ADA screening recommendations: when to screen to repeat screens based on findings

Screening for type 2 diabetes with an informal assessment of risk factors or validated tools should be considered in asymptomatic adults. B Testing for type 2 diabetes in asymptomatic people should be considered in adults of any age who are over- weight or obese (BMI >25 kg/m2 or $23 kg/m2 in Asian Americans) and who have one or more additional risk factors for diabetes. B For all people, testing should be- gin 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 type 2 diabetes, fasting plasma glucose, 2-h plasma glucose after 75-g oral glucose tolerance test, and A1C are equally appropriate. B In patients with diabetes, identify and treat other cardiovascular disease risk factors. Updated recommendations emphasize that testing for prediabetes and type 2 diabetes should be considered in children and adolescents younger than 18 years of age who are overweight or obese (BMI >85th percentile for age and sex, weight for height >85th percentile, or weight >120% of ideal for height), and have one or more additional risk factors for diabetes such as (1) maternal history of diabetes or gestational diabetes during the child’s gestation; (2) family history of type 2 diabetes in first- or seconddegree relative; (3) race/ethnicity (Native American, African American, Latino, Asian American, Pacific Islander; and/or (4) signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, or small- DIAGNOSTIC TESTS FOR DIABETES Diabetes may be diagnosed based on plasma glucose criteria, either the fasting plasma glucose (FPG) or the 2-h plasma glucose (2-h PG) value after a 75-g oral glucose tolerance test (OGTT) or A1C criteria (1,6) (Table 2.2). FPG, 2-h PG after 75-g OGTT, and A1C are equally appropriate for diagnostic 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 (7,8) has primarily been demonstrated among individuals with impaired glucose tolerance (IGT), not for individuals with isolated impaired fasting glucose (IFG) or for those with prediabetes defined by A1C criteria. The same tests may be used to screen for and diagnose diabetes and to detect individuals with prediabetes. Diabetes may be identified anywhere along the spectrum of clinical scenarios: in seemingly low-risk individuals who happen to have glucose testing, in individuals tested based on diabetes risk assessment, and in symptomatic patients. Fasting and 2-Hour Plasma Glucose The FPG and 2-h PG may be used to diagnose diabetes (Table 2.2). The concordance between the FPG and 2-h PG tests is imperfect, as is the concordance be- tween A1C and either glucose-based test. Numerous studies have confirmed that, compared with FPG and A1C cut points, the 2-h PG value diagnoses more people with diabetes. A1C The A1C test should be performed using a method that is certified by the NGSP () and standardized or traceable to the Diabetes Control and Complications Trial (DCCT) reference as- say. Although point-of-care A1C assays may be NGSP certified, proficiency testing is not mandated for performing the test, so use of point-of-care assays for diagnostic purposes is not recommended but may be considered in the future if proficiency testing is performed and documented. The A1C has several advantages com- pared with the FPG and OGTT, including greater convenience (fasting not required), greater preanalytical stability, and less day-to-day perturbations during stress and illness. However, these advantages may be offset by the lower sensitivity of A1C at the designated cut point, greater cost, limited availability of A1C testing in certain regions of the developing world, and the imperfect correlation between A1C and average glucose in certain individuals. National Health and Nutrition Examination Survey (NHANES) data indicate that an A1C cut point of $6.5% (48 mmol/mol) identifies one-third fewer cases of undiagnosed diabetes than a fasting glucose cut point of $126 mg/dL (7.0 mmol/L) (9). When using A1C to diagnose diabetes, it is important to recognize that A1C is an indirect measure of average blood glucose levels and to take other factors into consideration that may impact hemoglobin glycation independently of glycemia including age, race/ethnicity, and anemia/ hemoglobinopathies. Confirming the Diagnosis Unless there is a clear clinical diagnosis (e.g., patient in a hyperglycemic crisis or with classic symptoms of hyperglycemia and a random plasma glucose $200 mg/dL [11.1 mmol/L]), a second test is required for confirmation. It is recommended that the same