scholarly journals Below-Knee Arterial Calcification in Type 2 Diabetes: Association With Receptor Activator of Nuclear Factor κB Ligand, Osteoprotegerin, and Neuropathy

2014 ◽  
Vol 99 (11) ◽  
pp. 4250-4258 ◽  
Author(s):  
Olivier Bourron ◽  
Carole Elodie Aubert ◽  
Sophie Liabeuf ◽  
Philippe Cluzel ◽  
Frédérique Lajat-Kiss ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Nuclear Factor Κb ◽  
Arterial Calcification ◽  
Nuclear Factor ◽  
Disability Score ◽  
Calcification Score ◽  
Receptor Activator ◽  
Serum Rankl

Context: Calcification of the arterial wall in diabetes contributes to the arterial occlusive process occurring below the knee. The osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) system is suspected to be involved in the calcification process. Objective: The aim of the study was to investigate whether there is a link between arterial calcification in type 2 diabetes and 1) conventional cardiovascular risk factors, 2) serum RANKL and OPG levels, and 3) neuropathy. Patients and Methods: We objectively scored, in a cross-sectional study, infrapopliteal vascular calcification using computed tomography scanning in 198 patients with type 2 diabetes, a high cardiovascular risk, and a glomerular filtration rate >30 mL/min. Color duplex ultrasonography was performed to assess peripheral arterial occlusive disease, and mediacalcosis. Peripheral neuropathy was defined by a neuropathy disability score >6. RANKL and OPG were measured in the serum by routine chemistry. Results: Below-knee arterial calcification was associated with arterial occlusive disease. In multivariate logistic regression analysis, the variables significantly and independently associated with the calcification score were age (odds ratio [OR] = 1.08; 95% confidence interval [CI] = 1.04–1.13; P < .0001), male gender (OR = 3.53; 95% CI = 1.54–8.08; P = .003), previous cardiovascular disease (OR = 2.78; 95% CI = 1.39–5.59; P = .005), and neuropathy disability score (per 1 point, OR = 1.21; 95% CI = 1.05–1.38; P = .006). The association with ln OPG, significantly associated with calcification score in univariate analysis (OR = 3.14; 95% CI = 1.05–9.40; P = .045), was no longer significant in multivariate analysis. RANKL and OPG/RANKL were not significantly associated with the calcification score. Conclusions: Below-knee arterial calcification severity is clearly correlated with peripheral neuropathy severity and with several usual cardiovascular risk factors, but not with serum RANKL level.

scholarly journals Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Olivier Bourron ◽  
Franck Phan ◽  
Mamadou Hassimiou Diallo ◽  
David Hajage ◽  
Carole-Elodie Aubert ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Lower Limb ◽  
Arterial Calcification ◽  
Nuclear Factor ◽  
Calcification Score ◽  
Receptor Activator ◽  
Nuclear Factor Kb

Abstract Background Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. Methods Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model. Results At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (β coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p < 0.001), triglycerides (0.11, 0.03–0.20, p = 0.007), log(RANKL) (0.07, 0.02–0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15–0.57, p = 0.001), statin use (0.39, 0.06–0.72, p = 0.023) and duration of follow up (0.04, 0.01–0.06, p = 0.004). Conclusion In patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy. Trial registration NCT02431234

scholarly journals Circulating Receptor Activator of Nuclear factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in Type 2 Diabetes: a prospective, observational cohort study

2020 ◽  
Author(s):  
Olivier Bourron ◽  
Franck Phan ◽  
Mamadou Hassimiou Diallo ◽  
David Hajage ◽  
Carole-Elodie Aubert ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Lower Limb ◽  
Arterial Calcification ◽  
Nuclear Factor ◽  
Calcification Score ◽  
Receptor Activator ◽  
Nuclear Factor Kb

Abstract Background:Lower limb arterial calcification is a frequent, underestimated but serious diabetic complication. The DIACART study is a prospective cohort study designed to evaluate the determinants of lower limb arterial calcification progression in 198 patients with Type 2 Diabetes.Methods:Lower limb arterial calcification score was determined by computed tomography at baseline and after a mean follow up of 31+/-4 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and glycation markers were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model.Results:At baseline, mean+/-SD and median lower limb arterial calcification scores were, 2364+/- 5613 and 527 respectively and at the end of the study, 3739 +/- 6886 and 1355 respectively. In multivariate analysis, progression of lower limb arterial log calcification score was associated with (β coefficient [slope], 95%CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p < 0.001), triglycerides (0.11, 0.03–0.2, p = 0.007), log(RANKL) (0.07, 0.02–0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15–0.57, p = 0.001) and duration of follow up (0.04, 0.01–0.06, 0.004).Conclusion:In patients with Type 2 Diabetes, lower limb arterial calcification is a frequent and major pathological process which can progress rapidly. Circulating RANKL and triglycerides are independently associated with the progression of lower limb arterial calcification. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy.Trial registration: NCT02431234

scholarly journals Circulating Receptor Activator of Nuclear factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in Type 2 Diabetes: a prospective, observational cohort study.

