• Gahagan S, Silverstein J. Prevention and treatment of type 2 diabetes mellitus in children, with special emphasis on American Indian and Alaska Native children. American Academy of Pediatrics Committee on Native American Child Health. Pediatrics 2003 Oct;112(4):e328-e347. [137 references] PubMed

Weight and height should be plotted on a growth chart. The weight goal should be based on BMI (weight [kg]/height² [m²]). (The Web site for growth charts is: www.cdc.gov/nchs/about/major/nhanes/growthcharts/charts.htm.) Weight should be measured at each visit, but height may be measured twice a year.

The blood pressure goal is less than the 90th percentile on the basis of height and weight standards. The blood pressure is assessed at each visit. Blood pressure control is discussed in "Reducing Cardiovascular Risk" (see below and Table 3 in the original guideline).

The skin, especially the back of the neck, the underarms, and the groin, should be evaluated for acanthosis nigricans, a thickened, hyperpigmented skin condition (see Figure 1 in the original guideline). Acanthosis nigricans often correlates with high BMI and insulin resistance. The resolution of acanthosis nigricans may be a useful marker for decreasing insulin resistance. Insulin resistance may improve as weight decreases. The improvement of the skin condition as a result of better metabolic control is highly desirable to adolescents. Therefore, identification of this condition is especially useful as a motivator for adolescents. Other treatable skin conditions may occur in association with insulin resistance, including tinea capitis, tinea corporis, and tinea pedis. Hirsutism or significant acne may be markers of hyperandrogenism in girls. Hirsutism is related to hyperinsulinism and is another potential motivating factor for adolescents to accomplish nutritional and physical activity goals.

A thorough visual inspection of the feet, including pedal pulses (posterior tibial and dorsalis pedis) and a neurologic examination are recommended shortly after diagnosis and then annually (see Figure 2 in the original guideline). The monofilament examination for foot sensation is included to assess protective sensation. This examination is performed using the 5.07 (10-g) Semmes-Weinstein nylon monofilament mounted on a holder that has been standardized to deliver a 10-g force when applied properly. Because the sensory deficits appear first in the most distal portions of the foot and progress proximally in a "stocking" distribution, the toes are the first areas to lose protective sensation. The examination should include assessment for treatable nail conditions, such as paronychia and ingrown toenails. The main purpose of the foot examination in children is to teach that foot care is an important health habit.

A funduscopic examination with dilation to detect signs of diabetic retinopathy is recommended shortly after diagnosis and then annually by an experienced eye care professional.

Yeast vaginitis and balanitis are commonly seen in children and adolescents with type 2 diabetes mellitus. Inspection of the vulva and penis should be included in the physical examination to screen for yeast vaginitis and balanitis. Tanner staging of children and adolescents with type 2 diabetes mellitus should be performed every 3 to 6 months until puberty is complete, because early onset of puberty is noted in overnourished children. A gynecologic examination for girls and a genital examination for boys may provide an opportunity to obtain additional sexual history and to offer abstinence and contraceptive counseling. Menstrual irregularities may be symptoms of PCOS in postpubertal girls.

Laboratory Evaluation

The fasting plasma glucose (FPG) concentration is the standard test for diagnosis. Monitoring is based on the FPG concentration and additional blood glucose measurements throughout the day. Fasting is defined as no consumption of food or any beverage other than water for at least 8 hours before testing. Most monitoring is performed by self-monitoring of blood glucose (SMBG) concentrations. Tables 4 and 5 in the original guideline include diagnostic and self-monitoring values.

The 2-hour postprandial glucose test provides information about glucose metabolism that is not provided by FPG measurement. It can be used for diagnosis together with FPG testing and must be used for monitoring.

Measurement of glycosylated hemoglobin (HbA_1c) concentration should be performed quarterly. The results should be available at the time of the patient visit and discussed with the patient. Many diabetes clinics have standing orders for the performance of HbA_1c testing before the health care professional's consultation and discussion with the patient. The HbA_1c result can verify SMBG data and is useful for identifying the need to adjust insulin dosage when SMBG data are unavailable. Setting realistic short- and long-term goals in consultation with a pediatric endocrinologist or other health care professional knowledgeable about childhood type 2 diabetes mellitus is recommended whenever possible. The HbA_1c concentration goal is less than 7.0% (or <1% above the laboratory reference range). This may not be achievable for all patients. Realistic goals should be individualized for each patient. HbA_1c concentration greater than 8.0% is associated with a substantial increase in complications. Any sustained decrease is beneficial.

