Køster-Rasmussen Rasmus
Dan Med J. 2017 Jun;64(6).
This PhD thesis is about weight changes. What determines long-term weight changes in the adult general population? Is it possible that weight loss may not always be healthy? The present clinical guidelines for general practice advice most overweight persons and patients with type 2 diabetes to lose weight. Are the guidelines based on firm evidence? METHODS: The back-bone of the thesis is constituted by three scientific articles based on three different population based cohort studies. Multivariable modeling and other epidemiological methods were used. RESULTS: Article 1 examined weight changes in the general population in relation to smoking status, and proposed a graphical 'smoking cessation weight change model', demonstrating the importance of time, age and smoking status in relation to long-term weight changes. Article 2 suggested new methods to improve the processing of dietary data. It was demonstrated how median imputation for missing values and assumptions about standard portion sizes were inferior to stochastic methods conditioning on information about physiology of the individual. Article 3 evaluated the influence of prospectively planned intentional weight loss on long-term morbidity and mortality in patients with type 2 diabetes. Therapeutic intentional weight loss supervised by a medical doctor was not associated with reduced morbidity or mortality. In the general population the dietary intake of fructose and soft drinks sweetened with sugar was not associated with weight change over 9 years. Weight gain rates were large in young adults and incrementally smaller in middle aged adults. Subjects more than 60 years lost weight on average. Historical weight data suggest that the body weight increases throughout life to the age of 60-65years. A study with simulated data indicates that bias in baseline BMI may misleadingly have favored weight loss in earlier cohort studies of intentional weight loss and mortality. DISCUSSION: The findings regarding weight loss and mortality in patients with type 2 diabetes are in opposition to the prevailing observational literature. Harrington's meta-analysis of intentional weight loss and the underlying studies are evaluated along with the Look AHEAD trial and a number of diabetes prevention studies. Difficulties in conducting and interpreting weight change studies are discussed. CONCLUSIONS: Surprisingly, intentional therapeutic weight loss in patients with type 2 diabetes, supervised by a medical doctor, did not seem to reduce the long-term risk for CVD, CVD-mortality or all-cause mortality. The contradictions between our results and the prevailing observational evidence may be explained by methodological weaknesses favoring weight loss in earlier studies. Consequently, there is no good evidence to support that intentional weight loss will reduce the risk of CVD or mortality in any group of patients in general practice or in the general population. Age was a powerful determinant of weight changes and the 'normal weight development' can be taken into consideration when evaluating weight studies, and when general practitioners are following their patients over time. Compared with age, sex, education, and comorbidity, lifestyle factors like the dietary intake and physical activity seemed to be of less importance for long-term weight development. An exception to this was smoking or smoking cessation. Based on the scientific literature in the field and on the results of article 3, it seems uncertain whether weight loss is beneficial or harmful in terms of mortality and cardiovascular morbidity in patients with diabetes and in overweight people in general. Improvements in for instance psychosocial factors and diabetes prevention may well be short term as only few are able to a maintain weight loss. Rather than going for weight loss in overweight high risk patients, it seems more rational for general practitioners to focus on other lifestyle changes like for instance Mediterranean diet and increased exercise.
本博士论文围绕体重变化展开。是什么决定了成年普通人群的长期体重变化?体重减轻是否并非总是健康的?目前的全科医疗临床指南建议大多数超重者和2型糖尿病患者减重。这些指南有确凿的证据依据吗?
本论文的核心由三篇基于三项不同人群队列研究的科学文章构成。运用了多变量建模及其他流行病学方法。
文章1研究了普通人群中体重变化与吸烟状况的关系,并提出了一个图表式 “戒烟体重变化模型”,展示了时间、年龄和吸烟状况与长期体重变化的关联。文章2提出了改进饮食数据处理的新方法。研究表明,缺失值的中位数插补法以及关于标准份量大小的假设,不如基于个体生理信息的随机方法。文章3评估了前瞻性计划的有意减重对2型糖尿病患者长期发病率和死亡率的影响。由医生监督的治疗性有意减重与发病率或死亡率降低并无关联。在普通人群中,果糖和含糖软饮料的饮食摄入量与9年期间的体重变化无关。年轻人的体重增加率较高,中年人的体重增加率逐渐降低。60岁以上的人群平均体重减轻。历史体重数据表明,体重在60 - 65岁之前会持续增加。一项模拟数据研究表明,基线体重指数的偏差可能在早期有意减重与死亡率的队列研究中误导性地倾向于支持减重。
关于2型糖尿病患者减重与死亡率的研究结果与现有观察性文献相悖。对哈灵顿关于有意减重的荟萃分析及其基础研究,以及“展望”(Look AHEAD)试验和多项糖尿病预防研究进行了评估。讨论了开展和解释体重变化研究的困难。
令人惊讶的是,由医生监督的2型糖尿病患者的治疗性有意减重,似乎并未降低心血管疾病(CVD)、心血管疾病死亡率或全因死亡率的长期风险。我们的结果与现有观察性证据之间的矛盾,可能是由于早期研究中有利于减重的方法学缺陷所致。因此,没有充分证据支持有意减重会降低全科医疗中任何患者群体或普通人群的心血管疾病风险或死亡率。年龄是体重变化的有力决定因素,在评估体重研究以及全科医生长期跟踪患者时,可考虑“正常体重发展”情况。与年龄、性别、教育程度和合并症相比,饮食摄入和身体活动等生活方式因素对长期体重发展的重要性似乎较低。吸烟或戒烟是个例外。基于该领域的科学文献以及文章3的结果,就糖尿病患者和一般超重人群的死亡率和心血管疾病发病率而言,减重有益还是有害似乎并不确定。例如心理社会因素和糖尿病预防方面的改善可能只是短期的,因为只有少数人能够维持体重减轻。对于超重的高危患者,全科医生似乎更应关注其他生活方式的改变,比如地中海饮食和增加运动,而不是追求减重。