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肥満と肥満症

著者: 江崎治 前 国立国際医療研究センター 運動栄養肥満外来

監修: 野田光彦 国際医療福祉大学市川病院 糖尿病・代謝・内分泌内科

著者校正/監修レビュー済:2020/12/03
参考ガイドライン:
  1. 厚生労働省「日本人の食事摂取基準」策定検討会:「日本人の食事摂取基準(2020年版)」策定検討会報告書
患者向け説明資料

概要・推奨   

  1. 日本人においては、過体重(BMI≧25)でなくても、過去の体重と糖尿病罹患との間に正の関連が認められる。
  1. 過去のBMIが高いと、癌と動脈硬化性疾患による死亡率が増加する。特に、動脈硬化性疾患による死亡率とは直線的な正の関連が認められた。一方、過去のBMIが低いと呼吸器疾患による死亡が増加し、直線的な負の関連が認められた。
  1. 運動を含む生活習慣により少なくとも7%の体重減少が維持できると、糖尿病罹患が58%予防される。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
江崎治 : 特に申告事項無し[2021年]
監修:野田光彦 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 最近の栄養疫学の進歩を取り入れ、肥満者の食事指導の内容を刷新した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 肥満は体内の脂肪組織が過剰に増加した状態で、BMI 25kg/m2 以上の人を肥満と判定する。(<図表>
  1. 肥満症とは医学的に治療(減量)を必要とする病態をいい、疾患単位として扱う。腹部CTで内臓脂肪面積が100cm2を超える場合か、または肥満に起因ないし関連する健康障害(耐糖能障害、高血圧症など)を合併する場合に肥満症と診断する。
  1. メタボリックシンドロームでは肥満のなかにはよい肥満と悪い肥満があると考え、内臓肥満の疑いがあり(腹囲で推定)、かつ代謝マーカー(血糖値、血中脂質、血圧)の2つ以上が規定値を外れる人をメタボリックシンドローム(すなわち悪い肥満)と呼んでいる。しかし、スウェーデンの観察研究では、肥満に関わる代謝マーカーを考慮しなくても長期間観察すると、肥満自体(BMI高値)が心血管疾患や糖尿病のリスクになることが示されている。
  1. 肥満が高度になると、治療は困難になる。このため、予防がきわめて大切で、若年者はBMIが23以上にならないように食事内容(摂取カロリー)と身体活動量を調整する必要がある。
  1. 日本人の食事摂取基準 (2020年版)では、年齢別に、目標とするBMIの範囲が示されている(<図表>)。18~49歳ではBMI18.5~24.9、50~64歳ではBMI20.0~24.9、65歳以上ではBMI21.5~24.9となり、BMIの下の基準が高齢になるほど、高くなっている。この基準の根拠は、観察研究で高齢者ではBMIの少し高い群(65歳以上でBMI 22.5~27.4)で総死亡率がもっとも低くなることにある(<図表>)。その理由として、因果の逆転(病気が隠れている人は低体重になりやすいので、低体重の人は死亡率が高くなる)もあり得るが、低体重の人は、低栄養で免疫力が弱く肺炎で重症化しやすい、脂肪組織が少ないと体内エネルギーの蓄積量が少なくなり侵襲時の抵抗力が弱くなるなど、低体重が原因で死亡率が増加する可能性があるためである。しかし、総死亡率でなく、総合的な疾病の罹患リスク低減を目標とするならば、目標とするBMIは、QOLを考慮した健康寿命を最も長くする各年齢層でのBMIが良いが、残念ながら、このBMIは調べられていない。
 
日本人年齢別、目標BMI

 日本人の食事摂取基準(2020年版)では、年齢別に、目標とするBMIの範囲が示されている。18~49歳ではBMI18.5~24.9、50~64歳ではBMI20.0~24.9、65歳以上ではBMI21.5~24.9となり、BMIの下の基準が高齢になるほど、高くなっている。
 高齢者ではBMIは少し高い人(65歳以上でBMI 22.5~27.4)で死亡率が低いことによる(観察研究)。この理由として、因果の逆転(病気が隠れている人は低体重で、低体重の人は死亡率が高い)もあり得るが、低体重の人は、低栄養で免疫力が弱く肺炎にかかりやすい、脂肪組織が少ないとエネルギーの蓄積量が少ないため侵襲時の抵抗力が弱くなるなど、低体重が原因で死亡率が増加することが挙げられる。

 
日本での主要死因別にみたBMI(kg/m2)と死亡率の関連

BMIが23.0~24.9 の群を1とした時の各BMIでのハザード比を示した。わが国における7つのコホート研究のプール解析。追跡開始時年齢=40~103 歳、平均追跡年数=12.5 年、対象者数(解析者数)=男性 162,092 人、女性 191,330 人、死亡者数(解析者数)=男性 25,944 人、女性 16,036 人、調整済み変数=年齢、喫煙、飲酒、高血圧歴、余暇活動又は身体活動、その他(それぞれのコホート研究によって異なる)。
備考:追跡開始後 5 年未満における死亡を除外した解析である。
 
参考文献:
Sasazuki S, Inoue M, Tsuji I, Sugawara Y, Tamakoshi A, Matsuo K, Wakai K, Nagata C, Tanaka K, Mizoue T, Tsugane S; Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan. Body mass index and mortality from all causes and major causes in Japanese: results of a pooled analysis of 7 large-scale cohort studies. J Epidemiol. 2011;21(6):417-30.PMID: 21908941

 
  1. 日本人においては、過体重(BMI≥25)でなくても、過去の体重と糖尿病罹患との間に正の関連が認められる。(参考文献:[1][2]
  1. 日本人においても、肥満は強い糖尿病罹患リスクであり、BMIが23以上の人は、20以下の人に比べて、糖尿病罹患のハザード比は3倍も高い。
  1. 岐阜県在住の糖尿病に罹患していない男性16,829人、女性8,370人のBMI(35~59歳)を1988年から1991年までに得、その後約7年間観察したところ、男性869人、女性224人の新規糖尿病発症が認められた。1988年から1991年のBMIと糖尿病罹患の関連をCox 回帰分析法で調べた。年齢、喫煙、アルコール、運動、教育の5項目の交絡因子を調整しても、BMIが1増加するごとに糖尿病罹患のハザード比は男性で1.26(95%CI, 1.24-1.29) 女性1.24(95%CI, 1.20-1.29)増加した。(<図表>
  1. 追記:過去のBMIと糖尿病罹患には強い正の関連が認められ、肥満の予防が重要であることが示されている。
 
  1. 過去のBMIが高いと、癌と動脈硬化性疾患による死亡率が増加する。特に、動脈硬化性疾患による死亡率とは直線的な正の関連が認められた。一方、過去のBMIが低いと呼吸器疾患による死亡が増加し、直線的な負の関連が認められた(o)。(参考文献:[3]
  1. 日本人を含めて多くの観察研究では、痩せていても太っていても死亡率は増加する。このため、過去のBMIと死亡率との関連はU字型のカーブを示し、死亡率の最も少ないBMIは23.0-24.9で、少し小太りのほうが死亡率は低いという結果にある。しかし、死因を分析した韓国での観察研究から、痩せていて死亡率が増加するのは、呼吸器疾患による死亡が増加するためで、動脈硬化性疾患による死亡は、BMIが少ないほど少ないことが示されている。
  1. 120万人を対象とした韓国での12年間の観察研究で、BMIと死因の関連が調べられている。BMIの低かった人は呼吸器疾患(結核、COPD、喘息、肺炎)の死亡率が高く、BMIの高かった人は癌と動脈硬化関連疾患での死亡率が高いことが示された。呼吸器疾患に関しては、研究開始時点で診断できていない呼吸器疾患のある対象者が含まれていて(これらの人は最初からBMIが低い)、体重の少ない人で死亡率が高くなる可能性(因果の逆転)も否定できないが、体重が少ないことが原因となり、呼吸器疾患に罹患すると予後が悪くなることが考えられている。
  1. 肥満者では肺炎罹患のリスクは高くなるが、肺炎による死亡率のリスクは低くなることが、観察研究のメタアナリシスで示されている[4]。肥満が肺炎罹患のリスクになる理由として、肥満では胃食道逆流症が起こりやすく誤嚥性肺炎の原因になること、肥満は糖尿病と喘息のリスクで、糖尿病と喘息は肺炎のリスクであること、肥満の人は血清25(OH)D3濃度が低くなること(血清25(OH)D3濃度が低いと肺炎のリスクになる)、肥満の人はレプチン抵抗性を示すこと(レプチンの効果が減弱すると呼吸器感染症に罹りやすくなる)の4つが挙げられる。一方、肥満者で肺炎の死亡率リスクが低くなる理由として、肥満者は冠動脈疾患、2型糖尿病、心不全罹患のリスクが高いため、肥満の肺炎患者はより高度な治療を受けているかもしれないこと、肥満の肺炎患者ではTNF-α活性を制御する可溶性TNF-αレセプターが脂肪組織からより多く産生されるため、TNF-αが中和され、肺炎の程度が軽減されること、肥満の人は、肺炎による異化作用のストレスを打ち消すのに、十分なエネルギーの蓄えを持っていることの3つが挙げられる。
  1. 動脈硬化性疾患による死亡とはBMI依存性の直線的な正の関連が認められ、BMIは少ないほど動脈硬化性疾患による死亡数は少なくなっている(日本の結果と異なることに注意;日本人を対象とした研究では、心疾患や脳血管障害による死亡はBMIが低くかった人でも増加する。これは日本人特有の現象で、その他のアジア人でも認められていない。理由として、心筋機能の異常や心弁膜症の人は低体重の人が多く、低体重の人の中に、動脈硬化以外の原因の心疾患で死亡した人が含まれていた可能性が考えられている。また、低体重の人は血中コレステロール値が低い人が多く、脳出血のリスクになった可能性もある)。
 
