ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 11 P488

Multiple Endocrine Neoplasia Type 1 (MEN 1) is associated with insulin resistance and an increased prevalence of diabetes and impaired fasting glucose

RW McCallum1, V Parameswaran2 & JR Burgess2

1Western Infirmary, Glasgow, Lanarkshire, United Kingdom; 2Royal Hobart Hospital, Hobart, Tasmania, Australia.

MEN 1 is an autosomal dominant syndrome associated with benign and malignant neuroendocrine neoplasia. It is characterised by primary hyperparathyroidism, pituitary neoplasia and foregut lineage neuroendocrine tumours. It has also been associated with premature cardiovascular death. Since diabetes is associated with an increased risk of cardiovascular mortality we investigated the prevalence of diabetes (DM) and impaired fasting glucose (IFG) in a large cohort of patients with MEN 1.

Methods: Records for MEN 1 gene positive and gene negative siblings (control) in Tasmania were reviewed. 72 MEN 1 and 133 control patients were eligible for inclusion. Fasting glucose and insulin were compared between groups using WHO criteria. All MEN 1 patients had received evaluation of parathyroid, enteropancreatic and pituitary neoplasia by structural imaging and endocrine testing.

Results: 13 (18.1%) patients with MEN 1 compared to 5 (3.8%) control patients were diabetic. 6 (8.3%) patients had IFG compared to 4 (3%) of controls. The age of onset of IFG or DM in MEN 1 was younger than in the control group (49.6±2.56 v. 56.03±5.85 years). Glucose/Insulin ratio was reduced in MEN 1 patients compared to controls with DM/IFG (0.72±0.24 v.1.04±0.41). MEN 1 patients with DM/IFG had a significantly higher gastrin (P<0.05) and elevated PP, GIP and CgA (but not glucagon) and were more likely to have a history of pancreatic lesions than patients with normal glucose tolerance.

Discussion: Compared to controls there is a 4 and 2.5 fold greater prevalence of diabetes and IFG respectively in MEN 1. It is possible that insulin resistance may be induced by circulating pancreatic cytokines associated with gastrin hypersecretion. We suggest MEN1 patients may have an increased cardiovascular risk because of diabetes and IFG and should be screened and managed for metabolic risk factors.

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