The new 2017 American Diabetes Association (ADA) Standards of Medical Care in Diabetes contains recommendations for the management of diabetes and its complications.¹ The ADA statement has been updated based on the recent evidence regarding diabetes care and reiterates the focus on the control of traditional modifiable cardiovascular disease (CVD) risk factors through lifestyle and pharmacological interventions. These ADA evidenced-based recommendations for using pharmacological agents to treat risk factors are useful for minimizing CVD risk, taking into consideration the risk-benefit of treatments. In this article, we briefly discuss how the ADA recommendations can help with the management of CVD risk factors among individuals with diabetes.

The ADA recommendations place substantial emphasis on the role of lifestyle modifications, including diet and physical activity, for achieving better glycemic control and cardiovascular outcomes. Prior studies have shown that dietary factors influence mealtime insulin dosing and blood glucose levels. High protein (20-30%) and low carbohydrate diet can have salutary effects on fasting blood glucose, postprandial glucose, and insulin response.² There is no evidence that low protein intake below the recommended daily allowance (0.8 g/kg body weight/day) can delay the reduction in glomerular filtration rate.^3,4 Therefore, as part of individualized medical nutrition therapy, carbohydrate, fat, and protein counting should be used to guide flexible insulin therapy. The recent ADA statement has also made separate recommendations for exercise and physical inactivity as two measures of lifestyle behavior. Individuals with diabetes are recommended to perform 150 minutes or more of moderate-to-vigorous physical activity per week (with no two consecutive days without activity) or 75 minutes per week of vigorous physical activity if they are young and physically fit. Additionally, the new document recommends those with diabetes to reduce the daily time spent in sedentary behavior by interrupting prolonged sitting every 30 minutes.⁵ This recommendation means that not only do patients need to exercise for a certain amount of time per week, but also that they should avoid prolonged sitting for more than 30 minutes with walking or other types of physical activity. This is based on the recent evidence, such as a study of National Health & Nutrition Examination Survey including 5575 US adults, which demonstrated that longer sedentary time per day is associated with all-cause mortality.⁶

Under the new ADA statement, the optimal goals and thresholds to initiate pharmacological treatments to control CVD risk factors should be considered flexible. Benefits of treatment with lipid, blood pressure, and glucose-lowering medications must outweigh their potential side effects. Statins are the first-line lipid lowering medication.⁷ Similar to 2013 ACC/AHA guidelines for the prevention of cardiovascular disease,⁸ the new ADA statement has not specified any LDL goals for statin therapy. Statin is dosed based on patients' atherosclerotic CVD risk factors rather than single LDL levels. High-dose statin therapy is recommended for all patients with diabetes with a history of clinical atherosclerotic CVD or with at least one additional CVD risk factor. Moderate-dose statin therapy is also suggested for patients younger than 40 or older than 70 who have CVD risk factors. Full recommendations about statin therapy are shown in Table 1. Regarding aspirin therapy, and consistent with USPSTF recommendations, the new statement has only recommended treatment for patients with diabetes who are 50 years or older. Aspirin therapy in younger patients with diabetes who have multiple risk factors may be cautiously used, considering the side effects of treatment.

Table 1: Statin Therapy Indications and Intensity for Patients With Diabetes

Risk factor	Age	Statin intensity
History of atherosclerotic CVD	All age groups	High-dose statin
CVD risk factor†	<40 or >75	Moderate or high
	40-75	High dose
No risk factor	<40	None
	40-75	High dose
	>75	Moderate or high

In contrast to statin treatment that is not based on any LDL levels or target treatment thresholds, hypertension treatment is still based on blood pressure levels, and blood pressure control is encouraged for individuals with diabetes.⁹ However, tight blood pressure control for all patients with diabetes is a matter of controversy. A meta-analysis of randomized controlled trials, such as ACCORD (Action to Control Cardiovascular Risk in Diabetes)¹⁰ and ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation),¹¹ showed that compared with a standard treatment goal of systolic blood pressure (SBP) less than 140-160 mmHg, a more insensitive blood pressure control (SBP less than 130 mmHg) has no significant benefit on mortality or nonfatal myocardial infarction.¹² Nevertheless, a more intensive blood pressure control can be beneficial for select subgroups. For example, those with increased risk of stroke can benefit from an SPB close to 130 mmHg if this can be achieved with few drugs and minimal treatment side effects.¹³

Metformin is recommended as the first-line therapy for blood sugar control. It is well documented that metformin prevents CVD events in patients with diabetes.¹⁴ Recent studies have shown that specific Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists have cardiovascular outcome benefits for patients with a history of clinical CVD.¹⁵ Therefore, the ADA recommends clinicians to consider adding empagliflozin or liraglutide, as second-line therapies, to the standard of care for patients with longstanding poorly controlled type 2 diabetes who have a history of clinical atherosclerotic CVD. It will be increasingly important for cardiologists to become comfortable prescribing these therapies, and we expect to see increased attention placed on the cardiovascular outcome benefits of these drugs from ACC.org in the future.

