title: Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies.
abstract: BACKGROUND
  The adipocytokines leptin and adiponectin have been variously associated with diabetic microvascular complications. No comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications.
  
  
  METHODS
  This is a systematic review of cross-sectional studies comparing circulating adipocytokines in patients with type 2 diabetes mellitus (T2DM), with and without microvascular complications. Studies were retrieved from MEDLINE, EMBASE, Scopus and Cochrane databases. Study quality was evaluated using a modified Newcastle-Ottawa Scale. Meta-analysis was performed using an inverse-variance model, providing standardised mean differences (SMD) and 95% confidence intervals (CI). Heterogeneity was determined by I(2) statistic.
  
  
  RESULTS
  Amongst 554 identified studies, 28 were included in the review. Study quality range was 3.5-9 (maximum 11). Higher leptin levels were associated with microalbuminuria (SMD=0.41; 95% CI=0.14-0.67; n=901; p=0.0003), macroalbuminuria (SMD=0.68; 95% CI=0.30-1.06; n=406; p=0.0004), and neuropathy (SMD=0.26; 95% CI=0.07-0.44; n=609; p=0.008). Higher adiponectin levels were associated with microalbuminuria (SMD=0.55; 95% CI=0.29-0.81, n=274; p<0.001), macroalbuminuria (SMD=1.37; 95% CI=0.78-1.97, n=246; p<0.00001), neuropathy (SMD=0.25; 95% CI=0.14-0.36; n=1516; p<0.00001), and retinopathy (SMD=0.38; 95% CI=0.25-0.51; n=1306; p<0.00001). Meta-regression suggested no influence of body mass index and duration of diabetes on effect size, and a weak trend in terms of age on effect size.
  
  
  CONCLUSIONS
  Our meta-analysis suggests leptin and adiponectin levels are higher in T2DM patients with microvascular complications. Studies were limited by cross-sectional design. Large prospective analyses are required to validate these findings.
authors.affiliation: Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, 131 Garran Rd, Acton, ACT, 2601, Australia. Electronic address: alexander.rodriguez@monash.edu.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Rodríguez
authors.affiliation: Department of Internal Medicine, Botucatu Medical School, State University/UNESP, Sao Paulo, Faculdade de Medicina, Distrito de Rubião Júnior s/n, Botucatu, SP, CEP 18618-000, Brazil. Electronic address: vsnunes@fmb.unesp.br.
authors.forename: Vania dos Santos
authors.initials: Vdos S
authors.lastname: Nunes
authors.affiliation: Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, 131 Garran Rd, Acton, ACT, 2601, Australia. Electronic address: claudio.mastronardi@anu.edu.au.
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Mastronardi
authors.affiliation: Statistical Consulting Unit, The Australian National University, Canberra, John Dedman Mathematical Sciences Building, 27 Union Lane, Acton, ACT, 2601, Australia. Electronic address: teresa.neeman@anu.edu.au.
authors.forename: Teresa
authors.initials: T
authors.lastname: Neeman
authors.affiliation: Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, 131 Garran Rd, Acton, ACT, 2601, Australia. Electronic address: gilberto.pazfilho@anu.edu.au.
authors.forename: Gilberto J
authors.initials: GJ
authors.lastname: Paz-Filho
mesh_terms: D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood; D000368:Aged; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications* / Q000453:epidemiology; D003925:Diabetic Angiopathies / Q000097:blood* / Q000453:epidemiology; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: C499918:ADIPOQ protein, human; D054392:Adipokines; D052242:Adiponectin; D020738:Leptin
keywords: Adipocytokines; Adiponectin; Diabetes; Leptin; Nephropathy; Neuropathy; Retinopathy