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Risk of Type 1 Diabetes Development in Children With Incidental Hyperglycemia

A multicenter Italian study

¹ Department of Pediatrics, University of Genoa, G. Gaslini Institute, Genoa
² Department of Pediatrics
³ Biometric Unit, Scientific Direction
⁴ Service of Immunohematology and Transfusion, IRCCS Policlinico San Matteo, Pavia
⁵ Department of Laboratory Medicine, Padova
⁶ Istituto Scientifico (IRCCS), S. Raffaele, Milan, Italy

OBJECTIVE—The aim of our study was to determine whether children with incidental hyperglycemia are at an increased risk of developing type 1 diabetes.

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, 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.

Abbreviations: FPIR, first-phase insulin response • GADA, anti-GAD65 antibody • IA-2A, anti-tyrosine phosphatase-like protein autoantibody • IAA, insulin autoantibody • ICA, islet cell antibody • IVGTT, intravenous glucose tolerance test • JDF, Juvenile Diabetes Foundation • MHC, major histocompatibility complex • MODY, maturity-onset diabetes of the young • OGTT, oral glucose tolerance test • WHO, World Health Organization

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