It is important to screen for proteinuria at diagnosis and annually. Testing for microalbuminuria is indicated if proteinuria is absent. Microalbuminuria is a high urinary albumin concentration that is not detected on routine dipstick testing. Microalbuminuria is defined as a urinary albumin excretion of 20 to 200 micrograms per minute (30–300 mg per day). Annual screening for microalbuminuria permits early identification and treatment of patients who are at risk of nephropathy. The recommended method of detection is the measurement of the albumin-creatinine ratio in a spot urine collection. An alternative method uses reagent tablets or dipsticks that detect microalbuminuria. When positive, the results of rapid tests should be confirmed by the urinary albumin-creatinine ratio in a timed urine collection. A patient is not designated as having microalbuminuria unless 2 of 3 collections performed within a 3- to 6-month period show increased concentrations. This test is not valid if the patient has a urinary tract infection or during menses. Although microalbuminuria may be encountered in patients in whom type 2 diabetes mellitus is newly diagnosed, proteinuria is the hallmark of diabetic nephropathy (Figure 3 in the original guideline).

The serum creatinine concentration should be determined at diagnosis and when indicated for drug therapy. Annual serum creatinine screening is indicated for patients with hypertension or microalbuminuria and for people taking angiotensin-converting enzyme (ACE) inhibitors.

A fasting lipid profile, including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride concentrations, should be performed after diagnosis. The fasting lipid profile is best obtained after initial metabolic stabilization (1--3 months after diagnosis). The primary goal of therapy is to lower the LDL concentration, which is discussed further in "Reducing Cardiovascular Risk" (see below).

Liver function tests, including aspartate transaminase and alanine transaminase, should be performed before initiation of oral hypoglycemic therapy. Additional monitoring may be required depending on the person's drug regimen.

The concentrations of C peptide and insulin should not be measured routinely. When differentiation between type 1 and type 2 diabetes mellitus is difficult, consultation with a subspecialist with expertise in type 2 diabetes mellitus in children and adolescents is recommended. There currently is no definitive diagnostic tool to differentiate between type 1 and type 2 diabetes mellitus. The differentiation typically is made clinically on the basis of obesity, family history, ethnicity, age, pubertal status, and evidence of insulin resistance (e.g., acanthosis nigricans, PCOS).

Treatment

Goals of Treatment

The goals of treatment are adequate metabolic control (HbA_1c concentration <7%) and prevention of microvascular and macrovascular complications. More specific treatment objectives include the following:

• Eliminating symptoms of hyperglycemia
• Assisting the patient in maintaining a reasonable body weight (weight stabilization)
• Decreasing cardiovascular risk factors: hypertension, hyperlipidemia, hyperglycemia, microalbuminuria, sedentary lifestyle, and use of tobacco products
• Achieving overall improvement in the child's physical and emotional well-being

Recommended treatment modalities include dietary modification, increased physical activity, decreased sedentary behaviors, and pharmacologic intervention (primarily metformin and insulin). Therapy to achieve these goals should be individualized on the basis of the child's age, other illnesses, lifestyle, self-management skills, and level of motivation. Education and other interventions that enhance self-care behaviors are essential for the successful management of type 2 diabetes mellitus. In general, weight loss is not recommended for prepubertal children. Children with morbid obesity and resultant health consequences, such as sleep apnea, may be referred to a subspecialist for weight reduction or a multidisciplinary child obesity clinic. Weight stabilization is the goal until girls are menstruating and boys have reached Tanner stage 5. After pubertal growth is complete, weight loss may be appropriate.

Barriers to Care

Refer to the original guideline for a discussion of barriers to care, including barriers for AI/AN youth.

