The incidence of Type 2 diabetes, once called adult-onset diabetes, among American children is increasing. Although the exact number of children affected by Type 2 diabetes is unknown, the American Diabetes Association (ADA) states that the incidence is reaching alarming proportions.1 Type 2 diabetes has lifelong health complications including premature heart disease, stroke, blindness, kidney disease, and amputation. Clinicians will soon see lifelong health complications in patients at earlier ages.
According to the ADA, more than 15 million U.S. adults are being treated for Type 2 diabetes;1 however, the exact number of children with the disease is unknown. The incidence of Type 2 diabetes is associated with obesity, and the American Academy of Pediatrics estimates that one in five U.S. children is obese.2
In the past, only 1% to 2% of all children with diabetes were thought to have Type 2 diabetes. Researchers now estimate that 8% to 45% of all children with a recent diabetes diagnosis have Type 2 diabetes.1
Ethnic differences affect the incidence of Type 2 diabetes. In 1979, the first case of Type 2 diabetes was reported in a Pima Native American teenager in Arizona. An analysis from 1992 to 1996 revealed disease prevalence of 22.3 per 1,000 in 10 to 14-year-olds and 50.9 per 1,000 in 15 to 19-year-olds. Between 1988 and 1996, the Indian Health Service documented a 54% increase in prevalence of reported Type 2 diabetes cases in 15 to 19-year-olds.
The body's control of glucose depends on the balance between insulin secretion by pancreatic beta cells and insulin action, When an imbalance exists, hyperglycemia develops. Type 2 diabetes can present in two ways or a combination of both. First, the insulin produced by beta cells cannot be properly used, which causes beta cells to overproduce insulin, leading to hyperinsulinemia. The liver tries to compensate for the lack of used glucose, producing more and increasing the glucose level in the body. Second, the pancreas begins to fail in the production of insulin and demand is overcome by supply, resulting in hyperglycemia.
The primary activity of insulin is the regulation of glucose metabolism. Insulin also has several anabolic and catabolic actions on tissues. In muscle, insulin causes the rapid transmission of glucose and amino acids intracellularly, promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose to fat. Diabetes results when the pancreas either does not produce insulin (Type 1) or cells become resistant to insulin, with a progressive decline in insulin production (Type 2). The clinical presentation in children with Type 2 diabetes suggests that the initial abnormality is impaired insulin action, compounded with later beta-cell failure.
Puberty plays a role in the development of Type 2 diabetes in children. During puberty, resistance to insulin is increased, resulting in hyperinsulinemia. Hyperinsulinemic-euglycemic clamp studies have shown that insulinmediated glucose disposal is an average of 30% lower in adolescents between Tanner stages II and IV compared with prepubertal children in Tanner stage I and with young adults.3 Increasing levels of growth hormone most likely cause increased insulin resistance during puberty. When puberty is complete and growth hormone decreases, insulin resistance decreases. Thus, when children who are at a risk for developing Type 2 diabetes experience puberty, hyperglycemia develops. Hyperglycemia develops when insulin resistance is present and the pancreas cannot maintain insulin production.
The adverse effect of obesity on glucose metabolism is seen early in childhood. In healthy Caucasian children, total adiposity accounts for approximately 55% of the variance in insulin sensitivity? Obese children are hyperinsulinemic and have about 40% lower insulin-stimulated glucose metabolism compared with nonobese children. The amount of visceral fat in obese adolescents is directly correlated with insulin sensitivity.3
Clinicians should consider several factors when deciding whether a child is at risk for developing Type 2 diabetes: obesity, ethnicity, family history, sex, and age. Obesity is a hallmark symptom of Type 2 diabetes. According to the ADA, 85% of children with Type 2 diabetes are either overweight or obese at the time of diagnosis.1
African Americans, Hispanics, and Native Americans4 have an increased hereditary risk of Type 2 diabetes development, as an increased adult incidence exists in each of these populations.5 African-American children have higher insulin levels than other agematched Caucasian children. These two factors may predispose African Americans to Type 2 diabetes.1
Family history is another risk factor for Type 2 diabetes development. According to the ADA, 45% to 80% of children with Type 2 diabetes have at least one parent with diabetes and may have a family history of diabetes that spans several generations.1 In children with a family history, 74% to 100% have a first- or second-degree relative with the disease. Researchers have concluded that a maternal family history of diabetes is an important risk factor for children.6
A child's sex and age are additional risk factors for Type 2 diabetes. According to the ADA, U.S. women are more often diagnosed with Type 2 diabetes than men. Studies of children also indicate that the incidence among female children is higher than the incidence among male children. The mean age of children diagnosed with Type 2 diabetes is between 12 and 16.1
An ADA consensus panel has delineated which children should be tested for Type 2 diabetes. A substantial number of children with Type 2 diabetes can be detected when they are asymptomatic. If a child is overweight and has two other risk factors, testing should be performed every 2 years starting at age 10, or at the onset of puberty if it occurs prior to age 10. A fasting plasma glucose is the preferred testing method. ADA testing criteria are provided in Table 1. These criteria, however, should not be applied to the exclusion of clinical judgment. Testing should be performed on any high-risk or symptomatic child who does not meet these criteria.
