title: First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes.
abstract: OBJECTIVE
  A reduced first-phase insulin response to intravenous glucose is perceived as a sign of far-advanced deterioration of beta-cell function during the development of Type I (insulin-dependent) diabetes mellitus, but data on insulin responses at the onset of diabetes-related autoimmunity are lacking. We studied the first-phase insulin responses of small children soon after observed seroconversion to autoantibody positivity.
  
  
  METHODS
  In the Type I Diabetes Prediction and Prevention Study newborn infants are screened for HLA-DQB1-associated genetic risk for Type I diabetes and those with increased risk are followed-up for the emergence of islet-cell antibodies. If antibodies are detected, autoantibodies to three other antigens (insulin, GAD65 and IA-2) are also measured. To measure first-phase insulin responses, intravenous glucose tolerance tests were carried out in 52 (1 to 5-year-old) children who had recently seroconverted to islet-cell antibody positivity.
  
  
  RESULTS
  The first-phase insulin response was subnormal (<38 mU/l, the 5(th) percentile of insulin responses of 20 islet-cell antibody negative healthy children at this age) in 22 of the 52 children (42%). Stepwise multiregression analysis showed that islet-cell antibody greater than 20 JDFU (p=0.0005), insulin autoantibodies (p=0.0009) and an increasing number of positive autoantibodies (p=0.0011) were independent predictors of low first-phase insulin response.
  
  
  CONCLUSIONS
  A decreased first-phase insulin response could be an early phenomenon in the course of prediabetes in young children, implying a rapid autoimmune destruction or loss of function of beta cells as well as possible metabolic compensation mechanisms, since 11 out of the 22 high risk children remain nondiabetic for a considerable period of time despite low insulin responses.
authors.affiliation: The JDRF Center for Prevention of Type I Diabetes in Finland. paivi.keskinen@uta.fi
authors.forename: P
authors.initials: P
authors.lastname: Keskinen
authors.forename: S
authors.initials: S
authors.lastname: Korhonen
authors.forename: A
authors.initials: A
authors.lastname: Kupila
authors.forename: R
authors.initials: R
authors.lastname: Veijola
authors.forename: S
authors.initials: S
authors.lastname: Erkkilä
authors.forename: H
authors.initials: H
authors.lastname: Savolainen
authors.forename: P
authors.initials: P
authors.lastname: Arvilommi
authors.forename: T
authors.initials: T
authors.lastname: Simell
authors.forename: J
authors.initials: J
authors.lastname: Ilonen
authors.forename: M
authors.initials: M
authors.lastname: Knip
authors.forename: O
authors.initials: O
authors.lastname: Simell
mesh_terms: D001323:Autoantibodies / Q000032:analysis*; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D004198:Disease Susceptibility; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006801:Humans; D007223:Infant; D007328:Insulin / Q000097:blood*; D007330:Insulin Antibodies / Q000032:analysis; D008297:Male; D011236:Prediabetic State / Q000097:blood; D011379:Prognosis
chemical_list: D001323:Autoantibodies; D007328:Insulin; D007330:Insulin Antibodies; C024211:islet cell antibody