Effects of Different Antidiabetic Medications on Endothelial Glycocalyx, Myocardial Function, and Vascular Function in Type 2 Diabetic Patients: One Year Follow–Up Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Primary and Secondary Endpoints
2.3. Assessment of Arterial Stiffness
2.4. Flow-Mediated Dilation
2.5. Endothelial Glycocalyx
2.6. Echocardiography
2.7. Doppler Echocardiography
2.8. 2D Strain and Strain Rate Analysis
2.9. Ventricular-Arterial Interaction
2.10. LV Twisting and Untwisting
2.11. Laboratory Assays
2.12. Statistical Analysis
3. Results
3.1. Study Population
3.2. Interrelation between Metabolic, Endothelial, Vascular, and LV Function Markers at Baseline
3.3. Changes in Metabolic Parameters after 12-Month Glycaemic Control
3.4. Effect of Glycaemic Control on Vascular and Endothelial Function
3.5. Speckle Tracking Analysis
3.5.1. Longitudinal Strain
3.5.2. LV Twisting and Untwisting Velocity
3.6. Markers of Oxidative Stress
3.7. Interrelation between Metabolic, Endothelial, Vascular, and LV Function Markers after 12-Month Glycaemic Control
4. Discussion
4.1. Impact of Glycaemic Control on Vascular and Endothelial Function
4.2. Effect of Glycaemic Control on LV Myocardial Deformation
4.3. Glycaemic Control and Oxidative Stress
4.4. Study Limitations
5. Conclusions
Author Contributions
Conflicts of Interest
References
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Baseline (n = 100) | 12 months (n = 100) | p | |
---|---|---|---|
Clinical features | |||
Weight, kg | 88 ± 16 | 86 ± 15 | 0.560 |
BMI, kg/m2 | 31 ± 5 | 29 ± 6 | 0.167 |
Waist, cm | 104 ± 13 | 102 ± 14 | 0.421 |
SBP, mmHg | 138 ± 17 | 134 ± 16 | 0.042 |
DBP, mmHg | 86 ± 11 | 84 ± 11 | 0.093 |
cSBP, mmHg | 139 ± 20 | 134 ± 16 | 0.039 |
Metabolic characteristics | |||
HbA1c, % (mmol/mol) | 8.9 ± 1.8 (74 ± 24) | 7.1 ± 1.2 (54 ± 14) | 0.001 |
Fasting glucose, mg/dL | 165 ± 47 | 124 ± 40 | 0.007 |
Total cholesterol, mg/dL | 190 ± 34 | 186 ± 31 | 0.402 |
LDL cholesterol, mg/dL | 116 ± 32 | 109 ± 29 | 0.244 |
HDL cholesterol, mg/dL | 47 ± 10 | 52 ± 12 | 0.318 |
Triglycerides, mg/dL | 167 ± 92 | 159 ± 86 | 0.286 |
Creatinine, mmol/L | 1.1 ± 0.2 | 1.0 ± 0.2 | 0.734 |
eGFR, mL/min per 1.73 m2 | 85 ± 8 | 86 ± 9 | 0.321 |
Cardiac risk factors | |||
Smoking, % (n) | 37 (37) | 34 (34) | 0.675 |
Hypertension, % (n) | 50 (50) | 47 (47) | 0.277 |
Dyslipidemia, % (n) | 51 (51) | 48 (48) | 0.243 |
Family history CAD, % (n) | 21 (21) | 21 (21) | 0.889 |
Cardiovascular medication, % (n) | |||
Aspirin or clopidogrel | 8 (8) | 8 (8) | 0.910 |
Beta blockers | 19 (19) | 21 (21) | 0.753 |
Calcium channel blocker | 30 (30) | 33 (33) | 0.631 |
ACE inhibitor or ARB | 33 (33) | 36 (36) | 0.270 |
Diuretics | 14 (14) | 15 (15) | 0.798 |
Statins | 46 (46) | 49 (49) | 0.610 |
Fibrate | 5 (5) | 8 (8) | 0.270 |
Antidiabetic medication, % (n) | |||
Metformin | 85 (85) | 90 (90) | |
Sulfonylureas | 4 (4) | 5 (5) | |
Incretin-based agents | 0 (0) | 78 (78) | |
DPP-4 inhibitors | 0 (0) | 38 (38) | |
GLP-1 receptor agonists | 0 (0) | 40 (40) | |
Basal insulin analogs | 25 (25) | 39 (39) | |
Rapid-acting insulin analogs | 5 (5) | 7 (7) | |
