Type 2 diabetes mellitus: issues for the medical care of pediatric and adult patients. (Featured CME Topic: Pediatrics).

DIABETES MELLITUS is classically divided info 2 types, type 1 and type 2. The preconception is that type 1 diabetes solely affects children and type 2 diabetes affects only adults. As we begin to understand more about this disease, we are learning that it is not so easily compartmentalized. With the rising incidence of obesity in the United States, increasing numbers of children, adolescents, and adults, are now being diagnosed with type 2 diabetes. (1,2) Health care providers who care for pediatric patients, adult patients, or both, must now be knowledgeable about management issues that are specific to each age group.

In this article, we review type 2 diabetes and how it affects both pediatric and adult patients. Epidemiology, screening guidelines and prevention strategies, diagnostic criteria, treatment modalities, and sequelae that develop in the absence of diligent glycemic control are presented. While control of blood glucose level is helpful in preventing long-term complications, new data suggest that type 2 diabetes may be preventable. (1) Since the incidence of type 2 diabetes is increasing in both pediatric and adult populations, the health care industry must focus on (1) prevention or delay of onset/progression of this disease; (2) improving quality of life by delaying development of long-term complications; and (3) decreasing the overall economic burden of type 2 diabetes, which was expected to exceed $100 billion (direct and indirect costs) in 2001. (3)

EPIDEMIOLOGY

The incidence of type 2 diabetes in the pediatric population has increased approximately tenfold; nearly 50% of children and adolescents with newly diagnosed diabetes are now presenting with type 2 diabetes. Type 2 diabetes currently affects 8% of adults in the United States. (1) This amounts to approximately 16 million adults with the disease and an additional 13.4 million adults with impaired glucose tolerance (IGT).(4) Decreased physical activity, increasing obesity, and changes in food consumption have been implicated in this epidemic. (5)

PATHOGENESIS OF TYPE 2 DIABETES

Insulin, a peptide secreted by beta islet cells of the pancreas in response to postprandial rise in the serum glucose level, serves to in crease glucose uptake by peripheral tissues and suppress hepatic gluconeogenesis. There is an alternating rise and fall in the levels of insulin and glucagon that occurs to maintain glucose homeostasis. Glucose tolerance, the ability to maintain euglycemia, depends on 3 events that must occur in a tightly coordinated fashion: (1) stimulation of insulin secretion; (2) insulin-mediated suppression of endogenous (primarily hepatic) glucose production; and (3) insulin-mediated stimulation of glucose uptake by peripheral tissues. (4)

Type 2 diabetes is a disease caused by both insulin resistance and an insulin secretory defect. (6-10) There is impairment of postprandial glucose uptake by muscle with endogenously secreted insulin. (8,9) In patients with fasting hyperglycemia, insulin levels have been found to be twofold to fourfold higher than in nondia-betics. (6) In muscle tissue, there are defects in receptor function, insulin receptor-signal transduction pathway, glucose transport and phosphorylation, glycogen synthesis, and glucose oxidation that contribute to insulin resistance. (7) Basal rates of hepatic gluconeogenesis are also excessive, despite elevated insulin levels. Both defects contribute equally to excessive postprandial serum glucose levels. (9)

SCREENING AND PREVENTION

Approximately one third of all patients with diabetes may go undiagnosed. (11) According to a consensus statement from the American Diabetes Association (ADA) in 2001, the current screening guidelines have resulted in an overall 50% prevalence of complications at the time of diagnosis. This indicates that a diabetic state was present long before the diagnosis was made. (12) Although at present no randomized, controlled trials show the benefit of early diagnosis, (13) sufficient evidence justifies screening of high-risk individuals. The recommended screening test for nonpregnant individuals is fasting plasma glucose (FPG) level. (11) The screening parameters for children and adults are similar, differing only in interpretation of body mass index (BMI), frequency of interval FPG level checks, and some risk factors; BMI reference values vary according to both age and sex for pediatric patients.

