Dyslipidemias are a key risk factor in people with the metabolic syndrome and contribute significantly towards the long term risk for premature and accelerated atherosclerosis. Lipid disorders are also seen in many people with diabetes and are a major factor in the microvascular and especially in the macrovascular diabetic complications. The dyslipidemias merit rigorous and aggressive correction.

The major dyslipidemias are:

1) Increased levels of low density lipoprotein cholesterol (LDL-C)

2) Atherogenic dyslipidaemia describes a combination of

Increased serum triglycerides (TG);
Increased VLDL particle number;
Increased levels of small dense LDL-C particles;
Increased levels of apolipoprotein B (ApoB);

(The increased number of VLDL and LDL particles accounts for the increased level of total apo B).

Decreased levels of HDL-C particles,

All of these are atherogenic by themselves, but their atherogenicity is significantly increased when present in combination. Athergenic dyslipidemia is commonly observed in patients with both type 2 diabetes and the metabolic syndrome.

A simple strategy for assessing the sum of atherogenic particles is measurement of either LDL+VLDL cholesterol (non-HDL cholesterol) or total apo B. In persons with metabolic syndrome and atherogenic dyslipidemia, both LDL+VLDL cholesterol and total apo B typically are elevated. These measurements should be used increasingly both in risk assessment and as targets of therapy in persons with the metabolic syndrome.

A low HDL level is another characteristic of atherogenic dyslipidemia. As a risk predictor, a low HDL rivals an elevated total apo B (or VLDL+LDL cholesterol). Although HDL may be directly antiatherogenic, the presence of a low HDL level carries strong predictive power for development of ASCVD.

Target Levels

The latest recommendations state that in adults with diabetes, the optimal LDL-C level is less than 100 mg/dl (in patients with additional risks, the target has been brought down to 70mg/dl; High-risk patients are those with established ASCVD, diabetes, or 10-year risk for coronary heart disease >20%. For cerebrovascular disease, high-risk condition includes transient ischemic attack or stroke of carotid origin or >50% carotid stenosis). and the optimal HDL-C level is more than 40mg/dl in men and 50mg/dl in women; triglyceride levels should be less than 150 mg/dl;.

According to ATP III, atherogenic dyslipidemia can become a target for lipid-lowering therapy after the goal for LDL-C has been attained. In other words, as long as LDL-C remains above goal level, LDL-C is the primary target of therapy even in the metabolic syndrome. Other lipid risk factors are secondary. The LDL-C goals depend on estimates of absolute risk.

In patients with atherogenic dyslipidemia in whom serum triglyceride levels are 200 mg/dL, non-HDL-C becomes the next target of treatment after the LDL-C goal is reached.

If the serum triglyceride levels are significantly raised (>500mg/dl), then lowering these levels should take precedence even over lowering the LDL-C values.

Raising HDL-C becomes a tertiary aim.

In practice, all the lipid abnormalities are managed together rather than in sequence.

Lifestyle Changes

Where only lipid levels are abnormal, lifestyle intervention should be undertaken first.

Diet

Beyond weight control and reduction of total calories, the diet should be low in saturated fats, trans fats, cholesterol, sodium, and simple sugars. In addition, there should be ample intakes of fruits, vegetables, and whole grains;

Very high carbohydrate intakes can exacerbate the dyslipidemia of the metabolic syndrome.

Diet therapy is important in optimizing lipid levels. Total fat intake should be restricted to 25-30% of total calorie intake. It is essential to take into account "invisible" fat in the food.

Ensure correct essential fatty acid (EFA) intake, with near optimal omega 6 / omega 3 (w6/w3) ratio (5:1).

Cooking oils should be a judicious mix of PUFAs, MUFAS and saturated fats; no one oils is beneficial; cooking oils should contribute <6% total energy intake.

Many of these aspects have been discussed in detail in the section dealing with lifestyle changes.

Exercise

Increases in daily routine activities and a regular exercise regimen is necessary and must be encouraged.

Many of these aspects have been discussed in detail in the section dealing with lifestyle changes.

Importantly,

Rigorous management of other associated disorders such as obesity, hypertension, impaired glycemia and diabetes.

Smoking intake to be actively discouraged.

Rule out other secondary causes of dyslipidemias.

DIET AND LIFESTYLE MODIFICATIONS SHOULD BE GIVEN AN ADEQUATE TRIAL BEFORE COMMENCING LIPID LOWERING DRUG THERAPY UNLESS THERE ARE DEFINITE INDICATIONS WHICH NECESSITATE IMMEDIATE STARTING OF THE DRUGS.

Drugs Affecting Lipoprotein Metabolism

*Some commonly used medications or consumption

NOTE: This does not represent a complete list.

A practical approach to the pharmacologic treatment of lipid disorders

Abbreviations: LDL, Low-density lipoprotein; HDL, high-density lipoprotein; TG, triglyceride; TZDs, thiazolidinediones.

In general, therapy is started with a statin although when triglycerides are 500 mg/dL, triglyceride-lowering drugs should be considered alongside to prevent the development of acute pancreatitis.

Statins reduce all ApoB-containing lipoproteins and to achieve the LDL-C as well as for non-HDL-C goals.

If non-HDL-C remains elevated after the LDL-C goal is reached:

• Increase the statin dose further. Statins lower both LDL-C and non-HDL-C and in addition, reduce risk for ASCVD events in patients with the metabolic syndrome.
• Add a fibrate and if necessary nicotinic acid to the statin. Both fibrates and nicotinic acid reduce non-HDL-C and reportedly decrease risk for ASCVD in patients with the metabolic syndrome/type 2 diabetes mellitus.

If the Tg levels are relatively high, it may be better to start therapy with a statin and a fibrate.

If the HDL-C levels are low, combining a fibrate or nicotinic acid with LDL-C-lowering treatment becomes an option. Both fibrates and nicotinic acid raise HDL-C as well as reduce triglycerides and small LDL particles.

Patients with IFG, IGT, or diabetes who are treated with nicotinic acid deserve careful monitoring for worsening of hyperglycemia. Lower doses of nicotinic acid lessen this risk.

If a fibrate or nicotinic acid is used with a statin, higher doses of the statin generally should be avoided to minimize risks for myopathy or hepatic effects.

Changes in Serum Lipid Values with Different Classes of lipid lowering drugs

Although many of the drugs are started as monotherapy, in most patients with the metabolic syndrome or established T2DM it may be necessary to use combination therapies to reach the targeted levels.