title: Familial type 1 diabetes mellitus - gender distribution and age at onset of diabetes distinguish between parent-offspring and sib-pair subgroups.
abstract: BACKGROUND
  Familial type 1 diabetes mellitus (T1D) comprises parent-offspring and sib-pair subgroups.
  
  
  OBJECTIVE
  To compare the demographic and clinical characteristics in the two subgroups at diagnosis and evaluate the differences between index cases and second affected family members.
  
  
  METHODS
  Retrieved from our institutional registry of new T1D cases for the years 1979-2008 were a cohort of 194 familial cases (87 parent-offspring, 107 sib-pairs); 133 sporadic cases matched by age, gender, and year of diagnosis were selected as controls. Extracted from their medical files were demographic data, family background, clinical and laboratory findings.
  
  
  RESULTS
  The parent-offspring subgroup was characterized by male preponderance (p = 0.009). At diagnosis parents were significantly older than their offspring (p < 0.001) and probands were significantly younger than their affected siblings (p = 0.03). Clinical symptoms and metabolic decompensation were similar in the familial subgroups. Diabetic ketoacidosis (DKA) rate and hemoglobin A1c (HbA1c) levels were lower in second affected family members in both parent-offspring (p = 0.05 and p < 0.001) and sib-pair subgroups (p < 0.001, for both parameters). Consanguinity and T1D were more frequent in the extended family of familial than sporadic cases (p < 0.001 and p = 0.012, respectively) with no difference between the two subgroups.
  
  
  CONCLUSIONS
  The genetic background for T1D would appear to differ not only between familial and sporadic cases but also between parent-offspring and sib-pair subgroups. Whereas differences in age of onset are attributable to both genetic and environmental factors, the less severe clinical manifestations in second affected family members may result from increased awareness or a less aggressive disease process.
authors: The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tiqva 49202, Israel.
authors: Yael
authors: Y
authors: Lebenthal
authors: Liat
authors: L
authors: de Vries
authors: Moshe
authors: M
authors: Phillip
authors: Liora
authors: L
authors: Lazar
mesh_terms: D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D010290:Parents; D015995:Prevalence; D035781:Siblings