Table 1 outlines specific screening guidelines for children and adults. Major risk criteria for children are a BMI greater than the 85th percentile for age and sex, a weight-to-height ratio greater than the 85th percentile, and weight greater than 120% of ideal for height.2 Once a major criterion is met, the presence of any 2 of the following warrants blood glucose level screening: (1) family history of type 2 diabetes in first-degree or second-degree relative; (2) Native American, African American, Latino, Asian American, or Pacific Islander ethnicities; (3) presence of acanthosis nigricans, hypertension, dyslipidemia, or polycystic ovary syndrome. Screening should begin when the patient is aged 10 years (or at the onset of puberty, if it occurs before the age of 10 years) and a FPG level should be obtained every 2 years. (2) The American College of Endocrinology (ACE) has recommended that an oral glucose-tolerance test (OGTT) be used to screen children with 1 or more risk factors. (14)

In adults, screening should be done in asymptomatic individuals who are aged 45 years or older. Once screening is determined to be necessary, FPG level should be obtained every 3 years. If diabetes risk factors are present (Table 1), testing should be done at an earlier age and more frequently. The ACE suggests use of OGTT for screening individuals at high risk beginning when the patient is aged 30 years. (14)

A large, randomized clinical trial recently conducted by the Diabetes Prevention Program Research Group provided evidence that life-style modification and medical management can prevent or delay the onset of type 2 diabetes. (1) This trial randomly assigned 3,234 subjects >25 years of age with impaired fasting glucose (IFG) level or impaired glucose tolerance (IGT) to standard life-style modification plus placebo, standard life-style modification plus metformin therapy (850 mg, twice daily), or an intensive life-style modification program. Subjects enrolled in the intensive program adhered to a low-fat diet and a minimum of 150 minutes of physical activity per week; on average, a 7% weight reduction was achieved. Follow-up was maintained for a mean of 2.8 years.

The results supported the hypothesis that type 2 diabetes can be delayed in persons at high risk for the disease. Individuals assigned to intensive life-style modification showed a 58% reduction in the incidence of diabetes, compared with a 31% reduction in individuals assigned to standard life-style modification and metformin therapy. By combination of lifestyle changes and medical management, the development of long-term complications should be delayed or prevented, and a substantial reduction in the public health burden of type 2 diabetes may result.

DIAGNOSIS

Criteria for the diagnosis of diabetes are similar for children and adults. Diabetes can be diagnosed in one of 3 ways. (11) The patient must have symptoms of diabetes and a random plasma glucose level of >200 mg/dL, FPG (no caloric intake for at least 8 hours) level >125 mg/dL, or a 2-hour plasma glucose (PG) level >200 mg/dL during an OGTT. Although all 3 criteria are accepted by the ADA, the FPG level is the most often used because of its ease of use. The FPG level of 125 mg/dL as the diagnostic parameter for diabetes is the result of long-term, prospective studies that showed 10% to 15% of people with this blood glucose level have diabetic retinopathy within a 10-year follow-up period. (15) The FPG level of 125 mg/dL is equivalent to a 2-hour PG level of 200 mg/dL after a 50 g oral glucose load, and a hemoglobin [A.sub.1c] ([HbA.sub.lc]) value of 6.9%.

Two other subcategories are considered prediabetic states and lead to increased incidence of cardiovascular disease. (16) Impaired fasting glucose level means that the patient has a FPG level >110 mg/dL, but <125 mg/dL. Impaired glucose tolerance means that the patient has a plasma glucose level >140 mg/dL, but <200 mg/dL. These are important categories, since they are risk factors for future development of diabetes. Based on newly published data by the Diabetes Prevention Program Research Group, these patients may warrant aggressive life-style modification and metformin therapy. (1) The ADA has recently made recommendations for diagnosis and intervention for patients with IFG or IGT, conditions commonly referred to as prediabetes. (17)

TREATMENT

Initial Approach

In the 2002 ADA position statement, components of the initial visit are divided into medical history, physical examination, laboratory evaluation, and referrals." The medical history should include family history, results of previous and current treatment programs, review of laboratory testing, risk factors for atherosclerosis, review of systems, medications, and contraceptive and sexual/reproductive histories, as applicable. Thorough diet, exercise, and social (life-style) histories should be obtained.

Physical examinations require a full general examination and also evaluation for specific findings. Height and weight, sexual maturation staging (when applicable), blood pressure measurements, and orthostatic blood pressure measurements (if autonomic dysfunction is suspected) should be done. Fundoscopic examination, thyroid gland palpation, abdominal examination for hepatomegaly, foot examination, skin examination (for acanthosis nigricans and signs of lipodystrophy at insulin injection sites), and neurologic testing should be done, and signs of diseases that can cause secondary diabetes (eg, hemochromatosis, pancreatic disease) should be assessed.

For both pediatric and adult patients, the laboratory assessment should include fasting lipid profiles, a urine microalbumin level, [HBA.sub.lc] concentration, and thyroid stimulating hormone level (if clinically indicated). Serum creatinine level and electrocardiogram should be obtained in adults.

