We can no longer assume that all new-onset diabetes in children and adolescents is type 1. As type 2 diabetes creeps downward from adults into younger age groups, differentiating it from type 1 disease and starting appropriate treatment become vitally important.
We can no longer assume that all new-onset diabetes in children and adolescents is type 1. As type 2 diabetes creeps downward from adults into younger age groups, differentiating it from type 1 disease and starting appropriate treatment become vitally important.
Children and adolescents with new-onset diabetes traditionally have been assumed to have type 1 diabetes, an autoimmune disease characterized by ß-cell destruction and insulin deficiency. Type 2 diabetes, characterized by insulin resistance (reduced biologic effect of insulin) and impaired insulin secretion, has been associated with aging and obesity. In recent years, however, type 2 diabetes has become increasingly common among children and adolescents.1
The hallmark of diabetes mellitus is hyperglycemia resulting from metabolic defect(s) that impair insulin secretion, insulin action, or both. Historically, diabetes has been classified along therapeutic lines, as either insulin-dependent or non-insulin dependent, or by age of onset (juvenile or adult-onset). An etiologic classification is now preferred based on recent advances in immunologic and genetic techniques. Accordingly, diabetes resulting from deficient insulin secretion is classified as type 1 diabetes. The most common etiology is immune destruction of the insulin-producing ß-cells of the pancreas (type 1a). Type 1b diabetes is an etiologically distinct nonautoimmune form of phenotypic type 1 diabetes. Type 2 diabetes refers to disease resulting from insulin resistance, often with a concomitant insulin secretory defect.
Several forms of diabetes with specific genetic etiologies also are recognized. They include disorders arising from genetic defects of the ß-cells, such as maturity-onset diabetes of the young (MODY) and mitochondrial DNA mutations. Table 1 outlines the current classification of diabetes.2
Type 1: ß-cell destruction
Type 2:Insulin resistance secretory defect
Gestational diabetes mellitus
Other specific types
Genetic defects of ß-cell function (MODY 1, MODY 2, MODY 3)
Genetic defects of insulin action (type A insulin resistance, leprechaunism)
Diseases of exocrine pancreas (cystic fibrosis, hemochromatosis, pancreatitis, etc.)
Endocrinopathies leading to insulin resistance (Cushing syndrome, acromegaly, etc.)
Other genetic syndromes (Down, Turner, Klinefelter, Prader Willi, etc.)
Drug- and chemical-induced diabetes
Diabetes caused by infection (congenital rubella, cytomegalovirus)
A substantial and continuing rise in the number of adolescent patients diagnosed with type 2 diabetes was first documented in a large diabetes center in the Midwest between 1992 and 1998 (Figure 1).3 Subsequent reports from other centers support the emergence of type 2 diabetes as a worldwide public health problem that will increase in importance during the next decade.48
Current data from diabetes referral centers indicate that type 2 disease accounts for about 40% of cases in patients diagnosed with diabetes between 10 and 19 years of age.3 The prevalence of type 2 diabetes in the pediatric population may be underestimated, however, considering that children with new-onset diabetes are generally assumed, perhaps incorrectly, to have type 1 disease. Moreover, data from the National Health and Nutrition Examination Survey III (NHANES III) conducted by the National Center for Health Statistics suggest that up to one third of adults with type 2 diabetes are undiagnosed.9 If the same is true for children and adolescents, type 2 diabetes is even more common in this age group than current data indicate.
To help pediatricians deal with this growing health problem, we will review current knowledge regarding the epidemiology, risk factors, diagnosis, and treatment of type 2 diabetes in children and adolescents. The American Diabetes Association (ADA) recently held a consensus conference on type 2 diabetes in children, the report of which is available for readers seeking greater detail.10
Who are the children at risk of developing type 2 diabetes? Factors that should raise suspicion include obesity, certain clinical signs, ethnic origin, age and gender, and family history.
