Yamanouchi Toshikazu
Kita-Tokyo-Jueien/Department of Internal Medicine, Teikyo University, Tokyo, Japan.
Vasc Health Risk Manag. 2010 Apr 15;6:189-97. doi: 10.2147/vhrm.s5838.
To prevent hyperinsulinemia, which may cause atherosclerosis, thiazolidinediones (TZDs), also known as insulin sensitizers, are often added to the therapeutic regimen of patients with type 2 diabetes who are receiving insulin. The combination of insulin with pioglitazone, a TZD, reduces glycoated hemoglobin (HbA(1c)) by 0.6%-2.1%. The higher the HbA(1c) baseline the larger the therapeutic reduction of HbA(1c). This combination therapy has been shown to be beneficial even in lean Japanese patients with diabetes. It should be noted that such combination therapy is much more useful when the main clinical aim is lowering not postprandial, but fasting and nocturnal glycemia. The glycemic-lowering effects of pioglitazone alone occur slowly, whereas the addition of insulin to pioglitazone often shows a dramatic glucose-lowering effect. Thus, such combination therapy increases the possibility of frequent hypoglycemia within 1 to 2 months of combining the drugs. Severe hypoglycemia in patients using this therapy is rare. Patients treated with combination therapy who show a predominant reduction of glycemia often have severe edema; in 10%-20% of patients, combination therapy leads to drug-related congestive heart failure (CHF). However, this phenomenon is usually weakened if low doses of pioglitazone which are added to insulin therapy (ie, 15 mg/day or even 7.5 mg/day for women). It is well known that pioglitazone has an anti-atherosclerotic effect, although it is unclear if hyperinsulinemia induces atherogenic changes, either directly or indirectly, by the promotion of obesity. Until now, we have not confirmed whether the anti-atherosclerotic effects of pioglitazone exceed the supposed disadvantageous action of insulin when used in combination therapy. The addition of pioglitazone tends to reduce daily insulin dosages, but study findings have not been consistent. Improvement of lipid profiles has also been weak with this combination therapy. Long-term trials are needed before any conclusions can be reached concerning atherogenic effects of treatment for type 2 diabetes. Combination therapy of even small doses of pioglitazone with insulin should be primarily used for patients who achieve insufficient reduction in glycemia with insulin monotherapy.
为预防可能导致动脉粥样硬化的高胰岛素血症，噻唑烷二酮类药物（TZDs），也被称为胰岛素增敏剂，常被添加到接受胰岛素治疗的2型糖尿病患者的治疗方案中。胰岛素与噻唑烷二酮类药物吡格列酮联合使用，可使糖化血红蛋白（HbA1c）降低0.6% - 2.1%。HbA1c基线水平越高，其治疗后降低幅度越大。这种联合治疗已被证明对瘦型日本糖尿病患者也有益。需要注意的是，当主要临床目标是降低空腹和夜间血糖而非餐后血糖时，这种联合治疗更为有用。吡格列酮单药的降糖作用起效缓慢，而在吡格列酮基础上加用胰岛素通常会产生显著的降糖效果。因此，这种联合治疗在联合用药后的1至2个月内增加了频繁发生低血糖的可能性。使用这种治疗方法的患者发生严重低血糖的情况很少见。接受联合治疗且血糖主要降低的患者常出现严重水肿；在10% - 20%的患者中，联合治疗会导致药物相关性充血性心力衰竭（CHF）。然而，如果在胰岛素治疗中添加低剂量的吡格列酮（即15毫克/天，女性甚至7.5毫克/天），这种现象通常会减弱。众所周知，吡格列酮具有抗动脉粥样硬化作用，尽管尚不清楚高胰岛素血症是否通过促进肥胖直接或间接诱导致动脉粥样硬化改变。到目前为止，我们尚未证实吡格列酮在联合治疗中抗动脉粥样硬化作用是否超过胰岛素可能的不利作用。添加吡格列酮往往会降低每日胰岛素剂量，但研究结果并不一致。这种联合治疗对血脂谱的改善作用也较弱。在对2型糖尿病治疗的动脉粥样硬化作用得出任何结论之前，需要进行长期试验。即使是小剂量吡格列酮与胰岛素的联合治疗，也应主要用于单药胰岛素治疗血糖降低不足的患者。