Referrals can be made to, but are not limited to, ophthalmologists, nutritionists, endocrinologists or diabetes educators, and foot specialists, as indicated.

Nutrition Therapy

The primary treatment modalities for children and adults are medical nutrition therapy (MNT), exercise, and weight control. Medical nutrition therapy is integral to the successful management of diabetes and the associated comorbidities of dyslipidemia, hypertension, and nephropathy. Success in this area requires recognition of the importance of MNT by the primary care provider, involvement of a dietitian who has experience with diabetes, and a well-educated and compliant patient and family. For pediatric patients, the dietitian must have expertise in the nutritional needs of growing children and adolescents. Patients must first learn self-monitoring of blood glucose (SMBG) level. This skill will be necessary, should symptoms of hypoglycemia or hyperglycemia occur. In the pediatric population, this means teaching the patient and primary caregivers to recognize signs and symptoms of hypoglycemia and hyperglycemia and how to manage them.

Dietary recommendations should address behavior modification strategies for changing life-style and decreasing high-calorie, high-fat food choices. (18) Recommendations should also be culturally appropriate, sensitive to family resources, and provided to all caregivers. (2) Depending on whether the child or adult has dyslipidemia, hypertension, or nephropathy, the dietary restrictions will vary regarding caloric, total fat, cholesterol, sodium, and protein intake. Since dietary carbohydrate is the primary contributor to postprandial blood glucose level, the total amount of carbohydrate consumed at meals and snacks must be monitored and controlled. The main focus should be the establishment of long-term behavioral changes, rather than specific weight goals.

When assessing caloric needs of a child or adolescent, the remaining linear growth must be considered. The caloric goal for a younger child is to promote weight maintenance, allowing them to grow into their weight. For adolescents, adequate caloric intake will be needed for the pubertal growth spurt. If the peak growth spurt has already occurred, a decrease to 250 to 500 calories less than the daily average should be recommended, with a reduction in the amount of total fat, especially saturated fats. (11)

The ADA recommends 10% to 20% of daily caloric intake from protein, with the remaining 80% to 90% of calories distributed between dietary fat and carbohydrates. Less than 10% of these calories should be from saturated fat, leaving 70% to 80% of the total calories from polyunsaturated and monounsaturated fats and carbohydrates. (11) Current National Cholesterol Education Program (NCEP) guidelines recommend that all individuals >2 years of age limit fat intake to less than 30% of total calories, with saturated fats restricted to less than 10%. If low-density lipoprotein (LDL) cholesterol is a primary concern, saturated fats should be reduced to 7% of total calories and dietary cholesterol reduced to <200 mg/day. (11) If the patient with dyslipidemia is not responsive to dietary management, medical management may be necessary. For patients with hypertension, salt restriction may be advised. There are no recommended pediatric sodium-restriction guidelines. For the adult diabetic with hypertension, current salt-in take recommendations are <2,400 mg/day; for patients with hypertension and nephropathy, <2,000 mg/day is recommended. (11) Protein restriction is controversial. The general consensus is to prescribe a recommended daily allowance diet of 0.8 g/kg per day. Once the glomerular filtration rate (GFR) begins to fall, further restriction to 0.6 g/kg per day may be useful in slowing the decline of GFR. (11)

Exercise

Regular exercise should be an integral component of any diabetes treatment program. In addition to its favorable effects on glycemic control, exercise has also been shown to improve cardiovascular health, lipid status, and weight control. In line with the recommendations of the Surgeon General, patients are advised to participate in 30 minutes of moderate physical activity daily. (11,19)

Prescription of an exercise program must take into account issues such as degree of obesity and its associated physical limitations, coexisting cardiovascular disease, and morbidities such as retinopathy, nephropathy, and neuropathy. A stepwise introduction of progressively more demanding physical activity should be advised. Patients may do well with an initial prescription of 15 to 30 minutes of daily walking that can be progressively increased in either duration or intensity.

Pharmacologic Therapy

Currently, 5 types of glucose-lowering oral agents are available in the United States for the treatment of type 2 diabetes. (4) Since the pathophysiology of type 2 diabetes appears to be similar in children and adults, it is reasonable to assume that oral agents used in management of diabetes in adults will be effective in children. Efficacy and safety data are not available on treatment with any of these agents with the exception of metformin, which is approved for children aged 10 years and older (the extended-release form is not recommended for patients younger than 17 years) (2) Insulin is approved for treatment of pediatric patients with diabetes. The approach to pharmacologic therapy should be individualized. An algorithm is presented to guide medical treatment (Figure).

