A pre-meal of whey proteins induces differential effects on glucose and lipid metabolism in subjects with the metabolic syndrome: a randomised cross-over trial

  • Ann Bjørnshave
  • Jens Juul Holst
  • Kjeld Hermansen
Original Contribution

Abstract

Purpose

Postprandial lipaemia (PPL), an independent risk factor for cardiovascular disease, is affected by composition and timing of meals. We evaluated if whey proteins (WP) consumed as a pre-meal before a fat-rich meal reduce postprandial triglyceride (TG) and apolipoprotein B-48 (ApoB-48) responses in subjects with the metabolic syndrome (MeS).

Methods

An acute, randomised, cross-over trial was conducted. 20 subjects with MeS consumed a pre-meal of 0, 10 or 20 g WP 15 min prior to a fat-rich meal. The responses of TG and ApoB-48 were assessed. We also analysed postprandial responses of free fatty acids (FFA), glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and paracetamol (reflecting gastric emptying rates).

Results

WP pre-meal did not alter the TG or ApoB-48 responses. In contrast, the insulin response was more pronounced after a pre-meal of 20 g WP than with 10 g WP (P = 0.0005) and placebo (P < 0.0001). Likewise, the postprandial glucagon response was greater with a pre-meal of 20 g WP than with 10 g WP (P < 0.0001) and 0 g WP (P < 0.0001). A pre-meal with 20 g of WP generated lower glucose (P = 0.0148) and S-paracetamol responses (P = 0.0003) and a higher GLP-1 response (P = 0.0086) than placebo. However, the pre-meal did not influence responses of GIP, FFA or appetite assessed by a Visual Analog Scale.

Conclusions

Consumption of a WP pre-meal prior to a fat-rich meal did not affect TG and chylomicron responses. In contrast, the WP pre-meal stimulates insulin and glucagon secretion and reduces blood glucose as expected, and delays gastric emptying. Consequently, our study points to a differential impact of a WP pre-meal on lipid and glucose metabolism to a fat-rich meal in subjects with MeS.

Keywords

Pre-meal Whey proteins Dose–response Metabolic syndrome Postprandial lipaemia 

Abbreviations

AA

Amino acids

Apolipoprotein B-48

ApoB-48

CVD

Cardiovascular diseases

E

Energy

FFA

Free fatty acids

GIP

Glucose-dependent insulinotropic peptide

GLP-1

Glucagon-like peptide 1

iAUC

Incremental area under the curve

tAUC

Total area under the curve

MeS

Metabolic syndrome

PPL

Postprandial lipaemia

QQ

Quantile–quantile

TG

Triglycerides

VAS

Visual analog scale

WP

Whey proteins

Notes

Acknowledgements

We thank Eva Mølgaard Jensen Lene Trudsø Jensen and Lene Bruss Albæk for outstanding technical assistance. Furthermore, we would like thank Anne Marie Kruse, Peter Reiter, Mette Bohl, and Anne Grethe Schioldan for assistance during the meal tests. This work was supported by grants from The Danish Dairy Research Foundation, Arla Foods Ingredients Group P/S, and Innovation Fund Denmark—MERITS (4105-00002B). AB was supported by research grants from The Danish Diabetes Academy supported by the Novo Nordisk Foundation, Aarhus University and The Research Foundation of the Department of Endocrinology and Internal Medicine, Aarhus University Hospital. Protein powder was kindly provided by Arla Foods Ingredients Group P/S.

Compliance with ethical standards

Conflict of interest

Ann Bjørnshave, Jens Juul Holst and Kjeld Hermansen have no conflicts of interest and other funding disclosures to declare.

Supplementary material

394_2018_1684_MOESM1_ESM.pdf (15 kb)
Supplementary material 1 (PDF 16 KB)

References

  1. 1.
    Jagla A, Schrezenmeir J (2001) Postprandial triglycerides and endothelial function. Exp Clin Endocrinol Diabetes 109:S533–S547CrossRefGoogle Scholar
  2. 2.
    Carstensen M, Thomsen C, Gotzsche O, Holst JJ, Schrezenmeir J, Hermansen K (2004) Differential postprandial lipoprotein responses in type 2 diabetic men with and without clinical evidence of a former myocardial infarction. Rev Diabet Stud 1:175–184CrossRefGoogle Scholar
  3. 3.
    Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A (2007) Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 298:299–308CrossRefGoogle Scholar
  4. 4.
    Duez H, Lamarche B, Uffelman KD, Valero R, Cohn JS, Lewis GF (2006) Hyperinsulinemia is associated with increased production rate of intestinal apolipoprotein B-48-containing lipoproteins in humans. Arterioscler Thromb Vasc Biol 26:1357–1363CrossRefGoogle Scholar
  5. 5.
    Masuda D, Sugimoto T, Tsujii K, Inagaki M, Nakatani K, Yuasa-Kawase M, Tsubakio-Yamamoto K, Ohama T, Nishida M, Ishigami M, Kawamoto T, Matsuyama A, Sakai N, Komuro I, Yamashita S (2012) Correlation of fasting serum apolipoprotein B-48 with coronary artery disease prevalence. Eur J Clin Invest 42:992–999CrossRefGoogle Scholar
  6. 6.
    Lairon D (2008) Macronutrient intake and modulation on chylomicron production and clearance. Atheroscler Suppl 9:45–48CrossRefGoogle Scholar
  7. 7.
    Nilsson M, Stenberg M, Frid AH, Holst JJ, Bjorck IM (2004) Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins. Am J Clin Nutr 80:1246–1253CrossRefGoogle Scholar
  8. 8.
    Nilsson M, Holst JJ, Bjorck IM (2007) Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks. Am J Clin Nutr 85:996–1004CrossRefGoogle Scholar
  9. 9.
    Pal S, Ellis V, Dhaliwal S (2010) Effects of whey protein isolate on body composition, lipids, insulin and glucose in overweight and obese individuals. Br J Nutr 104:716–723CrossRefGoogle Scholar
  10. 10.
    Akhavan T, Luhovyy BL, Panahi S, Kubant R, Brown PH, Anderson GH (2014) Mechanism of action of pre-meal consumption of whey protein on glycemic control in young adults. J Nutr Biochem 25:36–43CrossRefGoogle Scholar
  11. 11.
    Bertelsen J, Christiansen C, Thomsen C, Poulsen PL, Vestergaard S, Steinov A, Rasmussen LH, Rasmussen O, Hermansen K (1993) Effect of meal frequency on blood glucose, insulin, and free fatty acids in NIDDM subjects. Diabetes Care 16:4–7CrossRefGoogle Scholar
  12. 12.
    Staub H (1921) Untersuchungen uber den zuckerstoffwechsel des munchen. Z Klin Med 91:44–48Google Scholar
  13. 13.
    Traugott K (1922) Über das verhalten des blutzuckerspiegels bei wiederholter und verschiedener art enteraler zuckerzufuhr und dessen bedeutung für die leberfunktion. Klin Wochenschr 1:892 (892–894; 894)CrossRefGoogle Scholar
  14. 14.
    Ma J, Stevens JE, Cukier K, Maddox AF, Wishart JM, Jones KL, Clifton PM, Horowitz M, Rayner CK (2009) Effects of a protein preload on gastric emptying, glycemia, and gut hormones after a carbohydrate meal in diet-controlled type 2 diabetes. Diabetes Care 32:1600–1602CrossRefGoogle Scholar
  15. 15.
    Akhavan T, Luhovyy BL, Brown PH, Cho CE, Anderson GH (2010) Effect of premeal consumption of whey protein and its hydrolysate on food intake and postmeal glycemia and insulin responses in young adults. Am J Clin Nutr 91:966–975CrossRefGoogle Scholar
  16. 16.
    Holmer-Jensen J, Mortensen LS, Astrup A, de Vrese M, Holst JJ, Thomsen C, Hermansen K (2013) Acute differential effects of dietary protein quality on postprandial lipemia in obese non-diabetic subjects. Nutr Res 33:34–40CrossRefGoogle Scholar
  17. 17.
    Mortensen LS, Hartvigsen ML, Brader LJ, Astrup A, Schrezenmeir J, Holst JJ, Thomsen C, Hermansen K (2009) Differential effects of protein quality on postprandial lipemia in response to a fat-rich meal in type 2 diabetes: comparison of whey, casein, gluten, and cod protein. Am J Clin Nutr 90:41–48CrossRefGoogle Scholar
