Diabetes Division, Texas Diabetes Institute, University of Texas Health Science Center, San Antonio, TX, USA.
Diabetes Metab Res Rev. 2011 May;27(4):373-82. doi: 10.1002/dmrr.1185.
To test potential differences between the actions of anti-diabetic medications, we examined the effects of oral hypoglycaemic agents versus glargine-apidra insulin therapy in T2DM.
T2DM subjects were randomized to either oral hypoglycaemic agents (pioglitazone, metformin and glipizide, n = 9) or insulin therapy (n = 12) for 6 months. Carotid intimal media thickness, vascular reactivity (flow-mediated vasodilatation; percent change in brachial artery basal diameter post-ischaemia) and sublingual nitrate were measured with ultrasonography. Euglycemic hyperinsulinemic (80 mU/m(2) ) clamp with [3]-3H-glucose and muscle biopsies were performed.
Fasting plasma glucose (257 to ~124 mg/dL, oral hypoglycaemic agents and ~256 to ~142 mg/dL, IT) and HbA(1c) (10.3 to 6.4%, OHA and ~10.7 to ~7.1%, IT) improved comparably. Endogenous glucose production (2.1 to 1.7 mg/kg/min, oral hypoglycaemic agents and ~2.3 to ~2.0 mg/kg/min, insulin therapy) and endogenous glucose production suppression by insulin (0.4 to 0.3 mg/kg min, oral hypoglycaemic agents and ~0.5 to ~0.7 mg/kg min, insulin therapy) were different. Total glucose disposal × 100 increased in the oral hypoglycaemic agents group (5.2 to 8.1; p = 0.03), but not in insulin therapy (6.0 to 5.4 mg/kg/min/µU/mL × 100). OHA reduced CIMT (0.080 to 0.068 cm; p < 0.05), whereas insulin therapy did not (0.075 to 0.072 cm). After sublingual nitrate, brachial artery basal diameter increased in the OHA group (8.7 to 18.2%), but not in insulin therapy (11.2 to 15.0%; p < 0.02). Except for plasma adiponectin (7 to ~15, oral hypoglycaemic agents versus ~6 to ~10, IT), changes in inflammatory markers in the circulation and in muscle (IκBα, super-oxidase dismutase 2, monocyte-chemo-attractant protein 1, p-ERK and JNK) were equivalent.
Oral hypoglycaemic agents and insulin therapy treated patients achieved adequate glycemic control and the effects on circulating and muscle inflammatory biomarkers were similar, but only oral hypoglycaemic agents improved insulin sensitivity, vascular function and carotid intimal media thickness. These findings in a small sample suggest that the use of oral hypoglycaemic agents provides additional benefits to patients with T2DM.
为了检验抗糖尿病药物作用的潜在差异，我们研究了口服降糖药与甘精胰岛素速效制剂在 2 型糖尿病中的疗效。
2 型糖尿病患者被随机分为口服降糖药组（吡格列酮、二甲双胍和格列吡嗪，n = 9）或胰岛素治疗组（n = 12），治疗 6 个月。采用超声检查测量颈动脉内膜中层厚度、血管反应性（血流介导的血管扩张；缺血后肱动脉基础直径的百分比变化）和舌下硝酸盐。进行 80 mU/m2 的正葡萄糖高胰岛素钳夹实验，并进行 [3]-3H-葡萄糖和肌肉活检。
空腹血糖（257 至124 mg/dL，口服降糖药和256 至142 mg/dL，胰岛素治疗）和糖化血红蛋白（10.3 至6.4%，OHA 和10.7 至7.1%，IT）改善相当。内源性葡萄糖生成（2.1 至1.7 mg/kg/min，口服降糖药和2.3 至2.0 mg/kg/min，胰岛素治疗）和胰岛素对内源性葡萄糖生成的抑制作用（0.4 至0.3 mg/kg min，口服降糖药和0.5 至0.7 mg/kg min，胰岛素治疗）不同。口服降糖药组的总葡萄糖处置量增加（5.2 至8.1；p = 0.03），但胰岛素治疗组没有（6.0 至5.4 mg/kg/min/µU/mL×100）。OHA 降低 CIMT（0.080 至0.068 cm；p < 0.05），而胰岛素治疗则没有（0.075 至0.072 cm）。舌下硝酸盐后，OHA 组肱动脉基础直径增加（8.7 至18.2%），但胰岛素治疗组没有（11.2 至15.0%；p < 0.02）。除了循环中的脂联素（7 至15，口服降糖药与6 至10，IT）外，循环和肌肉中的炎症标志物（IκBα、超氧化物歧化酶 2、单核细胞趋化蛋白 1、p-ERK 和 JNK）的变化也相当。
口服降糖药和胰岛素治疗使患者血糖控制达标，对循环和肌肉炎症生物标志物的影响相似，但只有口服降糖药能改善胰岛素敏感性、血管功能和颈动脉内膜中层厚度。这些在小样本中的发现表明，口服降糖药的使用为 2 型糖尿病患者提供了额外的益处。
