行政院衛生署豐原醫院營養科 報告者：謝惠敏 報告日期：99年12月31 實證營養報告 行政院衛生署豐原醫院營養科 報告者：謝惠敏 報告日期：99年12月31

Clinical Scenario 臨床劇本 維生素D是幫助腸道對鈣質吸收及維持骨骼代謝一個非常重要的營養素 許多研究報導顯示維生素D缺乏將增加下列疾病的危險性 氣喘、免疫性疾病（糖尿病、多發性硬化症、風濕性關節炎 ）、癌症

Step 1: Ask an answerable clinical question--P.I.C.O. 形成一個可以回覆的問題

PICO Question: Patient / Problem : Healthy people Intervention / Exposure : Vit D deficiency Comparison : Vit D Normal Outcome : The incidence of Type 2 DM Ex: In healthy people, do Vit D deficiency will increase the incidence of type 2 DM ? （在健康的受試者中，維生素D缺乏是否會增加第2型糖尿病的發生率？）

Step 2: Effective searches for the best Evidence 搜尋最佳的證據

搜尋策略的設計表 SEARCH STRATEGY DESIGN TABLE 主要詞彙 Primary Term 同義字 Synonym 1 Synonym 2 P Healthy people OR AND E Vitamin D deficiency 25(OH)D 25-hydroxyvitamin D C Placebo Vitamin D normal O Type 2 DM

敘述性研究以時間面區分 橫斷性研究（Cross-sectional study）: 在某一時間點進行的研究 縱向研究（Longitudinal studies）: 對某一群個體追蹤一段時間觀察的研究。研究因時間而改變的題材是最佳方式 世代研究(cohort studies)~追蹤一群健康個體研究他們暴露於危險因子之後的情形 ＊縱貫研究（Longitudinal stuolies）：相對於橫斷研究，它是一種允許相同現象跨越一段長時間觀察的設計，對量化研究來說，像大規模的調查研究，縱貫研究有其因難。儘管如此，研究因時間而改變的題材，縱貫研究通常是最佳方式。有三種類別的縱貫研究：即趨勢研究、世代研究及小樣本覆訪研究。 ＊趨向研究（Tend study）(從ㄧ母群抽不同樣本)是縱貫研究的一類，其研究某特定人群在跨越一段時間所發 生的變化。 ＊世代研究（Cohort study）(從特定母群抽不同樣本)是檢視某特定的次人群或世代，在跨越一段時間所發生的變化。 世代研究(將患有某種疾病的人與未換有該疾病的人做比較, 以觀察暴露於化學物質或其他 風險因子之間的差異病人之間的不同). ＊小樣本覆訪研究（Panel study）(從ㄧ母群抽同ㄧ樣本)，雖與趨向研究及世代研究相同，但小樣本覆訪研究是在不同時間檢視同一批受訪者。 10

Introduction of The Framingham Heart Study The Framingham Heart Study was established in 1948, when 5,209 residents of Framingham, Massachusetts were enrolled in a longitudinal cohort study designed to prospectively identify risk factors for cardiovascular disease. 5135 In 1971, an additional 5,124 participants (offspring of the original cohort subjects and their spouses) were enrolled in the Framingham Offspring Study. A total of 3799 cohort members participated in the fifth examination cycle (1991–1995). After exclusions, 3066 participants (1402 men and 1664 women) remained eligible for the present investigation. The participants were essentially all white. Participants were followed across the sixth (1996–1998) and seventh (1998–2001) offspring cohort examinations for a mean of 7 y for the development of incident T2D. 11

Timeline for the Framingham Offspring cohort examination 1728

Etiology (病因) Level Ⅱ evidence research A longitudinal cohort study 縱向世代研究 Study population : 3066 participants (1402 men and 1664 women) remained eligible for the present investigation. The participants were essentially all white.

Step 3: Critically appraise that evidence for its validity and importance 嚴格評讀文獻是否令人信服及其重要性

A.此一有害原因的研究結果能令人信服嗎? Are the results of this harm/etiology study valid?

