Introduction
Methods
Study population, definitions of incidence outcomes and selection criteria
Clinical measurements and assessments of risk factors
Targeted SRM-MS protein measurements
Statistical analysis
Results
Descriptive statistics
Characteristics | Incident type 2 diabetes | Incident (pre)diabetes | ||||
---|---|---|---|---|---|---|
Non-casesan = 660 | Casesbn = 123 | p valuee | Non-casescn = 446 | Casesdn = 255 | p valuee | |
Male (%) | 47.3 | 56.1 | 0.089 | 43.7 | 57.6 | 0.001 |
Characteristics at baseline | ||||||
Age (years) | 57.4 ± 9.4 | 63.4 ± 8.6 | <0.001 | 55.8 ± 9.1 | 59.9 ± 9.3 | <0.001 |
Waist circumference (cm) | 92.4 ± 13.8 | 102.2 ± 11.9 | <0.001 | 90.0 ± 12.4 | 97.5 ± 11.0 | <0.001 |
Height (cm) | 169.0 ± 9.4 | 167.9 ± 9.2 | 0.377 | 169.0 ± 9.5 | 168.8 ± 9.5 | 0.976 |
Physically inactive (%) | 35.5 | 51.2 | 0.001 | 33.6 | 41.6 | 0.044 |
Smoking (%) | 0.035 | 0.880 | ||||
Never | 45.0 | 55.3 | 45.1 | 45.1 | ||
Former | 39.2 | 36.6 | 39.0 | 37.6 | ||
Current | 15.8 | 8.1 | 15.9 | 17.3 | ||
Actual hypertension (%) | 34.7 | 57.7 | <0.001 | 26.9 | 47.1 | <0.001 |
Parental history of diabetes (%) | 0.010 | <0.001 | ||||
No | 61.4 | 48.8 | 67.3 | 46.7 | ||
Unknown | 15.0 | 20.3 | 11.7 | 24.3 | ||
One parent | 21.4 | 24.4 | 19.5 | 25.1 | ||
Both parents | 2.3 | 6.5 | 1.6 | 3.9 | ||
Sibling history of diabetes (%) | 6.2 | 15.4 | 0.001 | 4.3 | 8.6 | 0.028 |
Triglyceride level (mmol/l)f | 1.2 (0.8, 1.6) | 1.6 (1.2, 2.2) | <0.001 | 1.1 (0.8, 1.5) | 1.3 (0.9, 1.9) | <0.001 |
Total chol./HDL-cholesterol ratiof | 3.9 (3.2, 4.6) | 4.4 (3.8, 5.4) | <0.001 | 3.7 (3.1, 4.5) | 4.2 (3.5, 4.9) | <0.001 |
HbA1c (%) | 5.4 ± 0.3 | 5.8 ± 0.3 | <0.001 | 5.3 ± 0.3 | 5.5 ± 0.3 | <0.001 |
HbA1c (mmol/mol) | 35.6 ± 3.4 | 39.8 ± 3.6 | <0.001 | 34.9 ± 3.2 | 37.0 ± 3.2 | <0.001 |
Fasting glucosef,g (mmol/l) | 5.2 (4.9, 5.5) | 5.8 (5.4, 6.3) | <0.001 | 5.1 (4.8, 5.3) | 5.4 (5.2, 5.7) | <0.001 |
2-h-glucosef,g (mmol/l) | 5.8 (4.9, 6.9) | 8.3 (7.0, 9.2) | <0.001 | 5.4 (4.7, 6.3) | 6.3 (5.5, 7.0) | <0.001 |
Fasting insulinf,g (pmol/l) | 49.8 (36.6, 66.0) | 72.0 (53.4, 123.0) | <0.001 | 46.2 (34.2, 60.0) | 60.0 (44.4, 78.0) | <0.001 |
HOMA-IRf,g | 1.9 (1.4, 2.7) | 3.1 (2.3, 5.2) | <0.001 | 1.7 (1.3, 2.3) | 2.4 (1.8, 3.2) | <0.001 |
Characteristics at follow-up | ||||||
Fasting glucosef,g (mmol/l) | 5.4 (5.1, 5.8) | 6.8 (6.0, 7.3) | <0.001 | 5.3 (5.0, 5.5) | 6.0 (5.6, 6.3) | <0.001 |
2-h-glucosef,g (mmol/l) | 5.9 (5.0, 7.3) | 11.8 (10.3, 13.0) | <0.001 | 5.5 (4.7, 6.2) | 8.2 (7.3, 9.2) | <0.001 |
Fasting insulinf,g (pmol/l) | 55.4 (37.8, 81.0) | 96.0 (66.0, 132.0) | <0.001 | 49.2 (35.3, 68.8) | 74.9 (54.2, 104.5) | <0.001 |
HOMA-IRf,g | 2.2 (1.5, 3.3) | 4.8 (3.0, 6.9) | <0.001 | 1.9 (1.3, 2.8) | 3.4 (2.3, 4.7) | <0.001 |
Analyses focused on pathophysiological mechanisms
Prediction analyses
Basic prediction model | Selected proteins | Basic AUC (95% CI) | Extended AUC (95% CI) | Delta AUC (95% CI) | IDI overall (95% CI) | IDI cases (95% CI) | IDI controls (95% CI) | cfNRI overall (95% CI) | cfNRI cases (95% CI) | cfNRI controls (95% CI) |
---|---|---|---|---|---|---|---|---|---|---|
GDRSadapteda | MASP, adiponectin, apoE | 0.749 (0.687, 0.807) | 0.772 (0.712, 0.828) | 0.023 (–0.014, 0.051) | 0.031 (0.004, 0.059) | 0.026 (–0.004, 0.058) | 0.005 (–0.006, 0.015) | 0.393 (0.103, 0.680) | 0.119 (–0.179, 0.409) | 0.274 (0.114, 0.427) |
Age + sex + HbA1c | MASP, adiponectin, apoE | 0.816 (0.759, 0.870) | 0.828 (0.773, 0.881) | 0.012 (–0.014, 0.031) | 0.030 (0.000, 0.059) | 0.025 (–0.007, 0.059) | 0.004 (–0.006, 0.014) | 0.400 (0.116, 0.682) | 0.126 (–0.163, 0.415) | 0.275 (0.108, 0.434) |
GDRSadapted + HbA1cb | MASP, adiponectin, apoE, PZP | 0.823 (0.768, 0.875) | 0.828 (0.775 0.879) | 0.005 (–0.019, 0.024) | 0.025 (–0.006, 0.057) | 0.021 (–0.012, 0.057) | 0.003 (–0.006, 0.013) | 0.358 (0.050, 0.651) | 0.067 (–0.231, 0.364) | 0.291 (0.116, 0.460) |
Basic prediction model | Selected proteins | Basic AUC (95% CI) | Extended AUC (95% CI) | Delta AUC (95% CI) | IDI overall (95% CI) | IDI cases (95% CI) | IDI controls (95% CI) | cfNRI overall (95% CI) | cfNRI cases (95% CI) | cfNRI controls (95% CI) |
---|---|---|---|---|---|---|---|---|---|---|
GDRSadapteda | MASP | 0.723 (0.671, 0.773) | 0.725 (0.674, 0.775) | 0.002 (–0.017, 0.012) | 0.006 (–0.004, 0.014) | 0.004 (–0.007, 0.014) | 0.002 (–0.006, 0.009) | 0.097 (–0.145, 0.322) | 0.032 (–0.191, 0.250) | 0.065 (–0.097, 0.227) |
Age + sex + HbA1c | MASP, CRP | 0.719 (0.669, 0.771) | 0.731 (0.681, 0.781) | 0.012 (− 0.022, 0.033) | 0.021 (0.005, 0.036) | 0.013 (− 0.004, 0.031) | 0.008 (− 0.006, 0.020) | 0.270 (0.051, 0.481) | 0.100 (− 0.111, 0.308) | 0.170 (0.012, 0.326) |
GDRSadapted + HbA1cb | MASP | 0.754 (0.704, 0.802) | 0.757 (0.707, 0.805) | 0.003 (–0.014, 0.013) | 0.006 (–0.004, 0.016) | 0.004 (–0.008, 0.015) | 0.002 (–0.006, 0.010) | 0.122 (–0.116, 0.347) | 0.046 (–0.176, 0.263) | 0.076 (–0.090, 0.239) |