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他汀类药物治疗与1型糖尿病患者胰岛素敏感性降低相关:一项为期56个月的前瞻性观察性随访研究。

Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: A prospective, observational 56-month follow-up study.

作者信息

Duvnjak Lea, Blaslov Kristina

机构信息

Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia.

Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb, Croatia.

出版信息

J Clin Lipidol. 2016 Jul-Aug;10(4):1004-1010. doi: 10.1016/j.jacl.2016.04.012. Epub 2016 May 10.

Abstract

BACKGROUND

Statins are effective in the primary and secondary prevention of cardiovascular events in individuals with and without diabetes. Emerging evidence, however, suggests that statins might reduce insulin sensitivity and secretion in healthy population and in type 2 diabetes.

OBJECTIVE

We aimed to investigate the effect of statin therapy introduction on insulin sensitivity in patients with type 1 diabetes mellitus (T1DM).

METHODS

This prospective observational 56-month long study included 832 randomly selected T1DM patients aged 25 to 61 years. Uncontrolled dyslipidemia and clinician-perceived need for treatment, rather than randomization, were basis for individuals being started on either atorvastatin or simvastatin (10-40 mg); N = 345, 41.47%. Patients on statin treatment were compared with those unexposed to statin. Insulin sensitivity was assessed using equation derived from euglycemic-hyperinsulinemic clamp studies-estimated glucose disposal rate.

RESULTS

Patients who started statin therapy (N = 345, 59.42% atorvastatin and 40.58% simvastatin) experienced a greater decrease in insulin sensitivity (19.27% vs 12.82% P < .001) and metabolic control deterioration compared with statin-free group. The risk of decrease in insulin sensitivity attributable to statin use was 36.7% (hazard ratio 1.36; 95% confidence interval 1.31-1.43) after adjustment for age, gender, disease duration, smoking status, and the concomitant antihypertensive therapy.

CONCLUSION

Although there is still a lack of a clear molecular explanation on the adverse effects of statin therapy on insulin sensitivity, we showed that it deteriorates insulin sensitivity in T1DM. The cardiovascular benefits of statin treatment might outweigh the risk of developing insulin resistance, but, the possible metabolic control worsening merits to be considered.

摘要

背景

他汀类药物在有或无糖尿病的个体中对心血管事件的一级和二级预防均有效。然而,新出现的证据表明,他汀类药物可能会降低健康人群和2型糖尿病患者的胰岛素敏感性和分泌。

目的

我们旨在研究开始他汀类药物治疗对1型糖尿病(T1DM)患者胰岛素敏感性的影响。

方法

这项为期56个月的前瞻性观察性研究纳入了832名年龄在25至61岁之间随机选取的T1DM患者。开始阿托伐他汀或辛伐他汀(10 - 40毫克)治疗的依据是血脂异常未得到控制以及临床医生认为有治疗必要,而非随机分组;N = 345,占41.47%。将接受他汀类药物治疗的患者与未接受他汀类药物治疗的患者进行比较。使用从正常血糖 - 高胰岛素钳夹研究得出的公式(估计葡萄糖处置率)评估胰岛素敏感性。

结果

开始他汀类药物治疗的患者(N = 345,59.42%为阿托伐他汀,40.58%为辛伐他汀)与未使用他汀类药物的组相比,胰岛素敏感性下降幅度更大(分别为19.27%和12.82%,P <.001),且代谢控制恶化。在调整年龄、性别、病程、吸烟状况和同时使用的抗高血压治疗后,因使用他汀类药物导致胰岛素敏感性下降的风险为36.7%(风险比1.36;95%置信区间1.31 - 1.43)。

结论

尽管对于他汀类药物治疗对胰岛素敏感性产生不良影响仍缺乏明确的分子解释,但我们发现它会使T1DM患者的胰岛素敏感性恶化。他汀类药物治疗对心血管的益处可能超过发生胰岛素抵抗的风险,但是,代谢控制可能恶化这一点值得考虑。

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