Supervised 72 h fast is historically the gold standard screen for spontaneous hypoglycaemia. Consensus guidelines published in 2009 suggested that β-hydroxy-butyrate levels be measured every 6 h, and the glucose response to an i.v. injection of glucagon be assessed at the time of documented hypoglycaemia, or at the end of the 72 h fast. We incorporated these recommendations into our protocol, and here examine the results of the first 10 cases.
A rise in plasma β-hydroxy-butyrate levels ≥2.7 mmol/l may be interpreted as a surrogate for hypoinsulinaemia. During the 72 h fast period, all 10 patients in whom hypoglycaemia was ultimately excluded exhibited a rise in plasma β-hydroxy-butyrate levels. By the end of the fast, 50% had plasma β-hydroxy-butyrate levels ≥2.7 mmol/l indicating that their fasts could have been terminated earlier. Twenty percent had levels of 2.6 mmol/l and 30% were <2 mmol/l. We interpret the rise to confirm adherence to the fast, but patients in whom levels remain <2.7 mmol/l require the fast to continue.
This entire cohort also underwent glucagon stimulation at the end of the negative fast. No serious adverse reactions were reported, though nausea and flushing were common, and the challenge also prolonged the total test period. In the presence of hypoglycaemia, a rise in glucose by more than 1.4 mmol/l (25 mg/dl) in response to glucagon is consistent with insulin or IGF mediated hypoglycaemia. A smaller rise is found in normal subjects, and hypoglycaemia of other mechanisms. Hundred percent patients demonstrated a rise <1.4 mmol/l in this study.
We suggest that serial monitoring of plasma β-hydroxy-butyrate levels during a fast may allow premature termination of the fast if levels >2.7 mmol/l, and confirms adherence to the fast when spontaneous hypoglycaemia is not confirmed. However, glucagon challenge at the end of a negative fast adds little to the interpretation, and is unnecessary.