Supplementary data Figure legends
Supplementary Figure 1.
ACE2 activity among patients with normal AER. Among male patients with T1D and normal AER, treatment with ACEi causes significant increase in ACE2 activity (A).
Among female patients with T1D and normal AER, both ACEi and ARB treatment are associated with increased ACE2 activity. *P<0.05 when compared to patients with no RAS blockade treatment; †P<0.05 when compared to healthy control subjects. ACEi;
angiotensin convering enzyme inhibitor, AER; albumin excretion rate, ARB; angio- tensin II receptor blocker, RAS; renin-angiotensin system. Patients with micro- or macroalbuminuria are excluded. Data presented as mean±SEM.
Supplementary data Figure legends
Supplementary Figure 1A
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Supplementary Figure 1B
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Supplementary Table 1. Univariate correlations between circulating ACE2 activity and clinical variables in T1D patients
Men Women
rs P-value rs P-value
Age (years) 0.307 <0.001 0.364 <0.001
Diabetes duration (years) 0.198 <0.001 0.233 <0.001
HbA1c (%) -0.024 n.s. 0.001 n.s.
BMI (kg/m2) 0.003 n.s. -0.146 n.s.
Waist/Hip ratio 0.000 n.s. 0.028 n.s.
SBP (mmHg) 0.175 <0.001 0.144 0.006
DBP (mmHg) -0.018 n.s. -0.110 0.014
Pulse pressure 0.204 <0.001 0.205 <0.001
AER (mg/24 h) 0.048 n.s. 0.079 n.s.
eGFR (ml/min/1,73m2) -0.109 0.016 -0.150 0.004
Cholesterol (mmol/l) 0.014 n.s. -0.023 n.s.
TG (mmol/l) -0.010 n.s. -0.038 n.s.
HDL-C (mmol/l) 0.148 0.001 0.155 0.003
rs =Spearman correlation coefficient, BMI; body mass index, SBP; systolic blood pres- sure, DBP; diastolic blood pressure, AER; albumin excretion rate, eGFR; estimated Glomerular filtration rate, TG; triglycerides, HDL-C; HDL-cholesterol.
Table
Supplementary Table 2A. Demographic and biochemical characteristics of the study subjects (Male) included in the Pulse-wave analysis study
Patients with Type 1 diabetes, Male Normo-
albuminuria
Micro- albuminuria
Macro-
albuminuria Healthy Controls
n 130 22 28 57
ACE2 activity (ngE/ml) 28.1±0.8 33.6±2.5*† 28.8±2.1 26.4±1.03
AIx (%) 11.9±1.0* 17.6±2.9* 21.1±1.5*† -2.8±2.1
Age (years) 43.7±1.21* 46.6±2.4* 48.8±1.8* 36.3±1.4
Diabetes duration (years) 22.3±1.1 29.8±2.8† 30.2±1.7† -
HbA1C (%) 7.7±0.1* 8.2±0.3*† 8.1±0.2*† 5.2±0.05
BMI (kg/m2) 25.7±0.3* 25.1±0.8 26.7±0.8* 24.5±0.36
Waist/Hip ratio 0.90±0.01 0.95±0.02 0.98±0.02*† 0.91±0.01
SBP (mmHg) 136±1 136±5 151±4*†‡ 133±2
DBP (mmHg) 75±1 71±5 81±2‡ 76±2
Aortic SBP (mmHg) 121±1.2* 123±3.8* 136±3.7*†‡ 113±1.8
Aortic DBP (mmHg) 78±1 81±2.2 81±1*† 77±1.5
AER (mg/24 h) 10.5 (11.5) 46.0 (39.6) 1418.4 (2346) *†‡ 9.0 (10.7)
eGFR (ml/min/1,73m2) 111±2* 106±7 62±7*†‡ 99±2
Cholesterol (mmol/l) 4.5±0.07 4.7±0.19 4.5±0.19 4.60±1.12 TG (mmol/l) 0.94 (0.6) 0.95 (0.50) 1.36 (0.95)*†‡ 0.97 (0.73)
HDL-C (mmol/l) 1.5±0.04 1.5±0.1 1.55±0.10 1.40±0.03
Creatinine (μmol/l) 72 (14) 78 (34) 136 (125)*† ‡ 83 (15)
ACEi treatment n (%) 33 (25.4%)* 12 (54.5%)*† 19 (67.9%)*†‡ 0 ARB treatment n (%) 10 (7.7%)* 6 (27.3%)*† 13 (46.4%)*†‡ 0
*P<0.05 vs healthy control group; †P<0.05 vs normoalbuminuria group; ‡P<0.05 vs
microalbuminuria group; #P<0.05 vs macroalbuminuria group. AIx; Augmentation In- dex, BMI; body-mass index, SBP; systolic BP, DBP; diastolic blood pressure, AER;
albumin excretion rate, eGFR; estimated Glomerular filtration rate, TG; triglycerides, HDL-C; HDL-cholesterol, ACEi; angiotensin converting enzyme inhibitor, ARB; an- giotensin receptor blocker. Data is presented as mean±SEM except for AER, TG and creatinine, where median and interquartile range are presented.
