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Journal Club

Journal Club. Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE. Multivitamins in the Prevention of Cancer in Men The Physicians’ Health Study II Randomized Controlled Trial JAMA. 2012;308(18): 1871-1880.

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Journal Club

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  1. Journal Club Gaziano JM, Sesso HD, ChristenWG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE. Multivitamins in the Prevention of Cancer in Men The Physicians’ Health Study II Randomized Controlled Trial JAMA. 2012;308(18):1871-1880. Lee Y, Wang MY, Du XQ, Charron MJ, Unger RH. Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice. Diabetes. 2011 Feb;60(2):391-7. 埼玉医科大学　総合医療センター　内分泌・糖尿病内科 Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University 松田　昌文 Matsuda, Masafumi 2012年11月15日8:30-8:55 ８階　医局

  2. Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts (DrsGaziano, Sesso, Christen, Bubes, Schvartz, Manson, Glynn, and Buring and Mss Smith and MacFadyen); VA Boston Healthcare System, Boston, Massachusetts (DrGaziano); and Departments of Epidemiology (DrsSesso, Manson, and Buring) and Biostatistics (Dr Glynn), Harvard School of Public Health, Boston, Massachusetts. DrGaziano is also Contributing Editor, JAMA. JAMA. 2012;308(18):1871-1880. doi:10.1001/jama.2012.14641.

  3. Context Multivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality.

  4. Objective To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men. Design, Setting, and Participants A large-scale, randomized, double-blind, placebocontrolled trial (Physicians’ Health Study II) of 14 641 male US physicians initially aged 50 years or older (mean [SD] age, 64.3 [9.2] years), including 1312 men with a history of cancer at randomization, enrolled in a common multivitamin study that began in 1997 with treatment and follow-up through June 1, 2011. InterventionDaily multivitamin or placebo. Main Outcome Measures Total cancer (excluding nonmelanoma skin cancer), with prostate, colorectal, and other site-specific cancers among the secondary end points.

  5. Figure 1. Flow Diagram of Participants From Screening to Completion of the Multivitamin Component of the Physicians’ Health Study II

  6. A multivitamin (Centrum Silver or its placebo daily; Pfizer [formerly Wyeth, American Home Products, and Lederle]), vitamin E (400-IU synthetic -tocopherol or its placebo on alternate days; BASF Corporation), vitamin C (500-mg synthetic ascorbic acid or its placebo daily; BASF Corporation), and beta carotene (50-mg Lurotin or placebo on alternate days; BASF Corporation) in the prevention of cancer, cardiovascular disease, eye disease, and cognitive function among The formulations of the multivitamin preparation used in our trial and other multivitamin preparations have changed over time, reflecting evolving perspectives and priorities in nutrition. For example, since PHS II was initiated, in the commercial form of this multivitamin, vitamin D increased from 400 to 500 IU, vitamin A (% as beta carotene) decreased from 5000 IU (50%) to 2500 IU (40%), and 250 μg of lutein and 300 μg of lycopene were added. However, the formulation of the multivitamin used throughout PHS II remained the same,

  7. eTable 2. Vitamins and Minerals Contained in the Centrum Silver Formulation Used in the Physicians’ Health Study II Trial * 50% as beta carotene

  8. The beta carotene component was terminated on schedule in March 2003. Treatment and follow-up of the vitamin E and vitamin C components continued through August 31, 2007, their scheduled end, with findings of no overall association reported for cancer and cardiovascular disease.

  9. Results During a median (interquartile range) follow-up of 11.2 (10.7-13.3) years, there were 2669 men with confirmed cancer, including 1373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (multivitamin and placebo groups, 17.0 and 18.3 events, respectively, per 1000 person-years; hazard ratio [HR], 0.92; 95% CI, 0.86-0.998; P=.04). There was no significant effect of a daily multivitamin on prostate cancer (multivitamin and placebo groups, 9.1 and 9.2 events, respectively, per 1000 person-years; HR, 0.98; 95% CI, 0.88-1.09; P=.76), colorectal cancer (multivitamin and placebo groups, 1.2 and 1.4 events, respectively, per 1000 personyears; HR, 0.89; 95% CI, 0.68-1.17; P=.39), or other site-specific cancers. There was no significant difference in the risk of cancer mortality (multivitamin and placebo groups, 4.9 and 5.6 events, respectively, per 1000 person-years; HR, 0.88; 95% CI, 0.77-1.01; P=.07). Daily multivitamin use was associated with a reduction in total cancer among 1312 men with a baseline history of cancer (HR, 0.73; 95% CI, 0.56-0.96; P=.02), but this did not differ significantly from that among 13 329 men initially without cancer (HR, 0.94; 95% CI, 0.87-1.02; P=.15; P for interaction=.07).

  10. Conclusion In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer. Trial Registration clinicaltrials.gov Identifier: NCT00270647

  11. Message 50歳以上の男性医師1万4641人を対象に、毎日のマルチビタミン摂取の癌予防効果を無作為化比較試験で検討（Physicians’ Health Study 2）。追跡期間中央値11.2年で、マルチビタミン群の癌発症率はプラセボ群に比べ統計学的有意に低かった（1000人年当たり17.0対18.3、ハザード比0.92）。 マルチビタミン飲むとよいかも。（B12とかは血液の悪性腫瘍が腎臓が悪いと増えるかもしれないが。また心血管障害は減らないらしい。）

  12. the 1Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; the 2Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York; and the 3VA North Texas Health Care System, Dallas, Texas Diabetes 60:391–397, 2011

  13. OBJECTIVE—To determine the role of glucagon action in the metabolic phenotype of untreated insulin deficiency.

  14. RESEARCH DESIGN AND METHODS—We compared pertinent clinical and metabolic parameters in glucagon receptor-null (Gcgr－/ －) mice and wild-type (Gcgr+/+) controls after equivalent destruction of b-cells. We used a double dose of streptozotocin to maximize b-cell destruction.

  15. RESULTS—Gcgr+/+ mice became hyperglycemic (＞500 mg/dL), hyperketonemic, polyuric, and cachectic and had to be killed after 6 weeks. Despite comparable b-cell destruction in Gcgr－/－mice, none of the foregoing clinical or laboratory manifestations of diabetes appeared. There was marked a-cell hyperplasia and hyperglucagonemia(～1,200 pg/mL), but hepatic phosphorylated cAMP response element binding protein and phosphoenolpyruvatecarboxykinase mRNA were profoundly reduced compared with Gcgr +/+mice with diabetes—evidence that glucagon action had been effectively blocked. Fasting glucose levels and oral and intraperitoneal glucose tolerance tests were normal. Both fasting and nonfasting free fatty acid levels and nonfastingb-hydroxy butyrate levels were lower.

  16. CONCLUSIONS—We conclude that blocking glucagon action prevents the deadly metabolic and clinical derangements of type 1 diabetic mice.

  17. Message グルカゴン受容体欠損マウス (Gcgr-/-) で、STZでβ細胞を破壊しても、糖負荷試験で正常型であった。グルカゴンシグナルが糖尿病の病態において非常に重要。 Gcgr-/-では、血中グルカゴンは上昇しているが、受容体シグナルは完全に遮断されていることは確かめられている。 （2011年の論文だが、これまでREVIEWしていなかったので今回追加。）

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