Obesity. The most prominent clinical risk factor for type 2 diabetes in children and adolescents appears to be severe obesity. The average body mass index (BMI)weight in kilograms divided by the square of the height in metersof patients with type 2 diabetes in published reports ranges from 35 to 39 kg/m2, while the normal range (5th to 95th percentile) for the pediatric population is 15 to 27 kg/m2. About one third of children with type 2 diabetes have a BMI greater than 40 kg/m2, indicating morbid obesity, and 17% have a BMI greater than 45 kg/m2. Measurement of the waist-to-hip ratio (circumference of the waist compared to circumference of the hips) in a representative subgroup of adolescent type 2 patients indicates that obesity in such patients is central (the "apple" shape).11
An association between increasing childhood obesity and the emergence of type 2 diabetes as an important clinical entity has been suggested, but the exact causal relationship is not clear. It may be that childhood obesity has become so prevalent that associated complications are occurring at a clinically apparent level. Or, since the severity of childhood obesity also has worsened, a greater number of obese children may be sufficiently overweight to develop comorbidities.
Despite the strong association between obesity and type 2 diabetes, it is important to note that obese children and adolescents have the same risk for type 1 diabetes as other children. Since starting insulin treatment in patients with type 1 disease is critical, the diagnosis of type 2 diabetes should be made with caution and only when other supporting clinical, historical, and laboratory information is present. Type 2 diabetes has been identified in lean patients, though they represent a small subset in reported studies.
Clinical signs. Besides morbid obesity, a number of clinical signs should alert the physician to further investigate the type of diabetes present (Table 2). Acanthosis nigricanshyperpigmentation and thickening of the skin into velvety irregular folds in the neck and flexural areasreflects chronic hyperinsulinemia. It is rare in patients with type 1 diabetes but occurs in 60% to 90% of adolescents with type 2 diabetes. Acanthosis in an obese child with diabetes should therefore prompt consideration of type 2 disease. Obese children and adolescents who have acanthosis but not overt diabetes should be evaluated to exclude the possibility of undiagnosed hyperglycemia.
Type 2 diabetes in a first-degree relative
Ac anthosis nigricans
Previous diagnosis of obesity-related morbidity
Polycystic ovary syndrome
"Accidental" diagnosis of diabetes on routine physical exam
Hypertension is rare in patients with type 1 diabetes at presentation but may occur in 20% to 30% of patients with type 2 diabetes. The presence of both hypertension and acanthosis strongly suggests hyperinsulinemia. Obese adolescents with hypertension should be asked about family history of type 2 diabetes as well as symptoms of hyperglycemia. Also consider obtaining a fasting glucose and insulin or evaluating glucose tolerance in such patients to exclude undiagnosed diabetes or impaired glucose tolerance.
Ethnicity appears to play a role in susceptibility to type 2 diabetes. About two thirds of adolescents with type 2 disease in our study group and a group from San Diego were African-American or Mexican-American, respectively; the rest were Caucasian.3,12 Thus, type 2 diabetes appears to be more prevalent in some ethnic groups than others. These groups are the same as those with a higher prevalence of type 2 diabetes in adulthood. Published reports indicate, however, that pediatric patients with type 2 diabetes belong to all ethnic groupsHispanics, blacks, Caucasians, Japanese, First Nation children of Canada, and Ashkenazi or Sephardic Jews. Ethnicity thus is not a useful predictive factor in an individual case.
Age and gender. The mean age of adolescents with type 2 diabetes ranged from 13 to 14 years in the various series.3,4,7,12,13 Rare cases of type 2 diabetes among children as young as 5 years of age have been reported.12 Generally, age is not helpful in differentiating between type 1 and type 2 diabetes in adolescents. Because of the shape of the two prevalence curves, however, the younger the child, the more likely it is that he has type 1 diabetes.
In our series, all patients with type 2 diabetes were in puberty (Tanner stage III or greater), though some studies have reported prepubertal cases.3 The age of onset of puberty among obese children is usually earlier than among their peers. Since puberty is characterized by relative insulin resistance, it may be an aggravating factor in the appearance of overt type 2 diabetes in obese adolescents.
Girls appear to be more susceptible to type 2 diabetes than boys, with an overall female-to-male ratio of 1.7/1 regardless of race. Since the ratio is based on studies from diabetes centers and not from population screening, however, the gender discrepancy may result from a higher proportion of undiagnosed cases among boys caused by the known lower frequency of medical visits among adolescent males compared to females.
