Pilot trial to prevent type I diabetes: Progression to overt IDDM despite oral nicotinamide
| Autor: | J.S. Soeldner, R. A. Jackson, George S. Eisenbarth, R. Dumont Herskowitz |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
Niacinamide
medicine.medical_specialty endocrine system diseases medicine.medical_treatment Immunology Population Administration Oral Pilot Projects Autoimmune Diseases Prediabetic State Islets of Langerhans chemistry.chemical_compound Diabetes mellitus Internal medicine Alloxan medicine Humans Immunology and Allergy education Autoantibodies Proinsulin geography education.field_of_study geography.geographical_feature_category business.industry Insulin nutritional and metabolic diseases Islet medicine.disease Streptozotocin Diabetes Mellitus Type 1 Endocrinology chemistry Drug Evaluation Beta cell business medicine.drug |
| Zdroj: | Journal of Autoimmunity. 2:733-737 |
| ISSN: | 0896-8411 |
| DOI: | 10.1016/s0896-8411(89)80011-3 |
| Popis: | Immunologic and endocrine abnormalities may be present during a latency period of several years prior to overt diabetes, while glucose tolerance still remains normal [ 1]. In particular, cytoplasmic islet cell antibodies, insulin autoantibodies, and T-cell abnormalities can be present for years prior to development of overt hyperglycemia. We have found that with the emergence of these immunologic abnormalities, the first phase insulin release following intravenous glucose is progressively lost. In relatives of patients with insulin dependent diabetes mellitus (IDDM) who were found to have circulating cytoplasmic islet cell antibodies [greater than 40 Juvenile Diabetes Foundation (JDF) units], we have developed a dual parameter model which predicts confidence intervals of the time of onset of IDDM, based on the level of competitive insulin autoantibodies (CIAA), and the degree of loss of the first phase insulin release on intravenous glucose tolerance testing (IVGTT) [2]. This model consists of the formula: years to DM=2.2+0 .017 ( IVGTT insulin) -0.007 (concentration CIAA), and makes it possible for us to identify patients with a high risk of developing IDDM within 3 years' time. In such a population, we have initiated pilot trials of preventive therapy to determine whether the development of I D D M can be halted. In an animal model of Type I diabetes (the NOD mouse), nicotinamide at supraphysiologic dosages was found to protect pancreatic islet cells and to prevent Type I diabetes [3]. In addition, nicotinamide has long been known to block the development of diabetes following streptozotocin or alloxan, and to restore proinsulin synthesis to normal following injection of streptozotocin [4]. It was also shown to promote beta cell regeneration following partial pancreatectomy in the rat [5]. In |
| Databáze: | OpenAIRE |
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