Supplementary Table 2B. Demographic and biochemical characteristics of the study subjects (Women) included in the Pulse-wave analysis study
Patients with Type 1 diabetes, Female Normo-
albuminuria
Micro- albuminuria
Macro-
albuminuria Healthy Controls
n 93 28 18 57
ACE2 activity (ngE/ml) 21.5±0.7 24.3±2.4* 23.3±2.2 20.3±0.86
AIx (%) 19.8±1.1* 24.9±1.6*† 29.4±1.8*† 13.2±1.6
Age (years) 41.9±1.4 46.8±2.0* 46.0±2.6* 38.4±1.7
Diabetes duration (years) 23.8±1.5 31.8±2.6† 33.2±2.3† -
HbA1C (%) 7.99±0.12* 8.17±0.24*† 9.24±0.50*†‡ 5.1±0.04 BMI (kg/m2) 24.7±0.4* 24.6±1.05* 25.2±1.01* 22.8±0.29 Waist/Hip ratio 0.84±0.01 0.87±0.01* 0.86±0.02 0.83±0.01
SBP (mmHg) 132±2* 139±4* 147±4*† 124±2
DBP (mmHg) 74±1 76±1 80±3 75±1
Aortic SBP (mmHg) 120±2* 126±4* 136±4*† 112±2
Aortic DBP (mmHg) 77±1 77±1 81±3* 76±1
AER (mg/24 h) 8.3 (13.7) 32.3 (58.0) 550.0 (1304)*†‡ 12.3 (10.1)
eGFR (ml/min/1,73m2) 100±2* 93±5 50±6*†‡ 92±3
Cholesterol (mmol/l) 4.54±0.07 4.72±0.12 4.47±0.19 4.78±0.12 TG (mmol/l) 0.74 (0.38) 0.83 (0.73) 1.25 (1.17)*† 0.83 (0.39)
HDL (mmol/l) 1.73±0.05 1.76±0.07 1.51±0.08 1.70±0.03
Creatinine (μmol/l) 64 (14) 64 (20) 113 (93)*†‡ 67 (19.3)
ACE inhibitor treatment n (%) 9 (9.7%)* 11 (39.3%)*† 9 (50%)*†‡ 0 ATII receptor blocker n (%) 9 (9.7%)* 8 (28.6%)*† 9 (50%)*†‡ 0
*P<0.05 vs healthy control group; †P<0.05 vs normoalbuminuria group; ‡P<0.05 vs
microalbuminuria group; #P<0.05 vs macroalbuminuria group. AIx; Augmentation In- dex, BMI; body-mass index, SBP; systolic BP, DBP; diastolic blood pressure, AER;
albumin excretion rate, eGFR; estimated Glomerular filtration rate, TG; triglycerides, HDL-C; HDL-cholesterol, ACEi; angiotensin converting enzyme inhibitor, ARB; an- giotensin receptor blocker. Data is presented as mean±SEM except for AER, TG and creatinine, where median and interquartile range are presented.
