Iatrogenic hyperhomocysteinemia in patients with metabolic syndrome: A systematic review and metaanalysis

Ntaios, George; Savopoulos, Christos; Chatzopoulos, Stavros; Mikhailidis, Dimitri P.; Hatzitolios, Apostolos

doi:10.1016/j.atherosclerosis.2010.08.045

Cited by 29 publications

(20 citation statements)

References 106 publications

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“…This result is in contrast with the finding of the recent paper of Gonzales et al [25]. Hcy levels can be affected by several clinical or pharmacological conditions, such as renal disease, vitamin deficiency or supplementation [39], treatment with metformin [42]. In our study, we excluded patients with any condition modifying Hcy levels and there was no difference in the percentage of patients treated with metformin between NDF group and control.…”

Section: Discussioncontrasting

confidence: 82%

Lipoprotein(a) and homocysteine as genetic risk factors for vascular and neuropathic diabetic foot in type 2 diabetes mellitus

Gazzaruso

Coppola²,

Montalcini

et al. 2011

Endocrine

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Neuropathy and peripheral artery disease represent the main pathophysiological conditions underlying diabetic foot. Several studies showed that Lipoprotein(a)-Lp(a)-and homocysteine (Hcy) can be associated with diabetic complications, but their relationship with diabetic foot is unclear. Aim of this study was to investigate whether Lp(a) and Hcy were associated with diabetic foot ulcerations, classified according to the presence of peripheral artery disease (PAD) or neuropathy. From among consecutive type 2 diabetic attending at the Diabetic Foot Clinic 27 subjects with vascular diabetic foot (VDF), 43 with neuropathic diabetic foot (NDF) and 52 controls without foot ulceration, neuropathy, and PAD were enrolled. Both Lp(a) (26.1 ± 22.7 vs. 14.9 ± 19.5 mg/dl; P = 0.003) and Hcy levels (15.4 ± 5.7 vs. 12.2 ± 5.1 μmol/l; P = 0.022) were significantly greater in the VDF group than in controls. Lp(a) levels were significantly lower in the NDF group than in controls (6.9 ± 8.1 versus 14.9 ± 19.5 mg/dl; P = 0.009), while no difference in Hcy levels was found. Multiple logistic regression analysis showed that Hcy was associated with VDF (OR: 1.11; 95% CI: 1.07-14.1; P = 0.048). Lp(a) did not enter the model, but its P-value was very near to the significant level (OR: 1.09; 95% CI: 0.99-12.05; P = 0.059). Moreover, low Lp(a) levels were associated with NDF (OR: 0.84; 95% CI: 0.21-0.96; P = 0.039). Our study has shown for the first time that high Lp(a) and Hcy levels are associated with the development of VDF, while low Lp(a) levels appear to be associated with delayed wound healing in patients with neuropathic foot ulcerations.

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Section: Discussioncontrasting

confidence: 82%

Lipoprotein(a) and homocysteine as genetic risk factors for vascular and neuropathic diabetic foot in type 2 diabetes mellitus

Gazzaruso

Coppola²,

Montalcini

et al. 2011

Endocrine

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“…Boushey et al (20) reported that an increase in Hcy for 5 µM/L is associated with an odds ratio (OR) for coronary artery disease (CAD) of 1.6 for men. Also, several studies demonstrated a relationship between Hcy and risk of obesity, diabetes, dyslipidemia, hypertension and MetS (25-27), although Veerkamp et al (28) reported that no association was found between plasma Hcy concentration and plasma lipid levels, nor between Hcy and insulin resistance. In particular, the roles of insulin and/or insulin resistance in determining plasma Hcy have been demonstrated (29).…”

Section: Discussionmentioning

confidence: 99%

“…Previous observations and our study indicated that individuals with MetS a had higher Hcy level than control subjects (9, 13). Ntaios et al (25) found that several drugs used in MetS patients influence Hcy levels. Therefore, to determine the optimal cut-off point of Hcy for CVD, we must consider the presence of MetS or the medication usage for the subjects.…”

