Patient Care

Overview and Discussion of the 2017 VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care

Fed Pract. 2017 October;34(suppl 8):S14-S19

References

1. Centers for Disease Control and Prevention. 2017 National Diabetes Statistics Report. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics -report.pdf. Accessed 9/7/2017.

2. Miller DR, Safford MM, Pogach LM. Who has diabetes? Best estimates of diabetes prevalence in the Department of Veterans Affairs based on computerized patient data. Diabetes Care. 2004;27(suppl 2):B10-B21.

3. Bethel MA, Sloan FA, Belsky D, Feinglos MN. Longitudinal incidence and prevalence of adverse outcomes of diabetes mellitus in elderly patients. Arch Intern Med. 2007;167(9):921-927.

4. American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36(4):1033-1046.

5. U.S. Department of Veteran Affairs, U.S. Department of Defense.VA/DoD clinical practice guidelines: management of diabetes mellitus in primary care. https://www.healthquality.va.gov/guidelines/CD/diabetes/. Updated April 18, 2017. Accessed August 28, 2017.

6. U.S. Department of Veteran Affairs, U.S. Department of Defense. VA/DoD clinical practice guidelines: CPG policy guidance: guidelines for guidelines. https://www.healthquality.va.gov/documents/cpgGuidelinesForGuidelinesFinalRevisions051214.docx . Updated February 8, 2017. Accessed August 28,2017.

7. Andrews J, Guyatt G, Oxman AD, et al. GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol. 2013;66(7):719-725.

8. Agency for Healthcare Research and Quality. The SHARE approach. https://www.ahrq.gov/professionals/education/curriculum-tools/shareddecisionmaking/index.html. Updated February 2017. Accessed August 28, 2017.

9. Kirkman MS, Briscoe VJ, Clark N, et al; Consensus Development Conference on Diabetes and Older Adults. Diabetes in older adults: a consensus report. J Am Geriatr Soc. 2012;60(12):2342-2356.

10. VA/DoD Evidence-based Practice. Shared Decision Making, A Guide for Busy Clinicians. https://www.qmo.amedd.army.mil/asthma/SDM-POCKETGuide.pdf. Accessed 3/17/2017.

11. Bertakis KD, Azari R. Patient-centered care is associated with decreased health care utilization. J Am Board Fam Med. 2011;24(3):229-239.

12. Robinson JH, Callister LC, Berry JA, Dearing KA. Patient-centered care and adherence: definitions and applications to improve outcomes. J Am Acad Nurse Pract. 2008;20(12):600-607.

13. Mullan RJ, Montori VM, Shah ND, et al. The diabetes mellitus medication choice decision aid: a randomized trial. Arch Intern Med. 2009;169(17):1560-1568.

14. Branda ME, LeBlanc A, Shah ND, et al. Shared decision making for patients with type 2 diabetes: a randomized trial in primary care. BMC Health Serv Res. 2013;13:301.

15. Hsu WC, Lau KH, Huang R, et al. Utilization of a cloud-based diabetes management program for insulin initiation and titration enables collaborative decision making between healthcare providers and patients. Diabetes Technol Ther. 2016;18(2):59-67.

16. Buhse S, Mühlhauser I, Heller T, et al. Informed shared decision-making programme on the prevention of myocardial infarction in type 2 diabetes: a randomised controlled trial. BMJ Open. 2015;5(11):e009116.

17. Agency for Healthcare Research and Quality. Health literacy universal precautions tool kit, 2nd edition. Use the teach-back method: tool #5. http://www.ahrq .gov/professionals/quality-patient-safety/quality-resources/tools/literacy-toolkit/healthlittoolkit2-tool5.html. Updated February 2015. Accessed August 28, 2017.

18. Ajala O, English P, Pinkney J. Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes. Am J Clin Nutr. 2013;97(3):505-516.

19. Huo R, Du T, Xu Y, et al. Effects of Mediterranean-style diet on glycemic control, weight loss and cardiovascular risk factors among type 2 diabetes individuals: a meta-analysis. Eur J Clin Nutr. 2015;69(11):1200-1208.

20. Esposito K, Maiorino MI, Bellastella G, Chiodini P, Panagiotakos D, Giugliano D. A journey into a Mediterranean diet and type 2 diabetes: a systematic review with meta-analyses. BMJ Open. 2015;5(8):e008222.

21. Laine C, Taichman DB, Mulrow C. Trustworthy clinical guidelines. Ann Intern Med. 2011;154(11):774-775.

22. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837-853.

23. Beulens JW, Patel A, Vingerling JR, et al; AdRem project team; ADVANCE management committee. Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial. Diabetologia. 2009;52(10):2027-2036.

