Taken together the results presented in this thesis suggest that consumption of whole grain foods can contribute to the prevention of type 2 diabetes. Currently, it seems that physiological effects associated with the presence of non-digestible carbohydrates play a more important role in this preventive effect than reduction of postprandial glycemia.
Intake of whole grain foods is already recommended as part of a healthy food pattern, but especially persons with a risk of developing t2dm could benefit from this advice. Early interventions are needed to prevent irreversible damage by unnoticed hyperglycemia, which underlines the need of development of early biomarkers of this disease. In addition, detection of subpopulations most susceptible to dietary interventions due to their genetic make-up would enable more efficient personalized dietary advice. Currently, the assortment of whole grain products is small and the consumer acceptance of whole grain foods is low.
Our finding that non-digestible carbohydrates could mediate the protective effect are valuable for the development of cereal grain products with t2dm preventive potential (functional foods), which are more acceptable than traditional whole grain foods.
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates 1
for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047–53.
2 MI, Klein R, Welborn TA, Knuiman MW. Onset of niddm occurs at least 4–7 yr before clinical diagnosis. Diabetes Care 1992;15:815 9.
Valensi P, Schwarz
3 EH, Hall M, Felton AM, Maldonato A, Mathieu C. Pre-diabetes essential action: a European perspective. Diabetes Metab 2005;31:606 20.
Food and Agriculture Organization of the United Nations and World Health 4
organization. Diet, nutrition and prevention of chronic disease: Report of a joint who/fao expert consultation. 2003. Geneva, World Health Organisation.
Kolb H, Mandrup-Poulsen T. An immune origin of type 2 diabetes? Diabetologia 5
Fleischman A, Shoelson
6 SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care 2008;31:289–94.
Koska J, Ortega E, Bunt
7 JC et al. The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study. Diabetologia 2009;52:385–93.
8 ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006;444:847–53.
Houstis N, Rosen
9 ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 2006;440:944–8.
Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome: a 10
comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005;111:1448–54.
11 JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose for prevention of type 2 diabetes mellitus: the stop-niddm randomised trial. Lancet 2002;359:2072–7.
12 xR, Li GW, Hu YH et al. Effects of diet and exercise in preventing niddm in people with impaired glucose tolerance. The Da Qing igt and Diabetes Study. Diabetes Care 1997;20:537–44.
Faerch K, Borch-Johnsen K, Holst
13 JJ, Vaag A. Pathophysiology and aetiology of
impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes? Diabetologia 2009.
Faerch K, Vaag A, Holst
14 JJ, Hansen T, Jorgensen T, Borch-Johnsen K. Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study. Diabetes Care 2009;32:439–44.
Lau C, Toft U, Tetens I et al. Dietary patterns predict changes in two-hour post-oral 15
glucose tolerance test plasma glucose concentrations in middle-aged adults. J Nutr 2009;139:588–93.
Food and Agriculture Organization of the United Nations. Carbohydrates in human 16
nutrition: report of a joint fao/who expert consultation. Nutrition Paper no. 66. 1998.
Burkitt D. Refined carbohydrate foods and disease: some implications of dietary fiber.
London: Academic Press, 1975.
18 HC. Dietary-fiber hypothesis of the etiology of diabetes mellitus. Diabetes 1975;24:762–5.
Slavin J. Why whole grains are protective: biological mechanisms. Proc Nutr Soc 19
20 DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. jama 2002;287:2414–23.
Willett W, Manson J, Liu S. Glycemic index, glycemic load, and risk of type 2 diabetes.
Am J Clin Nutr 2002;76:274S–80S.
22 MD, Bickerton AS, Dennis AL, Vidal H, Frayn KN. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism.
Am J Clin Nutr 2005;82:559–67.
xiong Y, Miyamoto N, Shibata K et al. Short-chain fatty acids stimulate leptin 23
production in adipocytes through the G protein-coupled receptor gpr41. Proc Natl Acad Sci U S A 2004;101:1045–50.
24 KK, Liu RH. Antioxidant activity of grains. J Agric Food Chem 2002;50:6182–7.
Fardet, A., Rock, E, and Remesy, C. Is the in vitro antioxidant potential of whole-grain 25
cereals and cereal products well reflected in vivo? J Cereal Science 48, 258–276. 2008.
