醣時
本翻譯僅作學術交流用，無商業意圖，請勿轉載，如有疑議問請來信
即使肥胖者暫時無代謝異常，也不代表風險低。研究指出，多數代謝健康肥胖者會隨時間轉為代謝不健康，增加心血管疾病、糖尿病與死亡率風險，提醒肥胖本身仍需積極管理。
關於代謝健康肥胖的快速事實
Quick Facts on Metabolically Healthy Obesity
BYLINE: Mary Gillam, Medical Editor, Point of Care
https://elsevier.health/en-US/metabolically-healthy-obesity
介紹 Introduction
超重和肥胖是過度脂肪積累的狀態，對健康構成風險。隨著過去半個世紀來其流行率的增加，肥胖及其許多併發症已成為主要的公共健康問題。肥胖通常通過計算身體質量指數來診斷，這也可以用來分類肥胖的嚴重程度。身體質量指數與脂肪量的相關性中等，儘管對於給定的 BMI 值，個體的體脂百分比和合併症及健康風險因素的存在有相當大的變異性(1)。
Overweight and obesity are states of excessive fat accumulation that present risks to health. With their increased prevalence over the last half century, obesity and its many complications have become a leading major public health problem. Obesity is typically diagnosed by calculation of the body mass index, which also can be used to classify the severity of obesity. Body mass index correlates moderately well with adiposity, although there is considerable variability in percentage body fat and presence of comorbidities and health risk factors on an individual level for a given BMI value(1).
肥胖通常與一系列代謝異常相關，包括高血壓、葡萄糖不耐受、胰島素抵抗、血脂異常、非酒精性脂肪肝病和代謝綜合症，這些都是 2 型糖尿病和動脈粥樣硬化性心血管疾病的重要風險因素。(見圖 1)
Obesity is often associated with a constellation of metabolic abnormalities, including hypertension, glucose intolerance, insulin resistance, dyslipidemia, nonalcoholic fatty liver disease, and the metabolic syndrome, which are important risk factors for type 2 diabetes and atherosclerotic cardiovascular disease. (see Figure 1)
圖 1. 健康正常體重個體與代謝健康肥胖和代謝不健康肥胖之間的主要心臟代謝參數(8)。
然而，並非所有肥胖者都有代謝併發症。代謝健康肥胖是一個源於臨床觀察的概念，指的是一部分肥胖者並不表現出心臟代謝異常。這一群體的識別來自於數據分析，顯示這部分肥胖個體的肥胖相關心臟代謝疾病風險似乎低於根據體重指數與心臟代謝風險之間的正相關所估計的風險（2）。基於這些數據，隨後有爭議地提出，識別這些個體將是有用的，因為這些患者可能不需要積極治療，因為他們被認為不太可能發展出隨後的心臟代謝併發症（3）。然而，來自長期結果研究的最新數據顯示，相當一部分代謝健康的肥胖患者往往會轉變為代謝不健康的狀態，並實際上發展出心臟代謝疾病，包括明顯的冠狀動脈疾病本身 4–6。 轉換從代謝健康的肥胖到代謝不健康的肥胖的發現經常發生，這表明代謝健康的肥胖代表了一種短暫的狀態，而不是一個穩定的肥胖子群體。
However, not all people with obesity have metabolic complications. Metabolically healthy obesity is a concept derived from clinical observations that a subgroup of people with obesity do not exhibit cardiometabolic abnormalities. The identification of this group came from analysis of data showing that this subgroup of obese individuals appear to have a lower risk of obesity-related cardiometabolic diseases than that which would be estimated from the positive association between body mass index and cardiometabolic risk (2). Based on such data, it was subsequently suggested, albeit controversially, that identifying such individuals would be useful since these patients may not require aggressive treatment as they were thought to be less likely to develop subsequent cardiometabolic complications (3). However, more recent data from long-term outcome studies demonstrate that a substantial proportion of metabolically healthy obese patients often convert to a metabolically unhealthy state, and do in fact develop cardiometabolic disease, including overt coronary artery disease itself 4–6. The finding that conversions from metabolically healthy to metabolically unhealthy obesity occur regularly suggests that metabolically healthy obesity represents a transient state, rather than a defined subgroup of obesity that remains stable.
