Type 2 Diabetes in Adolescents, No Longer Rare

Diabetes mellitus, characterized by hyperglycemia, glycosuria, and long-term micro- and macrovascular complications, is the final common outcome of several different pathologic processes. The shared mechanism is the absolute or relative lack of functional insulin, with resulting failure of normal intracellular glucose transport.

Because the disease is not homogeneous, the most useful classification is based on etiologic mechanism. Type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]) is an autoimmune disease characterized by destruction of beta cells in genetically susceptible individuals that leads to absolute insulin deficiency. Maturity onset diabetes of the young (MODY) is a clinically heterogeneous set of disorders characterized by autosomal dominant inheritance and primary genetic defects in glucose-stimulated insulin secretion. Mutations have been identified in the glycolytic enzyme glucokinase, three liver-enriched transcription factors, and the gene that encodes the transcription factor, insulin promoter factor-1. Secondary diabetes can be due to pancreatic disease, genetic syndromes, drug intake, hormonal abnormalities, or quantitative or qualitative defects in insulin receptors. Type 2 diabetes (noninsulin-dependent diabetes mellitus[ NIDDM]) is a syndrome that commonly is associated with obesity, hypertension, and cardiovascular disease and is characterized by the combination of peripheral resistance to insulin action and insulin secretory defects.

Type 2 diabetes has been rare in the pediatric population, historically accounting for an estimated 2% of all newly diagnosed cases. However, there has been a recent marked increase among adolescents in various parts of the United States and internationally. For example, at the Children’s Hospital in Cincinnati, Ohio, a tenfold increase has been documented over the past decade, with type 2 diabetes now accounting for nearly 40% of new-onset diabetes cases among adolescents. The reasons for the increase are not entirely clear, but likely are related to current trends in childhood obesity and changes in eating and exercise behavior. Among adults, undiagnosed type 2 diabetes represents just half of all cases, raising concerns that this disorder might be even more common among adolescents than indicated by current data.

The increase in the incidence of type 2 diabetes among adolescents has affected all ethnic groups, but has concentrated in some groups more than others. In the Midwest, about two thirds of affected youngsters are African-Americans, while in Southern California two-thirds are Mexican-Americans. Both groups have a high prevalence of adult type 2 diabetes. Whereas type 1 diabetes affects both genders equally, type 2 diabetes has a female predominance among adolescents of 1.7:1, irrespective of race. The mean age of the patients in reported series is approximately 14 years (range, 10 to 19 years), with females diagnosed an average of 1 year earlier than males. The vast majority are in puberty (sexual maturity rating III or greater), suggesting that the relative insulin resistance that is characteristic of puberty plays a role in the clinical presentation of overt type 2 diabetes.

There is no definitive diagnostic test for type 2 diabetes; confirmation ultimately depends on long-term observation. However, a number of clinical clues suggest the diagnosis, the most prominent of which is obesity. The reported mean body mass index (BMI) for affected patients is approximately 38 kg/m² (normal range, 20 to 27 kg/m²), and about 40% of the children are morbidly obese (BMI >40 kg/m²). In one study, the sum of skinfold thickness was above 95% for age, race, and gender, consistent with central obesity and linked to obesity-related complications.

Additional clinical signs are those indicating the presence of insulin resistance, which are uncommon in type 1 diabetes. These include acanthosis nigricans (hyperpigmentation and thickening of the skin into velvety, irregular folds in the neck and flexural areas), which is present in 60% to 90% of adolescents who have type 2 diabetes, and hypertension, which is present in 20% to 30% of these individuals.

The third group of clinical clues differentiates the acute deterioration characteristic of type 1 diabetes from the insidious onset of type 2. For example, a large percentage of patients who have type 2 diabetes are diagnosed on the basis of urinalysis during routine physical examination. Similarly, the presence of vaginal monilial infection, indicative of long-standing hyperglycemia, is common among females diagnosed with type 2 diabetes. In contrast, patients who have type 1 disease generally present with symptoms directly attributable to the deteriorating metabolic state.

The presence of diabetic ketoacidosis (DKA) is not as helpful in differentiating type 1 from type 2 diabetes as once thought because African-American adolescents who have type 2 diabetes may present with ketosis or frank DKA, a phenomenon also seen in obese adult African-Americans who have type 2 diabetes. The presence of DKA, however, initially suggests a diagnosis of type 1 diabetes, and a high index of suspicion for possible type 2 diabetes is required when the previously mentioned clinical clues are noted in a patient who presents with new-onset DKA.

