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ABSTRACT
Cardiovascular disease remains the leading cause of death in
men and women in the United States. Aggressive treatment
of insulin resistance and its associated lipid abnormalities
remains a top priority for preventing cardiovascular morbid-
ity and mortality.
Keywords: type 2 diabetes, metabolic syndrome, cardiovas-
cular disease, atherogenic dyslipidemia, insulin resistance
Learning objectives
Describe the pathophysiology of lipoprotein metabolism.
Identify the 2012 ADA criteria for screening for diabetes
and dyslipidemia in adults.
Discuss strategies to aggressively treat lipoprotein abnor-
malities in patients with type 2 diabetes and metabolic
syndrome.
Copyright 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
CME
Copyright 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Lipoprotein abnormalities in patients with type 2 diabetes and metabolic syndrome
SCREENING
The 2012 ADA guidelines include criteria for screening
asymptomatic adults for diabetes and pre-diabetes. The
ADA recommends that healthcare providers consider
testing asymptomatic adults who are overweight (defined FIGURE 2. Cholesterol metabolism in patients with insulin
as a BMI of 25 kg/m2 or greater) and have one or more of resistance and dyslipidemia
these risk factors:
physical inactivity other clinical conditions that may indicate insulin resis-
first-degree relative with diabetes tance, such as morbid obesity or acanthosis nigricans
high-risk race or ethnicity (African American, Latino, history of CVD.4
Native American, Asian American, Pacific Islander) Overweight patients without any of the above risk
delivering a baby weighing more than 9 lbs or a diagnosis factors should begin diabetes testing at age 45. Patients
of gestational diabetes (women) who dont meet the definition of pre-diabetes should be
hypertension (defined as a BP of 140/90 mm Hg or greater, monitored every 3 years; those with pre-diabetes should
or taking antihypertensive medication) be monitored annually.3
HDL cholesterol of 35 mg/dL or less, and/or a triglyceride
level greater than 250 mg/dL DIAGNOSING METABOLIC SYNDROME AND
polycystic ovary syndrome (in women) TYPE 2 DIABETES
A1C of 5.7% or greater, impaired glucose tolerance, or Metabolic syndrome is recognized and defined by the Adult
impaired fasting glucose on previous testing Treatment Panel (ATP) III guidelines from the National
Copyright 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
CME
Copyright 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Lipoprotein abnormalities in patients with type 2 diabetes and metabolic syndrome
Omega-3 fatty acids The beneficial effect of EPA/DHA plasma glucose (1 to 2 hours after beginning a meal) of
in lowering triglycerides has only been demonstrated using less than 180 mg/dL.4
omega-3 derived from marine sources. The AHA recom- The ADA-recommended medical nutrition therapy should
mends 2 to 4 grams of EPA plus DHA per day for triglycer- begin with consultation with a registered dietitian, and
ide reduction. For every 1 gram of EPA/DHA, triglycerides may include:
are reduced 5% to 10%. The accompanying effects are weight loss for patients who are overweight or obese
increased LDL and HDL cholesterol.9 Supplementation a low-carbohydrate, low-fat, calorie-restricted, or
often is required, because achieving the required 2 to 4 Mediterranean diet for short-term (2 years) weight loss.
grams solely from dietary intake is difficult.9 Monitor lipid profiles, renal function, and protein intake
Fibrates Fenofibrate inhibits the synthesis of triglyc- for patients on low-carbohydrate diets.
erides and stimulates the catabolism of triglyceride-rich
lipoproteins. The FIELD trial showed a 22% reduction in
triglycerides but also reported an increase in pancreatitis.13 Most patients with type 2
Wan and colleagues found that fenofibrate decreased
triglycerides by 63% but caused significant adverse diabetes who need insulin can
reactions, including liver damage, GI intolerance, and
rhabdomyolysis.11 A 2010 review by Moutzouri and col- be successfully treated with
leagues found that fenofibrate as monotherapy decreased
triglycerides by 20% to 50% and also increased HDL basal insulin alone.
cholesterol.14
The most common adverse reactions to fenofibrate are
nausea, diarrhea, myalgia, and moderate increases in cre- primary prevention steps including a 7% weight loss, 150
atinine kinase. Patients who also are taking a statin during minutes per week of moderate physical activity (50%-70%
fenofibrate therapy are at increased risk for myalgia and of maximum heart rate) over 3 days per week, resistance
rhabdomyolysis.14 training, diet containing 14 grams of fiber per 1,000 kcal,
Niacin This drug is most effective when used to raise and limiting sugar-sweetened beverages.
