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Type 2 Diabetes in Children and Adolescents Type 2 Diabetes in Children and Adolescents American Diabetes Association ype 2 diabetes is a serious and costly disease the American Academy of Pediatrics, developed a affecting more than 15 million adult Ameri- consensus position on the following six questions: Tcans. The chronic complications of diabetes in- clude accelerated development of cardiovascular dis- 1. What is the classification of diabetes in children ease, end-stage renal disease, loss of visual acuity, and adolescents? and limb amputations. All of these complications 2. What is the epidemiology of type 2 diabetes in contribute to the excess morbidity and mortality in children and adolescents? individuals with diabetes. Moreover, the prevalence 3. What is the pathophysiology of type 2 diabetes in of type 2 diabetes in adults is increasing. Superim- children and adolescents? posed on this disturbing picture in adults are the 4. Who should be tested for diabetes? recent reports of the emerging problem of type 2 5. How should children and adolescents with type 2 diabetes in children and adolescents. diabetes be treated? If the incidence and prevalence of type 2 diabetes 6. Can type 2 diabetes in children and adolescents be in children are increasing and if this increase cannot prevented? be reversed, our society will face major challenges. That is, the burden of diabetes and its complications QUESTION 1: What Is the Classification of Diabetes in will affect many more individuals than currently Children and Adolescents? anticipated, and the cost of diabetes to our society The diagnostic criteria and etiologic classification will cause us to consume enormous resources. Also, (Table 1) of diabetes (Table 2) outlined by the ADA’s many more Americans will be taking potent medi- Expert Committee report apply to children (1). In the cations, which have attendant risks, for most of their pediatric population, the recent experience with non- lives. immune-mediated diabetes has highlighted the dif- Despite the wealth of experience and knowledge ficulty in distinguishing the etiology of diabetes in concerning the epidemiology, pathophysiology, and some children without sophisticated laboratory eval- medical management of type 2 diabetes in adults, we uation. This experience has created confusion over know little about the disease in children. To assess the criteria that should be used to classify diabetes in our present knowledge and understanding and to children. provide guidance to practitioners on medical man- Until recently, immune-mediated type 1 diabetes agement, the American Diabetes Association (ADA) was the only type of diabetes considered prevalent convened a consensus development conference on among children, with only 1–2% of children consid- type 2 diabetes in children and adolescents from 30 ered to have type 2 diabetes or other rare forms of August 1999 to 1 September 1999. diabetes. Recent reports indicate that 8–45% of chil- An eight-member panel of experts in diabetes in dren with newly diagnosed diabetes have nonim- children, complemented by representatives from the mune-mediated diabetes. The variation in the per- National Institute of Diabetes and Digestive and Kid- centages reported appears to depend on race/ ney Diseases, the Division of Diabetes Translation at ethnicity and sampling strategy. The majority of the Centers for Disease Control and Prevention, and these children have type 2 diabetes, but other types are being increasingly identified. For example, idio- pathic or nonimmune-mediated type 1 diabetes has been reported, particularly in the African-American Address correspondence and reprint requests to Richard Kahn, PhD, Amer- population. ican Diabetes Association, 1701 N. Beauregard St., Alexandria, VA 22311. Abbreviations: 2-h PG, 2-h plasma glucose; ADA, American Diabetes As- Individuals with nonimmune-mediated diabetes sociation; DKA, diabetic ketoacidosis; FDA, Food and Drug Administration; may have clinical presentations indistinguishable FPG, fasting plasma glucose; HHNK, hyperglycemic hyperosmolar non- from those of patients with immune-mediated type 1 ketotic; IA, insulin antibody; IFG, impaired fasting glucose; IGT, impaired diabetes. This is relevant because as the number of glucose tolerance; MODY, maturity-onset diabetes of the young; NHANES children with type 2 diabetes increases, it becomes III, Third National Health and Nutrition Examination Survey; OGTT, oral glucose tolerance test; PCOS, polycystic ovarian syndrome; SMBG, self- increasingly important to classify their diabetes cor- monitoring of blood glucose. rectly so that appropriate therapy may be instituted. A table elsewhere in this issue shows conventional and Syste`me Interna- The initial classification is usually