Long-Term Effects of Pioglitazone on Carotid Atherosclerosis in Japanese Patients with Type 2 Diabetes without a Recent History of Macrovascular Morbidity

Yamasaki, Yoshimitsu; Katakami, Naoto; Furukado, Shigetaka; Kitagawa, Kazuo; Nagatsuka, Kazuyuki; Kashiwagi, Atsunori; Daida, Hiroyuki; Kawamori, Ryuzo; Kaku, Kohei

doi:10.5551/jat.4663

Cited by 37 publications

(24 citation statements)

References 28 publications

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“…In contrast, the LDL cholesterol level was the only parameter to show a significant improvement in the non-pioglitazone group. Some of the positive effects of pioglitazone identified in the present study were also previously reported by our group, including the effects on glycated hemoglobin and HDL cholesterol 17) . Other researchers have also reported that pioglitazone therapy results in a significant reduction of systolic blood pressure in type 2 diabetic patients 23) .…”

Section: Discussionsupporting

confidence: 89%

“…In a recent multicenter study, we reported the effectiveness of pioglitazone in reducing the intimamedia thickness of the common carotid artery in Japanese subjects with type 2 diabetes for up to three years 17) . Based on these results, we designed the present study to examine the effects of pioglitazone on macrovascular diseases (all-cause death, nonfatal cerebral infarction and nonfatal myocardial infarction) in Japanese patients with type 2 diabetes at high risk of stroke.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Pioglitazone on Macrovascular Events in Patients with Type 2 Diabetes Mellitus at High Risk of Stroke: The PROFIT-J Study

Yoshii

Onuma

Yamazaki

et al. 2014

JAT

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Aim: The present study evaluated the effects of pioglitazone treatment on the incidence of primary cardiovascular events in Japanese subjects with type 2 diabetes mellitus at high risk of stroke. Methods: A prospective, multicenter, randomized, open label, comparative study was conducted among diabetic patients recruited from 50 medical institutions nationwide. A total of 522 patients with hypertension and/or dyslipidemia who had one or more silent cerebral infarcts, advanced carotid atherosclerosis or microalbuminuria at baseline were randomly treated with (n= 254) or without pioglitazone (n = 268) and observed for a medium of 672 days. The hypertension and dyslipidemia were concurrently treated according to the respective treatment guidelines. The primary outcome was the time to the first occurrence of a composite of all-cause death, nonfatal cerebral infarction and nonfatal myocardial infarction. Results: Treatment with pioglitazone resulted in significant reductions in the levels of HbA1c, diastolic blood pressure and LDL-cholesterol and a significant increase in the levels of HDL-cholesterol. The pioglitazone non-users exhibited a significant reduction in the LDL-cholesterol levels alone. Primary events were registered during the study period in nine patients in the pioglitazone group and 10 patients in the non-pioglitazone group. The difference in the cumulative incidence of the primary outcome was not significant between the two groups (1.8% per year). Conclusions: Pioglitazone therapy produces immediate and effective improvements in glycemic control, diastolic blood pressure and lipid profiles. While this study was too underpowered to determine the effects of pioglitazone on the incidence of cardiovascular events, the results indicated that two years of pioglitazone treatment did not produce any statistically significant reductions in the rate of primary cardiovascular events.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Effects of Pioglitazone on Macrovascular Events in Patients with Type 2 Diabetes Mellitus at High Risk of Stroke: The PROFIT-J Study

Yoshii

Onuma

Yamazaki

et al. 2014

JAT

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“…These three values were averaged. The greatest value among the six averaged IMT values (three from the left and three from the right) was used as the representative value (mean IMT) for each individual [18,19]. For the assessment of carotid artery stiffness, the systolic (Ds) and diastolic (Dd) inside diameter of the bilateral carotid artery were measured approximately 2 cm proximal to the carotid bifurcation at a plaque-free site on M-mode images from recordings made over five cardiac cycles [20].…”

Section: Measurement Of Intima-media Thickness and Stiffness Parametementioning

confidence: 99%

Visit-to-visit blood pressure variations

Nagai

Hoshide

Ishikawa

et al. 2012

Journal of Hypertension

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“…The maximal IMT was defined as the greatest axial thickness in the carotid arteries. The mean IMT was calculated as the average of the values of the maximal IMT and two surrounding points on both sides (each 1 cm distant from the point of the maximal IMT) 20) . The mean and maximal IMT values on the side with the highest values were used for the analysis.…”

Section: Measurement Of the Carotid Imtmentioning

confidence: 99%

Elevation of HDL-C in Response to Statin Treatment is Involved in the Regression of Carotid Atherosclerosis

Ishigaki¹,

Kono²,

Katagiri³

et al. 2014

JAT

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Aim: Atherosclerosis is strongly associated with an increased mortality in subjects with diabetes. The carotid intima-media thickness (IMT) is commonly measured as a surrogate marker for cardiovascular risk. Statins are well-established protective agents against atherosclerosis and reportedly suppress IMT progression in subjects with diabetes. To clarify the effects of statins on subclinical atherosclerosis, we herein investigated changes in the carotid IMT and lipid profiles in a multi-center, prospective, randomized trial. Methods: Hypercholesterolemic subjects with type 2 diabetes were randomly assigned to open-label treatment with either pravastatin or pitavastatin. The primary endpoint of this study was the IMT change after 36 months of statin treatment. Results: A total of 97 subjects (51 pitavastatin; 46 pravastatin) completed this 36-month study. The LDL-C decreased significantly from 163.4±27.9 mg/dl at baseline to 100.4±19.6 mg/dl at 36 months in the pitavastatin group and from 159.7±25.6 mg/dl to 118.5±22.1 mg/dl in the pravastatin group. The mean IMT showed moderate regression in both the pitavastatin (−0.070±0.215 mm, P＜0.05) and the pravastatin (−0.067±0.260 mm) group. However, there was no significant difference in the IMT change between the two groups. When the two groups were combined, the 36-month change in the mean IMT was significantly associated with HDL-C change (r= −0.24, P= 0.03). Multiple linear regression analysis revealed the change in HDL-C to be an independent variable showing a positive correlation with the carotid IMT reduction. Conclusion: The administration of statins for 3 years to subjects with type 2 diabetes resulted in a significant regression of the carotid IMT. An elevation of the plasma HDL-C with statin treatment was closely related to a regression of atherosclerosis.

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Long-Term Effects of Pioglitazone on Carotid Atherosclerosis in Japanese Patients with Type 2 Diabetes without a Recent History of Macrovascular Morbidity

Cited by 37 publications

References 28 publications

Effects of Pioglitazone on Macrovascular Events in Patients with Type 2 Diabetes Mellitus at High Risk of Stroke: The PROFIT-J Study

Effects of Pioglitazone on Macrovascular Events in Patients with Type 2 Diabetes Mellitus at High Risk of Stroke: The PROFIT-J Study

Visit-to-visit blood pressure variations

Elevation of HDL-C in Response to Statin Treatment is Involved in the Regression of Carotid Atherosclerosis

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