Seven insulin‐dependent patients without β‐cell function and eight with residual β‐cell function (evaluated by C‐peptide values 6 min after 1 mg of glucagon i.v.; mean 0·23, range 0·16–0·43 nmol/1) were studied during 12 h of insulin deprivation following maintenance of near‐normoglycaemia with intravenous insulin infusion. Significant differences between the two groups were found in blood glucose and 3‐hydroxybutyrate already after 3 and 4 h respectively. After 12 h the mean blood glucose concentration had reached 17·2 · SEM 1·3 mmol/l in the first group compared with 8·8 ± 1·4 mmol/l in the second group (P < 0·01) while 3‐hydroxybutyrate concentrations rose to 5·5 ± 0·5 mmol/l and 1·4±0·3 mmol/l in the two groups respectively (P<0·01).

The free insulin concentration in plasma was three‐fold higher in the group without β‐cell function just before discontinuing the insulin infusion as compared with the group with β‐cell function (P<0·05). During the first 10 h of insulin deprivation no significant difference in free insulin concentration was found between the two groups. However, after 12 h of insulin deprivation all the patients with residual β‐cell function had measurable amounts of free insulin in peripheral blood, whereas in the C‐peptide negative group only the three patients with the highest amount of insulin binding antibodies had measurable free insulin concentrations.

Glucagon concentrations although raised after 5 h of insulin deprivation were similar in the two groups.

Mean growth hormone concentrations were higher throughout the study in the C‐peptide negative patients, while cortisol levels were significantly higher (P<0·05) after 6 h. For all the patients final cortisol concentrations were directly correlated to final blood glucose (r=0·45, P<0·05) and final blood 3‐hydroxybutyrate (r=0·67, P<0·02).

The present study supports the metabolic importance of portal insulin supply to the liver and thus of residual β‐cell function. The data emphasizes the importance of the often minimal endogenous insulin reserve preserved in some insulin dependent diabetics in protection against rapid development of ketoacidosis both directly and through effects on cortisol and growth hormone secretion.