Dorkhan Mozhgan, Dencker Magnus, Stagmo Martin, Groop Leif
Department of Clinical Sciences, Division of Diabetes & Endocrinology, Lund University, Malmö University Hospital, Malmö, Sweden.
Cardiovasc Diabetol. 2009 Mar 20;8:15. doi: 10.1186/1475-2840-8-15.
Both insulin and thiazolidinediones (TZDs) are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides.
Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed.
After 26 weeks of treatment, the changes in HbA1c, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 +/- 19.6 to 22.8 +/- 44.0, p = 0.046), the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p < 0.05, between treatment groups). There was a borderline significant increase in ejection fraction in the pioglitazone group.
This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.
胰岛素和噻唑烷二酮类药物（TZDs）在治疗2型糖尿病患者的高血糖和改善胰岛素抵抗方面均有效，但都有包括体重增加和液体潴留在内的副作用。TZDs的使用因包括心力衰竭在内的不良心血管事件风险而受到进一步阻碍。本研究评估了吡格列酮或甘精胰岛素对心功能、心脏大小以及液体潴留替代标志物（如体重、血红蛋白和利钠肽）的影响。
30例使用二甲双胍和磺脲类药物血糖控制不佳的患者被随机分为两组，分别接受加用甘精胰岛素或吡格列酮治疗26周。在治疗开始前及26周后收集两组的超声心动图数据和血样。对左心室舒张末期和左心房收缩末期容积进行定量，测量体重并分析血样。
治疗26周后，两组的糖化血红蛋白、体重和血红蛋白变化相似。吡格列酮组高密度脂蛋白显著升高。虽然吡格列酮组利钠肽有所增加（NT-proBNP从11.4±19.6增至22.8±44.0，p = 0.046），但治疗组之间的差异不显著。吡格列酮组左心室舒张末期容积增加了11%，左心房收缩末期容积增加了17%（两组治疗组间比较，p均<0.05）。吡格列酮组射血分数有临界显著增加。
这项随机先导研究表明，吡格列酮治疗六个月可导致利钠肽显著增加和心脏大小改变。甘精胰岛素治疗未观察到这些变化，而甘精胰岛素也已知会引起液体潴留。需要进行更大规模的随机试验来证实这些发现。