BMIと喫煙歴による、癌、動脈硬化性疾患、呼吸器疾患のハザード比

120万人を対象とした12年間のコホート研究。主要な病気のある人は除く。

出典

img1:  Body-mass index and mortality in Korean men and women.
 
 N Engl J Med. 2006 Aug 24;355(8):779-87.・・・
問診・診察のポイント  
  1. 体重増加の時期を把握することは肥満の原因を推定するうえで重要なので、最初に患者の体重変動の経過を聞く。外来で診察時間が十分とれないときはアンケートに体重の変動について記載してもらう(<図表>)。抗精神薬、ステロイド剤(経口、吸入)服用の有無は必ず聞く。睡眠時無呼吸症候群は見落としやすい。昼間に眠たくなるかどうか、寝ているとき呼吸が止まることがあるかどうか聞き、疑いのある場合、Epworth sleepiness scale (ESS)(アンケート調査)を行い5点以上の場合、ポリソムノグラフィー(PSG)検査を行っている病院を紹介する(<図表>, <図表>)。女性の場合、妊娠の可能性と月経の状態(月経異常があればPCOSを疑う)を聞く。

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文献 

著者: T Nagaya, H Yoshida, H Takahashi, M Kawai
雑誌名: Diabet Med. 2005 Aug;22(8):1107-11. doi: 10.1111/j.1464-5491.2005.01602.x.
Abstract/Text AIMS: Obesity, the strongest risk factor for Type 2 diabetes mellitus, is less prevalent in Japanese than in other populations. We investigated the effects of body mass index (BMI, kg/m(2)) on the incidence of diabetes mellitus in a Japanese population.
METHODS: A follow-up study in 16 829 men and 8370 women who were apparently healthy at baseline (age 30-59 years, BMI 14.9-43.2 kg/m(2)). Incident diabetes mellitus was identified by 'fasting serum glucose > or = 7.00 mmol/l (126 mg/dl)' and/or 'under medical treatment for diabetes mellitus'. Hazard ratio, as an index for risk ratio, for incident diabetes mellitus according to BMI was estimated using Cox's proportional hazard models. Baseline age, smoking, drinking, exercise and education were computed as confounders.
RESULTS: During mean follow-up periods of 7.4 years for men and 7.1 years for women, 869 men and 224 women had incident diabetes mellitus. Although the subjects were averagely non-obese [mean (sd) BMI 23.1 (2.6) kg/m(2) for men, 22.3 (2.7) kg/m(2) for women], hazard ratio for incident diabetes mellitus increased in parallel with increases in BMI. Multivariate-adjusted hazard ratios (95% confidence intervals) for increases in BMI of 1 kg/m(2) were 1.26 (1.24, 1.29) for men and 1.24 (1.20, 1.29) for women.
CONCLUSION: BMI, even within the non-obese level, is a dose-dependent risk factor for diabetes mellitus in middle-aged Japanese. Increases in BMI of 1 kg/m(2) (= body-weight gain of 2.4-2.9 kg) may raise the risk by about 25%.

PMID 16026381  Diabet Med. 2005 Aug;22(8):1107-11. doi: 10.1111/j.1464・・・
著者: Akiko Nanri, Tetsuya Mizoue, Yoshihiko Takahashi, Yumi Matsushita, Mitsuhiko Noda, Manami Inoue, Shoichiro Tsugane, Japan Public Health Center-based Prospective Study Group
雑誌名: J Epidemiol Community Health. 2011 Dec;65(12):1104-10. doi: 10.1136/jech.2009.097964. Epub 2010 Jul 13.
Abstract/Text BACKGROUND: Few studies have examined the impact of weight change in different periods of lifetime on type 2 diabetes risk, and the association of weight loss with type 2 diabetes is unclear. We prospectively investigated the association of weight change since age 20 y and that during middle-to-late adulthood with the incidence of type 2 diabetes.
METHODS: Subjects were 52,014 men and women aged 45-75 y who participated in the Japan Public Health Center-Based Prospective Study and had no history of diabetes. ORs of self-reported physician-diagnosed type 2 diabetes for weight change between age 20 y and baseline survey (mean age 50.6 y) and during 5 y between baseline and second surveys were estimated using logistic regression analysis.
RESULTS: During the 5-year period following 5-year survey, 989 newly diagnosed cases of type 2 diabetes were self-reported. Weight gain from age 20 y was associated with an increased risk of type 2 diabetes. The multivariate-adjusted OR (95% CI) for a weight gain of ≥5 kg versus a stable weight were 2.61 (2.11 to 3.23) in men and 2.56 (1.95 to 3.35) in women. A weight gain of ≥5 kg over the 5-y following the baseline survey was also associated with an increased risk in women. No association with weight loss was observed for either period.
CONCLUSIONS: These results suggest that long-term weight gain from early adulthood to middle-age increases risk of type 2 diabetes in men and women and that risk is further enhanced by weight gain in later life in women.

PMID 20628079  J Epidemiol Community Health. 2011 Dec;65(12):1104-10. ・・・
著者: Sun Ha Jee, Jae Woong Sull, Jungyong Park, Sang-Yi Lee, Heechoul Ohrr, Eliseo Guallar, Jonathan M Samet
雑誌名: N Engl J Med. 2006 Aug 24;355(8):779-87. doi: 10.1056/NEJMoa054017. Epub 2006 Aug 22.
Abstract/Text BACKGROUND: Obesity is associated with diverse health risks, but the role of body weight as a risk factor for death remains controversial.
METHODS: We examined the association between body weight and the risk of death in a 12-year prospective cohort study of 1,213,829 Koreans between the ages of 30 and 95 years. We examined 82,372 deaths from any cause and 48,731 deaths from specific diseases (including 29,123 from cancer, 16,426 from atherosclerotic cardiovascular disease, and 3362 from respiratory disease) in relation to the body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters).
RESULTS: In both sexes, the average baseline BMI was 23.2, and the rate of death from any cause had a J-shaped association with the BMI, regardless of cigarette-smoking history. The risk of death from any cause was lowest among patients with a BMI of 23.0 to 24.9. In all groups, the risk of death from respiratory causes was higher among subjects with a lower BMI, and the risk of death from atherosclerotic cardiovascular disease or cancer was higher among subjects with a higher BMI. The relative risk of death associated with BMI declined with increasing age.
CONCLUSIONS: Underweight, overweight, and obese men and women had higher rates of death than men and women of normal weight. The association of BMI with death varied according to the cause of death and was modified by age, sex, and smoking history.

