通過生活方式干預來預防2型糖尿病高危人群的潛在作用已經(jīng)在幾個臨床試驗中得到證實。這些研究主要著重于增加體育活動、改變飲食習慣以及減輕超重參與者的體重。同時糾正幾個危險因素的綜合方法似乎是問題的關鍵。此外，對持續(xù)時間有限的生活方式干預的長期隨訪研究似乎對風險因素和糖尿病發(fā)病率有長期的后續(xù)效應（表1）。
這項研究的證據(jù)鼓舞了世界各地的國家和地方當局以及衛(wèi)生保健提供者啟動預防2型糖尿病及其并發(fā)癥的計劃和活動。基于臨床試驗和“現(xiàn)實世界”實施方案的經(jīng)驗，IMAGE（制定和實施歐洲糖尿病預防指南和培訓標準）研究組系統(tǒng)地整理了信息。IMAGE的可交付成果包括：歐洲預防2型糖尿病循證指南、歐洲預防2型糖尿病工具包、歐洲預防2型糖尿病質(zhì)量指標。現(xiàn)在需要的是政治支持，以制定預防糖尿病的國家行動計劃。成功的預防活動的先決條件包括：有政府和非政府層面以及不同層次的醫(yī)療保健領域若干利益攸關方的參與。此外，還必須建立結(jié)構(gòu)來確定高危人員并管理干預、隨訪和評估。
觀察性研究為多種生活方式相關因素增加或降低2型糖尿病風險提供了有力證據(jù)。因此，在預防2型糖尿病時，不僅要注意肥胖等單一因素，還要同時注意幾個因素。芬蘭糖尿病預防研究（DPS）明確地證明了這一方法。在最初的試驗期間，如果糖耐量受損（IGT）的高危人群達到了5個預先設定的生活方式目標中的4個或5個，那么他們中沒有一個人發(fā)展成糖尿病（1）。這些目標如下：
這樣的目標相對來說比較適度，因此許多人都有可能達到。此外，實行這樣的生活方式是長期，甚至終身可行的。然而，有人批評這些試驗數(shù)據(jù)過于樂觀，因為試驗人群包括自愿參與這種生活方式干預試驗的個人。有人質(zhì)疑這種試驗結(jié)果是否或在何種程度上可以適用于一般民眾。盡管這種批評可能是正確的，但參與試驗的人都是典型的糖耐量受損患者，他們超重、相對久坐不動、飲食在很多方面都與建議不一致（2）。
對生活方式干預試驗進行長期后續(xù)觀察期間所觀察到的長期效應——一個具有前景的發(fā)現(xiàn)是，持續(xù)有限時間段的生活方式干預似乎對2型糖尿病的發(fā)病率具有長期的殘余效應。第一項表明風險可能持續(xù)降低的研究是馬爾默可行性研究。最初，運動和飲食（n = 161）對IGT男性的2型糖尿病發(fā)病率的效應，與參考組（n = 56）的進行了比較，參考組由不想進行生活方式干預的類似男性構(gòu)成。因此，這些組沒有隨機分配。到5年研究期結(jié)束時，11％的干預組和29％的參照組患有糖尿病。12年的隨訪結(jié)果顯示，前IGT干預組男性的全因死亡率低于僅接受“常規(guī)治療”的非隨機糖耐量受損組男性（6.5 vs. 14.0％） 1,000人年，P = 0.009）。前IGT干預組的死亡率實際上與葡萄糖耐量正常的男性相似。
1986年在中國大慶開展了一項大規(guī)模的人群篩查計劃（110,660人接受口服葡萄糖耐量試驗篩查）以確定糖耐量受損患者。研究對象的隨機化不是隨機進行的，但是33個參與診所（整群隨機化）隨機分組，根據(jù)四種特定干預方案中的一種進行干預（僅飲食，單獨運動，飲食運動結(jié)合或無）?？偣灿?77名患有糖耐量受損的男性和女性參加了這項試驗，其中533名參加了1992年6年生活方式干預結(jié)束時的測量。大慶研究參與者相對精簡；基線時的平均BMI為25.8 kg / m2。在指定飲食干預的診所中，如果BMI為.25 kg / m2，則鼓勵參與者減輕體重，目標為24 kg / m2;否則，建議使用高碳水化合物（55-65％）和中等脂肪（25-30％）的飲食。風險因素模式的總體變化相對較小。瘦體重患者的體重沒有變化，基線BMI為0.25 kg/m2的受試者體重減少1 kg。同樣，這表明單獨體重可能不是預防2型糖尿病最關鍵的問題;此外，其他生活方式問題很重要，而體重可作為幾種飲食和活動因素的總結(jié)指標。
與對照組（68%）相比，三種（單純飲食、單純運動、飲食-運動相結(jié)合）干預組（41-46%）的2型糖尿病累積6年發(fā)病率較低。大青研究隊列的20年隨訪分析于2008年發(fā)表。結(jié)果顯示，聯(lián)合干預組與沒有干預的對照組相比，2型糖尿病發(fā)病率持續(xù)下降；此外，在干預后期間，風險降低基本保持不變。然而，隨訪期間2型糖尿病的發(fā)病率普遍較高：在最終分析中，80％的干預參與者和93%的對照參與者患有2型糖尿病。
此外，這項為期20年的隨訪研究旨在評估生活方式干預是否會對心血管疾?。–VD）或死亡率的風險產(chǎn)生長期影響。結(jié)果顯示，對照組或三個干預組合的CVD事件，CVD死亡率或總死亡率無統(tǒng)計學差異。觀察到CVD死亡率顯著降低17%，這可以看出至少暗示生活方式干預的益處。
芬蘭的DPS是一項多中心試驗，從1993年到2001年在芬蘭的五個診所進行。該研究的主要目的是確定患有糖耐量受損的高危個體，是否可以只通過改變生活方式來預防2型糖尿病。該研究共招募了522名男性和女性。參與者被隨機分配到對照組或強化干預組。
干預組的基線體重平均減少4.5 kg，對照組受試者為1.0 kg（P <0.001），第一年和3年后體重減輕分別為3.5和0.9 kg（P，0.001）。此外，干預組的中心性肥胖和葡萄糖耐量指標在1年和3年隨訪檢查中均顯著高于對照組。在1年和3年的考試中，干預組受試者根據(jù)飲食和運動日記報告他們的飲食和運動習慣有顯著更有益的變化。與對照組相比，干預組代謝綜合征的成分也顯著改善。
