To help mitigate the escalating prevalence of Type 2 Diabetes (T2D) and alleviate society of its associated morbidity and economic burden on health care, it is crucial to understand its aetiology. Both genetic and the environmental risk factors are known to be involved. Healthy diets have been proven to reduce the risk of T2D in primary prevention trials, however, which components and exact mechanisms are involved is not fully understood, in particular, the role of macronutrient intake. Body weight, glycaemic markers and T2D are all to some extent genetically regulated. There may also be genetic influences on how people digest, absorb or metabolise macronutrients. This poses the possibility that the interplay between genes and our diet may help us unravel T2D’s aetiology. The aim of this PhD was to investigate gene-diet interactions on the risk of incident T2D, focusing primarily on macronutrient intake as the dietary factor. First, I systematically evaluated the current evidence before taking a step-wise approach (hypothesis driven to hypothesis-free) to interrogate gene-macronutrient interactions. This identified 13 publications, with 8 unique interactions reported between macronutrients (carbohydrate, fat, saturated fat, dietary fibre, and glycaemic load derived from self-report of dietary intake and circulating n-3 polyunsaturated fatty acids) and genetic variants in or near TCF7L2, GIPR, CAV2 and PEPD (p < 0.05) on T2D. All studies were observational with moderate to serious risk of bias and limitations that included lack of adequate adjustment for confounders, lack of reported replication and insufficient correction for multiple testing. Second, these reported interactions did not replicate in a large European multi-centre prospective T2D case-cohort study called EPIC-InterAct. We concluded that the heterogeneity between our results and those published could be explained by methodological differences in dietary measurement, population under study, study design and analysis but also by the possibility of spurious interactions. Third, given the paucity of gene-macronutrient interaction research using genetic risk scores (GRS), we examined the interaction between three GRS (for BMI (97 SNPs), insulin resistance (53 SNPs) and T2D (48 SNPs)) and macronutrient intake (quantity and quality indicators) in EPIC-InterAct. We did not identify any statistically significant interactions that passed multiple testing corrections (p≥0.20, with a p value threshold for rejecting the null hypothesis of 0.0015 (based on 0.05/33 tests)). We also examined 15 foods and beverages identified as being associated with T2D, and no significant interactions were detected. Lastly, we applied a hypothesis-free method to examine gene-macronutrient interactions and T2D risk by using a genome-environment-wide-interaction-study. Preliminary findings showed no significant interactions for total carbohydrate, protein, saturated fat, polyunsaturated fat and cereal fibre intake on T2D. In conclusion, the consistently null findings in this thesis using a range of statistical approaches to examine interactions between genetic variants and macronutrient intake on the risk of developing T2D have two key implications. One, based on the specific interactions examined, this research does not confirm evidence for gene-diet interactions in the aetiology of T2D and two, this research suggests that the association between macronutrient intake and the risk of developing T2D does not differ by genotype.

O objetivo deste estudo foi avaliar o efeito de formulações de rações para frangos de corte utilizando programação linear e não linear sobre desempenho, características de carcaça e aspectos econômicos. Um mil e oitenta machos da linhagem Cobb 500&trade;, com um dia de idade, foram distribuídos em delineamento em blocos casualizados, com seis tratamentos e seis repetições de 30 aves cada. Os tratamentos foram: 1) ração formulada por programação linear com exigência nutricional das Tabelas Brasileiras para Aves e Suínos; 2) ração formulada por programação linear com exigência nutricional do Manual de Manejo Cobb&trade;; 3) ração formulada por programação linear com exigência nutricional de modelos matemáticos; 4) ração formulada por programação não linear em cenário normal de mercado; 5) ração formulada por programação não linear em cenário favorável de mercado; e 6) ração formulada por programação não linear em cenário desfavorável de mercado. Considerou-se cenário de mercado normal os valores do milho, do farelo de soja e do preço pago pelo kg de frango vivo em 26/03/2015, para o interior do Estado de São Paulo. Para o cenário favorável, os valores dos ingredientes baixaram 10% e o preço pago pelo kg de frango vivo subiu 10% e, para o cenário desfavorável, ocorreu o inverso. Foram avaliadas as características de desempenho e econômicas aos 21 e 42 dias de idade e também as características de carcaça aos 42 dias. Os dados foram submetidos à análise de variância e, em caso de significância (P&lt;0,05), aplicou-se o teste de Scott-Knott (5%). Os melhores resultados de desempenho e de características de carcaça foram associados aos tratamentos oriundos da programação linear, cujas concentrações de nutrientes foram mais elevadas, dos quais proteína bruta, aminoácidos e fósforo disponível são determinantes do desempenho superior de frangos de corte. Os tratamentos oriundos da programação não linear geraram melhores resultados econômicos, principalmente no cenário de mercado favorável, que apontou o menor custo para produção de 1 kg de peso corporal e maior lucro. Conclui-se que a formulação de ração com o uso da programação não linear, embora não maximize o desempenho, possibilita a obtenção de rações que otimizam o lucro. / The aim of this study was to evaluate the effect of feed formulations for broilers using linear and nonlinear programming on performance, carcass characteristics and economic aspects. One thousand and eighty, one-day-old male broilers, Cobb 500 &trade; strain, were distributed in a randomized block design, with six treatments and six replicates of 30 birds each. The treatments were: 1) feed formulated by linear programming with nutritional requirement of the Brazilian Tables for Poultry and Swine; 2) feed formulated by linear programming with nutritional requirement of Management Cobb&trade; Manual; 3) feed formulated by linear programming with nutritional requirement of mathematical models; 4) feed formulated by nonlinear programming on normal market scenario; 5) feed formulated by nonlinear programming on favorable market scenario; and 6) feed formulated by nonlinear programming on unfavorable market scenario. In the normal market scenario values of corn, soybean meal and the price paid for kg of live broiler were that practiced on March 26, 2015, for the state of São Paulo. To the favorable scenario, the values of the ingredients decreased 10% and the price paid for kg of live broiler increased by 10% and, for the unfavorable scenario, the opposite happened. The performance and economic characteristics at 21 and 42 days, and carcass characteristics at 42 days were evaluated. Data were submitted to analysis of variance and, in case of significance (P&lt;0.05), the Scott-Knott test (5%) were applied. Best performance and carcass characteristics results were associated with treatments derived from linear programming, whose nutrient concentrations were higher, of which crude protein, amino acids and available phosphorus are determining the superior performance of broilers. Treatments arising from the non-linear programming generated better economic results, especially in the favorable market scenario, which showed the lowest cost to produce 1 kg of body weight and higher profit. It was concluded that feed formulation using non-linear programming, even though does not maximize performance, allows to feed formulation that optimize profit.

