Burge M R, Hardy K J, Schade D S
Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87131-5271.
J Clin Endocrinol Metab. 1993 May;76(5):1192-8. doi: 10.1210/jcem.76.5.8496310.
To determine the etiology of euglycemic ketoacidosis, the effect of a 32-h fast on the rate of metabolic deterioration was examined in a group of 10 healthy subjects with type I diabetes mellitus. Patients were studied during 5 h of insulin withdrawal after 8 h (postprandial) and 32 h (fasted) of food deprivation. Study parameters included substrate levels, electrolytes, counterregulatory hormone levels, and rates of glucose and glycerol turnover. In the fasted state, mean peak plasma glucose concentrations were significantly lower than those in the 8-h postprandial state (13.3 +/- 1.6 vs. 17.4 +/- 1.4 mmol/L, respectively; P < 0.05), and mean rates of glucose production were also significantly lower at all time points in the fasting state. The rate of development of ketosis was significantly more rapid during insulin deficiency after a fast (8.82 +/- 0.63 vs. 6.23 +/- 0.30 micro/L.min; P < 0.05), while plasma nonesterified fatty acids and glycerol turnover showed a biphasic response to insulin withdrawal, which was also more robust after a fast. Metabolic acidosis, as reflected in the rate of decrease in serum bicarbonate concentration, was more severe after 32 h of fasting than in the postprandial state (mean nadir, 15.4 +/- 0.9 vs. 18.6 +/- 0.5 mmol/L; P < 0.001). In contrast to values in the postprandial state, serum glucagon levels rose during insulin withdrawal in the fasting state, and plasma norepinephrine levels also correlated positively with the ongoing metabolic decompensation. Other counterregulatory hormones did not differ significantly in the fasted vs. postprandial states in these short term metabolic studies. We conclude that a fast of moderate duration, such as might be expected to occur during the development of diabetic ketoacidosis, predisposes patients with type I diabetes to euglycemic ketoacidosis during periods of insulin deficiency. Furthermore, decreased rates of hepatic glucose production are responsible for the lower plasma glucose values observed during a fast. The development of ketosis continued progressively in both conditions, but the rate of rise of plasma ketones was increased in the fasted state. This accelerated development of ketosis may be attributable to the effects of elevated levels of glucagon and/or catecholamines on lipolysis.
为确定正常血糖性酮症酸中毒的病因，在一组10名患有I型糖尿病的健康受试者中，研究了32小时禁食对代谢恶化速率的影响。在进食8小时（餐后）和32小时（禁食）后停药胰岛素5小时期间对患者进行研究。研究参数包括底物水平、电解质、反调节激素水平以及葡萄糖和甘油周转率。在禁食状态下，平均血浆葡萄糖峰值浓度显著低于8小时餐后状态（分别为13.3±1.6与17.4±1.4 mmol/L；P<0.05），并且在禁食状态下所有时间点的葡萄糖生成平均速率也显著更低。禁食后胰岛素缺乏期间酮症的发展速率明显更快（8.82±0.63与6.23±0.30微升/分钟；P<0.05），而血浆非酯化脂肪酸和甘油周转率对胰岛素停药呈现双相反应，禁食后这种反应也更强烈。如血清碳酸氢盐浓度下降速率所反映的代谢性酸中毒，在禁食32小时后比餐后状态更严重（平均最低点，15.4±0.9与18.6±0.5 mmol/L；P<0.001）。与餐后状态的值相反，禁食状态下胰岛素停药期间血清胰高血糖素水平升高，并且血浆去甲肾上腺素水平也与正在进行的代谢失代偿呈正相关。在这些短期代谢研究中，其他反调节激素在禁食与餐后状态之间没有显著差异。我们得出结论，中等时长的禁食，如在糖尿病酮症酸中毒发展过程中可能预期发生的那样，使I型糖尿病患者在胰岛素缺乏期间易发生正常血糖性酮症酸中毒。此外，肝葡萄糖生成速率降低是禁食期间观察到的较低血浆葡萄糖值的原因。在两种情况下酮症的发展都持续进展，但禁食状态下血浆酮体的上升速率增加。这种酮症的加速发展可能归因于胰高血糖素和/或儿茶酚胺水平升高对脂肪分解的影响。
