Retinol-Binding Protein-4—A Predictor of Insulin Resistance and the Severity of Coronary Artery Disease in Type 2 Diabetes Patients with Coronary Artery Disease
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Sample Size Calculation
2.3. Aim and Hypotheses
2.4. Demographic and Clinical Information, and Anthropometric Measurements
2.5. Biochemical Parameters
2.6. RBP-4 Assay Protocol
2.7. Statistical Analysis
2.8. Operational Definitions
3. Results
3.1. Demographic and Clinical Factors of Study Population
3.2. The Severity of CAD
3.3. Association of Clinical Factors with RBP-4
3.4. Association of Clinical Factors with IR
3.5. Association of Clinical Factors with the Severity of CAD
3.6. Association of RBP-4 Levels with IR and the Severity of CAD
3.7. Association of IR and the Severity of CAD in Correlation with RBP-4 Levels and Clinical Factors (Secondary Analysis)
4. Discussion
Strengths and Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Association of RBP-4 with Clinical Factors | ||
---|---|---|
Group | Parameter | p-Value |
T2D + CAD | A1C | 0.034 |
hs-CRP | <0.001 | |
LDL-c | <0.001 | |
HDL-c | 0.001 | |
TG | 0.028 | |
Bi + I | <0.001 | |
Bi + SGLT2 + I | 0.001 | |
Bi + SU | <0.001 | |
Bi | <0.001 | |
SU | <0.001 | |
Nitrates | 0.008 | |
Diuretics | 0.002 | |
Cardiac glycosides | <0.001 | |
T2D-only | FPI | 0.032 |
TC | 0.031 | |
CAD-only | – | – |
Association of clinical factors with IR and the severity of CAD | ||
Group | Factor | p-value |
T2D + CAD | ||
IR | FPG | 0.011 |
FPI | <0.001 | |
hs-CRP | 0.025 | |
Bi + DPP4i + I | 0.008 | |
Antiplatelet agents | 0.003 | |
ACEI | 0.026 | |
Severity of CAD | FPG | a 0.007 b 0.012 |
FPI | a 0.045 | |
DPP4i | a <0.001 b <0.001 | |
SU + DPP4i | a 0.011 b 0.016 | |
Bi + DPP4i + I | a <0.001 b 0.003 | |
ACEI | a 0.032 b 0.029 | |
AB | a 0.008 b 0.020 | |
Fibrates | b <0.001 | |
Statins | b 0.018 | |
Hematinic agents | a 0.011 b 0.016 | |
T2D-only | ||
IR | FPI | <0.001 |
Severity of CAD | – | – |
CAD-only | ||
IR | FPG | 0.048 |
FPI | <0.001 | |
Severity of CAD | FPG | a <0.001 |
FPI | b <0.001 | |
A1C | b <0.001 | |
LDL-c | b 0.004 | |
HDL-c | a <0.001 | |
TG | b 0.001 | |
Association of RBP-4 with IR and the severity of CAD | ||
Group | Factor | p-value |
T2D + CAD | ||
IR | RBP-4 | 0.002 |
Severity of CAD | a 0.017 b 0.022 | |
T2D-only | ||
IR | RBP-4 | 0.042 |
Severity of CAD | – | |
CAD-only | ||
IR | RBP-4 | 0.031 |
Severity of CAD | a 0.002 b 0.001 |
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Parameter | OR (95% CI) | ||
---|---|---|---|
T2D + CAD (n = 150) | T2D-Only (n = 90) | CAD-Only (n = 60) | |
FPG (mmol/L) | 1.088 (0.983–1.204) | 0.937 (0.825–1.065) | 0.943 (0.328–2.707) |