Copyright 2006 Massachusetts Medical Society.
PMID 16926276  N Engl J Med. 2006 Aug 24;355(8):779-87. doi: 10.1056/N・・・
著者: Wei Nie, Yi Zhang, Sun Ha Jee, Keum Ji Jung, Bing Li, Qingyu Xiu
雑誌名: BMC Med. 2014 Apr 10;12:61. doi: 10.1186/1741-7015-12-61. Epub 2014 Apr 10.
Abstract/Text BACKGROUND: It is unclear whether an 'obesity survival paradox' exists for pneumonia. Therefore, we conducted a meta-analysis to assess the associations between increased body mass index (BMI), pneumonia risk, and mortality risk.
METHODS: Cohort studies were identified from the PubMed and Embase databases. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random effects model.
RESULTS: Thirteen cohort studies on pneumonia risk (n = 1,536,623), and ten cohort studies on mortality (n = 1,375,482) were included. Overweight and obese individuals were significantly associated with an increased risk of pneumonia (RR = 1.33, 95% CI 1.04 to 1.71, P = 0.02, I(2) = 87%). In the dose-response analysis, the estimated summary RR of pneumonia per 5 kg/m(2) increase in BMI was 1.04 (95% CI 1.01 to 1.07, P = 0.01, I(2) = 84%). Inversely, overweight and obese subjects were significantly associated with reduced risk of pneumonia mortality (RR = 0.83, 95% CI 0.77 to 0.91, P < 0.01, I(2) = 34%). The estimated summary RR of mortality per 5 kg/m(2) increase in BMI was 0.95 (95% CI 0.93 to 0.98, P < 0.01, I(2) = 77%).
CONCLUSIONS: This meta-analysis suggests that an 'obesity survival paradox' exists for pneumonia. Because this meta-analysis is based on observational studies, more studies are required to confirm the results.

PMID 24722122  BMC Med. 2014 Apr 10;12:61. doi: 10.1186/1741-7015-12-6・・・
著者: Dariush Mozaffarian, Tao Hao, Eric B Rimm, Walter C Willett, Frank B Hu
雑誌名: N Engl J Med. 2011 Jun 23;364(25):2392-404. doi: 10.1056/NEJMoa1014296.
Abstract/Text BACKGROUND: Specific dietary and other lifestyle behaviors may affect the success of the straightforward-sounding strategy "eat less and exercise more" for preventing long-term weight gain.
METHODS: We performed prospective investigations involving three separate cohorts that included 120,877 U.S. women and men who were free of chronic diseases and not obese at baseline, with follow-up periods from 1986 to 2006, 1991 to 2003, and 1986 to 2006. The relationships between changes in lifestyle factors and weight change were evaluated at 4-year intervals, with multivariable adjustments made for age, baseline body-mass index for each period, and all lifestyle factors simultaneously. Cohort-specific and sex-specific results were similar and were pooled with the use of an inverse-variance-weighted meta-analysis.
RESULTS: Within each 4-year period, participants gained an average of 3.35 lb (5th to 95th percentile, -4.1 to 12.4). On the basis of increased daily servings of individual dietary components, 4-year weight change was most strongly associated with the intake of potato chips (1.69 lb), potatoes (1.28 lb), sugar-sweetened beverages (1.00 lb), unprocessed red meats (0.95 lb), and processed meats (0.93 lb) and was inversely associated with the intake of vegetables (-0.22 lb), whole grains (-0.37 lb), fruits (-0.49 lb), nuts (-0.57 lb), and yogurt (-0.82 lb) (P≤0.005 for each comparison). Aggregate dietary changes were associated with substantial differences in weight change (3.93 lb across quintiles of dietary change). Other lifestyle factors were also independently associated with weight change (P<0.001), including physical activity (-1.76 lb across quintiles); alcohol use (0.41 lb per drink per day), smoking (new quitters, 5.17 lb; former smokers, 0.14 lb), sleep (more weight gain with <6 or >8 hours of sleep), and television watching (0.31 lb per hour per day).
CONCLUSIONS: Specific dietary and lifestyle factors are independently associated with long-term weight gain, with a substantial aggregate effect and implications for strategies to prevent obesity. (Funded by the National Institutes of Health and others.).

PMID 21696306  N Engl J Med. 2011 Jun 23;364(25):2392-404. doi: 10.105・・・
著者: Andrew Reynolds, Jim Mann, John Cummings, Nicola Winter, Evelyn Mete, Lisa Te Morenga
雑誌名: Lancet. 2019 Feb 2;393(10170):434-445. doi: 10.1016/S0140-6736(18)31809-9. Epub 2019 Jan 10.
Abstract/Text BACKGROUND: Previous systematic reviews and meta-analyses explaining the relationship between carbohydrate quality and health have usually examined a single marker and a limited number of clinical outcomes. We aimed to more precisely quantify the predictive potential of several markers, to determine which markers are most useful, and to establish an evidence base for quantitative recommendations for intakes of dietary fibre.
METHODS: We did a series of systematic reviews and meta-analyses of prospective studies published from database inception to April 30, 2017, and randomised controlled trials published from database inception to Feb 28, 2018, which reported on indicators of carbohydrate quality and non-communicable disease incidence, mortality, and risk factors. Studies were identified by searches in PubMed, Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. We excluded prospective studies and trials reporting on participants with a chronic disease, and weight loss trials or trials involving supplements. Searches, data extraction, and bias assessment were duplicated independently. Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, dose-response testing, and subgroup analyses. The GRADE approach was used to assess quality of evidence.
FINDINGS: Just under 135 million person-years of data from 185 prospective studies and 58 clinical trials with 4635 adult participants were included in the analyses. Observational data suggest a 15-30% decrease in all-cause and cardiovascular related mortality, and incidence of coronary heart disease, stroke incidence and mortality, type 2 diabetes, and colorectal cancer when comparing the highest dietary fibre consumers with the lowest consumers Clinical trials show significantly lower bodyweight, systolic blood pressure, and total cholesterol when comparing higher with lower intakes of dietary fibre. Risk reduction associated with a range of critical outcomes was greatest when daily intake of dietary fibre was between 25 g and 29 g. Dose-response curves suggested that higher intakes of dietary fibre could confer even greater benefit to protect against cardiovascular diseases, type 2 diabetes, and colorectal and breast cancer. Similar findings for whole grain intake were observed. Smaller or no risk reductions were found with the observational data when comparing the effects of diets characterised by low rather than higher glycaemic index or load. The certainty of evidence for relationships between carbohydrate quality and critical outcomes was graded as moderate for dietary fibre, low to moderate for whole grains, and low to very low for dietary glycaemic index and glycaemic load. Data relating to other dietary exposures are scarce.
INTERPRETATION: Findings from prospective studies and clinical trials associated with relatively high intakes of dietary fibre and whole grains were complementary, and striking dose-response evidence indicates that the relationships to several non-communicable diseases could be causal. Implementation of recommendations to increase dietary fibre intake and to replace refined grains with whole grains is expected to benefit human health. A major strength of the study was the ability to examine key indicators of carbohydrate quality in relation to a range of non-communicable disease outcomes from cohort studies and randomised trials in a single study. Our findings are limited to risk reduction in the population at large rather than those with chronic disease.
FUNDING: Health Research Council of New Zealand, WHO, Riddet Centre of Research Excellence, Healthier Lives National Science Challenge, University of Otago, and the Otago Southland Diabetes Research Trust.

