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正葡萄糖钳夹中建立高胰岛素平台与否对内源性胰岛素分泌的影响
正葡萄糖钳夹中建立高胰岛素平台与否对内源性胰岛素分泌的影响
刘 辉,喻红玲,柳佳利,李佳琦,谭惠文,余叶蓉

四川大学华西医院,成都 610041
Inhibiting effect of establishment of peripheral hyperinsulinemia on endogenous insulin secretion when using euglycemic clamp technique
(West China Hospital, Sichuan University, Chengdu 610041, China)

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起始页:167

摘要:[摘要] 目的:采用正葡萄糖钳夹技术,比较注射短效胰岛素后,建立或不建立外源性优势胰岛素平台对健康受试者内源性胰岛素分泌的影响。方法:男性健康受试者48例,随机分为A组(高胰岛素正葡萄糖钳夹试验)和B组(正葡萄糖钳夹试验,但不建立高胰岛素平台)。采用正葡萄糖钳夹技术,A组将血糖控制在(4.5±10%) mmol?L-1,B组的靶血糖值为皮下注射胰岛素前-60,-30和-15 min血糖的平均值-10%,比较皮下注射短效胰岛素制剂后1,2,3,4,5,6,7和8 h的血清C肽较给药前下降的百分比及曲线下面积。结果:皮下注射短效胰岛素后,两组的C肽浓度较基线均有不同程度的下降,整个试验过程中内源性胰岛素的分泌均受到不同程度的抑制。两组钳夹在皮下注射短效胰岛素后1~8 h,各点C肽下降百分比的曲线下面积差异无统计学意义[AUC0-1h:(5.6±6.2) min*% vs (8.5±6.5) min*%,P=0.054;AUC0-2h:(14.1±12.5) min*% vs (21.2±14.9) min*%,P=0.097;AUC0-3h:(22.6±18.4) min*% vs (31.6±21.4) min*%,P=0.159;AUC0-4h:(33.7±26.7) min*% vs (39.5±26.8) min*%,P=0.365;AUC0-5h:(49.4±36.6) min*% vs (47.3±31.6) min*%,P=0.875;AUC0-6h:(67.2±45.5) min*% vs (58.8±37.6) min*%,P=0.808;AUC0-7h:(85.4±55.2) min*% vs (70.1±44.2) min*%,P=0.593;AUC0-8h:(108.4±67.5) min*% vs (78.6±49.6) min*%,P=0.353]。结论:皮下注射短效胰岛素制剂后,不建立外源性优势胰岛素平台的正葡萄糖钳夹技术能有效抑制受试者内源性胰岛素的分泌,较真实地反映受试制剂的药动学和药效学特征,试验方法更简便安全,且费时较少。

关键词:[关键词] 正葡萄糖钳夹技术;内源性胰岛素的分泌;药动学;药效学

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Abstract:[Abstract] Objective:To investigate whether euglycemic clamp without hyperinsulinemia can inhibit endogenous insulin secretion after administration of short-action insulin in comparison with euglycemic hyperinsulinemic clamp technique (EHCT) in Chinese healthy male volunteers. Methods:Forty-eight Chinese healthy male volunteers were randomly divided into two groups (group A for EHCT, group B for euglycemic clamp without hyperinsulinemia). The target glucose was kept at (4.5±10%) mmol?L-1 in group A and 10% less than fasting blood-glucose in group B. The decrease percentages of C-peptide at the time of 1,2,3,4,5,6,7 and 8 h after administration and the AUC were compared. Results:C-peptide decreased to different extents compared to its baseline after administration of short-action insulin in both two groups. Endogenous insulin secretion was inhibited to different degrees during the period of glucose clamp in the two groups. The differences of AUC of decline of C-peptide at the time of 1,2,3,4,5,6,7 and 8 h after administration of short-action insulin between group A and B were not statistically significant [AUC0-1h:(5.6±6.2) min*% vs (8.5±6.5)min*%,P=0.054;AUC0-2h:(14.1±12.5) min*% vs (21.2±14.9) min*%,P=0.097;AUC0-3h:(22.6±18.4) min*% vs (31.6±21.4) min*%,P=0.159;AUC0-4h:(33.7±26.7) min*% vs (39.5±26.8) min*%,P=0.365;AUC0-5h:(49.4±36.6) min*% vs (47.3±31.6) min*%,P=0.875;AUC0-6h:(67.2±45.5) min*% vs (58.8±37.6) min*%,P=0.808;AUC0-7h:(85.4±55.2) min*% vs (70.1±44.2) min*%,P=0.593;AUC0-8h:(108.4±67.5) min*% vs (78.6±49.6) min*%,P=0.353]. Conclusion:Euglycemic clamp without hyperinsulinemia can inhibit endogenous insulin secretion after administration of short-action insulin, which may describe the PK/PD characteristics of insulin preparations more accurately, and is more convenient and time-saving.

Key words:[Key words] euglycemic clamp; secretion of endogenous insulin; pharmacokinetics; pharmacodynamics

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