. Insulin ac tion was evaluated by the euglycemic insulin clamp, and insulin secret ion was measured by C-peptide responses to oral glucose. Ketoacidosis was treated with insulin. Two subjects had a precipitating illness; fo ur had a history of NIDDM. At the time of study, subjects' glycemic co ntrol was good (HbA(1c) 5.7 +/- 1.6%). Nine subjects were treated with insulin, and 12 mere on either sulfonylurea treatment or diet alone. Men (n = 12) were younger than women (n = 9) (40.8 +/- 9.8 and 51.1 +/ - 6.3 years of age, respectively, P < 0.05) but similar in body mass i ndex (27.8 +/- 2.7 and 29.98 +/- 4.1 kg/m(2), respectively). Antibodie s to GAD and ICP were absent. All but one subject was insulin resistan t compared with normal subjects (glucose disposal 3.56 +/- 0.04 vs. 6. 86 +/- 0.02 mg.kg(-1).min(-1)), and insulin secretion was lower HLA DR 3 and DR4 frequency was higher than in nondiabetic black control subje cts (65 vs. 30%, P < 0.012). We conclude that black adults presenting with DKA have a subsequent clinical course and metabolic features (ins ulin resistance in the presence of good glycemic control and continued C-peptide response) characteristic of NIDDM. The absence of GAD or IC P antibodies makes beta-cell autoimmune destruction unlikely. The incr eased frequency of HLA DR3 and DR4 suggests genetic components of insu lin-dependent diabetes mellitus (IDDM) and NIDDM.