Team Management

Multidisciplinary team management is strongly recommended for youth with type 2 diabetes mellitus. A primary health care professional alone usually cannot provide focused diabetes education, nutrition management, and psychosocial support. The team usually is composed of a physician, a registered dietitian, a nurse clinician, a social worker, and the patient and the family. The patient and the family are integral members of the team, and participation of the child or adolescent with the diabetes team should be frequent and ongoing. The diabetes team monitors the patient's knowledge about diabetes and its acute and chronic complications. The team also assesses and monitors the patient’s knowledge and attitudes toward nutrition and physical activity. In addition, the team promotes the use of medications, SMBG, and problem-solving skills. Screening for barriers to self-care is recommended at each visit. The team assists in identification of achievable self-care goals that are appropriate for age and development level.

Many AI/AN health care facilities have existing diabetes clinics with multidisciplinary teams. It is highly recommended that these clinics organize a pediatric component so that youth receive developmentally appropriate care.

Lifestyle Modifications

The cornerstones of initial treatment of type 2 diabetes mellitus are acquiring and integrating healthful behaviors in nutrition, exercise, and weight management. Frequent contact with the health care team is required to accomplish these goals. The approach to healthful living must be emphasized throughout diabetes treatment. Initially, type 2 diabetes mellitus in asymptomatic youth may be managed by lifestyle modification without adjunctive medication. Basic diabetes education, counseling, and SMBG should be included. The natural history of type 2 diabetes mellitus is one of progressive insulin insufficiency and deterioration of metabolic control. Therefore, close monitoring and follow-up are important. Eventually, most people with type 2 diabetes mellitus require medication to achieve adequate metabolic control (Tables 4 and 5 in the original guideline).

Management Tools

Self-monitoring of Blood Glucose (SMBG)

The frequency of SMBG should be individualized. Daily fasting and 2-hour postprandial (after-dinner) glucose measurements are recommended. More frequent monitoring is recommended during initiation of treatment. Furthermore, monitoring frequency should be increased during the following situations: insulin treatment, medication dosage adjustments, initiation of new therapies, increased activity, rapid growth, illness, and emotional stress. The frequency of SMBG may be negotiated with the patient and the family. For people who take insulin, the recommended frequency of SMBG is before every meal and at bedtime. The recommended method is a blood glucose meter with memory. It can be instructive for patients to record their blood glucose results in a log to determine patterns. Reviewing these results with the patient at each visit is recommended. Many patients on medication will learn to make their own dosage adjustments on the basis of blood glucose patterns.

• Ideal targets: more than 50% of SMBG concentrations within target range:
  • Fasting: 80 to 120 mg/dL (4.4--6.7 mmol/L)
  • Postprandial (2 hours after start of meal): 100 to 160 mg/dL (5.6--8.9 mmol/L)
  • Bedtime: 100 to 160 mg/dL (5.6--8.9 mmol/L)

Medical Nutrition Therapy

Meal planning, nutrition education, and exercise are primary treatment strategies for type 2 diabetes mellitus. All people with diabetes should receive regular nutrition counseling and consult with a registered dietitian or nutritionist or a diabetes educator at least every 6 to 12 months. Some children may require more frequent evaluation and counseling. The success of the child in adopting healthful eating habits is much more likely when the entire family follows the dietary recommendations. Other family members may be able to serve as role models. Assisting the family and the patient in change related to eating behavior is recommended. For example, some families will choose to purchase more fruits and vegetables and make them more readily available to all family members. Families may choose to discourage eating outside of mealtimes and make rules about limiting eating while watching television. Weight management must be individualized for the patient initially and in follow-up visits. Each encounter is an opportunity for nutritional education.

Diabetes Education

Patients and their families require diabetes self-care information that is culturally relevant. It is important to recognize that there are many different tribal cultures. The National Standards for Diabetes Care and Patient Education provide guidelines for education program development with criteria specific for Native American health care facilities. In addition, adolescents have distinct needs related to the culture of youth.

Education alone is not enough to motivate people to adopt more healthful behaviors. Children and adolescents, in particular, are not easily motivated by long-term health consequences, which seem irrelevant to them. They are more likely to be influenced by immediate concerns, such as physical attractiveness, feelings of well-being and acceptance, and their desire to be able to do more in school or sports. The use of motivational interviewing or collaborative problem solving may be useful in helping children and adolescents make and maintain necessary behavior changes.

