Introduction
Methods
Variable | Valid n
| Total population
n = 2519 | Type 2 diabetes during follow-up |
p
| |
---|---|---|---|---|---|
No
n = 2346 | Yes
n = 173 | ||||
Age (years) | 2519 | 61.3 (10.4) | 61.4 (10.4) | 62.3 (10.3) | 0.74 |
Sex (men) | 2519 | 1841 (73.1%) | 1714 (73.1%) | 127 (73.4%) | 0.92 |
Fasting | 642 | 642 (25.5%) | 605 (25.8%) | 37 (21.4%) | 0.30 |
BMI (kg/m2) | 2519 | 25.9 (3.71) | 25.7 (3.56) | 28.1 (3.69) | <0.001 |
Current smoking | 2519 | 809 (32.1%) | 755 (32.2%) | 54 (31.2%) | 0.79 |
Hypertension | 2519 | 1114 (44.2%) | 1003 (42.8%) | 111 (64.2%) | <0.001 |
Systolic BP (mmHg) | 2491 | 139 (125–152) | 139 (125–152) | 140 (126–154) | 0.27 |
Diastolic BP (mmHg) | 2490 | 80 (75–88) | 80 (75–88) | 83 (76–90) | 0.01 |
Significant CADa
| 2519 | 1888 (75.0%) | 1744 (74.3%) | 144 (83.2%) | 0.01 |
Renal function and inflammation | |||||
Serum creatinine (μmol/l) | 2516 | 89 (81–98) | 89 (81–98) | 91 (83–100) | 0.26 |
eGFR (ml min−1 1.73 m−2) | 2516 | 91 (79–99) | 91 (79–99) | 91 (77–99) | 0.71 |
Serum CRP (nmol/l) | 2519 | 16.1 (7.90–32.4) | 15.8 (7.81–31.9) | 21.1 (10.3–37.0) | 0.02 |
Plasma neopterin (nmol/l) | 2504 | 8.09 (6.65–10.1) | 8.09 (6.65–10.1) | 8.11 (6.50–10.0) | 0.81 |
Plasma kynurenine (nmol/l) | 2516 | 1.67 (1.38–1.98) | 1.66 (1.38–1.97) | 1.75 (1.51–2.11) | 0.001 |
Plasma tryptophan (μmol/l) | 2516 | 70.3 (61.4–79.5) | 70.1 (61.3–79.2) | 72.5 (62.2–82.6) | 0.01 |
Plasma KTR (nmol/μmol) | 2516 | 23.6 (19.7–28.5) | 23.5 (19.7–28.5) | 23.7 (20.2–28.8) | 0.18 |
Serum lipids | |||||
ApoA-1 (g/l) | 2519 | 1.31 (1.14–1.48) | 1.31 (1.14–1.49) | 1.24 (1.11–1.44) | 0.01 |
ApoB (g/l) | 2519 | 0.87 (0.73–1.05) | 0.87 (0.73–1.04) | 0.91 (0.76–1.08) | 0.07 |
Triacylglycerol (mmol/l) | 2516 | 1.44 (1.06–2.03) | 1.41 (1.04–2.00) | 1.70 (1.25–2.56) | <0.001 |
Glucose homeostasis | |||||
Plasma glucose (mmol/l) | 2518 | 5.4 (5.0–6.1) | 5.4 (5.0–6.0) | 6.3 (5.7–7.8) | <0.001 |
HbA1c (%) | 2519 | 5.6 (5.0–6.0) | 5.6 (5.0–6.0) | 5.7 (5.1–6.1) | 0.16 |
HbA1c (mmol/mol) | 2519 | 38 (31–42) | 38 (31–42) | 39 (32–43) | – |
Serum insulin (pmol/l) | 607 | 21.8 (19.7–55.0) | 19.7 (19.7–55.0) | 39.4 (19.7–110) | 0.002 |
Serum C-peptide (nmol/l) | 607 | 0.71 (0.53–0.98) | 0.71 (0.51–0.96) | 0.91 (0.67–1.17) | 0.001 |
HOMA2 C-peptide | |||||
Beta cell activity | 607 | 113 (93–138) | 112 (92–138) | 121 (95–149) | 0.57 |
Insulin resistance | 607 | 1.6 (1.2–2.2) | 1.6 (1.1–2.2) | 2.0 (1.5–2.7) | <0.001 |
Urine biomarkers | |||||
Creatinine (mmol/l) | 2263 | 11.7 (7.8–16.6) | 11.8 (7.8–16.6) | 11.3 (8.3–16.4) | 0.77 |
Albumin:creatinine (mg/mmol) | 2111 | 0.51 (0.37–0.82) | 0.50 (0.37–0.81) | 0.60 (0.42–0.99) | 0.02 |
Kynurenine:creatinine (nmol/mmol) | 2263 | 182 (118–277) | 179 (117–275) | 221 (151–322) | 0.001 |