24. ACCORD Study Group, Gerstein HC, Miller ME, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364(9):818-828.

25. Duckworth W, Abraira C, Moritz T, et al; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129-139.

26. Hemmingsen B, Lund SS, Gluud C, et al. Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2011;(6):CD008143.

27. Hasan R, Firwana B, Elraiyah T, et al. A systematic review and meta-analysis of glycemic control for the prevention of diabetic foot syndrome. J Vasc Surg. 2016;63(suppl 2):22S-28S.e1-2.

28. Radin MS. Pitfalls in hemoglobin A1c measurement: when results may be misleading. J Gen Intern Med. 2014;29(2):388-394.

29. English E, Idris I, Smith G, Dhatariya K, Kilpatrick ES, John WG. The effect of anaemia and abnormalities of erythrocyte indices on HbA1c analysis: a systematic review. Diabetologia. 2015;58(7):1409-1421.

30. Goldstein DE, Little RR, Lorenz RA, et al. Tests of glycemia in diabetes. Diabetes Care. 2004;27(7):1761-1773.

31. Herman WH, Ma Y, Uwaifo G, et al; Diabetes Prevention Program Research Group. Differences in A_1c by race and ethnicity among patients with impaired glucose tolerance in the Diabetes Prevention Program. Diabetes Care. 2007;30(10):2453-2457.

32. Little RR, Rohlfing CL, Hanson S, et al. Effects of hemoglobin (Hb) E and HbD traits on measurements of glycated Hb (HbA1c) by 23 methods. Clin Chem. 2008;54(8):1277-1282.

33. Sacks DB, Arnold M, Bakris GL, et al; Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care. 2011;34(6):e61-e99.

34. Hayward RA, Reaven PD, Wiitala WL, et al; VADT Investigators. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;372(23):2197-2206.

35. Zoungas S, Chalmers J, Neal B, et al; ADVANCE-ON Collaborative Group. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med. 2014;371(15):1392-1406.

36. Tseng CL, Soroka O, Maney M, Aron DC, Pogach LM. Assessing potential glycemic overtreatment in persons at hypoglycemic risk. JAMA Intern Med. 2014;174(2):259-268.

37. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36(5):1384-1395.

38. ORIGIN Trial Investigators. Predictors of nonsevere and severe hypoglycemia during glucose-lowering treatment with insulin glargine or standard drugs in the ORIGIN trial. Diabetes Care. 2015;38(1):22-28.

39. Bruderer SG, Bodmer M, Jick SS, Bader G, Schlienger RG, Meier CR. Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK—a nested case-control analysis. Diabetes Obes Metab. 2014;16(9):801-811.

40. Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2016;164(11):740-751.

Nutrition Recommendations

Nutrition therapy is a key component of any successful DM management plan. The EBPWG added 2 strong recommendations for DM nutrition strategies. The first recommendation is to follow a Mediterranean diet, if this resonates with the patient’s values and preferences (Table 1).

Features commonly used to describe a traditional Mediterranean diet include:

High intake of vegetables, fruits, nuts, unrefined grains, and olive oil;
Moderate intake of fish and poultry;
Low or moderate intake of wine; and
Low intake of red meat, processed meat, dairy, and sweets.

The Mediterranean diet effectively improves glycemic control, delays the time to first pharmacologic intervention, and reduces cardiovascular risk factors in individuals with diabetes.¹⁸ An additional benefits of this dietary pattern includes significant hemoglobin A_1c (HbA_1c) reduction.^19,20 A Mediterranean diet also has been linked to improved cardiovascular outcomes and weight loss. In general, the evidence supporting a Mediterranean diet are robust, but securing and adapting to these types of foods can be challenging for some patients.

The second nutrition recommendation is to reduce the percentage of energy from carbohydrates to between 14% and 45% per day and/or eat foods with lower glycemic index. Patients who do not choose a Mediterranean diet can employ this dietary pattern. A systematic review compared dietary interventions, including lower carbohydrate and low-glycemic index diets, and showed both dietary interventions improved glycemic control.¹⁸ Unfortunately, many studies compare different intervention diets rather than comparing an intervention against a control diet. However, based on the available evidence, the Working Group endorses a Mediterranean diet and carbohydrate reduction and low glycemic index foods as dietary options in which the benefits seem to outweigh harms.

Target Hemoglobin A₁_c Range

The EBPWG reviewed several large, intensive glucose control trials to apply recent evidence to ongoing HbA_1c treatment targets. The CPG strongly reaffirms that rather than assigning a single glycemic goal for all patients, clinicians should use SDM to develop an HbA_1ctarget range that is risk-stratified (Table 2).