Physical Activity Education

Physical activity is a cornerstone of the management of type 2 diabetes mellitus. Physical goals should be stated concretely. Exercise is associated with improvement in short- and long-term metabolic control, and physical activity improves insulin sensitivity. All patients should be assessed for level of fitness and current exercise routines. Recommendations should be based on the patient's needs and current condition. It is important to assess the opportunities available within the family and the community. Adaptive physical education classes may be helpful for children who are overweight. Youth with obesity and type 2 diabetes mellitus are not likely to participate in organized sports, so other physical activity strategies are needed. Activities of daily living can be adapted to increase physical fitness. Sedentary activities should be limited, and positive alternatives should be emphasized. When making behavioral changes, simple, achievable goals promote efficacy. Children and adolescents are more likely to accept fitness goals when they are framed in terms of feeling better, looking better, or doing more.

Preconception Counseling and Management

A sexual activity history should be obtained at diagnosis in postpubertal youth. Counseling about the necessity of metabolic control for healthful pregnancy outcomes should start at puberty. Abstinence counseling should be provided, if appropriate. Family planning options should be discussed with adolescents who are or may become sexually active. Pregnancy should be deferred until optimal glycemic control has been achieved to decrease first-trimester risks to the fetus, including congenital heart disease, caudal regression, and neural tube defects, and third-trimester risks of macrosomia, neonatal hypoglycemia, and hypocalcemia, all of which are common in preexisting type 2 diabetes mellitus and gestational diabetes. All oral hypoglycemic agents are contraindicated during pregnancy. Furthermore, treatment of diabetes may increase fertility and the likelihood of pregnancy in young women. Metformin, in particular, may improve ovarian function and ovulation.

Immunizations

Usual childhood immunizations (including hepatitis B, influenza, and pneumococcal immunizations) are recommended. Tuberculosis screening by purified protein derivative should be documented once after the diagnosis of diabetes and performed at appropriate intervals, as indicated by community-specific tuberculosis prevalence.

Dental Examinations

Dental examinations are recommended every 6 months. Periodontal disease is more common in people with diabetes than in those without and has been called the sixth complication of diabetes (the other 5 complications involve the heart, kidney, eyes, skin, and feet).

Decreasing Cardiovascular Risk

Identification and Treatment of Hyperlipidemia

Children with type 2 diabetes mellitus are at risk of hyperlipidemia, which compounds their risk of premature cardiovascular disease. Although the American Heart Association recommends that children's total cholesterol concentration be less than 170 mg/dL (<4.40 mmol/L) and the LDL concentration be less than 110 mg/dL (<2.84 mmol/L), the ADA recommends a lower target concentration for LDL in adults with diabetes: less than 100 mg/dL (<2.59 mmol/L). Because of the higher risk of cardiovascular disease in children with diabetes, the lower acceptable value recommended by the ADA is preferred. A lipoprotein analysis after a 12-hour fast is recommended to obtain triglyceride concentrations for computation of accurate LDL concentrations. If a fasting measurement is not possible, then a measurement of the HDL concentration, along with the total cholesterol concentration, will provide an alternative. Other reliable analyses of the lipid profile may become available in the future. Children with an LDL concentration more than 100 mg/dL (>2.59 mmol/L) or a total cholesterol concentration more than 170 mg/dL (>4.40 mmol/L) should receive advice about other risk factors for cardiovascular disease, such as smoking and sedentary lifestyle. High triglyceride concentrations are increasingly recognized as an additional cardiovascular risk factor for people with diabetes. In addition to studies showing the benefit of decreasing the cholesterol concentration in adults, the Bogalusa Heart Study provides evidence that risk factors, such as a low HDL concentration, high triglyceride and LDL concentrations, and smoking, have clinical significance for development of cardiovascular disease beginning in childhood.