Copyright © 2019 Elsevier Ltd. All rights reserved.
PMID 30638909  Lancet. 2019 Feb 2;393(10170):434-445. doi: 10.1016/S01・・・
著者: C Sauvaget, J Nagano, N Allen, K Kodama
雑誌名: Stroke. 2003 Oct;34(10):2355-60. doi: 10.1161/01.STR.0000089293.29739.97. Epub 2003 Sep 18.
Abstract/Text BACKGROUND AND PURPOSE: Fruits and vegetables are known for their beneficial effects on chronic diseases. The purpose of the present study was to investigate the protective effect of a diet rich in fruits and vegetables on total stroke mortality and its 2 main subtypes in men and women separately.
METHODS: A prospective cohort study of 40 349 Japanese men and women was initiated in 1980-1981 and followed until 1998. Fruit and vegetable intake was assessed at baseline on the basis of the response to a food frequency questionnaire. During the 18-year follow-up period, deaths from stroke were registered.
RESULTS: A total of 1926 stroke deaths were identified during the follow-up period. An increasing frequency of intake of green-yellow vegetables and fruit was associated with a reduced risk of death from intracerebral hemorrhage and cerebral infarction. Daily intake of green-yellow vegetables was associated with a significant 26% reduction in the risk of death from total stroke in men and women compared with an intake of once or less per week. The protective effect associated with daily fruit and vegetable intake was observed for both cerebral infarction and intracerebral hemorrhage mortality but was slightly stronger and clearer for infarction than for hemorrhage, with a 32% reduction in men and a 30% reduction in women. Daily fruit intake was associated with a significant 35% reduction in risk of total stroke in men and a 25% reduction in women and was equally strong for both intracerebral hemorrhage and cerebral infarction.
CONCLUSIONS: Daily consumption of green-yellow vegetables and fruits is associated with a lower risk of total stroke, intracerebral hemorrhage, and cerebral infarction mortality. The protective effects are similar in both men and women.

PMID 14500940  Stroke. 2003 Oct;34(10):2355-60. doi: 10.1161/01.STR.00・・・
著者: Momoko Muto, Osamu Ezaki
雑誌名: J Atheroscler Thromb. 2018 May 1;25(5):375-392. doi: 10.5551/jat.41632. Epub 2017 Dec 20.
Abstract/Text AIM: The associations between dietary saturated fatty acids and the risks of stroke subtypes in cohort studies were examined by a meta-analysis of separate ethnic Japanese and non-Japanese cohorts, and causes of their difference were elucidated.
METHOD: Log hazard ratio (HR) with 95% confidence interval (CI) of the highest versus the lowest saturated fat intake from cohort studies were weighed by an inverse variance method to combine HRs.
RESULTS: Five studies of intracerebral hemorrhage and 11 studies/comparisons of ischemic stroke were selected. A meta-analysis of intracerebral hemorrhage excluding subarachnoid hemorrhage showed a strong inverse association in Japanese (n=3, HR=0.55, 95% CI 0.32-0.94) but not in non-Japanese (n=2, HR=0.98, 95% CI 0.62-1.53). A meta-analysis of ischemic stroke showed a mild inverse association in Japanese (n=4, HR=0.82, 95% CI 0.71-0.93) but not in non-Japanese (n=7, HR= 0.93, 95% CI 0.84-1.03). The effect size of saturated fat in reducing the risk of stroke in Japanese was stronger for intracerebral hemorrhage (45% reduction) than for ischemic stroke (18% reduction).
CONCLUSIONS: In Japanese but not in non-Japanese, a diet high in saturated fat is associated with a low risk of intracerebral hemorrhage and ischemic stroke. This may be due to differences in the range of intake of saturated fat, genetic susceptibility, incidence of lacunar infarction, and/or confounding factors such as dietary proteins. An intervention study targeting Japanese will be required to verify the causality.

PMID 29269706  J Atheroscler Thromb. 2018 May 1;25(5):375-392. doi: 10・・・
著者: Giancarlo Bilancio, Pierpaolo Cavallo, Carolina Ciacci, Massimo Cirillo
雑誌名: Nutrients. 2019 Jan 18;11(1). doi: 10.3390/nu11010196. Epub 2019 Jan 18.
Abstract/Text The World Health Organization recommends a minimum requirement of 0.8 g/day protein/kg ideal weight. Low protein diets are used against kidney failure progression. Efficacy and safety of these diets are uncertain. This paper reviews epidemiological studies about associations of protein intake with kidney function decline and mortality. Three studies investigated these associations; two reported data on mortality. Protein intake averaged >60 g/day and 1.2 g/day/kg ideal weight. An association of baseline protein intake with long-term kidney function decline was absent in the general population and/or persons with normal kidney function but was significantly positive in persons with below-normal kidney function. Independent of kidney function and other confounders, a J-curve relationship was found between baseline protein intake and mortality due to ≈35% mortality excess for non-cardiovascular disease in the lowest quintile of protein intake, a quintile where protein intake averaged <0.8 g/day/kg ideal weight. Altogether, epidemiological evidence suggests that, in patients with reduced kidney function, protein intakes of ≈0.8 g/d/kg ideal weight could limit kidney function decline without adding non-renal risks. Long-term lower protein intake could increase mortality. In most patients, an intake of ≈0.8 g/day/kg would represent a substantial reduction of habitual intake considering that average intake is largely higher.

PMID 30669401  Nutrients. 2019 Jan 18;11(1). doi: 10.3390/nu11010196. ・・・
著者: Maria J Pereira, Jan W Eriksson
雑誌名: Drugs. 2019 Feb;79(3):219-230. doi: 10.1007/s40265-019-1057-0.
Abstract/Text Sodium-glucose co-transporter 2 (SGLT2) inhibitors are glucose-lowering drugs that reduce plasma glucose levels by inhibiting glucose and sodium reabsorption in the kidneys, thus resulting in glucosuria. Their effects consequently include reductions in HbA1c, blood glucose levels, and blood pressure, but also reductions in body weight and adiposity. The ability to reduce body weight is consistently observed in individuals taking SGLT2 inhibitors, but this weight loss is moderate due to counter-regulatory mechanisms striving to maintain body weight. This has prompted exploration of SGLT2 inhibitors in combination with other agents acting via decreased food intake, e.g., glucagon-like peptide 1 receptor agonists (GLP1-RAs). The bodyweight effects are promising, and together with the signs of prevention of cardiovascular and renal events, such combinations including SGLT2 inhibitors are appealing. The weight loss is clinically important, as most individuals with type 2 diabetes are overweight or obese, but also because there is an unmet need for safe, effective, and durable weight loss interventions in obese individuals without diabetes.

PMID 30701480  Drugs. 2019 Feb;79(3):219-230. doi: 10.1007/s40265-019-・・・
著者: Cara B Ebbeling, Michael M Leidig, Henry A Feldman, Margaret M Lovesky, David S Ludwig
雑誌名: JAMA. 2007 May 16;297(19):2092-102. doi: 10.1001/jama.297.19.2092.
Abstract/Text CONTEXT: The results of clinical trials involving diet in the treatment of obesity have been inconsistent, possibly due to inherent physiological differences among study participants.
OBJECTIVE: To determine whether insulin secretion affects weight loss with 2 popular diets.
DESIGN, SETTING, AND PARTICIPANTS: Randomized trial of obese young adults (aged 18-35 years; n = 73) conducted from September 2004 to December 2006 in Boston, Mass, and consisting of a 6-month intensive intervention period and a 12-month follow-up period. Serum insulin concentration at 30 minutes after a 75-g dose of oral glucose was determined at baseline as a measure of insulin secretion. Outcomes were assessed at 6, 12, and 18 months. Missing data were imputed conservatively.
INTERVENTIONS: A low-glycemic load (40% carbohydrate and 35% fat) vs low-fat (55% carbohydrate and 20% fat) diet.
MAIN OUTCOME MEASURES: Body weight, body fat percentage determined by dual-energy x-ray absorptiometry, and cardiovascular disease risk factors.
RESULTS: Change in body weight and body fat percentage did not differ between the diet groups overall. However, insulin concentration at 30 minutes after a dose of oral glucose was an effect modifier (group x time x insulin concentration at 30 minutes: P = .02 for body weight and P = .01 for body fat percentage). For those with insulin concentration at 30 minutes above the median (57.5 microIU/mL; n = 28), the low-glycemic load diet produced a greater decrease in weight (-5.8 vs -1.2 kg; P = .004) and body fat percentage (-2.6% vs -0.9%; P = .03) than the low-fat diet at 18 months. There were no significant differences in these end points between diet groups for those with insulin concentration at 30 minutes below the median level (n = 28). Insulin concentration at 30 minutes after a dose of oral glucose was not a significant effect modifier for cardiovascular disease risk factors. In the full cohort, plasma high-density lipoprotein cholesterol and triglyceride concentrations improved more on the low-glycemic load diet, whereas low-density lipoprotein cholesterol concentration improved more on the low-fat diet.
CONCLUSIONS: Variability in dietary weight loss trials may be partially attributable to differences in hormonal response. Reducing glycemic load may be especially important to achieve weight loss among individuals with high insulin secretion. Regardless of insulin secretion, a low-glycemic load diet has beneficial effects on high-density lipoprotein cholesterol and triglyceride concentrations but not on low-density lipoprotein cholesterol concentration.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00130299.

