Pharmacists Play Pivotal Role in Increasing Awareness of Prediabetes

One in 3 American adults live with prediabetes, but 25% of individuals who have the condition are undiagnosed.¹ Prediabetes, as defined by the American Diabetes Association (ADA), is abnormal carbohydrate metabolism not yet at the level of type 2 diabetes (T2D). Diagnoses include elevated hemoglobin A_1C, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT).² IFG is an elevated fasting plasma glucose (FPG) level after an 8-hour fasting period. IGT is an elevated 2-hour plasma glucose level during an oral glucose tolerance test.³ Table 1^2,3 compares diagnostic test cutoffs when diabetes is a concern. The ADA associated A_1C between 5.5% and 6% and 6% and 6.5% with a 5-year risk of developing T2D between 9% and 25% and 25% and 50%, respectively. Those in the 6% to 6.5% range have 20 times’ higher risk than those with A_1C levels of 5%.²

Risk factors for prediabetes and diabetes include the following^1,2:

• Elevated body mass index (BMI)

• First-degree relative with diabetes

• High-density lipoprotein cholesterol level below 35 mg/dL and/or a triglyceride level above 250 mg/dL

• High-risk ethnicity or race, including American Indian, Asian American, Black, Hispanic, or Pacific Islander

• History of cardiovascular disease (CVD)

• History of gestational diabetes

• Hypertension (≥ 140/90 mm Hg or on antihypertensive therapy)

• Other clinical conditions associated with insulin resistance

° Acanthosis nigricans

° Small-for-gestational-age birth weight

° Stein-Leventhal syndrome, also known as polycystic ovary syndrome

• Sedentary lifestyle

Because prediabetes is often asymptomatic, patients can have the condition for years without knowing it. Insulin resistance is primarily because of excess weight, particularly with a higher percentage of body fat in the abdominal area.²

Diabetes Testing

A_1C levels average the patient’s glycemic concentration over 3 months. Table 2² estimates the average glucose over 3 months based on A_1C results. Health care providers should begin testing patients for prediabetes if they meet 1 or more of the following criteria²:

• Aged 35 years or older

• BMI 25 kg/m2 or higher, or 23 kg/m2 or higher in Asian Americans, and 1 or more risk factors

• History of gestational diabetes

• HIV diagnosis

A_1C readings have little variability. However, discrepancies occur with abnormal changes in red blood cell count, such as anemia, end-stage renal disease, glucose-6-phosphate dehydrogenase deficiency, pregnancy, recent blood transfusion(s), and use of erythropoietic-stimulating agent(s).⁴ For patients on the verge of needing therapy change or initiation, providers should double check readings with a blood glucose monitor or 14-day continuous glucose monitor.^2,4

Diet and Exercise

Among the 7.4% US adults with prediabetes, 80% are overweight and 50% have attempted to lose weight.⁵ The National Diabetes Prevention Program provides lifestyle change initiatives through counseling, motivational events, and “restart” opportunities. IT focuses on caloric deficits, healthy lifestyles, managing everyday challenges, physical activity, and self-monitoring.^2,6

The CDC recommends 5% to 7% weight loss in patients with prediabetes to prevent T2D.⁷ Exercise improves insulin sensitivity and reduces abdominal fat.⁸ Physical activity alone reduced the risk of T2D by 58% to 71%.⁷ A minimum of 150 minutes of moderate-intensity physical activity, equivalent to brisk walking, is recommended, broken up into at least 3 sessions per week and at least 10 minutes per session. Patients may include up to 75 minutes of strength training toward their 150-minute goal.²

Medications and Follow-Up

Metformin is a staple first-line treatment for patients with prediabetes. The ADA recommends metformin for patients with prediabetes aged 25 to 59 years, A_1C of 6% or more, a BMI of 35 kg/m² or higher, FPG of 110 mg/dL or more, and/or prior gestational diabetes. Metformin improves A_1C levels, CVD, and weight.^5,9 Metformin may cause bloating, diarrhea, and gastrointestinal discomfort. It is contraindicated in patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m². In instances of metformin overdose or renal failure, patients may present with rare but serious lactic acidosis.⁹