Family history. Adolescents with type 2 diabetes generally come from families in which the parents are also obese and tend to have insulin resistance or overt type 2 diabetes themselves. In published series, 60% to 80% of patients have had a family history of type 2 diabetes in one first-degree relative. Moreover, otherwise healthy siblings of patients with type 2 diabetes have been found to have elevated levels of C peptide and proinsulin, both of which are associated with a high risk of developing type 2 diabetes, and first-degree family members have turned out to have "undiagnosed diabetes" on subsequent evaluation.
Once a young proband has been identified, other family members should be screened for insulin resistance or overt diabetes. Families with type 2 diabetes should be differentiated, however, from families with maturity-onset diabetes of the young, which is an autosomal disorder associated with relatively mild hyperglycemia but not necessarily obesity.
Because there is significant overlap in the initial presentation of type 1 and type 2 diabetes in children and adolescents, presenting symptoms are not diagnostically reliable. Considering the presentation can provide some insight into the likely etiology, however. Table 3 summarizes typical characteristics of patients with type 1 and type 2 diabetes.
In general, patients with type 2 diabetes more often present with signs of chronic hyperglycemia, while patients with type 1 diabetes are more likely to present with acute metabolic decompensation. About 20% of adolescents with type 2 diabetes have polyuria, polydipsia, and weight loss as their presenting complaints, clinical signs common to both type 1 and type 2 diabetes. About one third of type 2 patients, however, are diagnosed by routine laboratory screening (usually urinalysis) as part of a school physical, rather than as a result of specific complaints. Such "accidental" diagnosis is rare in type 1 diabetes.
Similarly, 25% of girls with type 2 diabetes have a vaginal monilial infection as their chief complaint at presentation. While this is a typical complaint among adult females with type 2 diabetes and indicates glycosuria of long-standing, it is exceedingly rare as a presenting symptom in type 1 patients. The remaining type 2 patients present with a variety of complaints including severe infection (osteomyelitis, pharyngitis), obesity, dysuria, and enuresis.
Some adolescents, particularly African-Americans, who are eventually diagnosed with type 2 diabetes may present with diabetic ketoacidosis (DKA), traditionally considered the hallmark of type 1 diabetes. In our series, 42% of black patients with type 2 diabetes presented with ketonuria and 25% with DKA.14 In another study, about a third of Hispanic adolescents with type 2 diabetes presented with ketonuria.13 This phenomenon has been demonstrated among obese black adult patients who present with ketosis and DKA but follow a subsequent clinical course typical of type 2 diabetes.15
The mechanism behind ketosis in patients with type 2 diabetes is unclear. It is generally believed that insulin resistance combined with the deleterious effect of chronic hyperglycemia on insulin secretion and action ("glucose toxicity") results in relative insulin deficiency. When the deficiency becomes severe (because of long-standing hyperglycemia with decompensation or intercurrent illness), it leads to enhanced lipolysis and increased levels of free fatty acids, ketonemia, and ketonuria, characteristically seen in patients with type 1 diabetes. Why this phenomenon is more common in black and Hispanic patients with type 2 diabetes is unknown, though evidence indicates that basal insulin sensitivity in these groups is lower than in their Caucasian peers, possibly increasing their susceptibility to developing relative insulin deficiency.16
Adolescents with type 2 diabetes report a high-fat, low-fiber diet in spite of having knowledge of appropriate food choices. An increase in fat intake has been associated with the rising incidence of type 2 diabetes in children in Japan.17 Among 11 adolescent type 2 patients in our series, three met criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for binge eating disorder (BED) while six had significant characteristics of BED but did not meet strict criteria.11 BED is marked by eating larger amounts of food than most people would eat in a discrete time period accompanied by a sense of lack of control. It occurs in an estimated 20% to 50% of individuals who seek specialized obesity treatment. Unfortunately, our data do not indicate whether the patients in our study engaged in binge eating at the time of diagnosis or developed it as a result of rigid standards of dietary restraint.
As a group, adolescents with type 2 diabetes lead a sedentary lifestyle and do not participate in structured or routine exercise programs.11 In adults, low physical activity and high caloric intake are known risk factors for obesity and type 2 diabetes.
Are laboratory tests helpful in distinguishing between type 1 and type 2 disease in a patient with new-onset diabetes? The answer is not always clear-cut.
