Leukocyte telomere length is associated with elevated plasma glucose and HbA1c in young healthy men independent of birth weight

LG Grunnet, K Pilgaard, A Alibegovic, CB Jensen, L Hjort, Susan Ozanne, Martin Bennett, A Vaag, C Brøns, Apollo-University Of Cambridge Repository, Apollo-University Of Cambridge Repository
telomeres are protein-bound regions of repetitive nucleotide sequences (ttAGGG) at the end of human chromosomes, and their length is a marker of cellular aging. Intrauterine growth restriction is associated with shorter blood cell telomeres at birth and individuals with type 2 diabetes have shorter telomeres. Individuals with a low birth weight (LBW) have an increased risk of metabolic disease and type 2 diabetes. Therefore, we aimed to investigate the relationship between birth weight and
more » ... ere length and the association between birth weight, telomere length and cardiometabolic phenotype in adulthood. Young, healthy men with LBW (n = 55) and normal birth weight (NBW) (n = 65) were examined including blood pressure, blood samples and body composition. Leukocyte telomere length was determined using a high-throughput qPCR method. The LBW men were more insulin resistant as determined by the HOMA-IR index. There was no difference in telomere length between LBW and NBW subjects. When adjusting for birth weight and cohort effect, significant negative associations between telomere length and fasting glucose (p = 0.003) and HbA1c (P = 0.0008) were found. In conclusion, no significant difference in telomere length was found between LBW and NBW men. The telomere length was negatively associated with glucose concentrations and HbA1c levels within the normal non-diabetic range independent of birth weight. Telomeres are protein-bound regions of repetitive nucleotide sequences (TTAGGG) at the end of human chromosomes. They maintain genomic stability by protecting the ends of the chromosome from deterioration 1 . DNA damage responses are activated when telomeres are shortened to a critical length, causing cellular senescence. Telomeres are longest at birth and shorten in most somatic cells postnatally due to both cell division and oxidative stress 2 . In telomerase negative cells telomere shortening is irreversible and thus telomere length can be used as a biomarker for biological cellular aging 3 . In support of this, a number of studies have demonstrated that telomere shortening is affected by cell age 4,5 . Shorter telomeres have also been associated with a number of factors including male gender 6 , Caucasian race 4 , inflammation 7 , body composition and markers of glucose metabolism 8 . Results from a meta-analysis indicate that shortened leucocyte relative telomere length is significantly associated with type 2 diabetes and leucocyte telomere length with stroke and myocardial infarction 9,10 . Early-life environmental exposures impact on risk of developing cardiometabolic disease later in life as suggested by Hales and Barker 11 . It has been shown that fetal undernutrition resulting in a low birth weight (LBW) for gestational age, gives rise to a phenotype associated with increased risk of type 2 diabetes and cardiovascular
doi:10.17863/cam.41857 fatcat:fxuso2ujpbbbjowmg357gfsooq