The available pharmaceutical oral agents and their mechanisms of action are as follows:

Biguanides (metformin) decrease hepatic glucose output and primarily enhance hepatic and muscle insulin sensitivity without an effect on beta cell function.

Thiazolidinediones (rosiglitazone, pioglitazone) improve peripheral insulin sensitivity.

Insulin secretagogues include sulfonylureas (glyburide, glipizide, tolazamide, tolbutamide, glimepiride, gliclazide), which promote insulin secretion; and meglitinides (repaglinide, nateglinide), which promote short-term glucose-stimulated insulin secretion; nateglinide is more specifically an amino acid derivative.

Glucosidase inhibitors (acarose, miglitol) slow hydrolysis of complex carbohydrates and slow carbohydrate absorption. (4)

Pharmacologic therapy should be initiated if MNT, exercise, and weight control do not establish desired glycemic control within 3 months. The first oral agent used may be metformin. (2) The starting dose is 500 mg, twice daily, for both pediatric and adult patients. Metformin therapy will decrease [HbA.sub.1c] values by 1.5% to 2.0% (4) without the risk of hypoglycemia. In a recent randomized study that evaluated the safety and efficacy of metformin therapy (1,000 mg, twice daily) in children aged 10 to 16 years, side effects and reduction in [HbA.sub.1c] concentration were similar to those reported in adults. (20) Metformin therapy has the added advantages of weight loss promotion and reduction of LDL cholesterol (by 10% to 15%) and triglyceride levels. In adolescent or adult females with polycystic ovary syndrome, treatment with metformin also may normalize ovulatory abnormalities and increase the risk of unplanned pregnancy. Therefore, preconception and pregnancy counseling should be part of the treatment regimen. (2) Metformin therapy is contraindicated in patients with renal insufficiency (creatinine level of 1.4 mg/dL in women and 1.5 mg/dL in men), hepatic disease, alcohol abuse, and chronic heart failure, since it can increase the risk of a fatal lactic acidosis. (4) The most common side effect is gastrointestinal discomfort with diarrhea. (4)

Treatment with sulfonylureas can also be initiated as primary intervention, once MNT and exercise have failed to adequately control glycemic levels, or can be added an an adjunct to metformin therapy. Clinical trials have failed to show superiority of one sulfonylurea over another when given in maximally effective doses. (21,22) Large prospective studies have shown that glipizide, glyburide and glimepiride exert equipotent glucose-lowering effects. (21-25) Therapy should be initiated at the lowest effective dose and titrated upward every 1 to 2 weeks until the FPG level or [HbA.sub.1c] concentration goal is achieved. (4) Hypoglycemia is the most common side effect, and the risk is increased in patients with renal insufficiency.

Thiazolidinediones (TZDs) are another class of drugs that can be used to increase insulin sensitivity. The likely mechanism of action is stimulation. of muscle glucose metabolism and inhibition of hepatic gluconeogenesis. (26,27) Troglitazone was the agent initially studied, but because of its association with acute hepatic failure, it has since been removed from the market. Rosiglitazone and pioglitazone have been used in drug-naive patients, decreasing [HbA.sub.1c] values by 1.2% to 1.5%. (4) Both agents have been approved for use as monotherapy and in combination with metformin or a sulfonylurea. (4) Currently, the Food and Drug Administration (FDA) recommends monitoring alanine aminotransferase (ALT) level as a baseline before initiation of therapy, every 2 to 3 months for the first year of treatment, and then annually after that. (4) Thiazolidinedione therapy should not be initiated if baseline ALT values are 2.5 times the upper limit of normal, and these drugs should be discontinued if there is a twofol d increase from baseline in ALT. Because sodium retention is an issue, these agents are contraindicated in patients with class III or class IV heart failure. This class of drugs is currently not recommended for use in children and adolescents.

As a monotherapy, acarbose has been shown to decrease the [HbA.sub.1c] level by 0.7% to 1.0%. (28-34) This drug is most effective in patients with postprandial hyperglycemia. Gastrointestinal complaints, such as bloating, diarrhea, and flatulence, occur in up to 30% of patients. (4) It is contraindicated in patients with inflammatory bowel disease, plasma creatinine level >2.0 mg/dL, and cirrhosis.

