Testing to detect type 2 diabetes

Type 2 Diabetes Recommendations
Testing to detect type 2 diabetes in asymptomatic people should be considered in adults of any age who are overweight or obese (BMI ≥25 kg/m2 or ≥23 kg/m2 in Asian Americans) and who have one or more additional risk factors for diabetes. For all patients, particularly those who are overweight or obese, testing should begin at age 45 years. B

If tests are normal, repeat testing carried out at a minimum of 3-year intervals is reasonable. C

To test for diabetes, the A1C, FPG, and 2-h PG after 75-g OGTT are appropriate. B

In patients with diabetes, identify and, if appropriate, treat other CVD risk factors. B

Testing to detect type 2 diabetes should be considered in children and adolescents who are overweight or obese and who have two or more additional risk factors for diabetes. E

This form, previously referred to as “non-insulin-dependent diabetes” or “adult-onset diabetes,” accounts for ∼90–95% of all diabetes. Type 2 diabetes encompasses individuals who have insulin resistance and usually relative (rather than absolute) insulin deficiency. At least initially, and often throughout their lifetime, these individuals may not need insulin treatment to survive.

There are various causes of type 2 diabetes. Although the specific etiologies are not known, autoimmune destruction of β-cells does not occur, and patients do not have any of the other known causes of diabetes. Most, but not all, patients with type 2 diabetes are obese. Obesity itself causes some degree of insulin resistance. Patients who are not obese by traditional weight criteria may have an increased percentage of body fat distributed predominantly in the abdominal region.

Ketoacidosis seldom occurs spontaneously in type 2 diabetes; when seen, it usually arises in association with the stress of another illness such as infection. Type 2 diabetes frequently goes undiagnosed for many years because hyperglycemia develops gradually and at earlier stages is often not severe enough for the patient to notice the classic diabetes symptoms. Nevertheless, such patients are at an increased risk of developing macrovascular and microvascular complications.

Whereas patients with type 2 diabetes may have insulin levels that appear normal or elevated, the higher blood glucose levels in these patients would be expected to result in even higher insulin values had their β-cell function been normal. Thus, insulin secretion is defective in these patients and insufficient to compensate for insulin resistance. Insulin resistance may improve with weight reduction and/or pharmacological treatment of hyperglycemia but is seldom restored to normal.

The risk of developing type 2 diabetes increases with age, obesity, and lack of physical activity. It occurs more frequently in women with prior GDM, in those with hypertension or dyslipidemia, and in certain racial/ethnic subgroups (African American, American Indian, Hispanic/Latino, and Asian American). It is often associated with a strong genetic predisposition, more so than type 1 diabetes. However, the genetics of type 2 diabetes is poorly understood.

Testing for Type 2 Diabetes and Prediabetes in Asymptomatic Adults
Prediabetes and diabetes meet criteria for conditions in which early detection is appropriate. Both conditions are common and impose significant clinical and public health burdens. There is often a long presymptomatic phase before the diagnosis of type 2 diabetes. Simple tests to detect preclinical disease are readily available. The duration of glycemic burden is a strong predictor of adverse outcomes. There are effective interventions that prevent progression from prediabetes to diabetes (see Section 5. Prevention or Delay of Type 2 Diabetes) and reduce the risk of diabetes complications (see Section 8. Cardiovascular Disease and Risk Management and Section 9. Microvascular Complications and Foot Care).

Approximately one-quarter of people with diabetes in the U.S. are undiagnosed. Although screening of asymptomatic individuals to identify those with prediabetes or diabetes might seem reasonable, rigorous clinical trials to prove the effectiveness of such screening have not been conducted and are unlikely to occur. A large European randomized controlled trial compared the impact of screening for diabetes and intensive multifactorial intervention with that of screening and routine care (19). General practice patients between the ages of 40–69 years were screened for diabetes and randomized by practice to intensive treatment of multiple risk factors or routine diabetes care. After 5.3 years of follow-up, CVD risk factors were modestly but significantly improved with intensive treatment compared with routine care, but the incidence of first CVD events or mortality was not significantly different between the groups (19). The excellent care provided to patients in the routine care group and the lack of an unscreened control arm limit our ability to prove that screening and early intensive treatment impact outcomes. Mathematical modeling studies suggest that screening, beginning at age 30 or 45 years and independent of risk factors, may be cost-effective (<$11,000 per quality-adjusted life-year gained) (20).

