Abstract
Aims Circulating insulin-like growth factor- (IGF-) 1, vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) levels are often lower in individuals with diabetes mellitus (DM) and are important for repairing vascular and neuronal dysfunction. The purpose of this investigation was to determine the cross-sectional relations of physical activity to circulating concentrations of IGF-1, VEGF, and BDNF in individuals with and without DM. Methods In 1730 participants from the Framingham Offspring Study examination cycle 7, including those with DM (n = 179, mean age 64 years, 39% women) and without DM (n = 1551, mean age 60 years, 46% women), we related self-reported physical activity variables to circulating concentrations of IGF-1, VEGF, and BDNF using linear multivariable regression models. We also tested for interactions by age. Participants with prevalent cardiovascular disease, stroke, and dementia or taking hormone replacement therapy were excluded. Results In participants with DM, more ambulatory physical activity was associated with higher IGF-1 levels (β ± standard error (SE) = 0.22 ± 0.08, p = 0.009), and more total physical activity was related to higher BDNF levels (β ± SE = 0.18 ± 0.08, p = 0.035), but physical activity was not significantly related to circulating VEGF. In participants without DM, no associations were observed. Moreover, in the examination of interactions by age, the association of ambulatory physical activity with IGF-1 levels was only observed in older adults with DM (age ≥ 60 years, β ± SE = 0.23 ± 0.11, p = 0.042) but not in middle-aged adults with DM (age < 60 years, β ± SE = 0.06 ± 0.13, p = 0.645). Conclusion Our results suggest that more physical activity is associated with higher circulating IGF-1 and BDNF in participants with DM. These results, dissecting interactions by both age and DM status, may also help to explain some of the inconsistent results in studies relating physical activity to growth and neurotrophic factors.
Highlights
Individuals with diabetes mellitus (DM) have a higher burden of vascular and neurological damage than healthy individuals, potentially explaining increased rates of cardiovascular disease and cognitive decline in DM patients [1,2,3,4]
In our Framingham Offspring Study, in a community setting, our findings were threefold: firstly, in persons with DM, we observed that greater physical activity was associated with higher circulating insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF) levels; secondly, the association with insulin-like growth factor- (IGF-)1 was only significant in older adults (≥60 years) with DM; and no significant relations were observed in adults without DM
Inactivity may be harmful in individuals with DM because exercise programs are one of the major lifestyle interventions available to reduce DM complications [6, 9]. It is unclear whether growth and neurotrophic factors modulate the beneficial effect of physical activity in individuals with DM, but we present evidence to suggest that physical activity was more strongly related to circulating IGF-1 and BDNF levels in individuals with DM, even after adjusting for covariates and potential confounders
Summary
Individuals with diabetes mellitus (DM) have a higher burden of vascular and neurological damage than healthy individuals, potentially explaining increased rates of cardiovascular disease and cognitive decline in DM patients [1,2,3,4]. Growth factors with angiogenic and neurotrophic properties (such as insulin-like growth factor- (IGF-) 1, vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF)) are implicated in vascular and neurological repair in both animal and human studies [11,12,13]. Human exercise intervention studies have demonstrated an increase in circulating levels of IGF-1, VEGF, and BDNF [7, 16,17,18], more consistently in older adults [7, 19] compared to younger populations [8, 19,20,21]. It will be important to understand whether the association of exercise and physical activity with growth and neurotrophic factors may be higher in other populations with high vascular or neurological dysfunction, such as in persons with DM
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