Changes in carotid intima‐media thickening in patients with type 2 diabetes mellitus: Subanalysis of the Sitagliptin Preventive Study of Intima‐Media Thickness Evaluation

Mita, Tomoya; Katakami, Naoto; Shiraiwa, Toshihiko; Yoshii, Hidenori; Gosho, Masahiko; Shimomura, Iichiro; Watada, Hirotaka

doi:10.1111/jdi.12559

Cited by 8 publications

(4 citation statements)

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“…UCP2 inhibited oxidative stress and downregulated COX-2 expression through the GLP-1/GLP-1R/AMPK axis. In humans, dipeptidyl peptidase-4 inhibitors appear to have unique and/or additive antiatherosclerotic effects as add-on therapy to statins and/or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers [ 91 ]. Thus, UCP2 is revealed as an effective molecular target for drug intervention to combat both diabetes- and hypertension-related vascular diseases.…”

Section: Ucp2 As a Potential Therapeutic Target For The Treatment mentioning

confidence: 99%

Uncoupling Protein 2: A Key Player and a Potential Therapeutic Target in Vascular Diseases

Pierelli

Stanzione

Forte

et al. 2017

Oxidative Medicine and Cellular Longevity

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Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein that belongs to the uncoupling protein family and plays an important role in lowering mitochondrial membrane potential and dissipating metabolic energy with prevention of oxidative stress accumulation. In the present article, we will review the evidence that UCP2, as a consequence of its roles within the mitochondria, represents a critical player in the predisposition to vascular disease development in both animal models and in humans, particularly in relation to obesity, diabetes, and hypertension. The deletion of the UCP2 gene contributes to atherosclerosis lesion development in the knockout mice, also showing significantly shorter lifespan. The UCP2 gene downregulation is a key determinant of higher predisposition to renal and cerebrovascular damage in an animal model of spontaneous hypertension and stroke. In contrast, UCP2 overexpression improves both hyperglycemia- and high-salt diet-induced endothelial dysfunction and ameliorates hypertensive target organ damage in SHRSP. Moreover, drugs (fenofibrate and sitagliptin) and several vegetable compounds (extracts from Brassicaceae, berberine, curcumin, and capsaicin) are able to induce UCP2 expression level and to exert beneficial effects on the occurrence of vascular damage. As a consequence, UCP2 becomes an interesting therapeutic target for the treatment of common human vascular diseases.

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Section: Ucp2 As a Potential Therapeutic Target For The Treatment mentioning

confidence: 99%

Uncoupling Protein 2: A Key Player and a Potential Therapeutic Target in Vascular Diseases

Pierelli

Stanzione

Forte

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…On the one hand, CIMT is directly associated with the risk of myocardial infarction and stroke and is considered to be an effective tool for early diagnosis of atherosclerosis [3,4]. Some studies suggest that the progression of carotid IMT in coronary artery disease (CAD) can be used to predict coronary events and related mortality [5][6][7]. The link between CIMT and CAD may be related to inflammation, which is recognized to play a critical role in the pathogenesis of atherosclerosis [8].…”

Section: Introductionmentioning

confidence: 99%

Sitagliptin on Carotid Intima-Media Thickness in Type 2 Diabetes Mellitus Patients and Anemia: A Subgroup Analysis of the PROLOGUE Study

Chen

2020

Mediators of Inflammation

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Introduction. Randomized clinical trials have not shown an additional clinical benefit of sitagliptin treatment over conventional treatment alone. However, studies of sitagliptin treatment have not examined the relationship between anemia and treatment group outcomes. Methods. The PROLOGUE study is a prospective clinical trial of 442 participants with type 2 diabetes mellitus (T2DM) randomized to sitagliptin treatment or conventional treatment which showed no treatment differences [Estimated mean (± standard error) common carotid intima-media thickness (CIMT) was 0.827±0.007 mm and 0.837±0.007 mm, respectively, with a mean difference of -0.009 mm (97.2% CI −0.028 to 0.011, p=0.309) at 24 mo of follow-up]. This is a post hoc subanalysis using data obtained from the PROLOGUE study; the study population was divided into anemic groups (n=94) and nonanemic group (n=343) based on hemoglobin level. And we analyzed for the changes in each CIMT parameter from baseline to 24 months in subgroups. Results. The treatment group difference in baseline-adjusted mean common carotid artery- (CCA-) IMT at 24 months was −0.003 mm (95% CI −0.022 to 0.015, p=0.718) in the nonanemic subgroup and −0.007 mm (95% CI −0.043 to 0.030, p=0.724) in the anemic subgroup. Although there were no significant differences in the other CIMT parameters between the treatment groups in the anemic subgroup, the changes in mean and max ICA-IMT at 24 months in the nonanemic subgroup were significantly lower in the sitagliptin group than the conventional group [−0.104 mm (95% CI −0.182 to −0.026), p=0.009 and −0.142 mm (−0.252 to −0.033), p=0.011, respectively]. Conclusion. These data suggest that nonanemia may indicate a potentially large subgroup of those with T2DM patients that sitagliptin therapy has a better antiatherosclerotic effect than conventional therapy. Further research is needed to confirm these preliminary observations.

