Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and indi...Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety （QTc intervals） were set, respectively. Probucol significantly reduced total cholesterol （P 〈 0.001）, low-density lipoprotein cholesterol （LDL-C）, （P = 0.01）, and high-density lipoprotein cholesterol （HDL-C） （P 〈 0.001） compared with conventional therapy. Cilostazol was effective in increasing HDL-C （P = 0.002） and reducing triglycerides levels （P 〈 0.01） compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein （Ox-LDL, P = 0.065）. No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.展开更多
Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. Th...Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. Methods This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group （0.5 g, twice daily） or the control group using a 1： 1 treatment ratio. IR was determined using a homeostatic model assessment-IR （HOMA-IR） index. An Excel database was established to analyze foUow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate （eGFR）, body mass index （BMI）, cholesterol, triglycerides, high-density lipoprotein （HDL）, low-density lipoprotein （LDL）, and 24-h urinary protein. Results The HOMA-IR index of the probucol group after 24 weeks was significantly decreased （P 〈 0.001） compared to the value before treatment （average decrease： 1.45; range： -2.90 to -0.43）. The HOMA-IR index in the control group increased （average increase： 0.54; range： -0.38 to 1.87）. For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR （P = 0.041）, cholesterol （P = 0.001）, fasting insulin （P 〈 0.001）, and fasting C-peptide （P = 0.001）. Conclusions Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.展开更多
文摘Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety （QTc intervals） were set, respectively. Probucol significantly reduced total cholesterol （P 〈 0.001）, low-density lipoprotein cholesterol （LDL-C）, （P = 0.01）, and high-density lipoprotein cholesterol （HDL-C） （P 〈 0.001） compared with conventional therapy. Cilostazol was effective in increasing HDL-C （P = 0.002） and reducing triglycerides levels （P 〈 0.01） compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein （Ox-LDL, P = 0.065）. No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.
文摘Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. Methods This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group （0.5 g, twice daily） or the control group using a 1： 1 treatment ratio. IR was determined using a homeostatic model assessment-IR （HOMA-IR） index. An Excel database was established to analyze foUow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate （eGFR）, body mass index （BMI）, cholesterol, triglycerides, high-density lipoprotein （HDL）, low-density lipoprotein （LDL）, and 24-h urinary protein. Results The HOMA-IR index of the probucol group after 24 weeks was significantly decreased （P 〈 0.001） compared to the value before treatment （average decrease： 1.45; range： -2.90 to -0.43）. The HOMA-IR index in the control group increased （average increase： 0.54; range： -0.38 to 1.87）. For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR （P = 0.041）, cholesterol （P = 0.001）, fasting insulin （P 〈 0.001）, and fasting C-peptide （P = 0.001）. Conclusions Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.