The American Heart Association Step-One diet should be initiated for children with high total cholesterol or LDL concentrations. The Step-One diet includes fewer than 30% of total calories from fat, fewer than 10% of total calories from saturated fat, 10% or fewer calories from polyunsaturated fat, and cholesterol of no more than 100 mg/1000 cal. If cholesterol concentrations do not normalize despite a history of adherence to the Step-One diet, then the Step-Two diet is used. For more information, access the American Heart Association's Internet site at http://www.americanheart.org/. The assistance of a registered dietitian or other qualified nutrition professional is necessary to ensure adequacy of nutrients, vitamins, and minerals. Glycemic control, as well as therapy with metformin, can help to lower triglyceride and LDL concentrations. Cholesterol-lowering drug therapy should be considered for children older than 10 years if an adequate trial of diet therapy is unsuccessful after 6 to 12 months. An LDL concentration of 100 mg/dL or more (>2.59 mmol/L) and 1 of the following risk factors or physical inactivity indicate a need for cholesterol lowering medication: family history of premature cardiovascular disease (55 years or younger), cigarette smoking, high blood pressure, low HDL concentration (<35 mg/dL [<0.91 mmol/L]), and obesity (>95^th percentile weight for height).

The recommended cholesterol-lowering medications for children include cholestyramine and colestipol hydrochloride. These medications are difficult to take because of the frequency of dosing and adverse gastrointestinal effects. Although the efficacy and safety of these medications have been documented in children, long-term data on improved morbidity and mortality are lacking.

Blood Pressure Control

In adults, tight blood pressure control has been shown to have a greater impact on cardiovascular disease risk reduction than blood glucose control. Systemic hypertension is defined as systolic or diastolic pressure greater than or equal to the 95th percentile for age. However, for children with type 2 diabetes mellitus, the blood pressure goal is less than the 90th percentile. Accurate blood pressure measurement is critical to the evaluation of suspected hypertension. The patient should be resting and comfortable. Cuff size, the position of the arm, the person's position (sitting or supine), and the speed of inflation and deflation of the cuff can affect the measurement. The cuff bladder width should be approximately 40% of the arm circumference midway between the olecranon and the acromion. The arm should be supported, and the cubital fossa should be at the level of the heart. The bell of the stethoscope should be placed over the brachial artery pulse. The cuff should be inflated to 20 mm Hg above the point at which the radial pulse disappears. The cuff is then deflated at a rate of 2 to 3 mm Hg per second. Automated devices are not as accurate for determining diastolic pressure. The diagnosis of hypertension should be confirmed in 3 separate consecutive examinations. For mild hypertension (slightly above the 95th percentile), the initial assessment should evaluate the possibility of renal disease. The evaluation of severe hypertension (>99th percentile for age) should include an echocardiogram.

Conservative management (e.g., lifestyle changes, such as weight decrease in postpubertal patients, nutrition, and exercise) is recommended as initial therapy. Sodium restriction may be difficult for adolescents. Significant reduction in blood pressure may be noted with weight loss and exercise programs. If blood pressure reduction is not achieved by lifestyle changes, then drug therapy will be necessary. Angiotensin-converting enzyme (ACE) inhibitors are the usual first-line agents because of cardiovascular and renal benefits. Because ACE inhibitors are teratogenic, another agent might be preferable for girls of childbearing age. Beta-blockers are an alternative unless the child is taking insulin, as symptoms of hypoglycemia may be masked.

Smoking and Alcohol Cessation and Prevention and Increasing Physical Activity

Smoking cessation and prevention of smoking initiation are essential for decreasing the risk of cardiovascular problems. Smoking is associated with an increased incidence of diabetes in adults. It is important to screen for tobacco use and advise or refer for tobacco cessation if use is confirmed. Tobacco use information should be updated at each visit. Because of the greatly increased risk of macrovascular and microvascular disease in people who have diabetes and smoke, children and adolescents who do not smoke or use other tobacco products should receive positive reinforcement and information about the importance of continued abstinence.

Alcohol use may aggravate the hypoglycemia caused by sulfonylureas or insulin treatment, and it may increase the risk of lactic acidosis for patients who use metformin. Alcohol and drug use should be assessed at every visit. Adolescents are at risk of substance abuse, which may interfere with the achievement of treatment goals. Anticipatory guidance regarding alcohol avoidance is recommended, including for children and adolescents who do not use alcohol or other drugs. The benefits of not drinking should be emphasized. The effectiveness of creative strategies should be evaluated.

Increasing physical activity is a positive way to decrease risk of cardiovascular complications.

