title: Fasting and oral glucose-stimulated levels of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are highly familial traits.
abstract: OBJECTIVE
  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 non-diabetic 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 OGTT-derived 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 (h (2) ± 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 presented 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
  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.
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Universitetsparken 1, DK-2100 Copenhagen, Denmark. anette.gjesing@sund.ku.dk
authors.forename: A P
authors.initials: AP
authors.lastname: Gjesing
authors.forename: C T
authors.initials: CT
authors.lastname: Ekstrøm
authors.forename: H
authors.initials: H
authors.lastname: Eiberg
authors.forename: S A
authors.initials: SA
authors.lastname: Urhammer
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
authors.forename: T
authors.initials: T
authors.lastname: Hansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005215:Fasting; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1