Glucose-lowering agents used for intensified antidiabetic treatment, % (n) | |||
Metformin | 5 (5) | ||
Sulfonylureas | 1 (1) | ||
Incretin-based agents | 78 (78) | ||
DPP-4 inhibitors | 38 (38) | ||
GLP-1 receptor agonists | 40 (40) | ||
Basal insulin analogs | 14 (14) | ||
Rapid-acting insulin analogs | 2 (2) |
Characteristics | Baseline | Follow-up | ||||
---|---|---|---|---|---|---|
(n = 100) | (n = 100) | HbA1c ≤ 7% (≤53 mmol/mol) (n = 64) | Δ% (n = 64) | HbA1c >7% (>53 mmol/mol) (n = 36) | Δ% (n = 36) | |
PWV, m/s | 12 ± 3 | 10.8 ± 2 *** | 10.5 ± 2 | −13.9 | 11.2 ± 2 † | −5.1 |
AI, % | 17 (−0.5–30) | 11.5 (1–25) ** | 11.5 (1–25) | −32 | 10.5 (0.4–23) | −38 |
AI75, % | 16 (−1–28) | 11 (0.5–24) ** | 11 (0.5–24) | −31 | 10 (0.34–22) | −37.5 |
HR, bpm | 73 ± 11 | 74 ± 10 | 75 ± 10 | 2.7 | 73 ± 10 | 0 |
SBP, mmHg | 138 ± 17 | 134 ± 16 * | 133 ± 17 | −3.6 | 135 ± 14 | −2.2 |
DBP, mmHg | 86 ± 11 | 84 ± 11 | 84 ± 10 | −2.3 | 85 ± 12 | −1.2 |
cSBP, mmHg | 139 ± 20 | 134 ± 16 * | 132 ± 17 | −5.7 | 134 ± 15 | −2.9 |
FMD% | 8.1 ± 5 | 11.7 ± 8 ** | 14 ± 8 | 68.7 | 9.5 ± 7 † | 20 |
PBR, 5–25 μm | 2.12 ± 0.3 | 1.98 ± 0.2 * | 1.88 ± 0.2 | −10.9 | 2.01 ± 0.3 † | −5.6 |
PBR, 5–9 μm | 1.19 ± 0.1 | 1.14 ± 0.1 | 1.08 ± 0.2 | −9.2 | 1.12 ± 0.2 | −5.9 |
PBR, 10–19 μm | 2.26 ± 0.3 | 2.08 ± 0.3 * | 1.97 ± 0.3 | −13.2 | 2.10 ± 0.3 † | −6.6 |
PBR, 20–25 μm | 2.63 ± 0.5 | 2.46 ± 0.4 * | 2.35 ± 0.3 | −11 | 2.50 ± 0.5 † | −4.6 |
LVEF, % | 65 ± 10 | 67 ± 9 | 68 ± 9 | 4.6 | 67 ± 6 | 3 |
GLS, % | −15.2 ± 3 | −16.9 ± 3 ** | −17.6 ± 3 | 14.3 | −16 ± 3 †† | 6.7 |
GLSR S, 1/s | −0.78 ± 0.2 | −0.88 ± 0.2 ** | −0.91 ± 0.2 | 15 | −0.86 ± 0.2 † | 11.4 |
GLSR E, 1/s | 0.82 ± 0.3 | 0.96 ± 0.3 ** | 1.04 ± 0.4 | 28.4 | 0.87 ± 0.2 †† | 4.8 |
GLSR A, 1/s | 0.72 ± 0.3 | 0.75 ± 0.2 | 0.82 ± 0.2 | 13.8 | 0.70 ± 0.2 †† | 3 |
PWV/GLS | −0.84 ± 0.3 | −0.66 ± 0.2 *** | −0.62 ± 0.2 | −26.2 | −0.69 ± 0.2 | −17.9 |
pTw, deg | 16 ± 5 | 14.9 ± 7 ** | 15.4 ± 5 | −4.3 | 14.5 ± 8 | −8.8 |
pUtwVel, deg/s | −95 ± 45 | −109 ± 50 * | −112 ± 44 | 16.7 | −98 ± 49 † | 4.3 |
%dpTw-UtwMVO | 28 ± 9 | 37 ± 11 * | 38 ± 14 | 35.7 | 37 ± 13 | 32 |
%dpTw-UtwPEF | 46 ± 19 | 59 ± 18 * | 61 ± 20 | 29.8 | 58 ± 21 | 28.9 |
LA volume (mL/m2) | 40 ± 3 | 33 ± 2 * | 32 ± 2 | −20.1 | 38 ± 21 †† | −5.1 |
E/A | 0.95 ± 0.4 | 0.98 ± 0.3 | 1.04 ± 0.3 | 8.3 | 0.94 ± 0.3 | −2.1 |
E/e’ | 7.7 ± 1.8 | 7.8 ± 2.4 | 8.2 ± 2.3 | 9.3 | 7.4 ± 1.7 | −1.3 |
MDA, nM/L | 0.95 (0.56–1.7) | 0.75 * (0.50–1.5) | 0.71 (0.45–1.28) | −26.8 | 0.83 † (0.48–1.58) | −10.8 |
PCs, nmol/mg protein | 0.016 (0.008–0.021) | 0.013 * (0.009–0.016) | 0.010 (0.009–0.016) | −37.5 | 0.013 † (0.01–0.018) | −18.8 |
ΔGLS | |||
Univariate | |||
Unstandardized b | 95% CI | p value | |
Age | −0.292 | −0.815–0.231 | 0.061 |
BMI | −0.089 | −0.224–0.087 | 0.039 |
Duration of diabetes | −0.889 | −2.455–0.677 | 0.023 |
Smoking | −1.380 | −2.752–0.008 | 0.049 |
Hypertension | −3.170 | −8.095–1.755 | 0.017 |
HbA1c | −0.724 | −1.358–0.331 | 0.009 |
ΔHbA1c | 0.923 | −0.795–1.720 | 0.033 |
Incretin-based agents | 1.178 | −0.811–2.348 | 0.011 |
Multivariate | |||
Duration of diabetes | −0.209 | −0.756–0.343 | 0.048 |
Hypertension | −2.155 | −3.545–1.942 | 0.046 |
