The role of global and regional DNA methylation and histone modifications in glycemic traits and type 2 diabetes: A systematic review.

BACKGROUND: New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition and environmental influences. AIM: To systematically review studies investigating the association between epigenetic marks (DNA methylation and histone modifications) with T2D and glycemic traits (glucose and insulin levels, insulin resistance measured by HOMA-IR). METHOD AND RESULTS: Six bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, PubMed, Cochrane Central and Google Scholar) were screened until 28th August 2015. We included randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined the association between epigenetic marks (global, candidate or genome-wide methylation of DNA and histone modifications) with T2D, glucose and insulin levels and insulin metabolism. Of the initially identified 3879 references, 53 articles, based on 47 unique studies met our inclusion criteria. Overall, data were available on 10,823 participants, with a total of 3358 T2D cases. There was no consistent evidence for an association between global DNA-methylation with T2D, glucose, insulin and insulin resistance. The studies reported epigenetic regulation of several candidate genes for diabetes susceptibility in blood cells, muscle, adipose tissue and placenta to be related with T2D without any general overlap between them. Histone modifications in relation to T2D were reported only in 3 observational studies. CONCLUSIONS AND RELEVANCE: Current evidence supports an association between epigenetic marks and T2D. However, overall evidence is limited, highlighting the need for further larger-scale and prospective investigations to establish whether epigenetic marks may influence the risk of developing T2D.

Protein intake in early childhood and body composition at the age of 6 years: The Generation R Study.

BACKGROUND: Previous studies suggest that high protein intake in infancy leads to a higher body mass index (BMI) in later childhood. We examined the associations of total, animal and vegetable protein intake in early childhood with detailed measures of body composition at the age of 6 years. METHODS: This study was performed in 2911 children participating in a population-based cohort study. Protein intake at the age of 1 year was assessed with a validated food-frequency questionnaire and was adjusted for total energy intake. At the children's age of 6 years, we measured their anthropometrics and body fat (with dual-energy X-ray absorptiometry). We calculated age- and sex-specific s.d. scores for BMI, fat mass index (FMI) and fat-free mass index (FFMI). RESULTS: After adjustment for confounders, a 10 g per day higher total protein intake at 1 year of age was associated with a 0.05 s.d. (95% confidence interval (CI) 0.00, 0.09) higher BMI at age 6. This association was fully driven by a higher FMI (0.06 s.d. (95%CI 0.01, 0.11)) and not FFMI (-0.01 s.d. (95%CI -0.06, 0.05)). The associations of protein intake with FMI at 6 years remained significant after adjustment for BMI at the age of 1 year. Additional analyses showed that the associations of protein intake with FMI were stronger in girls than in boys (P for interaction=0.03), stronger among children who had catch-up growth in the first year of life (P for interaction<0.01) and stronger for intake of animal protein (both dairy and non-dairy protein) than protein from vegetable sources. CONCLUSIONS: Our results suggest that high protein intake in early childhood is associated with higher body fat mass, but not fat-free mass. Future studies are needed to investigate whether these changes persist into adulthood and to examine the optimal range of protein intake for infants and young children.