代謝不健康肥胖的描述、標準和流行程度
Description, criteria, and prevalence of metabolically unhealthy obesity
代謝健康肥胖的概念源於幾十年前的觀察，肥胖個體對糖尿病和動脈粥樣硬化的易感性不同，這在某種程度上可能與體脂分佈有關。目前，尚未建立一套普遍接受的代謝健康肥胖的定義標準。大多數專家一致認為，代謝健康肥胖通常以缺乏任何代謝和心血管疾病為特徵，包括 2 型糖尿病、血脂異常、高血壓和動脈粥樣硬化性心血管疾病（ASCVD）在肥胖者中。對於成年人提出的一套實用的代謝健康肥胖標準包括（1）肥胖診斷（BMI ≥30 kg/m2）和（2）以下指標的證明：血清三酸甘油脂 ≤150 mg/dl，血清高密度脂蛋白膽固醇濃度 >40 mg/dl（男性）或 >50 mg/dl（女性），收縮壓（SBP） ≤130 mmHg，舒張壓 ≤85 mmHg，無抗高血壓藥物治療，且無降低血清葡萄糖的藥物。
The concept of metabolically healthy obesity developed from observations made decades ago that individuals with obesity have a different susceptibility to diabetes and atherosclerosis, which, in part, could be related to body fat distribution. At present, a set of universally accepted defining criteria for metabolically healthy obesity has not been established. Most experts agree that metabolically healthy obesity is typically marked by the absence of any metabolic and cardiovascular disease, including type 2 diabetes, dyslipidemia, hypertension, and atherosclerotic cardiovascular disease ASCVD in a person with obesity. One set of practical criteria for metabolically healthy obesity that has been proposed for adults includes (1) a diagnosis of obesity (BMI ≥30 kg/m2) AND (2) demonstration of the following: serum triglycerides ≤150 mg/dl), serum HDL-cholesterol concentrations >40 mg/dl (in men) or >50 mg/dl (in women), systolic blood pressure (SBP) ≤130 mmHg, diastolic blood pressure ≤85 mmHg, no antihypertensive drug treatment and no drug to lower serum glucose (7).
新陳代謝健康狀態的其他生理特徵包括足夠的心肺適能、保留的胰島素分泌和敏感性，以及對下半身皮下脂肪分佈的偏好（相對於肝臟或內臟脂肪）（8）。 （圖 1）
Additional physiologic traits of a metabolically healthy state include adequate cardiorespiratory fitness, preserved insulin secretion and sensitivity, and a predilection for lower body subcutaneous fat distribution (as opposed to liver or visceral fat) (8). (Figure 1)
有關新陳代謝健康肥胖的流行率數據顯示出很大的變異範圍，並受到缺乏標準化標準的影響。最近的一項包含 12 個隊列和 7 個干預研究的綜合分析發現，約 35%的肥胖患者被認為是新陳代謝健康的，儘管存在顯著的地區、種族、年齡和性別差異，結果也受到用於定義新陳代謝健康的標準的影響（9）。
Data on the prevalence of metabolically healthy obesity show a great range of variation and are confounded by the lack of standardized criteria for this phenotype. One recent meta-analysis that included 12 cohort and 7 intervention studies found that ~35% of the obese patients were considered metabolically healthy, though there were significant regional, ethnic, age, and sex differences and results were influenced by the criteria used to define metabolic health (9).
新陳代謝不健康肥胖的自然歷史
Natural history of metabolically unhealthy obesity
代謝健康的肥胖是一種短暫的表型，可能在減重和體重恢復的循環中轉變為代謝不健康的肥胖，並且在對肥胖治療和復發的反應中相互轉換(10)。來自縱向研究的數據顯示，約 30%至 50%的代謝不健康肥胖者在 4 至 20 年的隨訪期間轉變為代謝健康的肥胖狀態(4,5)。來自超過 90,000 名參與者的護士健康研究的 30 年隨訪數據驗證了代謝健康肥胖與代謝不健康肥胖之間的頻繁轉變，並顯示整個 BMI 範圍內隨著年齡增長代謝健康的下降(6)。這些發現得到了包括 5900 多名個體的 12 項研究的元分析的支持，該分析顯示幾乎一半被分類為代謝健康肥胖的參與者發展出至少 1 種代謝異常(9)。
Metabolically healthy obesity is a transient phenotype which can convert into and from metabolically unhealthy obesity during cycles of weight loss and weight regain in response to obesity treatments and recidivism, respectively(10). Data from longitudinal studies indicate that ~30% to 50% of people with metabolically unhealthy obesity convert to a state of metabolically healthy obesity over the course of 4 to 20 years of follow-up (4,5). 30-year follow-up data from over 90,000 participants of the Nurses’ Health Study verified the frequent transition from metabolically healthy to metabolically unhealthy obesity and demonstrated a decline in metabolic health with age across the entire BMI range(6). These findings are corroborated by a meta-analysis of 12 studies including more than 5900 individuals with 3–10-year follow-up, which demonstrated that almost half of the participants classified with metabolically healthy obesity developed at least 1 metabolic abnormality(9).