1. 實驗組與對照組除了對治療的曝露有別外, 其他方面是否皆相似 1.實驗組與對照組除了對治療的曝露有別外, 其他方面是否皆相似? Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause? Yes 本研究為一個縱向性世代研究，單純只觀察受試者維生素D與糖尿病發生的相關性。 在統計時有分別校正年齡/性別/BMI 調整因子-腰圍、飲食、家族史、高血壓、HDL、TG、IFG

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2.實驗組與對照組的評量方法是否相同? 　 Were treatments/ exposures and clinical outcomes measured in the same ways in both groups (Was the assessment of outcomes either objective or blinded to exposure?) Yes

Method : (1) to test the hypothesis that vitamin D status is inversely associated with subsequent risk of T2D using a predicted 25(OH)D score, for standard cardiovascular risk factors have been detailed previously. (2) physical activity score was calculated from the number of self reported hours spent doing specific activities that were categorized and weighted according to oxygen consumption required to perform them (MET-h/d) Physical activity was assessed using a physical activity index, calculated from the number of hours spent each day at various activity levels, weighted according to the estimated oxygen consumption required for each activity. (3)Using the 126-item semiquantitative Harvard Harvard FFQ (version 88GP). The FFQ consists of a list of foods with a standardized serving size and a selection of 9 frequency categories ranging from never or ,1 serving/mo to .6 servings/d. (4)Serum 25(OH)D (5) Height, weight, and waist circumference were measured while the subjects were standing. BMI was calculated as weight in kilograms divided by the square of height in meters (kg/m2).

3.追蹤夠久、夠完整嗎? Was the follow-up of the study patients sufficiently long (for the outcome to occur) and complete? Yes.

4.因果關係夠明確嗎?　 Do the results of the harm study satisfy some of the diagnostic tests for causation? a.曝露在發作之前嗎? 　 Is it clear that the exposure preceded the onset of the outcome? b.與劑量具有相關反應嗎? 　 Is there a dose-response gradient? c.從”去曝露--再曝露”的研究上有正面證據嗎? 　 Is there any positive evidence from a “dechallenge-rechallenge” study? d.因果關係具有生物學上的意義嗎? 　 Does the association make biological sense? a. Yes b. Yes. P.1632 Table 3 c.No. This article didn’t mention about it. d. Yes. Table 3

individuals in the middle and highest tertile had a 30% and a 40% reduction in risk of development of T2D over the 7-y follow-up compared with individuals in the lowest tertile of the predicted 25(OH)D score, respectively (P for trend = 0.03). 22

B.此一有害原因的研究結果夠重要嗎? Are the valid results of this harm study important?

1.暴露與結果之間的相關性有多強？ What is the magnitude of the association between the exposure and outcome? (OR) = ad/bc NNH=1/[a/(a+b)−c/(c+d)]

NNH=1/[a/(a+b)−c/(c+d)] 1.暴露與結果之間的相關性有多強？ What is the magnitude of the association between the exposure and outcome? 維生素D缺乏 總計 發生 沒有 是 70 917 987 否 27 959 986 97 1876 (OR) = ad/bc NNH=1/[a/(a+b)−c/(c+d)] (OR) = ad/bc =67130/24759 =2.7 NNH=1/[a/(a+b)−c/(c+d)] =23.2

2.暴露與結果之相關性的估計有多精準？ What is the precision of the estimate of the association between the exposure and the outcome?

C.此一令人信服且結果重要的研究的會改變我們對病患的治療嗎? Can this valid and important evidence about harm be applied to our patient?

No. 研究對象與平常我們接觸的個案條件類似 1.我們的病患與研究中收錄的病患有明顯不同，以致於無法應用該研究的結果？ Is our patient so different from those included in the study that its results cannot apply? No. 研究對象與平常我們接觸的個案條件類似 2.此項治療對我們的病患潛在的益處為何?潛在的危害為何? What is our patient’s risk of benefit and harm from the agent? 由本研究可以得知：維生素D不足，確實有較高的第2型糖尿病發生率

3.我們的病人對治療的偏好、關心與期待為何? What are our patient’s preferences, concerns, and expectations from this treatment? 對於維生素D缺乏的個案，鼓勵其補充維生素D、多運動、曬太陽，以增加血液中25(OH)D含量，降低糖尿病的發生。 4.有哪些替代治療? What alternative treatments are available? 本研究僅為一世代觀察型研究，並未針對個案進行介入性研究，所以，文章中並未提及有何替代性治療方式。不過，針對維生素D缺乏的個案，臨床上仍建議以飲食及運動來提升血液中25(OH)D 。

Thanks for your Attention！