Additional considerations regarding testing for type 2 diabetes and prediabetes in asymptomatic patients include the following:

Testing recommendations for diabetes in asymptomatic adults are listed in Table 2.2. Age is a major risk factor for diabetes. Testing should begin at age 45 years for all patients, particularly those who are overweight or obese.

BMI and Ethnicity
Testing should be considered in adults of any age with BMI ≥25 kg/m2 and one or more additional risk factors for diabetes. However, recent data (21) and evidence from the ADA position statement “BMI Cut Points to Identify At-Risk Asian Americans for Type 2 Diabetes Screening” (22) suggest that the BMI cut point should be lower for the Asian American population. For diabetes screening purposes, the BMI cut points fall consistently between 23–24 kg/m2 (sensitivity of 80%) for nearly all Asian American subgroups (with levels slightly lower for Japanese Americans). This makes a rounded cut point of 23 kg/m2 practical. In determining a single BMI cut point, it is important to balance sensitivity and specificity so as to provide a valuable screening tool without numerous false positives. An argument can be made to push the BMI cut point to lower than 23 kg/m2 in favor of increased sensitivity; however, this would lead to an unacceptably low specificity (13.1%). Data from the WHO also suggest that a BMI ≥23 kg/m2 should be used to define increased risk in Asian Americans (23).

Evidence also suggests that other populations may benefit from lower BMI cut points. For example, in a large multiethnic cohort study, for an equivalent incidence rate of diabetes, a BMI of 30 kg/m2 in non-Hispanic whites was equivalent to a BMI of 26 kg/m2 in African Americans (24).

Certain medications, such as glucocorticoids, thiazide diuretics, and atypical antipsychotics (25), are known to increase the risk of diabetes and should be considered when ascertaining a diagnosis.

Diagnostic Tests
The A1C, FPG, and 2-h PG after 75-g OGTT are appropriate for testing. It should be noted that the tests do not necessarily detect diabetes in the same individuals. The efficacy of interventions for primary prevention of type 2 diabetes (26–32) has primarily been demonstrated among individuals with IGT, not for individuals with isolated IFG or for those with prediabetes defined by A1C criteria.

Testing Interval
The appropriate interval between tests is not known (33). The rationale for the 3-year interval is that with this interval, the number of false-positive tests that require confirmatory testing will be reduced and individuals with false-negative tests will be retested before substantial time elapses and complications develop (33).

Community Screening
Ideally, testing should be carried out within a health care setting because of the need for follow-up and treatment. Community testing outside a health care setting is not recommended because people with positive tests may not seek, or have access to, appropriate follow-up testing and care. Community testing may also be poorly targeted; i.e., it may fail to reach the groups most at risk and inappropriately test those at very low risk or even those who have already been diagnosed.

Testing for Type 2 Diabetes and Prediabetes in Children and Adolescents
In the last decade, the incidence and prevalence of type 2 diabetes in adolescents has increased dramatically, especially in ethnic populations (15). Recent studies question the validity of A1C in the pediatric population, especially among certain ethnicities, and suggest OGTT or FPG as more suitable diagnostic tests (34). However, many of these studies do not recognize that diabetes diagnostic criteria are based on long-term health outcomes, and validations are not currently available in the pediatric population (35). The ADA acknowledges the limited data supporting A1C for diagnosing diabetes in children and adolescents. However, aside from rare instances, such as cystic fibrosis and hemoglobinopathies, the ADA continues to recommend A1C in this cohort (36,37). The modified recommendations of the ADA consensus report “Type 2 Diabetes in Children and Adolescents” are summarized in Table 2.4.