Osteoprotegerin is independently associated with metabolic syndrome and microvascular complications in type 2 diabetes mellitus

Tavintharan, Subramaniam; Pek, L.T.; Liu, Jing; Ng, Xiao Wei; Yeoh, Lee Ying; su, Lim yong; Fang, Sum Chee

doi:10.1177/1479164114539712

Cited by 23 publications

(19 citation statements)

References 13 publications

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“…Osteoprotegerin, a member of the tumor necrosis factor receptor family, is released from vascular endothelial cells in response to inflammatory stimuli and is associated with increased cardiovascular risk and diabetes complications . Previously, we showed in our study cohort that higher OPG concentrations were associated with the risk of metabolic syndrome (MS) and microvascular complications . Pigment epithelium‐derived factor, a key adipokine, induces insulin resistance and inflammation signals and is associated with diabetes and obesity‐related disorders .…”

Section: Discussionmentioning

confidence: 59%

“…33 Previously, we showed in our study cohort that higher OPG concentrations were associated with the risk of metabolic syndrome (MS) and microvascular complications. 34 Pigment epithelium-derived factor, a key adipokine, induces insulin resistance and inflammation signals and is associated with diabetes and obesity-related disorders. 35,36 The ethnic differences in baseline LTL and inverse associations between changes in obesity indices and LTL observed in the present study were not substantially attenuated after further adjustment for hs-CRP, PEDF, and OPG, suggesting that this association may not be due to obesity-related inflammation.…”

Section: Discussionmentioning

confidence: 99%

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Ethnic disparities in relationships of obesity indices with telomere length in Asians with type 2 diabetes

Gurung

Yiamunaa

Liu

et al. 2018

Journal of Diabetes

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Background Obesity and shorter telomeres increase the risk for diabetes complications and mortality. However, the relationship between obesity and telomere length in diverse Asian populations with type 2 diabetes (T2D) is not well understood. This study examined the association of baseline and changes in obesity indices with telomere length in multiethnic Asian populations with T2D. Methods Leukocyte telomere length (LTL) was measured by quantitative polymerase chain reaction in the SMART2D cohort (n = 1431 at baseline, n = 1039 after 3.2 years median follow‐up). Associations between obesity indices and LTL were assessed by linear regression. Results Compared with Chinese, LTL was longer in Malays (P < 0.0001) and similar in Indians. Cross‐sectionally, body mass index (BMI)‐adjusted (residual) visceral fat area (VFA; β = −0.004, P = 0.006), and waist‐to‐hip ratio (β = −1.95, P = 0.030) were significantly associated with LTL in Chinese but not in Malays and Indians. Changes in BMI (r = −0.080; P = 0.053) and VFA (r = −0.126; P = 0.002) were inversely correlated with changes in LTL only in Chinese. Furthermore, in Chinese, 1‐SD incremental changes in BMI (β = −0.070; P = 0.040) and VFA (β = −0.088, P = 0.028) were significantly associated with larger telomere attrition, independent of age, sex, diabetes condition, baseline LTL, obesity, and inflammation markers. Conclusions Three‐year changes in BMI and VFA were associated with telomere dynamics in Chinese but not in Malays and Indians with T2D. Reducing obesity may reduce the risk of diabetes complications associated with shorter LTL in the Chinese population.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Ethnic disparities in relationships of obesity indices with telomere length in Asians with type 2 diabetes

Gurung

Yiamunaa

Liu

et al. 2018

Journal of Diabetes

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“…Previously, elevated circulating levels of OPG have been reported in T2DM, particularly in the presence of microvascular complications (Knudsen et al, 2003), with several studies (Nybo et al, 2010; Tavintharan et al, 2014; Terekeci et al, 2009), but not all (Bourron et al, 2014), having shown an association between increased levels of OPG and peripheral neuropathy. The mechanism of this association was not clear.…”

Section: Discussionmentioning

confidence: 99%

“…The etiology of diabetic neuropathy is multifactorial with metabolic, neurovascular, and inflammatory components. Three studies in persons with diabetes have demonstrated an association between higher OPG levels and peripheral neuropathy (Nybo, Poulsen, Grauslund, Henriksen, & Rasmussen, 2010; Tavintharan et al, 2014; Terekeci et al, 2009). OPN, in rodents, has been shown to be upregulated in denervated motor pathways with increased OPN protein expression in denervated Schwann cells following nerve injury (Wright et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Osteopontin and osteoprotegerin levels in type 2 diabetes and their association with cardiovascular autonomic function

