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. · 6.31 Impact Factor
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ABSTRACT: Recent linkage findings for psychiatric disorders, in particular schizophrenia, manic-depression, and Alzheimer disease, have raised a number of important conceptual issues regarding the genetic etiology of these diseases, as well as the appropriate interpretation of linkage results in studying complex diseases. Perspectives on mode of inheritance, genetic heterogeneity, and phenotypic variation are given.Genetic Epidemiology 01/1990; 7(1). · 2.95 Impact Factor
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ABSTRACT: This study was designed to characterize clinical and autoimmune features in all children with newly diagnosed IDDM diagnosed between 1994 and 1998 as well as to follow up their clinical progress. The study was performed on all newly diagnosed children with IDDM presented to the Alexandria University Children's Hospital between 1994 and 1998 (60 children). After the primary diagnosis and management, the patients were followed up every 2-3 months in the IDDM clinic. The details of any medical problem during the period of study were recorded during the visits. A questionnaire was completed for each newly diagnosed child. This questionnaire was divided into 4 sections and focused on demographic and family characteristics, family history of diabetes, previous medical history of the child and manifestations before diagnosis. Details of clinical and laboratory data at diagnosis were recorded. The clinical features evaluated were the duration of symptoms before admission to the hospital. All blood samples were obtained before initiation of insulin therapy to measure blood glucose, hemoglobin A 1C , venous blood gases, serum electrolytes and ketones. During each clinic visit, the children were examined with emphasis on nutritional and growth data and their anthropometric measurements recorded. The height standard deviation score, body mass indices and growth velocity per year were calculated and recorded. Hemoglobin A 1C was estimated every clinic visit. Hormonal evaluation for all children included measurement of free thyroxine (FT4), and IGF-1. The results included family history of autoimmune diseases, symptoms occurring within 3 months prior to diagnosis. Polyuria was the most common presenting symptom present in 87%, followed by fatigue/lethargy/malaise (53%), febrile illness (23%), nausea and vomiting (20%), and abdominal pain (15%). Secondary nocturnal enuresis occurred in (23%). Mumps was reported in 2 children while chicken pox was reported in 1 child 3-5 weeks before diabetes was diagnosed. The plasma glucose level was 22.3 ± 5.6 mmol/L, it was related neither to age nor to duration of symptoms. The HbA 1C concentration was 15.5 ± 2.9%. Levels of HbA 1C were correlated with serum glucose concentration. The frequency of DKA, its degree at presentation and associated biochemical changes is presented. As regards the progress of the disease, insulin was withdrawn in two of the 60 children in whom remission lasted 6 and 14 weeks respectively. The risk of readmission was 0.2 per patient during the first year and 0.12 during the second year. Re-admission for poor glycemic control was more common in young children. Children with good glycemic control had better linear growth compared to those with bad glycemic control. With follow up, 3 children developed hypothyroidism, 1 developed vitiligo, 1 developed chronic active hepatitis, 2 developed significant proteinuria. One child died of hepatorenal failure at the age of 5 years. In conclusion, children diagnosed as having diabetes below 5 years seem to present acutely and have highest risk of developing hypoglycemia during the first year after diagnosis.