PMID 17507345  JAMA. 2007 May 16;297(19):2092-102. doi: 10.1001/jama.2・・・
著者: Christopher D Gardner, John F Trepanowski, Liana C Del Gobbo, Michelle E Hauser, Joseph Rigdon, John P A Ioannidis, Manisha Desai, Abby C King
雑誌名: JAMA. 2018 Feb 20;319(7):667-679. doi: 10.1001/jama.2018.0245.
Abstract/Text Importance: Dietary modification remains key to successful weight loss. Yet, no one dietary strategy is consistently superior to others for the general population. Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets.
Objective: To determine the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss.
Design, Setting, and Participants: The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40. The trial enrollment was from January 29, 2013, through April 14, 2015; the date of final follow-up was May 16, 2016. Participants were randomized to the 12-month HLF or HLC diet. The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion (INS-30; blood concentration of insulin 30 minutes after a glucose challenge) were associated with weight loss.
Interventions: Health educators delivered the behavior modification intervention to HLF (n = 305) and HLC (n = 304) participants via 22 diet-specific small group sessions administered over 12 months. The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality.
Main Outcomes and Measures: Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern, diet and insulin secretion, and diet and weight loss.
Results: Among 609 participants randomized (mean age, 40 [SD, 7] years; 57% women; mean body mass index, 33 [SD, 3]; 244 [40%] had a low-fat genotype; 180 [30%] had a low-carbohydrate genotype; mean baseline INS-30, 93 μIU/mL), 481 (79%) completed the trial. In the HLF vs HLC diets, respectively, the mean 12-month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45% for fat, and 21% vs 23% for protein. Weight change at 12 months was -5.3 kg for the HLF diet vs -6.0 kg for the HLC diet (mean between-group difference, 0.7 kg [95% CI, -0.2 to 1.6 kg]). There was no significant diet-genotype pattern interaction (P = .20) or diet-insulin secretion (INS-30) interaction (P = .47) with 12-month weight loss. There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups.
Conclusions and Relevance: In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom.
Trial Registration: clinicaltrials.gov Identifier: NCT01826591.

PMID 29466592  JAMA. 2018 Feb 20;319(7):667-679. doi: 10.1001/jama.201・・・
著者: Karen Rees, Andrea Takeda, Nicole Martin, Leila Ellis, Dilini Wijesekara, Abhinav Vepa, Archik Das, Louise Hartley, Saverio Stranges
雑誌名: Cochrane Database Syst Rev. 2019 Mar 13;3:CD009825. doi: 10.1002/14651858.CD009825.pub3. Epub 2019 Mar 13.
Abstract/Text BACKGROUND: The Seven Countries study in the 1960s showed that populations in the Mediterranean region experienced lower coronary heart disease (CHD) mortality probably as a result of different dietary patterns. Later observational studies have confirmed the benefits of adherence to a Mediterranean dietary pattern on cardiovascular disease (CVD) risk factors but clinical trial evidence is more limited.
OBJECTIVES: To determine the effectiveness of a Mediterranean-style diet for the primary and secondary prevention of CVD.
SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9); MEDLINE (Ovid, 1946 to 25 September 2018); Embase (Ovid, 1980 to 2018 week 39); Web of Science Core Collection (Thomson Reuters, 1900 to 26 September 2018); DARE Issue 2 of 4, 2015 (Cochrane Library); HTA Issue 4 of 4, 2016 (Cochrane Library); NHS EED Issue 2 of 4, 2015 (Cochrane Library). We searched trial registers and applied no language restrictions.
SELECTION CRITERIA: We selected randomised controlled trials (RCTs) in healthy adults and adults at high risk of CVD (primary prevention) and those with established CVD (secondary prevention). Both of the following key components were required to reach our definition of a Mediterranean-style diet: high monounsaturated/saturated fat ratio (use of olive oil as main cooking ingredient and/or consumption of other traditional foods high in monounsaturated fats such as tree nuts) and a high intake of plant-based foods, including fruits, vegetables and legumes. Additional components included: low to moderate red wine consumption; high consumption of whole grains and cereals; low consumption of meat and meat products and increased consumption of fish; moderate consumption of milk and dairy products. The intervention could be dietary advice, provision of relevant foods, or both. The comparison group received either no intervention, minimal intervention, usual care or another dietary intervention. Outcomes included clinical events and CVD risk factors. We included only studies with follow-up periods of three months or more defined as the intervention period plus post intervention follow-up.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and assessed risk of bias. We conducted four main comparisons:1. Mediterranean dietary intervention versus no intervention or minimal intervention for primary prevention;2. Mediterranean dietary intervention versus another dietary intervention for primary prevention;3. Mediterranean dietary intervention versus usual care for secondary prevention;4. Mediterranean dietary intervention versus another dietary intervention for secondary prevention.
MAIN RESULTS: In this substantive review update, 30 RCTs (49 papers) (12,461 participants randomised) and seven ongoing trials met our inclusion criteria. The majority of trials contributed to primary prevention: comparisons 1 (nine trials) and 2 (13 trials). Secondary prevention trials were included for comparison 3 (two trials) and comparison 4 (four trials plus an additional two trials that were excluded from the main analyses due to published concerns regarding the reliability of the data).Two trials reported on adverse events where these were absent or minor (low- to moderate-quality evidence). No trials reported on costs or health-related quality of life.Primary preventionThe included studies for comparison 1 did not report on clinical endpoints (CVD mortality, total mortality or non-fatal endpoints such as myocardial infarction or stroke). The PREDIMED trial (included in comparison 2) was retracted and re-analysed following concerns regarding randomisation at two of 11 sites. Low-quality evidence shows little or no effect of the PREDIMED (7747 randomised) intervention (advice to follow a Mediterranean diet plus supplemental extra-virgin olive oil or tree nuts) compared to a low-fat diet on CVD mortality (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.50 to 1.32) or total mortality (HR 1.0, 95% CI 0.81 to 1.24) over 4.8 years. There was, however, a reduction in the number of strokes with the PREDIMED intervention (HR 0.60, 95% CI 0.45 to 0.80), a decrease from 24/1000 to 14/1000 (95% CI 11 to 19), moderate-quality evidence). For CVD risk factors for comparison 1 there was low-quality evidence for a possible small reduction in total cholesterol (-0.16 mmol/L, 95% CI -0.32 to 0.00) and moderate-quality evidence for a reduction in systolic (-2.99 mmHg (95% CI -3.45 to -2.53) and diastolic blood pressure (-2.0 mmHg, 95% CI -2.29 to -1.71), with low or very low-quality evidence of little or no effect on LDL or HDL cholesterol or triglycerides. For comparison 2 there was moderate-quality evidence of a possible small reduction in LDL cholesterol (-0.15 mmol/L, 95% CI -0.27 to -0.02) and triglycerides (-0.09 mmol/L, 95% CI -0.16 to -0.01) with moderate or low-quality evidence of little or no effect on total or HDL cholesterol or blood pressure.Secondary preventionFor secondary prevention, the Lyon Diet Heart Study (comparison 3) examined the effect of advice to follow a Mediterranean diet and supplemental canola margarine compared to usual care in 605 CHD patients over 46 months and there was low-quality evidence of a reduction in adjusted estimates for CVD mortality (HR 0.35, 95% CI 0.15 to 0.82) and total mortality (HR 0.44, 95% CI 0.21 to 0.92) with the intervention. Only one small trial (101 participants) provided unadjusted estimates for composite clinical endpoints for comparison 4 (very low-quality evidence of uncertain effect). For comparison 3 there was low-quality evidence of little or no effect of a Mediterranean-style diet on lipid levels and very low-quality evidence for blood pressure. Similarly, for comparison 4 where only two trials contributed to the analyses there was low or very low-quality evidence of little or no effect of the intervention on lipid levels or blood pressure.
AUTHORS' CONCLUSIONS: Despite the relatively large number of studies included in this review, there is still some uncertainty regarding the effects of a Mediterranean-style diet on clinical endpoints and CVD risk factors for both primary and secondary prevention. The quality of evidence for the modest benefits on CVD risk factors in primary prevention is low or moderate, with a small number of studies reporting minimal harms. There is a paucity of evidence for secondary prevention. The ongoing studies may provide more certainty in the future.