2020 ◽  
Author(s):  
Olivier Bourron ◽  
Franck Phan ◽  
Mamadou Hassimiou Diallo ◽  
David Hajage ◽  
Carole-Elodie Aubert ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Lower Limb ◽  
Arterial Calcification ◽  
Nuclear Factor ◽  
Calcification Score ◽  
Receptor Activator ◽  
Nuclear Factor Kb

Abstract Background: Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. Methods: Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 +/-3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model. Results: At baseline, mean+/-SD and median lower limb arterial calcification scores were, 2364+/- 5613 and 527 respectively and at the end of the study, 3739 +/- 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (β coefficient [slope], 95%CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p<0.001), triglycerides (0.11, 0.03–0.20, p=0.007), log(RANKL) (0.07, 0.02–0.11, p=0.016), previous ischemic cardiomyopathy (0.36, 0.15–0.57, p=0.001), statin use (0.39, 0.06–0.72, p=0.023) and duration of follow up (0.04, 0.01–0.06, p=0.004). Conclusion: In patients with Type 2 Diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy.Trial registration: NCT02431234

Polymorphism rs2073618 of the osteoprotegerin gene as a potential marker of subclinical carotid atherosclerosis in Caucasians with type 2 diabetes mellitus

VASA ◽  
2017 ◽  
Vol 46 (5) ◽  
pp. 355-362 ◽  
Author(s):  
Aleš Pleskovič ◽  
Sara Mankoč Ramuš ◽  
Zala Jenko Pražnikar ◽  
Marija Šantl Letonja ◽  
Andreja Cokan Vujkovac ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Carotid Plaque ◽  
Carotid Atherosclerosis ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Increased Risk ◽  
Receptor Activator

Abstract. Background: The OPG/RANKL/RANK (osteoprotegerin/receptor-activator of nuclear factor κB ligand/receptor-activator of nuclear factor κB) axis has been recently linked to the development of atherosclerosis and plaque destabilization. We have investigated whether polymorphism rs2073618 of the OPG gene is associated with subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). Patients and methods: 595 subjects with T2DM were enrolled in the cross-sectional study. Subclinical markers of carotid atherosclerosis (carotid intima media thickness, plaque thickness, and plaques presence) were assessed with ultrasound at the time of recruitment. Genotyping for rs2073618 (a missense variant located in exon I of the OPG gene) was performed, and OPG serum levels were determined by ELISA. Results: Compared to the GG genotype, the CC genotype of the rs2073618 polymorphism had a significantly increased risk for the presence of carotid plaque (OR = 2.54, 95 % CI = 1.22–5.28, p = 0.01). No statistically significant difference could be detected (p = 0.68) upon comparing median values of serum OPG levels among studied genotype groups in subjects with T2DM. Multivariable linear regression analyses in T2DM subjects demonstrated that GC and CC genotypes (p = 0.03 and p = 0.003), together with statin therapy (p = 0.009), were independent predictors of the number of carotid segments with plaques. Conclusions: Despite the fact that OPG rs2073618 genotypes failed to predict the serum OPG levels as there was no statistical difference among compared genotypes, our results demonstrate that the rs2073618 polymorphism could be a possible genetic marker for the prediction of increased risk for carotid plaque burden as a measure of advanced subclinical atherosclerosis in T2DM subjects.

scholarly journals Central Administration of Resveratrol Improves Diet-Induced Diabetes

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5326-5333 ◽  
Author(s):  
Giorgio Ramadori ◽  
Laurent Gautron ◽  
Teppei Fujikawa ◽  
Claudia R. Vianna ◽  
Joel K. Elmquist ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Nuclear Factor Κb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Central Administration ◽  
Beneficial Effects ◽  
Intracerebroventricular Infusion ◽  
Iκb Kinase

Abstract Resveratrol is a natural polyphenolic compound that activates nicotinamide adenosine dinucleotide-dependent deacetylase SIRT1. Resveratrol has recently been shown to exert potent antidiabetic actions when orally delivered to animal models of type 2 diabetes. However, the tissue(s) mediating these beneficial effects is unknown. Because SIRT1 is expressed in central nervous system (CNS) neurons known to control glucose and insulin homeostasis, we hypothesized that resveratrol antidiabetic effects are mediated by the brain. Here, we report that long-term intracerebroventricular infusion of resveratrol normalizes hyperglycemia and greatly improves hyperinsulinemia in diet-induced obese and diabetic mice. It is noteworthy that these effects are independent of changes in body weight, food intake, and circulating leptin levels. In addition, CNS resveratrol delivery improves hypothalamic nuclear factor-κB inflammatory signaling by reducing acetylated-RelA/p65 and total RelA/p65 protein contents, and inhibitor of nuclear factor-κB α and IκB kinase β mRNA levels. Furthermore, this treatment leads to reduced hepatic phosphoenolpyruvate carboxykinase 1 mRNA and protein levels and ameliorates pyruvate-induced hyperglycemia in this mouse model of type 2 diabetes. Collectively, our results unveiled a previously unrecognized key role for the CNS in mediating the antidiabetic actions of resveratrol.

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