Most diabetologists agree that if FPG level or [HbA.sub.1c] concentration goals are not met with 2 agents, and certainly if not with 3 agents, starting NPH insulin at bedtime (or twice a day) is effective. (2) A study of 518 patients with type 2 diabetes evaluated the efficacy and safety of insulin glargine compared with NPH insulin. Both treatment groups showed reductions in [HbA.sub.1c] concentrations, and those randomized to glargine insulin therapy showed a 25% reduction in nocturnal hypoglycemic events. The study concluded that glargine insulin given once daily is as effective as NPH insulin given once or twice daily. (35)

Treatment Goals

In general, the desired endpoints of treatment are optimal glycemic control, acceptable life-style, and normal linear growth for children and adolescents. Based on the available literature, patients should be advised to lower their plasma glucose levels as close to normal as possible in an effort to prevent complications. (36-41) Individual issues, such as concomitant disease, existing morbidities, hypoglycemia awareness, and patient age, should be considered. The ADA has recommended the following goals: [HbA.sub.1c] concentration, <7%; preprandial PG value, 90 to 130 mg/dL; and bedtime PG values, 110 to 150 mg/dL. (11) In an effort to lessen the likelihood of diabetic complications, the ACE has recommended even stricter goals: [HbA.sub.1c] concentration, <6.5%; FPG value, <110 mg/dL; and 2-hour PG value, <140 mg/dL. (12) The clinician must be aware that any decrease in a patient's average plasma glucose level will impart beneficial effects.

COMPLICATIONS

Several studies have shown the benefits of treatment in reducing diabetes-related morbidity. The Diabetes Control and Complications Trial (DCCT) looked at reduction of microvascular complications in patients with type 1 diabetes by intensively controlling serum glucose levels to achieve an [HbA.sub.1c] concentration of <8.0%. (11) Several arguments suggest that the results obtained in the DCCT can be extrapolated to patients with type 2 diabetes. (4) First, the microvascular complications found in type 1 diabetes are identical to those found in type 2 diabetes. (36-38) Second, epidemiologic studies have shown a close association between glycemic control and microvascular complications. (15,36,42,43) Third, in a Japanese trial, in which patients with type 2 diabetes were intensively treated with insulin to achieve near-normal glycemia, improvement in microvascular outcomes similar to the results of the DCCT were observed. Finally, short-term prospective studies (39,40) have shown that glycemic control reduces microalbuminuria and improves nerve conduction velocities in patients with type 2 diabetes.

A second study was done to evaluate whether intensive glycemic control was beneficial in type 2 diabetes. (41) The United Kingdom Prospective Diabetes Study showed that control of blood glucose level to achieve an [HbA.sub.1c] concentration of 7.0% reduced microvascular complication rates by 25%, treatment with metformin reduced the incidence of macrovascular complications, and lowering blood pressure to a mean of 144/82 mm Hg significantly reduced the incidence of cerebrovascular accidents and diabetes-related deaths.

Microvascular complications of type 2 diabetes are retinopathy, nephropathy, and neuropathy. Discussing the pathogenesis of each complication individually is beyond the scope of this paper. In general, retinopathy does not appear until after 3 to 5 years of diabetes duration, and rarely appears before puberty. (44) Diabetic retinopathy is estimated to be the most frequent cause of blindness in adults aged 20 to 74 years. (11) Proliferative retinopathy, macular edema, or both occur in 40% to 50% of patients with type 2 diabetes. (4) Because type 2 diabetes has an insidious onset, many adult patients have some degree of retinopathy at the time of diagnosis. Therefore, both the adolescent and adult patient should have a comprehensive eye examination shortly after the initial diagnosis of diabetesis made, and then annually (Table 2). (11)

Nephropathy does not correlate with increasing duration of diabetes, but it is correlated with coexisting hypertension. Diabetic nephropathy occurs in 20% to 40% of patients, is the single leading cause of end-stage renal disease, (11) and accounts for one third of patients who enter dialysis or transplant programs. (4) Its initial presence is marked by the appearance of microalbuminuria. The ADA recommends screening for microalbuminuria at the time of diagnosis and then annually for children, adolescents, and adults (Table 2). Current therapy for reducing the incidence of nephropathy is aimed at blood pressure reduction with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or calcium channel blockers. Epidemiologic analyses in adult patients show that blood pressure >120/80 mm Hg is associated with increased incidence of cardiovascular events and death. (45) Therefore, the target blood pressure is < 130/80 mm Hg for adults, (11) and achievement of age-appropriate levels in pediatric p atients. If this goal is not achieved with the aforementioned agents, treatment with [beta]blockers or thiazide diuretics is an acceptable alternative. When [beta]-blockers are prescribed, the patient should be warned about the risk of masking hypoglycemia.

