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داروهای کاهش دهنده چربی خون و دیابت

lipid and diabetes
نوشته شده توسط دکتر افشین عشقی

همانطوریکه قبلا گفتیم شایعترین دلیل مرگ و میر افراد دیابتی ، حوادث قلبی عروقی از قبیل سکته قلبی میباشد.

دیابت به تنهایی خودش یک عامل خطر بزرگ برای بروز بیماریهای قلبی عروقی ، مثل فشار خون و تشدید آن میباشد.

در کنار دیابت اگر عادات ناپسندی مثل کم تحرکی ، سیگار کشیدن ، مصرف نمک فراوان و وجود بیماری زمینه ای کلیوی و فشارخون وجود داشته باشند ، متاسفانه شدت عوارض و میزان مرگ و میر بالاتر میرود.

از سال 2014 توصیه های انجمن دیابت آمریکا برای شروع دارو درمانی برای چربی تغییر کرده و حتی مصرف داروهای کاهش دهنده چربی را برای کسانی که شانس بیشتری برای ابتلا به بیماریهای قلبی عروقی دارند ، بدون توجه به سطح پایه چربی (یعنی حتی کنترل بودن چربی) ، الزامی دانسته اند.

به توصیه های زیر توجه فرمایید:

  • Lifestyle modification focusing on the reduction of saturated fat, trans fat, and cholesterol intake; increase of n-3 fatty acids, viscous fiber and plant stanols/sterols; weight loss (if indicated); and increased physical activity should be recommended to improve the lipid profile in patients with diabetes. A

  • Statin therapy should be added to lifestyle therapy, regardless of baseline lipid levels, for diabetic patients:

    with overt CVD A

    without CVD who are over the age of 40 years and have one or more other CVD risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria). A

  • For lower-risk patients than the above (e.g., without overt CVD and under the age of 40 years), statin therapy should be considered in addition to lifestyle therapy if LDL cholesterol remains above 100 mg/dL or in those with multiple CVD risk factors. C

  • In individuals without overt CVD, the goal is LDL cholesterol <100 mg/dL (2.6 mmol/L). B

  • In individuals with overt CVD, a lower LDL cholesterol goal of <70 mg/dL (1.8 mmol/L), with a high dose of a statin, is an option. B

  • If drug-treated patients do not reach the above targets on maximum tolerated statin therapy, a reduction in LDL cholesterol of ∼30–40% from baseline is an alternative therapeutic goal. B

  • Triglyceride levels <150 mg/dL (1.7 mmol/L) and HDL cholesterol >40 mg/dL (1.0 mmol/L) in men and >50 mg/dL (1.3 mmol/L) in women are desirable. C However, LDL cholesterol–targeted statin therapy remains the preferred strategy. A

  • Combination therapy has been shown not to provide additional cardiovascular benefit above statin therapy alone and is not generally recommended. A

  • Statin therapy is contraindicated in pregnancy. B

Evidence for Benefits of Lipid-Lowering Therapy

Patients with type 2 diabetes have an increased prevalence of lipid abnormalities, contributing to their high risk of CVD. Multiple clinical trials have demonstrated significant effects of pharmacological (primarily statin) therapy on CVD outcomes in subjects with CHD and for primary CVD prevention (347,348). Subanalyses of diabetic subgroups of larger trials (349353) and trials specifically in subjects with diabetes (354,355) showed significant primary and secondary prevention of CVD events +/− CHD deaths in diabetic patients. Meta-analyses including data from over 18,000 patients with diabetes from 14 randomized trials of statin therapy (mean follow-up 4.3 years), demonstrate a 9% proportional reduction in all-cause mortality, and 13% reduction in vascular mortality, for each mmol/L reduction in LDL cholesterol (356). As in those without diabetes, absolute reductions in “hard” CVD outcomes (CHD death and nonfatal MI) are greatest in people with high baseline CVD risk (known CVD and/or very high LDL cholesterol levels), but the overall benefits of statin therapy in people with diabetes at moderate or high risk for CVD are convincing (357,358).

