What Is Prediabetes, and How Can Clinicians Best Help Patients?
1Professor of Medicine, John T. Milliken Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine in St Louis, St Louis, Missouri
Carmichael KA. What is prediabetes and how can clinicians best help patients? Consultant. 2023;63(1):18-19. doi:10.25270/con.2023.01.000004.
Received September 29, 2022. Accepted October 17, 2022. Published online January 12, 2023.
The authors report no relevant financial relationships.
Kim A. Carmichael, MD, Professor of Medicine, John T. Milliken Department of Medicine, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110-1010 (firstname.lastname@example.org)
Q. What is the definition of prediabetes?
A. The standards of care from the American Diabetes Association (ADA) include three potential criteria for defining prediabetes: (1) A fasting plasma glucose of 100-125 mg/dL, (2) a 2-hour postprandial glucose during a 75-g oral glucose tolerance test and 140-199 mg/dL, and (3) A1c of 5.7% to 6.4%.1, 2 An older reference did not include A1c levels but indicated that metabolic syndrome can be a diagnostic criterion instead.3 The WHO defines impaired fasting glucose at a higher level, between 110-124 mg/dL and the Canada Clinical Practice Guidelines use the A1c range from 6% to 6.4% as a standard for prediabetes.2 Screening with A1c may have limitations, however, in the presence of hemoglobinopathies or altered red blood cell turnover.1
Q. What are the potential complications of prediabetes?
A. Prediabetes is associated with multiple metabolic derangements, including insulin resistance, increased inflammatory mediators, greater hepatic glucose output, and endothelial vasodilator and fibrinolytic dysfunction, thereby increasing the risk of macrovascular and microvascular complications.2 There is an increased risk for coronary artery disease, diastolic heart failure, chronic kidney disease, and some studies have shown an association with increased risk for cancer and dementia.2 As prediabetes can be a component of the metabolic syndrome, there is often associated hypertension, dyslipidemia, and central obesity.2 Diabetic retinopathy may be seen in approximately 7.9% of patients with prediabetes, and there can be impairments in color vision, cataracts, and corneal surface disorders.2 Diabetic peripheral neuropathy may be seen in 49% of people with prediabetes and there is also increased risk for autonomic dysfunction and sleep disorders such as obstructive sleep apnea.2 Non-alcoholic fatty liver disease and its complications may also be serious comorbidities among people with prediabetes.2
Q. What are the risk factors for prediabetes and who should be screened?
A. As it is impractical and cost-prohibitive to screen all asymptomatic adults, the ADA has developed a risk assessment tool for diabetes and prediabetes.1 Screening should begin at age 35 but may be done at any age in the setting of overweight or obesity plus one or more other risk factors. These include having first-degree relatives with diabetes, high-risk ethnicity, hypertension or cardiovascular disease, dyslipidemia, acanthosis nigricans, HIV, history of physical inactivity, and women with polycystic ovary syndrome or history of gestational diabetes.1
Q. What strategies should be employed to manage prediabetes?
A. Lifestyle modification is the cornerstone of management for prediabetes.2-4 Among those reaching the goals of the Diabetes Prevention Program, with a minimum of 7% weight loss and maintaining 150 minutes of moderate physical activity per week, there was a risk reduction of 58% for developing type 2 diabetes within three years.4 This level of physical activity even without reaching the weight loss goal reduced incident diabetes by 44%. Cardiovascular risk reduction is also important, including hypertension and lipid management, smoking cessation, and weight loss.2-4
Dietary counseling should be individualized and may involve dieticians/nutritionists, pharmacists, education specialists, community health workers, and even certified technology-assisted programs.4 Bariatric surgery has also been shown to potentially reduce the risk of progression to type 2 diabetes by 75% within a minimum of 4 years.2
Pharmacologic intervention may often be useful for patients with prediabetes 2-4, although no medication is technically FDA-approved for such use. Metformin should be considered because it reduces progression to type 2 diabetes as well as reduces the risk of metabolic complications.2-4 The ADA also recommends metformin therapy for persons aged 25-59 with risks such as BMI ≥ 35 kg/M2, fasting plasma glucose ≥110 mg/dL, A1c ≥ 6%, or women with a history of gestational diabetes mellitus.4
Other pharmacologic interventions may be used, with variable clinical results. These have included acarbose3, thiazolidinediones alone3, thiazolidinediones in combination with ramipril or metformin,2 and dapagliflozin with exenatide.2 Incretin therapy alone such as GLP-1 agonists have been suggested as possible options for managing prediabetes.2-4
More recent studies have suggested potential benefits of vitamin D supplementation for persons with prediabetes. Although routine vitamin D may not improve beta cell function, there can be benefit among persons with low initial vitamin D levels (< 12 ng/mL or < 30 nmol/L).5 In clinical studies, however, supplementation to achieve levels of ≥100 nmol/L (≥ 40 ng/mL) may reduce the risk of progression to type 2 diabetes6, but this benefit may be limited to persons without obesity.7
Q. What is the bottom line?
A. Prediabetes is a serious medical concern as it involves significant metabolic abnormalities resulting in greater cardiovascular risk and increased potential for progression to type 2 diabetes. Early interventions including diet and lifestyle modifications and consideration of pharmacologic therapy should be employed.
- American Diabetes Association. Classification in diagnosis of diabetes: Standards of medical care in diabetes – 2022. Diabetes Care. 2022;45(Suppl. 1):S17-S38. doi:10.2337/dc22-S002
- Lawal Y, Bello F, Kaoje YS. Prediabetes deserves more attention: a review. Clin Diabetes 2020;38(4):328-338. doi:10.2337/cd19-0101
- Garber AJ, Handelsman Y, Dinhorn 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. Endocrine Practice. 2008;14(7):933-946. doi:10.4158/EP.14.7.93310.4158/EP.14.7.933
- American Diabetes Association. Prevention or delay of type 2 diabetes and associated comorbidities: Standards of medical care in diabetes – 2022. Diabetes Care. 2022;45(Suppl. 1):S39-S45.doi:10.2337/dc22-S003
- Rasouli N, Brodsky IG, Chatterjee R, et al. Effects of vitamin D supplementation on insulin sensitivity and secretion in prediabetes. J Clin Endocrinol Metab. 2022;107(1):230-240. doi:10.1210/clinem/dgab649
- Dawson-Hughes B, Staten MA, Knowler WC, et al. Intratrial exposure to vitamin D and new-onset diabetes among adults with prediabetes: A secondary analysis from the vitamin D and type 2 diabetes (D2d) study. Diab Care. 2020;43(12):2916-2922. doi:10.2337/dc20-1765
- Zhang Y, Tan H, Tang J, et al. Effects of vitamin D supplementation on prevention of type 2 diabetes in patients with prediabetes: A systematic review and meta-analysis. Diab Care. 2020;43(7):1650-1658. doi:10.2337/dc19-1708