FPI (pmol/L) | 0.995 (0.987–1.002) | 1.220 (1.041–1.430) | 0.936 (0.846–1.036) |
A1C (%) | 0.797 (0.654–0.970) | 1.048 (0.856–1.283) | 0.869 (0.268–2.820) |
hs-CRP (mg/L) | 1.317 (1.052–1.632) | 1.728 (0.776–3.845) | 1.214 (0.248–5.939) |
TC (mmol/L) | 1.017 (0.783–1.230) | 1.345 (1.033–1.589) | 1.476 (0.715–3.047) |
LDL-c (mmol/L) | 2.918 (1.428–3.385) | 0.602 (0.339–1.069) | 1.261 (0.533–2.986) |
HDL-c (mmol/L) | 0.490 (0.300–0.800) | 1.181 (0.265–5.264) | 0.965 (0.750–2.455) |
TG (mmol/L) | 1.402 (1.201–1.702) | 0.740 (0.437–1.255) | 0.983 (0.435–2.218) |
Hypertension | 0.244 (0.040–1.251) | 1.102 (0.175–6.940) | 3.062 (0.248–7.879) |
Dyslipidemia | 2.336 (0.708–7.708) | 2.800 (0.548–14.311) | 0.557 (0.096–3.244) |
Peripheral neuropathy | 0.635 (0.325–1.240) | 1.021 (0.440–2.368) | 5.667 (0.239–19.655) |
Chronic kidney disease (CKD) | 1.615 (0.691–3.778) | 1.483 (0.526–4.183) | 0.160 (0.009–2.823) |
Retinopathy | 0.547 (0.255–1.173) | 0.839 (0.338–2.083) | 5.667 (0.778–10.661) |
Anemia | 0.783 (0.048–12.760) | 0.731 (0.050–2.065) | 4.076 (0.421–40.755) |
Gastritis | 0.786 (0.333–1.546) | 4.371 (0.437–43.763) | 0.327 (0.026–4.034) |
Biguanides | 6.400 (2.024–20.237) | 0.613 (0.220–1.705) | – |
Sulphonylureas | 17.714 (5.812–53.993) | 1.482 (0.590–3.722) | – |
DPP4i | 8.400 (0.056–34.855) | 1.005 (0.399–2.529) | – |
AGI | 0.786 (0.045–1.433) | 0.731 (0.088–4.033) | – |
Meglitinides | 0.786 (0.088–2.113) | 1.031 (0.326–3.264) | – |
Biguanide + SU | 10.000 (3.240–30.866) | 1.360 (0.539–3.432) | – |
SU + DPP4i | 9.056 (0.076–65.877) | 0.907 (0.144–5.715) | – |
Biguanide + insulin | 1.206 (1.093–1.458) | – | – |
Biguanide + SU + insulin | 1.290 (0.310–5.365) | – | – |
Biguanide + DPP4i + insulin | 0.021 (0.006–0.043) | – | – |
Biguanide + SGLT2 + insulin | 1.161 (1.053–1.493) | – | – |
SGLT2 + insulin | 0.308 (0.034–2.821) | – | – |
Antiplatelet agents | 4.114 (0.469–36.102) | – | 0.008 (0.002–0.015) |
ACEI | 0.847 (0.443–1.619) | 0.724 (0.268–1.951) | 0.429 (0.090–2.043) |
ARB II | 0.530 (0.237–1.187) | 1.052 (0.429–2.579) | 2.909 (0.666–12.708) |
Calcium channel blockers | 1.041 (0.496–2.182) | 1.235 (0.534–2.859) | 1.818 (0.390–8.466) |
Beta blockers | 1.106 (0.578–2.114) | 1.029 (0.445–2.377) | 0.318 (0.064–1.574) |
Alpha blockers | 9.664 (0.099–45.123) | 0.731 0.045–3.912) | – |
Nitrates | 2.657 (1.331–5.303) | – | 2.629 (0.425–16.263) |
Fibrates | 7.690 (0.065–33.878) | – | – |
Statins | 0.040 (0.012–0.077) | 7.760 (0.013–27.112) | – |
Diuretics | 1.297 (1.141–1.624) | 1.283 (0.522–3.153) | 2.629 (0.425–16.263) |
Antianginal drugs | 1.983 (0.935–4.205) | – | 0.500 (0.046–5.423) |
Hematinic agents | 3.925 (0.402–38.903) | 0.676 (0.059–7.735) | 0.380 (0.061–2.354) |
