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

Abstract

BACKGROUND Chronic systemic inflammation links to type 2 diabetes mellitus (T2DM) onset, and the potential role of interleukins in this pathogenic process is increasingly recognized. PURPOSE To quantitatively evaluate circulating interleukin concentrations data available for T2DM patients. DATA SOURCES We performed a systematic review using PubMed, Web of Science, and the Cochrane Library. STUDY SELECTION Original 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 SYNTHESIS Data 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. LIMITATIONS Of 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. CONCLUSIONS Meta-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.