Association between plasma adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies.

Background: Patients with diabetes have increased risk of developing microvascular complications. Adipocytokines have been variously associated with these complications in observational clinical studies. However, there are no comprehensive data examining the associations between adipocytokines concentrations and the presence of these complications. Method(s): We performed a systematic review of cross-sectional studies comparing circulating adipocytokines in patients with type 2 diabetes (T2D) who were affected by at least one microvascular complication, with T2D patients without these complications. Relevant studies were retrieved from MEDLINE, EMBASE, Scopus and Cochrane databases. Study quality was evaluated using a modified Newcastle-Ottawa Quality Assessment Scale. Meta-analysis was performed using an inverse-variance model. Standardised mean differences (SMD) and 95% confidence intervals (CI) were calculated for leptin and adiponectin. Heterogeneity was determined by Q and I2 statistics, from which fixed or random effects models were applied. Result(s): 554 abstracts were identified; 28 studies satisfied our inclusion/ exclusion criteria. Study quality ranged from 4-10 (out of 11). Higher leptin levels were associated with the presence of microalbuminuria (SMD = 0.41; 95%CI = 0.14, 0.67; n = 901; p = 0.0003) and macroalbuminuria (SMD = 0.68; 95%CI = 0.30, 1.06; n = 406; p = 0.0004). Similarly, higher leptin levels were associated with the presence of neuropathy (SMD = 0.26; 95%CI = 0.07, 0.44; n = 609; p = 0.008). Higher adiponectin levels were associated with the presence of microalbuminuria (SMD = 0.55; 95%CI = 0.29, 0.81, n = 274; p < 0.001) and macroalbuminuria (SMD = 1.37; 95%CI = 0.78, 1.97, n = 246; p < 0.00001). In addition, higher adiponectin levels were associated with 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). Discussion(s): This systematic review and met