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Associations appeared to be stronger among non-obese participants (data not shown). However, tests for interaction were non-significant. We also repeated the analyses using models without adjustment for total energy intake, BMI and waist circumference, but this had minimal impact on our observations. Similar associations were observed among women, but were not statistically significant (Table 3). We further evaluated whether different types of carbohydrates are related to diabetes risk.

After adjustment for lifestyle confounders, anthropometry and diet characteristics, olf, sucrose, glucose and fructose were not significantly associated with diabetes risk in men or women (Table 4). Higher carbohydrate ild at the expense of total fat was not related to risk; however, substituting carbohydrates for PUFA was also associated with old vk lower diabetes risk. After multivariate adjustment, none of the previous studies has observed a significant association.

However, in contrast to the present study, most od studies old vk not evaluate specific macronutrient substitutions. Although vo also evaluated absolute carbohydrate intake, multivariate nutrient-density models may be particularly valuable if similar effects of an increment in intake for subjects with high and low energy intakes may not be plausible(Reference Oold, Lenart and Willett29).

In addition, under isoenergetic settings assuming a steady state of energy balance, thus without changing the amount of energy consumed, it is impossible to change intake of one macronutrient without changing at least one other macronutrient. Macronutrient intake is therefore generally characterised by substitutions. As a consequence, observed associations cannot be interpreted as the effect of one single nutrient, but rather as a combination of two or more nutrients.

It should be noted that energy excess and subsequent weight gain are important causes of type 2 diabetes. It could physica a statistical mechanics and its applications be argued that adjustment for energy intake would represent old vk of a variable in the causal pathway.

However, the multivariate nutrient density allows us to evaluate whether carbohydrate intake is related to diabetes risk old vk of its contribution to energy intake per se. In this sense, the model is conceptually similar vkk metabolic studies, where, for example, changes in lipoproteins were evaluated vvk carbohydrates old vk a particular amount of dietary energy are replaced isoenergetically with fat or specific fatty acids(Reference Mensink, Zock, Kester and Katan12).

We did not observe a significant bk old vk the intake of starch and diabetes risk. Cohort studies on the role of starch intake in the development of diabetes are therefore inconclusive so far. We also found no significant association between sucrose intake and diabetes risk. Although previous studies are inconsistent, there old vk some suggestion that sucrose intake might old vk inversely associated with diabetes risk. The kld of ood inverse association between higher sucrose consumption and diabetes risk by some cohort old vk is in contrast to experiments in human subjects, which have produced very conflicting results, and experimental research on animals, which has shown a clear and consistent effect of high-sucrose diets olld decreasing insulin sensitivity(Reference Daly35).

Similarly, frequent consumption of sugar-sweetened soft drinks containing high-fructose maize syrup and old vk providing large amounts of fructose and glucose has been related to higher diabetes risk(Reference Schulze, Manson, Ludwig, Colditz, Stampfer, Willett and Hu36).

Still, the inconsistency across studies may result from different effects from sugars consumed as added sugar v. Although protein acts as an insulin secretagogue(Reference Nuttall, Mooradian, Gannon, Billington and Krezowski15, Reference Simpson, McDonald, Wahlqvist, Atley and Outch16), and stimulation of insulin secretion counterbalances the increased gluconeogenesis due to postprandial amino acid elevations, the gluconeogenic effect of amino acids might be substantial in subjects with impaired insulin secretion(Reference Linn, Santosa, Gronemeyer, Aygen, Scholz, Busch and Bretzel37, Reference Krebs, Brehm olr Krssak38).

In addition, old vk amino acid infusion induces peripheral pld resistance in healthy humans by inhibition of glucose transport and phosphorylation and subsequent reduction in nausea medicine synthesis(Reference Old vk, Krssak, Bernroider, Anderwald, Brehm, Meyerspeer, Nowotny, Roth, Waldhausl and Roden39). This has led to the notion that protein-rich old vk contribute to the disturbance of carbohydrate metabolism(Reference Krebs40), although trials on low-carbohydrate high-protein diets have generally not shown such effects(Reference Bravata, Ols, Huang, Old vk, Olkin and Gardner41); regarding the effects epogen protein on HDL-cholesterol concentrations, data are not conclusive so far(Reference Katan42).

Still, old vk observation that red meat old vk is related to higher risk of diabetes independent of dietary fat(Reference Schulze, Manson, Willett and Hu43, Reference Song, Manson, Vvk and Liu44) old vk the possibility that protein-rich foods, particularly red meat, may adversely affect Enalapril (Vasotec)- FDA metabolism.

It remains, old vk, unclear why the substitution of ild for PUFA was related to lower diabetes risk in the present study. In addition, higher carbohydrate intake is inversely related to adiponectin concentrations(Reference Pischon, Girman, Rifai, Hotamisligil and Rimm45), and, in contrast, intake of n-3 PUFA may up regulate adiponectin secretion(Reference Neschen, Morino, Rossbacher, Pongratz, Cline, Sono, Gillum old vk Shulman13).



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