Cardiac glycosides | 18.444 (2.331–145.961) | – | – |
Parameter | HOMA-IR, OR (95% CI) | ||
---|---|---|---|
T2D + CAD (n = 150) | T2D-Only (n = 90) | CAD-Only (n = 60) | |
FPG (mmol/L) | 1.160 (1.031–1.306) | 1.010 (0.894–1.142) | 2.570 (1.097–5.773) |
FPI (pmol/L) | 1.233 (1.146–1.327) | 1.376 (1.197–1.581) | 1.368 (1.167–1.603) |
A1C (%) | 1.102 (0.913–1.331) | 1.098 (0.896–1.344) | 2.122 (0.759–5.932) |
hs-CRP (mg/L) | 2.378 (1.155–4.899) | 1.394 (0.636–3.057) | 3.502 (0.909–13.493) |
TC (mmol/L) | 0.813 (0.622–1.063) | 1.159 (0.809–1.660) | 0.775 (0.443–1.356) |
LDL-c (mmol/L) | 0.942 (0.650–1.366) | 1.119 (0.675–1.855) | 0.806 (0.405–1.606) |
HDL-c (mmol/L) | 0.738 (0.500–1.089) | 0.702 (0.159–3.100) | 0.524 (0.053–5.140) |
TG (mmol/L) | 0.973 (0.673–1.407) | 0.799 (0.482–1.324) | 0.627 (0.292–1.342) |
Hypertension | 0.614 (0.147–2.556) | 1.687 (0.268–10.617) | 6.304 (0.044–19.030) |
Dyslipidemia | 0.515 (0.176–1.505) | 1.951 (0.456–8.341) | 0.684 (0.149–3.134) |
Peripheral neuropathy | 0.633 (0.319–1.258) | 0.980 (0.426–2.253) | – |
Chronic kidney disease (CKD) | 0.990 (0.415–2.359) | 2.645 (0.893–7.831) | 2.867 (0.169–48.744) |
Retinopathy | 1.319 (0.629–2.768) | 0.879 (0.360–2.147) | – |
Anemia | 1.596 (0.098–26.032) | – | – |
Gastritis | – | 1.098 (0.148–8.152) | – |
Biguanides | 0.750 (0.365–1.540) | 0.689 (0.254–1.870) | – |
Sulphonylureas | 1.076 (0.496–2.332) | 0.714 (0.292–1.747) | – |
DPP4i | 0.006 (0.002–0.010) | 1.133 (0.455–2.822) | – |
AGI | 1.586 (0.066–2.887) | 0.915 (0.052–4.835) | – |
Biguanide + SU | 1.201 (0.509–2.835) | 0.413 (0.163–1.046) | – |
SU + DPP4i | 0.012 (0.006–0.030) | 4.718 (0.506–43.984) | – |
Biguanide + insulin | 0.681 (0.333–1.394) | – | – |
Biguanide + SU + insulin | 1.630 (0.391–6.787) | – | – |
Biguanide + DPP4i + insulin | 1.860 (1.043–2.027) | – | – |
Biguanide + SGLT2 + insulin | 1.033 (0.445–2.395) | – | – |
SGLT2 + insulin | 2.455 (0.398–15.155) | – | – |
Antiplatelet agents | 1.454 (1.032–1.895) | – | 6.011 (0.042–36.772) |
ACEI | 1.444 (1.227–1.868) | 2.353 (0.872–6.351) | 3.800 (1.006–14.351) |
ARB II | 1.829 (0.845–3.961) | 0.524 (0.214–1.285) | 0.429 (0.123–1.495) |
Calcium channel blockers | 0.662 (0.303–1.446) | 0.644 (0.280–1.481) | 1.768 (0.488–6.397) |
Beta blockers | 0.824 (0.426–1.594) | 1.318 (0.575–3.024) | 2.111 (0.509–8.751) |
Alpha blockers | 2.702 (0.038–16.806) | – | 0.364 (0.033–1.452) |
Nitrates | 0.768 (0.382–1.544) | – | 0.433 (0.086–2.196) |
Fibrates | 2.607 (0.028–6.442) | – | – |
Statins | 0.009 (0.004–0.014) | 15.436 (0.078–66.022) | – |
Diuretics | 1.699 (0.853–3.384) | 0.750 (0.305–1.843) | 0.433 (0.086–2.195) |
Antianginal drugs | 0.594 (0.267–1.320) | – | 9.923 (0.950–33.701) |