Diabetes must be diagnosed before the clinician can specify whether Type 1 or Type 2 is present. The ADA's diagnostic criteria are provided in Table 2. Table 3 outlines the symptomatology and clinical presentation of diabetes Types 1 and 2.'1 The American College of Endocrinology issued guidelines for glycemic control, recommending that glycosolated hemoglobin be universally adopted as the primary assessment of glycemic control. They also recommended a fasting blood glucose level target of less than 110 mg/dl and a 2-hour post-prandial glucose level of less than 140 mg/dl.7 The ADA, along with the centers for Disease Control and Prevention and the National Institutes of Health, are reviewing these recommendations and evaluating the need to update clinical practice recommendations.
The type of diabetes can usually be identified in most patients. If the clinician is unsure which type is present, additional testing should be performed, such as fasting levels of C-peptide, a precursor to insulin, and insulin levels. In Type 2 diabetes, these levels are generally normal or elevated. Beta cell autoantibody measurements can also be measured and should be absent in Type 2 diabetes cases.1
Several medical conditions can be seen in tandem with Type 2 diabetes: acanthosis nigricans (hyperpigmented patches of skin, which is present in 90% of children with Type 2 diabetes), hyperlipidemia, hypertension, and polycystic ovary syndrome. These conditions may aid the clinician in identifying children at risk for diabetes.1
First-line treatment for Type 2 diabetes in children depends on symptom severity at diagnosis. Critically ill children with diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic states must be immediately referred to pediatric or adolescent endocrinologists. Clinical symptoms suggesting initial treatment with insulin include dehydration, ketosis, and acidosis. High morbidity and mortality rates are associated with these conditions; therefore, appropriate referral is necessary.
When patients are diagnosed with Type 2 diabetes and are not acutely ill, clinicians can begin treatment with lifestyle modifications, such as diet and exercise. Lifestyle modifications are key factors in diabetes management. The clinician should arrange a child and family consultation with a dietician. Changes in lifestyle to decrease sedentary activity and increase physical activity should be encouraged. Successful treatment with diet and exercise is achieved when cessation of excessive weight gain exists with normal linear growth.
If diet and exercise do not result in plasma glucose levels of less than 126 mg/dl and glycosolated hemoglobin AIC levels less than 7%, pharmacologic therapy should be considered. Currently, insulin therapy is the only approved drug for diabetes treatment in children. Pediatric diabetologists, however, commonly treat these children with oral glucose-lowering drugs. Little evidence exists to suggest that insulin is superior to oral agents for the initial treatment of children who are not critically ill.8
Five types of oral, glucose-lowering drugs are available in the United States. The pathophysiology of Type 2 diabetes in children, adolescents, and adults appears similar. Children are treated with these drugs; however, safety and efficacy data are not available nor have these drugs been specifically approved for children.
The biguanides, sulfonylureas, meglitinides, and the alpha-glucosidase inhibitors have been used successfully to treat children with Type 2 diabetes. The thiazolidinediones, however, have been associated with fatal hepatic failure; consequently, they are not recommended for children.
