First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes.
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.
Keskinen
P
P
The JDRF Center for Prevention of Type I Diabetes in Finland. paivi.keskinen@uta.fi
Korhonen
S
S
Kupila
A
A
Veijola
R
R
Erkkilä
S
S
Savolainen
H
H
Arvilommi
P
P
Simell
T
T
Ilonen
J
J
Knip
M
M
Simell
O
O
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
D001323:Autoantibodies; D007328:Insulin; D007330:Insulin Antibodies; C024211:islet cell antibody