title: Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels?
abstract: OBJECTIVE
  The objective of this study was to assess the effects of a continuous overnight infusion of des-acyl ghrelin (DAG) on acylated ghrelin (AG) levels and glucose and insulin responses to a standard breakfast meal (SBM) in eight overweight patients with type 2 diabetes. Furthermore, in the same patients and two additional subjects, the effects of DAG infusion on AG concentrations and insulin sensitivity during a hyperinsulinemic-euglycemic clamp (HEC) were assessed.
  
  
  METHODS
  A double-blind, placebo-controlled cross-over study design was implemented, using overnight continuous infusions of 3 and 10  μg DAG/kg per h and placebo to study the effects on a SBM. During a HEC, we studied the insulin sensitivity.
  
  
  RESULTS
  We observed that, compared with placebo, overnight DAG administration significantly decreased postprandial glucose levels, both during continuous glucose monitoring and at peak serum glucose levels. The degree of improvement in glycemia was correlated with baseline plasma AG concentrations. Concurrently, DAG infusion significantly decreased fasting and postprandial AG levels. During the HEC, 2.5  h of DAG infusion markedly decreased AG levels, and the M-index, a measure of insulin sensitivity, was significantly improved in the six subjects in whom we were able to attain steady-state euglycemia. DAG administration was not accompanied by many side effects when compared with placebo.
  
  
  CONCLUSIONS
  DAG administration improves glycemic control in obese subjects with type 2 diabetes through the suppression of AG levels. DAG is a good candidate for the development of compounds in the treatment of metabolic disorders or other conditions with a disturbed AG:DAG ratio, such as type 2 diabetes mellitus or Prader-Willi syndrome.
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France b.ozcan@erasmusmc.nl.
authors.forename: Behiye
authors.initials: B
authors.lastname: Özcan
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Sebastian J C M M
authors.initials: SJ
authors.lastname: Neggers
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Anne Reifel
authors.initials: AR
authors.lastname: Miller
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Hsiu-Chiung
authors.initials: HC
authors.lastname: Yang
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Virginia
authors.initials: V
authors.lastname: Lucaites
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Abribat
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Soraya
authors.initials: S
authors.lastname: Allas
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Huisman
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Visser
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Patric J D
authors.initials: PJ
authors.lastname: Delhanty
authors.affiliation: Department of Internal MedicineErasmus University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The NetherlandsLilly Research LaboratoriesLilly Corporate Center, Indianapolis, Indiana 46285, USAAlizé Pharma69 130 Ecully, France.
authors.forename: Aart Jan
authors.initials: AJ
authors.lastname: van der Lely
mesh_terms: D000215:Acylation; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D054439:Ghrelin / Q000097:blood* / Q000627:therapeutic use; D015309:Glucose Clamp Technique; D006801:Humans; D008297:Male; D062407:Meals; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy*
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; C422650:ghrelin, des-n-octanoyl