與代謝健康肥胖轉變為代謝不健康肥胖相關的主要因素是胰島素敏感性下降和空腹血糖增加（11）。從代謝健康肥胖轉變為代謝不健康肥胖的風險在那些 BMI 非常高、年齡較大、存在肝脂肪變性、異常代謝標準數量較多（特別是接近正常範圍上限的值）、生活方式指數較差（飲食組成、休閒時間體育活動和吸煙的綜合指標）以及在觀察期間體重增加的人群中更高（5,12–14）。綜合這些縱向研究表明，肥胖者的代謝健康並不是一種穩定的狀態，隨著年齡增長和持續體重增加而容易惡化。
The major factors associated with the conversion of metabolically healthy obesity to metabolically unhealthy obesity are a decline in insulin sensitivity and an increase in fasting blood glucose (11). The risk of transitioning from metabolically healthy obesity to metabolically unhealthy obesity is greater in those with a very high BMI, older age, presence of hepatic steatosis, higher number of abnormal metabolic criteria (especially values that are close to the upper limit of the normal range), a poor lifestyle index (a composite of diet composition, leisure time physical activity, and cigarette smoking), and weight gain during the observation period (5,12–14). Taken together, these longitudinal studies demonstrate that metabolic health among those who are obese is not a stable condition and is prone to deteriorate with aging and continued weight gain.
代謝不健康肥胖中的心血管風險
Cardiovascular risk in in metabolically unhealthy obesi
一般而言，2 型糖尿病、心血管疾病和全因死亡率的風險在代謝不健康的肥胖者中最高，其次是代謝健康的肥胖者，而在代謝健康且瘦的人群中風險最低（5,11,15–18）。
In general, the risks of type 2 diabetes, cardiovascular disease, and all-cause mortality are greatest in people with metabolically unhealthy obesity, followed by those with metabolically healthy obesity and least in those who are metabolically healthy and lean (5,11,15–18).
在代謝健康的肥胖者中，心血管事件（心肌梗塞、突發性心臟死亡、心力衰竭和周邊血管疾病）的風險低於代謝不健康的肥胖者，但仍高於代謝健康且體重正常的人（16,17）。來自健康改善網絡研究的報告顯示，代謝健康的肥胖者仍然面臨心血管疾病的風險增加，特別是心力衰竭，甚至冠狀動脈疾病（16）。同樣，對護士健康研究參與者的分析發現，能夠長期維持代謝健康的代謝健康肥胖者，其心血管疾病的風險仍比體重穩定的正常體重女性高出 57%（6）。在同一研究中顯示，與穩定的代謝健康肥胖者相比，從代謝健康轉變為代謝不健康的肥胖女性的心血管疾病風險明顯增加（6）。 最後，一項匯總了 18 項前瞻性觀察研究數據的綜合分析，涵蓋了 585,000 名參與者，隨訪中位數為 10 年，發現基線時代謝健康肥胖者的心血管事件風險比代謝健康且瘦的人高出約 50%（15）。
The risk of cardiovascular events (myocardial infarction, sudden cardiac death, heart failure, and peripheral vascular disease) is lower in people with metabolically healthy obesity than in those with metabolically unhealthy obesity, but is still higher than in people who are metabolically healthy and lean (16,17). A report from The Health Improvement Network study demonstrated that those with metabolically healthy obesity still had an increased risk of cardiovascular disease, particularly heart failure, and even coronary artery disease (16). Likewise, an analysis of participants of the Nurses´ Health Study found that metabolically healthy obese individuals who were able to maintain metabolic health over a long time still had a 57% higher risk of cardiovascular disease than those women with a stable normal body weight (6). In the same study it was shown that the risk of cardiovascular disease clearly increased in women who converted from metabolically healthy to metabolically unhealthy obesity compared to those with stable metabolically healthy obesity (6). Finally, a meta-analysis that pooled data from 18 prospective observational studies and included 585,000 participants followed over a median of 10 years found that the risk of cardiovascular events was about 50% greater in people with metabolically healthy obesity at baseline than in people who were metabolically healthy and lean (15).
