Type 2 Diabetes Mellitus in Youth: A Growing Challenge
An epidemic of obesity is sweeping our nation. As one walks through a crowded airport or mall, the prevalence of obesity is immediately apparent. In people over 20 years of age, obesity now affects about 33% of the population.1 In children and adolescents, obesity has increased by almost 50% over the past 20 years and has an estimated prevalence of at least 25%.2 While genetics plays a role in this trend, it is also likely that increased fast food consumption and a more sedentary lifestyle are contributing factors.
Major complications and risks associated with childhood obesity include psychosocial disturbances, hypertension, hyperlipidemia, respiratory dysfunction, slipped capital femoral epiphyses, and diabetes mellitus. As body mass index (BMI, kg/height in m2) increases to values above 27, the risk for developing these complications markedly increases. Consequently, it is essential for pediatricians, family physicians, and others who work with youth to identify those who are at risk. With early intervention and management strategies that emphasize exercise, dietary adjustment, and behavioral modification, it may be possible to prevent these worrisome complications.
Unfortunately, in many cases, intervention strategies are ineffective, and complications occur. One of the most common complications is type 2 diabetes mellitus. In fact, recent findings reported at a consensus conference on type 2 diabetes in children indicate that 845% of children with newly recognized diabetes have type 2 diabetes.3
The increasing incidence of type 2 diabetes in youth is not specific to North America. Interestingly, the incidence of type 2 diabetes among Japanese school children increased from 0.2 to 7.3 per 100,000 between 1976 and 1995. Much of this increase was accounted for by the 13- to 15-year-old group, which had an incidence of 13.9 per 100,000.4 As in North America, the Japanese experience appears to reflect changing food patterns and an increase in the prevalence of obesity.5
For most physicians and health care providers, evaluating and treating a child or adolescent with type 2 diabetes is a new challenge. This article is designed to provide guidance in meeting this challenge. We are entering a new frontier, and for this reason, there is a paucity of evidenced-based information available to direct our thinking. It is in this spirit that we offer the following recommendations.
The presentation of children who have type 2 diabetes is typically more insidious than that of those with type 1 diabetes. Children and adolescents with type 1 diabetes are usually ill, whereas patients who have type 2 diabetes often seek medical care because of excessive weight gain and fatigue as a result of insulin resistance. A history of increased thirst and polyuria is relatively uncommon in our experience. In some patients, androgen-mediated problems such as acne, hirsutism, and menstrual disturbances may be the chief complaint. Except for concerns about excessive weight gain, the history is often somewhat vague and needs clarification. Many times, parents say that their children do not seem to eat much, and that observation is consistent with the need for fewer calories to maintain weight in the face of decreased lean body mass.6
Family history provides important clues. The parents of children who are obese are often overweight as well. If both parents are obese, about 80% of their children are overweight, and if one parent is overweight, the occurrence of obesity in their children decreases to 40%.7
Typically, other family members, such as aunts and uncles, are also obese. Since insulin resistance usually underlies excessive weight gain, family members with acanthosis nigricans (see description under "Physical Examination") and type 2 diabetes are commonly reported.
Ethnic background is another important historical consideration. Over the past 20 years, the incidence of type 2 diabetes in minority populations has increased dramatically.8 Children and adolescents with African-American, Mexican-American, and Native-American backgrounds are at greatest risk and are responsible for much of the rise.
In addition to the above information, one should gather historical data about food intake patterns, nutritional knowledge, family meal habits, previous attempts to intervene, television-watching habits, and exercise frequency and duration. A 3-day food record is often helpful. Questions should be asked to determine the family's perception of the problem and whether there has been an impact on body image, self-esteem, social interactions, and school performance.
Accurate anthropometric measurements of height and weight should be obtained in a sensitive manner and plotted on the appropriate growth chart. Previous height and weight measurements are helpful, since they permit calculation of growth velocities and visual display of growth patterns. Blood pressure should be checked using a cuff of appropriate size.