test be repeated without delay using a new blood sample for confirmation because there will be a greater likelihood of concurrence. For ex- ample, if the A1C is 7.0% (53 mmol/mol) and a repeat result is 6.8% (51 mmol/mol), the diagnosis of diabetes is confirmed. If two different tests (such as A1C and FPG) are both above the diagnostic threshold, this also confirms the diagnosis. On the other hand, if a patient has discordant results from two different tests, then the test result that is above the diagnostic cut point should be repeated. The diagnosis is made on the basis of the confirmed test. For example, if a patient meets the diabetes criterion of the A1C (two results $6.5% [48 mmol/mol]) but not FPG (,126 mg/dL [7.0 mmol/L]), that person should nevertheless be considered to have diabetes. Since all the tests have preanalytic and analytic variability, it is possible that an abnormal result (i.e., above the diagnostic threshold), when repeated, will produce a value below the diagnostic cut point. This scenario is likely for FPG and 2-h PG if the glucose samples remain at room temperature and are not centrifuged promptly. Because of the potential for preanalytic variability, it is critical that samples for plasma glucose be spun and separated immediately after they are drawn. If patients have test results near the margins of the diagnostic threshold, the health care professional should follow the patient closely and repeat the test in 3–6 months. Description In 1997 and 2003, the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (17,18) recognized a group of individuals whose glucose levels did not meet the criteria for diabetes but were too high to be considered nor- mal. “Prediabetes” is the term used for individuals with IFG and/or IGT and/or A1C 5.7–6.4% (39–47 mmol/mol). Pre- diabetes should not be viewed as a clinical entity in its own right but rather as an increased risk for diabetes (Table 2.3) and cardiovascular disease (CVD). Prediabetes is associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension. Diagnosis The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (17,18) defined IFG as FPG levels be- tween 100 and 125 mg/dL (between 5.6 and 6.9 mmol/L) and IGT as 2-h PG after 75-g OGTT levels between 140 and 199 mg/dL (between 7.8 and 11.0 mmol/L). It should be noted that the World Health Organization (WHO) and numerous other diabetes organizations define the IFG cutoff at 110 mg/dL (6.1 mmol/L). As with the glucose measures, several prospective studies that used A1C to predict the progression to diabetes as defined by A1C criteria demonstrated a strong, continuous association between A1C and subsequent diabetes. In a systematic review of 44,203 individuals from 16 cohort studies with a follow-up interval averaging 5.6 years (range 2.8– 12 years), those with A1C between 5.5 and 6.0% (between 37 and 42 mmol/mol) had a substantially increased risk of diabetes (5-year incidence from 9 to 25%). An A1C range of 6.0–6.5% (42–48 mmol/mol) had a 5-year risk of developing diabetes between 25 and 50% and a relative risk 20 times higher compared with A1C of 5.0% (31 mmol/mol) (19). In a communitybased study of African American and non-Hispanic white adults without diabetes, baseline A1C was a stronger predictor of subsequent diabetes and cardiovascular events than fasting glucose (20). Other analyses suggest that A1C of 5.7% (39 mmol/mol) or higher is associated with a diabetes risk similar to that of the high-risk participants in the Diabetes Prevention Program (DPP) (21), and A1C at baseline was a strong predictor of the development of glucose- defined diabetes during the DPP and its follow-up (22). Hence, it is reasonable to consider an A1C range of 5.7–6.4% (39–47 mmol/mol) as identifying individuals with prediabetes. Similar to those with IFG and/or IGT, individuals with A1C of 5.7–6.4% (39– 47 mmol/mol) should be informed of their increased risk for diabetes and CVD and counseled about effective strategies to lower their risks (see Section 5 “Prevention or Delay of Type 2 Diabetes”). Similar to glucose measurements, the continuum of risk is curvilinear, so as A1C rises, the diabetes risk rises disproportionately (19). Aggressive interventions and vigilant follow-up should be pursued for those considered at very high risk (e.g., those with A1C .6.0% [42 mmol/mol]). · Guideline recommendations to start medications recommendations A complete medical evaluation should be performed at the initial visit to - Confirm the diagnosis and classify diabetes. - Detect diabetes