Background
Methods
Subjects and outcomes
Advanced glycation products (AGEs) in skin biopsies
Statistical methods
Results
Clinical characteristics of participants
Primary | Secondary | P value | |
---|---|---|---|
N = 216 | 123 | 93 | |
DCCT baseline | |||
Female (%) | 53 % | 41 % | |
Age (years) | 27.1 (6.8) | 29.6 (6.5) | 0.009 |
Duration (months) | 2.7 (1.4) | 8.6 (4) | <0.001 |
HbA1c (%) (mmol/mol) | 9.1 (1.8) | 8.9 (1.5) | |
Mean blood glucose (mg/dl) | 230.4 (82.8) | 225.6 (71.5) | |
Triglycerides (mg/dl) | 72.4 (50.5) | 92.9 (51.6) | <0.001 |
Cholesterol (mg/dl) | 178.3 (32.7) | 179.1 (36.5) | 0.006 |
Retinopathy (%) | |||
10/10: None | 100 | 0 | |
20/≤20: Microaneurysms only | 0 | 60 | |
30/≤30: Mild NPDR | 0 | 28 | |
45/≤45: Moderate NPDR | 0 | 11 | |
AER >40 mg/24 h | 1 | 10 | 0.003 |
Confirmed clinical neuropathy (%) | 3 | 14 | 0.004 |
sBP (mmHg) | 114.7 (11.9) | 119.4 (10.5) | |
dBP (mmHg) | 72.9 (8.5) | 75.1 (7.8) | |
AGEs and solubility parameters | |||
Acid soluble (%) | 0.5 (0.3) | 0.6 (0.4) | |
CEL (pmol/mg collagen) | 141.4 (104) | 152.5 (111.1) | |
CML (pmol/mg collagen) | 527.8 (140.4) | 548.1 (119.2) | |
Furosine (pmol/mg collagen) | 756.2 (239.9) | 786.2 (219.8) | |
G-H1 (pmol/mg collagen) | 66.8 (30.7) | 63.6 (38) | |
GSPNE (nmol/mg collagen) | 2.5 (0.6) | 2.6 (0.7) | |
MG-H1 (nmol/mg collagen) | 0.8 (0.4) | 0.8 (0.5) | |
Pentosidine (pmol/mg collagen) | 25.3 (6.2) | 26.6 (8.6) | |
Pepsin Soluble (%) | 6.8 (3.5) | 6.5 (3) |
Primary | Secondary | P value | |
---|---|---|---|
Intima-media thickening study (N = 127) | |||
EDIC year 1 | 6 (0.7) | 6.2 (0.8) | |
EDIC year 6 | 6.2 (0.8) | 6.5 (0.8) | 0.003 |
EDIC year 12 | 6.8 (0.9) | 7.1 (1.1) | |
Coronary calcium study (N = 187) | |||
CAC Mean (Agatston units) | 23 (109.2) | 91.7 (281) | 0.002 |
Cardiac MRI studies (N = 142) | |||
Left ventricular end diastolic mass (g) | 146.6 (33.2) | 149.6 (35.8) | |
End diastolic volume (ml) | 144.1 (34.4) | 140.6 (31.6) | |
End systolic volume (ml) | 56.5 (16.3) | 55.4 (17.7) | |
Stroke volume (ml) | 87.5 (21.7) | 85.2 (19.4) | |
Cardiac output (L/min) | 6 (1.5) | 5.9 (1.3) | |
Ejection fraction (%) | 60.8 (5) | 61 (6.9) | |
LV mass/end diastolic volume (g/ml) | 1 (0.2) | 1.1 (0.2) |
Coronary artery calcium deposition
N | Furosine | CML | Pentosidine | Pepsin soluble | Acid soluble | CEL | G-H1 | MG-H1 | Glucosepane | |
---|---|---|---|---|---|---|---|---|---|---|
Coronary artery calcification | ||||||||||
CAC score (correlation coefficient, p value, FDR#)^
| 187 |
0.16* 0.026 (0.143) | 0.12 0.09 | 0.12 0.11 | −0.14 0.57 | 0.05 0.47 | −0.08 0.26 | 0.11 0.11 | 0.04 0.55 | 0.07 0.33 |
CAC score = 0 vs. CAC score >0 (mean ± std) | 131 | 749 (240) | 528 (129) | 25.3 (6.7) | 6.7 (3.1) | 0.5 (0.3) | 151 (103) | 61 (28) | 0.8 (0.5) | 2.6 (0.6) |
56 | 817 (230) | 560 (148) | 27.6 (8.5) | 6.3 (2.5) | 0.6 (0.4) | 146 (124) | 71 (38) | 0.8 (0.5) | 2.5 (0.7) | |
P Value (FDR)+,#
|
0.039
| 0.13 | 0.15 | 0.76 | 0.32 | 0.22 | 0.12 | 0.7 | 0.32 | |
CAC score <100 vs. CAC score >100 (mean ± std) | 170 | 766 (241) | 535 (135) | 25.8 (7.4) | 6.6 (3.0) | 0.5 (0.3) | 148 (108) | 64 (30) | 0.8 (0.4) | 2.6 (0.6) |
17 | 808 (223) | 567 (142) | 27.2 (6.3) | 5.9 (2.7) | 0.6 (0.6) | 162 (130) | 72 (41) | 0.9 (0.5) | 2.6 (0.7) | |
P-Value (FDR)+,#
