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スタチンによるDM発症の増加、HMGCR阻害そのものによる

Swerdlow DI, Preiss D, Kuchenbaecker KB, Holmes MV, Engmann JE, Shah T, Sofat R, Stender S, Johnson PC, Scott RA, Leusink M, Verweij N, Sharp SJ, Guo Y, Giambartolomei C, Chung C, Peasey A, Amuzu A, Li K, Palmen J, Howard P, Cooper JA, Drenos F, Li YR, Lowe G, Gallacher J, Stewart MC, Tzoulaki I, Buxbaum SG, van der A DL, Forouhi NG, Onland-Moret NC, van der Schouw YT, Schnabel RB, Hubacek JA, Kubinova R, Baceviciene M, Tamosiunas A, Pajak A, Topor-Madry R, Stepaniak U, Malyutina S, Baldassarre D, Sennblad B, Tremoli E, de Faire U, Veglia F, Ford I, Jukema JW, Westendorp RG, de Borst GJ, de Jong PA, Algra A, Spiering W, Maitland-van der Zee AH, Klungel OH, de Boer A, Doevendans PA, Eaton CB, Robinson JG, Duggan D; DIAGRAM Consortium; MAGIC Consortium; InterAct Consortium; Kjekshus J, Downs JR, Gotto AM, Keech AC, Marchioli R, Tognoni G, Sever PS, Poulter NR, Waters DD, Pedersen TR, Amarenco P, Nakamura H, McMurray JJ, Lewsey JD, Chasman DI, Ridker PM, Maggioni AP, Tavazzi L, Ray KK, Seshasai SR, Manson JE, Price JF, Whincup PH, Morris RW, Lawlor DA, Smith GD, Ben-Shlomo Y, Schreiner PJ, Fornage M, Siscovick DS, Cushman M, Kumari M, Wareham NJ, Verschuren WM, Redline S, Patel SR, Whittaker JC, Hamsten A, Delaney JA, Dale C, Gaunt TR, Wong A, Kuh D, Hardy R, Kathiresan S, Castillo BA, van der Harst P, Brunner EJ, Tybjaerg-Hansen A, Marmot MG, Krauss RM, Tsai M, Coresh J, Hoogeveen RC, Psaty BM, Lange LA, Hakonarson H, Dudbridge F, Humphries SE, Talmud PJ, Kivimäki M, Timpson NJ, Langenberg C, Asselbergs FW, Voevoda M, Bobak M, Pikhart H, Wilson JG, Reiner AP, Keating BJ, Hingorani AD, Sattar N. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet. 2015 Jan 24;385(9965):351-61. doi: 10.1016/S0140-6736(14)61183-1. Epub 2014 Sep 24. PMID: 25262344; PMCID: PMC4322187.

14/9/24

Lancet

メタ解析

遺伝子研究43本(最大223,463人)のメタ解析と、スタチンのRCT(129,170人)のメタ解析の比較
HMGCR遺伝子のLDLを下げるアレル(rs17238484-G)1個あたり
LDL -0.06mmol/L、体重 +0.30kg、腹囲 +0.32cm、インスリン +1.62%、血糖 +0.23%
2型DM OR 1.02、別の多型rs12916-Tでも OR 1.06
RCTでは、スタチンで1年後のLDL -0.92mmol/L、平均4.2年で体重 +0.24kg、DM発症 OR 1.12
スタチンによるDM発症の増加は、少なくとも一部は標的であるHMGCRの阻害によって説明される

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