1.
A randomized controlled trial of diet and physical activity in BRCA mutation carriers.
Pasanisi, P, Bruno, E, Manoukian, S, Berrino, F
Familial cancer. 2014;(2):181-7
Abstract
High serum levels of insulin-like growth factor I (IGF-I) are associated with an increased risk of sporadic breast cancer (BC). Furthermore, insulin and markers of insulin resistance, such as abdominal obesity, high blood glucose, high serum testosterone and metabolic syndrome, may affect both BC incidence and prognosis. We hypothesized that all these factors might be relevant also for hereditary BC, due to a deleterious mutation of BRCA genes. Epidemiological observation suggested that weight, energy intake (usually associated with higher bio-availability of growth factors) and physical activity may be relevant in BRCA mutation carriers. Mechanistic studies hypothesized a functional interaction between BRCA genes and the IGF-I system. We have provided some evidence that high serum levels of IGF-I are associated with a significantly increased penetrance. We are recruiting a larger cohort of BRCA mutation carriers in order to test potential modulators of penetrance and prognosis. Within this cohort, we have planned a randomized controlled trial to test whether moderate calorie and protein restriction, together with physical activity, decrease IGF-I. Eligible study subjects are women with or without BC, aged 18-70, with a proven deleterious BRCA mutation, and without metastases. All the women will receive recommendations for the dietary prevention of cancer. The women will be then randomized into an active life-style intervention group and into a control group that will receive only the baseline recommendations. We expect to significantly reduce IGF-I in the intervention group. This trial and the subsequent cohort follow-up might open up primary prevention options for genetic BC.
2.
Insulin-like growth factor I, growth hormone, and insulin sensitivity: the effects of a one-year cholecalciferol supplementation in middle-aged overweight and obese subjects.
Kamycheva, E, Berg, V, Jorde, R
Endocrine. 2013;(2):412-8
Abstract
Both altered GH-IGF-I axis and low serum levels of 25-hydroxyvitamin D (25(OH)D) are linked to measures of metabolic syndrome. Our hypothesis was that there is a relation between GH, IGF-I, and 25(OH)D; and that vitamin D supplementation may have an effect on the levels of GH, IGF-I, and IGF-I/IGFBP-3 ratio. 318 overweight and obese subjects completed a one-year randomized intervention with either 40,000 or 20,000 IU cholecalciferol per week or placebo. GH, IGF-I, IGFBP-3 and measures of insulin resistance were evaluated at baseline and at the end of study. There was a significant relation between entities of GH-IGF-I axis and insulin resistance. Subjects with severe obesity had significantly lower serum 25(OH)D and had a significant linear decline in IGF-I/IGFBP-3 ratio with increasing serum 25(OH)D quartiles. Vitamin D status was an independent predictor of GH-IGF-I axis and supplementation with vitamin D decreased IGF-I/IGFBP-3 ratio in subjects without severe obesity. No corresponding effect of vitamin D supplementation on BMI or insulin resistance was observed. Adverse effects of GH-IGF-I axis on glucose metabolism and the development of metabolic syndrome may be in part associated with the changes in vitamin D status.