Risk of Type 1 Diabetes Development in Children With Incidental Hyperglycemia

Abstract

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 Ϯ 3.62, mean Ϯ 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 Ͼ5.6 mmol/l confirmed on two occasions. Subjects were tested for immunological, metabolic, and immunogenetic markers.RESULTS -Islet cell antibodies Ͼ5 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 Ͻ1st 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 ϭ 0.012 and P ϭ 0.005, respectively), and the HLA-DR other/other allele was less frequent than in normal control subjects (P ϭ 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 Ͻ1st 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. Diabetes Care 24:1210 -1216, 2001T ype 1 diabetes results from cellmediated autoimmune destruction of ␤-cells in the pancreas (1). Multiple genes contribute to the predisposition of the disease, and major histocompatibility complex (MHC) is the most important one (1). Moreover, evidence suggests that environmental factors, which are still poorly defined, may play a role in either precipitating the disease and/or dominantly shaping its course (1). Various autoantibodies against ␤-cell components are present in the serum of newly diagnosed patients with type 1 diabetes (1). More importantly, these circulating autoantibodies may be present for months to years preceding the onset of clinical diabetes (2). The rate of ␤-cell destruction is quite variable, as it is rapid in some individuals and slow in others (3). Some patients, particularly children and adolescents, may present with ketoacidosis at the first manifestation of the disease (4). Others have modest fasting hyperglycemia that can rapidly change to severe hyperglycemia and/or ketoacidosis in the presence of infection ...

Oral glucose tolerance test in Italian overweight/obese children and adolescents results in a very high prevalence of impaired fasting glycaemia, but not of diabetes

“…In our children affected by minor alterations of glycaemia (IFG and IGT, not DM), the prevalence of autoimmunity (3.6%) is higher than that found in a previous study where GADA and IA2 were present in around 1-2% of schoolchildren from a general population [27]. However, in children with incidental hyperglycaemia, a higher-than-normal frequency of immunological markers for type 1 diabetes was reported [28], similar to our.…”

Glucokinase mutations in young children with hyperglycemia

“…The presence of incidental hyperglycemia in a healthy child, not associated with intercurrent illness, has been described as a risk factor for developing T1DM [20]. As demonstrated in this study, genetic evaluation for MODY mutations should be performed in young children with even mild fasting hyperglycemia not associated with physiological stress, especially if a mild increase of blood glucose levels during the OGTT and negative pancreatic autoantibodies are observed in a non-obese child with a family history of diabetes [21].…”

β-Cell Autoimmunity in Pediatric Celiac Disease: The Case for Routine Screening?

“…All samples were analyzed for GADA, IA-2A, and IAA with radiobinding assays (6). Personal and family histories for other autoimmune disorders were recorded.…”