Susceptibility to type 2 diabetes mellitus—from genes to prevention

Abstract

Knowledge of the genetics of type 2 diabetes mellitus (T2DM) has evolved tremendously over the past few years. Following advances in technology and analytical approaches, collaborative case–control genome-wide association studies have revealed up to 65 loci credibly associated with T2DM. Prospective population studies have demonstrated that aggregated genetic risk scores, so-called because they sum the genetic risk attributed to each locus, can predict incident T2DM among individuals of various age ranges and diverse ethnic backgrounds. With each set of T2DM loci discovered, increasing the number of loci in these scores has improved their predictive ability, although a prediction plateau may already have been reached. The current literature shows that intensive lifestyle interventions are effective for preventing T2DM at any level of genetic risk and might be particularly efficacious among individuals with high genetic susceptibility. By contrast, counselling to inform patients about their personal T2DM genetic risk profiles does not seem to improve motivation or attitudes that lead to positive lifestyle behaviour changes. Future studies should investigate the role of genetics for both T2DM prediction and prevention in young populations in the hope of reducing disease burden for future generations.

Association of a 62 Variants Type 2 Diabetes Genetic Risk Score With Markers of Subclinical Atherosclerosis

“…We used an unweighted GRS for non-European ancestry cohorts because most of the T2D SNPs come from GWAS conducted among people of European ancestry. However, weighting has little effect on the GRS 35 , makes models fit slightly better, but does not change the ranking of individuals from low to high risk 15, 35 .…”

“…We have also shown that an additive genetic risk score (GRS 62 ) comprised of 62 validated T2D-associated SNPs 11-14 predicts incident T2D in European and African Americans 15, 16 .…”

Tip 2 diyabetin moleküler genetik temeli; Son gelişmeler

“…Epigenetik deği-şimlerin de T2DM ve onun fenotipik özellikleriyle ilişkili olduğuna dair kanıtların olması, bu alanda da yapılacak araştırmalara ihtiyaç olduğunu ve T2DM tahmini ile ilgili katkı sunabileceğini göstermektedir (124,128,129). (149). Yakın zamanda yapılan bir çalışma, pek çok T2DM lokusunun glukoz homeostazisi üzerindeki potansiyel bozucu etkisinin, yüksek fiziksel aktivite ya da sağlıklı yaşam tarzı davranışları ile ortadan kaldırılabildiğini ya da en azından hafifletilebildiğini veya tam tersi düşük fiziksel aktivite ve batı tarzı diyet faktörle-rinin bu bozucu etkiyi daha da artırabildiğini göstermiş-tir (89).…”

Role of KCNJ11 Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus

“…The PPARG gene is implicated in adipogenesis and the development of insulin resistance. Deleterious mutations in this gene impair insulin resistance and can cause lack of response to insulin 23 . From recent genome-wide association .…”