Screening and Monitoring of Prediabetes

Screening for Prediabetes

AACE recommends that individuals who meet any of the clinical risk criteria noted below should be screened for prediabetes or type 2 diabetes (T2D) (1).

• Age ≥45 years without other risk factors
• CVD or family history of T2D
• Overweight or obese
• Sedentary lifestyle
• Member of an at-risk racial or ethnic group:
• Asian
• African American
• Hispanic
• Native American (Alaska Natives and American Indians)
• Pacific Islander
• High-density lipoprotein cholesterol (HDL-C) <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L)
• Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and/or metabolic syndrome
• Polycystic ovary syndrome (PCOS), acanthosis nigricans, or nonalcoholic fatty liver disease (NAFLD)
• Hypertension (blood pressure >140/90 mm Hg or on antihypertensive therapy)
• History of gestational diabetes or delivery of a baby weighing more than 4 kg (9 lb)
• Antipsychotic therapy for schizophrenia and/or severe bipolar disease
• Chronic glucocorticoid exposure
• Sleep disorders in the presence of glucose intolerance (A1C >5.7%, IGT, or IFG on previous testing), including obstructive sleep apnea (OSA), chronic sleep deprivation, and night-shift occupation

In the event of normal results, repeat testing at least every 3 years. Clinicians may consider annual screening for patients with 2 or more risk factors (1).

Medications and Prediabetes Risk
Specific medications that increase prediabetes risk include:

1. Antidepressants: The ongoing use of antidepressant medications may modestly increase the risk of developing prediabetes or T2D, although the elevation in absolute risk is modest (2).
2. Psychotropic agents: Certain treatments for schizophrenia or bipolar disease may increase prediabetes, T2D, and/or CVD risk. Substantial weight gain has been associated with psychotropic agents, including some antipsychotic medications. These medications are also associated with adiposity-dependent and possibly adiposity-independent changes in insulin sensitivity and lipid metabolism (3). Among the second- and first-generation antipsychotics, respectively, clozapine and olanzapine and thioridazine and chlorpromazine have been associated with an increased risk of T2DM and dyslipidemia.

Diagnostic Criteria
A diagnosis of prediabetes should be made according to glucose criteria, although the metabolic syndrome is considered a prediabetes equivalent (1).

Glucose criteria. Glucose criteria for the diagnosis of prediabetes and diabetes appear in Table 1 (1,4). Prediabetes may be identified by the presence of impaired glucose tolerance (IGT; plasma glucose 140-199 mg/dL 2 hours after ingesting 75 g of glucose) and/or impaired fasting glucose (IFG; fasting glucose 100-125 mg/dL). A1C values between 5.5% and 6.4% inclusive should be a signal to do more specific glucose testing but should not be considered diagnostic. For prediabetes, A1C testing should be used only as a screening tool; FPG measurement or an oral glucose tolerance test (OGTT) should be used for definitive diagnosis.

Table 1. Glucose Threshold Guidelines for Diagnosis of Prediabetes and Diabetes (1)

Abbreviations: A1C = hemoglobin A1C; FPG = fasting plasma glucose; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; PG = plasma glucose.
*A1C should be used only for screening prediabetes. The diagnosis of prediabetes, which may manifest as either IFG or IGT, should be confirmed with glucose testing.
†Glucose criteria are preferred for the diagnosis of DM. In all cases, the diagnosis should be confirmed on a separate day by repeating glucose or A1C testing. When A1C is used for diagnosis, follow-up glucose testing should be done when possible to help manage DM.

Metabolic syndrome criteria. The presence of metabolic syndrome—also known as insulin resistance syndrome—based on National Cholesterol Education Program IV Adult Treatment Panel III (NCEP ATP III) criteria, is a prediabetes equivalent (1,4). The San Antonio Heart Study analyzed the risks associated with metabolic syndrome, NCEP risk factor categories, and 2-hour glucose values and found very high risk in patients with both IFG and metabolic syndrome. Patients with normal fasting glucose levels and metabolic syndrome, as well as those with IFG without metabolic syndrome, were also found to be at increased risk (5). Metabolic syndrome predicts future diabetes better than IFG (1,4). Approximately one-half of patients with IGT meet the NCEP ATP III criteria for the diagnosis of metabolic syndrome (3).

Table 2 shows the metabolic syndrome criteria. Three of 5 metabolic syndrome criteria are sufficient for identification; however, recent evidence suggests that even 2 of 5 metabolic syndrome criteria may be adequate (1,3).

Table 2. Clinical Identification of Metabolic Syndrome* (6)

*The ATP III panel did not find adequate evidence to recommend routine measurement of insulin resistance (eg, plasma insulin), proinflammatory state (eg, high-sensitivity C-reactive protein), or prothrombotic state (eg, fibrinogen or PAI-1) in the diagnosis of the metabolic syndrome.
†Some male persons can develop multiple metabolic risk factors when the waist circumference is only marginally increased, eg, 94-102 cm (37-39 in). Such persons may have a strong genetic contribution to insulin resistance. They should benefit from changes in life habits, similarly to men with categorical increases in waist circumference.

Monitoring
Monitoring patients with prediabetes to assess their glycemic status should include at least annual reassessment of FPG and/or an OGTT. For individuals in whom progression is suspected, annual measurements of FPG and A1C, with 2-hour OGTT, should be conducted (1,4).

CVD risk factors (especially elevated blood pressure and/or dyslipidemia) and excessive weight gain should be addressed and monitored at regular intervals (1,4).

An annual fasting lipid profile should be conducted for all adult patients, including total cholesterol, triglycerides, HDL-C, and LDL-C. If LDL-C is at goal, but triglyceride concentrations are >200 mg/dL, calculate non–HDL-C (total cholesterol – HDL-C), or check the patient's apolipoprotein B level. Other tests of uncertain significance at diagnosis, but which may improve risk stratification in follow-up, include C-reactive protein, lipoprotein(a), lipoprotein-associated phospholipase A2, LDL particle number, and LDL size (1,7).

Patients with prediabetes should also be assessed for microalbuminuria and have their blood pressure checked at least annually (4).

References

1. Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists and American College of Endocrinology: clinical practice guidelines for developing a diabetes mellitus comprehensive care plan—2015. Endocr Pract. 2015;21:1-87.
2. Kivimaki M, Hamer M, Batty GD, et al. Antidepressant medication use, weight gain, and risk of type 2 diabetes: a population-based study. Diabetes Care. 2010;33:2611-2616.
3. Newcomer JW. Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry. 2007;68(suppl 4):8-13.
4. Garber AJ, Handelsman Y, Einhorn D, et al. Diagnosis and management of prediabetes in the continuum of hyperglycemia: when do the risks of diabetes begin? A consensus statement from the American College of Endocrinology and the American Association of Clinical Endocrinologists. Endocr Pract. 2008;14:933-946.
5. Lorenzo C, Williams K, Hunt KJ, Haffner SM. The National Cholesterol Education Program - Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome as predictors of incident cardiovascular disease and diabetes. Diabetes Care. 2007;30:8-13.
6. National Cholesterol Education Program Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143-421.
7. Jellinger PS, Smith DA, Mehta AE, et al. American Association of Clinical Endocrinologists' guidelines for management of dyslipidemia and prevention of atherosclerosis. Endocr Pract. 2012;18(suppl 1):1-78.