Inflammatory Markers and Measures of Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

Figures

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  Figure 1. Inflammatory biomarker correlations with CAN measures in TINSAL‐T1DN. Spearman's rank correlation coefficients of inflammatory markers to CAN measures. Blue and red represent positive and negative correlations, respectively. Both a deeper color and more elliptical shape indicate a stronger association. CAN indicates cardiovascular autonomic neuropathy; EGF, estimated glomerular filtration; E/I ratio, expiration/inspiration ratio; FGF‐2; HR, heart rate; IFNa2, interferon alpha 2; IFNg, interferon γ; IL, interleukin; LFA, low‐frequency power; MCP; MIP; RFA, high‐frequency power; RMSSD, root mean square of the differences of successive RR intervals; SDNN, standard deviation of the normal RR interval; suPAR, soluble urokinase plasminogen activator receptor; TGFa, transforming growth factor‐α; TINSAL‐T1DN, Targeting Inflammation with Salsalate in Individuals with T1D Neuropathy; Val.Average; and VEGF, vascular endothelial growth factor.

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  Figure 2. Violin plots demonstrating the distributions of suPAR across tertile groups of CAN measures in TINSAL‐T1DN. A, 30:15 ratio; (B) SDNN; (C) RMSSD; (D) LFA; (E) RFA; and (F) LFA/RFA ratio. CAN indicates cardiovascular autonomic neuropathy; LFA low‐frequency power; RFA, high‐frequency power; RMSSD, root mean square of the differences of successive RR intervals; SDNN, standard deviation of the normal RR interval; suPAR, soluble urokinase plasminogen activator receptor; and TINSAL‐T1DN, Targeting Inflammation with Salsalate in Individuals with T1D Neuropathy.

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  Figure 3. suPAR ratios between tertile groups of CAN measures in TINSAL‐T1DN. In the forest plots, the black squares represent the estimated suPAR ratios, and the bars represent 95% CIs. P values are also shown. Model 1: univariable analysis; Model 2: multivariable analysis, adjusted for age, sex, and HbA1c. CAN indicates cardiovascular autonomic neuropathy; HbA1c, glycated hemoglobin; LFA, low‐frequency power; RFA, high‐frequency power; RMSSD, root mean square of the differences of successive RR intervals; SDNN, standard deviation of the normal RR interval; suPAR, soluble urokinase plasminogen activator receptor; and TINSAL‐T1DN, Targeting Inflammation with Salsalate in Individuals with T1D Neuropathy.

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  Figure 4. suPAR ratios between tertile groups of CAN measures in PERL. In the forest plots, the black squares represent the estimated suPAR ratios, and the bars represent 95% CIs. P values are also shown. Model 1: univariable analysis; Model 2: multivariable analysis adjusted for age, sex, and HbA1c; Model 3: multivariable analysis further adjusted for eGFR in addition to parameters adjusted in Model 2. CAN indicates cardiovascular autonomic neuropathy; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin; PERL, Preventing Early Renal Function Loss in Diabetes; RMSSD, root mean square of the differences of successive RR intervals; SDNN, standard deviation of the normal RR interval; and suPAR, soluble urokinase plasminogen activator receptor.

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  Figure 5. Violin plots demonstrating the distributions of suPAR across tertile groups of CAN measures in PERL. A, RMSSD; and B, SDNN. CAN indicates cardiovascular autonomic neuropathy; PERL, Preventing Early Renal Function Loss in Diabetes; RMSSD, root mean square of the differences of successive RR intervals; SDNN, standard deviation of the normal RR interval; and suPAR, soluble urokinase plasminogen activator receptor.