Effects of differing durations of antecedent hypoglycemia on counterregulatory responses to subsequent hypoglycemia in normal humans
Effects of differing durations of antecedent hypoglycemia on counterregulatory responses to subsequent hypoglycemia in normal humans
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DOI：
10.2337/diabetes.49.11.1897
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发表时间：
2000-11-01
期刊：
影响因子：
7.7
通讯作者：
Costa, F
中科院分区：
文献类型：
--
作者：
Davis, SN;Mann, S;Costa, F
这项研究的目的是确定前驱低血糖持续时间是否调节随后反调节失败的程度。研究对象为31名夜间禁食的健康瘦人(男16人，女15人)。有15名受试者(8名男性/7名女性)接受了两个独立的为期2天的随机试验，间隔至少2个月。在第1天，2-h高胰岛素血症(9pmol.Kg(-1)。分别于上午和下午行正血糖(5.2+/-0.1mmo1/L)或低血糖(2.9+/-0.1 mmo1/L)葡萄糖钳夹(持续低血糖)。在其他受试者中，16人参加了为期两天的研究，其中第一天包括上午和下午的短期低血糖实验(低血糖最低点为2.9+/-0.1 mmol，持续5分钟)，其中10人接受了另外一项为期两天的研究，其中第一天包括上午和下午的中段低血糖(低血糖最低点2.9+/-0.1 mmol，持续30分钟)。次日清晨(第2天)，所有受试者再进行2 h高胰岛素-低血糖钳夹(2.9+/-0.1 mm o l/L)，在所有降糖试验中严格控制血糖下降速率(0.0 7 m o l/m in)，使血糖在30m in时达到最低点。尽管第二天的血糖和胰岛素水平相同，但在反调节生理反应方面存在显著差异。持续时间不同的第1天低血糖与第1天正常血糖相比，稳态肾上腺素、胰升糖素、生长激素、皮质醇和胰腺多肽水平同样显著降低(P<；0.01)，肌肉交感神经活动和内源性葡萄糖产生也同样因第1天低血糖(相对于第1天正常血糖)而减弱(P<；0.01)，第2天低血糖症状显著减轻CP<；0.01)在第1天持续中期低血糖后，但不是短期低血糖后，两次持续时间较短的中度低血糖可以显著抑制关键的神经内分泌和代谢调节反应。持续较长时间的低血糖可降低低血糖症状评分，但不是短期低血糖。我们的结论是，在健康的隔夜禁食人群中，1)神经内分泌、自主神经系统和代谢反调节反应对即使是短暂的先前低血糖的钝化效应也很敏感，2)先前低血糖的持续时间导致了一系列钝化的生理反应，低血糖症状意识比神经内分泌反应更不容易受到影响。
The aim of this study was to determine whether the duration of antecedent hypoglycemia regulates the magnitude of subsequent counterregulatory failure. A total of 31 lean healthy overnight-fasted individuals (16 men/15 women) were studied. There were 15 subjects (8 men/7 women) who underwent two separate 2-day randomized experiments separated by at least 2 months. On day 1, 2-h hyperinsulinemic (9 pmol . kg(-1) . min(-1)) euglycemic (5.2 +/- 0.1 mmol/l) or hypoglycemic (2.9 +/- 0.1 mmol/l) glucose clamps (prolonged hypoglycemia) were carried out in the morning and afternoon. Of the other subjects, 16 participated in a 2-day study in which day 1 consisted of morning and afternoon short-duration hypoglycemia experiments (hypoglycemic nadir of 2.9 +/- 0.1 mmol for 5 min), and 10 of these individuals underwent an additional 2-day study in which day 1 consisted of morning and afternoon intermediate-duration hypoglycemia (hypoglycemic nadir of 2.9 +/- 0.1 mmol for 30 min). The next morning (day 2) all subjects underwent an additional 2-h hyperinsulinemic-hypoglycemic clamp (2.9 +/- 0.1 mmol/l), The rate of fall of glucose (0.07 mmol/min) was carefully controlled during all hypoglycemic studies so that the glucose nadir was reached at 30 min. Despite equivalent day 2 plasma glucose and insulin levels, there were significant differences in counterregulatory physiological responses. Steady-state epinephrine, glucagon, growth hormone, cortisol, and pancreatic polypeptide levels were similarly significantly blunted (P < 0.01) by the differing duration day 1 hypoglycemia compared with day 1 euglycemia, Muscle sympathetic nerve activity and endogenous glucose production were also similarly blunted (P < 0.01) by day 1 hypoglycemia (relative to day 1 euglycemia), Day 2 hypoglycemic symptoms were significantly reduced CP < 0.01) after day 1 prolonged intermediate- but not short-duration hypoglycemia, In summary, two episodes of short-duration moderate hypoglycemia can produce significant blunting of key neuroendocrine and metabolic counterregulatory responses. Hypoglycemic symptom scores are reduced by prolonged but not short-duration prior hypoglycemia. We conclude that in healthy overnight fasted humans, 1) neuroendocrine, autonomic nervous system, and metabolic counterregulatory responses are sensitive to the blunting effects of even short-duration prior hypoglycemia, and 2) the duration of antecedent hypoglycemia results in a hierarchy of blunted physiological responses with hypoglycemic symptom awareness less vulnerable than neuroendocrine responses.