Sir
Jean Yves Reginster and colleagues
noted no change in glucose homoeostasis, with fasting glucose decreasing slightly in the glucosamine group. We have some concerns about the potential adverse effects of long-term glucosamine therapy on glucose homoeostasis.
The use of fasting glucose as a sole measure of glucose homoeostasis is insufficient, since other features of insulin resistance can arise in the presence of glucose concentrations in the normal range,
and fasting glucose alone does not take into account the ability of pancreatic P cells to secrete insulin upon glucose challenge.
There is growing evidence that glucosamine can lead to defects in glucose homoeostasis–mainly increased insulin resistance and reduced insulin secretion.
Glucosamine infusion in vivo impairs insulin-mediated glucose metabolism in skeletal muscles.
The underlying mechanism is thought to be related to increased insulin resistance by accelerated hexosamine metabolism through the desensitisation of the insulin-responsive glucose transport. Thus, the incoming glucose is routed through the hexosamine pathway with subsequent phosphorylation of fructose-6-phosphate to glucosamine-6-phosphate by hexokinase.
We describe a case to further illustrate the potential effect of glucosamine on glucose homoeostasis.
A man aged 53 years with osteoarthritis and rheumatoid arthritis presented in 1976 with episodes of loss of consciousness, later identified as due to spontaneous hypoglycaemia secondary to an insulinoma in the tail of the pancreas (plasma glucose 2·1 mmol/L, insulin 93·3 pmol/L, C peptide 652 pmol/L). He underwent surgical resection and was discharged with a prescription of diazoxide 100 mg twice daily. In 1983, he developed recurrent episodes of hypoglycaemia and further investigations showed that he had secondary hepatic micrometastases. A trial of somatostatin was ineffective in controlling his hypoglycaemic episodes and he underwent hepatic embolisation on three occasions. Intermittent hypoglycaemia remained at a frequency of one major episode on alternate days, despite treatment with diazoxide 100 mg three times daily and bendroflumethiazide 10 mg once daily.
In 1998, he was started on glucosamine sulphate 500 mg twice daily for osteoarthritis, and his rheumatoid arthritis was inactive (he received no steroid therapy). Since the start of glucosamine therapy, he has had no further major hypoglycaemic episodes and minor episodes have been infrequent (about once a month). Our patient refused to undergo a trial of glucosamine withdrawal for biochemical documentation in fear of further disabling attacks.
Glucosamine sulphate is not a recognised treatment for metastatic insulinoma, but it probably contributed to symptom control in this patient. Given the effect of glucosamine on glucose homoeostasis, glycaemic monitoring is warranted in patients on long-term therapy, and it should be used cautiously in patients with diabetes.
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