Relationship between Fatty Acid Habitual Intake and

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Endocrine, Metabolic & Immune Disorders - Drug Targets, 2015;15(3):234-41.

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Relationship between Fatty Acid Habitual Intake and Early Inflammation Biomarkers in Individuals with and without Type 2 Diabetes in Mexico Ana L. Guadarrama-López1, Roxana Valdés-Ramos1,*, Martha Kaufer-Horwitz2, Laurence S. Harbige3, Irazú Contreras1 and Beatriz E. Martínez-Carrillo1 1

Center for Research and Graduate Studies in Health Sciences, Faculty of Medicine, Universidad Autónoma del Estado de México, Toluca, México; 2Obesity and Eating Disorders Clinic, Dept. of Endocrinology & Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México; 3Faculty of Engineering and Science, Universities at Medway, University of Greenwich, United Kingdom Abstract: Background: Lifestyle changes have led to a high global incidence of type 2 Diabetes mellitus (T2DM). Evidence suggests beneficial effects of the intake of n-3 and n-6 polyunsaturated fatty acids (PUFA) in patients with T2DM.

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A. L. Guadarrama-López

Objective: To investigate the relationship between habitual fatty acid intake and inflammatory biomarkers in Mexican individuals with and without T2DM. Methods: A cross-sectional study of 120 adults with and 120 without T2DM; anthropometric assessments (BMI, waist circumference and body fat), blood pressure, PUFA intake, biochemical analyses (glucose and lipid profile) and inflammation biomarkers (IFN-γ, TNF-α, IL-1 β, IL-2, IL-6, IL-8 and IL-13) was undertaken. Results: Low n-3 intake was found in both groups (0.68 ± 0.55g/day in T2DM vs 0.81 ± 0.53 g/day in non-T2DM). Comparison between groups showed significantly higher concentrations of triacylglcerols (p=.001) and IL-6 (p=.018) in the T2DM group, as well as significant correlations between serum TNF-α and total n-3 fatty acid intake (r=.507, p= .001), EPA (r=.284, p=.002), DHA (r=.404, p=.001), and a weak but significant correlation between serum IL-1β and total PUFA (r=.245, p=.005), total n-3 (r=.214, p=.019) and total n-6 (r=.241, p=.008) intake. Conclusions: Patients with T2DM had a tendency for higher pro-inflammatory cytokines than subjects without T2DM. There was an association between PUFA intake and pro-inflammatory biomarkers in patients with T2DM. Further studies of anti-inflammatory nutrients and plasma and cell fatty acid profiles are needed to corroborate the present findings in patients with and without T2DM.

Keywords: Anti-inflammatory cytokines, n-3, n-6, pro-inflammatory cytokines, type 2 diabetes mellitus. INTRODUCTION According to the World Health Organization (WHO), there are more than 346 million people with diabetes mellitus around the world, from which 90% are type 2. Global estimations predict an increase of epidemic proportions reaching 366 million people by the year 2030 [1]. Results from the Mexican National Health and Nutrition Survey (ENSANUT 2012) indicated that the prevalence of Diabetes mellitus in Mexico is 9.2% (6.4 million people) [2]. For more than 15 years, evidence has been gathered, supporting the hypothesis that low grade chronic inflammation is a risk factor for the development of type two Diabetes mellitus (T2DM) [3-7]; however these mechanisms are not clearly understood. Existing theories include production of proinflammatory cytokines such as IL-1β and TNF-α, and an *Address correspondence to this author at the Center for Research and Graduate Studies in Health Sciences. Facultad de Medicina, Universidad Autónoma del Estado de México, Paseo Tollocan esq. Jesús Carranza, Col. Moderna de la Cruz, Toluca, Edo, Méx, 50180 México; Tel: +52-7222174142 ext. 122; Fax: +52-722-2173552; E-mail: [email protected] 1871-5303/15 $58.00+.00

increase in central fat mass, due to chronic inflammation [8]. Additionally, acute phase proteins such as C reactive protein (CRP), ICAM-1 (intercellular adhesion molecules 1) and VCAM (vascular cell adhesion protein 1) and some cytokines are related with, through a number of metabolic pathways, the regulation of insulin and the functions of lipoprotein lipases and adipokines which are thought to contribute to the development of insulin resistance [9]. Dietary factors may also increase acute phase proteins, for instance, a hyperenergetic diet increases CRP concentrations; while a high fat diet increases sialic acid, which is considered a marker of the acute phase response and cardiovascular and diabetes risk [10-11]. High concentrations of n-6 fatty acids are found in lymphocyte membranes, and there is a higher requirement for these fatty acids during the normal immune response [12]. In addition arachidonic acid metabolites are involved in the development and function of immune system cells such as thymocytes, macrophages Th1 and Th2 cells, and TNF-α, IL-1 and IL-2 regulation [12]. In vitro studies have demonstrated that low n-6 polyunsaturated fatty acids [PUFA] concentrations © 2015 Bentham Science Publishers

2 Endocrine, Metabolic & Immune Disorders - Drug Targets, 2015, Vol. 15, No. 2

improve B and T lymphocyte proliferation and there is also evidence of reduction in the production of pro-inflammatory cytokines like IL-1β and TNF-α with the n-6 fatty acids gamma-linolenic (GLA), and dihomogammalinoleic (DHLA) [12, 13]. Furthermore, it has been shown that low concentrations of n-3 PUFA stimulate lymphoproliferation of B and T cells [12, 14-15]. In humans supplementation with the long chain n-3 PUFA’s eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] has been associated with a decrease in helper T-cells [16], as well as IL-1β, IL-2, TNF-α, IL-6 and IL-8 production [12, 15, 17]. Some studies indicate that the adequate balance between n-6 and n-3 PUFA could improve the evolution of non- immune and immune mediated inflammatory diseases [13, 15, 18-21] including T2DM, as they improve insulin action by suppressing hepatic lipogenesis, reducing the release of triacylglycerols from liver, improving ketogenesis and oxidation of fatty acids in liver and skeletal muscle [22-23]. In addition cytokines such as TNF-α could be an additionally important molecule in relation to dys-regulated lipid, fatty acid and glucose metabolism and the development of metabolic abnormalities in T2DM, including insulin resistance [24]. Furthermore, high IL-1β concentrations are involved in the β-cell dysfunction by insulin signaling which leads to insufficient insulin secretion [5, 25], thus, an inflammatory process might have implications for the development of T2DM. The aim of this study was to investigate the relationship between fatty acid habitual intake and circulating lipids and biomarkers of inflammation in subjects with and without T2DM in a population of the state of Mexico. MATERIAL AND METHODS: Study Design This was an observational, descriptive and crosssectional study of 240 subjects residing in the State of Mexico, Mexico; 120 with T2DM and 120 without T2DM regularly attending a public health clinic were randomly recruited. Inclusion criteria: aged between 25 and 60 years, BMI (in kg/m²)