de Boer H, Jansen M, Koerts J, Verschoor L
Department of Internal Medicine, Ziekenhuis Rijnstate Arnhem, Arnhem, The Netherlands.
Diabetes Obes Metab. 2004 Mar;6(2):114-9. doi: 10.1111/j.1463-1326.2004.00322.x.
Patients with type 2 diabetes who are failing on oral agents will generally gain a large amount of body fat when switched to insulin treatment. This adverse effect may be related to chronic hyperinsulinism induced by long-acting insulin compounds.
To test the concept that regain of glycaemic control can be achieved without causing weight gain, using a regimen free of long-acting insulin.
In a 3-month open-label pilot study including 25 patients with moderate overweight and secondary failure, we investigated whether nocturnal glycaemic control could be achieved with glimepiride administered at 20:00 hours. The starting dose was 1-2 mg, with subsequent titration up to a maximum of 6 mg. Rapid-acting insulin analogues were used three times daily to regain postprandial glucose control.
Glycaemic control at 3 months was established with glimepiride in a dose of 4.4 +/- 0.3 mg/day (mean +/- standard error of the mean), and a total daily insulin dose of 24.1 +/- 2.6 IU. Fasting glucose levels decreased from 12.7 +/- 0.6 mmol/l to 8.1 +/- 0.3 mmol/l (p < 0.001), and target levels were reached in 14 of 25 patients (56%). Mean HbA1c decreased from 10.5 +/- 0.4 to 7.7 +/- 0.2% (p < 0.001). Symptomatic nocturnal hypoglycaemia was not reported. Body weight did not change (85.7 +/- 3.6 kg vs. 85.7 +/- 3.3 kg, p = 0.99).
The data suggest that this new approach may be useful in about 50% of type 2 diabetes patients presenting with failure on maximal oral treatment.
口服降糖药治疗效果不佳的2型糖尿病患者改用胰岛素治疗后通常会大量增加体脂。这种不良反应可能与长效胰岛素制剂引起的慢性高胰岛素血症有关。
使用不含长效胰岛素的治疗方案，验证在不导致体重增加的情况下实现血糖控制恢复的概念。
在一项为期3个月的开放标签试验性研究中，纳入25例中度超重且口服降糖药继发失效的患者，我们研究了20:00服用格列美脲是否能实现夜间血糖控制。起始剂量为1 - 2mg，随后滴定至最大剂量6mg。每日三次使用速效胰岛素类似物以恢复餐后血糖控制。
3个月时，格列美脲剂量为4.4±0.3mg/天（均值±均值标准误），每日胰岛素总剂量为24.1±2.6IU，血糖得到控制。空腹血糖水平从12.7±0.6mmol/L降至8.1±0.3mmol/L（p<0.001），25例患者中有14例（56%）达到目标水平。平均糖化血红蛋白从10.5±0.4降至7.7±0.2%（p<0.001）。未报告有症状的夜间低血糖。体重未改变（85.7±3.6kg对85.7±3.3kg，p = 0.99）。
数据表明，这种新方法可能对约50%最大剂量口服治疗失败的2型糖尿病患者有用。
