Immunomodulatory Role of Eosinophils in Development of Obesity Induced Insulin Resistance in Humans

Abstract

Background: Eosinophils have been implicated in the pathogenesis of Type 2 Diabetes (T2D) but there are contradictory reports. Eosinophils infiltrating adipose tissue are suggested to be protective against development of T2D. This study was planned to investigate relationship of eosinophils with obesity induced insulin resistance. Methodology: Phase I: A case-control study with 102 new T2D, 73 prediabetes and 91 normal subjects (N=266) based on OGTT was undertaken. Normal total leucocyte count (TLC) in all subjects was an additional inclusion criteria. Phase II: 9 new T2D, 2 prediabetes and 9 normal subjects based on Phase I criteria were selected for studying cytokines. Phase III: 27 new T2D, 33 prediabetes and 24 normal subjects based on OGTT but without measuring TLC were recruited to quantify the important cytokines identified in previous phase. Demographic profile, metabolic profile, hematological profile, renal profile, lipid profile, insulin resistance profile, TLC, differential leucocyte count, cytokines and cytokine ratios were compared based on grouping by Homa-IR and#8804;2 and HomaIRgt2. Results: In Phase I, insulin resistance did not show any relation to measures of obesity. Peripheral eosinophils had no relation with insulin resistance in new T2D subjects. A significant increase in AMC and a significant decrease in LMR with higher insulin resistance were noted. There was also a weak positive correlation of monocytes and AMC with Homa-IR. AMC could also predict Homa-IR by a regression equation. In Phase II, IFN-and#947; predicted Homa-IR by a regression equation. Seven cytokines related either directly or indirectly to Homa-IR were identified, namely IL-2, IL-4, IL-5, IL-6, IL-13, IFN- and#947; and TNF-and#945;. In Phase III, cytokines identified in Phase II were quantified. With no TLC being taken into account, it was found that more subjects had higher insulin resistance and cytokines ranges were very different from previous phase. Conclusion: In early T2D, especially with normal TLC, measures of obesity do not seem to impact insulin resistance. Eosinophils showed no relation with Homa-IR. AMC and IFN- and#947; showed a definite relationship with insulin resistance and another eight cytokines too showed possible relation to the same. However, our study was limited by the extremely small sample in phase II and further studies must be done with larger numbers to study the same. Our study also indicates that further research must be done with stricter inclusion and exclusion criteria esp. normal TLC as the entire scenario seems to change with just a change in this factor. newline