PMID 30864165  Cochrane Database Syst Rev. 2019 Mar 13;3:CD009825. doi・・・
著者: F M Sacks, L P Svetkey, W M Vollmer, L J Appel, G A Bray, D Harsha, E Obarzanek, P R Conlin, E R Miller, D G Simons-Morton, N Karanja, P H Lin, DASH-Sodium Collaborative Research Group
雑誌名: N Engl J Med. 2001 Jan 4;344(1):3-10. doi: 10.1056/NEJM200101043440101.
Abstract/Text BACKGROUND: The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension.
METHODS: A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order.
RESULTS: Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P=0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during the DASH diet (P<0.01). The effects of sodium were observed in participants with and in those without hypertension, blacks and those of other races, and women and men. The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level; and the difference was greater with high sodium levels than with low ones. As compared with the control diet with a high sodium level, the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension, and 11.5 mm Hg lower in participants with hypertension.
CONCLUSIONS: The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially, with greater effects in combination than singly. Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods.

PMID 11136953  N Engl J Med. 2001 Jan 4;344(1):3-10. doi: 10.1056/NEJM・・・
著者: William C Knowler, Elizabeth Barrett-Connor, Sarah E Fowler, Richard F Hamman, John M Lachin, Elizabeth A Walker, David M Nathan, Diabetes Prevention Program Research Group
雑誌名: N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
Abstract/Text BACKGROUND: Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.
METHODS: We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups.
RESULTS: The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin.
CONCLUSIONS: Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.

PMID 11832527  N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/N・・・
著者: Look AHEAD Research Group, Rena R Wing, Paula Bolin, Frederick L Brancati, George A Bray, Jeanne M Clark, Mace Coday, Richard S Crow, Jeffrey M Curtis, Caitlin M Egan, Mark A Espeland, Mary Evans, John P Foreyt, Siran Ghazarian, Edward W Gregg, Barbara Harrison, Helen P Hazuda, James O Hill, Edward S Horton, Van S Hubbard, John M Jakicic, Robert W Jeffery, Karen C Johnson, Steven E Kahn, Abbas E Kitabchi, William C Knowler, Cora E Lewis, Barbara J Maschak-Carey, Maria G Montez, Anne Murillo, David M Nathan, Jennifer Patricio, Anne Peters, Xavier Pi-Sunyer, Henry Pownall, David Reboussin, Judith G Regensteiner, Amy D Rickman, Donna H Ryan, Monika Safford, Thomas A Wadden, Lynne E Wagenknecht, Delia S West, David F Williamson, Susan Z Yanovski
雑誌名: N Engl J Med. 2013 Jul 11;369(2):145-54. doi: 10.1056/NEJMoa1212914. Epub 2013 Jun 24.
Abstract/Text BACKGROUND: Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients.
METHODS: In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years.
RESULTS: The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51).
CONCLUSIONS: An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).

PMID 23796131  N Engl J Med. 2013 Jul 11;369(2):145-54. doi: 10.1056/N・・・
著者: W Jack Rejeski, Edward H Ip, Alain G Bertoni, George A Bray, Gina Evans, Edward W Gregg, Qiang Zhang, Look AHEAD Research Group
雑誌名: N Engl J Med. 2012 Mar 29;366(13):1209-17. doi: 10.1056/NEJMoa1110294.
Abstract/Text BACKGROUND: Adults with type 2 diabetes mellitus often have limitations in mobility that increase with age. An intensive lifestyle intervention that produces weight loss and improves fitness could slow the loss of mobility in such patients.
METHODS: We randomly assigned 5145 overweight or obese adults between the ages of 45 and 74 years with type 2 diabetes to either an intensive lifestyle intervention or a diabetes support-and-education program; 5016 participants contributed data. We used hidden Markov models to characterize disability states and mixed-effects ordinal logistic regression to estimate the probability of functional decline. The primary outcome was self-reported limitation in mobility, with annual assessments for 4 years.
RESULTS: At year 4, among 2514 adults in the lifestyle-intervention group, 517 (20.6%) had severe disability and 969 (38.5%) had good mobility; the numbers among 2502 participants in the support group were 656 (26.2%) and 798 (31.9%), respectively. The lifestyle-intervention group had a relative reduction of 48% in the risk of loss of mobility, as compared with the support group (odds ratio, 0.52; 95% confidence interval, 0.44 to 0.63; P<0.001). Both weight loss and improved fitness (as assessed on treadmill testing) were significant mediators of this effect (P<0.001 for both variables). Adverse events that were related to the lifestyle intervention included a slightly higher frequency of musculoskeletal symptoms at year 1.
CONCLUSIONS: Weight loss and improved fitness slowed the decline in mobility in overweight adults with type 2 diabetes. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT00017953.).

PMID 22455415  N Engl J Med. 2012 Mar 29;366(13):1209-17. doi: 10.1056・・・
著者: Suzanne Phelan, Alka M Kanaya, Leslee L Subak, Patricia E Hogan, Mark A Espeland, Rena R Wing, Kathryn L Burgio, Vicki DiLillo, Amy A Gorin, Delia S West, Jeanette S Brown, Look AHEAD Research Group
雑誌名: J Urol. 2012 Mar;187(3):939-44. doi: 10.1016/j.juro.2011.10.139. Epub 2012 Jan 20.
Abstract/Text PURPOSE: We determined the effect of weight loss on the prevalence, incidence and resolution of weekly or more frequent urinary incontinence in overweight/obese women with type 2 diabetes after 1 year of intervention in the Look AHEAD (Action for Health in Diabetes) trial.
MATERIALS AND METHODS: Women in this substudy (2,739, mean ± SD age 57.9 ± 6.8 years, body mass index 36.5 ± 6.1 kg/m(2)) were randomized into an intensive lifestyle weight loss intervention or a diabetes support and education control condition.
RESULTS: At baseline 27% of participants reported urinary incontinence on a validated questionnaire (no significant difference by intensive lifestyle intervention vs diabetes support and education). After 1 year of intervention the intensive lifestyle intervention group in this substudy lost 7.7 ± 7.0 vs 0.7 ± 5.0 kg in the diabetes support and education group. At 1 year fewer women in the intensive lifestyle intervention group reported urinary incontinence (25.3% vs 28.6% in the diabetes support and education group, p = 0.05). Among participants without urinary incontinence at baseline 10.5% of intensive lifestyle intervention and 14.0% of diabetes support and education participants experienced urinary incontinence after 1 year (p = 0.02). There were no significant group differences in the resolution of urinary incontinence (p >0.17). Each kg of weight lost was associated with a 3% reduction in the odds of urinary incontinence developing (p = 0.01), and weight losses of 5% to 10% reduced these odds by 47% (p = 0.002).
CONCLUSIONS: Moderate weight loss reduced the incidence but did not improve the resolution rates of urinary incontinence at 1 year among overweight/obese women with type 2 diabetes. Weight loss interventions should be considered for the prevention of urinary incontinence in overweight/obese women with diabetes.

Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID 22264468  J Urol. 2012 Mar;187(3):939-44. doi: 10.1016/j.juro.201・・・
著者: Gary D Foster, Kelley E Borradaile, Mark H Sanders, Richard Millman, Gary Zammit, Anne B Newman, Thomas A Wadden, David Kelley, Rena R Wing, F Xavier Pi-Sunyer, David Reboussin, Samuel T Kuna, Sleep AHEAD Research Group of Look AHEAD Research Group
雑誌名: Arch Intern Med. 2009 Sep 28;169(17):1619-26. doi: 10.1001/archinternmed.2009.266.
Abstract/Text BACKGROUND: The belief that weight loss improves obstructive sleep apnea (OSA) has limited empirical support. The purpose of this 4-center study was to assess the effects of weight loss on OSA over a 1-year period.
METHODS: The study included 264 participants with type 2 diabetes and a mean (SD) age of 61.2 (6.5) years, weight of 102.4 (18.3) kg, body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 36.7 (5.7), and an apnea-hypopnea index (AHI) of 23.2 (16.5) events per hour. The participants were randomly assigned to either a behavioral weight loss program developed specifically for obese patients with type 2 diabetes (intensive lifestyle intervention [ILI]) or 3 group sessions related to effective diabetes management (diabetes support and education [DSE]).
RESULTS: The ILI participants lost more weight at 1 year than did DSE participants (10.8 kg vs 0.6 kg; P < .001). Relative to the DSE group, the ILI intervention was associated with an adjusted (SE) decrease in AHI of 9.7 (2.0) events per hour (P < .001). At 1 year, more than 3 times as many participants in the ILI group than in the DSE group had total remission of their OSA, and the prevalence of severe OSA among ILI participants was half that of the DSE group. Initial AHI and weight loss were the strongest predictors of changes in AHI at 1 year (P < .01). Participants with a weight loss of 10 kg or more had the greatest reductions in AHI.
CONCLUSIONS: Physicians and their patients can expect that weight loss will result in significant and clinically relevant improvements in OSA among obese patients with type 2 diabetes. Trial Registration clinicaltrials.gov Identifier: NCT00194259.

