Islet cell autoimmunity and progression to insulin-dependent diabetes mellitus in genetically high- and low-risk siblings of diabetic children. The Childhood Diabetes in Finland (DiMe) Study Group. 1996

J Karjalainen, and P Vähasalo, and M Knip, and E Tuomilehto-Wolf, and E Virtala, and H K Akerblom
Department of Paediatrics, University of Oulu, Finland.

Insulin-dependent diabetes mellitus (IDDM) risk was evaluated in 765 siblings based on prospective observation of islet cell antibodies (ICAs) and insulin autoantibodies (IAAs) as a function of the degree of HLA identity to the proband and HLA-DR alleles. Twenty-eight (3.7%) siblings progressed to IDDM over a median observation period of 5.8 years. ICAs had higher sensitivity than IAAS (100% vs. 33% , P < 0.001), whereas persistent ICA positivity and double ICA/IAA positivity defined the highest actuarial risk (47% and 70%). Diabetes manifested after a mean of 3.2 years from the detection of ICAs in those siblings who were initially ICA negative and, importantly, the risk was equal to that of the siblings constantly positive from the first sample obtained. Although the combination of HLA identity and ICAs at or above 80 Juvenile Diabetes Foundation units carried the highest positive predictive value (77%), the high-risk HLA markers were insufficient to predispose siblings with low ICA levels to IDDM and low-risk HLA markers did not provide complete protection against high ICA levels and from subsequent IDDM. These results emphasize ICAs as the primary tool for risk evaluation in siblings followed by restricted HLA subtyping to reduce the population to be subjected to clinical intervention trials.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D008297 Male Males
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D003922 Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus
D005260 Female Females
D005387 Finland A country in northern Europe, bordering the Baltic Sea, Gulf of Bothnia, and Gulf of Finland, between Sweden and Russia. The capital is Helsinki. Aland Islands,Åland Islands
D006239 Haplotypes The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. Haplotype

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