Hematinic agents | 1.607 (0.220–11.735) | 0.536 (0.047–6.128) | 2.308 (0.456–11.690) |
Cardiac glycosides | 0.263 (0.058–1.232) | – | – |
Parameter | Severity of CAD, OR (95% CI) | |
---|---|---|
T2D + CAD (n = 150) | CAD-Only (n = 60) | |
FPG (mmol/L) | a 1.815 (1.710–1.935) b 1.875 (1.771–1.992) | a1.651 (1.201–2.110) b 0.458 (0.151–1.388) |
FPI (pmol/L) | a 1.011 (0.997–1.026) b 1.015 (1.001–1.030) | a 0.984 (0.885–1.094) b 1.553 (1.054–2.105) |
A1C (%) | a 0.898 (0.712–1.133) b 0.939 (0.747–1.179) | a 0.626 (0.161–2.444) b 1.318 (1.087–1.858) |
hs-CRP (mg/L) | a 0.652 (0.369–1.154) b 0.801 (0.518–1.237) | a 3.229 (0.548–19.036) b 2.726 (0.526–14.473) |
TC (mmol/L) | a 0.880 (0.632–1.227) b 0.772 (0.546–1.092) | a 0.685 (0.314–1.492) b 1.424 (0.712–2.848) |
LDL-c (mmol/L) | a 1.169 (0.722–1.895) b 0.901 (0.543–1.494) | a 0.510 (0.197–1.321) b 1.722 (1.296–2.538) |
HDL-c (mmol/L) | a 1.007 (0.602–1.686) b 1.059 (0.635–1.764) | a3.754 (1.185–76.172) b 2.218 (0.130–3.789) |
TG (mmol/L) | a 1.090 (0.689–1.724) b 0.726 (0.437–1.207) | a 0.736 (0.285–1.899) b 1.299 (1.007–1.523) |
Hypertension | a 2.963 (0.331–26.504) b 1.143 (0.100–13.105) | a 4.144 (0.349–20.714) b 5.329 (0.957–29.532) |
Dyslipidemia | a 0.926 (0.207–4.147) b 1.373 (0.330–5.711) | a 1.875 (0.171–20.609) b 2.000 (0.207–19.336) |
Peripheral neuropathy | a 0.783 (0.320–1.912) b 0.660 (0.271–1.609) | – – |
Chronic kidney disease (CKD) | a 0.875 (0.272–2.818) b 0.763 (0.240–2.424 | a 0.055 (0.015–0.368) b 0.976 (0.843–1.280) |
Retinopathy | a 0.791 (0.298–2.097) b 1.006 (0.371–2.728) | – – |
Anemia | a 1.006 (0.954–1.087) b 1.014 (0.076–1.632) | a 1.065 (0.045–2.060) b 0.063 (0.036–0.123) |
Gastritis | – – | a 1.800 (0.101–31.988) b 2.900 (0.166–50.815) |
Biguanides | a 1.203 (0.491–2.945) b 1.500 (0.602–3.740) | – – |
Sulphonylureas | a 1.008 (0.387–2.625) b 1.800 (0.646–5.018) | – – |
DPP4i | a 1.269 (1.008–1.865) b 2.149 (1.320–3.326) | – – |
Biguanide + SU | a 1.319 (0.450–3.872) b 1.466 (0.490–4.387) | – – |
SU + DPP4i | a 1.654 (1.054–2.022) b 1.754 (1.132–2.503) | – – |
Biguanide + insulin | a 0.525 (0.194–1.418) b 0.441 (0.164–1.184) | – – |
Biguanide + SU + insulin | a 2.850 (0.451–17.999) b 1.833 (0.348–9.652) | – – |
Biguanide + DPP4i + insulin | a 1.545 (1.008–1.967) b 1.877 (1.210–3.116) | – – |
Biguanide + SGLT2 + insulin | a 1.778 (0.612–5.165) b 1.367 (0.487–3.837) | – – |
SGLT2 + insulin | a 0.891 (0.078–10.210) b 0.875 (0.076–10.033) | – – |
Antiplatelet agents | a 1.123 (0.098–12.872) b 1.745 (0.174–17.492) | a 4.647 (0.077–8.945) b 0.945 (0.768–1.490) |
ACEI | a 1.487 (1.085–3.532) b 1.166 (1.032–2.890) | a 0.833 (0.126–5.504) b 0.889 (0.151–5.241) |
