Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients With Uncomplicated Type 1 Diabetes
Article Figures & Tables
Figures
- Figure 1
Flow diagram for study participants.
- Figure 2
GFR response during a euglycemic clamp day at baseline and after 8 weeks of treatment with FBX in individual patients with T1D and T1D-N (GFR <135 mL/min/1.73 m2, n = 42) (A) and T1D-H (GFR ≥135 mL/min/1.73 m2, n = 6) (B).
- Figure 3
GFR (A), ERPF (B), FF (C), RA (D), RE (E), and PGLO (F) responses to clamped hyperglycemia in patients with T1D at baseline and after 8 weeks of treatment with FBX. T1D group, n = 48. Δ in each outcome represents the difference between the outcome measured at hyperglycemic clamp day and euglycemic clamp day. RA, RE, and PGLO in patients with T1D calculated by Gomez equations (assumption: PGLO of 56.4 mmHg in patients with T1D). Values are reported as the mean ± SD.
- Figure 4
GFR (A), ERPF (B), FF (C), RA (D), RE (E), and PGLO (F) responses to ANG II infusion (1 and 3 ng/kg/min) during a euglycemic clamp day in patients with T1D at baseline and after 8 weeks of treatment with FBX. T1D group, n = 48. Δ in each outcome represents the difference between the outcome measured after and before the 3 ng/kg/min ANG II infusion during a euglycemic clamp day. RA, RE, and PGLO in patients with T1D calculated by Gomez equations (assumption: PGLO of 56.4 mmHg in patients with T1D). Values are reported as the mean ± SD.
- Figure 5
IL-5 (A), IL-9 (B), and IL-18 (C) response to clamped hyperglycemia in T1D at baseline and after 8 weeks of treatment with FBX. T1D group, n = 48. Values are reported as the mean ± SD.
Tables
- Table 1
Baseline demographic characteristics of HCs and patients with T1D
Parameter HCs (n = 24) Patients with T1D (n = 49) Males 12 (50%) 25 (51%) Age (years) 25.5 ± 4.5 26.3 ± 5.4 Diabetes duration (years) 14.3 ± 7.2 BMI (kg/m2) 23.6 ± 3.4 25.1 ± 3.4 Cholesterol 4.2 ± 0.8 4.6 ± 0.8 HDL cholesterol 1.5 ± 0.5 1.5 ± 0.4 LDL cholesterol 2.4 ± 0.7 2.6 ± 0.7 Triglycerides 1.0 ± 0.7 1.1 ± 0.7 Hemoglobin A1c, mmol/mol (%) 31.7 ± 2.4 (5.0 ± 0.2) 62.3 ± 14.8 (7.8 ± 1.3)* 24-h urine sodium (mmol/day) 155 ± 65 150 ± 76 24-h protein intake (g/kg/day)† 1.1 ± 0.3 1.0 ± 0.3* Estradiol (females only) 226 ± 169 217 ± 250 Progesterone (females only) 3.3 ± 4.2 3.1 ± 7.5 Values are reported as the mean ± SD, unless otherwise indicated. n, number of participants.
*P < 0.05 vs. HCs.
†24-h protein intake was estimated as follows: ([urine urea × 0.18] + 14)/weight (in kg).
- Table 2
Diet parameters and plasma marker response to FBX treatment in HCs and patients with T1D studied under euglycemic and hyperglycemic clamp conditions
Parameter HC (n = 24) T1D (n = 49) Euglycemia Hyperglycemia Baseline FBX P value Baseline FBX P value Baseline FBX P value Diet parameters Hemoglobin A1c, mmol/mol (%) 5.05 ± 0.22 4.97 ± 0.23 0.0167 62.3 ± 14.8 (7.8 ± 1.3)* 62.4 ± 13.9 (7.9 ± 1.3) 0.8831 24-h urine sodium (mmol/day) 155 ± 65 152 ± 74 0.7968 150 ± 76 132 ± 83 0.1126 24-h protein intake (g/kg/day)† 1.1 ± 0.3 1.1 ± 0.3 0.2726 1.0 ± 0.3* 1.0 ± 0.4 0.8264 Plasma analysis Aldosterone (ng/dL) 291 ± 164 283 ± 260 0.8852 76 ± 56 67 ± 39 0.1265 60 ± 54 60 ± 47 0.9976 Renin (ng/L) 14.4 ± 10.4 12.1 ± 8.5 0.3343 10.3 ± 22.9 10.1 ± 16.5 0.9376 6.8 ± 15.6 5.1 ± 5.8 0.4028 PUA (µmol/L) 303 ± 71 131 ± 55 <0.0001 240 ± 62 124 ± 53 <0.0001 221 ± 61 108 ± 42 <0.0001 Estradiol (females only) 226 ± 169 285 ± 220 0.1997 217 ± 249 245 ± 260 0.6742 Progesterone (females only) 3.3 ± 4.2 4.3 ± 5.9 0.5248 3.1 ± 7.5 2.1 ± 3.8 0.5487 Values are reported as the mean ± SD, unless otherwise indicated. n, number of participants.
*P < 0.05 vs. HC.
