Sunday, March 3, 2019

A Spoonful of Medicine Helps the Sugar Go Down


Diabetes mellitus is one of the most common chronic conditions in the world and a significant risk factor for heart disease.  It is a major contributor to global morbidity and mortality. What is diabetes and how can it be controlled to reduce the burden of heart disease and cardiac death? Diabetes is a disease characterized by high blood sugar.  Type I diabetes starts at an early age and occurs because the body does not produce enough insulin (insulin is a hormone secreted by the pancreas and is responsible for regulating the sugar in the body). Type II diabetes occurs in adults, accounts for 90% of the cases of diabetes, and is the result of the body resisting the effects of insulin.  The prevalence of Type II diabetes keeps rising, paralleling the obesity epidemic. It has been estimated that 13% of all U.S. adults have diabetes.  Diabetes is diagnosed by a single blood draw, looking at two tests, glucose (blood sugar) and hemoglobin A1C (a three-month average of the blood sugar). Diabetes is present if hemoglobin A1C is greater than 6.5% or the fasting blood sugar is greater than 126 mg/dl or the nonfasting blood sugar is greater than 200 mg/dl.

Heart disease is the main cause of death among patients with diabetes. Diabetics have a twofold to fourfold increased risk for blockage in the heart arteries, a heart attack or cardiac death and a twofold to fivefold increased risk for congestive heart failure (fluid in the lungs). In addition, diabetic patients are at increased risk for stroke and blockage in the leg arteries.   Therefore the treatment goals for the diabetic patient include lowering the blood sugar, reducing the risk for complications of diabetes (for example kidney disease and blindness) and especially reducing the risk for heart disease.

Cardiovascular risk factor management in Type II diabetes starts with diet.  Patients are often referred to specialized dieticians to help with monitoring caloric intake and carbohydrate consumption. A Mediterranean-style diet can greatly reduce blood sugar.  The goal is to lower the hemoglobin A1C to < 7%. Overweight and obese patients are counseled about weight loss; even a modest reduction in weight of 3-5% can make a big difference.  For severely obese patients, weight loss surgery (for example, gastric sleeve) is often recommended. With significant weight loss, diabetic medications can be weaned down and in many cases stopped.  Diabetic patients with elevated blood pressure should be placed on medication, with a blood pressure goal between 120 and 140.  Diabetics whose LDL cholesterol is high should be prescribed a statin, with an LDL goal < 70 mg/dl. Achieving these aims is not easy.  In a large recent study of 73,000 diabetic patients, 73% met the hemoglobin A1C target, 69% met the blood pressure goal and 48% hit the LDL number. Unfortunately, however, only 21% met all three goals.

Recently, the medical management of the patient with Type II diabetes underwent a revolution.  There are twelve classes of medications (including insulin) and at least 36 individual drugs approved for the treatment of diabetes.  Picking the right drug or the right combination of drugs can be difficult. It is generally agreed that treatment start with metformin, which has been shown to lower hemoglobin A1C and reduce cardiac events.  Picking the right target for treatment is just as difficult. For the past 20 years, the medical therapy of diabetes focused on intensive control of blood sugar. However, this approach did not reduce cardiovascular events and may have increased them.  Then in 2008 the Food and Drug Administration mandated that any new diabetes drug must prove its cardiovascular safety before being approved for use.  This resulted in the discovery of new drugs which did just that; they were shown to lower the risk for major heart events and reduce cardiac deaths. This has led to a fundamental shift in diabetes management, away from lowering blood sugar and toward reducing cardiac risk.  In fact, for the first time ever, the American Diabetes Association and the American College of Cardiology have aligned their medication recommendations for treating Type II diabetes.  

The new agents fall into two classes of diabetes medications: sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor (GLP-1) agonists.  Both classes of agents substantially reduce the risk for heart attack, stroke and cardiac death. Both reduce blood pressure and promote weight loss. The best-studied SGLT2 inhibitor is empagliflozin (Jardiance), a once a day oral medication. The classic GLP-1 agonist is liraglutide (Victoza), a once weekly injection. It is felt that SGLT2 inhibitors are better for CHF patients while the GLP-1 agonists are better at reducing heart attack and stroke. 

The bottom line, according to both diabetes doctors and cardiologists, is that patients with Type II diabetes and established heart disease start treatment with lifestyle management (especially diet and weight loss).  If medication is needed, then metformin is the first line agent.  If a second line agent is necessary, then either an SGLT2 inhibitor or a GLP-1 agonist should be used, depending on patient characteristics.