Insulin and C peptide levels. In patients with type 2 diabetes, both plasma insulin and C peptide concentrations are usually high, reflecting underlying insulin resistance.18 Chronic hyperglycemia, however, can cause transient insulin deficiency ("glucose toxicity") with a low initial plasma insulin concentration despite insulin resistance. Insulin and C peptide levels therefore may be deceptively low in the presence of acute metabolic deterioration at the time of presentation. Conversely, "insulin reserve" can persist in patients with type 1 diabetes for up to two years. Thus, although measurement of insulin and C peptide can be helpful in distinguishing type 1 and type 2 diabetes, particularly when elevated, a significant degree of overlap exists.
Autoantibody levels. Autoantibodies to the islet cell (ICAs), insulin (IAA), glutamic acid decarboxylase (GAD), and tyrosine phosphatase (ICA-512), employed individually or in combination, may be helpful diagnostic tools. Autoantibodies have been reported to be positive in up to 90% of patients with type 1 diabetes at the time of presentation.19 Conversely, the presence of autoantibodies in adults with clinically suspected type 2 diabetes who have positive antibodies is associated with a high risk of eventually becoming insulin dependent, a condition termed latent autoimmune diabetes. Thus the absence of antibodies, in the right clinical context, suggests type 2 diabetes, while their presence suggests type 1 disease. Assessment of autoantibodies is not necessary in all patients with new- onset diabetes, but it may be useful when other clinical signs, such as obesity, acanthosis, or family history, make type 2 diabetes a diagnostic consideration.
The diagnosis of type 2 diabetes in a child or adolescent with new-onset diabetes is indeed difficult. The ability to distinguish definitively between type 1 and type 2 disease at onset is often limited, specifically if the patient presents following an acute deterioration. Whenever there is a doubt, and until proven otherwise, patients should be treated with insulin as if they have type 1 diabetes.
Clinical reassessment in light of the subsequent course should be done at each visit in patients with suspected type 2 diabetes. Type 2 patients who are treated with insulin may have recurrent hypoglycemic episodes, insulin requirements per weight that are unusually low (after overcoming initial insulin resistance) or high, and long periods off insulin without decompensation.
No relevant studies of the optimal approach to managing type 2 diabetes in children have yet been done, and no validated treatment protocols exist. Current treatment is based on our understanding of the pathophysiology of type 2 diabetes and studies in adult patients.
Primary efforts should focus on treating the underlying causes of the disorder, namely obesity, poor diet, and sedentary lifestyle, particularly in patients who are asymptomatic at presentation (Figure 2). The majority of children with type 2 diabetes are adolescents and present challenges to health-care providers attempting to promote behavior and lifestyle changes. Moreover, adolescents with type 2 diabetes often come from families whose members overwhelmingly are sedentary, unrestrained eaters. Treating them can be frustrating, and although occasional individuals manage to lose weight and regain metabolic control, a considerable number either drop out of treatment or stay overweight with poor diabetes control.20,21 These facts must be taken into account when planning treatment strategies. Unlike adults with type 2 diabetes, adolescents generally require an intensive, multidisciplinary approach if treatment is to succeed.
Continuous education plays a critical role in the management of adolescents with diabetes. As with other chronic disorders, education must be repeated at relatively frequent intervals. Otherwise, patients quickly resume their old habits. All family members should be included in the program, since they are often overweight and themselves at high risk for developing type 2 diabetes. Maintenance of a low-fat, low-calorie, high-fiber diet by the entire family enables the adolescent patient to comply more reliably with recommendations.
Since patients may be diagnosed initially as having type 1 diabetes, it is important that they be reassigned and educated regarding their correct diagnosis as soon as possible. Education should focus on the difference in etiology and natural history of type 1 and type 2 diabetes, treatment options, and possible complications and how to avoid them.
Extensive resources on type 2 diabetes for both physicians and patients are available through the ADA and its Web site, www.diabetes.org . A number of pharmaceutical companies also provide written and Internet information for patients. Unfortunately, this material is currently geared exclusively to adults, and pediatricians may need to modify it to make it applicable to their younger patients and families. Recognition of early-onset type 2 diabetes will, we hope, lead to preparation of materials more suited to children and adolescents.
Dietary treatment should aim for gradual, sustained weight loss and set realistic goalsmoderate weight reduction, for example, rather than normalization of body weight, as the latter goal will quickly discourage patients. Even modest weight loss can markedly improve glycemic control and insulin resistance. Besides weight loss, dietary goals should include achieving optimum metabolic control of blood glucose levels and decreasing lipids and lipoproteins.
