胰岛素类似物赖脯胰岛素对1型糖尿病患者夜间血糖控制的影响。

The effect of the insulin analog lispro on nighttime blood glucose control in type 1 diabetic patients.

作者信息

Ahmed A B, Home P D

机构信息

Human Metabolism and Diabetes Research Centre, University of Newcastle upon Tyne, U.K.

出版信息

Diabetes Care. 1998 Jan;21(1):32-7. doi: 10.2337/diacare.21.1.32.

DOI:10.2337/diacare.21.1.32

PMID:9538967

Abstract

OBJECTIVE

Unmodified regular insulin has a long absorption tail, unlike the fast-acting insulin analog lispro, and may contribute to hypoglycemia in the early part of the night. A randomized crossover double-blind study was performed to compare blood glucose concentrations in the early part of the night in type 1 diabetic patients receiving lispro or unmodified regular human insulin, in random order, on 2 separate study days.

RESEARCH DESIGN AND METHODS

We studied 23 C-peptide-negative patients; 12 were using a premeal plus basal insulin regimen, and 11 were using twice-daily insulin injections. Patients were admitted to the investigation unit at 5:00 P.M. and received a single dose of lispro or unmodified regular human insulin before the evening meal. In both groups, the NPH insulin dose remained unchanged. Identical meals and snacks were eaten at the same time during both study days.

RESULTS

Average postprandial (6:00-10:00 P.M.) blood glucose concentrations were significantly lower after lispro therapy compared with human insulin (7.1 +/- 0.4 [SE] vs. 8.5 +/- 0.4 mmol/l, P = 0.0002). Nighttime (midnight to 4:00 A.M.) blood glucose concentrations were significantly higher after lispro compared with human insulin (10.3 +/- 0.4 vs. 9.1 +/- 0.4 mmol/l, P = 0.02). This difference was greatest in patients on the premeal plus basal insulin regimen (11.6 +/- 0.5 vs. 8.7 +/- 0.4 mmol/l, P < 0.001). The incidence of nocturnal hypoglycemia (midnight to 4:00 A.M., blood glucose < 3.5 mmol/l) was less with lispro compared with unmodified insulin (1 vs. 6 patients, P = 0.04). Nighttime (midnight to 4:00 A.M.) 3-hydroxybutyrate (102 +/- 13 vs. 51 +/- 7 mumol/l, P = 0.000) and glycerol (52 +/- 3 vs. 42 +/- 2 mumol/l, P < 0.01) were significantly higher after lispro therapy compared with human insulin in patients on the premeal plus bolus insulin regimen.

CONCLUSIONS

Lispro can improve postprandial blood glucose control and reduce the incidence of nocturnal hypoglycemia at the expense of nocturnal hyperglycemia and hyperketonemia in patients using a premeal plus basal insulin regimen.

摘要

目的

与速效胰岛素类似物赖脯胰岛素不同，未修饰的普通胰岛素具有较长的吸收尾段，可能会导致夜间早期发生低血糖。我们进行了一项随机交叉双盲研究，以比较1型糖尿病患者在两个独立研究日，随机顺序接受赖脯胰岛素或未修饰的普通胰岛素后，夜间早期的血糖浓度。

研究设计与方法

我们研究了23例C肽阴性患者；12例采用餐时加基础胰岛素治疗方案，11例采用每日两次胰岛素注射治疗方案。患者于下午5点入住研究单位，晚餐前接受单剂量的赖脯胰岛素或未修饰的普通胰岛素。两组中，中性鱼精蛋白锌胰岛素剂量保持不变。在两个研究日期间，患者在相同时间进食相同的餐食和零食。

结果

与普通胰岛素相比，赖脯胰岛素治疗后的餐后（下午6点至10点）平均血糖浓度显著更低（7.1±0.4[标准误] vs. 8.5±0.4 mmol/L，P = 0.0002）。与普通胰岛素相比，赖脯胰岛素治疗后的夜间（午夜至凌晨4点）血糖浓度显著更高（10.3±0.4 vs. 9.1±0.4 mmol/L，P = 0.02）。这种差异在采用餐时加基础胰岛素治疗方案的患者中最为明显（11.6±0.5 vs. 8.7±0.4 mmol/L，P < 0.001）。与未修饰的胰岛素相比，赖脯胰岛素治疗后的夜间低血糖（午夜至凌晨4点，血糖<3.5 mmol/L）发生率更低（1例 vs. 6例患者，P = 0.04）。在采用餐时加推注胰岛素治疗方案的患者中，与普通胰岛素相比，赖脯胰岛素治疗后的夜间（午夜至凌晨4点）3-羟基丁酸（102±13 vs. 51±7 μmol/L，P = 0.000）和甘油（52±3 vs. 42±2 μmol/L，P < 0.01）显著更高。