Metformin (Glucophage), a biguanide, is generally the first drug used. Biguanides decrease hepatic glucose output and enhance hepatic and muscle insulin sensitivity, directly affecting beta cell function. Researchers have examined the use of metformin in the pediatric population (ages 10 to 16) and concluded that metformin is safe and effective as first-line therapy for children with Type 2 diabetes when diet alone is not sufficient to normalize glucose levels.9 Metformin, which does not have the same risk of hypoglycemia as does the sulfonylureas, reduces hemoglobin Arc and overall glucose levels. Metformin has been found to stabilize or lower weight and lower low-density lipoproteins, cholesterol, and triglyceride levels.
Metformin is contraindicated in patients with renal insufficiency because of the risk of lactic acidosis. Metformin-dri use should be discontinued with administration of any radiographic contrast or any condition that requires hospital admission. Use is also contraindicated in patients with hepatic disease, severe infections, or hypoxemia metformin. Gastrointestional disturbance is the most common adverse effect.1
Metformin treatment may normalize ovulatory abnormalities in girls with polycystic ovary syndrome and increase the risk of unplanned pregnancy. Preconception and pregnancy counseling should be part of the treatment regimen for all girls of childbearing age.8
Glycemic control should be evaluated at 3- and 6-month intervals from the time of diagnosis. If monotherapy with metformin is not sufficient, a second drug should be considered, such as insulin or a sulfonylurea. Other insulin secretogogues, such as meglitinide, or a glucosidase inhibitor maybe considered but have been used less frequently in children.
Special consideration should be given to children with extremely high glucose levels and symptomatic children. Initiating treatment with insulin to regulate the glucose level may be the most effective method to bring hyperglycemia and symptoms under control. Insulin therapy may include bedtime insulin alone, twice daily insulin, or a multidose regimen, depending on home glucose readings, daily activity levels, and patient adherence. Once glucose levels are stabilized, adding metformin and decreasing insulin is a therapeutic option. Monitoring for urine ketones during this period may identify patients with Type 1 diabetes who have been misdiagnosed.
Clinicians must also screen patients for diabetes complications. The ADA recommends yearly eye examinations and microalbumin screening and yearly monitoring for hypertension and hyperlipidemia. Foot screenings should be performed at each office visit.1
Early identification of patients at risk for developing Type 2 diabetes is the first step in the prevention process. Lifestyle modification and patient and family education is essential and may help prevent or delay disease onset. Weight management, nutrition counseling, and increased physical activity are integral parts of effective lifestyle modification. A sedentary lifestyle is strongly associated with development of Type 2 diabetes; therefore, patients should exercise for 30 minutes each day and limit sedentary activities such as television and computer games. Appropriate pharmacologic therapy coupled with patient education can help improve symptom management and quality of life for patients and their families.
1. American Diabetes Association: Type 2 diabetes in children and adolescents. Diabetes Care 2000;23(3):381-89.
2. Dietz WH: Health consequences of obesity in youth: Childhood predictors of adult disease. Diabetes Care 1998;101(3):518-27.
3. Arsinian SA, Kalhan SC: Correlations between fatty acid and glucose metabolism: Potential explanation of insulin resistance of puberty. Diabetes
4. Huether SE, Tomky D: Alterations of hormonal regulation. In: SE Huether, McCance KL, eds. Pathophysiology: The biologic basis for disease in adults and children. St Louis, Mo.: Mosby, 1998;656-706.
5. Kim TF: Diabetes type 1 or type 2? Factors to consider. Family Practice News 2000;30( 10):53.
6. Bjomholt J, Ern Erikssen G, et al.: Type 2 diabetes and maternal family history: An impact beyond slow glucose removal in low-risk individuals? Results from 22.5 years of follow-up of healthy nondiabetic men. Diabetes Care 2000;23(9):1255-62.
7. Chernin T: New diabetes guidelines call for more aggressive screening. Drug Topics 2001;(9):20.
8. Type 2 diabetes in children and adolescents. Pediatrics 2000;105(3):671-80.
9. Arslanian S, Jones K, Mcvie R, et al.: Metformin improves glycemic control in children with type 2 diabetes. Diabetes 2000; 49(5):A75.
Deborah Kupecz, NP PhD
Drug News Editor
Jennifer Glenn, RN, MSN
ABOUT THE AUTHOR
Jennifer Glenn, RN, MSN, is a family nurse practitioner in the emergency department, Fort Sanders Parkwest Hospital, Knoxville, Tenn.
Copyright Springhouse Corporation Dec 2001
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