Perez-Jimenez J, Saura-Calixto F. Literature data may underestimate the actual 26
antioxidant capacity of cereals. J Agric Food Chem 2005;53:5036–40.
Granfeldt Y, Wu x, Bjorck I. Determination of glycaemic index; some methodological 27
aspects related to the analysis of carbohydrate load and characteristics of the previous evening meal. Eur J Clin Nutr 2006;60:104–12.
Nilsson A, Ostman E, Preston T, Bjorck I. Effects of
28 gi vs content of cereal fibre of the
evening meal on glucose tolerance at a subsequent standardized breakfast. Eur J Clin Nutr 2007.
Stevenson E, Williams C, Nute M, Humphrey L, Witard O. Influence of the glycaemic 29
index of an evening meal on substrate oxidation following breakfast and during exercise the next day in healthy women. Eur J Clin Nutr 2007.
Ceriello A. Cardiovascular effects of acute hyperglycaemia: pathophysiological 30
underpinnings. Diab Vasc Dis Res 2008;5:260–8.
Dickinson S, Hancock
31 DP, Petocz P, Ceriello A, Brand-Miller J. High-glycemic index carbohydrate increases nuclear factor-kappaB activation in mononuclear cells of young, lean healthy subjects. Am J Clin Nutr 2008;87:1188–93.
32 PJ, Sutherland WH, McGrath MM, de Jong SA, Walker RJ, Williams MJ.
Postprandial cytokine concentrations and meal composition in obese and lean women.
Obesity (Silver Spring) 2008;16:2046–52.
Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H, Dandona P. Glucose challenge 33
stimulates reactive oxygen species (ros) generation by leucocytes. J Clin Endocrinol Metab 2000;85:2970–3.
34 MA, Niedereichholz U, Ettler R et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 1997;273:e981–e988.
Irwin N, McClean
35 PL, O’Harte FP, Gault VA, Harriott P, Flatt PR. Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro3)gip prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice. Diabetologia 2007;50:1532–40.
Yamada C, Yamada Y, Tsukiyama K et al. Genetic inactivation of
36 gip signaling reverses
aging-associated insulin resistance through body composition changes. Biochem Biophys Res Commun 2007;364:175–80.
Alvarez P, Alvarado C, Mathieu F, Jimenez L, De la Fuente
37 M. Diet supplementation for
5 weeks with polyphenol-rich cereals improves several functions and the redox state of mouse leucocytes. Eur J Nutr 2006;45:428–38.
Rezar V, Pajk T, Marinsek
38 LR et al. Wheat bran and oat bran effectively reduce oxidative stress induced by high-fat diets in pigs. Ann Nutr Metab 2003;47:78–84.
Esposito K, Nappo F, Marfella R et al. Inflammatory cytokine concentrations are 39
acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 2002;106:2067–72.
Ghanim H, Mohanty P, Pathak R, Chaudhuri A, Sia
40 CL, Dandona P. Orange juice or
fructose intake does not induce oxidative and inflammatory response. Diabetes Care 2007;30:1406–11.
Bellido C, Lopez-Miranda J, Blanco-Colio
41 LM et al. Butter and walnuts, but not olive
oil, elicit postprandial activation of nuclear transcription factor kappaB in peripheral blood mononuclear cells from healthy men. Am J Clin Nutr 2004;80:1487–91.
42 LM, Valderrama M, varez-Sala LA et al. Red wine intake prevents nuclear factor-kappaB activation in peripheral blood mononuclear cells of healthy volunteers during postprandial lipemia. Circulation 2000;102:1020–6.
43 MD, Currie JM, Morgan LM, Jewell DP, Frayn KN. Prior short-term consumption of resistant starch enhances postprandial insulin sensitivity in healthy subjects. Diabetologia 2003;46:659–65.
44 AM, Juneja LR, Slavin JL. Comparison of different fibers for in vitro production of short chain fatty acids by intestinal microflora. J Med Food 2005;8:113–6.
45 GA, Krause JA, Miller TL, Wolin MJ. Cornstarch fermentation by the colonic microbial community yields more butyrate than does cabbage fiber fermentation;
cornstarch fermentation rates correlate negatively with methanogenesis. Am J Clin Nutr 1992;55:70–7.