Pharmacological Treatment of the Pathogenetic Defects in Type 2 Diabetes The randomized multicenter South Danish Diabetes Study
Pharmacological Treatment of the Pathogenetic Defects in Type 2 Diabetes The randomized multicenter South Danish Diabetes Study
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DOI：
10.2337/dc10-0531
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发表时间：
2011-01-01
期刊：
影响因子：
16.2
通讯作者：
Beck-Nielsen, Henning
中科院分区：
文献类型：
--
作者：
Gram, Jeppe;Henriksen, Jan Erik;Beck-Nielsen, Henning
目的-确定门冬胰岛素与NPH胰岛素联合二甲双胍/安慰剂和罗格列酮/安慰剂治疗的效果。该假设是，联合纠正2型糖尿病的主要发病缺陷，将导致最佳的血糖control.RESEARCH设计和方法-这项研究是一项为期2年的兴奋剂驱动的随机部分安慰剂对照的多中心试验，在371例2型糖尿病患者至少口服降糖治疗。在析因设计中，患者被分配至8个治疗组之一，分别为餐时门冬胰岛素与睡前NPH胰岛素每日1次、二甲双胍每日2次与安慰剂、罗格列酮每日2次与安慰剂。结果：门冬胰岛素组A1 C下降幅度大于NPH组（-0.41 ± 0.10%，P < 0.001）。与安慰剂相比，二甲双胍降低A1 C（-0.60 +/-0.10%，P < 0.001），罗格列酮也是如此（-0.55 +/-0.10%，P < 0.001）。三联疗法（罗格列酮、二甲双胍和任何胰岛素）导致A1 C的降低幅度大于罗格列酮加胰岛素（-0.50 +/-0.14%，P < 0.001）和二甲双胍加胰岛素（-0.45 +/-0.14%，P < 0.001）。门冬胰岛素与体重增加较高相关（1.6 +/- 0.6 kg，P < 0.01）和轻度日间低血糖的发生率较高（4.9 +/- 7.5对1.7 +/- 5.4例/人/年，P < 0.001）与NPH相比。结论-餐后高血糖的胰岛素治疗导致A1 C低于空腹高血糖的治疗，代价是体重增加和低血糖发作。然而，胰岛素治疗必须与外周和肝脏胰岛素抵抗的治疗相结合，以使血糖正常化，在这种情况下，胰岛素方案不太重要。
OBJECTIVE- To determine the effect of treatment with insulin aspart compared with NPH insulin, together with metformin/placebo and rosiglitazone/placebo. The hypothesis was that combined correction of major pathogenetic defects in type 2 diabetes would result in optimal glycemic control.RESEARCH DESIGN AND METHODS- This study was a 2-year investigator-driven randomized partly placebo-controlled multicenter trial in 371 patients with type 2 diabetes on at least oral antiglycemic treatment. Patients were assigned to one of eight treatment groups in a factorial design with insulin aspart at mealtimes versus NPH insulin once daily at bedtime, metformin twice daily versus placebo, and rosiglitazone twice daily versus placebo. The main outcome measurement was change in A1C.RESULTS- A1C decreased more in patients treated with insulin aspart compared with NPH (-0.41 +/- 0.10%, P < 0.001). Metformin decreased A1C compared with placebo (-0.60 +/- 0.10%, P < 0.001), as did rosiglitazone (-0.55 +/- 0.10%, P < 0.001). Triple therapy (rosiglitazone, metformin, and any insulin) resulted in a greater reduction in A1C than rosiglitazone plus insulin (-0.50 +/- 0.14%, P < 0.001) and metformin plus insulin (-0.45 +/- 0.14%, P < 0.001). Aspart was associated with a higher increase in body weight (1.6 +/- 0.6 kg, P < 0.01) and higher incidence of mild daytime hypoglycemia (4.9 +/- 7.5 vs. 1.7 +/- 5.4 number/person/year, P < 0.001) compared with NPH.CONCLUSIONS- Insulin treatment of postprandial hyperglycemia results in lower A1C than treatment of fasting hyperglycemia, at the expense of higher body weight and hypoglycemic episodes. However, insulin therapy has to be combined with treatment of both peripheral and liver insulin resistance to normalize blood glucose, and in this case, the insulin regimen is less important.