Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus

 

Abstract

Background

People with type 2 diabetes mellitus are at increased risk from cardiovascular disease. Dietary omega-3 polyunsaturated fatty acids (PUFAs) are known to reduce triglyceride levels, but their impact on cholesterol levels, glycemic control and vascular outcomes are not well known.

Objectives

To determine the effects of omega-3 PUFA supplementation on cardiovascular outcomes, cholesterol levels and glycemic control in people with type 2 diabetes mellitus.

Search methods

We carried out a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, bibliographies of relevant papers and contacted experts for identifying additional trials.

Selection criteria

All randomised controlled trials were included where omega-3 PUFA supplementation or dietary intake was randomly allocated and unconfounded in people with type 2 diabetes. Authors of large trials were contacted for missing information.

Data collection and analysis

Trials were assessed for inclusion. Authors were contacted for missing information. Data was extracted and quality assessed independently in duplicate. Fixed-effect meta-analysis was carried out.

Main results

Twenty three randomised controlled trials (1075 participants) were included with a mean treatment duration of 8.9 weeks. The mean dose of omega-3 PUFA used in the trials was 3.5 g/d. No trials with vascular events or mortality endpoints were identified. Among those taking omega-3 PUFA triglyceride levels were significantly lowered by 0.45 mmol/L (95% confidence interval (CI) -0.58 to -0.32, P < 0.00001) and VLDL cholesterol lowered by -0.07 mmol/L (95% CI -0.13 to 0.00, P = 0.04). LDL cholesterol levels were raised by 0.11 mmol/L (95% CI 0.00 to 0.22, P = 0.05). No significant change in or total or HDL cholesterol, HbA1c, fasting glucose, fasting insulin or body weight was observed. The increase in VLDL remained significant only in trials of longer duration and in hypertriglyceridemic patients. The elevation in LDL cholesterol was non-significant in subgroup analyses. No adverse effects of the intervention were reported.

Authors' conclusions

Omega-3 PUFA supplementation in type 2 diabetes lowers triglycerides and VLDL cholesterol, but may raise LDL cholesterol (although results were non-significant in subgroups) and has no statistically significant effect on glycemic control or fasting insulin. Trials with vascular events or mortality defined endpoints are needed.

 

Plain language summary

Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus

People with type 2 diabetes are known to be at increased risk of cardiovascular disease (such as heart attack or stroke). Type 2 diabetes mellitus is the fourth leading cause of death in developed countries with a two fold excess mortality and a two to four fold increased risk of coronary heart disease and stroke. The typical dyslipidemia (abnormality in blood lipids) associated with type 2 diabetes is a combination of hypertriglyceridemia (high levels of fats (triglycerides) in the blood), low levels of HDL (high density lipoprotein) cholesterol and abnormal LDL (low density lipoprotein) composition. Low levels of HDL cholesterol and high levels of LDL cholesterol are associated with an increased risk of cardiovascular disease, while the raised levels of triglycerides are less clearly linked to an increased risk of cardiovascular disease. Several pharmacologic approaches have been used to treat diabetic dyslipidemia and standard dietary approaches focus on restriction of saturated fat and limitation of simple carbohydrate and alcohol intake. In the late 1980s, several investigators reported on the use of dietary supplementation with fish oil as a means of treating diabetic dyslipidemia. Dietary fats and oils from different sources differ considerably in their fatty acid composition. Animal fat is rich in saturated fatty acids, vegetable and marine oils are rich in polyunsaturated fatty acids. Most fish oils are of the so-called omega-3 variety (omega-3 polyunsaturated fatty acids (PUFAs)).
We identified 23 randomised trials (maximum duration of eight months) including 1075 people in which omega-3 PUFA was compared to a vegetable oil or placebo. None of the trials looked at cardiovascular endpoints in cardiovascular disease or death as an outcome measure.
The review shows that although some types of fat in the blood are reduced through omega-3 supplementation, others including LDL cholesterol (which may promote heart disease) were increased. Control of blood sugar levels was not affected by the treatment. There were no other adverse effects of the interventions noted. Clinical outcome trials of sufficient duration are required to establish conclusively the role of omega-3 PUFA in type 2 diabetes but our results do not suggest a major harmful effect on the balance of blood fats and confirm that it has no adverse affect on blood sugar control.

