Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study

Maria Lankinen, Ursula Schwab, Marjukka Kolehmainen, Jussi Paananen, Kaisa Poutanen, Hannu Mykkänen, Tuulikki Seppänen-Laakso, Helena Gylling, Matti Uusitupa, Matej Orešič, Maria Lankinen, Ursula Schwab, Marjukka Kolehmainen, Jussi Paananen, Kaisa Poutanen, Hannu Mykkänen, Tuulikki Seppänen-Laakso, Helena Gylling, Matti Uusitupa, Matej Orešič

Abstract

Background: Due to the growing prevalence of type 2 diabetes, new dietary solutions are needed to help improve glucose and lipid metabolism in persons at high risk of developing the disease. Herein we investigated the effects of low-insulin-response grain products, fatty fish, and berries on glucose metabolism and plasma lipidomic profiles in persons with impaired glucose metabolism.

Methodology/principal findings: Altogether 106 men and women with impaired glucose metabolism and with at least two other features of the metabolic syndrome were included in a 12-week parallel dietary intervention. The participants were randomized into three diet intervention groups: (1) whole grain and low postprandial insulin response grain products, fatty fish three times a week, and bilberries three portions per day (HealthyDiet group), (2) Whole grain enriched diet (WGED) group, which includes principally the same grain products as group (1), but with no change in fish or berry consumption, and (3) refined wheat breads (Control). Oral glucose tolerance, plasma fatty acids and lipidomic profiles were measured before and after the intervention. Self-reported compliance with the diets was good and the body weight remained constant. Within the HealthyDiet group two hour glucose concentration and area-under-the-curve for glucose decreased and plasma proportion of (n-3) long-chain PUFAs increased (False Discovery Rate p-values <0.05). Increases in eicosapentaenoic acid and docosahexaenoic acid associated curvilinearly with the improved insulin secretion and glucose disposal. Among the 364 characterized lipids, 25 changed significantly in the HealthyDiet group, including multiple triglycerides incorporating the long chain (n-3) PUFA.

Conclusions/significance: The results suggest that the diet rich in whole grain and low insulin response grain products, bilberries, and fatty fish improve glucose metabolism and alter the lipidomic profile. Therefore, such a diet may have a beneficial effect in the efforts to prevent type 2 diabetes in high risk persons.

Trial registration: ClinicalTrials.gov NCT00573781.

Conflict of interest statement

Competing Interests: Fazer bakeries Oy, Vaasan & Vaasan Oy, KE Leipä Oy, Leipomo Ruistähkä, Leipomo Koskelonseutu, Raisio Oyj, Pakkasmarja Oy and Joswola Oy are commercial companies. They volunteered to contribute their products to the intervention. The authors gave this opportunity to many companies and do not have any commitment with these companies. Therefore they state that no competing interest exists.

Figures

Figure 1. Flow diagram of the study.
Figure 1. Flow diagram of the study.
Figure 2. Changes in dietary intake during…
Figure 2. Changes in dietary intake during the 12-week intervention in the HealthyDiet (n = 36), Whole grain enriched diet (WGED) (n = 34) and Control (n = 35) groups.
Bars represent mean of absolute changes ± SD. Means without a common letter differ in mixed model comparison, FDR p<0.05.
Figure 3. Bar charts of glucose metabolism…
Figure 3. Bar charts of glucose metabolism parameters in each group before and after the intervention.
A) plasma 2 hour glucose, B) area under the curve (AUC) for glucose, C) Insulinogenic index (IGI) and D) Disposition index (DI) in OGTT. Values are means ± SEM, n = 37, 34 and 35 in the HealthyDiet, Whole grain enriched diet (WGED) and Control groups, respectively, except for IGI and DI, n = 36 before and n = 35 after the intervention in the HealthyDiet group, and n = 32 before and after the intervention in the WGED group.
Figure 4. Associations between glucose metabolism and…
Figure 4. Associations between glucose metabolism and plasma EPA and DHA content.
Changes in insulinogenic index (IGI) (A and B) and disposition index (DI) (C and D) during the intervention period (95% Confidence interval) according to quartiles of changes in plasma EPA (A and C) and DHA (B and D) content (%). * p<0.01 in Kruskal-Wallis test. All groups combined, n = 99. Ranges of changes in EPA quartiles: 1 = −2.3–0.4% units; 2 = −0.3−0.1% units; 3 = 0.1−0.6% units; 4 = 0.6−4.2% units, and in DHA quartiles: 1 = −2.4–0.6% units; 2 = −0.6–0.1% units; 3 = −0.04−0.7% units; 4 = 0.7−3.0% units.