Tryptophan:creatinine (μmol/mmol) | 2263 | 4.86 (3.68–6.47) | 4.82 (3.68–6.46) | 5.32 (3.70–6.75) | 0.43 |
FE of kynurenineb
| 2260 | 8.25 (5.42–12.1) | 8.15 (5.36–12.1) | 9.52 (6.29–13.0) | 0.03 |
FE of tryptophanb
| 2260 | 5.27 (3.81–7.08) | 5.27 (3.81–7.07) | 5.28 (3.83–7.26) | 0.80 |
Urine KTR (nmol/μmol) | 2263 | 36.3 (27.7–49.4) | 36.2 (27.5–48.9) | 39.8 (31.3–61.1) | <0.001 |
Medications | |||||
Aspirin | 2519 | 2084 (82.7%) | 1937 (82.6%) | 147 (85.0%) | 0.42 |
Statins | 2519 | 2020 (80.2%) | 1877 (80.0%) | 143 (82.7%) | 0.40 |
β-blockers | 2519 | 1830 (72.6%) | 1696 (72.3%) | 134 (77.5%) | 0.14 |
Loop diuretics | 2519 | 231 (9.2%) | 205 (8.7%) | 26 (15.0%) | 0.006 |
Thiazides | 2519 | 159 (6.3%) | 141 (6.0%) | 18 (10.4%) | 0.02 |
ACE inhibitors and/or ARB | 2519 | 723 (28.7%) | 643 (27.4%) | 80 (46.2%) | <0.001 |
Results
Covariate | SD | Plasma (loge) KTRa (nmol/μmol) | Urine (loge) KTRb (nmol/μmol) | ||
---|---|---|---|---|---|
βc (95% CI) |
p
| βc (95% CI) |
p
| ||
Age (years) | 10.4 | 0.12 (0.08, 0.16) | <0.001 | 0.15 (0.11, 0.20) | <0.001 |
Sex (men) | – | −0.012 (−0.046, 0.022) | 0.50 | 0.024 (−0.017, 0.066) | 0.25 |
BMI (kg/m2) | 3.71 | 0.066 (0.033, 0.099) | <0.001 | 0.023 (−0.017, 0.063) | 0.26 |
eGFR (ml min−1 1.73 m−2) | 0.24 | −0.22 (−0.26, −0.17) | <0.001 | −0.125 (−0.178, −0.072) | <0.001 |
CADd (dichotomous) | – | 0.015 (−0.022, 0.052) | 0.43 | 0.021 (−0.024, 0.066) | 0.36 |
Urine albumin:creatinine ratio (mg/mmol) | 0.88 | −0.009 (−0.042, 0.024) | 0.59 | 0.043 (0.003, 0.083) | 0.03 |
HbA1c (%) | 0.15 | 0.009 (−0.022, 0.041) | 0.56 | 0.006 (−0.032, 0.044) | 0.77 |
Triacylglycerol (mmol/l) | 0.50 | −0.001 (−0.034, 0.032) | 0.95 | −0.067 (−0.107, −0.027) | 0.001 |
ApoA-1 (g/l) | 0.20 | −0.094 (−0.128, −0.059) | <0.001 | −0.061 (−0.103, −0.019) | 0.004 |
CRP (nmol/l) | 1.08 | 0.039 (0.006, 0.072) | 0.02 | 0.092 (0.052, 0.132) | <0.001 |
Neopterin (nmol/l) | 0.37 | 0.46 (0.42, 0.50) | <0.001 | 0.28 (0.23, 0.33) | <0.001 |
Use of statins | – | 0.047 (0.013, 0.082) | 0.007 | 0.013 (−0.029, 0.055) | 0.54 |
Use of loop diuretics | – | 0.011 (−0.022, 0.044) | 0.52 | −0.028 (−0.068, 0.012) | 0.18 |
Use of thiazides | – | −0.016 (−0.049, 0.018) | 0.36 | −0.006 (−0.046, 0.033) | 0.75 |
Use of ACE inhibitors and/or ARB | – | 0.019 (−0.016, 0.053) | 0.28 | 0.0001 (−0.041, 0.041) | 0.99 |
Use of β-blocker | – | −0.015 (−0.048, 0.019) | 0.38 | −0.032 (−0.073, 0.008) | 0.12 |
Per SD increase | Q4 vs Q1 | |||
---|---|---|---|---|
HR (95% CI) |
p
| HR (95% CI) |
p
| |
Plasma (loge) KTR | ||||
Model 1c
| 1.14 (0.97, 1.33) | 0.11 | 1.27 (0.80, 2.03) | 0.31 |
Model 2d
| 0.99 (0.78, 1.22) | 0.91 | 0.97 (0.54, 1.73) | 0.92 |
Urine (loge) KTR | ||||
Model 1c
| 1.39 (1.19, 1.62) | <0.001 | 2.59 (1.56, 4.30) | <0.001 |
Model 2d
| 1.38 (1.16, 1.64) | <0.001 | 2.35 (1.39, 3.96) | 0.001 |