Altered glucose homeostasis is associated with increased serum apelin levels in type 2 diabetes mellitus

PLoS One. 2012;7(12):e51236. doi: 10.1371/journal.pone.0051236. Epub 2012 Dec 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anthropometry
  • Apelin
  • Bariatric Surgery
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / surgery
  • Female
  • Glucose / metabolism*
  • Homeostasis* / drug effects
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Intercellular Signaling Peptides and Proteins / blood*
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis

Substances

  • APLN protein, human
  • Apelin
  • Hypoglycemic Agents
  • Intercellular Signaling Peptides and Proteins
  • Glucose

Grants and funding

This work was funded by research grants from the University of Cagliari (ex-60% 2009–11 http://www.unica.it/), from the Ministry of Education, University and Research (PRIN 2008, n. 2008J2FS4T, http://prin.cineca.it/) and from the Foundation Banco di Sardegna (Research Projects 2011, http://www.fondazionebancodisardegna.it/), all awarded to MGB. MGC was funded by a research grant from Sapienza University of Rome (http://www.uniroma1.it/) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.