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Common genetic determinants of glucose homeostasis in healthy children: the European Youth Heart Study
- Source :
- Diabetes. December 1, 2009, Vol. 58 Issue 12, p2939, 7 p.
- Publication Year :
- 2009
-
Abstract
- OBJECTIVE--The goal of this study was to investigate whether the effects of common genetic variants associated with fasting glucose in adults are detectable in healthy children. RESEARCH DESIGN AND METHODS--Single nucleotide polymorphisms in MTNR1B (rs10830963), G6PC2 (rs560887), and GCK (rs4607517) were genotyped in 2,025 healthy European children aged 9-11 and 14-16 years. Associations with fasting glucose, insulin, homeostasis model assessment (HOMA)-insulin resistance (IR) and HOMA-B were investigated along with those observed for type 2 diabetes variants available in this study (CDKN2A/B, IGF2BP2, CDKAL1, SLC30A8, HHEX-IDE, and Chr 11p12). RESULTS--Strongest associations were observed for G6PC2 and MTNR1B, with mean fasting glucose levels (95% CI) being 0.084 (0.06-0.11) mmol/l, P = 7.9 x [10.sup.-11] and 0.069 (0.04-0.09) mmol/l, P = 1.9 x [10.sup.-7] higher per risk allele copy, respectively. A similar but weaker trend was observed for GCK (0.028 [-0.006 to 0.06] mmol/l, P = 0.11). All three variants were associated with lower β-cell function (HOMA-B P = 9.38 x [10.sup.-5], 0.004, and 0.04, respectively). SLC30A8 (rs13266634) was the only type 2 diabetes variant associated with higher fasting glucose (0.033 mmol/l [0.01-0.06], P = 0.01). Calculating a genetic predisposition score adding the number of risk alleles of G6PC2, MTNR1B, GCK, and SLC30A8 showed that glucose levels were successively higher in children carrying a greater number of risk alleles (P = 7.1 x [10.sup.-17]), with mean levels of 5.34 versus 4.91 mmol/l comparing children with seven alleles (0.6% of all children) to those with none (0.5%). No associations were found for fasting insulin or HOMA-IR with any of the variants. CONCLUSIONS--The effects of common polymorphisms influencing fasting glucose are apparent in healthy children, whereas the presence of multiple risk alleles amounts to a difference of >1 SD of fasting glucose.<br />Diabetes is characterized by chronic hyperglycemia resulting from a defect in insulin secretion by the pancreatic β-cells and/or insulin action in peripheral tissues. Although the exact mechanisms underlying the development [...]
- Subjects :
- Homeostasis -- Genetic aspects -- Physiological aspects -- Research -- Measurement
Children -- Health aspects
Single nucleotide polymorphisms -- Research -- Physiological aspects -- Measurement -- Genetic aspects
Blood sugar -- Measurement -- Control -- Research -- Physiological aspects -- Genetic aspects
Health
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 58
- Issue :
- 12
- Database :
- Gale General OneFile
- Journal :
- Diabetes
- Publication Type :
- Periodical
- Accession number :
- edsgcl.214093332
- Full Text :
- https://doi.org/10.2337/db09-0374