PMID 19786682  Arch Intern Med. 2009 Sep 28;169(17):1619-26. doi: 10.1・・・
著者: Lucy F Faulconbridge, Thomas A Wadden, Richard R Rubin, Rena R Wing, Michael P Walkup, Anthony N Fabricatore, Mace Coday, Brent Van Dorsten, David L Mount, Linda J Ewing, Look AHEAD Research Group
雑誌名: Obesity (Silver Spring). 2012 Apr;20(4):783-93. doi: 10.1038/oby.2011.315. Epub 2011 Oct 20.
Abstract/Text Depressed individuals are frequently excluded from weight loss trials because of fears that weight reduction may precipitate mood disorders, as well as concerns that depressed participants will not lose weight satisfactorily. The present study examined participants in the Look AHEAD study to determine whether moderate weight loss would be associated with incident symptoms of depression and suicidal ideation, and whether symptoms of depression at baseline would limit weight loss at 1 year. Overweight/obese adults with type 2 diabetes (n = 5,145) were randomly assigned to an Intensive Lifestyle Intervention (ILI) or a usual care group, Diabetes Support and Education (DSE). Of these, 5,129 participants completed the Beck Depression Inventory (BDI) and had their weight measured at baseline and 1 year. Potentially significant symptoms of depression were defined by a BDI score ≥10. Participants in ILI lost 8.6 ± 6.9% of initial weight at 1 year, compared to 0.7 ± 4.8% for DSE (P < 0.001, effect size = 1.33), and had a reduction of 1.4 ± 4.7 points on the BDI, compared to 0.4 ± 4.5 for DSE (P < 0.001, effect size = 0.23). At 1 year, the incidence of potentially significant symptoms of depression was significantly lower in the ILI than DSE group (6.3% vs. 9.6%) (relative risk (RR) = 0.66, 95% confidence interval (CI) = 0.5, 0.8; P < 0.001). In the ILI group, participants with and without symptoms of depression lost 7.8 ± 6.7% and 8.7 ± 6.9%, respectively, a difference not considered clinically meaningful. Intentional weight loss was not associated with the precipitation of symptoms of depression, but instead appeared to protect against this occurrence. Mild (or greater) symptoms of depression at baseline did not prevent overweight/obese individuals with type 2 diabetes from achieving significant weight loss.

PMID 22016099  Obesity (Silver Spring). 2012 Apr;20(4):783-93. doi: 10・・・
著者: Donald A Williamson, Jack Rejeski, Wei Lang, Brent Van Dorsten, Anthony N Fabricatore, Katie Toledo, Look AHEAD Research Group
雑誌名: Arch Intern Med. 2009 Jan 26;169(2):163-71. doi: 10.1001/archinternmed.2008.544.
Abstract/Text BACKGROUND: Inconsistent findings have been reported regarding improved health-related quality of life (HRQOL) after weight loss. We tested the efficacy of a weight management program for improving HRQOL in overweight or obese adults diagnosed as having type 2 diabetes mellitus.
METHODS: We conducted a randomized multisite clinical trial at 16 outpatient research centers with 2 treatment arms and blinded measurements at baseline and the end of year 1. A total of 5145 participants (mean [SD] age, 58.7 [6.9] years; mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 36.0 [5.9]; 59.5% women; 63.1% white) were randomized to an intensive lifestyle intervention (ILI) or to diabetes support and education (DSE). Main outcome measures included the 36-Item Short-Form Health Survey physical component summary (PCS) and mental health component summary (MCS) scores and Beck Depression Inventory II (BDI-II) scores. Baseline mean (SD) scores were 47.9 (7.9) for PCS, 54.0 (8.1) for MCS, and 5.7 (5.0) for BDI-II.
RESULTS: Improved HRQOL was demonstrated by the PCS and BDI-II scores (P < .001) in the ILI arm compared with the DSE arm. The largest effect was observed for the PCS score (difference, -2.91; 99% confidence interval, -3.44 to -2.37). The greatest HRQOL improvement occurred in participants with the lowest baseline HRQOL levels. Mean (SD) changes in weight (ILI, -8.77 [8.2] kg and DSE, -0.86 [5.0] kg), improved fitness, and improved physical symptoms mediated treatment effects associated with the BDI-II and PCS.
CONCLUSIONS: Overweight adults diagnosed as having type 2 diabetes experienced significant improvement in HRQOL by enrolling in a weight management program that yielded significant weight loss, improved physical fitness, and reduced physical symptoms.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00017953.

PMID 19171813  Arch Intern Med. 2009 Jan 26;169(2):163-71. doi: 10.100・・・
著者: Mario Morino, Mauro Toppino, Pietro Forestieri, Luigi Angrisani, Marco Ettore Allaix, Nicola Scopinaro
雑誌名: Ann Surg. 2007 Dec;246(6):1002-7; discussion 1007-9. doi: 10.1097/SLA.0b013e31815c404e.
Abstract/Text OBJECTIVE: To define mortality rates and risk factors of different bariatric procedures and to identify strategies to reduce the surgical risk in patients undergoing bariatric surgery.
SUMMARY BACKGROUND DATA: Postoperative mortality is a rare event after bariatric surgery. Therefore, comprehensive data on mortality are lacking in the literature.
METHODS: A retrospective analysis of a large prospective database was carried out. The Italian Society of Obesity Surgery runs a National Registry on bariatric surgery where all procedures performed by members of the Society should be included prospectively. This Registry represents at present the largest database on bariatric surgery worldwide.
RESULTS: Between January 1996 and January 2006, 13,871 bariatric surgical procedures were included: 6122 adjustable silicone gastric bandings (ASGB), 4215 vertical banded gastroplasties (VBG), 1106 gastric bypasses, 1988 biliopancreatic diversions (BPD), 303 biliointestinal bypasses, and 137 various procedures. Sixty day mortality was 0.25%. The type of surgical procedure significantly influenced (P < 0.001) mortality risk: 0.1% ASGB, 0.15% VBG, 0.54% gastric bypasses, 0.8% BPD. Pulmonary embolism represented the most common cause of death (38.2%) and was significantly higher in the BPD group (0.4% vs. 0.07% VBG and 0.03% ASGB). Other causes of mortality were the following: cardiac failure 17.6%, intestinal leak 17.6%, respiratory failure 11.8%, and 1 case each of acute pancreatitis, cerebral ischemia, bleeding gastric ulcer, intestinal ischemia, and internal hernia. Therefore, 29.4% of patients died as a result of a direct technical complication of the procedure. Additional significant risk factors included open surgery (P < 0.001), prolonged operative time (P < 0.05), preoperative hypertension (P < 0.01) or diabetes (P < 0.05), and case load per Center (P < 0.01).
CONCLUSIONS: Mortality after bariatric surgery is a rare event. It is influenced by different risk factors including type of surgery, open surgery, prolonged operative time, comorbidities, and volume of activity. In defining the best bariatric procedure for each patient the different mortality risks should be taken into account. Choice of the procedure, prevention, early diagnosis, and therapy for cardiovascular complications may reduce postoperative mortality.