Diabetes With Statin Use

There is an increased risk of incident diabetes with statin use (359,360), which may be limited to those with diabetes risk factors. These patients may benefit additionally from diabetes screening when on statin therapy. In an analysis of one of the initial studies suggesting that statins are linked to risk of diabetes, the cardiovascular event rate reduction with statins outweighed the risk of incident diabetes even for patients at highest risk for diabetes (361). The absolute risk increase was small (over 5 years of follow-up, 1.2% of participants on placebo developed diabetes and 1.5% on rosuvastatin) (362). A meta-analysis of 13 randomized statin trials with 91,140 participants showed an odds ratio of 1.09 for a new diagnosis of diabetes, so that (on average) treatment of 255 patients with statins for 4 years resulted in one additional case of diabetes, while simultaneously preventing 5.4 vascular events among those 255 patients (360). The relative risk-benefit ratio favoring statins is further supported by meta-analysis of individual data of over 170,000 persons from 27 randomized trials. This demonstrated that individuals at low risk of vascular disease, including those undergoing primary prevention, received benefits from statins that included reductions in major vascular events and vascular death without increase in incidence of cancer or deaths from other causes (348).

Low levels of HDL cholesterol, often associated with elevated triglyceride levels, are the most prevalent pattern of dyslipidemia in persons with type 2 diabetes. However, the evidence base for drugs that target these lipid fractions is significantly less robust than that for statin therapy (363). Nicotinic acid has been shown to reduce CVD outcomes (364), although the study was done in a nondiabetic cohort. Gemfibrozil has been shown to decrease rates of CVD events in subjects without diabetes (365,366) and in a subgroup with diabetes in one of the larger trials (365). However, in a large trial specific to diabetic patients, fenofibrate failed to reduce overall cardiovascular outcomes (367).

Combination Therapy

Combination therapy, with a statin and a fibrate or statin and niacin, may be efficacious for treatment for all three lipid fractions, but this combination is associated with an increased risk for abnormal transaminase levels, myositis, or rhabdomyolysis. The risk of rhabdomyolysis is higher with higher doses of statins and with renal insufficiency and seems to be lower when statins are combined with fenofibrate than gemfibrozil (368). In the ACCORD study, the combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal MI, or nonfatal stroke, as compared with simvastatin alone, in patients with type 2 diabetes who were at high risk for CVD. Prespecified subgroup analyses suggested heterogeneity in treatment effects according to sex, with a benefit of combination therapy for men and possible harm for women, and a possible benefit for patients with both triglyceride level ≥204 mg/dL and HDL cholesterol level ≤34 mg/dL (369). The AIM-HIGH trial randomized over 3,000 patients (about one-third with diabetes) with established CVD, low levels of HDL cholesterol, and triglyceride levels of 150–400 mg/dL to statin therapy plus extended release niacin or matching placebo. The trial was halted early due to lack of efficacy on the primary CVD outcome (first event of the composite of death from coronary heart disease (CHD), nonfatal MI, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization) and a possible increase in ischemic stroke in those on combination therapy (370). Hence, combination lipid-lowering therapy cannot be broadly recommended.

Dyslipidemia Treatment and Target Lipid Levels

Unless they have severe hypertriglyceridemia at risk for pancreatitis, for most diabetic patients the first priority of dyslipidemia therapy is to lower LDL cholesterol to <100 mg/dL (2.60 mmol/L) (371). Lifestyle intervention, including MNT, increased physical activity, weight loss, and smoking cessation, may allow some patients to reach lipid goals. Nutrition intervention should be tailored according to each patient’s age, diabetes type, pharmacological treatment, lipid levels, and other medical conditions. Recommendations should focus on the reduction of saturated fat, cholesterol, and trans unsaturated fat intake and increases in n-3 fatty acids, viscous fiber (such as in oats, legumes, and citrus), and plant stanols/sterols. Glycemic control can also beneficially modify plasma lipid levels, particularly in patients with very high triglycerides and poor glycemic control.