Peripheral and autonomic neuropathies occur in 50% to 60% of patients with type 2 diabetes. A peripheral, symmetric, sensorimotor neuropathy is the most common form of diabetic neuropathy and correlates with the duration of disease. (44) A common symptom is nighttime paresthesia, which can be described as lancinating or burning. The principal risk of sensory loss are Charcot's foot and development of calluses, which become a source of repeated trauma and infected ulcers. Autonomic dysfunction can affect gastric or intestinal motility, erectile function, bladder function, cardiac function, and vascular tone. (44) Table 2 lists recommended screening for peripheral neuropathy.

Heart attack and stroke occur 2 to 4 times more frequently in persons with diabetes than in those without the disease. (4) Cardiovascular disease is the major cause of death in adults with diabetes. Inadequately controlled hypertension and dyslipidemia are 2 comorbidities that contribute to the development of coronary artery disease (CAD) and stroke. It is well recognized that lipid disorders and hypertension also occur in children with diabetes. Type 2 diabetes is an independent risk factor for CAD, hypertension, and dyslipidemia. (11) Therefore, aggressive management of adult patients with dyslipidemia is recommended. Treatment may include prescription of a hydroxymethylglutaryl co-enzyme A reductase inhibitor (statin), niacin, or fibrinate, alone or in combination with MNT, to achieve NCEP target goals (Table 3). The main intervention for dyslipidemia in pediatric patients is MNT, coupled with efforts to achieve optimal glycemic control with sparing of lipid-lowering agents.

Preventive treatments, such as immunizations, smoking-cessation counseling, and aspirin therapy, should be considered for patients with diabetes (Table 2). Aspirin is used as primary and secondary therapy to prevent cardiovascular events. The recommended dose is between 75 and 325 mg in patients with known CAD; however, no evidence supports the initiation of aspirin therapy for primary prevention in patients younger than 30 years. (11) At all ages, smoking cessation needs to be addressed, since it is the most important modifiable cause of premature death."

CONCLUSION

As more is learned about diabetes prevention, treatment, and management of diabetic complications and comorbidities, early diagnosis and treatment in children and adults become increasingly important issues. These concerns are especially critical, given the rising incidence of obesity in the United States and the associated increased occurrence of type 2 diabetes in both pediatric and adult age groups. We have reviewed the epidemiology, screening guidelines and prevention strategies, diagnostic criteria, treatment modalities, and sequelae that develop in the absence of diligent glycemic control. Specific guidelines applicable to either pediatric or adult patients have been provided. This information will assist the primary care provider in providing health care to these various age groups and guide age-appropriate interventions that will ultimately improve the patient's quality of life while reducing morbidity and mortality rates

TABLE 1.

Screening Guidelines for Diabetes *

                    Criteria

Childhood
  (age 10 years     Overweight (BMI >85th percentile)
  or at puberty)    Any 2 additional risk factors:
                      Family history of type 2 diabetes
                      High-risk race/ethnicity
                      Conditions associated with
                      insulin resistance
                        (HBP, acanthosis nigricans,
                          dyslipidemia, PCOS)

Adulthood
  (age > 45 years)  Test at earlier age if 1 or more
                      risk factors
                      are present:
                      Inactivity
                      First-degree relative with
                        diabetes
                      High-risk race/ethnicity
                      HBP
                      Dyslipidemia
                      History of IGT or IFG
                      Conditions associated with
                        insulin resistance

                    Screening Freequency         Screening Test

Childhood
  (age 10 years     Every 2 years                Fasting blood glucose
  or at puberty)







Adulthood
  (age > 45 years)  Every 3 years if normal      Fasting blood glucose
                    Every 1-2 years if abnormal











* As developed by the American Diabetes Association.

BMI = Body mass index, HBP = high blood pressure, PCOS = polycystic
overy syndrome, IGT = impaired glucose tolerance, IFG = impaired fasting
glucose level.
TABLE 2.