HDL cholesterol. At high doses, niacin can make blood management including an individualized macronutrient
glucose control more difficult by increasing blood glucose prescription, diet containing less than 7% saturated fat,
levels. At modest doses (750 to 2,000 mg/day), niacin can and minimizing trans-fat intake.
improve LDL, HDL, and triglyceride levels with minimal limiting daily alcohol intake to 1 drink (adult women)
effects on blood glucose.4 and 2 drinks (adult men).4
Statins HMG-CoA reductase inhibitors have been shown The goal of the ADAs recommended dyslipidemia/lipid
to reduce LDL cholesterol by 30% to 40%.4 Higher initial management is an LDL cholesterol level less than 100 mg/
triglyceride levels respond well to statin therapy, provid- dL (less than 70 mg/dL in patients with CVD). If those
ing a 10% to 52% reduction. Numerous studies support targets are unsuccessful, an alternative goal is a 30% to
the use of statins for hypertriglyceridemia, but few trials 40% reduction in LDL cholesterol. The goal of glycemic
address the effect of statins on severe hypertriglyceridemia.10 control is an A1C of less than 7%. Recommended lifestyle
The most common adverse reactions to statin therapy are modifications include weight loss; physical activity; limiting
pain, pharyngitis, myalgia, and headache. The STELLAR alcohol intake; decreasing intake of saturated fat, trans-fat,
trial reported that patients on higher statin doses were at and cholesterol; and increasing intake of omega-3 fatty
the greatest risk for myalgia.15 acids, viscous fiber, and plant stanols/sterols.
Combination therapy To achieve optimal glycemic control, Statin therapy is recommended for the following patients
combination therapy may be required.4 Statins in combi- without consideration of lipid profile:
nation with niacin or fibrate may be beneficial in treating patients with diagnosed CVD
LDL, HDL, and triglycerides, but can potentially increase patients without CVD who are over age 40 and have one
transaminase levels and increase the risk of myositis and or more risk factors for CVD
rhabdomyolysis. The risk of rhabdomyolysis is greater patients at lower risk and under age 40 whose LDL
with higher statin doses and in patients with poor renal cholesterol is more than 100 mg/dL.
function. This risk decreases when a statin is combined Little evidence-based data supports treating low HDL and
with fenofibrate instead of gemfibrozil. elevated triglycerides. For patients with severe hypertriglyc-
eridemia, treat with lifestyle changes and pharmacologic
CURRENT TREATMENT GUIDELINES therapy to decrease the risk of acute pancreatitis. Treatment
The ADA recommends the following glycemic goals for options include fibric acid derivative, niacin, and fish oil.4
patients with diabetes: A1C of less than 7%, preprandial The American Heart Association (AHA) recommends
plasma glucose of 70 to 130 mg/dL, and peak postprandial these intensive therapeutic lifestyle changes:
Copyright 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
CME
A Mediterranean-style diet; 5% to 10% weight loss; and atherogenic dyslipidemia has been advocated by the
increase in dietary fiber and omega-3 fatty acids; elimina- ADA, AHA, NCEP, and NLA. By diagnosing and aggres-
tion of trans-fats; and reduction of simple carbohydrates, sively treating patients at increased risk for cardiovascular
fructose, saturated fats, and alcohol. disease, clinicians can reduce the burden these diseases
Moderate physical activity, which can decrease triglyceride place on patients and society. JAAPA
levels 20% to 30%.9
Earn Category I CME credit by reading this article and the article begin-
ning on page 20 and successfully completing the posttest on page 28.
Successful completion is defined as a cumulative score of at least 70%
In patients with very correct. This material has been reviewed and is approved for 1 hour of
clinical Category I (Preapproved) CME credit by the AAPA. The term of
high triglycerides, approval is for 1 year from the publication date of July 2013.
Copyright 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.