Israelian Zarmen, Szoke Ervin, Woerle Juergen, Bokhari Syed, Schorr Manju, Schwenke Dawn C, Cryer Philip E, Gerich John E, Meyer Christian
Department of Endocrinology, Carl T. Hayden VA Medical Center, Phoenix, AZ 85012, and Department of Medicine, University of Rochester School of Medicine, NY 14642, USA.
Metabolism. 2006 May;55(5):593-8. doi: 10.1016/j.metabol.2005.11.013.
In type 2 diabetes mellitus (T2DM), little is known about hormonal responses to hypoglycemia. In particular, beta-cell responses to hypoglycemia have not been carefully investigated and potentially because of confounding factors or insufficient power, conflicting data have been obtained regarding growth hormone responses. We therefore compared hormonal responses including rates of insulin secretion during a 2-hour hyperinsulinemic hypoglycemic clamp in a relatively large number of nondiabetic (n=21) and moderately insulin-deficient subjects with T2DM (homeostasis model assessment of beta-cell function [HOMA-%B], 751+/-160 vs 1144+/-83 [pmol/L]/[mmol/L], P<.04) (n=14) matched for age, sex, and body mass index. Subjects with T2DM were excluded for antecedent hypoglycemia, and baseline glycemia was controlled by a variable infusion of insulin overnight. Although both groups of subjects had indistinguishable plasma glucose levels at baseline and virtually identical levels of plasma insulin and glucose throughout the hypoglycemic clamp, insulin secretion decreased more slowly in the subjects with T2DM. The time required for insulin secretion to decline to half its baseline level was markedly increased (38.9+/-4.9 vs 22.3+/-1.3 minutes [SD], P<.01), and insulin secretion decreased to a lesser extent (-0.79+/-0.17 vs -1.51+/-0.09 [pmol/L]/kg per minute, P<.002). Moreover, responses of glucagon (28.3+/-7.3 vs 52.8+/-7.0 ng/L, P<.05) and growth hormone (2.9+/-0.8 vs 6.3+/-0.9 ng/mL, P<.04) were reduced in the subjects with T2DM, whereas responses of epinephrine, norepinephrine, and cortisol were similar to those in nondiabetic subjects (all P>0.6). We conclude that multiple defects exist in hormonal responses to hypoglycemia in T2DM with moderate beta-cell failure. These include delayed and reduced decreases in insulin secretion, and impaired increases of plasma glucagon and growth hormone.
在2型糖尿病（T2DM）中，关于低血糖时的激素反应知之甚少。特别是，β细胞对低血糖的反应尚未得到仔细研究，可能由于混杂因素或样本量不足，关于生长激素反应的数据存在矛盾。因此，我们比较了在2小时高胰岛素低血糖钳夹试验期间的激素反应，包括胰岛素分泌率，研究对象为相对大量的非糖尿病患者（n = 21）和中度胰岛素缺乏的T2DM患者（β细胞功能稳态模型评估[HOMA-%B]，分别为751±160与1144±83 [pmol/L]/[mmol/L]，P <.04）（n = 14），两组在年龄、性别和体重指数方面相匹配。患有T2DM且有低血糖史的患者被排除，通过夜间可变胰岛素输注控制基线血糖水平。尽管两组受试者在基线时血浆葡萄糖水平无差异，且在低血糖钳夹试验期间血浆胰岛素和葡萄糖水平几乎相同，但T2DM患者的胰岛素分泌下降更缓慢。胰岛素分泌降至基线水平一半所需的时间显著延长（38.9±4.9 vs 22.3±1.3分钟[标准差]，P <.01），且胰岛素分泌下降幅度较小（-0.79±0.17 vs -1.51±0.09 [pmol/L]/kg每分钟，P <.002）。此外，T2DM患者的胰高血糖素反应（28.3±7.3 vs 52.8±7.0 ng/L，P <.05）和生长激素反应（2.9±0.8 vs 6.3±0.9 ng/mL，P <.04）降低，而肾上腺素、去甲肾上腺素和皮质醇的反应与非糖尿病患者相似（所有P>0.6）。我们得出结论，中度β细胞功能衰竭的T2DM患者在低血糖激素反应方面存在多种缺陷。这些缺陷包括胰岛素分泌下降延迟且幅度减小，以及血浆胰高血糖素和生长激素升高受损。