ARB II | a 1.253 (0.453–3.468) b 1.006 (0.371–2.728) | a 1.607 (0.255–10.132) b 1.636 (0.289–9.255) |
Calcium channel blockers | a 0.567 (0.209–1.537) b 1.032 (0.362–2.946) | a 1.200 (0.182–7.926) b 1.636 (0.289–9.255) |
Beta blockers | a 0.703 (0.299–1.654) b 0.548 (0.231–1.299) | a 0.375 (0.036–3.865) b 0.500 (0.052–4.834) |
Alpha blockers | a 1.795 (1.076–4.644) b 1.900 (1.056–3.012) | – – |
Nitrates | a 1.153 (0.485–2.742) b 2.112 (0.853–5.230) | a 1.875 (0.171–20.609) b 1.111 (0.103–11.965) |
Fibrates | a 0.029 (0.006–0.144) b 1.056 (1.008–1.768) | – – |
Statins | a 25.265 (0.122–46.004) b 1.087 (1.004–1.255) | – – |
Diuretics | a 0.975 (0.395–2.404) b 0.950 (0.385–2.346) | a 16.240 (3.209–57.778) b 13.325 (1.620–25.921) |
Antianginal drugs | a 0.729 (0.276–1.923) b 1.367 (0.487–3.837) | – – |
Hematinic agents | a 1.540 (1.021–2.006) b 1.444 (1.058–2.244) | a 0.533 (0.049–5.862) b 0.900 (0.084–9.692) |
Cardiac glycosides | a 1.025 (0.277–3.797) b 3.862 (0.667–22.350) | – – |
Parameter | OR (95% CI) | ||
---|---|---|---|
T2D + CAD (n = 150) | T2D-Only (n = 90) | CAD-Only (n = 60) | |
Insulin resistance | 1.667 (1.341–1.303) * | 1.594 (1.255–1.880) * | 1.385 (1.089–1.665) * |
Severity of CAD | a 1.494 (1.160–2.726) ¥ b 1.733 (1.308–2.144) ¥ | – | a 1.622 (1.099–4.923) ¥ b 4.111 (1.381–26.379) ¥ |
Parameter | OR (95% CI) | p-Value |
---|---|---|
Insulin resistance | 1.166 (1.009–3.042) * | 0.030 |
Severity of CAD | a 1.647 (1.212–1.972) ¥ b 1.815 (1.044–3.040) ¥ | 0.044 0.036 |
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Perumalsamy, S.; Ahmad, W.A.W.; Huri, H.Z. Retinol-Binding Protein-4—A Predictor of Insulin Resistance and the Severity of Coronary Artery Disease in Type 2 Diabetes Patients with Coronary Artery Disease. Biology 2021, 10, 858. https://doi.org/10.3390/biology10090858
Perumalsamy S, Ahmad WAW, Huri HZ. Retinol-Binding Protein-4—A Predictor of Insulin Resistance and the Severity of Coronary Artery Disease in Type 2 Diabetes Patients with Coronary Artery Disease. Biology. 2021; 10(9):858. https://doi.org/10.3390/biology10090858
Chicago/Turabian StylePerumalsamy, Sangeetha, Wan Azman Wan Ahmad, and Hasniza Zaman Huri. 2021. "Retinol-Binding Protein-4—A Predictor of Insulin Resistance and the Severity of Coronary Artery Disease in Type 2 Diabetes Patients with Coronary Artery Disease" Biology 10, no. 9: 858. https://doi.org/10.3390/biology10090858
APA StylePerumalsamy, S., Ahmad, W. A. W., & Huri, H. Z. (2021). Retinol-Binding Protein-4—A Predictor of Insulin Resistance and the Severity of Coronary Artery Disease in Type 2 Diabetes Patients with Coronary Artery Disease. Biology, 10(9), 858. https://doi.org/10.3390/biology10090858