Screening and Monitoring of Prediabetes

Screening for Prediabetes

AACE recommends that all individuals aged ≥30 years who meet any of the clinical risk criteria noted below should be screened for prediabetes or type 2 diabetes mellitus (T2DM).¹ The criteria for testing for diabetes in asymptomatic adult individuals are:

• Testing should be considered in all adults who are overweight (BMI ≥25 kg/m²) and who have ≥1 of the additional risk factors noted below. Note that at-risk BMI levels may be lower in some ethnic groups, such as Asian populations.^1-5
• Additional risk factors:
• Physical inactivity
• First-degree relative with diabetes
• High-risk race/ethnicity (eg, African American, Latino, Native American, Asian American, Pacific Islander)
• Hypertension (blood pressure>140/90 mmHg or on therapy for hypertension)
• HDL cholesterol level 250 mg/dL (2.82 mmol/L)
• A1C ≥5.5%, IGT, IFG, or metabolic syndrome on previous testing
• Delivered a baby weighing>9 pounds or patient was previously diagnosed with gestational diabetes mellitus (women)
• Polycystic ovary syndrome (PCOS) (women)
• Other clinical conditions associated with insulin resistance (eg, severe obesity, acanthosis nigricans)
• History of CVD
• Smoking

If a patient does not meet any of the above criteria, testing for T2DM should begin at age 45 years.² In the event of normal results, repeat testing at least every 3 years. More frequent testing should be considered depending on risk status and initial results (eg, those with prediabetes should be tested yearly).²

Medications and Prediabetes Risk

Specific medications that increase prediabetes risk include:

• Anti-depressants: The ongoing use of antidepressant medications may modestly increase the risk of developing prediabetes or T2DM, although the elevation in absolute risk is modest.⁶
• Psychotropic agents: Certain treatments for schizophrenia or bipolar disease may increase prediabetes, T2DM, 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.⁷ 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.⁷
• Human immunodeficiency virus (HIV) treatment: Multiple medications used in the treatment of HIV and its comorbidities have been shown to increase the risk of developing prediabetes or T2DM. Diabetes is 4 times more common in HIV-infected men exposed to highly active anti-retroviral therapy (HAART) vs HIV seronegative men.⁸

In a recent study, nucleoside analogs (reverse transcriptase inhibitors; NRTIs), previously believed to not increase metabolic abnormalities, were shown to increase diabetes risk.⁸ HIV-associated diabetes is also associated with medications used to manage certain comorbid conditions of HIV/AIDS. The antimicrobial pentamidine and megesterol acetate (used as an appetite stimulant) are both possible iatrogenic triggers of HIV-associated diabetes.

Diagnostic Criteria

A diagnosis of prediabetes can be made using IFG/IGT, metabolic syndrome criteria, or A1C values; any of these 3 approaches is acceptable.

IFG/IGT criteria. Prediabetes is identified by IFG (glucose levels 100-125 mg/dL [5.6-6.9 mmol/L])^1-3 and/or IGT (glucose levels 140-199 mg/dL [7.8-11 mmol/L]) following a 2-hour 75-g oral glucose tolerance test (OGTT) given in the morning (after an appropriate overnight fast). Before the OGTT test, patients should be receiving adequate carbohydrate intake, should not be physically active during the test, and must not be smokers.³ Note that IGT should be considered a more important risk than IFG.

Metabolic syndrome criteria. The presence of metabolic syndrome, based on National Cholesterol Education Program IV Adult Treatment Panel III (NCEP ATP III) criteria and also known as insulin resistance syndrome, is a prediabetes equivalent.^1,3 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.⁹ Metabolic syndrome, however, predicts future diabetes better than IFG.^1,3 Approximately one-half of patients with IGT meet the NCEP ATP III criteria for the diagnosis of metabolic syndrome.³ Metabolic syndrome criteria are shown in the table below. 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 1. Clinical Identification of Metabolic Syndrome

* 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.

A1C criteria. A1C values between 5.5% and 6.4% should be a signal to conduct more specific glucose testing. FPG or OGTT should be used for the definitive identification of prediabetes.¹

Glucose threshold guidelines for the diagnosis of prediabetes and diabetes are shown below.

Table 2. Glucose Threshold Guidelines for Diagnosis of Prediabetes and Diabetes

Abbreviations: IFG, impaired fasting glucose; IGT, impaired glucose tolerance.

Monitoring

Monitoring patients with prediabetes to assess their glycemic status should include at least annual reassessment of FPG and/or an OGTT. For individuals where progression is suspected, annual measurements of FPG and A1C, with 2-hour OGTT, should all be conducted.^1,3

While the American Diabetes Association (ADA) advocates using A1C as a diagnostic measure,² AACE recommends A1C primarily for screening and monitoring and not for prediabetes identification. This is because the A1C test can be misleading or inaccurate in some populations.^1,3,11

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

An annual fasting lipid profile should be conducted for all adult patients, including total cholesterol, triglycerides, HDL-C, and LDL-C.¹ 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.^1,12 Other tests of uncertain significance at diagnosis, but that may improve risk stratification in follow-up, include C-reactive protein, lipoprotein(a), lipoprotein-associated phospholipase A2, LDL particle number, and LDL size.¹

Patients with prediabetes should also be assessed for microalbuminuria and have their blood pressure checked at least annually.³

References

1. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17(Suppl 2):1-53.
2. American Diabetes Association. Standards of medical care in diabetes–2013. Diabetes Care. 2013;36(Suppl 1):S11-66.
3. 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(7):933-946.
4. Nichols GA, Hillier TA, Brown JB. Normal fasting plasma glucose and risk of type 2 diabetes diagnosis. Am J Med. 2008;121(6):519-524.
5. Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33(7):1674-1685.
6. 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(12):2611-2616.
7. Newcomer JW. Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry. 2007;68 Suppl 4:8-13.
8. Kalra S, Kalra B, Agrawal N, Unnikrishnan A. Understanding diabetes in patients with HIV/AIDS. Diabetol Metab Syndr. 2011;3(1):2.
9. 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(1):8-13.
10. National Cholesterol Education Program. Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. 2002; Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol.
11. Goldberg RM, Cheng AYY, Punthaker Z, Clement M. Use of glycated hemoglobin (A1C) in the diagnosis of type 2 diabetes mellitus in adults. Canadian Journal of Diabetes. 2010;2010(July):247-249.
12. 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.