Fat distribution (central or gynoid) and body habitus should be described along with the presence or absence of acanthosis nigricans. When present, acanthosis is typically seen at the base of the neck and in the axillae, anogenital area, and skin folds. It is velvety in appearance and has a brown-black color. Many times, patients and parents think the acanthosis is dirty skin and unsuccessfully try to remove it with soap and water. Acanthosis is a helpful physical sign, since it is a manifestation of hyperinsulinism and insulin resistance.
Increased androgen effects, such as acne and increased terminal hair, are also helpful physical signs because of their association with insulin resistance. Inspection and palpation of the thyroid gland should be done as part of a thorough general evaluation that includes cardiovascular and abdominal exams as well as Tanner staging.
Laboratory Testing and Imaging
Depending on the clinical presentation, the following studies should be considered: fasting blood glucose and insulin, lipoproteins (cholesterol, high-density lipoprotein, triglycerides), cortisol, free T4, thyroid-stimulating hormone, serum acetone, hemoglobin A1c (HbA1c), and urinalysis (glycosuria, ketonuria). Islet cell antibodies and glutamic acid decarboxylase autoantibodies may prove useful in differentiating the type of diabetes if insulin resistance is absent or the obesity is not marked. A karyotype and specialized genetic studies may be necessary if unusual phenotypic features are present to suggest a chromosomal syndrome that may be associated with insulin resistance and obesity. In some cases, an oral glucose tolerance test or home monitoring using a blood glucose meter may prove helpful.
Insulin resistance in children and adolescents is often associated with advanced skeletal maturation, so a radiograph of the left hand and wrist may be indicated for assessment of bone age.
The differential diagnosis of children and adolescents who present with excessive weight gain and obesity includes insulin resistance with or without diabetes mellitus, hypercortisolemia, hypothyroidism, excessive caloric consumption (exogenous), and chromosomal disorders (e.g., Prader-Labhart-Willi syndrome). If fasting plasma glucose exceeds 126 mg/dl or if glucose is >200 mg/dl when checked randomly or at 2 h after eating a meal or during a glucose tolerance test, then that child or adolescent has diabetes.
Classification of the type of diabetes is sometimes confusing. When obesity is present along with evidence of insulin resistance (acanthosis nigricans and/or insulin-to-glucose ratio >0.20) and there are no islet autoantibodies, then that child has type 2 diabetes. The presence of autoantibodies, with or without obesity, indicates type 1A (autoimmune) diabetes. If the patient is AfricanAmerican and has a family history (autosomal dominant with onset at <40 years of age), the presentation is more acute, insulin sensitivity is normal, acanthosis and autoantibodies are absent, and the obesity is not marked, then the patient most likely has atypical diabetes. Normal insulin sensistivity and the absence of obesity, acanthosis, and autoantibodies in a Caucasian patient who has a family history (autosomal dominant in three or more generations) is consistent with maturity-onset diabetes of youth (MODY). The absence of autoantibodies in a patient who is not markedly obese and who does not have a family history is typical of type 1B (idiopathic) diabetes.
During the process of classification, it is important to remember that the presence of ketonuria may not be a reliable indicator of diabetes type, since up to 33% of children with type 2 diabetes spill ketones at the time of diagnosis. In newly diagnosed children and adolescents, type 2 diabetes accounts for about 1020%, atypical diabetes 510%, type 1B 57%, and MODY is rare.8,9 An approach to diagnostic evaluation and classification is summarized in Figure 1.
Given its beneficial effect on insulin sensitivity, regular aerobic exercise is the mainstay of treatment for obesity, with or without diabetes. Ideally, the exercise should be daily for about 2030 min. A sustained heart rate of about 80% of maximum is a reasonable goal. Initially, this target may be difficult to attain and will only be reached after several weeks of conditioning. Target heart rate is calculated using the following formula: beats per minute = 0.80 (220 age in years).
Although elegantly simple, regular exercise is often difficult for many children and adolescents. Schedules and inaccessibility of exercise equipment, safe places to walk, and swimming pools are often mentioned as impediments. Even in homes where exercise bicycles and treadmills are available, it is a challenge for many older children and adolescents to establish a routine given the distractions of video games and television. For younger children, use of exercise equipment is not practical. Consequently, the best solution is often an organized activity such as soccer, basketball, gymnastics, or tae kwon do. Frequent family visits to community athletic facilities are often successful. Private athletic clubs may be helpful, too, since many have personal trainers available who can help design exercise routines and provide motivation.
