Chpt 15 Diagnois and Magement of type 2

[Guest guest]

Diagnosis and Management of Type 2 Diabetes, 10th Edition, Ch 15, Pt2

Long-Term Complications and Treatments: Dyslipidemia

Diagnosis_and_Management_of_Type_2_DiabetesSteve V. Edelman, MD

R. Henry, MD

Dyslipidemia

Lipid abnormalities that accelerate atherosclerosis and increase the risk of

CV disease are significantly more common in patients with type 2 diabetes

than in nondiabetic individuals. In addition, central obesity associated

with type 2 diabetes is also a risk factor for CV disease. These combined

factors have resulted in CV disease becoming a major cause of morbidity and

mortality in type 2 diabetes. The characteristic lipid abnormalities in type

2 diabetes are....

Advertisement

<http://ads.diabetesincontrol.com/www/delivery/ck.php?oaparams=2__bannerid=2

5__zoneid=17__cb=b1e5a89424__oadest=http%3A%2F%2Fad.doubleclick.net%2Fjump%2

FN6625.148224.DIABETESINCONTROL%2FB5128550.3%3Babr%3D%21ie4%3Babr%3D%21ie5%3

Bsz%3D300x250%3Bord%3D%5Btimestamp%5D%3F>

Advertisement

*

Hypertriglyceridemia usually due to elevated triglyceride-rich, very

low-density lipoprotein (VLDL) levels and sometimes increased chylomicrons

as well;

* Decreased HDL levels;

* Phenotype B pattern (excessive amounts of small, dense LDL and

intermediate-density lipoprotein particles), which contributes to an

increased CV risk.

Given this higher risk of premature CV disease in type 2 diabetes, all

patients should be screened for lipid abnormalities at the initial

evaluation using a fasting lipid profile to determine serum triglycerides,

total cholesterol, HDL cholesterol, and LDL cholesterol levels. Shown in

Table 15.3 are acceptable, borderline, and high-risk lipid levels for

adults. LDL cholesterol is calculated from the formula:

LDL = total cholesterol – HDL – (triglycerides ÷ 5)

This calculation is not accurate if the triglycerides are >400 mg/dL, and

LDL should be measured directly by ultracentrifugation. The recommendations

for treatment decisions based on elevated LDL are shown in Table 15.4.

Pharmacologic therapy should be initiated after nutrition and behavioral

interventions. However, when clinical CV disease is present or LDL is very

high (>200 mg/dL), pharmacologic therapy should be initiated at the same

time.

Because lipid abnormalities often reflect poor glycemic control, the first

treatment approach to dyslipidemia in type 2 diabetes should be optimizing

diabetes control with diet, exercise, and pharmacologic therapy as needed.

As glycemic control improves, lipid levels also usually improve,

particularly when insulin resistance is the underlying metabolic abnormality

responsible for the lipid disorder.

Limiting calories and saturated fat intake has proved to be highly effective

in improving, but not usually normalizing, the dyslipidemia of type 2

diabetes. Increased intake of soluble fiber, particularly from oat and bean

products, has been shown to reduce LDL cholesterol levels. The NCEP has

designed a stepped approach for restricting dietary fat and cholesterol that

can be modified to incorporate specific requirements for diabetic nutrition.

Edelman15-Tab15_3

Edelman15-Tab15-4

The following guidelines should be implemented with the assistance of a

registered dietitian:

* Step 1 diet guidelines: limit saturated fat intake to 8% to 10% of

daily calories, with 30% of calories from total fat; limit cholesterol to

<300 mg cholesterol per day. If this approach is not adequate for meeting

lipid goals, initiate Step 2.

* Step 2 diet guidelines: limit saturated fat intake to <7% of daily

calories; limit cholesterol intake to <200 mg/day.

* If triglycerides are >1000 mg/dL, all dietary fats should be reduced

to lower circulating chylomicrons.

Recommendations for effective diet therapy for the treatment of lipid

disorders in diabetes are shown in Table 15.5.

TABLE 15.5 — Diet Recommendations for the Treatment of Lipid Disorders in

Diabetes

* Calorie restriction and increased physical activity for weight loss

as indicated

* Saturated and trans-unsaturated fat intake <10% and preferably <7%

of total energy intake

* Total dietary cholesterol intake <200 mg/day

* Emphasis on complex carbohydrates (at least five portions per day of

fruits/vegetables); soluble fibers (legumes, oats, certain

fruits/vegetables) have additional benefits on total cholesterol, LDL

cholesterol level, and glycemic control

* Replacing saturated fat with carbohydrate or monounsaturated fats

(e.g., canola oil, olive oil)

Lipid-lowering pharmacologic agents are usually necessary when the lipid

profile does not normalize in response to diet, exercise, and other efforts

to improve glycemic control. The ADA follows an order of priority for the

treatment of diabetic dyslipidemia (Table 15.6). LDL cholesterol is

considered the first priority, followed by HDL cholesterol raising,

triglyceride lowering, and treatment of combined hyperlipidemia. Commonly

used pharmacologic agents for the treatment of dyslipidemia are listed in

Table 15.7:

