Effects of autonomic neuropathy on glucose, fatty acid, and ketone body metabolism following insulin withdrawal in patients with insulin-dependent diabetes

Abstract

It has been postulated that sympathetic denervation due to autonomic neuropathy may protect against the development of diabetic ketoacidosis in patients with insulin-dependent diabetes. We tested this hypothesis by withdrawing exogenous insulin from five men with established insulin-dependent diabetes and severe symptomatic autonomic neuropathy. Six men also with insulin-dependent diabetes of more than 5-years duration but no clinical evidence of neuropathy served as controls. Normoglycemia was maintained during the night before the study using a variable intravenous insulin infusion that was terminated at 0800 h the following morning (time 0 min). During a 600-min observation period following termination of the insulin infusion the rise (mean ± SEM) in blood glucose concentration between 0 min and 600 min was comparable between the autonomic neuropathy and contol groups (9.2 ± 1.3 versus 8.3 ± 1.1 mmol/L; p > 0.1). The rise in plasma nonesterified fatty acids was significantly less for the autonomic neuropathy patients (0.96 ± 0.06 versus 1.65 ± 0.14 mmol/L; p < 0.01) with a similar trend for the rise in total ketone body concentration (2.74 ± 0.85 versus 3.72 ± 0.38 mmol/L). Capillary pH at 600 min, however, was not significantly different between the groups (23 ± 2 versus 20 ± 1 mmol/L). In conclusion, plasma fatty acids and ketone body concentrations rise less rapidly following withdrawal of insulin in patients with insulin-dependent diabetes and autonomic neuropathy suggesting that such patients may have a degree of protection against the development of diabetic ketoacidosis.