References

    1. Anderson JW. Whole grains protect against atherosclerotic cardiovascular disease. Proc Nutr Soc. 2003;62:135–142.
    1. Laaksonen DE, Toppinen LK, Juntunen KS, Autio K, Liukkonen KH, et al. Dietary carbohydrate modification enhances insulin secretion in persons with the metabolic syndrome. Am J Clin Nutr. 2005;82:1218–1227.
    1. Mellen PB, Walsh TF, Herrington DM. Whole grain intake and cardiovascular disease: a meta-analysis. Nutr Metab Cardiovasc Dis. 2008;18:283–290.
    1. He K, Song Y, Daviglus ML, Liu K, Van Horn L, et al. Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies. Circulation. 2004;109:2705–2711.
    1. Breslow JL. N-3 Fatty Acids and Cardiovascular Disease. Am J Clin Nutr. 2006;83:1477S–1482S.
    1. Hanhineva K, Torronen R, Bondia-Pons I, Pekkinen J, Kolehmainen M, et al. Impact of dietary polyphenols on carbohydrate metabolism. Int J Mol Sci. 2010;11:1365–1402.
    1. Lutsey PL, Jacobs DR, Jr, Kori S, Mayer-Davis E, Shea S, et al. Whole grain intake and its cross-sectional association with obesity, insulin resistance, inflammation, diabetes and subclinical CVD: The MESA Study. Br J Nutr. 2007;98:397–405.
    1. Leinonen K, Liukkonen K, Poutanen K, Uusitupa M, Mykkanen H. Rye bread decreases postprandial insulin response but does not alter glucose response in healthy Finnish subjects. Eur J Clin Nutr. 1999;53:262–267.
    1. Juntunen KS, Laaksonen DE, Autio K, Niskanen LK, Holst JJ, et al. Structural differences between rye and wheat breads but not total fiber content may explain the lower postprandial insulin response to rye bread. Am J Clin Nutr. 2003;78:957–964.
    1. Rosen LA, Blanco Silva LO, Andersson UK, Holm C, Ostman EM, et al. Endosperm and whole grain rye breads are characterized by low post-prandial insulin response and a beneficial blood glucose profile. Nutr J. 2009;8:42–52.
    1. Kallio P, Kolehmainen M, Laaksonen DE, Kekalainen J, Salopuro T, et al. Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT Study. Am J Clin Nutr. 2007;85:1417–1427.
    1. Lankinen M, Schwab U, Gopalacharyulu PV, Seppanen-Laakso T, Yetukuri L, et al. Dietary carbohydrate modification alters serum metabolic profiles in individuals with the metabolic syndrome. Nutr Metab Cardiovasc Dis. 2010;20:249–257.
    1. Maatta-Riihinen KR, Kamal-Eldin A, Mattila PH, Gonzalez-Paramas AM, Torronen AR. Distribution and contents of phenolic compounds in eighteen Scandinavian berry species. J Agric Food Chem. 2004;52:4477–4486.
    1. Basu A, Rhone M, Lyons TJ. Berries: emerging impact on cardiovascular health. Nutr Rev. 2010;68:168–177.
    1. Nettleton JA, Katz R. N-3 Long-Chain Polyunsaturated Fatty Acids in Type 2 Diabetes: a Review. J Am Diet Assoc. 2005;105:428–440.
    1. Ramel A, Martinez A, Kiely M, Morais G, Bandarra NM, et al. Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults. Diabetologia. 2008;51:1261–1268.
    1. Giacco R, Cuomo V, Vessby B, Uusitupa M, Hermansen K, et al. Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids? Nutr Metab Cardiovasc Dis. 2007;17:572–580.
    1. Fedor D, Kelley DS. Prevention of insulin resistance by n-3 polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care. 2009;12:138–146.
    1. Taouis M, Dagou C, Ster C, Durand G, Pinault M, et al. N-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle. Am J Physiol Endocrinol Metab. 2002;282:E664–71.
