Adult-Onset Atypical (Type 1) Diabetes
Additional insights and differences with type 1A diabetes in a European Mediterranean population
- Eva Aguilera, MD1,
- Roser Casamitjana, MD, PHD2,
- Guadalupe Ercilla, MD3,
- Josep Oriola, PHD,2,
- Ramon Gomis, MD, PHD1 and
- Ignacio Conget, MD, PHD1
- 1Endocrinology and Diabetes Unit, IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), Hospital Clínic i Universitari, Barcelona, Spain
- 2Hormonal Unit, IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), Hospital Clínic i Universitari, Barcelona, Spain
- 3Immunology Unit, IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), Hospital Clínic i Universitari, Barcelona, Spain
- Address correspondence and reprint requests to Dr. I. Conget, Endocrinology and Diabetes Unit, Villarroel 170, 08036 Barcelona, Spain. E-mail: iconget{at}clinic.ub.es
Abstract
OBJECTIVE—In 1997, the American Diabetes Association proposed two subcategories for type 1 diabetes: type 1A or immunomediated diabetes and type 1B or idiopathic diabetes characterized by negative β-cell autoimmunity markers, lack of association with HLA, and fluctuating insulinopenia. The aim of this study was to examine clinical characteristics, β-cell function, HLA typing, and mutations in maturity-onset diabetes of the young (MODY) genes in patients with atypical type 1 diabetes (type 1 diabetes diagnosed at onset, without pancreatic autoantibodies and fluctuating insulinopenia).
RESEARCH DESIGN AND METHODS—Eight patients with atypical type 1 diabetes (all men, 30.7 ± 7.6 years) and 16 newly diagnosed age- and sex-matched patients with type 1A diabetes were studied retrospectively. Islet cell, GAD, tyrosine phosphatase and insulin antibodies, and basal and stimulated plasma C-peptide were measured at onset and after 1 year. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1α and HNF-4α genes were performed from genomic DNA.
RESULTS—Atypical patients displayed significantly higher BMI and better β-cell function at onset and after 12 months. Three patients carried protective or neutral type 1 diabetes haplotypes, five patients displayed heterozygosity for susceptible and protective haplotypes, and seven patients showed Aspβ57. We found a nondescribed variant Pro436Ser in exon 10 of the HNF-4α gene in one atypical patient without susceptible haplotypes.
CONCLUSIONS—In our population, there are atypical forms of young adult-onset ketosis-prone diabetes initially diagnosed as type 1 diabetes, differing from type 1 diabetes in the absence of β-cell autoimmunity, persistent β-cell function capacity, fluctuating insulin requirements and ketosis-prone episodes, as well as clinical features of type 2 diabetes. Only one subgroup could be strictly classified as having type 1B diabetes. Additional information is still needed to improve our understanding of the mechanisms that finally lead to the disease.
- GADAb, GAD antibody
- IAAb, insulin autoantibody
- IA2Ab, tyrosine phosphatase antibody
- MODY, maturity-onset diabetes of the young
- SSO, specific-sequence oligonucleoprobe
Footnotes
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- Accepted January 19, 2004.
- Received October 22, 2003.
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