Diabetologia

, Volume 45, Issue 12, pp 1639–1648

First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes

  •  P. Keskinen
  •  S. Korhonen
  •  A. Kupila
  •  R. Veijola
  •  S. Erkkilä
  •  H. Savolainen
  •  P. Arvilommi
  •  T. Simell
  •  J. Ilonen
  •  M. Knip
  •  O. Simell
Article

Abstract

Aims/hypothesis. 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 5th 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.

Conclusion/interpretation. 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.

Autoantibodies HLA risk markers insulin secretion prediabetic state Type I diabetes 

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  •  P. Keskinen
    • 1
  •  S. Korhonen
    • 1
  •  A. Kupila
    • 1
  •  R. Veijola
    • 1
  •  S. Erkkilä
    • 1
  •  H. Savolainen
    • 1
  •  P. Arvilommi
    • 1
  •  T. Simell
    • 1
  •  J. Ilonen
    • 1
  •  M. Knip
    • 1
  •  O. Simell
    • 1
  1. 1.The JDRF Center for Prevention of Type I Diabetes in Finland
  2. 2.Tampere University Hospital, Department of Pediatrics, P.O. Box 2000, 33521 Tampere, Finland
  3. 3.Department of Pediatrics, University of Turku, Turku, Finland
  4. 4.Department of Pediatrics, Medical School, University of Tampere, and Tampere University Hospital, Tampere, Finland
  5. 5.Department of Pediatrics, University of Oulu, Oulu, Finland
  6. 6.Department of Virology, University of Turku, Turku, Finland
  7. 7.Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

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