    1. Browning LM, Krebs JD, Moore CS, Mishra GD, O'Connell MA, et al. The impact of long chain n-3 polyunsaturated fatty acid supplementation on inflammation, insulin sensitivity and CVD risk in a group of overweight women with an inflammatory phenotype. Diabetes Obes Metab. 2007;9:70–80.
    1. Rasic-Milutinovic Z, Perunicic G, Pljesa S, Gluvic Z, Sobajic S, et al. Effects of N-3 PUFAs supplementation on insulin resistance and inflammatory biomarkers in hemodialysis patients. Ren Fail. 2007;29:321–329.
    1. Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, et al. The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. N Engl J Med. 1993;328:238–244.
    1. Blank ML, Smith ZL, Lee YJ, Snyder F. Effects of eicosapentaenoic and docosahexaenoic acid supplements on phospholipid composition and plasmalogen biosynthesis in P388D1 cells. Arch Biochem Biophys. 1989;269:603–611.
    1. Oh da Y, Talukdar S, Bae EJ, Imamura T, Morinaga H, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 2010;142:687–698.
    1. Lankinen M, Schwab U, Erkkila A, Seppanen-Laakso T, Hannila ML, et al. Fatty fish intake decreases lipids related to inflammation and insulin signaling–a lipidomics approach. PLoS One. 2009;4:e5258.
    1. Wymann MP, Schneiter R. Lipid signalling in disease. Nat Rev Mol Cell Biol. 2008;9:162–176.
    1. Roberts LD, McCombie G, Titman CM, Griffin JL. A matter of fat: an introduction to lipidomic profiling methods. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;871:174–181.
    1. Lorenzo C, Wagenknecht LE, Rewers MJ, Karter AJ, Bergman RN, et al. Disposition Index, Glucose Effectiveness, and Conversion to Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care. 2010;33:2098–2103.
    1. Elbein SC, Hasstedt SJ, Wegner K, Kahn SE. Heritability of pancreatic beta-cell function among nondiabetic members of Caucasian familial type 2 diabetic kindreds. J Clin Endocrinol Metab. 1999;84:1398–1403.
    1. Pluskal T, Castillo S, Villar-Briones A, Oresic M. MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinformatics. 2010;11:395.
    1. R Development Core Team. R: A language and environment for statistical computing. . 2010. Available at: ., 2010.
    1. Pinheiro J, Bates D, DebRoy S, Sarkar D the R Core team. nlme: Linear and Nonlinear Mixed Effects Models. R package version. 2009;3:1–96.
    1. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B. 1995;57:289–300.
    1. Stull AJ, Cash KC, Johnson WD, Champagne CM, Cefalu WT. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. J Nutr. 2010;140:1764–1768.
    1. Egert S, Fobker M, Andersen G, Somoza V, Erbersdobler HF, et al. Effects of dietary alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on parameters of glucose metabolism in healthy volunteers. Ann Nutr Metab. 2008;53:182–187.
    1. Wolever TM, Mehling C. High-carbohydrate-low-glycaemic index dietary advice improves glucose disposition index in subjects with impaired glucose tolerance. Br J Nutr. 2002;87:477–487.
    1. Wolever TM, Mehling C, Chiasson JL, Josse RG, Leiter LA, et al. Low glycaemic index diet and disposition index in type 2 diabetes (the Canadian trial of carbohydrates in diabetes): a randomised controlled trial. Diabetologia. 2008;51:1607–1615.
