title: Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals.
abstract: OBJECTIVE
  The newly identified liver- and fat-derived hormone, betatrophin, has recently been linked to insulin resistance and pancreatic beta cell growth in mice. These preclinical findings have suggested betatrophin as a potential candidate for novel glucose-lowering treatment concepts involving beta cell regeneration. However, the role of betatrophin in human insulin resistance and type 2 diabetes is currently unknown. Hence, the aim of this study was to investigate circulating betatrophin concentrations in two distinct cohorts with insulin resistance.
  
  
  METHODS
  Betatrophin concentrations were analysed in (1) age- and sex-matched lean (n = 20) and morbidly obese individuals (n = 19), and (2) age-, sex- and BMI-matched non-diabetic (n = 19) and type 2 diabetic individuals (n = 18).
  
  
  RESULTS
  Betatrophin concentrations did not differ between lean and morbidly obese or between non-diabetic and type 2 diabetic participants. No association was found with variables of beta cell function and glucose homeostasis. However, betatrophin did correlate significantly with plasma atherogenic lipids including total cholesterol, LDL-cholesterol and apolipoprotein B in morbidly obese and type 2 diabetic patients but not in controls. Insulin-resistant individuals with hypercholesterolaemia (≥5.2 mmol/l) had significantly higher betatrophin concentrations than those with normal cholesterol (<5.2 mmol/l).
  
  
  CONCLUSIONS
  Betatrophin is a recently identified hormone, the circulating concentrations of which are unaltered in human insulin resistance but correlate significantly with atherogenic lipid profiles in high-risk cohorts with morbid obesity or type 2 diabetes. Betatrophin could therefore be a novel pathomechanistic player in dysfunctional lipid metabolism associated with high cardiovascular risk.
authors.affiliation: Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Fenzl
authors.forename: Bianca K
authors.initials: BK
authors.lastname: Itariu
authors.forename: Lana
authors.initials: L
authors.lastname: Kosi
authors.forename: Monika
authors.initials: M
authors.lastname: Fritzer-Szekeres
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kautzky-Willer
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
authors.forename: Florian W
authors.initials: FW
authors.lastname: Kiefer
mesh_terms: D000328:Adult; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D001786:Blood Glucose / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood; D036361:Peptide Hormones / Q000097:blood*
chemical_list: C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D001786:Blood Glucose; D008078:Cholesterol, LDL; D007328:Insulin; D036361:Peptide Hormones