Systemic metabolic markers and myocardial glucose uptake in type 2 diabetic and coronary artery disease patients treated for 16 weeks with rosiglitazone, a PPARγ agonist
Systemic metabolic markers and myocardial glucose uptake in type 2 diabetic and coronary artery disease patients treated for 16 weeks with rosiglitazone, a PPARγ agonist
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DOI：
10.3109/07853890.2013.853369
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发表时间：
2014-02-01
影响因子：
4.4
通讯作者：
Nuutila, Pirjo
中科院分区：
文献类型：
--
作者：
Badeau, Robert M.;Honka, Miikka-Juhani;Nuutila, Pirjo
导言。使用罗格列酮治疗，一种过氧化物酶体增殖物激活的受体-伽玛。激动剂在2型糖尿病(T2 DM)患者中的应用正受到密切关注，因为它会对心血管结果产生不利影响。在有冠心病的T2 DM患者中，罗格列酮短期治疗可增加心肌葡萄糖摄取(MGU)。血清代谢和脂蛋白亚类的改变，可能与罗格列酮诱导的改善有关，目前尚不清楚。将合并冠心病的2型糖尿病患者分为安慰剂组(26例)和治疗组(罗格列酮4~8 mg；25例)。治疗16周后，采用血清核磁共振代谢组学方法检测治疗前后与T2 DM相关的循环低分子代谢物和脂蛋白亚类及血脂水平。罗格列酮治疗后代谢指标的显著变化与[F-18]氟脱氧葡萄糖正电子发射断层扫描测定的MGU值相关。与安慰剂相比，治疗显著增加了循环中的谷氨酰胺，降低了乳酸浓度。罗格列酮治疗后循环乳酸浓度与MGU呈显著负相关。在有冠心病的T2 DM患者中，短期罗格列酮治疗引起了代谢的轻微改善：血清乳酸和谷氨酰胺浓度变化，反映了胰岛素敏感性的改善，循环乳酸浓度与心肌葡萄糖摄取增加呈负相关。
Introduction. Treatment with rosiglitazone, a peroxisome proliferator-activated receptor-gamma. agonist, in type 2 diabetic mellitus (T2DM) patients is under scrutiny because it affects adversely cardiovascular outcomes. In T2DM patients, with existing coronary heart disease, short-term treatment with rosiglitazone increases myocardial glucose uptake (MGU). Serum metabolic and lipoprotein subclass changes, which may be associated with this rosiglitazone-induced improvement, are unknown.Methods. Patients with both T2DM and coronary heart disease were separated into placebo (n = 26) and treatment (rosiglitazone 4-8 mg; n = 25) groups. After 16 weeks of treatment, serum NMR metabolomics was used to measure circulating low-molecular-weight metabolites and lipoprotein subclasses and lipids that are associated with T2DM before and after the treatment. Significant metabolic measure changes after rosiglitazone treatment were correlated to MGU values assessed with [F-18] fluorodeoxyglucose positron emission tomography.Results. Compared to placebo, the treatment significantly increased circulating glutamine and decreased lactate concentrations. Circulating lactate concentrations showed a significant inverse association with MGU after rosiglitazone treatment.Conclusion. In T2DM patients with existing coronary heart disease, short-term rosiglitazone treatment caused minor improvements in metabolism: serum lactate and glutamine concentrations changed, reflecting improvements in insulin sensitivity, and circulating lactate concentrations inversely correlated to increases in myocardial glucose uptake.