Increased circulating interleukin concentrations in type 2 diabetes mellitus: A systematic review and meta-analysis

Abstract

BACKGROUNDChronic systemic inflammation links to type 2 diabetes mellitus (T2DM) onset, and the potential role of interleukins in this pathogenic process is increasingly recognized.PURPOSETo quantitatively evaluate circulating interleukin concentrations data available for T2DM patients.DATA SOURCESWe performed a systematic review using PubMed, Web of Science, and the Cochrane Library.STUDY SELECTIONOriginal studies reporting data on circulating interleukin concentrations in at least one group of T2DM patients [obese T2DM, overweight T2DM, or lean T2DM] and healthy weight controls (HWCs) were included.DATA EXTRACTION AND SYNTHESISData were extracted from 43 included studies uniquely encompassing 2,646 T2DM patients and 6,605 HWCs by independent investigators. We used a random-effects model to pool data in the Comprehensive Meta-Analysis Version 2 software. Effect sizes were calculated as the standardized mean difference in interleukin concentrations between groups and then transformed into Hedge’s g statistic.LIMITATIONSOf the ILs included in the analysis (interleukin 2, 4, 6, 8, 10, 12, 17, 18, 22, and 33), 70% were with a high level of between-study heterogeneity and could not be fully accounted for by factors such as BMI, sex, age, and publication year. More studies are warranted to identify more contributing clinical variables.CONCLUSIONSMeta-analysis outcomes demonstrated higher circulating concentrations of IL-4, IL-6, IL-17, and IL-18 in T2DM patients, strengthening the clinical evidence that T2DM is accompanied by a systemic inflammatory response.ARTICLE HIGHLIGHTSWhy did we undertake this study? Possible changes in circulating concentrations for most interleukins (ILs) in type 2 diabetes mellitus (T2DM) patients remains uncertain.What is the specific question(s) we wanted to answer? We wanted to quantitatively assess available data on circulating IL concentrations in T2DM patients and healthy weight control (HWC) subjects.What did we find? Increased circulating concentrations of IL-4, IL-6, IL-17, and IL-18 were found in T2DM patients compared with HWC.What are the implications of our findings? These findings affirm T2DM pathogenesis correlates with systemic inflammation, evidenced by elevated circulating concentrations of both pro- and anti-inflammatory interleukins.