We generally follow the recommendations of the ADA and individualize the diet according to personal lifestyle. An individualized diet is particularly important for teenagers, who may have been diagnosed initially as having type 1 diabetes and given a diet that included mandatory snacks between meals.
Since eating disorders are quite prevalent among adolescents with type 2 diabetes, attention should be directed to searching for such disorders, and dietary interventions should take into account the risk of inciting or exacerbating a latent disorder
Exercise is of primary importance in managing type 2 diabetes since even moderate exercise improves control. Although adolescents with type 2 diabetes are very obese with extremely low exercise performance, they should be encouraged to choose any physical activity they can accomplish on a routine basis, ideally two to three times a week. Daily walking, for example, is recommended in obese adult type 2 diabetes patients for weight reduction and improvement of insulin sensitivity.22
Our experience, however, indicates that adolescents are more likely to maintain a scheduled, formal activity than one that requires self-motivation. As an alternative, recent studies suggest that counseling focused on reducing time spent in sedentary activities, such as watching television, may increase activity levels as effectively as directly promoting physical activity and may seem less intimidating to the sedentary adolescent.
As with any chronic disease in this age group that influences daily activity and has long-term health implications, emotional support must play a significant role in therapy. In our experience, many patients have been treated for depression or eating disorders before diagnosis and therefore need careful and continuous follow-up.
Patients who are symptomatic at presentation or fail conservative therapy may require pharmacologic intervention (Figure 3). Since patients with type 2 diabetes have insulin resistance, it is logical to start with a drug that improves insulin sensitivity, such as metformin (Glucophage).23 Metformin decreases hepatic glucose production and increases muscle glucose uptake. It has no effect on pancreatic insulin secretion and requires the presence of insulin to be effective. When endogenous secretion of insulin is adequate, as is generally the case in type 2 diabetes, metformin can be used alone to overcome insulin resistance.
Patients who present with severe hyperglycemia or ketosis, however, require insulin therapy in addition to metformin because of transient insulin deficiency resulting from glucose toxicity. In such cases, we recommend starting metformin at the same time as insulin and, once control is achieved, gradually reducing the insulin dose as tolerated.
Since the use of metformin in adolescents has not been extensively studied and is not currently approved by the Food and Drug Administration, it should be undertaken with caution. Lactic acidosis is a potentially life-threatening condition that has been associated with metformin therapy, having a worldwide incidence of approximately three cases per 100,000 patient-years exposure.24 The risk can be minimized by not giving metformin to patients at risk of significant drug accumulation (those with renal impairment, for example) or patients at risk of developing lactic acidosis independent of therapy because their ability to clear lactate is compromised by conditions such as those associated with tissue hypoperfusion or hypoxic states and substantial liver impairment or excessive alcohol intake.
We generally start metformin therapy with 500 mg at bedtime, and if tolerated for a week with no GI side effects, increase the dose to 500 mg twice a day and titrate accordingly. Most obese adolescents can be managed with maximum doses of metformin (2,500 mg per day given in two or three divided doses). We recommend a daily multivitamin for patients on reducing diets and routinely monitor metabolic status. We also recommend vitamin B12 and folate supplementation since these nutrients may be deficient in reducing diets.
There is currently no reported experience in adolescents with type 2 diabetes with newer, so-called insulin sensitizing drugs, such as thiazolidinediones (troglitazone, rosiglitazone, pioglitazone). Although this group of agents seems promising, the first one released, troglitazone, has been associated with fatal hepatic side effects in adults and was recently withdrawn from the market. The other agents in the group are thought to have less risk of side effects, but are only recently released and thus should be used with caution in adolescents until greater experience has been accumulated.
Sulfonylureas have no obvious advantage over metformin or insulin sensitizers and can be associated with side effects, such as hypoglycemia. Studies in adult patients have indicated that sulfonylureas may be useful in combination with newer agents, but such trials have not been performed in the pediatric population. The short-acting insulin secretagogue repaglinide may be useful as an adjunctive agent when metformin fails to normalize gylcemic excursion. The requirement that the drug be taken with each meal often creates significant compliance problems for adolescents, however. Similarly, acarbose, which slows carbohydrate hydrolysis and absorption, has potential as adjunctive therapy but is associated with side effects, such as diarrhea and flatulence, that many adolescents find intolerable.