complications and potential comorbid conditions. - Review previous treatment and risk factor control in patients with established diabetes. - Begin patient engagement in the formulation of a care management plan. - Develop a plan for continuing care. Recommendations - Provide routine vaccinations for children and adults with diabetes according to age-related recommendations. C - Annual vaccination against influenza is recommended for all persons with diabetes $6 months of age. - Vaccination against pneumonia is recommended for all people with diabetes 2 through 64 years of age with pneumococcal polysaccharide vaccine (PPSV23). At age $65 years, administer the pneumococcal conjugate vaccine (PCV13) at least 1 year after vaccination with PPSV23, followed by another dose of vaccine PPSV23 at least 1 year after PCV13 and at least 5 years after the last dose of PPSV23. - Administer 3-dose series of hepatitis B vaccine to unvaccinated adults with diabetes who are age 19–59 years. - Consider administering 3-dose series of hepatitis B vaccine to un- vaccinated adults with diabetes who are age $60 years. First line medication options and medication side effects Recommendations - Metformin, if not contraindicated and if tolerated, is the preferred initial pharmacologic agent for the treatment of type 2 diabetes. - Long-term use of metformin may be associated with biochemical vitamin B12 deficiency, and periodic measurement of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy. B - Consider initiating insulin therapy (with or without additional agents) in patients with newly diagnosed type 2 diabetes who are symptomatic and/or have A1C $10% (86 mmol/mol) and/or blood glucose levels $300 mg/dL (16.7 mmol/L). If noninsulin monotherapy at maximum tolerated dose does not achieve or maintain the A1C target after 3 months, add a second oral agent, a glucagon-like peptide 1 receptor agonist, or basal insulin. - A patient-centered approach should be used to guide the choice of pharmacologic agents. Considerations include efficacy, hypoglycemia risk, impact on weight, potential side ef- fects, cost, and patient preferences. - For patients with type 2 diabetes who are not achieving glycemic goals, insulin therapy should not be delayed. - In patients with long-standing suboptimally controlled type 2 diabetes and established atherosclerotic cardiovascular disease, empagliflozin or liraglutide should be considered as they have been shown to reduce cardiovascular and all-cause mortality when added to standard care. Ongoing studies are investigating the cardio- vascular benefits of other agents in these drug classes. Initial Therapy Metformin monotherapy should be started at diagnosis of type 2 diabetes unless there are contraindications. Metformin is effective and safe, is inexpensive, and may reduce risk of cardiovascular events and death (22). Metformin may be safely used in patients with estimated glomerular filtration rate (eGFR) as low as 30 mL/min/1.73 m2 (23), and the U.S. label for metformin was recently re- vised to reflect its safety in patients with eGFR $30 mL/min/1.73 m2 (24). Patients should be advised to stop the medication in cases of nausea, vomiting, or dehydration. Metformin is associated with vitamin B12 deficiency, with a recent report from the Diabetes Prevention Pro- gram Outcomes Study (DPPOS) suggesting that periodic testing of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy (25). In patients with metformin contraindications or intolerance, consider an initial drug from another class depicted in Fig. 8.1 under “Dual Therapy” and proceed accordingly. When A1C is $9% (75 mmol/mol), consider initiating dual combination therapy (Fig. 8.1) to more expeditiously achieve the target A1C level. Insulin has the advantage of being effective where other agents may not be and should be considered as part of any combination regimen when hyperglycemia is severe, especially if symptoms are pre- sent or any catabolic features (weight loss, ketosis) are present. Consider initiating combination insulin injectable therapy (Fig. 8.2) when blood glucose is $300 mg/dL (16.7 mmol/L) or A1C is $10% (86 mmol/mol) or if the patient has symptoms of hyperglycemia (i.e., polyuria or polydipsia). As the patient’s glucose toxicity resolves, the regimen may, potentially, be simplified. Combination Therapy Although there are numerous trials com- paring dual therapy with metformin alone, ew directly compare drugs as add-on therapy. A comparative effectiveness meta- analysis (23) suggests that each new class