†24-h protein intake: estimated by the formula ([urine urea × 0.18] + 14)/weight (in kg).
- Table 3
Renal, intraglomerular, and systemic hemodynamic function and vascular parameter response to FBX treatment in HCs and patients with T1D studied under euglycemic and hyperglycemic clamp conditions
Parameter HC (n = 24) T1D (n = 49) Euglycemia Hyperglycemia Baseline FBX P value Baseline FBX P value Baseline FBX P value Renal hemodynamic function ERPF (mL/min/1.73 m2) 654 ± 111 639 ± 91 0.3818 647 ± 131 657 ± 113 0.5329 676 ± 133 665 ± 124 0.4235 GFR (mL/min/1.73 m2) 117 ± 17 119 ± 15 0.2836 115 ± 19 113 ± 16 0.1893 130 ± 21 133 ± 19 0.2142 FF 0.18 ± 0.04 0.19 ± 0.03 0.3124 0.18 ± 0.04 0.17 ± 0.03 0.1019 0.20 ± 0.04 0.21 ± 0.05 0.1064 RBF (mL/min/1.73 m2) 1,058 ± 202 1,035 ± 178 0.4044 1,051 ± 219 1,063 ± 185 0.6300 1,071 ± 209 1,052 ± 203 0.3956 RVR (mmHg/L/min) 0.077 ± 0.015 0.077 ± 0.015 0.6896 0.081 ± 0.022 0.077 ± 0.014 0.1327 0.080 ± 0.016 0.082 ± 0.020 0.4171 Intraglomerular hemodynamic parameters PGLO (mmHg) 48.9 ± 2.7 49.4 ± 2.5 0.2275 54.4 ± 4.1 53.4 ± 3.2 0.0497 54.9 ± 4.0 56.1 ± 4.1 0.0664 RA (dyne ⋅ s ⋅ cm−5) 2,246 ± 640 2,208 ± 704 0.6845 2,167 ± 885 2,010 ± 662 0.1905 2,170 ± 721 2,132 ± 815 0.7373 RE (dyne ⋅ s ⋅ cm−5) 994 ± 263 1,028 ± 197 0.3931 1,690 ± 424 1,604 ± 331 0.1299 1,871 ± 423 1,997 ± 573 0.0829 RA/RE ratio 2.39 ± 0.86 2.20 ± 0.76 0.1504 1.31 ± 0.52 1.29 ± 0.47 0.6641 1.21 ± 0.44 1.11 ± 0.43 0.1667 Systemic hemodynamic function HR (bpm) 62 ± 8 61 ± 9 0.4042 67 ± 11 66 ± 10 0.8605 64 ± 11 64 ± 12 0.7484 SBP (mmHg) 107 ± 9 106 ± 8 0.3267 112 ± 10 109 ± 9 0.0491 113 ± 9 112 ± 9 0.4405 DBP (mmHg) 64 ± 6 64 ± 7 0.6106 67 ± 6 66 ± 7 0.2823 69 ± 7 69 ± 7 0.6546 Vascular parameters Aortic AIX (%) −7.7 ± 9.7 −9.6 ± 8.1 0.4353 −3.0 ± 11.5 −4.1 ± 11.8 0.4247 −1.8 ± 14.3 −1.5 ± 12.5 0.8605 Carotid AIX (%) −3.6 ± 13.6 −4.3 ± 14.1 0.7529 0.5 ± 15.0 1.6 ± 14.7 0.4740 4.4 ± 15.7 2.5 ± 14.9 0.1723 Carotid radial PWV (m/s) 7.1 ± 1.0 6.8 ± 1.1 0.2340 7.3 ± 1.1 7.2 ± 1.1 0.7043 7.6 ± 1.0 7.3 ± 1.3 0.0728 Carotid femoral PWV (m/s) 5.5 ± 1.1 5.3 ± 1.0 0.5332 5.8 ± 1.0 5.6 ± 1.2 0.2979 5.8 ± 0.9 5.6 ± 1.1 0.0972 FMD (%) 4.2 ± 3.1 5.0 ± 3.4 0.2428 4.1 ± 4.4 5.3 ± 3.4 0.8251 4.2 ± 4.1 4.8 ± 3.6 0.1733 FMD/flow 0.047 ± 0.038 0.073 ± 0.076 0.1616 0.051 ± 0.056 0.050 ± 0.048 0.9343 0.056 ± 0.041 0.061 ± 0.050 0.5058 GMD (%) 15.5 ± 6.0 15.9 ± 4.7 0.6629 11.9 ± 5.1 11.1 ± 6.3 0.2777 13.0 ± 5.7 12.6 ± 5.2 0.3596 HR variability RMSSD (ms) 64.1 ± 29.1 80.9 ± 46.9 0.0293 63.5 ± 42.6 63.6 ± 43.8 0.9796 67.8 ± 44.2 66.5 ± 47.3 0.7555 SDNN (ms) 77.4 ± 22.8 88.2 ± 37.8 0.0769 76.2 ± 33.9 78.9 ± 36.9 0.4579 79.0 ± 35.9 77.4 ± 39.0 0.6982 Values are reported as the mean ± SD, unless otherwise indicated. n, number of participants.
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