Eleen Schupp1, Rinke Stienstra1,2, Cees J. Tack1, Bastiaan E. de Galan1,3, Rick I. Meijer1, Hypo-RESOLVE consortium; 1 Department of Internal Medicine, Radboudumc, Nijmegen, Netherlands; 2 Division of Human Nutrition and Health, Wageningen University, Wageningen, Netherlands; 3 Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, Netherlands
Background: Glycaemic variability (GV) has been associated to the progression of complications in both type 1 (T1D) and type 2 diabetes (T2D), but the underlying mechanism is not completely clear. We hypothesize that inflammation may be a mediating factor. The aim of this study is to determine the associations between GV and inflammation, and whether these differ between T1D and T2D.
Methods: This was a post-hoc analysis from the Hypo-METRICS study, involving 166 participants with T1D and 184 participants with insulin-treated T2D, who wore a CGM for 10 weeks. Mean glucose, standard deviation (SD), coefficient of variation (CV) and glycaemic variability percentage (GVP) were calculated from the CGM data. Circulating inflammatory proteins were measured using Olink Proteomics AB inflammation panel and compared between groups with high or low GV in both T1D and T2D. Whole blood flow cytometry was performed to determine the number of circulating immune cells (total white blood cells, neutrophils, monocytes and lymphocytes) in a subset of 31 T1D and 86 T2D participants. Spearman correlations were used for the associations with the different GV metrics.
Results: Several inflammatory proteins were higher in participants with high GV compared to low GV, but the proteins differed between T1D and T2D. In T1D, mean glucose was positively correlated with the number of circulating neutrophils (rs=0.43, p=0.017). Conversely, both CV (rs=-0.36, p=0.047) and GVP (rs=-0.42, p=0.017) were inversely correlated with the number of circulating lymphocytes in T1D. In T2D, there were no such correlations, except that GVP was inversely correlated with the number of circulating lymphocytes (rs=-0.26, p=0.014).
Conclusion: GV is associated with circulating inflammatory protein levels and white blood cells, both in T1D and T2D. This association seems more pronounced in T1D, possibly because of the more profound GV in T1D. Based on these results, the link between GV and inflammation deserves further exploration.