A family history of type 2 diabetes among first-degree relatives may be helpful because these adolescents generally come from families in which the prevalence of both obesity and type 2 diabetes is extremely high. About 80% of adolescents who have NIDDM have at least one affected parent, and 27% have both. However, there is no clear autosomal dominant inheritance pattern, as in MODY. Interestingly, in addition to overt diabetes, hyperinsulinemia and insulin resistance are common among “healthy” first-degree family members.

There is no reliable difference in glycosylated hemoglobin (HbA1c) levels at the time of presentation, although elevated HbA1c levels are uncommon in type 1 diabetes due to the generally rapid deterioration. However, when type 2 diabetes is suspected, elevation of serum C-peptide and insulin concentrations as well as the absence of islet cell antibodies may be helpful in diagnosis when combined with the course of the disease. Because prolonged hyperglycemia can lead to a transient deterioration in beta cell function (glucose toxicity), insulin levels may be quite low in patients presenting with overt metabolic deterioration.

Finally, there appear to be common behavioral and personality characteristics of adolescents who have type 2 diabetes. For example, the vast majority is sedentary and reports no physical activity. In addition, both patients and their first-degree family members typically consume a diet rich in fat and deficient in fiber. Interestingly, 82% of probands in one study had recurrent episodes of binge eating (consuming large amounts of food with feelings of impaired control and distress), and in 27%, the frequency of these episodes met the criteria for binge eating disorder.

Unlike type 1 diabetes, in which absolute insulin deficiency requires insulin therapy, type 2 diabetes is the metabolic result of other primary abnormalities, namely, obesity, poor diet, and sedentary life-style, and long-term treatment should address these causes. The family unit is an important focus of treatment both because attempts at changing eating habits and physical activity are more successful when applied to all family members and because family members, including siblings, may be at very high risk for the disorder.

Because of their age, pediatric patients often are diagnosed initially as having IDDM. Thus, it is important that once the correct diagnosis is made, patients and family members understand the differences in pathogenesis and treatment of types 1 and 2 diabetes. In type 2 diabetes, mismanagement may have no immediately noticeable effect on health, and patients may not recognize the risks of their neglect. Therefore, they require closely monitored compliance and support. In addition, specific measures may be necessary to address disordered behavior patterns and attention should be paid to the presence or development of eating disorders.

Dietary intervention should aim for optimum metabolic control of blood glucose levels and gradual sustained weight loss. Goals must be realistic (eg, moderate weight reduction and not normalization of body weight) to avoid discouragement. It is crucial that patients understand that even modest weight loss can result in marked improvement in glycemic control, insulin resistance, plasma lipoprotein pattern, and blood pressure. Similarly, clinicians should emphasize that even moderate exercise, such as daily walking, will lead to improved glycemic control and development of increased exercise capacity.

A substantial number of adolescent patients who have type 2 diabetes are started on insulin therapy because of an initial diagnosis of type 1 diabetes or the initial presence of ketosis. In most cases, however, patients can be weaned off insulin after stabilization of the acute metabolic deterioration and institution of dietary interventions. All efforts should be made to control glycemia without chronic insulin therapy because exogenous insulin therapy heightens the risk of hypoglycemia, and the resulting peripheral hyperinsulinemia may promote hypertension and hyperlipidemia. Nevertheless, insulin ultimately may be required in many patients because of long-term poor compliance. Given the lack of studies on this population, the approach should be based on currently preferred regimens in adults.

To date there are no studies on the use of oral hypoglycemic agents in adolescents. Metformin increases peripheral sensitivity to insulin and decreases glucose production in the liver. It has no effect on pancreatic insulin secretion and requires the presence of insulin to be effective. It also promotes weight loss. Because insulin resistance is the predominant abnormality in many of these patients, metformin or related formulations may prove to be the drugs of choice in this population. Sulfonylureas are used widely in the treatment of adult type 2 diabetes and may be effective in combination with metformin because they enhance beta-cell insulin secretion in response to glycemic stimuli. Troglitazone, an insulin-sensitizing agent recently approved by the United States Food and Drug Administration for adult use, also improves hyperglycemia and insulin resistance. However, there are concerns about elevated liver enzymes and liver failure in some patients, and the use of this drug in the adolescent population has not been explored carefully.

• Copyright © 1998 by the American Academy of Pediatrics