Department of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, Leiden, The Netherlands.
Diabetes Metab Res Rev. 2013 Jan;29(1):33-8. doi: 10.1002/dmrr.2343.
The aim of this study was to determine whether insulin resistance is present in lean patients with uncomplicated type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion (CSII), compared with matched healthy controls.
We studied eight patients (four men and four women) with type 1 diabetes mellitus on continuous subcutaneous insulin infusion and eight healthy controls, matched for age, gender and body mass index. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies with infusion of [6,6-(2) H(2)] glucose.
Endogenous glucose production did not differ in the basal state between patients and controls. However, endogenous glucose production was less suppressed during clamp conditions in patients compared with controls (64% vs 79%, p = 0.01), indicating decreased hepatic insulin sensitivity. During the clamp study, glucose disposal rate was ~38% lower in patients compared with controls (24.4 ± 2.5 vs 39.7 ± 5.6 µmol/kgLBM/min, p = 0.04). Accordingly, the rate of infusion of glucose was ~51% lower in patients (17.7 ± 2.8 vs 39.7 ± 5.7 µmol/kgLBM/min, p = 0.02). Finally, non-esterified fatty acids levels were ~2.5 times higher in patients during steady state clamp conditions (150 ± 26 vs 58 ± 4 pmol/L, p = 0.01), reflecting decreased insulin sensitivity of lipolysis.
Insulin resistance is a prominent feature of lean patients with type 1 diabetes mellitus, despite long term and stable treatment with continuous subcutaneous insulin infusion. Insulin resistance in type 1 diabetes involves both lipolysis, hepatic and peripheral glucose metabolism.
本研究旨在比较长期接受持续皮下胰岛素输注（CSII）治疗的无并发症 1 型糖尿病消瘦患者与匹配的健康对照者之间是否存在胰岛素抵抗。
我们研究了 8 名（4 男 4 女）接受持续皮下胰岛素输注的 1 型糖尿病患者和 8 名健康对照者，年龄、性别和体重指数相匹配。通过输注[6,6-（2）H2]葡萄糖的高胰岛素正葡萄糖钳夹研究来测量胰岛素敏感性。
患者和对照组在基础状态下的内源性葡萄糖生成没有差异。然而，与对照组相比，患者在钳夹状态下的内源性葡萄糖生成抑制较少（64%对 79%，p=0.01），表明肝胰岛素敏感性降低。在钳夹研究期间，与对照组相比，患者的葡萄糖处置率低约 38%（24.4±2.5 对 39.7±5.6µmol/kgLBM/min，p=0.04）。因此，患者的葡萄糖输注率低约 51%（17.7±2.8 对 39.7±5.7µmol/kgLBM/min，p=0.02）。最后，在稳态钳夹条件下，患者的非酯化脂肪酸水平高约 2.5 倍（150±26 对 58±4pmol/L，p=0.01），反映了脂肪分解的胰岛素敏感性降低。
尽管长期稳定地接受持续皮下胰岛素输注治疗，1 型糖尿病消瘦患者仍存在明显的胰岛素抵抗。1 型糖尿病的胰岛素抵抗涉及脂解、肝和外周葡萄糖代谢。