Treatment of Microalbuminuria

Microalbuminuria is a sign of incipient diabetic nephropathy and is a risk factor for cardiovascular complications. Microalbuminuria may be encountered in people who have a new diagnosis of type 2 diabetes mellitus. Proteinuria, conversely, is the hallmark of diabetic nephropathy. ACE inhibitors are indicated for proteinuria or microalbuminuria and have been shown to slow the rate of progression of nephropathy in adults. Improved glycemic and blood pressure control slows the progression of nephropathy. ACE inhibitors are an additional important treatment modality, as shown in the evaluation and treatment algorithm (Figure 3 in the original guideline).

Pharmacologic Management on the Basis of Clinical Manifestations

The options for pharmacologic treatment include insulin; oral hypoglycemic agents, especially metformin; and any combination thereof. Intensive blood glucose control with insulin or sulfonylureas has been shown to decrease microvascular but not macrovascular complications. The choice of medications is discussed in relation to the patient's status at diagnosis. The following sections are given in order of increasing severity and decreasing incidence.

Impaired Glucose Metabolism

Patients with impaired glucose tolerance and impaired fasting glucose have glucose concentrations too high to be considered normal but do not meet the diagnostic criteria for diabetes. They are considered to have prediabetes. Patients with impaired fasting glucose have FPG concentrations of 110 mg/dL or more (>6.1 mmol/L) but less than 126 mg/dL (<7.0 mmol/L). Patients with prediabetes have 2-hour oral glucose tolerance test (OGTT) results between 140 and 200 mg/dL (7.8 and 11.1 mmol/L [Table 5 in the original guideline]). Compared with the FPG, the 2-hour OGTT will identify more people as having impaired glucose tolerance. Although the 2-hour OGTT is more sensitive than the FPG, it is not as reproducible. It is, therefore, important to identify which test was used for diagnosis. An increase in the postprandial glucose concentration precedes an increase in the FPG concentration in adults. The natural history of impaired glucose tolerance in children and adolescents has not been studied. The United States Diabetes Prevention Program has shown that lifestyle interventions are more effective than metformin and both approaches are more promising than conventional treatment in reducing progression to diabetes in adults with impaired glucose tolerance. Similarly, a study of Finnish adults was interrupted because of the success of the lifestyle intervention arm. Patients with prediabetes and their families should receive nutrition and physical activity intervention and support. Their risk of diabetes should be discussed. Monitoring of weight, nutrition, physical activity, and FPG should be performed regularly (at least every 3 months). Some diabetes centers recommend SMBG for high-risk patients with impaired glucose metabolism.

Asymptomatic Diabetes

People with diabetes may be identified as part of community-based case-finding efforts or by primary health care professionals who test asymptomatic children and youth who are at risk of type 2 diabetes mellitus. Patients with an FPG concentration of 126 mg/dL or more (>7.0 mmol/L) or a 2-hour plasma glucose concentration of 200 mg/dL or more (>11.1 mmol/L), using a glucose load of 75 g of anhydrous glucose dissolved in water, but who do not have polyuria, polydipsia, or weight loss are considered to have asymptomatic type 2 diabetes mellitus. When diabetes is identified early, treatment with lifestyle modifications and SMBG (fasting and postprandial) may be instituted. If plasma glucose or HbA_1c concentrations remain increased for 3 months, then treatment with oral agents or insulin should be started. Patients who attain euglycemia through lifestyle modification should be monitored every 3 months.

People with an FPG concentration greater than 250 mg/dL (>13.9 mmol/L) should be treated as if they have symptoms, even if they report none.

Symptomatic Diabetes Without Ketoacidosis

Symptoms include polyuria and polydipsia, nocturia, sleep apnea, vaginitis, dysuria, and even weight loss. Many families do not recognize polyuria and polydipsia in adolescents. Educational approaches to raise adolescent awareness about the potential significance of the symptoms of increased thirst and urination could encourage teenagers to alert their families and primary health care professionals.

Insulin

Initial treatment with subcutaneous insulin is suggested for children with FPG concentrations greater than 250 mg/dL (>13.9 mmol/L) and for children who are symptomatic. First Nations children with type 2 diabetes mellitus have been treated with subcutaneous insulin for 2 to 6 weeks followed by abrupt discontinuation of treatment with acceptable metabolic control.