Treatment Goals and Health Care Monitoring: Type 2 Diabetes

                                   Monitoring Schedule
      Management Goal                    Child/Adolescent

Glycemic control              Every 3-6 months
  ([HbA.sub.1c] < 7.0%)
Lipid management              Every 5 years
  (LDL, HDL, Tg)
Blood pressure                Each visit
  (normotensive for age/sex)
Aspirin therapy               Not indicated

Nephropathy                   Annually
  (urine microalbumin)
Retinopathy                   Annually
  (dilated fundoscopy)
Neuropathy                    Annually
  (monofilament testing)
Immunizations                 Routine pediatric/adolescent
                               and annual influenza
Smoking cessation             Annually

                                   Monitoring Schedule
      Management Goal                      Adult

Glycemic control              Every 3-6 months
  ([HbA.sub.1c] < 7.0%)
Lipid management              Annually
  (LDL, HDL, Tg)
Blood pressure                Each Visit
  (normotensive for age/sex)
Aspirin therapy               Secondary prevention if > 21
                               years of age
Nephropathy                   Annually
  (urine microalbumin)
Retinopathy                   Annually
  (dilated fundoscopy)
Neuropathy                    Annually
  (monofilament testing)
Immunizations                 Annual influenza, single
                               pneurmococcal
Smoking cessation             Annually

[HbA.sub.1c] = Hemoglobin [A.sub.1c], LDL = low-density lipoprotein
cholesterol, HDL = high-density lipoprotein cholesterol, Tg =
triglyceride.
TABLE 3.

Target Serum Lipid Levels for Adult Patients With Diabetes

        Lipid      Target Level

LDL cholesterol  <100 mg/dL
HDL cholesterol   >45 mg/dL (men)
                  >55 mg/dL (women)
Triglycerides    <150 mg/dL

References

(1.) Diabetes Prevention Program Research Group: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346:393-403

(2.) American Diabetes Association: Type 2 diabetes in children and adolescents. Pediatrics 2000; 105:671-680

(3.) American College of Endocrinology: ACE guidelines for glycemic control. Endocr Pract 2002; 8:S6-S11

(4.) DeFronzo RA: Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 1999; 131:281-303

(5.) Stern MP, Gonzalez C, Mitchell BD, et al: Genetic and environmental determination of type II diabetes in Mexico City and San Antonio. Diabetes 1992; 41:484-492

(6.) DeFronzo RA, Ferrannini E, Simonson DC: Fasting hyperglycemia in non-insulin dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake. Metabolism 1989; 38:387-395

(7.) DeFronzo RA: Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev 1997; 5:177-269

(8.) Mitrakou A, Kelley D, Veneman T, et al: Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM. Diabetes 1990; 39:1381-1390

(9.) Ferarannini E, Simonson DC, Katz LD, et al: The disposal of an oral glucose load in patients with non-insulin dependent diabetes. Metabolism 1988; 37:79-85

(10.) Porte D, Kahn SE: Beta-cell dysfunction and failure in type 2 diabetes: potential mechanisms. Diabetes 2001; 50(suppl 1):S160-S163

(11.) American Diabetes Association: Clinical practice recommendations 2002. Diabetes Care 2002; 25 (suppl 1):S1-S147

(12.) American College of Endocrinology: ACE Consensus Conference on Guidelines for Glycemic Control. Endocr Pract Suppl Nov/Dec 2001, pp 1-5

(13.) Engelgau ME, Narayan KMV, Herman WH: Screening for type 2 diabetes. Diabetes Care 2000; 10:1563-1580

(14.) Hellman R: Screening and diagnostic testing for diabetes and related conditions. Endocr Pract 2002; 8(suppl 1):21-24

(15.) American Diabetes Association: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2001; 24:S5-S20

(16.) Fuller JH, Shipley MJ, Rose G, et al: Coronary-heart disease risk and impaired glucose tolerance: the Whitehall study. Lancet 1980; 1:1373-1376

(17.) American Diabetes Association and National Institute of Diabetes, Digestive and Kidney Diseases: The prevention or delay of type 2 diabetes. Diabetes Care 2002; 25:742-749

(18.) Willet WC, Dietz WH, Colditz GA: Guidelines for healthy weight. N Engl J Med 1999; 341:427-434

(19.) US Department of Health and Human Services: Physical Activity and Health: A Report of the Surgeon General. Washington, DC, US Government Printing Office, 1996

(20.) Jones KL, Arslanian S, Peterokova VA, et al: Effect of metformin in pediatric patients with type 2 diabetes: a randomized control trial. Diabetes Care 2002; 25:89-94

(21.) Simonson DC, Kourides IA, Feinglos M, et al: Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. results of two multicenter, randomized, placebo-controlled clinical trials, the Glipizide Gastrointestinal Therapeutic System Study Group. Diabetes Care 1997; 20:597-606

(22.) Rosenstock J, Samols E, Muchmore DB, et al: Glimeperide, a new once-daily sulfonylurea. a double-blind placebo-controlled study of NIDDM patients. Glimepiride Study Group. Diabetes Care 1996; 19:1194-1199

