Similar Genetic Features and Different Islet Cell Autoantibody Pattern of Latent Autoimmune Diabetes in Adults (LADA) Compared With Adult-Onset Type 1 Diabetes With Rapid Progression
- Nóra Hosszúfalusi, MD, PHD1,
- Ágnes Vatay, MD1,
- Katalin Rajczy, PHD2,
- Zoltán Prohászka, MD, PHD1,
- Éva Pozsonyi, MD2,
- Laura Horváth, MD, PHD1,
- Andrea Grosz, MD3,
- László Gerõ, MD, DSC4,
- László Madácsy, MD, DSC5,
- László Romics, MD, DSC1,
- István Karádi, MD, DSC1,
- George Füst, MD, DSC1 and
- Pál Pánczél, MD, PHD1
- 1Third Department of Internal Medicine, Semmelweis University, Budapest
- 2National Institute of Hematology and Immunology, Budapest
- 3Polyclinic of Hospitaler Brothers of Saint John’s of God, Budapest
- 4First Department of Internal Medicine, Semmelweis University, Budapest
- 5First Department of Pediatrics, Semmelweis University, Budapest, Hungary
OBJECTIVE—To compare the clinical parameters, C-peptide levels, pattern of islet cell-specific autoantibodies, and prevalence of predisposing genotypes in subjects with latent autoimmune diabetes in adults (LADA) and those with adult-onset type 1 diabetes with rapid progression.
RESEARCH DESIGN AND METHODS—We evaluated the clinical parameters, C-peptide levels, and islet cell-specific autoantibodies in 54 LADA, 57 adult-onset type 1 diabetic, and 190 type 2 diabetic patients. Islet cell autoantibodies were also compared between subgroups of newly diagnosed patients with LADA and those with newly diagnosed adult-onset and childhood-onset type 1 diabetes. The genetic study was performed in subjects with LADA and those with adult-onset type 1 diabetes in comparison with a control population.
RESULTS—There were no differences in the clinical parameters between LADA and adult-onset type 1 diabetes. Patients with LADA had lower BMI (P < 0.0001), waist-to-hip ratio (0.0029), total cholesterol (P = 0.001), and triglycerides (P = 0.001); higher HDL cholesterol levels (P < 0.0001); and lower prevalence of hypertension (P = 0.0028) compared with patients with type 2 diabetes. C-peptide levels were similar at onset (P = 0.403) but decreased less rapidly in LADA than in adult-onset type 1 diabetes (P = 0.0253). Single-autoantibody positivity was more often seen in LADA than in type 1 diabetes (P = 0.0001). The prevalence of predisposing HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 genotypes and the DR4-DQB1*0302 haplotype were increased in both LADA and adult-onset type 1 diabetic subjects compared with the control population. There were no differences in the frequencies of these risk alleles and haplotypes between the two patient groups.
CONCLUSIONS—Subjects with LADA had clinical characteristics similar to those with adult-onset type 1 diabetes with rapid progression. C-peptide levels did not differ at onset but decreased less rapidly in LADA. Patients with LADA rather had single islet cell-specific autoantibody positivity. The prevalence of HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 risk alleles and the DR4-DQB1*0302 high-risk haplotype did not differ in the two forms of autoimmune diabetes.
- GADA, GAD 65 autoantibody
- ICA, islet-cell cytoplasma autoantibody
- IA-2A, tyrosine phosphatase-like protein IA-2 autoantibody
- JDF, Juvenile Diabetes Foundation
- LADA, latent autoimmune diabetes in adults
- SSP, sequence-specific polymorphism
- UKPDS, U.K. Prospective Diabetes Study
Address correspondence and reprint requests to Nóra Hosszúfalusi, Budapest Kútvölgyi út 4, H-1125, Hungary. E-mail:.
Received for publication 1 February 2002 and accepted in revised form 14 October 2002.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
See accompanying editorial, p. 536.
- DIABETES CARE