[HTML][HTML] Systematic evaluation of validated type 2 diabetes and glycaemic trait loci for association with insulin clearance
Diabetologia, 2013•Springer
Aims/hypothesis Insulin clearance is a highly heritable trait, for which few quantitative trait
loci have been discovered. We sought to determine whether validated type 2 diabetes
and/or glycaemic trait loci are associated with insulin clearance. Methods Hyperinsulinaemic–
euglycaemic clamps were performed in two Hispanic-American family cohorts totalling 1329
participants in 329 families. The Metabochip was used to fine-map about 50 previously
identified loci for type 2 diabetes, fasting glucose, fasting insulin, 2 h glucose or HbA 1c. This …
loci have been discovered. We sought to determine whether validated type 2 diabetes
and/or glycaemic trait loci are associated with insulin clearance. Methods Hyperinsulinaemic–
euglycaemic clamps were performed in two Hispanic-American family cohorts totalling 1329
participants in 329 families. The Metabochip was used to fine-map about 50 previously
identified loci for type 2 diabetes, fasting glucose, fasting insulin, 2 h glucose or HbA 1c. This …
Aims/hypothesis
Insulin clearance is a highly heritable trait, for which few quantitative trait loci have been discovered. We sought to determine whether validated type 2 diabetes and/or glycaemic trait loci are associated with insulin clearance.
Methods
Hyperinsulinaemic–euglycaemic clamps were performed in two Hispanic-American family cohorts totalling 1329 participants in 329 families. The Metabochip was used to fine-map about 50 previously identified loci for type 2 diabetes, fasting glucose, fasting insulin, 2 h glucose or HbA1c. This resulted in 17,930 variants, which were tested for association with clamp-derived insulin clearance via meta-analysis of the two cohorts.
Results
In the meta-analysis, 38 variants located within seven loci demonstrated association with insulin clearance (p < 0.001). The top signals for each locus were rs10241087 (DGKB/TMEM195 [TMEM195 also known as AGMO]) (p = 4.4 × 10−5); chr1:217605433 (LYPLAL1) (p = 3.25 × 10−4); rs2380949 (GLIS3) (p = 3.4 × 10−4); rs55903902 (FADS1) (p = 5.6 × 10−4); rs849334 (JAZF1) (p = 6.4 × 10−4); rs35749 (IGF1) (p = 6.7 × 10−4); and rs9460557 (CDKAL1) (p = 6.8 × 10−4).
Conclusions/interpretation
While the majority of validated loci for type 2 diabetes and related traits do not appear to influence insulin clearance in Hispanics, several of these loci do show evidence of association with this trait. It is therefore possible that these loci could have pleiotropic effects on insulin secretion, insulin sensitivity and insulin clearance.
Springer
