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Decrease in gall-bladder surface area, as obtained by ultrasound, was measured in 52 patients with insulin-dependent diabetes (27 with and 25 without autonomic neuropathy) 60 minutes after administration of the bile stimulant Biloptin. The post-stimulation area was 33 +/- 6% of initial value in patients with autonomic neuropathy, and 67 +/- 8% (P less than 0.0005) in those without autonomic neuropathy. Comparison with insulin-dependent chronic diabetics matched for sex, age and duration of illness, demonstrated that heart-rate variability in cholelithiasis was less than in the control subjects (P less than 0.05). It is concluded that autonomic neuropathy, measured by the occurrence of spontaneous vagotomy, in insulin-dependent diabetics is an important risk factor in the overall pathogenesis of cholelithiasis.

Gastric emptying following the ingestion of 200 ml orange juice was investigated sonographically in 24 insulin-dependent diabetics with and without autonomic neuropathy and in 11 control subjects. Furthermore, the relationship between emptying and blood glucose was determined. The duration of gastric emptying in all patients was negatively correlated with the heart rate variation (P less than 0.01) and was longer in patients with autonomic neuropathy than in control subjects or patients without autonomic neuropathy (t1/2 48 +/- 12 min vs. 20 +/- 9 min and 24 +/- 5 min, respectively, P less than 0.0005). The rise in blood glucose was positively correlated with the heart rate variation in all patients (P less than 0.01) and was slower in autonomic neuropathy (1.2 vs. 2.9 mg/dl X min, P less than 0.0005). The delayed carbohydrate absorption in autonomic neuropathy with slower gastric emptying could be important in the management of diabetic patients in whom metabolic control is difficult.