截至2000年3月，當研究的隨訪中位時間為3年時，在522例隨機分入DPS的糖耐量受損患者中共診斷出86例糖尿病病例。干預組糖尿病累積發(fā)生率為11％（95％CI 6-15），4年后對照組為23％（95％CI 17-29）; 因此，與對照組相比，干預組試驗期間患糖尿病的風險降低了58％（P <0.001）。事后分析表明，除了減輕體重外，采用中等脂肪和高纖維含量的飲食，以及增加體力活動，與糖尿病風險降低獨立相關。
使用在DPS延長隨訪期間收集的數(shù)據(jù)進行的分析顯示，在中位總共7年的總體隨訪后，2型糖尿病的累積發(fā)病率顯著下降?？偢M期間的相對風險降低為43%。干預期間無糖尿病患者干預對糖尿病風險的影響：在干預后進行的3年中位隨訪后，在有221名風險人群的干預組中有31個新增2型糖尿病案例，而在有185名風險人群的對照組中有38例。相應的發(fā)病率分別為4.6和7.2/100人年（對數(shù)秩檢驗，P = 0.0401）（即相對風險降低36%）。
DPS的10年隨訪結(jié)果顯示干預組和對照組的總死亡率（2.2對3.8 / 1,000人年）和心血管疾病發(fā)病率（22.9對22.0 / 1000人年）沒有差異。有趣的是，當DPS組（基線時的所有IGT）與芬蘭人群為基礎的IGT患者隊列進行比較時，DPS隊列的校正風險比率較低：干預組和對照組的總死亡率分別為0.21（95%CI 0.09-0.52）和0.39（0.20）-0.79），心血管事件發(fā)生率為0.89（0.62±1.27）和0.87（0.60-1.27）。
糖尿病預防計劃（DPP）是一項在美國進行的多中心隨機臨床試驗。它比較了三種干預措施的有效性和安全性：強化生活方式干預或標準生活方式建議與二甲雙胍或安慰劑相結(jié)合。飲食干預的目標是通過消耗健康的低熱量低脂飲食來實現(xiàn)并保持7%的體重減輕，并且每周150分鐘進行中等強度的體力活動（例如快走）。與安慰劑對照組相比，2.8年后的強化生活方式干預減少了2型糖尿病風險平均隨訪58%。生活方式干預也優(yōu)于二甲雙胍治療，與安慰劑相比，其導致2型糖尿病風險降低31%。在1年的訪問中，平均體重減輕為7kg（~7%）。
在發(fā)現(xiàn)同樣在DPP中，2型糖尿病發(fā)病率降低58%與生活方式干預相關，與DPS類似，隨機試驗停止，參與者被邀請參加糖尿病預防計劃成果研究）。在隨訪期間，所有參與者，無論其原始治療組如何，都獲得了生活方式咨詢。在10年的總體隨訪期間（從最初的隨機化開始），與對照組相比，原始生活方式干預組的2型糖尿病發(fā)病率降低了34%。然而，在干預后隨訪期間，所有治療組的2型糖尿病發(fā)病率相似（前干預組為每100人年5.9人，安慰劑對照組為5.6%），證實了在前安慰劑對照組開展的生活方式干預取得了成功，即使在沒有任何積極干預的幾年隨訪以后。
[附]英文原文
Long-Term Benefits From Lifestyle Interventions for Type 2 Diabetes Prevention
The potential to prevent type 2 diabetes in high-risk individuals by lifestyle intervention was established in several clinical trials. These studies had a strong focus on increased physical activity and dietary modification as well as weight reduction among overweight participants. The key issue seems to be a comprehensive approach to correct several risk factors simultaneously. Furthermore, long-term follow-up studies of lifestyle interventions lasting for a limited time period seem to have a long-lasting carry-over effect on risk factors and diabetes incidence (Table1).
