Diabetesinstitut Heidelberg, Germany.
Ther Adv Endocrinol Metab. 2013 Aug;4(4):113-21. doi: 10.1177/2042018813501188.
In diabetic nephropathy the decline of renal function causes modifications of the insulin and carbohydrate metabolism resulting in changed insulin requirements. The aim of the present study was to identify potential differences in the requirements of human insulin and various insulin analogues in patients with type 1 diabetes mellitus and renal dysfunction.
The insulin requirements of 346 patients with type 1 diabetes mellitus under everyday life circumstances were assessed in an observational study. Simultaneously, laboratory parameters were measured and the estimated glomerular filtration rate (eGFR) was calculated using the formula by Cockcroft-Gault. Medical history and concomitant medication were recorded. The insulin requirements of long- and short-acting insulin were tested for a relationship with the eGFR and laboratory parameters.
The dosage of long-acting human insulin did not show any relation to eGFR. In contrast, a strong positive relation between dosage and renal function was found for insulin glargine and insulin detemir. After classification according to renal function, the insulin dosage at eGFR less than 60 ml/min was 29.7% lower in glargine-treated and 27.3% lower in detemir-treated patients compared with eGFR greater than 90 ml/min. Considering the whole range of eGFR, short-acting human insulin did not show a relation with renal function. Only after classification according to renal function was a dose reduction found for human insulin at eGFR less than 60 ml/min. In contrast, requirements of insulin lispro were significantly related to eGFR over the whole range of eGFR. At eGFR less than 60 ml/min the insulin dosage was 32.6% lower than at eGFR greater than 90 ml/min. The requirements of insulin aspart did not show any association with the eGFR.
Patients with type 1 diabetes mellitus show different insulin requirements according to the renal function depending on the applied insulin. This finding is essential for the adjustment of insulin therapy in patients with diabetic nephropathy to achieve balanced glycemic control. To determine the underlying mechanisms, further studies on the pharmacokinetics and pharmacodynamics of the different insulins in patients with diabetic nephropathy are needed.
在糖尿病肾病中，肾功能下降导致胰岛素和碳水化合物代谢发生变化，从而导致胰岛素需求改变。本研究的目的是确定 1 型糖尿病伴肾功能障碍患者对人胰岛素和各种胰岛素类似物的需求是否存在差异。
在一项观察性研究中，评估了 346 名 1 型糖尿病患者在日常生活中的胰岛素需求。同时，测量了实验室参数，并使用 Cockcroft-Gault 公式计算了估算肾小球滤过率（eGFR）。记录了病史和伴随用药。测试了长效和短效胰岛素的胰岛素需求与 eGFR 和实验室参数之间的关系。
长效人胰岛素的剂量与 eGFR 无任何关系。相比之下，胰岛素甘精和胰岛素地特的剂量与肾功能呈强正相关。根据肾功能分类后，eGFR 小于 60ml/min 的甘精组和地特组胰岛素剂量分别比 eGFR 大于 90ml/min 的患者低 29.7%和 27.3%。考虑到整个 eGFR 范围，短效人胰岛素与肾功能无关系。只有在根据肾功能分类后，eGFR 小于 60ml/min 的患者才发现人胰岛素剂量减少。相比之下，胰岛素赖脯胰岛素的需求与整个 eGFR 范围显著相关。eGFR 小于 60ml/min 时，胰岛素剂量比 eGFR 大于 90ml/min 时低 32.6%。胰岛素门冬氨酸的需求与 eGFR 无任何关联。
1 型糖尿病患者根据所应用的胰岛素，根据肾功能表现出不同的胰岛素需求。这一发现对于调整糖尿病肾病患者的胰岛素治疗以实现平衡的血糖控制至关重要。为了确定潜在的机制，需要进一步研究不同胰岛素在糖尿病肾病患者中的药代动力学和药效动力学。
