Definition, epidemiology and classification of diabetes in children and adolescents

Abstract

Diabetes mellitus is a group of metabolic diseases characterised by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The abnormalities in carbohydrate, fat, and protein metabolism that are found in diabetes are due to deficient action of insulin on target tissues. If ketones are present in blood or urine, treatment is urgent, because ketoacidosis can evolve rapidly. Diagnostic criteria for diabetes are based on blood glucose measurements and the presence or absence of symptoms (E) 4, 86. Three ways to diagnose diabetes are possible and each, in the absence of unequivocal hyperglycemia, must be confirmed, on a subsequent day, by any one of the three methods given in Table 1. Diabetes in children usually presents with characteristic symptoms such as polyuria, polydipsia, blurring of vision, and weight loss, in association with glycosuria and ketonuria. In its most severe form, ketoacidosis or rarely a non-ketotic hyperosmolar state may develop and lead to stupor, coma and in absence of effective treatment, death. The diagnosis is usually confirmed quickly by measurement of a marked elevation of the blood glucose level. In this situation if ketones are present in blood or urine, treatment is urgent. Waiting another day to confirm the hyperglycemia may be dangerous in allowing ketoacidosis to evolve rapidly. In the absence of symptoms or presence of mild symptoms of diabetes, hyperglycemia detected incidentally or under conditions of acute infective, traumatic, circulatory or other stress may be transitory and should not in itself be regarded as diagnostic of diabetes. The diagnosis of diabetes should not be based on a single plasma glucose concentration. Diagnosis may require continued observation with fasting and/or 2 hour post-prandial blood glucose levels and/or an oral glucose tolerance test (OGTT). An OGTT should not be performed if diabetes can be diagnosed using fasting, random or post-prandial criteria as excessive hyperglycemia can result. It is rarely indicated in making the diagnosis of type 1 diabetes in childhood and adolescence (E) 86. If doubt remains, periodic re-testing should be undertaken until the diagnosis is established. IGT and IFG are intermediate stages in the natural history of disordered carbohydrate metabolism between normal glucose homeostasis and diabetes (E) 11, 65. IFG and IGT are not interchangeable and represent different abnormalities of glucose regulation. IFG is a measure of disturbed carbohydrate metabolism in the basal state whilst IGT is a dynamic measure of carbohydrate intolerance after a standardised glucose load. Patients with IFG and/or IGT are now referred to as having “pre-diabetes” indicating the relatively high risk for development of diabetes in these patients (A) 33, 38. They can be observed as intermediate stages in any of the disease processes listed in Table 2. IFG and IGT may be associated with the metabolic syndrome, which includes obesity (especially abdominal or visceral obesity), dyslipidaemia of the high-triglyceride and/or low-HDL type, and hypertension. Individuals who meet criteria for IGT or IFG may be euglycemic in their daily lives as shown by normal or near–normal glycated haemoglobin levels, and those with IGT may manifest hyperglycemia only when challenged with an OGTT. Categories of fasting plasma glucose are defined as follows: FPG<5.6 mmol/l (100 mg/dl) = normal fasting glucose FPG 5.6–6.9 mmol/l (100–125 mg/dl) = IFG FPG≥ 7.0 mmol/l (126 mg/dl) = provisional diagnosis of diabetes (the diagnosis must be confirmed, as described above under “Diagnostic Criteria”) The corresponding categories when the OGTT is used are as follows: 2 hour postload glucose<7.8 mmol/l (140 mg/dl) = normal glucose tolerance 2 hour postload glucose 7.8—11.1 mmol/l (140–199 mg/dl) = IGT 2 hour postload glucose>11.1 mmol/l (200 mg/dl) = provisional diagnosis of diabetes (the diagnosis must be confirmed, as described above). Individuals have an absolute deficiency of insulin secretion and are prone to ketoacidosis Most cases are primarily due to T-cell mediated pancreatic islet β-cell destruction, which occurs at a variable rate, and becomes clinically symptomatic when approximately 90% of pancreatic beta cells are destroyed (C) 25. Serological markers of an autoimmune pathologic process, including islet cell, GAD, IA-2, IA- 2β, or insulin autoantibodies, are present in 85-90% of individuals when fasting hyperglycemia is detected (B) 68, 82. Susceptibility to autoimmune type 1 diabetes is determined by multiple genes; in a recent meta-analysis more than 40 distinct genomic locations provided evidence for association with T1D 7. HLA genes having the strongest known association, there is linkage to specific combinations of alleles at the DRB1, DQA1 and DQB1 loci, with both susceptible or protective haplotypes 21, 45 (B). Individuals at increased risk of developing type 1 diabetes can often be identified by measurement of diabet