The research evidence has inspired national and local authorities and health care providers all over the world to start programs and activities to prevent type 2 diabetes and its complications. Based on the experiences from the clinical trials, as well as from the “real world” implementation programs, the IMAGE (Development and Implementation of a European Guideline and Training Standards for Diabetes Prevention) Study Group collated information in a systematic manner. The IMAGE deliverables include a European evidence-based guideline for the prevention of type 2 diabetes, a toolkit for the prevention of type 2 diabetes in Europe, and the quality indicators for the prevention of type 2 diabetes in Europe. What is needed now is political support to develop national action plans for diabetes prevention. The prerequisites for successful prevention activities include involvement of a number of stakeholders on the governmental and nongovernmental level as well as on different levels of health care. Furthermore, structures to identify high-risk individuals and manage intervention, follow-up, and evaluation have to be established.
Observational studies have provided firm evidence that multiple lifestyle-related factors either increase or decrease the risk of type 2 diabetes. Thus, in type 2 diabetes prevention, it is important to pay attention not only to one single factor such as obesity but also to several factors simultaneously. This method was unequivocally demonstrated by the Finnish Diabetes Prevention Study (DPS), where none of the high-risk individuals with impaired glucose tolerance (IGT) developed diabetes during the initial trial period if they reached four or five out of five predefined lifestyle targets (1). These targets were as follows: weight loss .5%, intake of fat,30% energy, intake of saturated fats ,10% energy, increase of dietary fiber to $15 g/1,000 kcal, and increase of physical activity to at least 4 h/week. Such targets are relatively modest and therefore possible to reach by many people. Moreover, to practice such a lifestyle is feasible for the long term, even for an entire lifetime.However, the trial data have been criticized for presenting an over-optimistic outlook, since the trial population comprised individuals who volunteered to participate in such a lifestyle intervention trial. It has been questioned whether or to what extent such trial results can be translated to the general population. Although this critique may be valid, the individuals participating in the trial were typical Finnish people with IGT who were overweight, were relatively sedentary, and whose diet was discordant with recommendations in many ways (2).
