Rare Cancer Syndrome Linked to Lower Diabetes Risk

Patients with PTEN mutations have greater insulin sensitivity but are also more likely to be obese

WEDNESDAY, Sept. 12 (HealthDay News) -- People with Cowden syndrome, with tumor-suppressor phosphatase and tensin homologue (PTEN) mutations that increase their risk of cancer, have enhanced sensitivity to insulin even though they are more likely to be obese, according to a study published in the Sept. 13 issue of the New England Journal of Medicine.

Noting that the PTEN gene is important in cellular growth and metabolic signaling, Aparna Pal, M.R.C.P., from the University of Oxford in the United Kingdom, and colleagues examined insulin sensitivity and beta-cell function in 15 patients with Cowden syndrome (with loss-of-function PTEN mutations) and 15 matched controls. In addition, insulin signaling was measured from muscle and adipose-tissue biopsy specimens in five mutation carriers and five matched controls. Anthropometric indexes were compared between the 15 patients and 2,097 healthy adults from a population-based study.

The researchers found that PTEN mutation carriers had significantly lower measures of insulin resistance based on mean fasting plasma insulin levels and glucose infusion rate after hyperinsulinemic euglycemic clamping, which correlated with increased insulin signaling. Comparison with a population of healthy adults showed that PTEN mutation carriers were significantly more likely to be obese based on body mass index due to increased adiposity, without affecting fat distribution.

"We demonstrate an apparently divergent effect of PTEN mutations: increased risks of obesity and cancer but a decreased risk of type 2 diabetes owing to enhanced insulin sensitivity," Pal and colleagues conclude.

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