Section: Discussionmentioning

confidence: 99%

Use of Serum Homocysteine to Predict Cardiovascular Disease in Korean Men with or without Metabolic Syndrome

Kang¹,

Park²,

Lee³

et al. 2012

J Korean Med Sci

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The aim of this study was to examine whether serum homocysteine (Hcy) levels correlated with cardiovascular disease (CVD) depending on the presence or absence of metabolic syndrome (MetS) in Korean men. We conducted a case-control study, including 138 CVD and 290 non-CVD age-matched control subjects. The subjects were divided into four subgroups: 34 CVD/MetS, 104 CVD, 77 MetS, and 213 normal subgroups. The mean Hcy was significantly higher, whereas HDL and intake of vitamin B1 and B2 were lower in the CVD group (P < 0.05) than non-CVD group. When compared to the control group, subjects with CVD/MetS, CVD and MetS exhibited high Hcy levels, with the highest observed in the CVD/MetS subgroup (P < 0.001). Multivariate stepwise linear regression between CVD and markers of CVD showed Hcy significantly correlated with CVD (P < 0.05). To predict CVD based on Hcy, Hcy threshold of 11.72 µM in non-MetS subjects had an area under the curve (AUC) of 0.664 (95% CI 0.598-0.731). In MetS subjects, the AUC was 0.618 and Hcy threshold was 13.32 µM (95% CI 0.509-0.726). The results of our study show that the presence of MetS needs to be considered when using Hcy levels for predicting CVD.

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“…The range of concentrations of chemical compounds used in this study was selected based on the preliminary studies of the concentration (0e10,000 mM)-and time (6,12,24,48, 72 h)-dependency experiments (data not shown).…”

Section: Determination Of Cell Viabilitymentioning

confidence: 99%

Improved antioxidative defence protects insulin-producing cells against homocysteine toxicity

Scullion

Hahn

Tyka

et al. 2016

Chemico-Biological Interactions

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Homocysteine (HC) is considered to play an important role in the development of metabolic syndrome complications. Insulin-producing cells are prone to HC toxicity and this has been linked to oxidative stress. However, the exact mechanisms remain unknown. Therefore it was the aim of this study to determine the nature of reactive oxygen species responsible for HC toxicity. Chronic exposure of RINm5F and INS1E insulin-producing cells to HC decreased cell viability and glucose-induced insulin secretion in a concentration-dependent manner and led to a significant induction of hydrogen peroxide generation in the cytosolic, but not the mitochondrial compartment of the cell. Cytosolic overexpression of catalase, a hydrogen peroxide detoxifying enzyme, provided a significant protection against viability loss and hydrogen peroxide generation, while mitochondrial overexpression of catalase did not protect against HC toxicity. Overexpression of CuZnSOD, a cytosolic superoxide dismutating enzyme, also protected against HC toxicity. However, the best protection was achieved in the case of a combined overexpression of CuZnSOD and catalase. Incubation of cells in combination with alloxan resulted in a significant increase of HC toxicity and an increase of hydrogen peroxide generation. Overexpression of CuZnSOD or catalase protected against the toxicity of HC plus alloxan, with a superior protection achieved again by combined overexpression. The results indicate that HC induces oxidative stress in insulin-producing cells by stimulation of superoxide radical and hydrogen peroxide generation in the cytoplasm. The low antioxidative defence status makes the insulin-producing cells very vulnerable to HC toxicity.

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Iatrogenic hyperhomocysteinemia in patients with metabolic syndrome: A systematic review and metaanalysis

Cited by 29 publications

References 106 publications

Lipoprotein(a) and homocysteine as genetic risk factors for vascular and neuropathic diabetic foot in type 2 diabetes mellitus

Lipoprotein(a) and homocysteine as genetic risk factors for vascular and neuropathic diabetic foot in type 2 diabetes mellitus

Use of Serum Homocysteine to Predict Cardiovascular Disease in Korean Men with or without Metabolic Syndrome

Improved antioxidative defence protects insulin-producing cells against homocysteine toxicity

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