The importance of diabetes registries and clinical biology for the study and treatment of type 1 (insulin-dependent) diabetes mellitus.
The Belgian Diabetes Registry (BDR) has studied the epidemiology of Type 1 diabetes with clinical onset before age 40 years in the Antwerp district. Both in the age categories 0-14 years and 15-39 years, the incidence approximates 10 new cases per 100,000 inhabitants per years. Most patients are adults. Juvenile-onset diabetic patients who were so far more intensively studied must therefore not be considered as "prototypes" for the disease, but rather represent "atypical" cases with rapid evolution. Participation in international programs (EURODIAB ACE, DIAMOND) has characterized the incidence of Type 1 diabetes in Belgium as being intermediate between values in low-incidence regions (5 to 10 cases/100,000 inhabitants/yr such as in parts of Southern or Eastern Europe) and values in high-incidence regions 30 to 40 cases/100,000 inhabitants/yr such as in Finland and Sardinia). Type 1 diabetes is a heterogenous disease in terms of clinical presentation, etiological factors and biological markers. Clinical and fundamental research on Type 1 diabetes needs to study patient groups which faithfully reflect this heterogeneity. This is best achieved by recruiting patients through diabetes registries. In Belgium, the BDR presently registers about 40% of all new cases of Type 1 diabetes with onset before age 40 years. Until now, more than 1700 patients and about 1100 first degree relatives are registered. This group is representative of the Belgian population of Type 1 diabetic patients with onset before age 40 years. High quality-assays for immune and genetic markers of Type 1 diabetes were designed and validated through repeated participation in international quality control programs. By systematically performing these assays on the representative non-selected samples of BDR-patients, it became possible to further clarify the clinical biology of Type 1 diabetes and to demonstrate hitherto unrecognized associations among disease markers. Certain of these markers (insulin auto-antibodies, IAA; islet cell antibodies, ICA; HLA DQA1*0301-DQB1*0302 risk haplotype) are more frequent for clinical onset before age 10 years and appear associated in that age category. Other markers (glutamate decarboxylase antibodies; GAD-Ab) occur more frequently at onset between age 10 and 40 years, where they are preferentially associated with increased genetic risk. Yet another genetic marker (1/1 susceptibility genotype in the 5' polymorphic region of the insulin gene) occurs regardless of age and presence of auto-antibodies, preferentially in patients without the highest HLA-linked genetic risk. Age-dependent differences in marker frequency and -associations possibly reflect age-dependent differences in etiological factors, in order of appearance of biological markers, or in progression rate of the disease. Presently, more than 90% of the patients under age 40 years carry at least one diabetes-associated immune or genetic marker, which opens perspectives for a better classification of the disease, especially in adults. Preliminary follow-up studies in first-degree relatives of registered patients confirm the diabetes-predictive value of the markers studied. A group of subjects at high risk for the disease could thus be identified. These subjects qualify for participation in preventive intervention trials. In this respect BDR officially represents Belgium in several international programs: EURODI-AB ACE for marker-studies, ICARUS for diabetes prediction, ENDIT for diabetes-prevention and GETREM for optimal diabetes treatment. This collaboration will focus in the near future on neonatal screening and follow-up, objective classification criteria for diabetes in adults, refined diabetes-prediction and preventive intervention studies. BDR may also serve as a tool for systematic research on the complications, innovative treatments and socio-economical aspects of diabetes.
Gorus
F K
FK
Department of Metabolism and Endocrinology, Diabetes Research Center-Vrije Universiteit Brussel.
D000293:Adolescent; D000328:Adult; D001530:Belgium / Q000453:epidemiology; D015415:Biomarkers; D002648:Child; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D005819:Genetic Markers; D006801:Humans; D015994:Incidence; D011237:Predictive Value of Tests; D012042:Registries
D015415:Biomarkers; D005819:Genetic Markers