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ABSTRACT
Background:
Endothelial dysfunction has been documented in patients with type 2 diabetes especially when combined with hypertension. We prospectively investigated the effects of pioglitazone in improving endothelial function in hypertensive type 2 diabetic patients during the 6-month follow-up.
Methods:
Hypertensive type 2 diabetic patients were randomly assigned to pioglitazone (n = 25) or placebo (n = 25). Primary endpoint was to compare changes in brachial artery flow-mediated dilation (baFMD) between the 2 groups during the 6-month follow-up. Secondary endpoints were to compare changes in the circulating levels of microRNA-17, -21, 92a, -126, and -145 which have been known as indicators of endothelial cell migration and atherosclerosis progression during the 6-month follow-up. Inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitive C-reactive protein, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were compared during the follow-up.
Results:
The prevalences of risk factors such as hyperlipidemia, smoking, stroke, and family history of coronary artery disease did not show significant differences between the 2 groups. Increases in baFMD (0.33 ± 0.34 mm vs. 0.02 ± 0.25 mm, p < 0.05, respectively) and in the level of circulating microRNA-21 (0.23 ± 0.05 vs. -0.06 ± 0.04, p < 0.05, respectively) were significantly greater in the pioglitazone group when compared to the placebo group during the 6-month follow-up. No significant differences in the prevalences of new onset heart failure, fracture, and bladder cancer were noted during the follow-up between the 2 groups. Decreases in the levels of inflammatory marker such as IL-6 (-2.54 ± 2.32 pg/mL vs. -1.34 ± 2.12 pg/mL, p < 0.05, respectively), TNF-α (-1.54 ± 1.51 pg/mL vs. 0.14 ± 1.12 pg/mL, p < 0.05, respectively), sICAM-1 (-39 ± 52 ng/mL vs. 6 ± 72 ng/mL, p < 0.05, respectively), and sVCAM-1 (-154 ± 198 ng/mL vs. -11 ± 356 ng/mL, p < 0.05, respectively) were significantly greater in the pioglitazone group compared to the placebo group during the follow-up.
References
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Fig. 1.
Comparison of changes in brachial artery flow-mediated dilatation during the 6-month follow-up between the pioglitazone and control groups.
Fig. 2.
(A) MicroRNA-21 increased significantly only in the pioglitazone group during the 6-month F/U, and (B) significant correlation was found between the changes in microRNA-21 and changes in brachial artery flow-mediated dilatation. (C) No significant differences were found with changes in microRNA-17, -92a, -126, and -145. baFMD, brachial artery flow-mediated dilation; F/U, follow-up.
Table 1.
Baseline patient characteristics
Table 2.
Changes in brachial artery flow-mediated dilatation during the 6-month follow-up
| Variable | Pioglitazone group (n = 25) | Control group (n = 25) | ||
|---|---|---|---|---|
| Baseline | After 6 months | Baseline | After 6 months | |
| Brachial artery diameter at rest (mm) | 4.47 ± 0.58 | 4.51 ± 0.49 | 4.59 ± 0.59 | 4.57 ± 0.57 |
| Flow-mediated dilatation (mm) | 4.58 ± 0.58 | 4.91 ± 0.43*,† | 4.71 ± 0.59 | 4.73 ± 0.58 |
| Changes from at rest (mm) | 0.11 ± 0.06 | 0.40 ± 0.08*,† | 0.12 ± 0.07 | 0.16 ± 0.07 |
| Changes from baseline (mm) | 0.33 ± 0.34† | 0.02±0.25 | ||
Table 3.
Changes in the level of inflammatory markers during the 6-month follow-up
| Variable | Pioglitazone group (n = 25) | Control group (n = 25) | ||
|---|---|---|---|---|
| Baseline | After 6 months | Baseline | After 6 months | |
| Interleukin-6 (pg/mL) | 3.91 ± 3.12 | 1.45 ± 1.10* | 3.56 ± 3.21 | 2.23 ± 1.71* |
| Changes from baseline (pg/mL) | -2.54 ± 2.32† | -1.34 ± 2.12 | ||
| Tumor necrosis factor-α (pg/mL) | 5.71 ± 4.19 | 4.16 ± 2.56* | 5.16 ± 3.41 | 4.99 ± 3.11 |
| Changes from baseline (pg/mL) | -1.54 ± 1.51† | 0.14 ± 1.12 | ||
| High-sensitive C-reactive protein (mg/L) | 4.89 ± 4.11 | 1.80 ± 1.57* | 5.11 ± 4.22 | 1.89 ± 1.81* |
| Changes from baseline (mg/L) | -3.09 ± 3.01 | -3.21 ± 2.98 | ||
| Adiponectin (μ g/mL) | 5.29 ± 4.17 | 6.76 ± 4.14* | 5.55 ± 3.85 | 6.49 ± 4.66* |
| Changes from baseline (μ g/mL) | 1.47 ± 0.89† | 0.98 ± 0.88 | ||
| sICAM-1 (ng/mL) | 430 ± 154 | 391 ± 133* | 416 ± 131 | 422 ± 172 |
| Changes from baseline (ng/mL) | -39 ± 52† | 6 ± 72 | ||
| sVCAM-1 (ng/mL) | 1107 ± 344 | 954 ± 328* | 1088 ± 429 | 1077 ± 401 |
| Changes from baseline (ng/mL) | -154 ± 198† | -11 ± 356 | ||
Table 4.
Changes in the level of lipid profiles during the 6-month follow-up
| Variable | Pioglitazone group (n = 25) | Control group (n = 25) | ||
|---|---|---|---|---|
| Baseline | After 6 months | Baseline | After 6 months | |
| Total cholesterol (mg/dL) | 220 ± 54 | 144 ± 41* | 215 ± 44 | 141 ± 32* |
| Changes from baseline (mg/dL) | -76 ± 62 | -75 ± 43 | ||
| Low density lipoprotein cholesterol (mg/dL) | 143 ± 73 | 73 ± 53* | 146 ± 108 | 77 ± 39* |
| Changes from baseline (mg/dL) | -70 ± 39 | -68 ± 42 | ||
| High density lipoprotein cholesterol (mg/dL) | 44 ± 27 | 46 ± 18 | 40 ± 22 | 45 ± 12 |
| Changes from baseline (mg/dL) | 2 ± 9 | 4 ± 7 | ||
| Triglyceride (mg/dL) | 127 ± 71 | 110 ± 94 | 123 ± 74 | 113 ± 69 |
| Changes from baseline (mg/dL) | -16 ± 70 | -10 ± 59 | ||
Table 5.
Comparison of adverse clinical events between the 2 groups during the 6-month follow-up
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