O objetivo deste estudo foi avaliar o efeito de formulações de rações para frangos de corte utilizando programação linear e não linear sobre desempenho, características de carcaça e aspectos econômicos. Um mil e oitenta machos da linhagem Cobb 500&trade;, com um dia de idade, foram distribuídos em delineamento em blocos casualizados, com seis tratamentos e seis repetições de 30 aves cada. Os tratamentos foram: 1) ração formulada por programação linear com exigência nutricional das Tabelas Brasileiras para Aves e Suínos; 2) ração formulada por programação linear com exigência nutricional do Manual de Manejo Cobb&trade;; 3) ração formulada por programação linear com exigência nutricional de modelos matemáticos; 4) ração formulada por programação não linear em cenário normal de mercado; 5) ração formulada por programação não linear em cenário favorável de mercado; e 6) ração formulada por programação não linear em cenário desfavorável de mercado. Considerou-se cenário de mercado normal os valores do milho, do farelo de soja e do preço pago pelo kg de frango vivo em 26/03/2015, para o interior do Estado de São Paulo. Para o cenário favorável, os valores dos ingredientes baixaram 10% e o preço pago pelo kg de frango vivo subiu 10% e, para o cenário desfavorável, ocorreu o inverso. Foram avaliadas as características de desempenho e econômicas aos 21 e 42 dias de idade e também as características de carcaça aos 42 dias. Os dados foram submetidos à análise de variância e, em caso de significância (P&lt;0,05), aplicou-se o teste de Scott-Knott (5%). Os melhores resultados de desempenho e de características de carcaça foram associados aos tratamentos oriundos da programação linear, cujas concentrações de nutrientes foram mais elevadas, dos quais proteína bruta, aminoácidos e fósforo disponível são determinantes do desempenho superior de frangos de corte. Os tratamentos oriundos da programação não linear geraram melhores resultados econômicos, principalmente no cenário de mercado favorável, que apontou o menor custo para produção de 1 kg de peso corporal e maior lucro. Conclui-se que a formulação de ração com o uso da programação não linear, embora não maximize o desempenho, possibilita a obtenção de rações que otimizam o lucro. / The aim of this study was to evaluate the effect of feed formulations for broilers using linear and nonlinear programming on performance, carcass characteristics and economic aspects. One thousand and eighty, one-day-old male broilers, Cobb 500 &trade; strain, were distributed in a randomized block design, with six treatments and six replicates of 30 birds each. The treatments were: 1) feed formulated by linear programming with nutritional requirement of the Brazilian Tables for Poultry and Swine; 2) feed formulated by linear programming with nutritional requirement of Management Cobb&trade; Manual; 3) feed formulated by linear programming with nutritional requirement of mathematical models; 4) feed formulated by nonlinear programming on normal market scenario; 5) feed formulated by nonlinear programming on favorable market scenario; and 6) feed formulated by nonlinear programming on unfavorable market scenario. In the normal market scenario values of corn, soybean meal and the price paid for kg of live broiler were that practiced on March 26, 2015, for the state of São Paulo. To the favorable scenario, the values of the ingredients decreased 10% and the price paid for kg of live broiler increased by 10% and, for the unfavorable scenario, the opposite happened. The performance and economic characteristics at 21 and 42 days, and carcass characteristics at 42 days were evaluated. Data were submitted to analysis of variance and, in case of significance (P&lt;0.05), the Scott-Knott test (5%) were applied. Best performance and carcass characteristics results were associated with treatments derived from linear programming, whose nutrient concentrations were higher, of which crude protein, amino acids and available phosphorus are determining the superior performance of broilers. Treatments arising from the non-linear programming generated better economic results, especially in the favorable market scenario, which showed the lowest cost to produce 1 kg of body weight and higher profit. It was concluded that feed formulation using non-linear programming, even though does not maximize performance, allows to feed formulation that optimize profit.

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