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 inc idental hyperglycemia are at an increased risk of developing type 1 diabete s. RESEARCH DESIGN AND METHODS - A total of 748 subjects, 1-18 years of age (9 .04 +/- 3.62, mean +/- SD), without family history of type 1 diabetes, with out obesity, and not receiving drugs were studied and found to have inciden tal elevated glycemia defined as fasting plasma glucose >5.6 mmol/l confirm ed 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 antityrosine 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 th an in normal control subjects (P = 0.000027). After a median follow-up of 4 2 months (range 1 month to 7 years), 16 (2.1%) subjects (11 males and 5 fem ales), 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 g enetic susceptibility to type 1 diabetes. Diabetes symptoms were recorded i n 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 su bjects under or over 10 years, whereas the cumulative risk of type 1 diabet es was increased in subjects with one or more autoantibodies and in those w ith FPIR < 1st centile. CONCLUSIONS - Children with incidental hyperglycemia have a higher-than-nor mal frequency of immunological, metabolic, or genetic markers for type 1 di abetes and have an increased risk of developing type 1 diabetes.