糖尿病者にスタチンは禁忌―緊急提言

医療現場では多くの場合、糖尿病者により厳しいコレステロールの管理を求め（リスクのない人は LDL-C 値として 160mg/dL 未満、糖尿病者は 120mg/dL 未満）、多くの場合、スタチン（コレステロール低下剤）の使用を必須なものとしている。しかし糖尿病者に対してもスタチンには心疾患予防効果は認められず、スタチン類はむしろ糖尿病を新規発症させることが確かと
なった。またその生化学的基盤も明らかにされてきた。すなわち糖尿病者にスタチンは禁忌であり、医師の合理的な判断による特別なケースを除き、その使用を制限するよう提言する。

Statins have been recognized clinically to raise blood glucose and glycated protein (HbA1c) levels enhancing the development of insulin resistance. However, most clinicians appear to adopt the interpretation that the benefit (prevention of CHD) outweighs the risk (new-onset of diabetes mellitus). Consistently, "Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2012" recommends diabetics to maintain LDL-C levels below 120 mg/dL; 40 mg/dL lower than the value for those without risky complications. This recommendation necessitates many diabetics to use statins. However, we pointed out that statins exhibited no significant benefit for the prevention of CHD in the trials performed by scientists independent of industries after 2004, when a new regulation on clinical trials took effect in EU (Cholesterol Guidelines for Longevity, 2010). Here, we reviewed clinical evidence that statins could induce diabetes mellitus, and biochemical evidence that statins are toxic to mitochondria; they suppress electron transport and ATP generation through decreased prenyl-intermediate levels. They also inhibit seleno-protein synthesis and dolichol-mediated glycation of insulin receptor leading to insulin resistance and cardiac failure, similarly to the case of Se-deficiency. These mechanisms of statin actions are consistent with clinically observed decreases in blood ketone body, mitochondrial dysfunctions and enhanced glucose intolerance. Based on these lines of evidence, we urgently propose that statins are contraindicant to diabetics and their prescription should be restricted to special cases* for which medical doctors rationally decide to be necessary.