(23.) Groop LC: Sulfonylureas in NIDDM. Diabetes Care 1992; 15:737-754

(24.) Groop L, Groop PH, Stenmen S, et al: Comparison of pharmacokinetics, metabolic effects and mechanisms of action of glyburide and glipizide during long-term treatment. Diabetes Care 1987; 10:671-678

(25.) Jeppesen J, Zhou MY, Chen YD, et al: Effect on glipizide on postprandial lipaemia in patients with NIDDM. Diabetologia 1996; 37:781-787

(26.) Spiegelman BM: PPAR-[gamma]:adipogenic regulator and thiazolinedione receptor. Diabetes 1998; 47:507-514

(27.) Maggs DG, Buchanan TA, Burant CF, et al: Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. a randomized, double-blind placebo-controlled trial. Ann Intern Med 1998; 128:176-185

(28.) Clissold SP, Edwards C: Acarbose. a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1988; 35:214-243

(29.) Lebovitz HE: A new oral therapy for diabetes management: alpha-glucosidase inhibition with acarbose. Clin Diabetes 1995; 13:99-103

(30.) Krentz AJ, Ferner RE, Bailey CJ: Comparative tolerability profiles of oral antidiabetic agents. Drug Saf 1994; 11:223-241

(31.) Chiasson JL, Josse RG, Hunt JA, et al: The efficacy of acarbose in the treatment of patients with non-insulin dependent diabetes mellitus. a multicenter controlled clinical trial. Ann Intern Med 1994; 121:928-953

(32.) Coniff RF, Shapiro JA, Robbins D, et al: Reduction of glycosylated hemoglobin and postprandial hyperglycemia by acarbose in patients with NIDDM. a placebo-controlled dose comparison study. Diabetes Care 1995; 18:817-824

(33.) Hillebrand I, Boehme K, Frank G, et al: The effects of the [alpha]-glucose inhibitor BAY g 5421 (acarbose) on meal-stimulated elevations of circulating glucose, insulin, and triglyceride levels in man. Res Exp Med (Berl) 1979; 175:81-86

(34.) Bayraktar M, Van Thiel DH, Adalar N: A comparison of acarbose versus metformin as an adjuvant therapy in sulfonylurea-treated NIDDM patients. Diabetes Care 1996; 19:252-254

(35.) White JR, Campbell RK: Recent developments in the pharmacological reduction of blood glucose in patients with type 2 diabetes. Clin Diabetes 2001; 19:153-158

(36.) Klein R: Hyperglycemia and microvascular and macrovascular disease in diabetes care. Diabetes Care 1995; 18:258-268

(37.) Parving HH, Gall MA, Skott MA, et al: Pathogenesis of type 2 diabetes, prevalence and causes of albuminuria in noninsulin diabetic patients. Kidney Int 1992; 41:758-762

(38.) Sima AA, Nathaniel V. Bril V, et al: Histopathological heterogeneity of neuropathy in insulin-dependent and noninsulin-dependent diabetes, and demonstration of axo-glial dysfunction in human diabetic neuropathy. J Clin Invest 1998; 81:349-364

(39.) Vora JP, Dolben J, Williams JD, et al: Impact of initial treatment on renal function in newly diagnosed type 2 (noninsulin-dependent) diabetes mellitus. Diabetologia 1993; 36:374-740

(40.) Nathan DM: Inferences and implications, do results from the Diabetes Control and Complications Trial apply in NIDDM? Diabetes Care 1995; 18:251-257

(41.) American Diabetes Association: Implications of the United Kingdom Prospective Diabetes Study. Diabetes Care 2001; 24:S28-S32

(42.) McCance DR, Hanson RL, Charlas MA, et al: Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes. BMJ 1996; 308:1323-1328

(43.) Engelgau MM, Thompson TJ, Herman WH, et al: Comparison of fasting and 2-hour glucose and [HbA.sub.1c] levels for diagnosing diabetes: diagnostic criteria and performance revisited. Diabetes Care 1997; 20:985-991

(44.) Nathan DM: Long-term complications of diabetes mellitus. N Engl J Med 1993; 328:1676-1685

(45.) Hansson L, Zanchett A, Carruthers SG, et al: Effects of intensive blood-pressure lowering and low-dose aspirin on patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet 1998; 351:1755-1762

From the Departments of Internal Medicine, Clinical Nutrition, and pediatrics, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey.

Reprint requests to James R. Kerrigan, MD, Pennsylvania State University, Milton S. Hershey Medical Center, PO Box 850, Hershey, PA 17033-0850.