在接受二甲双胍加磺脲类药物治疗但血糖控制不佳的2型糖尿病患者中，甘精胰岛素与加用罗格列酮的比较。
Comparison of glargine insulin versus rosiglitazone addition in poorly controlled type 2 diabetic patients on metformin plus sulfonylurea.
作者信息
Triplitt Curtis, Glass Leonard, Miyazaki Yoshiniro, Wajcberg Estela, Gastaldelli Amalia, De Filippis Elena, Cersosimo Eugenio, DeFronzo Ralph A
机构信息
Diabetes Division, MSC 7886, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
出版信息
Diabetes Care. 2006 Nov;29(11):2371-7. doi: 10.2337/dc06-0564.
OBJECTIVE
We sought to examine the mechanisms by which the addition of glargine insulin or rosiglitazone improves glycemic control in type 2 diabetic subjects poorly controlled on maximally effective doses of metformin plus sulfonylurea.
RESEARCH DESIGN AND METHODS
Subjects (aged 47 +/- 11 years, BMI 31 +/- 5 kg/m(2), HbA(1c) [A1C] 9.4 +/- 1.3%) received bedtime glargine insulin (titrated based on the fasting plasma glucose [FPG], n = 10) or rosiglitazone (4 mg twice daily, n = 10). At baseline and after 4 months, A1C was measured and an oral glucose tolerance test and a 3-h euglycemic insulin (80 mU/m(2) per min) clamp with [3-(3)H]glucose were performed.
RESULTS
A1C and FPG decreased similarly in the glargine insulin (9.1 +/- 0.4 to 7.6 +/- 0.3% and 212 +/- 14 to 139 +/- 5 mg/dl, respectively, both P < 0.0001) and rosiglitazone (9.4 +/- 0.3 to 7.6 +/- 0.4% and 223 +/- 14 to 160 +/- 19 mg/dl, respectively, both P < 0.005) groups. After 4 months, endogenous glucose production (EGP) declined similarly with glargine insulin (2.27 +/- 0.10 to 1.73 +/- 0.12 mg . kg(-1) . min(-1), P < 0.0001) and rosiglitazone (2.21 +/- 0.12 to 1.88 +/- 0.12 mg . kg(-1) . min(-1), P = 0.01). The hepatic insulin resistance index declined in the rosiglitazone group (32 +/- 3 to 21 +/- 1 mg . kg(-1) . min(-1) x microU/ml, P = 0.03 vs. baseline and P < 0.05 vs. glargine insulin) and did not change in the glargine group (22 +/- 5 to 20 +/- 3 mg . kg(-1) . min(-1) x microU/ml, P = NS). At 4 months, glargine insulin (3.6 +/- 0.5 to 4.2 +/- 0.4 mg . kg(-1) . min(-1), P < 0.01) and rosiglitazone (2.7 +/- 0.3 to 3.8 +/- 0.3 mg . kg(-1) . min(-1), P < 0.0005) increased R(d), but the increment was greater in the rosiglitazone group (P < 0.05). Diastolic blood pressure was reduced only by rosiglitazone (P < 0.01).
CONCLUSIONS
Triple therapy with glargine insulin or rosiglitazone similarly reduced A1C, primarily by suppressing basal EGP (hepatic). Glargine insulin reduced basal EGP by increasing plasma insulin levels, while rosiglitazone decreased basal hepatic glucose production by improving hepatic insulin sensitivity.
目的
我们试图研究在接受最大有效剂量二甲双胍加磺脲类药物治疗但血糖控制不佳的2型糖尿病患者中，加用甘精胰岛素或罗格列酮改善血糖控制的机制。
研究设计与方法
受试者（年龄47±11岁，体重指数31±5kg/m²，糖化血红蛋白[A1C]9.4±1.3%）接受睡前甘精胰岛素治疗（根据空腹血糖[FPG]进行滴定，n = 10）或罗格列酮治疗（4mg，每日两次，n = 10）。在基线和4个月后，测量糖化血红蛋白，并进行口服葡萄糖耐量试验和用[3-(3)H]葡萄糖进行的3小时正常血糖胰岛素（80mU/m²每分钟）钳夹试验。
结果
甘精胰岛素组（分别从9.1±0.4%降至7.6±0.3%，FPG从212±14mg/dl降至139±5mg/dl，P均<0.0001）和罗格列酮组（分别从9.4±0.3%降至7.6±0.4%，FPG从223±14mg/dl降至160±19mg/dl，P均<0.005）的糖化血红蛋白和空腹血糖下降情况相似。4个月后，甘精胰岛素组（从2.27±0.10mg·kg⁻¹·min⁻¹降至1.73±0.12mg·kg⁻¹·min⁻¹，P<0.0001）和罗格列酮组（从2.21±0.12mg·kg⁻¹·min⁻¹降至1.88±0.12mg·kg⁻¹·min⁻¹，P = 0.01）的内源性葡萄糖生成（EGP）下降情况相似。罗格列酮组的肝胰岛素抵抗指数下降（从32±3mg·kg⁻¹·min⁻¹×μU/ml降至21±1mg·kg⁻¹·min⁻¹×μU/ml，与基线相比P = 0.03，与甘精胰岛素组相比P<0.05），而甘精胰岛素组未变化（从22±5mg·kg⁻¹·min⁻¹×μU/ml降至20±3mg·kg⁻¹·min⁻¹×μU/ml，P = 无统计学意义）。在4个月时，甘精胰岛素组（从3.6±0.5mg·kg⁻¹·min⁻¹升至4.2±0.4mg·kg⁻¹·min⁻¹，P<0.01）和罗格列酮组（从2.7±0.3mg·kg⁻¹·min⁻¹升至3.8±0.3mg·kg⁻¹·min⁻¹，P<0.0005）的葡萄糖输注率（R(d)）增加，但罗格列酮组的增加幅度更大（P<0.05）。仅罗格列酮降低了舒张压（P<0.01）。
结论
甘精胰岛素或罗格列酮三联疗法同样降低了糖化血红蛋白，主要是通过抑制基础内源性葡萄糖生成（肝脏）。甘精胰岛素通过提高血浆胰岛素水平降低基础内源性葡萄糖生成，而罗格列酮通过改善肝脏胰岛素敏感性降低基础肝脏葡萄糖生成。
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