因此，發展心血管事件的風險取決於代謝特徵表型是否保持穩定和健康，或惡化並轉變為代謝不健康的肥胖，且風險與從基線發展出的代謝異常數量直接相關（5,16）。
Hence, the risk of developing cardiovascular events depends on whether the metabolic profile phenotype remains stable and healthy, or worsens and converts to metabolically unhealthy obesity and the risk is directly related to the number of metabolic abnormalities that develop from baseline (5,16).
代謝不健康肥胖的糖尿病風險
Risk of diabetes in metabolically unhealthy obesity
在代謝健康不良的肥胖個體中，發展第二型糖尿病的風險顯著提高；在代謝健康但肥胖的個體中，風險中等偏高，而在代謝健康且瘦的人群中，風險相對較低。一項前瞻性隊列研究的綜合分析估計，與健康且瘦的人相比，代謝健康不良的肥胖者發展第二型糖尿病的風險高出 5 到 20 倍，而代謝健康的肥胖者與健康且瘦的人相比，發展第二型糖尿病的風險高出 4 倍。一項對 34,000 名年輕男性進行的隊列研究，在 6 年的時間內跟蹤體重和代謝參數，發現基線時代謝健康的超重和肥胖個體仍然比健康瘦的人有更高的第二型糖尿病風險。這些研究的總結表明，隨著時間的推移，代謝健康的肥胖相比於代謝功能障礙的肥胖，發展新發糖尿病的風險較低，但長期的代謝狀態仍然不理想。
The risk of developing type 2 diabetes is substantially elevated in obese individuals who are metabolically unhealthy; it is moderately high in individuals who are obese but metabolically healthy and relatively low in people who are metabolically healthy and lean. A meta-analysis of prospective cohort studies estimated that the risk of developing type 2 diabetes is 5- to 20-fold greater in obese people who are metabolically unhealthy compared to those who are healthy and lean, whereas those with metabolically healthy obesity have a 4-fold greater risk of developing type 2 diabetes compared to those who are healthy and lean 11. One cohort study that followed body weight and metabolic parameters among 34,000 young men over a 6-year time frame found that overweight and obese individuals who were metabolically healthy at baseline still had an increased risk of developing type 2 diabetes, as compared to healthy lean individuals (19). The summation of these studies demonstrates that over time, metabolically healthy obesity confers less risk for developing incident diabetes compared to obesity with metabolic dysfunction, but the long-term metabolic status still remains unfavorable.
代謝不健康肥胖的死亡風險
Mortality risk in in metabolically unhealthy obesity
一般來說，超重和肥胖與全因死亡風險增加有關（20）。肥胖但代謝健康的個體是否面臨更高的死亡風險尚不確定，因為現有的死亡風險數據存在矛盾（15,18,21–23）。有一些證據表明，代謝健康肥胖者的死亡風險較高。一項包含超過 10,000 名個體的前瞻性隊列研究，隨訪 20 年發現，那些肥胖但沒有任何心代謝異常的個體，其死亡風險仍然是健康非肥胖個體的 2 倍（22）。一項系統性回顧和荟萃分析，結合了八個隊列和 61,000 名患者的數據，發現代謝健康的肥胖者與代謝健康的正常體重個體相比，死亡率更高（23）。值得注意的是，分類為超重的個體的死亡風險未達到統計學意義，這證實了先前的結果，即死亡風險隨著體重指數的增加而呈連續變化（24）。
In general, overweight and obesity are associated with an excess risk of all-cause mortality (20). Whether obese individuals who are metabolically fit are at increased risk for death is uncertain as the available data on risk of mortality is conflicting (15,18,21–23). There is some evidence that the risk of mortality is elevated for individuals with metabolically healthy obesity. One prospective cohort study that included over 10,000 individuals followed for 20 years found that those individuals who were obese but without any cardiometabolic abnormalities still had a 2-fold greater risk of mortality as compared to the reference group of healthy non-obese individuals (22). A systematic review and meta-analysis that combined data from eight cohorts and 61,000 patients found that metabolically healthy obese individuals had a higher rate of mortality compared with metabolically healthy normal-weight individuals (23). Notably, the mortality risk for those categorized as overweight did not achieve statistical significance, corroborating previous results that mortality risks fall along a continuum in proportion to body mass index (24).