Clearly, the type of exercise must be customized for each patient and coupled with a form of motivation that will lead to a regular routine and the confidence that success breeds. Even though significant weight loss may not occur, the improvement in insulin sensitivity that derives from regular exercise will often produce much better glycemic control.
Many people mistakenly believe that a diet is the solution to obesity. In growing children and adolescents, however, a marked reduction in caloric and nutrient intake may have a deleterious effect on height gain. Furthermore, a reduction in caloric intake will not necessarily lead to improvement in the patient's obesity, since insulin sensitivity is not typically facilitated by dietary restriction alone. Successful weight reduction occurs when insulin resistance decreases, and that effect is most readily achieved in conjunction with exercise.
A nutrition consultation, after keeping a 3-day food history, is often helpful, since it provides an opportunity for dietary education. During the course of the consultation, the benefits of a diet that limits carbohydrate consumption and fat can be discussed. Portion size, appropriate calories for age, and ideas for healthy food choices should also be presented. Avoidance of eating while watching television and encouragement of positive family habits, such as eating together, are also helpful topics, since parents and other members of the family are often overweight, too.
If diabetes occurs, then further instruction to help ensure blood glucose consistency may prove beneficial. An excellent resource for this purpose is Guiducci's book, Diabetes and Kids: A Guide to Nutrition.10
The use of oral hypoglycemic agents in the pediatric population is limited, since many patients are able to achieve acceptable glycemic control through exercise and healthy eating. If diabetes is not adequately controlled, however, then sulfonylureas and metformin (Glucophage) are typically prescribed.
In our clinic, we have used either glyburide (DiaBeta, Micronase, Glynase) or metformin. Recently, we have prescribed metformin more often than glyburide, since it does not produce hypoglycemia when used as monotherapy, and it appears to improve insulin sensitivity and help with the androgen overproduction that accompanies insulin resistance. Metformin should be used with caution, however, in patients who are ketosis-prone because of the risk of lactic acidosis.
If monotherapy does not lead to acceptable control, then combination therapy with glyburide and metformin is a consideration. The attendant problems with combination therapy, though, are the risk of hypoglycemia and poor adherence. These problems are especially worrisome in adolescents, who are the ones most likely to need combination therapy as a result of their schedules, exercise routines, and desire to not appear different from their peers.
The other option if monotherapy is insufficient is insulin. However, the use of insulin is accompanied by concerns related to weight gain and the need for a more complex management routine.
In general, we have avoided the use of acarbose (Precose), a nonabsorbable-glucosidase inhibitor, because of its side effects (flatulence, abdominal bloating, and diarrhea). At present, the use of thiazolidenediones, which are insulin sensitizers, is not recommended in the pediatric population given the association of troglitazone (Rezulin [withdrawn from the U.S. market at press time]) with liver toxicity. Additional studies to examine the safety and efficacy of other drugs in this class, including rosiglitazone (Avandia) and pioglitazone (Actos), are needed to define their potential benefit in children and adolescents.
Lifestyle issues are of great importance in the pediatric population, in terms of both pathogenesis and management of type 2 diabetes. In many instances, the issues facing children are similar to those seen in adults.
Glasgow and his colleagues at the Oregon Research Institute have studied barriers that keep people from optimal diabetes management.11 In their studies of both type 1 and type 2 diabetes, they found that the activities related to diabetes management that were seen as presenting significantly more barriers also were the activities that yielded the lowest adherence scores. Four general activities that patients and family members must do are control the diet, maintain an adequate exercise regimen, take medication (insulin or oral agents), and monitor blood glucose levels. The results of the work by Glasgow's group imply that tasks resulting in more rapid feedback, such as taking medication or insulin, were the least likely to be skipped and thus provided the least barriers. Activities that were long-term in nature and provided no clear-cut feedback were more likely to be seen as presenting significant barriers to good diabetes care.