When summarizing evidence regarding the risks and benefits of treatment, the guidelines strongly recommend that absolute risk reduction (ARR) be considered rather than relative risk reduction (RRR).²¹ As an example of the difference between the ARR and RRR, in the United Kingdom Prospective Diabetes Study (UKPDS) there was a 37% RRR for microvascular complications (eg, retinopathy, neuropathy, and nephropathy) with an HbA_1c reduction from 7.9% to 7.0%. However, the ARR was about 5.0%, and the number needed to treat for benefit was almost 20.²² In addition, when initial HbA_1c is lower, the incremental health benefits by further reducing HbA_1c are smaller because of the lower overall incidence of microvascular complications. Therefore, a patent with a lower initial HbA_1c is less likely to derive benefit from treatment than are individuals with a higher HbA_1c (eg, > 9%.

The ARR of complications must be balanced against the risk of therapy. Several major trials tested the hypothesis that intensive glycemic control (target HbA_1c at least < 7%) improved cardiovascular outcomes in patients with T2DM.^23-25 These trials did not demonstrate cardiovascular benefit from intensive control to reach HbA_1c < 7%, and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study revealed possible cardiovascular harm.²⁴

In addition, because these studies enrolled patients with established T2DM, they demonstrated less reduction in microvascular complications than was seen in newly diagnosed patients in UKPDS.²² Systematic reviews comparing intensive and conventional glucose control showed no significant differences in all-cause mortality or death from cardiovascular disease.^26,27 Therefore, intensive control of T2DM has the greatest impact on microvascular complications and is most successful when initiated early in the disease process.

A target HbA_1c range is recommended rather than a threshold value (eg, HbA_1c < 8.0%) for several reasons. Most important the clinical trials that provide evidence for improved glycemic control used an HbA_1c value recorded over time, not a single value measured at one point in time. Many factors influence HbA_1c measurements other than just glycemic control.²⁸ These include anemia, chronic kidney disease, race/ethnicity, and hemoglobinapathies.^29-32 Patients can have clinically significant variation in HbA_1c results between test samples, even when obtained from the same laboratory.³³ For these reasons, the CPG continues to recommend use of fasting glucose ≥ 126 mg/dL to establish a DM diagnosis when the HbA_1c is < 7.0%. This limits the likelihood that patients will be incorrectly diagnosed with DM, which can affect insurability, disability, or the trajectory of a military career. For patients with diagnosed T2DM, glycemic control over time remains important, but overreliance on a single HbA_1c test could lead to overtreatment and potential adverse outcomes.

The EBPWG considered the target HbA_1c and outcomes in UKPDS, ACCORD, Veterans Affairs Diabetes Trial (VADT), and the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) when considering HbA_1c target ranges.^23,25,34,35 Indeed, target HbA_1c ranges, with both lower and upper bounds, were considered a better way to balance the potential risks and benefits of therapy. For example, a target HbA_1c range of 6% to 7% might be appropriate in patients with a life expectancy more than 10 to 15 years with no significant microvascular disease and no other socioeconomic limitations to therapy. For patients with established microvascular disease or a life expectancy < 10 years, target ranges from 7% to 9% might be appropriate depending on patient-specific factors. A patient with advanced disease or limited life expectancy is less likely to derive benefit from intensive control, yet they would be exposed to the adverse effects from intensive therapy. For these patients, consider a less-intensive HbA_1c target range. Although life expectancy can be difficult to estimate, this framework can be helpful to reach a target range using SDM with the patient.

An important issue in current DM management is potential overtreatment, which sits at the intersection of overuse of low value practices and medication safety. Up to 65% of older veterans with DM taking hypoglycemic agents might be overtreated based on the presence of DM complications, medical comorbidities, and decreased life expectancy that confer more risk than benefit from lower HbA_1c levels.³⁶ Harms from intensive glycemic control, such as increased risk of death from cardiovascular events and severe hypoglycemia must be considered.²⁴ Patient-specific factors that could increase risk of hypoglycemia include the use of specific drugs (insulin and sulfonylureas), advanced age (> 75 years), cognitive impairment, chronic renal insufficiency, and food insufficiency.^37-39

The CPG did not address specific pharmacologic treatment options because these can change rapidly as the literature evolves. Instead, the CPG refers clinicians to current criteria issued by the VA and DoD, which are updated frequently. In line with recent reviews, the CPG continues to recommend metformin as a first-line therapy for most patients with T2DM.⁴⁰ An important consideration in the future will be the potential for cardiovascular risk reduction from specific medications or classes of medication independent of HbA_1c reduction. As ongoing clinical trials are completed, SDM, ARR, and potential harm from therapy will remain important considerations.