title: In middle-aged siblings of patients with type 2 diabetes mellitus normal glucose tolerance is associated with insulin resistance and with increased insulin secretion. The SPIDER study.
abstract: OBJECTIVE
  To evaluate the frequency of impaired glucose tolerance (IGT) and of Type 2 diabetes mellitus (Type 2 DM) in siblings of patients with Type 2 DM, and to assess insulin release and insulin sensitivity in siblings with normal glucose tolerance (NGT), compared with NGT spouses of probands without family history of Type 2 DM.
  
  
  METHODS
  We evaluated 87 families including 103 Type 2 DM patients (87 probands), and we carried out an oral glucose tolerance test (OGTT) in 130 siblings and in 60 spouses. Among NGT subjects, 12 siblings and 16 spouses underwent a low-dose insulin-glucose infusion test (LDIGIT) to evaluate C-peptide release and insulin sensitivity.
  
  
  RESULTS
  After the OGTT, 24 siblings were classified as having Type 2 DM, 31 as IGT, and only 14 spouses as IGT (P=0.0012 vs siblings). NGT siblings (n=75) showed higher insulin levels at 120 min than NGT spouses (n=46) at OGTT, in spite of identical blood glucose levels; at LDIGIT, NGT siblings secreted more C-peptide and showed a lower insulin sensitivity than NGT spouses.
  
  
  CONCLUSIONS
  These data indicate that middle-aged siblings of probands with Type 2 DM have a high frequency of IGT and Type 2 DM, and that NGT siblings have increased insulin resistance and increased insulin secretion when compared with adequate controls.
authors.affiliation: Università degli Studi di Milano, Cattedra di Medicina Interna, Istituto San Raffaele, Unità di Malattie Metaboliche, Milano, Italy. antonio.pontiroli@unimi.it
authors.forename: A E
authors.initials: AE
authors.lastname: Pontiroli
authors.forename: L D
authors.initials: LD
authors.lastname: Monti
authors.forename: S
authors.initials: S
authors.lastname: Costa
authors.forename: P E
authors.initials: PE
authors.lastname: Sandoli
authors.forename: A
authors.initials: A
authors.lastname: Pizzini
authors.forename: S B
authors.initials: SB
authors.lastname: Solerte
authors.forename: E
authors.initials: E
authors.lastname: Mantovani
authors.forename: P M
authors.initials: PM
authors.lastname: Piatti
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003625:Data Collection; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D018454:Spouses
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin