TY - JOUR
T1 - Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A and MTNR1B affect different aspects of pancreatic beta cell function
AU - Bik-Simonis, A.M.C.
AU - Nijpels, M.G.A.A.M.
AU - van Haeften, T.
AU - Houwing-Duistermaat, J.J.
AU - Boomsma, D.I.
AU - Reiling, E.
AU - van Hove, E.C.
AU - Diamant, M.
AU - Kramer, M.H.H.
AU - Heine, R.J.
AU - Maassen, J.A.
AU - Slagboom, P.E.
AU - Willemsen, G.
AU - Dekker, J.M.
AU - Eekhoff, E.M.W.
AU - de Geus, E.J.C.
AU - Hart, L.M.
PY - 2010
Y1 - 2010
N2 - OBJECTIVE - Recently, results from a meta-analysis of genome-wide association studies have yielded a number of novel type 2 diabetes loci. However, conflicting results have been published regarding their effects on insulin secretion and insulin sensitivity. In this study we used hyperglycemic clamps with three different stimuli to test associations between these novel loci and various measures of β-cell function. RESEARCH DESIGN AND METHODS - For this study, 336 participants, 180 normal glucose tolerant and 156 impaired glucose tolerant, underwent a 2-h hyperglycemic clamp. In a subset we also assessed the response to glucagon-like peptide (GLP)-1 and arginine during an extended clamp (n = 123). All subjects were genotyped for gene variants in JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, THADA, ADAMTS9, NOTCH2/ADAMS30, DCD, VEGFA, BCL11A, HNF1B, WFS1, and MTNR1B. RESULTS - Gene variants in CDC123/CAMK1D, ADAMTS9, BCL11A, and MTNR1B affected various aspects of the insulin response to glucose (all P < 6.9 × 10-3). The THADA gene variant was associated with lower β-cell response to GLP-1 and arginine (both P < 1.6 × 10
AB - OBJECTIVE - Recently, results from a meta-analysis of genome-wide association studies have yielded a number of novel type 2 diabetes loci. However, conflicting results have been published regarding their effects on insulin secretion and insulin sensitivity. In this study we used hyperglycemic clamps with three different stimuli to test associations between these novel loci and various measures of β-cell function. RESEARCH DESIGN AND METHODS - For this study, 336 participants, 180 normal glucose tolerant and 156 impaired glucose tolerant, underwent a 2-h hyperglycemic clamp. In a subset we also assessed the response to glucagon-like peptide (GLP)-1 and arginine during an extended clamp (n = 123). All subjects were genotyped for gene variants in JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, THADA, ADAMTS9, NOTCH2/ADAMS30, DCD, VEGFA, BCL11A, HNF1B, WFS1, and MTNR1B. RESULTS - Gene variants in CDC123/CAMK1D, ADAMTS9, BCL11A, and MTNR1B affected various aspects of the insulin response to glucose (all P < 6.9 × 10-3). The THADA gene variant was associated with lower β-cell response to GLP-1 and arginine (both P < 1.6 × 10
U2 - https://doi.org/10.2337/db09-1048
DO - https://doi.org/10.2337/db09-1048
M3 - Article
C2 - 19833888
SN - 0012-1797
VL - 59
SP - 293
EP - 301
JO - Diabetes
JF - Diabetes
IS - 1
ER -