based on the tional (SI) units and conversion factors for many substances. clinical picture at presentation. Typically, children This statement was endorsed by the American Academy of Pediatrics in January 2000. with immune-mediated type 1 diabetes are not over- PEDIATRICS (ISSN 0031 4005). Copyright © 2000 by the American Acad- weight and have recent weight loss, polyuria, and emy of Pediatrics. polydipsia. As the U.S. population becomes increas- AMERICAN DIABETES ASSOCIATIONDownloaded from www.aappublications.org/news by guestPEDIATRICS on October 1, Vol. 2021 105 No. 3 March 2000 671 TABLE 1. Criteria for the Diagnosis of Diabetes sistance and obesity, are common in youth with type • Symptoms of diabetes plus casual plasma glucose 2 diabetes. Acanthosis is a cutaneous finding charac- concentration Ն200 mg/dl (11.1 mmol/l). Casual is defined terized by velvety hyperpigmented patches most as any time of day without regard to time since last meal. prominent in intertriginous areas and is present in as The classic symptoms of diabetes include polyuria, many as 90% of children with type 2 diabetes (A. polydipsia, and unexplained weight loss. or Fagot-Campagna, D. J. Pettitt, M. M. Engelgau, N. R. • FPG Ն126 mg/dl (7.0 mmol/l). Fasting is defined as no Burrows, L. S. Geiss, R. Valdez, G. Beckles, J. Saad- caloric intake for at least 8 h. dine, E. W. Gregg, D. E. Williamson, K. M. Venkat or Narayan, J Pediatrics. In press). It is recognized more • 2-h PG Ն200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health frequently in darker-skinned obese individuals. Organization (20), using a glucose load containing the PCOS is a reproductive disorder characterized by equivalent of 75-g anhydrous glucose dissolved in water. hyperandrogenism and chronic anovulation not due In the absence of unequivocal hyperglycemia with acute metabolic to specific diseases of the ovaries, adrenals, and pi- decompensation, these criteria should be confirmed by repeat tuitary. Lipid disorders and hypertension also occur testing on a different day. The third measure (OGTT) is not in children with type 2 diabetes. recommended for routine clinical use. Adapted from the Report of Currently, children with type 2 diabetes are usu- the Expert Committee on the Diagnosis and Classification of Di- ally diagnosed over the age of 10 years and are in abetes Mellitus (1). middle to late puberty. As the childhood population becomes increasingly overweight, type 2 diabetes ingly overweight, however, the percentage of chil- may be expected to occur in younger prepubertal dren with immune-mediated type 1 diabetes who are children. obese is increasing. As many as 24% may be over- Children with idiopathic type 1 diabetes may be weight at the time of diagnosis. Children with im- difficult to distinguish from those with immune-me- mune-mediated diabetes usually have a short dura- diated type 1 diabetes. The majority of those de- tion of symptoms and frequently have ketosis; 30– scribed with idiopathic type 1 diabetes have what 40% have ketoacidosis at presentation (2). After has been termed atypical diabetes mellitus (ADM, metabolic stabilization, they may have an initial pe- type 1.5, or “Flatbush” diabetes) and are African- riod of diminished insulin requirement (i.e., honey- American (3,4). Their family history is positive for moon period), after which they require insulin for early-onset diabetes in many relatives in multiple survival and are at continual risk for ketoacidosis. Of generations. Insulin may not be required for survival children with immune-mediated type 1 diabetes, 5% after the resolution of the acute metabolic deteriora- have a first- or second-degree relative with the same tion. Metabolic control, however, is poor without disease. insulin therapy, and ketoacidosis may recur. In contrast, most children with type 2 diabetes are Maturity-onset diabetes of the young (MODY) is a overweight or obese at diagnosis and present with rare form of diabetes in children that includes several glycosuria without ketonuria, absent or mild poly- disorders caused by monogenic defects in ␤-cell uria and polydipsia, and little or no weight loss. But function inherited in an autosomal-dominant fashion up to 33% have ketonuria at diagnosis, and 5–25% of (5). Recent studies suggest that the clinical spectrum patients who are subsequently classified as having of MODY is broad, ranging from asymptomatic hy- type 2 diabetes have ketoacidosis at presentation. perglycemia to a severe acute presentation. MODY These patients may have ketoacidosis without any has been reported in all races/ethnicities. These gene associated stress, other illness, or infection. Children abnormalities are thought to be rare, and molecular with type 2 diabetes usually have a family history
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