Yki-Järvinen H, Kauppila M, Kujansuu E, Lahti J, Marjanen T, Niskanen L, Rajala S, Ryysy L, Salo S, Seppälä P
Second Department of Medicine, University of Helsinki, Finland.
N Engl J Med. 1992 Nov 12;327(20):1426-33. doi: 10.1056/NEJM199211123272005.
Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment.
We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group).
The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001).
In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration.
胰岛素被广泛用于改善非胰岛素依赖型糖尿病（NIDDM）患者的代谢控制，但关于胰岛素治疗的最佳方案尚无共识。
我们采用五种方案对153例NIDDM患者进行了为期三个月的治疗：（1）口服降糖药治疗加早餐前（上午7点）给予NPH胰岛素（上午-NPH组）；（2）口服降糖药治疗加晚餐前（晚上9点）给予NPH胰岛素（晚上-NPH组）；（3）早餐和晚餐前给予NPH和普通胰岛素（比例为70单位比30单位）（两次胰岛素注射组）；（4）晚上9点给予NPH胰岛素和餐时给予普通胰岛素（多次胰岛素注射组）；（5）继续口服降糖药治疗（对照组）。
所有四个胰岛素治疗组糖化血红蛋白的平均（±标准误）值下降相似（分别为1.7±0.3%、1.9±0.2%、1.8±0.3%和1.6±0.3%）。这四个组的下降幅度显著大于对照组（0.5±0.2%；与所有胰岛素治疗组相比，P<0.001）。晚上-NPH组体重增加显著少于其他胰岛素治疗组（上午-NPH组为2.2±0.5kg，两次胰岛素注射组为1.8±0.5kg，多次胰岛素注射组为2.9±0.5kg；P<0.05）。此外，晚上-NPH组平均日间血清游离胰岛素浓度的增幅比其他胰岛素治疗组小50%至65%。胰岛素治疗组主观幸福感的改善显著大于对照组（P<0.001）。
在接受口服降糖药治疗的NIDDM患者中，晚上加用NPH胰岛素改善血糖控制的方式与早上加用NPH胰岛素、两次胰岛素注射方案或多次胰岛素注射方案相似，但体重增加和高胰岛素血症较少。因此，数据表明NIDDM患者不能从多次胰岛素注射中获益，夜间胰岛素给药似乎比白天给药更可取。