Maser

Lenhard

Pohlig

et al. 2016

Journal of Diabetes and its Complications

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Aims Osteopontin (OPN) and osteoprotegerin (OPG) are bone metabolism biomarkers potentially associated with nerve function. We evaluated the association of cardiovascular autonomic nerve function, OPN, and OPG in 50 individuals with type 2 diabetes mellitus (T2DM). Methods RR-variation during deep breathing (i.e., mean circular resultant (MCR) and expiration/inspiration (E/I) ratio) was used to assess parasympathetic nerve function. Participants’ demographics, HbA1c, 25-hydroxyvitamin D (25(OH)D), BMI, HOMA-IR, calcium, parathyroid hormone, creatinine, OPN, and OPG were determined. Results Using stepwise multiple linear regression analysis with MCR or E/I ratio as the dependent variable, OPN was independently associated with reduced autonomic function. A previous report showed a significant association of cardiovascular autonomic function with age, 25(OH)D insufficiency, and the interaction of age × 25(OH)D insufficiency. Here we report a novel association for OPN and its interaction with age indicating that for those who are younger, elevated OPN levels are related to a greater loss of autonomic function (MCR model R2 = 0.598, p < 0.001; E/I model R2 = 0.594, p < 0.001). Conclusion Our results suggest that OPN is associated with reduced parasympathetic function, particularly in younger individuals with T2DM. Further studies are needed to determine if OPN is neuroprotective, involved in the pathogenesis of autonomic dysfunction, or a bystander.

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“…Diabetic vascular disease is the leading cause of death and disability in diabetic patients; 30-40% of the patients are subject to at least one vascular complications after 10 years (Tavintharan et al, 2014). Numerous studies have shown the association of diabetes mellitus vascular complications with oxidative stress in endothelial cells and endothelial cells derived from progenitor cells (mainly in the bone marrow) (Kizub et al, 2014;Prieto et al, 2014;Yiu and Tse, 2014).…”

Section: Introductionmentioning

confidence: 99%

Effect of procyanidine on VEGFR-2 expression and transduction pathway in rat endothelial progenitor cells under high glucose conditions

Y¹,

Wj²,

Zhu³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The protective effect of procyanidine and its oligomers against high glucose-mediated oxidative stress injury in endothelial progenitor cells (EPCs), and effect of procyanidin on vascular endothelial growth factor receptor-2 (VEGFR-2) expression and downstream signal pathway were analyzed in vitro. Rat bone marrow mononuclear cells were isolated, cultured under normal and high glucose (HG) conditions, and the changes in cell morphology observed. The EPCs were identified, and the oxidative stress products produced by EPCs (under normal and HG conditions) were quantified. Subsequently, an appropriate number of EPCs were cultured with and without procyanidin (OPC), and the MDA concentration and relative expression of VEGFR-2, AKT, IkB-a, and nuclear factor (NF)-kB were detected 1, 3, 5, and 7 days post-culture. We observed minor (round, translucent, gradually adhering) and significant (fusiform morphology/ pebble distribution) cell morphological changes 3 and 7 days post-culture, respectively. Apoptosis and oxidative stress product release in EPCs cultured with HG increased significantly compared to the control group (P < 0.05). The oxidative stress product generation and relative expression of VEGFR-2, AKT, IkB-a, and NF-kB were not significantly affected by OPC addition in normal glucose conditions (P > 0.05); alternately, products generated as a result of oxidative stress were significantly reduced, the relative expression of VEGFR-2, AKT, and NF-kB protein was upregulated, and that of IkB-a was downregulated (P < 0.05) in HG + OPC EPCs. Therefore, procyanidin may promote cell proliferation by alleviating oxidative damage to EPCs under HG conditions, and upregulating VEGFR-2 expression and its downstream signal pathway.

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Osteoprotegerin is independently associated with metabolic syndrome and microvascular complications in type 2 diabetes mellitus

Cited by 23 publications

References 13 publications

Ethnic disparities in relationships of obesity indices with telomere length in Asians with type 2 diabetes

Ethnic disparities in relationships of obesity indices with telomere length in Asians with type 2 diabetes

Osteopontin and osteoprotegerin levels in type 2 diabetes and their association with cardiovascular autonomic function

Effect of procyanidine on VEGFR-2 expression and transduction pathway in rat endothelial progenitor cells under high glucose conditions

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