title: Altered glucose homeostasis is associated with increased serum apelin levels in type 2 diabetes mellitus.
abstract: BACKGROUND
  Apelin is an adipokine that plays a role in the regulation of glucose homeostasis and in obesity. The relationship between apelin serum concentration and dysmetabolic conditions such as type 2 diabetes (T2D) is still controversial. Aims of our study are: 1) determine the circulating levels of apelin in a large cohort of Italian subjects with T2D, T1D and in non-diabetic controls; 2) identify putative metabolic determinants of modified apelin concentrations, in order to search possible mechanism of apelin control; 3) investigate changes in apelin levels in response to sharp modifications of glucose/insulin metabolism in T2D obese subjects before and 3 days after bariatric surgery.
  
  
  METHODS
  We recruited 369 subjects, 119 with T2D, 113 with T1D and 137 non-diabetic controls. All subjects underwent a complete clinical examination, including anthropometric and laboratory measurements. Serum apelin levels were determined by EIA (immunoenzyme assay).
  
  
  RESULTS
  Patients with T2D had significantly higher serum apelin levels compared to controls (1.23 ± 1.1 ng/mL vs 0.91 ± 0.7 ng/mL, P<0.001) and to T1D subjects (0.73 ± 0.39 ng/mL, P<0.001). Controls and T1D subjects did not differ significantly in apelin levels. Apelin concentrations were directly associated with fasting blood glucose (FBG), body mass index (BMI), basal Disposition Index (DI-0), age, and diagnosis of T2D at bivariate correlation analysis. Multiple regression analysis confirmed that diagnosis of T2D, basal DI-0 and FBG were all determinants of serum apelin levels independently from age and BMI. Bariatric surgery performed in a subgroup of obese diabetic subjects (n = 12) resulted in a significant reduction of apelin concentrations compared to baseline levels (P = 0.01).
  
  
  CONCLUSIONS
  Our study demonstrates that T2D, but not T1D, is associated with increased serum apelin levels compared to non-diabetic subjects. This association is dependent on impaired glucose homeostasis, and disappears after bariatric surgery, providing further evidence regarding the relationship between apelin and the regulation of glucose metabolism.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors.forename: Maria Gisella
authors.initials: MG
authors.lastname: Cavallo
authors.forename: Federica
authors.initials: F
authors.lastname: Sentinelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Barchetta
authors.forename: Carmine
authors.initials: C
authors.lastname: Costantino
authors.forename: Michela
authors.initials: M
authors.lastname: Incani
authors.forename: Laura
authors.initials: L
authors.lastname: Perra
authors.forename: Danila
authors.initials: D
authors.lastname: Capoccia
authors.forename: Stefano
authors.initials: S
authors.lastname: Romeo
authors.forename: Efisio
authors.initials: E
authors.lastname: Cossu
authors.forename: Frida
authors.initials: F
authors.lastname: Leonetti
authors.forename: Luciano
authors.initials: L
authors.lastname: Agati
authors.forename: Marco G
authors.initials: MG
authors.lastname: Baroni
mesh_terms: D000328:Adult; D000886:Anthropometry; D000073861:Apelin; D050110:Bariatric Surgery; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis
chemical_list: C115436:APLN protein, human; D000073861:Apelin; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D005947:Glucose