TY - JOUR
T1 - Fasting and oral glucose-stimulated levels of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are highly familial traits
AU - Gjesing, Anette Marianne Prior
AU - Ekstrøm, Claus Thorn
AU - Eiberg, Hans Rudolf Lytchoff
AU - Urhammer, S.A.
AU - Holst, Jens Juul
AU - Pedersen, Oluf
AU - Hansen, Teis
PY - 2012/5
Y1 - 2012/5
N2 - Aims/hypothesis Heritability estimates have shown a varying degree of genetic contribution to traits related to type 2 diabetes. Therefore, the objective of this study was to investigate the familiality of fasting and stimulated measures of plasma glucose, serum insulin, serum C-peptide, plasma glucose-dependent insulinotropic polypeptide (GIP) and plasma glucagon-like peptide-1 (GLP-1) among nondiabetic relatives of Danish type 2 diabetic patients. Methods Sixty-one families comprising 193 non-diabetic offspring, 29 non-diabetic spouses, 72 non-diabetic relatives (parent, sibling, etc.) and two non-related relatives underwent a 4 h 75 g OGTT with measurements of plasma glucose, serum insulin, serum C-peptide, plasma GIP and plasma GLP-1 levels at 18 time points. Insulin secretion rates (ISR) and beta cell responses to glucose, GIP and GLP-1 were calculated. Familiality was estimated based on OGTTderived measures. Results A high level of familiality was observed during the OGTT for plasma levels of GIP and GLP-1, with peak familiality values of 74±16% and 65±15%, respectively (h2±SE). Familiality values were lower for plasma glucose, serum insulin and serum C-peptide during the OGTT (range 8-48%, 14-44% and 15-61%, respectively). ISR resented the highest familiality value at fasting reaching 59±16%. Beta cell responsiveness to glucose GLP-1 and GIP also revealed a strong genetic influence, with peak familiality estimates of 62±13%, 76±15% and 70±14%, respectively. Conclusions/interpretation Our results suggest that circulating levels of GIP and GLP-1 as well as beta cell response to these incretins are highly familial compared with more commonly investigated measures of glucose homeostasis such as fasting and stimulated plasma glucose, serum insulin and serum C-peptide.
AB - Aims/hypothesis Heritability estimates have shown a varying degree of genetic contribution to traits related to type 2 diabetes. Therefore, the objective of this study was to investigate the familiality of fasting and stimulated measures of plasma glucose, serum insulin, serum C-peptide, plasma glucose-dependent insulinotropic polypeptide (GIP) and plasma glucagon-like peptide-1 (GLP-1) among nondiabetic relatives of Danish type 2 diabetic patients. Methods Sixty-one families comprising 193 non-diabetic offspring, 29 non-diabetic spouses, 72 non-diabetic relatives (parent, sibling, etc.) and two non-related relatives underwent a 4 h 75 g OGTT with measurements of plasma glucose, serum insulin, serum C-peptide, plasma GIP and plasma GLP-1 levels at 18 time points. Insulin secretion rates (ISR) and beta cell responses to glucose, GIP and GLP-1 were calculated. Familiality was estimated based on OGTTderived measures. Results A high level of familiality was observed during the OGTT for plasma levels of GIP and GLP-1, with peak familiality values of 74±16% and 65±15%, respectively (h2±SE). Familiality values were lower for plasma glucose, serum insulin and serum C-peptide during the OGTT (range 8-48%, 14-44% and 15-61%, respectively). ISR resented the highest familiality value at fasting reaching 59±16%. Beta cell responsiveness to glucose GLP-1 and GIP also revealed a strong genetic influence, with peak familiality estimates of 62±13%, 76±15% and 70±14%, respectively. Conclusions/interpretation Our results suggest that circulating levels of GIP and GLP-1 as well as beta cell response to these incretins are highly familial compared with more commonly investigated measures of glucose homeostasis such as fasting and stimulated plasma glucose, serum insulin and serum C-peptide.
U2 - 10.1007/s00125-012-2484-6
DO - 10.1007/s00125-012-2484-6
M3 - Journal article
C2 - 22349073
SN - 0012-186X
VL - 55
SP - 1338
EP - 1345
JO - Diabetologia
JF - Diabetologia
IS - 5
ER -