LONG-TERM EFFECTS OBSERVED DURING THE EXTENDED FOLLOW-UP OF LIFESTYLE INTERVENTION TRIALS—A promising finding is that lifestyle interventions lasting for a limited time period seem to have a long-lasting carry-over effect on type 2 diabetes incidence. The first study to suggest that a sustained risk reduction may exist was the Malm? Feasibility Study (8). Originally, the effect of exercise and diet (n = 161) on incidence of type 2 diabetes among men with IGT was compared with a reference group (n = 56) of similar men who did not want to join the lifestyle intervention. Thus, the groups were not assigned at random. By the end of the 5-year study period, 11% of the intervention group and 29% of the reference group had developed diabetes. The 12-year follow-up results (9) revealed that all-cause mortality among men in the former IGT intervention group was lower than that among the men in the nonrandomized IGT group who received “routine care” only (6.5 vs. 14.0 per 1,000 person-years, P = 0.009). Mortality in the former IGT intervention group was actually similar to that in men with normal glucose tolerance.
A large population-based screening program (110,660 individuals screened with an oral glucose tolerance test) to identify people with IGT was carried out in Da Qing, China, in 1986 (6). The randomization of study subjects was not done at random, but the 33 participating clinics (cluster randomization) were randomized to carry out the intervention according to one of the four specified intervention protocols (diet alone, exercise alone, diet-exercise combined, or none). Altogether, 577 men and women with IGT participated in the trial, and of them, 533 participated in the measurements at the end of the 6-year lifestyle intervention in 1992. The Da Qing study participants were relatively lean; the mean BMI was 25.8 kg/m2 at baseline. In clinics assigned to dietary intervention, the participants were encouraged to reduce weight if BMI was .25 kg/m2, aiming for, 24 kg/m2; otherwise, a high-carbohydrate (55-65%) and moderate-fat (25-30%) diet was recommended. The overall changes in risk factor patterns were relatively small. Body weight did not change in lean subjects, and there was a modest,1 kg reduction in subjects with baseline BMI .25 kg/m2. Again, this indicates that body weight alone may not be the most critical issue in the prevention of type 2 diabetes; also, other lifestyle issues are important, whereas body weight may work as a summary indicator of several dietary and activity factors.
The cumulative 6-year incidence of type 2 diabetes was lower in the three (diet alone, exercise alone, diet-exercise combined) intervention groups (41-46%) compared with the control group (68%). The 20-year follow-up analyses of the original Da Qing study cohort were published in 2008 (10). The results showed that the reduction in type 2 diabetes incidence persisted in the combined intervention group compared with control participants with no intervention; furthermore, the risk reduction remained essentially the same during the postintervention period. However, type 2 diabetes incidence during the follow-up was generally high: in the final analyses, 80% of the intervention participants and 93% of the control participants had developed type 2 diabetes.
Furthermore, the 20-year follow-up study aimed to assess whether the lifestyle intervention had a long-term effect on the risk of cardiovascular disease (CVD) or mortality. The results showed no statistically significant differences in CVD events, CVD mortality, or total mortality either in the control group or the three intervention groups combined. A non-significant 17% reduction in CVD death was observed, which can be seen at least suggestive for benefits of lifestyle intervention.
The Finnish DPS was a multicenter trial carried out in five clinics in Finland from 1993 to 2001. The main aim of the study was to find out whether type 2 diabetes is preventable with lifestyle modification alone among high-risk individuals with IGT. A total of 522 men and women were recruited into the study. The participants were randomly allocated either into the control group or the intensive intervention group (2).