The utility of coronary artery calcium (CAC) score for guiding treatment is not thoroughly discussed in ADA statement. CAC score, a measure of biologic age,¹⁶ is well-established as an inexpensive, non-invasive tool that can stratify CVD risk beyond traditional risk factors. Better risk stratification among patients with diabetes may help clinicians to select patients who would benefit more from initiating or deferring the most aggressive preventive medications. For example, prior studies have found that number needed to treat (NNT) for statin and aspirin therapy for patients with diabetes and CAC = 0 was higher than patients with higher CAC score.^17,18 Although not yet addressed in the ADA statement, these findings may indicate a potential role for CAC to improve clinical decision making in patients with diabetes in the context of physician-patient risk discussion.¹⁹

In conclusion, the new ADA statement highlights the role of lifestyle modifications such as diet and physical activity and updates recommendations regarding the use of preventive pharmacological treatment. Particular attention should be paid to lower carbohydrate diets and reduced sedentary behavior in patients with diabetes, and cardiologists should begin becoming comfortable with SGLT2 inhibitors GLP-1 agonists as second line glycemic agents in clinical practice.

References

1. Standards of medical care in diabetes--2017: summary of revisions. Diabetes Care 2017;40:S4-5.
2. Ley SH, Hamdy O, Mohan V, Hu FB. Prevention and managemetn of type 2 diabetes: dietary components and nutritional strategies. Lancet 2014;383:1999-2007.
3. Robertson L, Waughn N, Robertson A. Protein restriction for diabetec renal disease. Cochrane Database Syst Rev 2007:CD002181.
4. Pan Y, Guo LL, Jin HM. Low-protein diet for diabetic nephropathy: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2008;88:660-6.
5. Dempsey PC, Larsen RN, Sethi P, et al. Benefits for type 2 diabetes of interrupting prolonged sitting with brief bouts of light walking or simple resistance activities. Diabetes Care 2016;39:964-72.
6. Loprinzi PD, Loenneke JP, Ahmed HM, Blaha MJ. Joint effects of objectively-measured sedentary time and physical activity on all-cause mortality. Prev Med 2016;90:47-51.
7. Valensi P, Picard S. Lipids, lipid-lowering therapy and diabetes complications. Diabetes Metab 2011;37:15-24.
8. Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2935-59.
9. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507-20.
10. ACCORD Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood-pressure controle in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-85.
11. Zoungas S, Chalmers J, Neal B, et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med 2014;371:1392-406.
12. McBrien K, Rabi DM, Campbell N, et al. Intensive and standard blood pressure targets in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med 2012;172:1296-303.
13. Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 2015;313:603-15.
14. Holman R. Metformin as first choice in oral diabetes treatment: the UKPDS experience. Journ Annu Diabetol Hotel Dieu 2007:13-20.
15. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28.
16. Shaw LJ, Raggi P, Berman DS, Callister TQ. Coronary artery calcium as a measure of biologic age. Atherosclerosis 2006;188:112-9.
17. Kianoush S, Al Rifai M, Whelton SP, et al. Stratifying cardiovascular risk in diabetes: the role of diabetes-related clinical characteristics and imaging. J Diabetes Complications 2016;30:1408-15.
18. Silverman MG, Blaha MJ, Budoff MJ, et al. Potential implications of coronary artery calcium testing for guiding aspirin use among asymptomatic individuals with diabetes. Diabetes Care 2012;35:624-6.
19. Martin SS, Sperling LS, Blaha MJ, et al. Clinician-patient risk discussion for atherosclerotic cardiovascular disease prevention: importance to implementation of the 2013 ACC/AHA guidelines. J Am Coll Cardiol 2015;65:1361-8.

Keywords: Albuminuria, Aspirin, Benzhydryl Compounds, Blood Glucose, Blood Pressure, Body Weight, Cardiovascular Diseases, Cholesterol, LDL, Coronary Vessels, Diabetes Mellitus, Type 2, Diet, Carbohydrate-Restricted, Drug Combinations, Gliclazide, Glomerular Filtration Rate, Glucagon-Like Peptide 1, Glucose, Glucosides, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Indapamide, Insulin, Metformin, Myocardial Infarction, Perindopril, Recommended Dietary Allowances, Renal Insufficiency, Chronic, Risk Factors, Sedentary Behavior, Smoking

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