_____

TABLE 15.6 — Order of Priorities for Treatment of Diabetic Dyslipidemia in

Adults

* LDL cholesterol lowering:

* Lifestyle interventions

* Preferred: HMG CoA reductase inhibitor (statin)

* Others: bile-acid binding resin, cholesterol absorption inhibitor,

fenofibrate, or niacin

* HDL cholesterol raising:

* Lifestyle interventions

* Nicotinic acid or fibrates

* Triglyceride lowering:

* Lifestyle interventions

* Glycemic control

* Fibric acid derivative (gemfibrozil, fenofibrate), niacin, high-dose

statins (in those who also have high LDL cholesterol)

* Combined hyperlipidemia:

* First choice: improved glycemic control plus high-dose statin

* Second choice: improved glycemic control plus statin plus fibric

acid derivative

* Third choice: improved glycemic control plus statin plus nicotinic

acid

Decision for treatment of high LDL cholesterol before elevated triglycerides

is based on clinical trial data indicating safety as well as efficacy of the

available agents. The combination of statins with nicotinic acid,

fenofibrate, or especially gemfibrozil may carry an increased risk of

myositis. Patients with triglyceride levels >400 mg/dL require special

consideration. Adapted from American Diabetes Association. Diabetes Care.

2004;27 (suppl 1):S69.

_____

* When elevated LDL cholesterol is the primary lipoprotein

abnormality: HMG-CoA reductase inhibitors (atorvastatin, fluvastatin,

lovastatin, pravastatin, simvastatin) are indicated. These agents reduce

cholesterol synthesis and are useful as monotherapy for the familial forms

of hypercholesterolemia, or in combination with Bass. Most HMG-CoA reductase

inhibitors are indicated for the reduction of both LDL cholesterol and

triglyceride levels. When serum triglycerides are consistently elevated >200

mg/dL, with or without low HDL levels, medication is warranted in addition

to a low-fat diet.

Edelman15-Tab15-7

* BASs (Colestid, Questran, Welchol) have several disadvantages in

patients with diabetes. The older bile binders, in particular, must be taken

1 hour before or 4 hours after other oral medications so there is no

interference with absorption. Bile binders also cause fairly significant

constipation, and this is especially bothersome in the diabetic population

because it exacerbates the constipation of diabetic gastroparesis. In

addition, bile binders also can worsen hypertriglyceridemia in patients with

diabetes. The newest BAS, colesevelam (Welchol) may provide an additional

benefit in patients with type 2 diabetes with dyslipidemia since it is not

only indicated for the treatment of primary dyslipidemia as monotherapy or

in combination with a HMG-CoA reductase inhibitor, but was recently approved

to improve glycemic control in adults with type 2 diabetes (see Chapter 8,

Oral Agents) and appears to be better tolerated, in terms of GI adverse

events (e.g., constipation), than the older BASs.

* Nicotinic acid is highly effective at improving all lipoprotein

parameters, although it significantly worsens glucose intolerance and is

contraindicated in most patients with type 2 diabetes. Niaspan is a new

slow-release niacin preparation that may be tolerated in a subset of severe

dyslipidemic individuals with diabetes.

* Despite earlier warnings that HMG-CoA reductase inhibitors should

not be used with gem-fibrozil (Lopid) or fenofibrate (Tricor) in patients

with mixed disorders, they offer a safe and effective approach to diabetic

patients with elevated triglycerides and LDL cholesterol values. When

adding one medication to the other, creatinine phosphokinase (CPK) should be

measured and LFTs should be performed in 3 weeks and again in 6 weeks, along

with a lipoprotein profile. Once a stable dose is maintained and the CPK and

LFTs monitoring these values frequently becomes unnecessary. Caution should

be used if the patient is on other medications that could cause hepatitis or

myositis. Last, this combination should only be used in compliant patients

who will not get lost to medical follow-up.

* When hypertriglyceridemia is the primary lipid abnormality

(triglyceride levels consistently >200 mg/dL with or without low HDL

levels), a fibric acid derivative is the drug of choice; gemfibrozil reduces

triglyceride levels usually with small decreases in LDL cholesterol and

small increases in HDL cholesterol. Fenofibrate is a fenofibric acid

derivative that may lower LDL cholesterol in addition to reducing

triglyceride values and increasing HDL levels. These agents are particularly

effective at decreasing hepatic VLDL production and enhancing the clearance

of VLDL triglycerides by stimulating lipoprotein lipase, and they are well

tolerated.

* Low HDL levels are extremely difficult to treat. Nicotinic acid can

be of benefit but often leads to deterioration in glucose control. Fibrates

also improve HDL modestly. Perhaps the best medications to increase HDL in

type 2 diabetic subjects are the glitazones, which can increase HDL up to

20%.

* An effective therapeutic option for combined dyslipidemia is the use

of an HMG-CoA reductase inhibitor that is indicated for the treatment of

elevated LDL cholesterol and triglyceride levels. LDL cholesterol can be

reduced up to 60% and triglycerides up to 40% with an HMG-CoA reductase

inhibitor.

Next Week: Microvascular Complications

You can purchase this text