The recommended starting dose of insulin is individualized from 0.5 to 1.0 U/kg body weight per day. Additional insulin may be given if blood glucose concentrations do not fall below 150 mg/dL (8.3 mmol/L) before meals. Insulin dosing must be adjusted on the basis of the blood glucose concentration. Children and adolescents with type 2 diabetes mellitus often require much higher doses of insulin because of insulin resistance. Insulin regimens must be individualized.

For more information on insulin refer to the original guideline.

Oral Agents

Metformin

The ADA consensus statement recommends that "if treatment goals with nutrition education and exercise are not met, pharmacologic therapy is indicated. The first oral agent should be metformin." Metformin works by decreasing hepatic glucose production and enhancing insulin sensitivity. It is contraindicated for people with renal or hepatic disease, conditions that lead to hypoxia (e.g., unstable asthma), or severe infection or those who abuse alcohol. It should be withheld before radiographic studies requiring the administration of radiocontrast dye. Metformin improves ovarian function, especially in women with PCOS, making family planning and contraception (when indicated) important.

Sulfonylureas

The primary mechanism of action of the sulfonylureas is enhancement of insulin secretion. In adults in whom type 2 diabetes mellitus has recently been diagnosed, good results have been achieved with mild to moderate fasting hyperglycemia (220–240 mg/dL [12.2–13.3 mmol/L]), good beta cell function as reflected by a high fasting C peptide concentration, and the absence of islet-cell or glutamic acid decarboxylase antibodies. No sulfonylureas are currently approved for use in children, although studies in the pediatric population with second-generation agents are ongoing. In most studies in adults, sulfonylureas have had neutral or slightly beneficial effects on plasma lipid concentrations. Weight gain is common with use, a negative effect in patients in whom weight loss is a major goal. Most pediatric endocrinologists use sulfonylureas with other agents when monotherapy with metformin or insulin sensitizers has failed. Table 6 in the original guideline outlines the pharmacologic characteristics of select sulfonylureas.

For more information on oral agents including repaglinide, thiazolidinediones, and acarbose, refer to the original guideline.

Combining Oral Agents

Because type 2 diabetes mellitus is a progressive disease with decreasing beta cell function, most people with an initial acceptable response to monotherapy will require additional agents as their disease progresses.

Because metformin promotes weight loss and decreases lipid concentrations, it is preferred for use by overweight people with type 2 diabetes mellitus and dyslipidemia. The dose of metformin or sulfonylureas can be increased over a 4- to 8-week period until acceptable glucose control is achieved or the maximum dose is reached. If monotherapy fails with metformin, then a sulfonylurea should be added. It is prudent to assess whether the person is taking the medication as directed before initiating combination therapy. Patients may not take their medication for a variety of reasons, including denial of illness; fear of being labeled diabetic; fear of adverse effects, such as hypoglycemia; actual adverse symptoms; and lack of knowledge about the need for long-term treatment. If combination therapy with 2 oral agents does not achieve the desired therapeutic goal, then bedtime insulin or a third oral agent may be considered. Referral to a specialist in type 2 diabetes mellitus for children and adolescents is recommended when combination therapy has failed.

Symptomatic Diabetes with Ketoacidosis

Children with diabetic ketoacidosis require initial treatment with intravenous insulin followed by subcutaneous insulin. High doses may be required because of the insulin resistance characteristic of type 2 diabetes mellitus. Health care professionals, nurses, and laboratory professionals who care for a large number of patients with diabetic ketoacidosis are more likely to have the necessary clinical competence to provide this high-acuity care. When care by such personnel is not possible, consultation with a subspecialist is recommended. Excellent treatment protocols and guidelines are available for the treatment of ketoacidosis. Once the patient's condition is stable, the important lifestyle modifications discussed previously can be addressed. As people often are willing to consider major lifestyle changes during a crisis, this may be an optimal teachable moment.

For information about availability, see the "Availability of Companion Documents" and "Patient Resources" fields below.

• Gahagan S, Silverstein J. Prevention and treatment of type 2 diabetes mellitus in children, with special emphasis on American Indian and Alaska Native children. American Academy of Pediatrics Committee on Native American Child Health. Pediatrics 2003 Oct;112(4):e328-e347. [137 references] PubMed

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