The Pittsburgh study of insulin-dependent diabetes mellitus. Risk for diabetes among relatives of IDDM.
ABSTRACT AN analysis has been made of the family histories of a survey of 1280 cases of IDDM entering Children's Hospital of Pittsburgh between December 31, 1964 and January 1, 1981, discharged on insulin and initial age of onset under 17 yr. Family histories revealed an increased occurrence of IDDM among relatives in the affected families. The risk to siblings was estimated by age-corrected proband exclusion (3.3%) by age 20 and by the Li-Mantel segregation ratio estimator (6.0%). The comparison of these risk measures is discussed. The occurrence of IDDM among the parents is 2.6% and of NIDDM among the parents is 2.4%. A comparison of risk to relatives (parents, sibs, uncles, half-sibs) observed in the Pittsburgh Study to those of six other studies reveal essentially equivalent rates. There is no increased risk to siblings of a diabetic who had an early age of onset. There is an increased risk to siblings of a diabetic (10.5%) in families where at least one parent has insulin-dependent diabetes mellitus (IDDM) and also an increased risk to siblings of a diabetic (8.8%) when at least one parent has non-insulin-dependent diabetes (NIDDM). The average age of onset for second cases in a family is significantly older than age of onset in single case families.
Journal of Clinical Endocrinology & Metabolism 02/2001; 86(2):574-582. DOI:10.1210/jc.86.2.574 · 6.31 Impact Factor
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ABSTRACT: Type 1 diabetes mellitus (T1DM) is an autoimmune disease arising through a complex interaction of both genetic and immunologic factors. Similar to the majority of autoimmune diseases, T1DM usually has a relapsing remitting disease course with autoantibody and T cellular responses to islet autoantigens, which precede the clinical onset of the disease process. The immunological diagnosis of autoimmune diseases relies primarily on the detection of autoantibodies in the serum of T1DM patients. Although their pathogenic significance remains uncertain, they have the practical advantage of serving as surrogate biomarkers for predicting the clinical onset of T1DM. Type 1 diabetes is a polygenic disease with a small number of genes having large effects, (i.e. HLA) and a large number of genes having small effects. Risk of T1DM progression is conferred by specific HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3) or DRB1*04-DQB1*0302 (DR4)]. In addition, HLA alleles such as DQB1*0602 are associated with dominant protection from T1DM in multiple populations.Molecular Aspects of Medicine 01/2015; 42. DOI:10.1016/j.mam.2014.12.004 · 10.30 Impact Factor
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ABSTRACT: Although the Haptoglobin (Hp) 1-1 genotype is associated with a lower coronary artery disease (CAD) risk in diabetes, we recently reported an increased stroke incidence in type 1 diabetes with Hp 1-1. We, thus, evaluated differences in earlier brain vascular abnormality markers by Hp using neuroimaging. Neuroimaging was completed in 94 participants of the Pittsburgh Epidemiology of Diabetes Complications study with Hp genotyping available (mean age, 49 and duration, 41 years). White matter hyperintensities volume (WMH), lacunar infarcts and gray matter atrophy were quantified. Sixteen percent were homozygous for Hp 1 and 43% for Hp 2. A significant trend toward increased WMH was observed with greater duration and the number of Hp 1 alleles. Associations were strongest for the inter-hemispheric connecting fibers of the corpus callosum. Allowing for duration, gender, waist/hip ratio, HbA1c, systolic blood pressure and lipids in models with backward elimination, results were similar. No significant differences by Hp were noted for atrophy or lacunar infarcts. Consistent with its direct association with stroke, the Hp 1-1 genotype is associated with higher WMH in this population. Further, including mechanistic, studies on the role of the Hp genotype in cerebrovascular disease and the implications for worsening cognitive function are needed.Diabetes 09/2014; 64(2). DOI:10.2337/db14-0723 · 8.47 Impact Factor