PMID 18043102  Ann Surg. 2007 Dec;246(6):1002-7; discussion 1007-9. do・・・
著者: Ignacio Jáuregui-Lobera
雑誌名: Nutrients. 2013 May 15;5(5):1595-608. doi: 10.3390/nu5051595. Epub 2013 May 15.
Abstract/Text It is estimated that the prevalence of anaemia in patients scheduled for bariatric surgery is higher than in the general population and the prevalence of iron deficiencies (with or without anaemia) may be higher as well. After surgery, iron deficiencies and anaemia may occur in a higher percentage of patients, mainly as a consequence of nutrient deficiencies. In addition, perioperative anaemia has been related with increased postoperative morbidity and mortality and poorer quality of life after bariatric surgery. The treatment of perioperative anaemia and nutrient deficiencies has been shown to improve patients' outcomes and quality of life. All patients should undergo an appropriate nutritional evaluation, including selective micronutrient measurements (e.g., iron), before any bariatric surgical procedure. In comparison with purely restrictive procedures, more extensive perioperative nutritional evaluations are required for malabsorptive procedures due to their nutritional consequences. The aim of this study was to review the current knowledge of nutritional deficits in obese patients and those that commonly appear after bariatric surgery, specifically iron deficiencies and their consequences. As a result, some recommendations for screening and supplementation are presented.

PMID 23676549  Nutrients. 2013 May 15;5(5):1595-608. doi: 10.3390/nu50・・・
著者: Viktoria L Gloy, Matthias Briel, Deepak L Bhatt, Sangeeta R Kashyap, Philip R Schauer, Geltrude Mingrone, Heiner C Bucher, Alain J Nordmann
雑誌名: BMJ. 2013 Oct 22;347:f5934. Epub 2013 Oct 22.
Abstract/Text OBJECTIVE: To quantify the overall effects of bariatric surgery compared with non-surgical treatment for obesity.
DESIGN: Systematic review and meta-analysis based on a random effects model.
DATA SOURCES: Searches of Medline, Embase, and the Cochrane Library from their inception to December 2012 regardless of language or publication status.
ELIGIBILITY CRITERIA: Eligible studies were randomised controlled trials with ≥ 6 months of follow-up that included individuals with a body mass index ≥ 30, compared current bariatric surgery techniques with non-surgical treatment, and reported on body weight, cardiovascular risk factors, quality of life, or adverse events.
RESULTS: The meta-analysis included 11 studies with 796 individuals (range of mean body mass index at baseline 30-52). Individuals allocated to bariatric surgery lost more body weight (mean difference -26 kg (95% confidence interval -31 to -21)) compared with non-surgical treatment, had a higher remission rate of type 2 diabetes (relative risk 22.1 (3.2 to 154.3) in a complete case analysis; 5.3 (1.8 to 15.8) in a conservative analysis assuming diabetes remission in all non-surgically treated individuals with missing data) and metabolic syndrome (relative risk 2.4 (1.6 to 3.6) in complete case analysis; 1.5 (0.9 to 2.3) in conservative analysis), greater improvements in quality of life and reductions in medicine use (no pooled data). Plasma triglyceride concentrations decreased more (mean difference -0.7 mmol/L (-1.0 to -0.4) and high density lipoprotein cholesterol concentrations increased more (mean difference 0.21 mmol/L (0.1 to 0.3)). Changes in blood pressure and total or low density lipoprotein cholesterol concentrations were not significantly different. There were no cardiovascular events or deaths reported after bariatric surgery. The most common adverse events after bariatric surgery were iron deficiency anaemia (15% of individuals undergoing malabsorptive bariatric surgery) and reoperations (8%).
CONCLUSIONS: Compared with non-surgical treatment of obesity, bariatric surgery leads to greater body weight loss and higher remission rates of type 2 diabetes and metabolic syndrome. However, results are limited to two years of follow-up and based on a small number of studies and individuals.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012003317 (www.crd.york.ac.uk/PROSPERO).

PMID 24149519  BMJ. 2013 Oct 22;347:f5934. Epub 2013 Oct 22.
著者: Antonio E Pontiroli, Alberto Morabito
雑誌名: Ann Surg. 2011 Mar;253(3):484-7. doi: 10.1097/SLA.0b013e31820d98cb.
Abstract/Text BACKGROUND: Bariatric surgery has been reported to reduce long-term mortality in operated participants in comparison with nonoperated participants.
METHODS: We performed a systematic review and meta-analysis of clinical trials published as full articles dealing with cardiovascular (CV) mortality, all-cause mortality (noncardiovascular), and global mortality (sum of CV and all-cause mortality). Pooled-fixed effects of estimates of the risk of mortality in participants undergoing surgery were calculated compared with controls.
RESULTS: Of 44,022 participants from 8 trials (14,052 undergoing surgery and 29,970 controls), death occurred in 3317 participants (400 in surgery, 2917 in controls); when the kind of death was specified, 321 CV deaths (118 in surgery, 203 in controls), and 523 all-cause deaths (218 in surgery, 305 in controls) occurred. Compared with controls, surgery was associated with a reduced risk of global mortality (OR = 0.55, CI, 0.49-0.63), of CV mortality (OR = 0.58, CI, 0.46-0.73), and of all-cause mortality (OR = 0.70, CI, 0.59-0.84).Data of all-cause mortality were not heterogeneous; heterogeneity of data of CV mortality decreased when studies were grouped according to size (large vs small studies). The reduction of risk was smaller in large than in small studies (OR = 0.61 vs 0.21, 0.63 vs 0.16, 0.74 vs 0.35 for global, CV, and all-cause mortality, respectively). The effect of gastric banding and gastric by-pass (3797 vs 10,255 interventions) was similar for global and all-cause mortality (OR = 0.57 vs 0.55, and 0.66 vs 0.70, respectively), different for CV mortality (OR = 0.71 vs 0.48). At meta-regression analysis, a trend for a decrease of global mortality (Log OR) linked to increasing BMI appeared.
CONCLUSION: This meta-analysis indicates that (1) bariatric surgery reduces long-term mortality; (2) risk reduction is smaller in large than in small studies; and (3) both gastric banding and gastric by-pass reduce mortality with a greater effect of the latter on CV mortality.

PMID 21245741  Ann Surg. 2011 Mar;253(3):484-7. doi: 10.1097/SLA.0b013・・・
著者: Guilherme M Campos, Jad Khoraki, Matthew G Browning, Bernardo M Pessoa, Guilherme S Mazzini, Luke Wolfe
雑誌名: Ann Surg. 2020 Feb;271(2):201-209. doi: 10.1097/SLA.0000000000003554.
Abstract/Text OBJECTIVE: The aim of this study was to obtain estimates of changes in perioperative outcomes and utilization of bariatric surgery in the United States from 1993 to 2016.
BACKGROUND: Bariatric surgery has evolved over the past 2 decades. Nationally representative information on changes of perioperative outcomes and utilization of surgery in the growing eligible population (class III obesity or class II obesity with comorbidities) is lacking.
METHODS: Adults with obesity diagnosis who underwent primary bariatric surgery in the United States from 1993 to 2016 were identified in the National Inpatient Sample database. Estimates of the yearly number, types and cost of surgeries, patients' and hospital characteristics, complications and mortality rates were obtained. Prevalence of obesity and comorbidities were obtained from the National Health and Nutrition Examination Survey and changes in utilization of surgery were estimated.
RESULTS: An estimated 1,903,273 patients underwent bariatric surgery in the United States between 1993 and 2016. Mean age was 43.9 years (79.9% women, 70.9% white race, 70.7% commercial insurance); these and other characteristics changed over time. Surgeries were exclusively open operations in 1993 (n = 8,631; gastric bypass and vertical banded gastroplasty, 49% each) and 98% laparoscopic (n = 162,969; 69.8% sleeve gastrectomy and 27.8% gastric bypass) in 2016. Complication and mortality rates peaked in 1998 (11.7% and 1%) and progressively decreased to 1.4% and 0.04% in 2016. Utilization increased from 0.07% in 1993 to 0.62% in 2004 and remained low at 0.5% in 2016.
CONCLUSIONS: Perioperative safety of bariatric surgery improved over the last quarter-century. Despite growth in number of surgeries, utilization has only marginally increased. Addressing barriers for utilization may allow for greater access to surgical therapy.

PMID 31425292  Ann Surg. 2020 Feb;271(2):201-209. doi: 10.1097/SLA.000・・・

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