Pisu E, De Benedictis D, Baggiore C, Diana A, Marengo C, Bozzo C, Renzetti A, Pagano G
Istituto di Medicina Interna dell'Università degli Studi di Torino, Italy.
Diabet Med. 1990 Nov;7(9):805-9. doi: 10.1111/j.1464-5491.1990.tb01496.x.
In order to investigate the mechanism of amelioration of metabolic abnormalities with supplementary doses of insulin, islet B-cell function and insulin sensitivity were measured in 10 patients with Type 2 diabetes in secondary failure to oral agents. A small dose of ultralente insulin (0.26 +/- 0.07 U kg-ideal-body-weight-1) was added in the morning before breakfast. After 3 months insulin therapy and progressive improvement of metabolic control (HbA1 from 10.5 +/- 0.4 to 9.0 +/- 0.3% at the end of insulin treatment, p less than 0.001), basal C-peptide and incremental area during an oral glucose tolerance test were unchanged. In vivo peripheral insulin sensitivity (euglycaemic clamp with insulin infusion of 40, 160, and 600 mU m-2 min-1, respectively) was significantly improved (glucose requirement: to 4.7 +/- 1.0 from 3.0 +/- 0.6 mg kg-1 min-1, p less than 0.05 at first insulin level; to 10.8 +/- 0.5 from 9.3 +/- 0.7 mg kg-1 min-1, p less than 0.01 at second level; to 13.3 +/- 0.6 from 11.8 +/- 0.8 mg kg-1 min-1, p less than 0.025 at third level). Basal hepatic glucose production was also significantly reduced (from 4.3 +/- 0.4 to 3.3 +/- 0.3 mg kg-1 min-1, p less than 0.05), and residual glucose production further suppressed after insulin supplement (from 1.1 +/- 0.4 to 0.3 +/- 0.2 mg kg-1 min-1 after 120 min at 100 mU l-1 plasma insulin, p less than 0.05). Specific insulin binding to mononuclear leucocytes was unchanged (from 3.1 +/- 0.3 to 3.5 +/- 0.3%, NS).
为了研究补充胰岛素改善代谢异常的机制，对10例口服降糖药继发失效的2型糖尿病患者的胰岛B细胞功能和胰岛素敏感性进行了测定。早餐前早晨加用小剂量超长效胰岛素（0.26±0.07U·kg理想体重⁻¹）。胰岛素治疗3个月且代谢控制逐步改善（胰岛素治疗结束时糖化血红蛋白从10.5±0.4%降至9.0±0.3%，p<0.001）后，基础C肽和口服葡萄糖耐量试验期间的增量面积未改变。体内外周胰岛素敏感性（分别以40、160和600mU·m⁻²·min⁻¹的胰岛素输注进行正常血糖钳夹试验）显著改善（葡萄糖需求量：在第一个胰岛素水平时从3.0±0.6mg·kg⁻¹·min⁻¹降至4.7±1.0mg·kg⁻¹·min⁻¹，p<0.05；在第二个水平时从9.3±0.7mg·kg⁻¹·min⁻¹升至10.8±0.5mg·kg⁻¹·min⁻¹，p<0.01；在第三个水平时从11.8±0.8mg·kg⁻¹·min⁻¹升至13.3±0.6mg·kg⁻¹·min⁻¹，p<0.025）。基础肝糖生成也显著降低（从4.3±0.4mg·kg⁻¹·min⁻¹降至3.3±0.3mg·kg⁻¹·min⁻¹，p<0.05），补充胰岛素后残余糖生成进一步受到抑制（在血浆胰岛素浓度为100mU·l⁻¹时120分钟后从1.1±0.4mg·kg⁻¹·min⁻¹降至0.3±0.2mg·kg⁻¹·min⁻¹，p<0.05）。胰岛素与单核白细胞的特异性结合未改变（从3.1±0.3%至3.5±0.3%，无显著性差异）。