In those with clinical CVD or over age 40 years with other CVD risk factors, pharmacological treatment should be added to lifestyle therapy regardless of baseline lipid levels. Statins are the drugs of choice for LDL cholesterol lowering and cardioprotection. In patients other than those described above, statin treatment should be considered if there is an inadequate LDL cholesterol response to lifestyle modifications and improved glucose control or if the patient has increased cardiovascular risk (e.g., multiple cardiovascular risk factors or long diabetes duration).

Very little clinical trial evidence exists for type 2 diabetic patients under the age of 40 years or for type 1 diabetic patients of any age. In the Heart Protection Study (lower age limit 40 years), the subgroup of ∼600 patients with type 1 diabetes had a proportionately similar reduction in risk to patients with type 2 diabetes, although not statistically significant (350). Although the data are not definitive, similar lipid-lowering goals for both type 1 and type 2 diabetic patients should be considered, particularly if they have other cardiovascular risk factors.

Alternative Lipoprotein Goals

Most trials of statins and CVD outcome tested specific doses of statins against placebo or other statins, rather than aiming for specific LDL cholesterol goals (372). Placebo-controlled trials generally achieved LDL cholesterol reductions of 30–40% from baseline. Hence, LDL cholesterol lowering of this magnitude is an acceptable outcome for patients who cannot reach LDL cholesterol goals due to severe baseline elevations in LDL cholesterol and/or intolerance of maximal, or any, statin doses. Additionally for those with baseline LDL cholesterol minimally above 100 mg/dL, prescribing statin therapy to lower LDL cholesterol about 30–40% from baseline is probably more effective than prescribing just enough to get LDL cholesterol slightly below 100 mg/dL.

Clinical trials in high-risk patients, such as those with acute coronary syndromes or previous cardiovascular events (373375), have demonstrated that more aggressive therapy with high doses of statins to achieve an LDL cholesterol of <70 mg/dL led to a significant reduction in further events. A reduction in LDL cholesterol to <70 mg/dL is an option in very-high-risk diabetic patients with overt CVD (371). Some experts recommend a greater focus on non-HDL cholesterol, apolipoprotein B (apoB), or lipoprotein particle measurements to assess residual CVD risk in statin-treated patients who are likely to have small LDL particles, such as people with diabetes (376), but it is unclear whether clinical management would change with these measurements.

In individual patients, the high variable response seen with LDL cholesterol lowering with statins is poorly understood (377). Reduction of CVD events with statins correlates very closely with LDL cholesterol lowering (347). If initial attempts to prescribe a statin leads to side effects, clinicians should attempt to find a dose or alternative statin that is tolerable. There is evidence for significant LDL cholesterol lowering from even extremely low, less than daily, statin doses (378). When maximally tolerated doses of statins fail to significantly lower LDL cholesterol (<30% reduction from the patient’s baseline), there is no strong evidence that combination therapy should be used to achieve additional LDL cholesterol lowering. Niacin, fenofibrate, ezetimibe, and bile acid sequestrants all offer additional LDL cholesterol lowering to statins alone. However, there is insufficient evidence that such combination therapy for LDL cholesterol lowering provides a significant increment in CVD risk reduction over statin therapy alone.

Treatment of Other Lipoprotein Fractions or Targets

Hypertriglyceridemia should be addressed with dietary and lifestyle changes. Severe hypertriglyceridemia (>1,000 mg/dL) may warrant immediate pharmacological therapy (fibric acid derivative, niacin, or fish oil) to reduce the risk of acute pancreatitis. If severe hypertriglyceridemia is absent, then therapy targeting HDL cholesterol or triglycerides lacks the strong evidence base of statin therapy. If the HDL cholesterol is <40 mg/dL and the LDL cholesterol between 100 and 129 mg/dL, a fibrate or niacin might be used, especially if a patient is intolerant to statins. Niacin is the most effective drug for raising HDL cholesterol. It can significantly increase blood glucose at high doses, but at modest doses (750–2,000 mg/day), significant improvements in LDL cholesterol, HDL cholesterol, and triglyceride levels are accompanied by only modest changes in glucose that are generally amenable to adjustment of diabetes therapy

http://care.diabetesjournals.org/content/37/Supplement_1/S14.full

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