Risk of type 1 diabetes development in children with incidental hyperglycemia: A multicenter Italian study.
OBJECTIVE
The aim of our study was to determine whether children with incidental hyperglycemia are at an increased risk of developing type 1 diabetes.


METHODS
A total of 748 subjects, 1-18 years of age (9.04 +/- 3.62, mean +/- SD), without family history of type 1 diabetes, without obesity, and not receiving drugs were studied and found to have incidental elevated glycemia defined as fasting plasma glucose >5.6 mmol/l confirmed on two occasions. Subjects were tested for immunological, metabolic, and immunogenetic markers.


RESULTS
Islet cell antibodies >5 Juvenile Diabetes Foundation units were found in 10% of subjects, elevated insulin autoantibody levels in 4.6%, GAD antibody in 4.9%, and anti-tyrosine phosphatase-like protein autoantibodies in 3.9%. First-phase insulin response (FPIR) was <1st centile in 25.6% of subjects. The HLA-DR3/DR3 and HLA-DR4/other alleles were more frequent in hyperglycemic children than in normal control subjects (P = 0.012 and P = 0.005, respectively), and the HLA-DR other/other allele was less frequent than in normal control subjects (P = 0.000027). After a median follow-up of 42 months (range 1 month to 7 years), 16 (2.1%) subjects (11 males and 5 females), 4.1-13.9 years of age, became insulin dependent. All had one or more islet autoantibodies, and the majority had impaired insulin response and genetic susceptibility to type 1 diabetes. Diabetes symptoms were recorded in 11 patients and ketonuria only in 4 patients. The cumulative risk of type 1 diabetes was similar in males and females, and it was also similar in subjects under or over 10 years, whereas the cumulative risk of type 1 diabetes was increased in subjects with one or more autoantibodies and in those with FPIR <1st centile.


CONCLUSIONS
Children with incidental hyperglycemia have a higher-than-normal frequency of immunological, metabolic, or genetic markers for type 1 diabetes and have an increased risk of developing type 1 diabetes.
Lorini
R
R
Department of Pediatrics, University of Genoa, G. Gaslini Institute, Genoa, Italy. renatalorini@ospedale-gaslini.ge.it
Alibrandi
A
A
Vitali
L
L
Klersy
C
C
Martinetti
M
M
Betterle
C
C
d'Annunzio
G
G
Bonifacio
E
E
D000293:Adolescent; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood; D001786:Blood Glucose / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D018572:Disease-Free Survival; D005215:Fasting; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000453:epidemiology* / Q000276:immunology; D007223:Infant; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology; D007558:Italy / Q000453:epidemiology; D008297:Male; D012016:Reference Values; D012307:Risk Factors; D013997:Time Factors
D001323:Autoantibodies; D001786:Blood Glucose; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007328:Insulin; C024211:islet cell antibody