Glucose is the major source of energy in humans, with levels in vivo determined by a balance of glucose absorption via the gut, production primarily by the liver, and utilization by both insulin-sensitive and insulin-insensitive tissues. Blood and plasma fasting glucose levels are tightly regulated within a narrow physiologic range by a feedback mechanism that targets a particular fasting glucose set point for each individual. Within healthy, nondiabetic populations there is substantial variation in fasting glucose levels. Approximately one-third of this variation is genetic. Disruption of normal glucose homeostasis and substantial elevations of fasting glucose are hallmarks of type 2 diabetes (T2D) and typically result from sustained reduction in pancreatic beta-cell function and insulin secretion (summary by Chen et al., 2008 and Prokopenko et al., 2009).
Genetic Heterogeneity
Genetic loci influencing fasting plasma glucose have been identified on 2q24-q32 (FGQTL1), related to single-nucleotide polymorphisms (SNPs) in the vicinity of the G6PC2 gene (608058); on 7p15-p13 (FGQTL2; 613219), related to SNPs in the vicinity of the glucokinase gene (GCK; 138079); on 11q21-q22 (FGQTL3; 613233), related to SNPs in the vicinity of the MTNR1B gene (600804); on 7p21.2 (FGQTL4; 613462), in the vicinity of the DGKB gene (604070); on 2p23.3-p23.2 (FGQTL5; 613463) due to variation in the GCKR gene (600842); and on 3q21 (FGQTL6; 613460), in the vicinity of the ADCY5 gene (600293).
See 613219 for a discussion of birth weight as a quantitative trait, another glycemic-influenced trait with an effect on T2D risk. See also 606035 for a discussion of a fasting insulin quantitative trait locus on chromosome 6q22-q24. [from
OMIM]