Lipid goals in patients who have diabetes

Diabetes is a CHD-risk equivalent, as defined by the ATPIII recommendations. Based on the evidence from the LDL-lowering clinical trials that were summarized above, most patients who have diabetes should have an LDL goal of less than 100 mg/dL (Table 3). If LDL is grater than 130 mg/dL, treatment with LDL-lowering drugs should be initiated simultaneously with therapeutic lifestyle changes (TLC) to achieve the LDL goal [1]. The American Diabetes Association (ADA) has the same recommendations for LDL goal [42]. In addition, the ADA recommends a triglyceride goal of less than 150 mg/dL and an HDL cholesterol goal of greater than 40 mg/dL in men and greater than 50 mg/dL in women (see Table 3). According to ATPIII, however, when triglyceride levels are elevated (200-499 mg/dL) after achieving LDL goal, non-HDL cholesterol should be the secondary target of therapy. No HDL goal is specified in ATPIII because of the lack of sufficient evidence. It is recommended that if HDL remains low after LDL and non-HDL goals are achieved or if triglyceride is less than 200 mg/dL but HDL is low (isolated low HDL cholesterol), drugs for increasing HDL can be considered.

Following the recent evidence from the newer Statin Trials including HPS, ASCOT-LLA, and PROVE-IT, as well as, CARDS summarized earlier, the ATP III panel of the NCEP recently updated their current guidelines [43]. The salient features of this update are depicted in Box 1. It is now recommended that LDL-lowering drug therapy be considered simultaneously with lifestyle changes in high risk patients if LDL exceeds 100 mg/dL. In patients in very high risk category, such as patients with diabetes and CVD, a therapeutic option is to lower LDL-cholesterol goal to <70 mg/dL, regardless ofthe baseline LDL-cholesterol.

Combined End Point

0.68

0.82

Nonfatal Myocardial Infarction

A

0.59

0.97 A

0.60 A

a

III 1

1 T-

1.2 1.4 Favors Placebo -

1.2 1.4 Favors Placebo -

Diabetes (n=769) No Diabetes (n =1748)

Fig. 2. Hazard ratios for major cardiovascular events with gemfibrozil compared with placebo in patients who do and do not have diabetes. (From Rubins HB, Robins SJ, Collins D, Nelson DB, Elam MB, Schaefer EJ, et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med 2002;162(22):2597-604; with permission.)

Moreover, when LDL-lowering drug therapy is used in high risk patients, the intensity of therapy should be sufficient to achieve at least a 30% to 40% reduction in LDL-cholesterol levels, which correlates roughly to a 30% to 40% reduction in risk for myocardial infarction or CVD mortality [43].

In patients who have triglycerides that are greater than 500 mg/dL and diabetic lipemia (triglycerides higher than 1000 mg/dL), the initial aim is to decrease triglycerides to prevent acute pancreatitis. This requires a combination of a very low fat diet, weight reduction, increased physical activity, and a triglyceride-lowering drug. After triglyceride levels have been lowered to less than 500 mg/dL, the LDL and other lipid targets should be assessed.

Principles of lipid management in diabetes

Treatment of lipid disorders that frequently are associated with diabetes, includes TLCs, optimal glycemic control, and pharmacologic agents. The priorities are decreasing LDL cholesterol and non-HDL cholesterol; these are followed by decreasing triglycerides and increasing HDL, as per recommendations by ATPIII and all diabetes/endocrine organizations. LDL-lowering trials with statins, particularly including the new evidence from the HPS, make a persuasive argument for the efficacy and safety of the statin therapy which is underused in this high-risk population. In highly-motivated individuals, LDL cholesterol reductions of 30%, by dietary approaches (comparable to with statins), were demonstrated [44]. In most patients, however, LDL cholesterol reductions of more than 10% to 15% are not easily achievable with nonpharmacologic approaches. Therefore, the ATPIII recommends simultaneous initiation of statin therapy if LDL cholesterol is greater than 130 mg/dL. The statins provide LDL cholesterol reductions of up to 55% to 60%; the most recently available agent,

Table 3

Categories of risk based on lipid levels (mg/dL) in adults who have diabetes, as defined by the American Diabetes Association

Table 3

Categories of risk based on lipid levels (mg/dL) in adults who have diabetes, as defined by the American Diabetes Association

LDL

HDL

Risk

cholesterol

cholesterola

Triglycerides

High

>130

<40

<400

Borderline

100-129

40-59

150-399

Low

<100

>60

<150

a For women, the HDL cholesterol value should be increased by 10 mg/dL.

a For women, the HDL cholesterol value should be increased by 10 mg/dL.

rosuvastatin, is the most potent (Table 4) [1,45]. The simultaneous adherence to dietary measures, including soluble fiber, soy protein, plant sterols, and weight-management, is essential to maintain the lipid goals with lower dosages of drugs. The effectiveness of statins and other lipid-lowering agents in diabetic patients is comparable to that in nondiabetic patients [46,47].

If LDL cholesterol is 100 mg/dL to 129 mg/dL at baseline or on treatment, therapeutic options include intensifying the LDL-lowering therapy; adding a drug to modify other atherogenic components (fibrate or nicotinic acid), or intensifying control of other risk factors, including hypertension and hyperglycemia. Fibrates or niacin also would be indicated in patients who have hyper-triglyceridemia or low HDL cholesterol who already are at or close to LDL goals. In the DAIS trial, fenofibrate retarded the progression of atherosclerosis [37]; in VA-HIT, gemfibrozil therapy was associated with significant reductions in clinical end points [38-40]. The findings of the HPS, however, raise the concern that the level of CHD risk, rather than the baseline LDL level, determines the benefits of further LDL-lowering by statins [22,23]. The US Food and Drug Administration recently revised the consumer package insert for simvastatin based on these results and it recommends consideration of this therapy for all patients who have CHD or diabetes, based on their proven high risk for CVD events.

Nicotinic acid (niacin) is associated with the greatest increase in HDL cholesterol and is considered to be a drug of choice in patients who have low HDL [1,46], particularly in combination therapy with other agents. The principal concern is its tolerability and adherence to higher dosage. Recent multi-center trials showed no significant effects on glycemic control with up to 3 g of crystalline niacin [48] or 1 g to 1.5 g of extended release niacin, niaspan [47,49]. It is the only agent that is effective in lowering LP(a) levels. Recently, the availability of ezitimibe, a cholesterol absorption inhibitor that acts at the site of putative cholesterol transfer in the gut, has expanded the options for LDL lowering [50]. It decreases LDL cholesterol an average of 15% to 20% and the effects are additive to the effect of statins. Thus, the addition of 10 mg of ezitimibe to low-dosage statins decreased LDL cholesterol in an amount that was approximately equivalent to tripling the dosage of the statins [50]. It is well-tolerated and, in this regard, provides an alternative to the poorly-tolerated bile-acid sequestrants.

Box 1. Update of NCEP-ATPIII Recommendations for LDL-C in High Risk Persons

4 Steps To Permanent Weight Loss

4 Steps To Permanent Weight Loss

I can't believe I'm actually writing the book that is going to help you achieve the level of health and fitness that you always dreamed of. Me, little scrawny sickly Darlene that was always last picked in gym class. There's power in a good story here so get this book now.

Get My Free Ebook


Post a comment