Oghagbon, Efosa Kenneth (2017) Polyunsaturated fatty acids and inflammatory biomarkers in the pathogenesis of type II diabetes. PhD thesis, University of Greenwich.

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Abstract

Various studies have reported elevated levels of pro-inflammatory cytokines (IL-6, TNF-α, MCP-1, IL-1β) and different fatty acid (FA) patterns are associated with type 2 diabetes mellitus (DM2). In addition, an association of hypovitaminoses D with DM2 has been observed in some populations. No study has simultaneously evaluated multiple cytokines, FA profiles and vitamin D in DM2 patients in Nigeria. Neither has any study compared the FA profiles and inflammatory biomarkers in DM2 population of an African country with one outside the African continent. This study measured cytokines and FAs in DM2 patients and healthy controls from Nigeria and Mexico. The plasma phosphatidylcholine (PC) FA composition was measured by gas liquid chromatography (GLC) using appropriate FA standards. This was preceded by the preparation of FA methyl esters following thin layer chromatography (TLC) and identification of the PC band using an authentic standard. Cytokines (adiponectin, resistin, leptin, IL-1β, IL-6, IL-4, IL-8, IL-10, IL-12, TNF-α, IFN-γ, TGF-β and MCP-1) were measured by a multiplex assay that utilises Luminex software technology and vitamin D by chemiluminescence microparticle immunoassay methodology. The FA profiles are reported as mean % weight ± SD and the data obtained compared between DM2 and healthy controls in both Nigeria and Mexico. The DM2 and controls of each country were compared within and between their respective groups. A recent literature report of the levels of cytokines in DM2 sufferers from Mexico and control subjects were compared with the Nigerian DM2 cytokines values. Results are reported as mean ± SD except for the cytokines which are reported as mean ± s.e.m. Only the cytokine, insulin and HOMA indices (HOMA-B and HOMA-IR) data were logarithmically transformed before statistical analyses.

Palmitic acid (C16:0) was found to be significantly higher in DM2 subjects in both populations (Nigerian DM2: 30.83 ± 3.86, controls: 29.04 ± 4.22; Mexico DM2: 30.96 ± 2.45, controls: 29.48 ± 2.20). This is in keeping with other studies, and elevated palmitate is known to increase inflammation mainly by activating TLR4 in macrophages, hence linked with the IR and DM2. Stearic acid (C18:0) was lower in DM2 subjects compared to controls in both countries (Nigerian DM2: 15.88 ± 2.21, controls: 17.57 ± 2.43; Mexico DM2: 13.76 ± 1.88, controls: 14.99 ± 1.20). This pattern has only been shown in a few studies, as others have found higher levels of stearic acid in DM2. Vaccenic acid (C18:1n-7) levels were only higher in Nigerian controls (1.26 ± 0.32) compared to the DM2 subjects (1.05 ± 0.39). Arachidonic acid (C20:4n-6) was significantly lower in DM2 subjects relative to the controls in both countries (Nigerian DM2: 9.17 ± 2.12, controls: 10.31 ± 2.12; Mexico DM2: 6.14 ± 1.52, controls: 6.73 ± 1.54). This suggests either alteration of metabolism of the parent n-6 FAs to their longer chain metabolites, or increased consumption of C20:4n-6 in the patients. The mean level of C18:2n-6 was significantly higher in Mexican DM2 subjects than in Nigerians’ (Mexico: 26.17 ± 2.43; Nigeria; 18.41 ± 4.31) and the level of C20:4n-6 was higher in the Nigerian diabetics (9.17 ± 2.12) than in Mexican DM2 samples (6.14 ± 1.52). Similarly, the level of C18:3n-3 was higher in Mexican DM2 (0.34 ± 0.12) than in Nigerian diabetics (0.17 ± 0.10), but the levels of EPA (C20:5n-3) and DHA (C22:6n-3) were higher in Nigerian DM2 (EPA: 0.82 ± 0.78, DHA: 3.79 ± 1.87) than in diabetics from Mexico (EPA: 0.29 ± 0.15, DHA: 1.47 ± 0.53). Compared to the Nigerian subjects, there maybe a more disordered metabolism of parent FAs (C18:2n-6 and C18:3n-3) to longer chain PUFAs in the Mexican DM2 and healthy control populations.

Plasma IL-6 levels in Nigerian DM2 patients was significantly higher (DM2: mean 215.86 pg/ml ± 43.91) compared to controls (81.02 pg/ml ± 33.97). The level of IL-6 in a Mexican diabetic study was (18.30 pg/ml ± 11.7). The elevation of proinflammatory IL-6 in DM2 has been widely reported in various studies and it is said to impair insulin signalling by activation of NF-κβ and JNK pathways thus leading to impaired exocytosis of GLUT4 molecules. The logarithmic value of HOMA-B was lower in Nigerian DM2 (1.22 ± 0.08) than in the controls (1.44 ± 0.08) and the transformed values of HOMA-IR showed a higher value in the Nigerian DM2 subjects (0.45 ± 0.07) compared to their controls (0.09 ± 0.08). These are consistent with the glycaemic status of the group. The negative correlation between FPG and HOMA-B (r = -0.407, p = 0.002) only among the DM2 subjects is in keeping with the impact of the disease on pancreatic β-cell reserve. There were multiple weak to moderate correlations between plasma PC fatty acids, cytokines and adipokines (adiponectin, resistin, leptin, IL-1β, IL-6, IL-4, IL-8, IL-10, IL-12, TNF-α, IFN-γ, TGF-β, MCP-1) both in Nigerian controls and DM2. Vitamin D showed no significant differences in mean plasma vitamin D levels between Nigerian diabetics (61.00 nmol/L ± 17.31) and controls (56.28 nmol/L ± 18.41). Results of this study therefore show some important FAs profile similarities in both the Nigerian and Mexican DM subjects and a possible role for IL-6 in DM2 disease mechanisms in both populations. In relation to the fatty acid and inflammatory biomarker findings of this study the role of diet in DM2 in both countries clearly needs further investigation.

Item Type:	Thesis (PhD)
Uncontrolled Keywords:	Inflammatory biomarkers; plasma cytokines; plasma vitamin D3 levels; fatty acids; type II diabetes; Nigerian patients; Mexican patients;
Subjects:	Q Science > QP Physiology R Medicine > RA Public aspects of medicine
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	08 Apr 2019 16:58
URI:	http://gala.gre.ac.uk/id/eprint/23495

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