著者

奥山 治美 浜崎 智仁 大櫛 陽一 浜 六郎 内野 元 渡邊 浩幸 橋本 道男

出版者

日本脂質栄養学会

雑誌

脂質栄養学 (ISSN:13434594)

巻号頁・発行日

vol.22, no.2, pp.173-186, 2013 (Released:2013-10-01)

参考文献数

60

被引用文献数

1 1

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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.

著者

奥山 治美 浜 六郎 大櫛 陽一 浜崎 智仁 内野 元

出版者

日本脂質栄養学会

雑誌

脂質栄養学 (ISSN:13434594)

巻号頁・発行日

vol.27, no.1, pp.30-38, 2018 (Released:2018-07-16)

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An open-label, randomized controlled trial in type 2 diabetics with hypertension, dyslipidemia, or both was reported (J-DOIT3 study).The participants were randomly assigned to receive conventional or intensive therapy with respect to HbA1c, blood pressure and LDL-C (n=1,271 in each group),and were followed for 8.5 years at 81 clinical sites. Both the participants and doctors in charge were aware of the group assigned. The experimental design was essentially as recommended in the [Comprehensive risk management chart for the prevention of cerebro- and cardiovascular diseases 2015] from the Joint Committee consisted of 13 internal medicine-related societies in Japan, and the Japan Atherosclerotic Society Guidelines 2017. Therefore, the conclusion from the J-DOIT3 study is expected in medical field to affect the current and future medications for the prevention of atherosclerotic cerebro- and cardiovascular diseases (ASCVD).While analyzing the results of this study,we encountered serious problems associated with the methodology, logics and its interpretations, which were summarized in this review. The follow-up study appears to be in progress as described in the Discussion, but we interpret that the intensive therapy used in the J-DOIT3 study is risky in view of currently available evidence. We propose the authors of the study to let the participants know of the results on its objective endpoint, and newly obtain Informed Consents including the potential risks of the intensive intervention based on the progress in this field after the start of this study.

著者

大櫛 陽一 浜 六郎 浜崎 智仁 内野 元

出版者

日本脂質栄養学会

雑誌

脂質栄養学 (ISSN:13434594)

巻号頁・発行日

vol.27, no.1, pp.39-47, 2018 (Released:2018-07-16)

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A nationwide multicenter randomized controlled study (JDCS) was performed in type-2 diabetes patients. The conventional (CON) group received usual care including anti-diabetic, anti-hypertensive and anti-hyperlipidemic agents to maintain their targeted levels, and the intervention (INT) group additionally received intensive education on lifestyle modifications and adherence to treatment by telephone counselling and at each time outpatient clinic visit for 8 years. The JDCS appears to be based on an assumption that usual treatment of diabetes is appropriate for the prevention of diabetes complications, and that the lack of patients’ compliance is the major cause of unsuccessful treatments. No significant differences between the two groups were found in most of the test results (BMI, blood pressure, fasting glucose level, TC, HDL, lipoprotein-a), use of agents, life style (energy intake, smoking and alcohol intake) at 4 years of intervention. The exercise level was higher at 5 years of intervention, and triglyceride level was lower at 8 years. The incidence of coronary heart disease, retinopathy and neuropathy did not differ significantly between the two groups, but stroke incidence was lower in the INT group. We conducted new analyses on the changes of some explanatory variables in each group. The proportion of participants with pharmacological treatment including insulin significantly increased in both groups except sulfonylureas which about 60% of the participants used at the baseline. On the other hand, those without pharmacological treatment decreased from 19% to 4% in both groups. These indicate that both groups failed in diabetes treatment together. As for the exercise and the smoking cessation, these may prevent stroke, but do not contribute to improvement of diabetes. It is not convincing enough for us to support the validity of publicizing the treatment of diabetes patients used in the JDCS study performed at 59 universities and general hospitals in Japan.