 

摘要

背景

Omega−3多元不飽和脂肪酸(PUFA)對第2型糖尿病之影響

第2型糖尿病的患者罹患心血管疾病的風險較高。現已知飲食中的omega−3多元不飽和脂肪酸(PUFA)能降低三酸甘油脂的濃度，但其對於膽固醇濃度、血糖控制及血管病變結果的影響，目前仍不清楚。

目標

為了判定補充omega−3 PUFA對第2型糖尿病患者之心血管病變結果，膽固醇濃度及血糖控制的效果。

搜尋策略

我們對the Cochrane Library，MEDLINE，EMBASE及相關文獻的參考書目進行了全面的檢索，並且和專家聯繫，以找出額外的試驗。

選擇標準

我們選擇所有以第2型糖尿病患者為對象，且隨機、不混淆地分配omega−3 PUFA補充或飲食攝取的隨機對照試驗(randomised controlled trials)。我們亦聯絡了大型試驗的作者，以取得不全的資訊。

資料收集與分析

我們分析了各個試驗，以評估是否適合被納入。同時亦聯絡作者，以取得不全的資訊。我們亦獨立且重複的進行了資料的萃取及試驗品質的分析。最後，我們則進行了固定效應的統合分析(fixedeffect metaanalysis)。

主要結論

我們共收集了23個平均治療期間為8.9周的隨機對照試驗(共有1075位受試者)。在試驗中所使用的omega−3 PUFA之平均劑量為3.5克/日。在這些試驗中，並無以血管病變或死亡做為試驗終點者。在服用omega−3 PUFA之受試者中，三酸甘油脂的濃度顯著地降低了0.45 mmol/L(95％信賴區間(CI) −0.58到 −0.32，P<0.00001)，而VLDL膽固醇則降低了0.07 mmol/L(95%信賴區間0.00到0.22，P = 0.05)。至於在總膽固醇、HDL膽固醇、HbA1c、空腹血糖、空腹胰島素或體重方面則未發現顯著的變化。VLDL的濃度，僅在較長期間的試驗，或是以高三酸甘油脂血症的患者為對象的試驗中有顯著的上升。至於LDL濃度的增加，在次群體的分析中，則未有顯著的意義。在試驗期間，亦未有不良作用發生的報告。

作者結論

在第2型糖尿病的病人身上，補充omega−3 PUFA可降低三酸甘油脂及VLDL膽固醇的濃度，但可能會增加LDL膽固醇的濃度(儘管在次群體的分析結果是不顯著的)；同時，其對於血糖控制及空腹時的胰島素濃度，亦無在統計學上顯著的影響。我們仍需要以血管病變或死亡為終點的試驗。

翻譯人

本摘要由臺灣大學附設醫院林志弘翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

目前，仍未有足夠的證據顯示第2型糖尿病患者攝取omega−3脂肪的利多於弊。我們已知第2型糖尿病患者罹患心血管疾病(如心臟病或中風)的風險較高。第2型糖尿病為已開發國家的第4位死因，其死亡率高出2倍，而發生冠狀動脈心臟病及中風的風險則為2到4倍。典型與第2型糖尿病有關的血脂異常為高三酸甘油脂血症，HDL(高密度脂蛋白)膽固醇的濃度較低，與LDL(低密度脂蛋白)膽固醇之成份異常之組合。較低的HDL膽固醇濃度與較高的LDL膽固醇濃度，會增加心血管疾病發生的風險，至於三酸甘油脂的濃度增加與心血管疾病的風險增加之間，則較無明顯關聯。對於糖尿病血脂異常，已有數種的藥物治療方法，而標準的飲食控制方法則著重於限制飽和脂肪，單純碳水化合物與酒精的攝取。在1980年代的後期，有幾位研究人員發表了利用在飲食中補充魚油來治療糖尿病之血脂異常的方法。根據來源的不同，飲食中的脂肪和油脂在脂肪酸的構成上有著相當的不同。動物性脂肪富含飽和脂肪酸，而植物性和海產的油脂則富含多元性不飽和脂肪酸。大部分的魚油都是屬於所謂的omega−3族群(omega−3多元性不飽和脂肪酸(PUFAs))。我們找出了23個比較omega−3 PUFA和植物油或安慰劑的隨機試驗(時間最長達8個月)，其中共包括了1075位受試者。沒有任何一個試驗比較心血管疾病發生或是死亡的結果。回顧的結果顯示：儘管在補充omega−3之後，血液中的某些脂肪會減低，但諸如LDL膽固醇(可能促成心臟病)之類的其他脂肪則會增加。此治療並不會影響血糖的控制。而對此治療也未發現其他的不良作用。目前尚須時間夠長的臨床試驗結果來確實地判定omega−3 PUFA於第2型糖尿病中的角色；然而，如依照我們的結果，則應不會有對血液中脂肪平衡有主要害處的影響，且對於血糖的控制亦無負面的影響。