title: GLP-1 responses are heritable and blunted in acquired obesity with high liver fat and insulin resistance.
abstract: 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.
authors.affiliation: Corresponding author: Kirsi H. Pietiläinen, kirsi.pietilainen@helsinki.fi.
authors.forename: Niina
authors.initials: N
authors.lastname: Matikainen
authors.forename: Leonie H
authors.initials: LH
authors.lastname: Bogl
authors.forename: Antti
authors.initials: A
authors.lastname: Hakkarainen
authors.forename: Jesper
authors.initials: J
authors.lastname: Lundbom
authors.forename: Nina
authors.initials: N
authors.lastname: Lundbom
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Aila
authors.initials: A
authors.lastname: Rissanen
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D054795:Incretins / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; D010446:Peptide Fragments; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1