In patients with prediabetes and elevated CVD risk, the American Association of Clinical Endocrinology (AACE) recommends angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for CVD and renal benefits.¹⁰ Alternatively, thiazolidinediones may provide cardioprotective effects. The results of 1 study showed that pioglitazone and rosiglitazone decreased CVD by 72% and 62% after 2 to 3 years, respectively.⁵

A separate meta-analysis recommended against prophylactic statin therapy in prediabetes for cardiovascular protection because of a 20% increased relative risk of T2D.¹¹ However, in patients with prediabetes and dyslipidemia, the AACE recommends maximally tolerated statins for CVD prevention.¹

Patients with new-onset prediabetes without medication therapy should seek testing annually. Exceptions include patients with:

• Maintenance therapy and within glycemic goals; providers recommend following up with a health care provider for testing at least every 6 months.

• A prior history of gestational diabetes; testing includes lifelong follow-up with the provider for a minimum of every 3 years.

• Unmet glycemic goals and/or starting a new therapy; providers recommend following up for testing within 3 months.

Otherwise, providers should evaluate patients at elevated risk for prediabetes for a minimum of every 3 years, with more frequent testing depending on results.

Conclusion

Prediabetes can be daunting because of extensive recommendations, including lifestyle modifications, medication therapy, and monitoring. Patients with new-onset prediabetes often have concerns or questions for health care providers to better understand the disease.

References

1. Khan T, Wozniak GD, Kirley K. An assessment of medical students’ knowledge of prediabetes and diabetes prevention. BMC Med Educ. 2019;19(1):285.
doi:10.1186/s12909-019-1721-9

2. American Diabetes Association. Standards of medical care in diabetes—2022. Diabetes Care. 2022;45(suppl 1):S1-S264.

3. Brannick B, Dagogo-Jack S. Prediabetes and cardiovascular disease: pathophysiology and interventions for prevention and risk reduction. Endocrinol Metab Clin North Am. 2018;47(1):33-50. doi:10.1016/j.ecl.2017.10.001

4. Shepard JG, Airee A, Dake AW, McFarland MS, Vora A. Limitations of A1c interpretation. South Med J. 2015;108(12):724-729. doi:10.14423/SMJ.0000000000000381

5. Echouffo-Tcheugui JB, Selvin E. Prediabetes and what it means: the epidemiological evidence. Annu Rev Public Health. 2021;42:59-77.
doi:10.1146/annurev-publhealth-090419-102644

National Diabetes Prevention Program. CDC. Updated August 27, 2021. Accessed August 17, 2022. https://www.cdc.gov/diabetes/prevention/index.html

7. Prediabetes – your chance to prevent type 2 diabetes. CDC. Updated December 21, 2021. Accessed August 24, 2022. https://www.cdc.gov/diabetes/basics/prediabetes.html

8. Evert AB, Dennison M, Gardner CD, et al. Nutrition therapy for adults with diabetes or prediabetes: a consensus report. Diabetes Care. 2019;42(5):731-754. doi:10.2337/dci19-0014

9. Hostalek U, Gwilt M, Hildemann S. Therapeutic use of metformin in prediabetes and diabetes prevention. Drugs. 2015;75(10):1071-1094. doi:10.1007/s40265-015-0416-8

10. Common comorbidities and complications of prediabetes. American Association of Clinical Endocrinology. Accessed August 24, 2022. https://pro.aace.com/disease-state-resources/diabetes/common-comorbidities-and-complications-prediabetes

11. Sheng Z, Cao JY, Pang YC, et al. Effects of lifestyle modification and anti-diabetic medicine on prediabetes progress: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2019;10:455. doi:10.3389/fendo.2019.00455