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 I2 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 b 0.001), macroalbuminuria (SMD = 1.37; 95% CI = 0.78–1.97, n = 246; p b 0.00001), neuropathy (SMD = 0.25; 95% CI = 0.14–0.36; n = 1516; p b 0.00001), and retinopathy (SMD = 0.38; 95% CI = 0.25–0.51; n = 1306; p b 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. Discussion: 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.