Details

Autor(en) / Beteiligte

• Ren, Jie
• Xiang, Anny H.
• Trigo, Enrique
• Takayanagi, Miwa
• Beale, Elizabeth
• Lawrence, Jean M.
• Hartiala, Jaana
• Richey, Joyce M.
• Allayee, Hooman
• Buchanan, Thomas A.
• Watanabe, Richard M.

Titel

Genetic variation in MTNR1B is associated with gestational diabetes mellitus and contributes only to the absolute level of beta cell compensation in Mexican Americans

Ist Teil von

• Diabetologia, 2014-07, Vol.57 (7), p.1391-1399

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Aims/hypothesis MTNR1B is a type 2 diabetes susceptibility locus associated with cross-sectional measures of insulin secretion. We hypothesised that variation in MTNR1B contributes to the absolute level of a diabetes-related trait, temporal rate of change in that trait, or both. Methods We tested rs10830963 for association with cross-sectional diabetes-related traits in up to 1,383 individuals or with rate of change in the same phenotypes over a 3–5 year follow-up in up to 374 individuals from the family-based BetaGene study of Mexican Americans. Results rs10830963 was associated cross-sectionally with fasting glucose ( p  = 0.0069), acute insulin response (AIR; p  = 0.0013), disposition index ( p  = 0.00078), glucose effectiveness ( p  = 0.018) and gestational diabetes mellitus (OR 1.48; p  = 0.012), but not with OGTT 30 min Δinsulin (the difference between the 30 min and fasting plasma insulin concentration) or 30 min insulin-based disposition index. rs10830963 was also associated with rate of change in fasting glucose ( p  = 0.043), OGTT 30 min Δinsulin ( p  = 0.01) and AIR ( p  = 0.037). There was no evidence for an association with the rate of change in beta cell compensation for insulin resistance. Conclusions/interpretation We conclude that variation in MTNR1B contributes to the absolute level of insulin secretion but not to differences in the temporal rate of change in insulin secretion. The observed association with the rate of change in insulin secretion reflects the natural physiological response to changes in underlying insulin sensitivity and is not a direct effect of the variant.