Hyperhomocysteinemia correlates with insulin resistance and low-grade systemic inflammation in obese prepubertal children

Health Center of Pozoblanco, 14400 Pozoblanco, Córdoba, Spain.
Metabolism (Impact Factor: 3.89). 01/2006; 55(1):72-7. DOI: 10.1016/j.metabol.2005.07.008
Source: PubMed


Obesity is an independent risk factor for the development of cardiovascular disease frequently associated with hypertension, dyslipemia, diabetes, and insulin resistance. Higher homocysteine (Hcy) levels are observed in the hyperinsulinemic obese adults and suggest that Hcy could play a role in the higher risk of cardiovascular disease in obesity. We analyzed total Hcy levels in obese prepubertal children and their possible association with both metabolic syndrome and various inflammatory biomarkers and leptin. We studied 43 obese children (aged 6-9 years) and an equal number of nonobese children, paired by age and sex. The obese subjects presented significantly elevated values for insulin (P = .003), C-reactive protein (P = .033), and leptin (P < .001). No significant differences were found in Hcy levels between the obese and nonobese children. However, Hcy concentration was significantly higher in the hyperinsulinemic obese children than in the normoinsulinemic group (P = .002). Using multivariant regression analysis, in the obese group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .001) and leptin (P partial = .02) are independent predictive factors for Hcy. In the control group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .005) and leptin (P partial = .031) also are independent predictive factor for Hcy. Increased plasma Hcy, particularly in hyperinsulinemic obese children, may be causally involved in the pathogenesis of atherosclerosis and/or cardiovascular disease, both of which are common in obesity.

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    • "In healthy children, the reference values for Hcy and Cys are unknown, as is whether the most increased concentrations are related to a future risk of CVD [9]. Punctilious studies have described an association of higher concentrations of Hcy in the pediatric age group with obesity and increased abdominal circumference [10], insulin resistance [11], dyslipidemia [12], and systemic arterial hypertension [13]. Until now, similar studies for Cys have not been available. "
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    ABSTRACT: Objective: To evaluate homocysteine and total cysteine levels in prepubertal children and to determine the association between these levels and obesity, increased waist circumference, glucose levels, and lipid profile alterations. Methods: Using a cross-sectional study, 677 prepubertal students 6 to 11 y old were assessed. The weight, height, and waist circumference of the students were measured. Laboratory analyses included triacylglycerols, total cholesterol and its fractions, glucose, vitamin B12, folate, homocysteine, and cysteine. Chi-square tests and logistic regression (forward-stepwise) were used for statistical analysis; the significance level was set at 5%. Results: The median age of the students was 8.9 y (6.5-11.5), and the prevalences of overweight and obesity were 90 in 677 (13.3%) and 81 in 677 (12.0%), respectively. An increase in waist circumference was observed in 180 of 677 children (26.6%). Inadequate levels of low-density lipoprotein cholesterol, triacylglycerols, and high-density lipoprotein cholesterol were found in 95 (14.0%), 129 (19.1%), and 179 (26.4%) of the 677 students, respectively. The median homocysteine and total cysteine plasma levels were 5.6 μmol/L (0.1-11.7) and 365.7 μmol/L (191.5-589.2), respectively. A multivariate analysis showed that children with a waist circumference above the 90th percentile (7.3 μmol/L) were 2.4 times (95% confidence interval 1.4-4.0) more likely to have increased homocysteine levels and that children with increased waist circumferences and those with high low-density lipoprotein cholesterol levels were 2.7 (95% confidence interval 1.6-4.6) and 2.1 (95% confidence interval 1.1-4.0) times more likely, respectively, to have total cysteine levels above the 90th percentile (445.0 μmol/L). Conclusion: The association of abdominal obesity in prepuberty with levels of homocysteine and cysteine found in this study of a prepubertal population could be an early and independent predictor of cardiovascular risk.
    Nutrition 09/2012; 29(1). DOI:10.1016/j.nut.2012.05.015 · 2.93 Impact Factor
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    • "Homocysteine, a thiol containing amino acid, has emerged as a determinant for many complex metabolic disorders in the past few years. Hyperhomocysteinemia is a well-known independent risk factor for cardiovascular diseases [1] [2] and is also associated with diabetic complications [3] [4] [5] [6], obesity, [7] [8] and metabolic syndrome [9]. Hyperhomocysteinemia may lead to any of the above metabolic disorders by elicitation of oxidative stress [10], systemic inflammation, [11] and/or endothelial dysfunction [12]. "
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    ABSTRACT: Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects) and replicated top signals in an independent sample set (2.085 subjects). The variant MTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR = 0.78 (95%  CI = 0.67-0.92), P = 0.003) and was also associated with 2 h postload plasma glucose (P = 0.04), high-density lipoprotein cholesterol (P = 0.004), and total cholesterol (P = 0.01) in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.
    Experimental Diabetes Research 01/2012; 2012:960318. DOI:10.1155/2012/960318 · 4.33 Impact Factor
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