Body weight reduction from baseline was on average 4.5 kg in the intervention group and 1.0 kg in the control group subjects (P , 0.001) after the first year and at 3 years, weight reductions were 3.5 and 0.9 kg (P , 0.001), respectively. Also, indicators of central adiposity and glucose tolerance improved significantly more in the intervention group than in the control group at both the 1-year and 3-year follow-up examinations. At the 1-year and 3-year examinations, intervention group subjects reported significantly more beneficial changes in their dietary and exercise habits, based on dietary and exercise diaries (2). The components of the metabolic syndrome also improved significantly in the intervention group compared with the control group (11).
By March 2000, a total of 86 incident Cases of diabetes had been diagnosed among the 522 subjects with IGT randomized into the DPS when the median follow-up duration of the study was 3 years. The cumulative incidence of diabetes was 11% (95% CI 6–15) in the intervention group and 23%(95%CI 17–29) in the control group after 4 years; thus, the risk of diabetes was reduced by 58% (P , 0.001) during the trial in the intervention group compared with the control group (1). Post hoc analyses have shown that in addition to weight reduction, adopting a diet with moderate fat and high fiber content (12), as well as increasing physical activity (13), was independently associated with diabetes risk reduction.
An analysis using the data collected during the extended follow-up of the DPS revealed that after a median of 7 years total follow-up, amarked reduction in the cumulative incidence of type 2 diabetes was sustained (14). The relative risk reduction during the total follow-up was 43%. The effect of intervention on diabetes risk was maintained among patients who after the intervention period were without diabetes: after the median postintervention follow-up time of 3 years, the number of incident new cases of type 2 diabetes was 31 in the intervention group among 221 people at risk and 38 in the control group among 185 people at risk. The corresponding incidences were 4.6 and 7.2 per 100 person-years, respectively (log-rank test, P = 0.0401) (i.e., 36% relative risk reduction).
The 10-year follow-up results of the DPS showed that total mortality (2.2 vs. 3.8 per 1,000 person-years) and cardiovascular morbidity (22.9 vs. 22.0 per 1,000 person-years) were not different between the intervention and control groups (15). Interestingly, when the DPS groups (all IGT at baseline) were compared with a Finnish population-based cohort of people with IGT, the adjusted hazard ratios were lower in the DPS cohort: 0.21 (95% CI 0.09–0.52) and 0.39 (0.20-0.79) for total mortality in the intervention and control groups, respectively, and 0.89 (0.62 1.27) and 0.87 (0.60–1.27) for cardiovascular events.
The Diabetes Prevention Program (DPP) was a multicenter randomized clinical trial carried out in the U.S. (16). It compared the efficacy and safety of three interventions: an intensive lifestyle intervention or standard lifestyle recommendations combined with metformin or placebo. The goals of the dietary intervention were to achieve and maintain 7% weight reduction by consuming a healthy low-calorie low-fat diet and to engage in physical activities of moderate intensity (such as brisk walking) $150 min per week. The intensive lifestyle intervention re- duced type 2 diabetes risk after 2.8 years mean follow-up by 58% compared with the placebo control group. Lifestyle intervention was also superior to metformin treatment, which resulted in a 31% type 2 diabetes risk reduction compared with placebo. At the 1-year visit, the mean weight loss was 7 kg (~7%).
After finding that also in the DPP a 58% risk reduction in type 2 diabetes incidence was associated with lifestyle intervention, similar to that in the DPS, the randomized trial was stopped and the participants were invited to join the Diabetes Prevention Program Outcomes Study (17). During the follow-up, all participants, regardless of their original treatment group, were offered lifestyle counseling. During the overall follow-up of 10 years (from the initial randomization), type 2 diabetes incidence in the original lifestyle intervention group was reduced by 34% compared with the control group. However, during the postintervention follow-up, type 2 diabetes incidence was similar in all treatment groups (5.9 per 100 person- years in the former intervention group and 5.6% in the placebo control group), confirming that lifestyle intervention that was initiated in the former placebo control group was successful, even after several years of follow-up without any active intervention.
【附】原文鏈接：
http://care.diabetesjournals.org/content/34/Supplement_2/S210