GLP-1 responses are heritable and blunted in acquired obesity with high liver fat and insulin resistance
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GLP-1 responses are heritable and blunted in acquired obesity with high liver fat and insulin resistance. / Matikainen, Niina; Bogl, Leonie H; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Kaprio, Jaakko; Rissanen, Aila; Holst, Jens Juul; Pietiläinen, Kirsi H.
In: Diabetes Care, Vol. 37, No. 1, 01.2014, p. 242-51.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - GLP-1 responses are heritable and blunted in acquired obesity with high liver fat and insulin resistance
AU - Matikainen, Niina
AU - Bogl, Leonie H
AU - Hakkarainen, Antti
AU - Lundbom, Jesper
AU - Lundbom, Nina
AU - Kaprio, Jaakko
AU - Rissanen, Aila
AU - Holst, Jens Juul
AU - Pietiläinen, Kirsi H
PY - 2014/1
Y1 - 2014/1
N2 - OBJECTIVE Impaired incretin response represents an early and uniform defect in type 2 diabetes, but the contributions of genes and the environment are poorly characterized. RESEARCH DESIGN AND METHODS We studied 35 monozygotic (MZ) and 75 dizygotic (DZ) twin pairs (discordant and concordant for obesity) to determine the heritability of glucagon-like peptide 1 (GLP-1) responses to an oral glucose tolerance test (OGTT) and the influence of acquired obesity to GLP-1, glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) during OGTT or meal test. RESULTS The heritability of GLP-1 area under the curve was 67% (95% CI 45-80). Cotwins from weight-concordant MZ and DZ pairs and weight-discordant MZ pairs but concordant for liver fat content demonstrated similar glucose, insulin, and incretin profiles after the OGTT and meal tests. In contrast, higher insulin responses and blunted 60-min GLP-1 responses during the OGTT were observed in the heavier as compared with leaner MZ cotwins discordant for BMI, liver fat, and insulin sensitivity. Blunted GLP-1 response to OGTT was observed in heavier as compared with leaner DZ cotwins discordant for obesity and insulin sensitivity. CONCLUSIONS Whereas the GLP-1 response to the OGTT is heritable, an acquired unhealthy pattern of obesity characterized by liver fat accumulation and insulin resistance is closely related to impaired GLP-1 response in young adults.
AB - OBJECTIVE Impaired incretin response represents an early and uniform defect in type 2 diabetes, but the contributions of genes and the environment are poorly characterized. RESEARCH DESIGN AND METHODS We studied 35 monozygotic (MZ) and 75 dizygotic (DZ) twin pairs (discordant and concordant for obesity) to determine the heritability of glucagon-like peptide 1 (GLP-1) responses to an oral glucose tolerance test (OGTT) and the influence of acquired obesity to GLP-1, glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) during OGTT or meal test. RESULTS The heritability of GLP-1 area under the curve was 67% (95% CI 45-80). Cotwins from weight-concordant MZ and DZ pairs and weight-discordant MZ pairs but concordant for liver fat content demonstrated similar glucose, insulin, and incretin profiles after the OGTT and meal tests. In contrast, higher insulin responses and blunted 60-min GLP-1 responses during the OGTT were observed in the heavier as compared with leaner MZ cotwins discordant for BMI, liver fat, and insulin sensitivity. Blunted GLP-1 response to OGTT was observed in heavier as compared with leaner DZ cotwins discordant for obesity and insulin sensitivity. CONCLUSIONS Whereas the GLP-1 response to the OGTT is heritable, an acquired unhealthy pattern of obesity characterized by liver fat accumulation and insulin resistance is closely related to impaired GLP-1 response in young adults.
U2 - 10.2337/dc13-1283
DO - 10.2337/dc13-1283
M3 - Journal article
C2 - 23990519
VL - 37
SP - 242
EP - 251
JO - Diabetes Care
JF - Diabetes Care
SN - 0149-5992
IS - 1
ER -
ID: 117853594