參考文獻 REFERENCES
1. Neeland IJ, Ross R, Després JP 等。內臟脂肪和異位脂肪、動脈粥樣硬化及心代謝疾病：立場聲明。柳葉刀糖尿病與內分泌學。2019;7(9):715-725。doi:10.1016/S2213-8587(19)30084-1
1. Neeland IJ, Ross R, Després JP, et al. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. Lancet Diabetes Endocrinol. 2019;7(9):715-725. doi:10.1016/S2213-8587(19)30084-1
2. Sims EAH. 是否有肥胖但新陳代謝健康的人？新陳代謝。2001;50(12):1499-1504. doi:10.1053/meta.2001.27213
2. Sims EAH. Are there persons who are obese, but metabolically healthy? Metabolism. 2001;50(12):1499-1504. doi:10.1053/meta.2001.27213
3. Stefan N, Häring HU, Schulze MB. 新陳代謝健康的肥胖：肥胖治療中的低垂果實？《柳葉刀糖尿病與內分泌學》。2018;6(3):249-258. doi:10.1016/S2213-8587(17)30292-9
3. Stefan N, Häring HU, Schulze MB. Metabolically healthy obesity: the low-hanging fruit in obesity treatment? Lancet Diabetes Endocrinol. 2018;6(3):249-258. doi:10.1016/S2213-8587(17)30292-9
4. Echouffo-Tcheugui JB, Short MI, Xanthakis V, 等。肥胖亞表型的自然歷史：在法蘭明翰心臟研究中二十年來的動態變化及預後。《臨床內分泌與新陳代謝雜誌》。2018;104(3):738-752. doi:10.1210/jc.2018-01321
4. Echouffo-Tcheugui JB, Short MI, Xanthakis V, et al. Natural History of Obesity Subphenotypes: Dynamic Changes over Two Decades and Prognosis in the Framingham Heart Study. J Clin Endocrinol Metab. 2018;104(3):738-752. doi:10.1210/jc.2018-01321
5. Mongraw-Chaffin M, Foster MC, Anderson CAM, et al. 新陳代謝健康的肥胖、轉變為代謝症候群及心血管風險。美國心臟病學會雜誌。2018;71(17):1857-1865. doi:10.1016/j.jacc.2018.02.055
5. Mongraw-Chaffin M, Foster MC, Anderson CAM, et al. Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk. J Am Coll Cardiol. 2018;71(17):1857-1865. doi:10.1016/j.jacc.2018.02.055
6. Eckel N, Li Y, Kuxhaus O, Stefan N, Hu FB, Schulze MB. 從代謝健康到不健康表型的轉變及其與 90,257 名女性（護士健康研究）中不同 BMI 類別的心血管疾病風險的關聯：來自前瞻性隊列研究的 30 年隨訪。柳葉刀糖尿病內分泌學。2018;6(9):714-724. doi:10.1016/S2213-8587(18)30137-2
6. Eckel N, Li Y, Kuxhaus O, Stefan N, Hu FB, Schulze MB. Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses’ Health Study): 30 year follow-up from a prospective cohort study. Lancet Diabetes Endocrinol. 2018;6(9):714-724. doi:10.1016/S2213-8587(18)30137-2
7. Lavie CJ, Laddu D, Arena R, Ortega FB, Alpert MA, Kushner RF. 健康體重與肥胖預防：JACC 健康促進系列。美國心臟病學會雜誌。2018;72(13):1506-1531. doi:10.1016/j.jacc.2018.08.1037
7. Lavie CJ, Laddu D, Arena R, Ortega FB, Alpert MA, Kushner RF. Healthy Weight and Obesity Prevention: JACC Health Promotion Series. J Am Coll Cardiol. 2018;72(13):1506-1531. doi:10.1016/j.jacc.2018.08.1037
8. Lonardo A, Mantovani A, Lugari S, Targher G. 非酒精性脂肪肝病（NAFLD）與代謝健康或代謝不健康肥胖之間的流行病學和病理生理學關聯。肝臟病學年鑑。2020;19(4):359-366. doi:10.1016/j.aohep.2020.03.001
8. Lonardo A, Mantovani A, Lugari S, Targher G. Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity. Ann Hepatol. 2020;19(4):359-366. doi:10.1016/j.aohep.2020.03.001
9. Lin H, Zhang L, Zheng R, Zheng Y. 代謝健康肥胖的流行率、代謝風險及生活方式干預的效果：系統評價和荟萃分析。Med (United States). 2017;96(47). doi:10.1097/MD.0000000000008838
