Ketosis-prone diabetes: dissection of a heterogeneous syndrome using an immunogenetic and beta-cell functional classification, prospective analysis, and clinical outcomes

J Clin Endocrinol Metab. 2003 Nov;88(11):5090-8. doi: 10.1210/jc.2003-030180.

Abstract

Ketosis-prone diabetes is heterogeneous. Its causes could include novel beta-cell functional defects. To characterize such defects, 103 patients with diabetic ketoacidosis were evaluated for beta-cell autoimmunity and human leukocyte antigen (HLA) class II alleles, with longitudinal measurements of beta-cell function and biochemical and clinical parameters. They were classified into four A beta groups, based on the presence of glutamic acid decarboxylase (GAD)65, GAD67, or IA-2 autoantibodies (A+ or A-) and beta-cell functional reserve (beta+ or beta-). The group distribution was: 18 A+beta-, 23 A-beta-, 11 A+beta+, and 51 A-beta+. Collectively, the two beta- groups differed from the two beta+ groups in earlier onset and longer duration of diabetes, lower body mass index, less glycemic improvement, and persistent insulin requirement. HLA class II genotyping showed that the A-beta- group differed from the A+beta- group in having lower frequencies of two alleles strongly associated with autoimmune type 1 diabetes susceptibility: DQA*03 and DQB1*02. Similarly, the A-beta+ group differed from the A+beta+ group in having a lower frequency of DQB1*02. Ketosis-prone diabetes comprises at least four etiologically distinct syndromes separable by autoantibody status, HLA genotype, and beta-cell functional reserve. Novel, nonautoimmune causes of beta-cell dysfunction are likely to underlie the A-beta+ and A-beta- syndromes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / blood
  • Blood Glucose
  • Diabetes Mellitus, Type 1 / classification*
  • Diabetes Mellitus, Type 1 / ethnology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 2 / classification*
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetic Ketoacidosis / classification*
  • Diabetic Ketoacidosis / ethnology
  • Diabetic Ketoacidosis / genetics
  • Diabetic Ketoacidosis / immunology
  • Ethnic Groups
  • Female
  • Gene Frequency
  • Glutamate Decarboxylase / immunology
  • Histocompatibility Testing
  • Humans
  • Islets of Langerhans / immunology*
  • Isoenzymes / immunology
  • Male
  • Middle Aged
  • Predictive Value of Tests

Substances

  • Autoantibodies
  • Blood Glucose
  • Isoenzymes
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • glutamate decarboxylase 2