The Effect of Asymptomatic Nocturnal Hypoglycemia on Glycemic Control in Diabetes Mellitus

Abstract

To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-dependent diabetes mellitus, we studied, on three nights, 10 patients receiving their usual regimens of continuous subcutaneous insulin infusion. During a control night, the patients' mean (±SE) plasma glucose level reached a nadir of 4.5±0.2 mmol per liter at 3 a.m.; the fasting glucose level was 5.9±0.3 mmol per liter at 7:30 a.m., and a peak glucose level of 8.6±0.3 mmol per liter was reached at 10 a.m., after breakfast. During nights two and three, supplemental insulin was infused intravenously from 10 p.m. to 2 a.m. to simulate a clinical overdose of insulin. On these nights, either hypoglycemia (2.4±0.2 mmol per liter) was permitted to occur or a nearly normal glucose level (5.5 mmol per liter) was maintained by infusion of glucose. The subjects were asymptomatic on all three nights. Despite comparable plasma free insulin levels from 4 to 11 a.m., both fasting (7.3±0.2 mmol per liter) and postbreakfast (12.5±0.4 mmol per liter) plasma glucose levels were significantly higher after hypoglycemia than when hypoglycemia was prevented (6.2±0.2 mmol per liter and 8.7±0.4 mmol per liter, respectively; P<0.001 in both cases). Fasting levels of plasma glucose correlated directly with overnight plasma levels of epinephrine (r = 0.78, P<0.001), growth hormone (r = 0.57, P<0.009), and cortisol (r = 0.52, P<0.02) but correlated inversely with the overnight nadir of plasma glucose (r = -0.62, P<0.005).