9. Lin H, Zhang L, Zheng R, Zheng Y. The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: A systematic review and meta-analysis. Med (United States). 2017;96(47). doi:10.1097/MD.0000000000008838
10. Appleton SL, Seaborn CJ, Visvanathan R 等。代謝健康肥胖表型中的糖尿病和心血管疾病結果：一項隊列研究。《糖尿病護理》。2013;36(8):2388-2394。doi:10.2337/dc12-1971
10. Appleton SL, Seaborn CJ, Visvanathan R, et al. Diabetes and cardiovascular disease outcomes in the metabolically healthy obese phenotype: A cohort study. Diabetes Care. 2013;36(8):2388-2394. doi:10.2337/dc12-1971
11. Bell JA, Hamer M, Batty GD, Singh-Manoux A, Sabia S, Kivimäki M。健康肥胖成人中代謝風險因素的發生率：20 年隨訪。《美國心臟病學會雜誌》。2015;66(7):871-873。doi:10.1016/j.jacc.2015.06.014
11. Bell JA, Hamer M, Batty GD, Singh-Manoux A, Sabia S, Kivimäki M. Incidence of metabolic risk factors among healthy obese adults: 20-year follow-up. J Am Coll Cardiol. 2015;66(7):871-873. doi:10.1016/j.jacc.2015.06.014
12. Guo F, Garvey WT. 在代謝健康和不健康肥胖中的心血管代謝疾病風險：成年人代謝健康狀態的穩定性。肥胖。2016;24(2):516-525. doi:10.1002/oby.21344
12. Guo F, Garvey WT. Cardiometabolic disease risk in metabolically healthy and unhealthy obesity: Stability of metabolic health status in adults. Obesity. 2016;24(2):516-525. doi:10.1002/oby.21344
13. Hashimoto Y, Hamaguchi M, Fukuda T, Ohbora A, Kojima T, Fukui M. 脂肪肝作為非超重個體從代謝健康轉變為代謝異常的風險因素。內分泌學。2017;57(1):89-97. doi:10.1007/s12020-017-1313-6
13. Hashimoto Y, Hamaguchi M, Fukuda T, Ohbora A, Kojima T, Fukui M. Fatty liver as a risk factor for progression from metabolically healthy to metabolically abnormal in non-overweight individuals. Endocrine. 2017;57(1):89-97. doi:10.1007/s12020-017-1313-6
14. Espinosa De Ycaza AE, Donegan D, Jensen MD. 代謝健康的超重/肥胖表型的長期代謝風險。國際肥胖期刊。2018;42(3):302-309. doi:10.1038/ijo.2017.233
14. Espinosa De Ycaza AE, Donegan D, Jensen MD. Long-term metabolic risk for the metabolically healthy overweight/obese phenotype. Int J Obes. 2018;42(3):302-309. doi:10.1038/ijo.2017.233
15. Zheng R, Zhou D, Zhu Y. 代謝健康肥胖的心血管疾病和全因死亡率的長期預後：系統評價和荟萃分析。流行病學與社區健康雜誌。2016;70(10):1024-1031. doi:10.1136/jech-2015-206948
15. Zheng R, Zhou D, Zhu Y. The long-term prognosis of cardiovascular disease and all-cause mortality for metabolically healthy obesity: A systematic review and meta-analysis. J Epidemiol Community Health. 2016;70(10):1024-1031. doi:10.1136/jech-2015-206948
16. Caleyachetty R, Thomas GN, Toulis KA 等。代謝健康的肥胖與 350 萬男性和女性中的心血管疾病事件。美國心臟病學會雜誌。2017;70(12):1429-1437。doi:10.1016/j.jacc.2017.07.763
16. Caleyachetty R, Thomas GN, Toulis KA, et al. Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women. J Am Coll Cardiol. 2017;70(12):1429-1437. doi:10.1016/j.jacc.2017.07.763
17. Eckel N, Meidtner K, Kalle-Uhlmann T, Stefan N, Schulze MB。代謝健康的肥胖與心血管事件：系統評價和荟萃分析。歐洲預防心臟病學雜誌。2015;23(9):956-966。doi:10.1177/2047487315623884