The implications of the above results indicate that the most challenging barriers facing children, adolescents, and their families are related to their choice of appropriate long-term lifestyle activities, such as regular exercise and healthy eating. These lifestyle decisions are happening at a time when all members of the family are spending more time using computers, watching television, and playing video games. Consequently, a conscious effort must be made within families to modify the sedentary lifestyle activities that are contributing to the risk of obesity and type 2 diabetes. These efforts need to be modeled by parents and directed at all family membersnot just the one with obesity or newly recognized type 2 diabetes. Helpful suggestions that can be adapted for these purposes are found in Wysocki's book, The Ten Keys to Helping Your Child Grow Up With Diabetes.12
As with type 1 diabetes, the foundation for success is education. As a result, children and adolescents with obesity and their parents should receive a clear explanation about the pathogenesis of obesity and the associated risk of developing type 2 diabetes. The rationale for diagnostic testing, monitoring, exercise, and healthy eating should be discussed.
If overt diabetes occurs, then additional education about management is necessary. A team approach is essential. A patient's primary care provider, diabetes specialist, diabetes nurse educator, nutrition educator, and psychologist are all key members of the team that works closely with the patient and family to design a customized care plan that takes into consideration ethnic background. If medication is used, a pharmacist may also play a valuable role in the educational process. Additional people who should be made aware of the care plan may include, but are not limited to, the patient's school nurse, teacher, coach, physical education instructor, and school secretary. Successful application of the care plan is clearly the product of a cooperative team working in harmony.
Patients should receive a blood glucose meter along with instructions about how to do fingerstick blood glucose readings at home. Ideally, measurements are done before breakfast and 2 h after a meal each day. The goals at our clinic are a fasting blood glucose of 80120 mg/dl and a 2-h postprandial reading of <180 mg/dl.
If a patient is receiving glyburide as monotherapy or in conjunction with metformin or insulin, then education should be provided about the prevention and treatment of hypoglycemia.
Visits to the clinic for education and adjustment of the treatment plan need to be tailored to patients and their family. An HbA1c should be done every 3 months. Our clinic's goal is an HbA1c of <7%, which correlates with an average blood glucose of <150 mg/dl.
If a child or adolescent who is being treated with exercise and diet has results that exceed these levels, then the addition of an oral hypoglycemic agent needs to be considered. Combination therapy with metformin or insulin may be needed if the HbA1c and average blood glucose do not improve with monotherapy. In patients who have overt diabetes, annual eye examinations, urine microalbumin testing, and lipoprotein profiles are necessary.
Treatment guidelines are summarized in Figure 2.
The best strategy to prevent type 2 diabetes in the pediatric population is to identify children and adolescents with obesity who are at risk and then intervene with regular exercise and healthy eating. However, successful implementation of this strategy will require an increased awareness among parents, health care providers, and school personnel about the relationship between obesity and decisions that promote more sedentary lifestyles and increased consumption of convenience foods that are high in carbohydrates and calories. Lifestyle intervention must also recognize the critical roles of ethnic background, family functioning, and genetics in the pathogenesis of obesity.
Clearly, we are facing a huge challenge. We must rise to the occasion, though, if we are to ensure the future health of our youth.
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10Guiducci L: Diabetes and Kids: A Guide to Nutrition. Portland, Ore., Nutrition and Kids, 1997.
11Glasgow RD, McCaul KD, Schafer LC: Barriers to regimen adherence among patients with insulin-dependent diabetes mellitus. J Behav Med 9:65-77, 1986.
12Wysocki T: The Ten Keys to Helping Your Child Grow Up With Diabetes. Alexandria, Va., American Diabetes Association, 1997.
James R. Hansen, MD, is the medical director and Maya K. Hunter, MD, is a staff endocrinologist at Emanuel Children's Diabetes and Endocrine Center in Portland, Ore. Michael J. Fulop, PsyD, is a clinical psychologist who specializes in diabetes at the Emanuel Children's Diabetes and Endocrine Center and at the Behavioral Diagnostics and Treatment Clinic in Portland, Ore.
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