Unlike the adult population, a substantial number of adolescent patients with type 2 diabetes are started on insulin therapy because the initial diagnosis is thought to be type 1. In addition, patients who present with severe hyperglycemia or diabetic ketoacidosis require insulin acutely for reversal of metabolic decompensation and stabilization (Figure 3). In most cases, however, the patient can be weaned off insulin eventually.
While effective in promoting glycemic control, insulin therapy heightens the risk of hypoglycemia, may lead to increased weight gain, entails frequent injections, and, most important, is associated with hyperinsulinemia, which may promote hypertension and hyperlipidemia. However, based on experience in adults, it is likely that many patients will eventually require insulin, alone or in combination with oral agents, due to long-term poor compliance, waning ß-cell function, and waning effectiveness of oral agents.
The effect of early-onset type 2 diabetes in children on morbidity and mortality has yet to be studied. After four-year follow-up of six Hispanic adolescents with type 2 diabetes, two had been hospitalized for uncontrolled diabetes and three had evidence of acute or chronic diabetic complications.13 Extrapolation from adult data makes it clear that early onset of type 2 diabetes likely has important implications for long-term health risk, including early-onset cardiovascular disease, large and small vessel atherosclerosis, nephropathy, retinopathy, and peripheral neuropathy.
Although the optimal health-care maintenance of adolescents with type 2 diabetes has not been determined in clinical trials, it is our policy to treat these patients intensively since the risks for long-term morbidity are very high. We recommend frequent home blood glucose monitoring with the goal of adjusting therapy to maintain tight control of glycemic excursion. We also recommend frequent clinical visits, initially every two to four weeks to establish weight loss and then every two to three months. We determine HbA1c levels at each visit to support home blood glucose records and do a yearly evaluation for dyslipidemia, microalbuminuria, renal function, retinopathy, and vitamin levels. The clinician caring for these children should also stay alert to the development of other obesity-related disorders, such as hypertension and sleep apnea.
Whenever possible, treatment should be managed by a multidisciplinary team led by a pediatric endocrinologist. Patients diagnosed with new-onset type 2 diabetes should be referred to a diabetes specialist for initiation of medical and nutrition therapy and appropriate education. Subsequent care should be coordinated between the diabetes care team and the primary care pediatrician, depending on the particulars of the case and the resources of the primary care practice.
Since siblings of adolescents with type 2 diabetes have been shown to be at high risk for both insulin resistance and overt diabetes,11 consider evaluating them for these conditions, especially if obesity, acanthosis nigricans, or hypertension are present. Similarly, children who come from families in which type 2 diabetes is prevalent and are obese or have hypertension, acanthosis nigricans, or dyslipidemia are candidates for evaluation for insulin resistance, impaired glucose tolerance, or undiagnosed diabetes. Early initiation of dietary and lifestyle modifications in these high-risk patients may prevent progression of their disorder.
Type 2 diabetes is an increasingly important adolescent health problem with unknown, but potentially significant, long-term consequences. A growing percentage of adolescents presenting with new-onset diabetes, with or without ketosis, have type 2 diabetes. Since the distinction between type 2 and type 1 diabetes has implications for optimal long-term therapy and comorbidity, it is vital that the correct diagnosis be made as soon as possible.
The primary modifiable pathology in type 2 patients is severe obesity, and the primary goals of treatment are controlling weight and promoting increased physical activity, along with tight control of glucose excursion. In addition, continuous emotional support of the patient and family are critical to long-term success.
The exact causes of the increasing prevalence of type 2 diabetes have not been definitively identified, but the trend appears to reflect the impact of contemporary changes in diet and lifestyle on children and adolescents with an inherited predisposition to develop obesity and its complications. While emergence of overt type 2 diabetes in some individuals reveals the effect of diet and lifestyle on the most vulnerable in the population, however, the lifestyle changes themselves are generalized. Efforts to reverse the epidemic must, therefore, focus on reversing the changes by promoting increased daily physical activity and moderation of high-calorie diets for all children and teens.