17. Eckel N, Meidtner K, Kalle-Uhlmann T, Stefan N, Schulze MB. Metabolically healthy obesity and cardiovascular events: A systematic review and meta-analysis. Eur J Prev Cardiol. 2015;23(9):956-966. doi:10.1177/2047487315623884
18. Hamer M, Stamatakis E. 新陳代謝健康的肥胖與全因及心血管疾病死亡風險。J Clin Endocrinol Metab. 2012;97(7):2482-2488. doi:10.1210/jc.2011-3475
18. Hamer M, Stamatakis E. Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. J Clin Endocrinol Metab. 2012;97(7):2482-2488. doi:10.1210/jc.2011-3475
19. Twig G, Afek A, Derazne E, et al. 體重過重和肥胖的代謝健康年輕成年人糖尿病風險。糖尿病護理。2014;37(11):2989-2995. doi:10.2337/dc14-0869
19. Twig G, Afek A, Derazne E, et al. Diabetes risk among overweight and obese metabolically healthy young adults. Diabetes Care. 2014;37(11):2989-2995. doi:10.2337/dc14-0869
20. Adams KF, Schatzkin A, Harris TB, et al. 超重、肥胖與 50 至 71 歲人群中的死亡率：一項大型前瞻性隊列研究。新英格蘭醫學雜誌。2006;355(8):763-778. doi:10.1056/nejmoa055643
20. Adams KF, Schatzkin A, Harris TB, et al. Overweight, Obesity, and Mortality in a Large Prospective Cohort of Persons 50 to 71 Years Old. N Engl J Med. 2006;355(8):763-778. doi:10.1056/nejmoa055643
21. Kuk JL, Rotondi M, Sui X, Blair SN, Ardern CI. 擁有肥胖但沒有其他代謝風險因素的個體在男性和女性中並不顯著增加全因死亡風險。Clin Obes. 2018;8(5):305-312. doi:10.1111/cob.12263
21. Kuk JL, Rotondi M, Sui X, Blair SN, Ardern CI. Individuals with obesity but no other metabolic risk factors are not at significantly elevated all-cause mortality risk in men and women. Clin Obes. 2018;8(5):305-312. doi:10.1111/cob.12263
22. Johnson W, Bell JA, Robson E, Norris T, Kivimäki M, Hamer M. 基線風險因素較差是否解釋了健康肥胖與死亡風險增加之間的關聯？白廳 II 研究。Int J Obes. 2019;43(8):1578-1589. doi:10.1038/s41366-018-0192-0
22. Johnson W, Bell JA, Robson E, Norris T, Kivimäki M, Hamer M. Do worse baseline risk factors explain the association of healthy obesity with increased mortality risk? Whitehall II Study. Int J Obes. 2019;43(8):1578-1589. doi:10.1038/s41366-018-0192-0
23. Kramer CK, Zinman B, Retnakaran R. 代謝健康的超重和肥胖是否是良性狀況？：一項系統評價和荟萃分析。Ann Intern Med. 2013;159(11):758-769. doi:10.7326/0003-4819-159-11-201312030-00008
23. Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions?: A systematic review and meta-analysis. Ann Intern Med. 2013;159(11):758-769. doi:10.7326/0003-4819-159-11-201312030-00008
24. Flegal KM, Kit BK, Orpana H, Graubard BI. 使用標準體重指數類別的超重和肥胖與全因死亡率的關聯：一項系統評價和荟萃分析。JAMA – J Am Med Assoc. 2013;309(1):71-82. doi:10.1001/jama.2012.113905
24. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories a systematic review and meta-analysis. JAMA – J Am Med Assoc. 2013;309(1):71-82. doi:10.1001/jama.2012.113905
25. Magkos F. 新陳代謝健康的肥胖：名稱中有什麼？美國臨床營養學雜誌。2019;110(3):533-537. doi:10.1093/ajcn/nqz133
25. Magkos F. Metabolically healthy obesity: What’s in a name? Am J Clin Nutr. 2019;110(3):533-537. doi:10.1093/ajcn/nqz133