| 0.32 | 0.25 | 0.38 | 0.27 | 0.73 | 0.87 | 0.49 | 0.29 | 0.65 | |
Common IMT (correlation) | ||||||||||
Year 6 | 127 | 0.17 | 0.14 | 0.13 | −0.11 | 0.02 | 0.10 | −0.06 |
0.21* |
0.19* |
Change: year 6–year 1 | 127 | 0.04 0.68 | 0.04 0.20 |
0.23* 0.01 | −0.20 * 0.016 | 0.02 0.94 | 0.07 0.29 | 0.05 0.45 |
0.22* 0.059 |
0.18* 0.047 |
Year 12 | 127 | 0.15 | 0.06 | −0.04 | 0.00 | 0.02 | 0.05 | −0.02 | 0.06 | 0.16 |
Change: year 12–year 1 | 127 | 0.07 | 0.06 | 0.02 | −0.13 | −0.05 | 0.03 | 0.10 | 0.01 | 0.15 |
Cardiac MRI studies | ||||||||||
LV Mass (g) | 142 | 0.10 0.25 | 0.16 0.058 | 0.14 0.11 |
−0.17* 0.04 | −0.16 0.054 | −0.02 0.83 | 0.03 0.75 |
0.17*
0.049 | 0.07 0.44 |
End diastolic volume (ml) | 142 | −0.05 | −0.02 | 0.09 | −0.10 | −0.10 | 0.06 | −0.12 | 0.00 | −0.07 |
End systolic volume (ml) | 142 | −0.06 | −0.02 | 0.07 | −0.07 | 0.00 | 0.07 | −0.06 | 0.01 | −0.09 |
Stroke volume (ml) | 142 | −0.03 | −0.03 | 0.07 | −0.07 | −0.12 | 0.04 | −0.10 | −0.03 | −0.03 |
Cardiac (L/min) | 142 | 0.14 | 0.02 | 0.06 | −0.08 | −0.08 | 0.01 | −0.01 | −0.08 | 0.05 |
Ejection fraction (%) | 142 | 0.02 | −0.05 | −0.07 | 0.05 | −0.07 | −0.02 | −0.04 | −0.04 | 0.01 |
LV mass/end diastolic volume (g/ml) | 142 |
0.18* |
0.22** | 0.08 | −0.13 | −0.13 | −0.05 | 0.09 |
0.19* | 0.15 |
CAC score (quantitative)* | |||
---|---|---|---|
Covariate effects from multiple models | X2
| P value | Geometric mean ratio (95 % CI)^
|
Furosine: | |||
Unadjusted for A1c | 5.7 |
0.017
| 5.6 (1.4, 22.7) |
Adjusted for | |||
DCCT mean A1c | 1.3 | 0.26 | 3.8 (0.4, 37.3) |
EDIC mean A1c | 4.4 |
0.035
| 5.0 (1.1, 22.2) |
DCCT mean A1c: | |||
Unadjusted | 5.0 |
0.025
| 1.9 (1.1, 3.3) |
Adjusted for | |||
Furosine | 0.2 | 0.68 | 1.2 (0.5, 3.0) |
EDIC mean A1c: | |||
Unadjusted | 0.6 | 0.52 | 1.1 (0.7, 1.8) |
CAC >0** | |||
---|---|---|---|
Covariate effects from multiple models | t value | P value | Odds ratio (95 % CI)#
|
DCCT mean A1c: | |||
Unadjusted | 2.2 | 0.031 | 1.3 (1.0, 1.6) |
EDIC mean A1c: | |||
Unadjusted | 0.8 | 0.41 | 1.1 (0.9, 1.5) |
CAC >100** | |||
---|---|---|---|
Covariate effects from multiple models | t value | P value | Odds ratio (95 % CI)#
|
DCCT mean A1c: | |||
Unadjusted | 0.4 | 0.68 | 1.1 (0.7, 1.6) |
EDIC mean A1c: | |||
Unadjusted | 0 | 0.71 | 1.1 (0.6, 2.0) |
Intima media thickness (IMT)
IMT change from year 1 to year 6 | |||
---|---|---|---|
Covariate effects from multiple models* | t value | P value | LSMean difference (95 % CI)^
|
MG-H1 | |||
Unadjusted | 2.6 |
0.012
| 0.01 (0.00, 0.02) |
Adjusted for | |||
DCCT mean A1c | 2.5 |
0.014
| 0.01 (0.00, 0.02) |
EDIC mean A1c | 2.7 |
0.008
| 0.01 (0.00, 0.02) |
Pentosidine | |||
Unadjusted | 2.4 |
0.016
| 0.01 (0.00, 0.03) |
Adjusted for | |||
DCCT mean A1c | 2.4 |
0.020
| 0.02 (0.00, 0.03) |
EDIC mean A1c | 2.3 |
0.022
| 0.01 (0.00, 0.03) |
Glucosepane | |||
Unadjusted | 2.0 |
0.048
| 0.01 (0.00, 0.02) |
Adjusted for | |||
DCCT mean A1c | 0.7 | 0.48 | 0.00 (−0.01, 0.01) |
EDIC mean A1c | −0.4 | 0.67 | −0.00 (−0.01, 0.01) |
Pepsin soluble | |||
Unadjusted | −2.0 |
0.048
| −0.03 (−0.06, -0.00) |
Adjusted for | |||
DCCT mean A1c | −1.9 | 0.06 | −0.03 (−0.07, 0.00) |
EDIC mean A1c | −1.7 | 0.08 | −0.03 (−0.06, 0.00) |
DCCT mean A1c: | |||
Unadjusted | 0.7 | 0.48 | 0.02 (−0.01, 0.01) |
EDIC mean A1c: | |||
Unadjusted | 1.5 | 0.14 | 0.05 (−0.00, 0.02) |