HbA1c | −0.523 | −1.576–1.190 | 0.039 |
ΔHbA1c | 0.876 | −1.109–2.141 | 0.041 |
Incretin-based agents | 0.687 | −3.518–5.269 | 0.037 |
ΔPWV | |||
Univariate | |||
Unstandardized b | 95% CI | p value | |
Age | −0.880 | −1.297–0.172 | 0.018 |
BMI | −0.061 | −0.179–0.055 | 0.070 |
Smoking | −1.438 | −3.608–0.731 | 0.017 |
ΔHbA1c | 0.562 | −0.133–0.992 | 0.004 |
Incretin-based agents | 2.244 | −0.872–3.617 | 0.002 |
Multivariate | |||
Age | −0.435 | −0.423–0.038 | 0.021 |
Smoking | −1.203 | −2.443–0.085 | 0.036 |
ΔHbA1c | 0.447 | −0.064–1.088 | 0.025 |
Incretin-based agents | 1.237 | −0.215–2.514 | 0.029 |
ΔPBR | |||
Univariate | |||
Unstandardized b | 95% CI | p value | |
BMI | −0.058 | −0.054–0.170 | 0.009 |
Duration of diabetes | −0.188 | −0.449–0.073 | 0.093 |
Hypertension | −0.603 | −0.764–0.178 | 0.033 |
Dyslipidemia | −0.831 | −1.010–0.147 | 0.030 |
ΔHbA1c | 0.650 | 0.224–0.997 | 0.016 |
Incretin-based agents | 0.687 | 0.305–1.035 | 0.037 |
Basal insulin analogs | 0.864 | −1.183–2.519 | 0.010 |
Multivariate | |||
BMI | −0.031 | −0.059–−0.021 | 0.041 |
Hypertension | −0.427 | −0.837–−0.018 | 0.044 |
Dyslipidemia | −0.245 | −1.804–0.343 | 0.045 |
ΔHbA1c | 0.395 | −0.039–0.772 | 0.038 |
Incretin-based agents | 0.429 | −0.029–0.787 | 0.047 |
Basal insulin analog | 0.628 | 0.539–1.918 | 0.042 |
ΔFMD% | |||
Univariate | |||
Unstandardized b | 95% CI | p value | |
Age | −0.417 | −1.502–0.919 | 0.034 |
Duration of diabetes | −2.269 | −4.565–0.027 | 0.017 |
HbA1c | −0.171 | −2.043–1.701 | 0.084 |
Incretin-based agents | 1.491 | −1.953–4.253 | 0.014 |
Basal insulin analogs | 1.092 | 0.345–2.495 | 0.013 |
Multivariate | |||
Age | −0.399 | −0.432–0.012 | 0.046 |
Duration of diabetes | −0.980 | −2.135–0.532 | 0.029 |
Incretin-based agents | 1.159 | 0.913–2.384 | 0.034 |
Basal insulin analogs | 0.894 | 0.574–1.898 | 0.046 |
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Lambadiari, V.; Pavlidis, G.; Kousathana, F.; Maratou, E.; Georgiou, D.; Andreadou, I.; Kountouri, A.; Varoudi, M.; Balampanis, K.; Parissis, J.; et al. Effects of Different Antidiabetic Medications on Endothelial Glycocalyx, Myocardial Function, and Vascular Function in Type 2 Diabetic Patients: One Year Follow–Up Study. J. Clin. Med. 2019, 8, 983. https://doi.org/10.3390/jcm8070983
Lambadiari V, Pavlidis G, Kousathana F, Maratou E, Georgiou D, Andreadou I, Kountouri A, Varoudi M, Balampanis K, Parissis J, et al. Effects of Different Antidiabetic Medications on Endothelial Glycocalyx, Myocardial Function, and Vascular Function in Type 2 Diabetic Patients: One Year Follow–Up Study. Journal of Clinical Medicine. 2019; 8(7):983. https://doi.org/10.3390/jcm8070983
Chicago/Turabian StyleLambadiari, Vaia, George Pavlidis, Foteini Kousathana, Eirini Maratou, Dimitrios Georgiou, Ioanna Andreadou, Aikaterini Kountouri, Maria Varoudi, Konstantinos Balampanis, John Parissis, and et al. 2019. "Effects of Different Antidiabetic Medications on Endothelial Glycocalyx, Myocardial Function, and Vascular Function in Type 2 Diabetic Patients: One Year Follow–Up Study" Journal of Clinical Medicine 8, no. 7: 983. https://doi.org/10.3390/jcm8070983