    1. Schmitz G, Ruebsaamen K. Metabolism and atherogenic disease association of lysophosphatidylcholine. Atherosclerosis. 2010;208:10–18.
    1. Aiyar N, Disa J, Ao Z, Ju H, Nerurkar S, et al. Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells. Mol Cell Biochem. 2007;295:113–120.
    1. Yetukuri L, Soderlund S, Koivuniemi A, Seppanen-Laakso T, Niemela PS, et al. Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol. J Lipid Res. 2010;51:2341–2351.
    1. Hayashi K, Takahashi M, Nishida W, Yoshida K, Ohkawa Y, et al. Phenotypic modulation of vascular smooth muscle cells induced by unsaturated lysophosphatidic acids. Circ Res. 2001;89:251–258.
    1. Block RC, Duff R, Lawrence P, Kakinami L, Brenna JT, et al. The effects of EPA, DHA, and aspirin ingestion on plasma lysophospholipids and autotaxin. Prostaglandins Leukot Essent Fatty Acids. 2010;82:87–95.
    1. Lagarde M, Bernoud N, Brossard N, Lemaitre-Delaunay D, Thies F, et al. Lysophosphatidylcholine as a preferred carrier form of docosahexaenoic acid to the brain. J Mol Neurosci. 2001;16:201–4; discussion 215-21.
    1. Smedman AE, Gustafsson IB, Berglund LG, Vessby BO. Pentadecanoic acid in serum as a marker for intake of milk fat: relations between intake of milk fat and metabolic risk factors. Am J Clin Nutr. 1999;69:22–29.
    1. Warensjo E, Smedman A, Stegmayr B, Hallmans G, Weinehall L, et al. Stroke and plasma markers of milk fat intake–a prospective nested case-control study. Nutr J. 2009;8:21.
    1. Iggman D, Arnlov J, Vessby B, Cederholm T, Sjogren P, et al. Adipose tissue fatty acids and insulin sensitivity in elderly men. Diabetologia. 2010;53:850–857.
    1. Biong AS, Veierod MB, Ringstad J, Thelle DS, Pedersen JI. Intake of milk fat, reflected in adipose tissue fatty acids and risk of myocardial infarction: a case-control study. Eur J Clin Nutr. 2006;60:236–244.
    1. Wolk A, Furuheim M, Vessby B. Fatty acid composition of adipose tissue and serum lipids are valid biological markers of dairy fat intake in men. J Nutr. 2001;131:828–833.
    1. Brevik A, Veierod MB, Drevon CA, Andersen LF. Evaluation of the odd fatty acids 15∶0 and 17∶0 in serum and adipose tissue as markers of intake of milk and dairy fat. Eur J Clin Nutr. 2005;59:1417–1422.
    1. Saadatian-Elahi M, Slimani N, Chajes V, Jenab M, Goudable J, et al. Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2009;89:331–346.
    1. Ozogul Y, Ozogul F, Cicek E, Polat A, Kuley E. Fat content and fatty acid compositions of 34 marine water fish species from the Mediterranean Sea. Int J Food Sci Nutr. 2008:1–12.
    1. Aggelousis G, Lazos ES. Fatty Acid Composition of the Lipids from Eight Freshwater Fish Species from Greece. Journal of Food Composition and Analysis. 1991:68–76.
    1. Dudek JA, Elkins ER. Effects of cooking on the fatty acid profiles of selected seafoods. In: Simonopoulos AP, Kifer RR, editors. Health effects of polyunsaturated fatty acids in seafoods. Florida: Academic Press; 1986. pp. 431–450.
    1. Lankinen M, Schwab U, Seppanen-Laakso T, Mattila I, Juntunen K, et al. Metabolomic Analysis of Plasma Metabolites That May Mediate Effects of Rye Bread on Satiety and Weight Maintenance in Postmenopausal Women. J Nutr. 2011;141:31–36.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera