SUPPLEMENTAL DIGITAL CONTENT Supplemental digital content 1
Table S1. Additional adjustments in the association of T2D with cPWV and δPWV (as compared to normal glucose metabolism)
T2D and cPWV T2D and δPWV
Models β 95% CI p β 95% CI p
1. Crude 0.955 (0.654; 1.256) <0.001 0.821 (0.516; 1.126) <0.001
2. Model 1 + sex, age, MAP 0.377 (0.124; 0.629) 0.004 0.311 (0.027; 0.595) 0.032 3. Model 2 + prior CVD, eGFR, smoking 0.376 (0.119; 0.632) 0.004 0.301 (0.013; 0.589) 0.040
4. Model 3 + cfPWVa 0.342 (0.082; 0.602) 0.010 0.283 (-0.011; 0.577) 0.059
5. Model 3 + use of RAS-inhibitor 0.322 (0.051; 0.594) 0.020 0.331 (0.026; 0.636) 0.033 6. Model 3 + hypertension (office BP)b 0.348 (0.079; 0.618) 0.011 0.185 (-0.115; 0.485) 0.227 7. Model 3 + hypertension (24h BP)c 0.362 (0.080; 0.644) 0.012 0.282 (-0.027; 0.592) 0.074 8. Model 3 + use of anti-hypertensive medication 0.399 (0.124; 0.674) 0.005 0.317 (0.008; 0.625) 0.044 9. Model 3 + use of β-blocker 0.383 (0.118; 0.648) 0.005 0.228 (-0.068; 0.525) 0.131
10. Model 3 + HRd 0.362 (0.098; 0.626) 0.007 0.510 (0.222; 0.797) 0.001
11. Model 3 + BMI 0.340 (0.065; 0.614) 0.015 0.218 (-0.090; 0.525) 0.165
12. Model 3 + waiste 0.379 (0.102; 0.657) 0.007 0.213 (-0.098; 0.523) 0.179
13. Model 3 + waist-to-hip ratiof 0.366 (0.088; 0.645) 0.010 0.207 (-0.104; 0.518) 0.191 14. Model 3 + LDL-cholesterol, use of lipid-
modifying medicationg
0.388 (0.093; 0.683) 0.010 0.193 (-0.139; 0.525) 0.255 15. Model 3 + total cholesterol/HDL-ratio,
triglycerides, use of lipid-modifying medicationh
0.332 (0.033; 0.631) 0.030 0.202 (-0.134; 0.538) 0.237 16. Model 3 + albuminuriai 0.369 (0.107; 0.632) 0.006 0.303 (0.007; 0.599) 0.045 N=746. β, regression coefficient; BMI, body mass index; BP, blood pressure; cfPWV carotid-to-femoral pulse wave velocity; CI, confidence interval; cPWV, local carotid pulse wave velocity; CVD, cardiovascular disease; δPWV, systolic-diastolic difference in carotid pulse wave velocity; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein-cholesterol; HR, heart rate at time of vascular measurement; LDL, low-density lipoprotein cholesterol; MAP, mean arterial pressure; RAS, renin angiotensin system; st B, standardized beta; T2D, type 2 diabetes. Data of prediabetes as compared to normal glucose metabolism is not shown.
Due to missing variables the number of included individuals used in the analyses for specific variables are a735, b745; c704; d745; e744; f742; g739; h742; i736.
Table S2. Associations of prediabetes with cPWV and δPWV (as compared to normal glucose metabolism)
Prediabetes and cPWV Prediabetes and δPWV
Models β 95% CI β 95% CI
1. Crude 0.714 (0.355; 1.072) 0.429 (0.066; 0.792)
2. Model 1 + sex, age, MAP 0.069 (-0.220; 0.358) -0.119 (-0.444; 0.207)
3. Model 2 + prior CVD, eGFR, smoking 0.069 (-0.222; 0.360) -0.115 (-0.442; 0.211) 4. Model 3 + use of RAS-inhibitor 0.048 (-0.245; 0.341) -0.103 (-0.432; 0.226)
5. Model 3 + δPWV/cPWV* 0.101 (-0.177; 0.378) -0.139 (-0.450; 0.172)
N=746. β, regression coefficient; CI, confidence interval; cPWV, local carotid pulse wave velocity; CVD, cardiovascular disease; δPWV, systolic-diastolic difference in carotid pulse wave velocity; eGFR, estimated glomerular filtration rate; MAP, mean arterial pressure;
RAS-inhibitor, renin-angiotensin-system-inhibitor; T2D, type 2 diabetes.