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“…A surrogate marker of atherosclerosis is intima-media thickness (IMT), which is the combined thickness of the tunica intima and media of a circulatory vessel detectable non-invasively with ultrasonographic techniques [5]. It is a valuable indicator of CVD risk, significantly correlated with current and future CVD when its absolute value and progression rates are determined [6]. Based on data from many studies, carotid artery IMT (cIMT) progression is considered an indicator of atherosclerosis with a high predictive value for future CVD and related mortality [7].…”

Section: Introductionmentioning

confidence: 99%

Comparative effects of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on carotid artery intima-media thickness progression: a network meta-analysis

Huang

Mills

Romero

et al. 2019

Cardiovasc Diabetol

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BackgroundCarotid artery intima-media thickness (cIMT) progression is a surrogate marker of atherosclerosis with a high predictive value for future CVD risk. This study evaluates the comparative efficacies of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on cIMT progression.MethodsWe conducted a network meta-analysis (NMA) to evaluate the relative efficacies of several drug classes in modifying cIMT progression. After a literature search in several electronic databases, studies were selected by following predetermined eligibility criteria. An inverse variance-heterogeneity model was used for NMA. Sensitivity analyses were performed to check the reliability of the overall NMA, and transitivity analyses were performed to examine the effects of modifiers on the NMA outcomes.ResultsData were taken from 47 studies (15,721 patients; age: 60.2 years [95% confidence interval (CI) 58.8, 61.6]; BMI: 27.2 kg/m2 [95% CI 26.4, 28.0]; and gender: 58.3% males [95% CI 48.3, 68.3]). Treatment duration was 25.8 months [95% CI 22.9, 28.7]. Of the 13 drug classes in the network, treatment with phosphodiesterase III inhibitors was the most effective in retarding annual mean cIMT against network placebo (weighted mean difference (WMD) − 0.059 mm [95% CI − 0.099, − 0.020) followed by the calcium channel blockers (WMD − 0.055 mm [95% CI − 0.099, 0.001]) and platelet adenosine diphosphate inhibitors (WMD − 0.033 mm [95% CI − 0.058, 0.008]). These 3 drug classes also attained the same positions when the NMA was conducted by using first-year changes in mean cIMT. In transitivity analyses, longer treatment duration, higher body mass index (BMI), and a higher baseline cIMT were found to be independently associated with a lesser reduction in annual mean cIMT. However, in a multivariate analysis with these 3 modifiers, none of these factors was significantly associated with annual change in mean cIMT. In the placebo group, age was inversely associated with annual change in mean cIMT independently.ConclusionPhosphodiesterase III inhibitors and calcium channel blockers are found more effective than other drug classes in retarding cIMT progression. Age, BMI, and baseline cIMT may have some impact on these outcomes.Electronic supplementary materialThe online version of this article (10.1186/s12933-019-0817-1) contains supplementary material, which is available to authorized users.

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Changes in carotid intima‐media thickening in patients with type 2 diabetes mellitus: Subanalysis of the Sitagliptin Preventive Study of Intima‐Media Thickness Evaluation

Cited by 8 publications

References 5 publications

Uncoupling Protein 2: A Key Player and a Potential Therapeutic Target in Vascular Diseases

Uncoupling Protein 2: A Key Player and a Potential Therapeutic Target in Vascular Diseases

Sitagliptin on Carotid Intima-Media Thickness in Type 2 Diabetes Mellitus Patients and Anemia: A Subgroup Analysis of the PROLOGUE Study

Comparative effects of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on carotid artery intima-media thickness progression: a network meta-analysis

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