Most important, effective intervention requires a public health approach that delivers the message widely, emphasizing a healthy lifestyle rather than athletic prowess or an ideal body. Pediatricians and family physicians can have a significant impact by working with the schools, local media, and other community resources as well as by offering anticipatory guidance within their practices.
1. Pinhas-Hamiel O, Standiford D, Daniels SR, et al: A persistent increase of noninsulin-dependent diabetes mellitus (NIDDM) among adolescents. Inter J Obesity 1998;22(suppl 3[S206]):4l4
2. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1998;21(Suppl 1):5
3. Pinhas-Hamiel O, Dolan LM, Daniels SR, et al: Increasing incidence of non-insulindependent diabetes mellitus in children and adolescents. J Pediatr 1996; 128:608
4. Scott CR, Smith JM, Cradock MM, et al: Characteristics of youth-onset noninsulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus at diagnosis. Pediatrics 1997;100(l):84
5. Glaser N, Jones KL: Noninsulin-dependent diabetes mellitus in childhood. Pediatr Res 1995;37:89A
6. Owada M, Hanaoka Y, Tanimoto Y, et al: Descriptive epidemiology of noninsulin-dependent diabetes mellitus detected by urine glucose screening in school children in Japan. Acta Paediatr Jpn 1990;32:716
7. Harris SB, Perkins BA, Whalen-Brough E: Noninsulin-dependent diabetes mellitus among First Nations children. New entity among First Nation people of northwestern Ontario. Can Fam Physician 1996;42:869
8. Pinhas-Hamiel O, Koren I, Vardi P: Type 2 diabetes among adolescents in Israel. Harefua 2000;138(3):186
9. Harris M: Undiagnosed type 2 diabetes: Clinical and public health issues. Diabetes Care 1993;16:643
10. American Diabetes Association: Type 2 diabetes in children and adolescents. Diabetes Care 2000;23:381
11. Pinhas-Hamiel O, Standiford DS, Hamiel D, et al: The type 2 diabetes family: A setting for development and treatment of adolescent type 2 diabetes. Arch Pediatr Adolesc Med 1999;153:1063
12. Glaser NS, Jones KL: Noninsulin-dependent diabetes mellitus in Mexican-American children. West J Med 1998;168(l):11
13. Neufeld ND, Raffel L, Landon C: Early presentation of type 2 diabetes in Mexican-American youth. Diabetes Care 1998;21(l):80
14. Pinhas-Hamiel O, Dolan LM, Zeitler P: Diabetic ketoacidosis among obese African-American adolescents with type 2 diabetes. Diabetes Care 1997;20:484
15. Umpierrez GE, Casals MMC, Gebhart SSP, et al: Diabetic ketoacidosis in obese African-Americans. Diabetes 1995;44:790
16. Arslanian S, Suprasongsin C: Differences in the in vivo insulin secretion and sensitivity of healthy black vs. white adolescents. J Pediatr 1996;129:400
17. Kitagawa T, Owada M, Urakami T, et al: Increased incidence of noninsulin-dependent diabetes mellitus among Japanese school children correlates with an increased intake of animal protein and fat. Clin Pediatr 1998;37:111
18. Service FJ, Rizza RA, Zimmmerman BR, et al: The classification of diabetes by clinical and C-peptide criteria. A prospective population-based study. Diabetes Care 1997;20:198
19. Rowley MJ, Mackay IR, Chen QY, et al: Antibodies to glutamic acid decarboxylase discriminate major types of diabetes mellitus. Diabetes 1992;41(4):548
20. Dean H: Type 2 diabetes-y in First Nation children in Canada. Clin Pediatr 1998;37:89
21. Owada M, Nitadori Y, Kitagawa T: Treatment of type 2 diabetes in youth. Clin Pediatr 1998;37:117
22. Yamanouchi K, Shinozaki T, Chikada K, et al: Daily walking combined with diet is a useful means for obese type 2 diabetes patients not only to reduce body weight but also to improve insulin sensitivity. Diabetes Care 1995;18:775
23. DeFronzo R, Goodman A: Efficacy of metformin in patients with noninsulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med 1995;333:541
24. Howlett HC, Bailey CJ: A risk-benefit assessment of metformin in type 2 diabetes mellitus. Drug Saf 1999;20(6):489
Phil Zeitler. Type 2 diabetes: Not just for grownups anymore. Contemporary Pediatrics 2001;1:102.