* as appropriate. Data of type 2 diabetes as compared to normal glucose metabolism not shown (see table 2).
Table S3a. Additional general characteristics of the study population according to glucose metabolism status
Total study
population
Normal glucose metabolism
Prediabetes Type 2 diabetes P-value Advanced glycation endproducts
SAF, AUa 2.70 ± 0.53 2.58 ± 0.48 2.70 ± 0.46 2.95 ± 0.57 <0.001
Pentosidine, nmol/mmol LYSb 0.47 (0.38; 0.56) 0.49 (0.40; 0.57) 0.44 (0.38; 0.54) 0.44 (0.35; 0.56) 0.028
CML, nmol/mmol LYSb 74.4 ± 14.9 77.4 ± 14.4 72.5 ± 14.0 69.4 ± 15.0 <0.001
CEL, nmol/mmol LYSb 34.2 ± 10.3 33.1 ± 9.5 34.7 ± 10.8 36.0 ± 11.3 0.003
Other glucose measures
Fasting insulin, pmol/Lc 61 (42; 93) 52 (39; 70) 73 (49; 124) 83 (56; 122) <0.001 HOMA2-IRd 1.39 (0.96; 2.10) 1.14 (0.87; 1.55) 1.67 (1.15; 2.72) 1.98 (1.41; 2.76) <0.001 Data are presented as mean ± SD, median [interquartile-range] or frequencies (in %) as appropriate. Linear trend across glucose metabolism status was tested by ANOVA for continuous variables normally distributed, log transformed if necessary. For dichotome variables a chi-square test was used.
AU, arbitrary units, CEL, Nɛ-(carboxyethyl)lysine; CML, Nɛ-(carboxymethyl)lysine; HOMA2-IR, Homeostasis Model Assessment 2 for Insulin Resistance; SAF, skin autofluorescence.
Numbers for specific variables according to glucose metabolism status are: aSAF 720, 404/121/195; bplasma AGE 743, 414/126/203; cinsulin 743, 415/126/202;
dHOMA2-IR 712, 401/122/189.
References
1. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 2004; 27:1487-1495.
Table S3b. Additional adjustments in the associations of T2D with cPWV and δPWV (as compared to normal glucose metabolism)
T2D and cPWV T2D and δPWV
Models β 95% CI β 95% CI
1. Crude 0.955 (0.654; 1.256) 0.821 (0.516; 1.126)
2. Model 1 + sex, age, MAP 0.377 (0.124; 0.629) 0.311 (0.027; 0.595)
3. Model 2 + prior CVD, eGFR, smoking 0.376 (0.119; 0.632) 0.301 (0.013; 0.589)
4. Model 3 + SAF (AU)a 0.389 (0.128; 0.650) 0.248 (-0.047; 0.543)
5. Model 3 + pentosidine (nmol/mmol LYS)b 0.367 (0.105; 0.628) 0.294 (0.000; 0.587) 6. Model 3 + CML (nmol/mmol LYS)b 0.356 (0.090; 0.621) 0.301 (0.003; 0.599) 7. Model 3 + CEL (nmol/mmol LYS)b 0.361 (0.101; 0.621) 0.303 (0.011; 0.595)
8. Model 3 + HbA1c (%)c 0.233 (-0.121; 0.588) 0.158 (-0.240; 0.557)
9. Model 3 + insulin (pmol/L)d 0.394 (0.126; 0.661) 0.279 (-0.022; 0.580)
10. Model 3 + HOMA2-IRe 0.400 (0.115; 0.685) 0.246 (-0.070; 0.563)
N=746. AU, arbitrary units, β, regression coefficient; CI, confidence interval; CEL, Nɛ-(carboxyethyl)lysine; CML, Nɛ-(carboxymethyl)lysine; cPWV, local carotid pulse wave velocity in m/s; CVD, cardiovascular disease; δPWV, systolic-diastolic difference in carotid pulse wave velocity in m/s; eGFR, estimated glomerular filtration rate; HOMA2-IR, Homeostasis Model Assessment 2 for Insulin Resistance; MAP, mean arterial pressure; SAF, skin autofluorescence; T2D, type 2 diabetes.
* as appropriate. Data of prediabetes as compared to normal glucose metabolism not shown.
aSAF-data available in=720; bplasma AGE data available in n=743; cHbA1c data available in n=742; dinsulin data available in n=743, these results did not alter after excluding those treated with insulin; eHOMA2-IR data available in n=712, these results did not alter after excluding those treated with insulin [1].
