Diabetes, Lipids, and Risk for Cardiovascular Disease

Educational Objectives

The goal of this lecture is to improve the treatment of diabetes. After hearing and assimilating this lecture, the clinician will better be able to:

1. Prescribe appropriate lipid-lowering therapy for patients with diabetes.

Summary

Diabetes, Lipids, and Risk for ­Cardiovascular Disease

Interview with: Robert Eckel, MD

ACC/AHA Cholesterol Guideline: The American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (2013) recommends statins for patients:

• with atherosclerotic cardiovascular (CV) disease

• 40 to 75 years of age with diabetes

• with genetic hypercholesterolemia (low-density lipoprotein [LDL] cholesterol ≥190 mg/dL)

• at high risk for CV disease based on a risk calculator

Lifestyle recommendations emphasize healthy dietary patterns rather than eating or avoiding particular foods. Forty minutes of moderate to vigorous physical activity three to four times a week is recommended.

American Diabetes Association (ADA) guidelines: The ADA endorsed the ACC/AHA guidelines generally, but with some differences. The ADA recommends reducing cholesterol intake and maintaining a high intake of omega-3 fatty acids, plant sterols, and fiber. The ADA does not endorse the risk calculator, the use of which has not been adequately tested and proven to reduce the risk for CV disease.

HDL cholesterol and triglycerides: The ADA and ACC/AHA agree that there is no evidence that additional therapies to treat high triglycerides or low high-density lipoprotein (HDL) cholesterol are beneficial. The ADA recommends considering lifestyle interventions, including weight loss, for patients with triglycerides >150 mg/dL and HDL cholesterol <50 mg/dL in women and <40 mg/dL in men.

Dietary recommendations: The ACC/AHA found no convincing evidence that restriction of carbohydrates (based on glycemic index or glycemic load) is an important determinant of risk for CV disease. They continue to recommend restricting saturated fat, which raises levels of LDL cholesterol. The guideline emphasizes overall dietary patterns (eg, Mediterranean and DASH diets).

Statins and risk for diabetes: Statins are associated with an increased incidence of new-onset type 2 diabetes, which may relate to the slight weight gain that can occur in people who take statins. A patient who has an increase in body mass index from 26.5 to 28 may already have been prone to developing diabetes. Weight gain from statins may not result from the drugs themselves, but rather from a tendency of people taking them to become less strict about their diet. The ACC/AHA cholesterol panel concluded that the benefit in reducing CV risk with statins outweighs the increased incidence of type 2 diabetes.

Diabetes, lipids, and CV disease: People with diabetes have a 1.5- to 3-fold increased risk for CV events, and LDL cholesterol level is an important risk factor. Fasting triglyceride level predicts disease, but it is controversial whether high triglyceride levels alone are causative or the risk relates to the fact that high levels are associated with low HDL cholesterol levels, proinflammatory cytokines, and other components of the metabolic syndrome.

Trials looking at lowering triglyceride levels have not shown causation, but that may relate to the designs of the studies. The VA-FIT trial, which has not yet begun, is designed to examine the benefit of lowering triglyceride levels in people with hypertriglyceridemia (200-500 mg/dL) who are already taking a statin.

HDL cholesterol: Epidemiologically, high levels of HDL cholesterol are shown to be protective, and low levels increase risk. Clinical trials of adding drugs that raise HDL cholesterol levels to a statin have not shown benefit. Raising HDL cholesterol with lifestyle modification (eg, weight loss, increased physical activity, moderate alcohol consumption) may be preferable. In addition, the function of HDL cholesterol may be more important than the level.

“Patients with type 2 diabetes age 40 to 75 should be on a statin unless there is a contraindication.”

Take-home message: For primary prevention, adult patients with diabetes should be on at least a moderate dose of a statin, and perhaps on a higher dose if they are at greater risk. For people outside the age range, the risk calculator, which estimates 10-year and lifetime risk, can help with the decision. Monitor patients on a statin for side effects. Measure lipid levels to ensure adherence. Cholesterol goals can be used in the clinic. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) showed that lowering LDL cholesterol from 70 mg/dL to 54 mg/dL in patients with recent acute coronary syndromes is beneficial, particularly for patients with type 2 diabetes.

Readings

Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317:703-13; Adler AI et al: Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000;321:412-9; Aiello LP et al: Intensive diabetes therapy and ocular surgery in type 1 diabetes. N Engl J Med 2015;372:1722-33; Cannon CP et al: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015;372:2387-97; Cushman WC et al: Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-85; Gerstein HC: Reduction of cardiovascular events and microvascular complications in diabetes with ACE inhibitor treatment: HOPE and MICRO-HOPE. Diabetes Metab Res Rev 2002;18 Suppl 3:S82-5;Holman RR et al: 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-89; Holman RR et al: Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med 2008;359:1565-76; Ibsen H et al: Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? The LIFE study. Diabetes Care 2006;29:595-600; Lemmer B: The importance of circadian rhythms on drug response in hypertension and coronary heart disease — from mice and man. Pharmacol Ther 2006;111:629-51; Nathan DM: The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. Diabetes Care 2014;37:9-16; Pop-Busui R et al: Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 2010;33:1578-84.

Disclosures

For this lecture, the following was disclosed: Dr. Anderson reported relationships with Amylin Pharmaceuticals (B), Daichi Sankyo Company (B), Eli Lilly and Company (B), Novo Nordisk (B), and sanofi-aventis UC (A). Dr. Eckel and the members of the planning committee reported nothing to disclose.

Acknowledgements

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

DI070101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.