  18. 18.
    Holmer-Jensen J, Hartvigsen ML, Mortensen LS, Astrup A, de Vrese M, Holst JJ, Thomsen C, Hermansen K (2012) Acute differential effects of milk-derived dietary proteins on postprandial lipaemia in obese non-diabetic subjects. Eur J Clin Nutr 66:32–38CrossRefGoogle Scholar
  19. 19.
    Mortensen LS, Holmer-Jensen J, Hartvigsen ML, Jensen VK, Astrup A, de Vrese M, Holst JJ, Thomsen C, Hermansen K (2012) Effects of different fractions of whey protein on postprandial lipid and hormone responses in type 2 diabetes. Eur J Clin Nutr 66:799–805CrossRefGoogle Scholar
  20. 20.
    Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr, International Diabetes Federation Task Force on Epidemiology and Prevention, Hational Heart, Lung, and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645CrossRefGoogle Scholar
  21. 21.
    Bohl M, Bjornshave A, Rasmussen KV, Schioldan AG, Amer B, Larsen MK, Dalsgaard TK, Holst JJ, Herrmann A, O’Neill S, O’Driscoll L, Afman L, Jensen E, Christensen MM, Gregersen S, Hermansen K (2015) Dairy proteins, dairy lipids, and postprandial lipemia in persons with abdominal obesity (DairyHealth): a 12-wk, randomized, parallel-controlled, double-blinded, diet intervention study. Am J Clin Nutr 101:870–878CrossRefGoogle Scholar
  22. 22.
    Kuhre RE, Wewer Albrechtsen NJ, Hartmann B, Deacon CF, Holst JJ (2015) Measurement of the incretin hormones: glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. J Diabetes Complicat 29:445–450CrossRefGoogle Scholar
  23. 23.
    Parhofer KG (2015) Interaction between glucose and lipid metabolism: more than diabetic dyslipidemia. Diabetes Metab J 39:353–362CrossRefGoogle Scholar
  24. 24.
    Unger RH, Orci L (1976) Physiology and pathophysiology of glucagon. Physiol Rev 56:778–826CrossRefGoogle Scholar
  25. 25.
    Schmid R, Schusdziarra V, Schulte-Frohlinde E, Maier V, Classen M (1989) Role of amino acids in stimulation of postprandial insulin, glucagon, and pancreatic polypeptide in humans. Pancreas 4:305–314CrossRefGoogle Scholar
  26. 26.
    Gunnerud UJ, Heinzle C, Holst JJ, Ostman EM, Bjorck IM (2012) Effects of pre-meal drinks with protein and amino acids on glycemic and metabolic responses at a subsequent composite meal. PLoS One 7:e44731CrossRefGoogle Scholar
  27. 27.
    Bonuccelli S, Muscelli E, Gastaldelli A, Barsotti E, Astiarraga BD, Holst JJ, Mari A, Ferrannini E (2009) Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms. Am J Physiol Endocrinol Metab 297:E532–E537CrossRefGoogle Scholar
  28. 28.
    Lopez-Miranda J, Williams C, Lairon D (2007) Dietary, physiological, genetic and pathological influences on postprandial lipid metabolism. Br J Nutr 98:458–473CrossRefGoogle Scholar
  29. 29.
    Martins IJ, Mortimer BC, Miller J, Redgrave TG (1996) Effects of particle size and number on the plasma clearance of chylomicrons and remnants. J Lipid Res 37:2696–2705Google Scholar
  30. 30.
    Stanstrup J, Schou SS, Holmer-Jensen J, Hermansen K, Dragsted LO (2014) Whey protein delays gastric emptying and suppresses plasma fatty acids and their metabolites compared to casein, gluten, and fish protein. J Proteome Res 13:2396–2408CrossRefGoogle Scholar
  31. 31.
    Deane AM, Nguyen NQ, Stevens JE, Fraser RJ, Holloway RH, Besanko LK, Burgstad C, Jones KL, Chapman MJ, Rayner CK, Horowitz M (2010) Endogenous glucagon-like peptide-1 slows gastric emptying in healthy subjects, attenuating postprandial glycemia. J Clin Endocrinol Metab 95:215–221CrossRefGoogle Scholar
  32. 32.
    Power ML, Schulkin J (2008) Anticipatory physiological regulation in feeding biology: cephalic phase responses. Appetite 50:194–206CrossRefGoogle Scholar
  33. 33.
    Frid AH, Nilsson M, Holst JJ, Bjorck IM (2005) Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am J Clin Nutr 82:69–75CrossRefGoogle Scholar
  34. 34.
    Nilsson AC, Ostman EM, Granfeldt Y, Bjorck IM (2008) Effect of cereal test breakfasts differing in glycemic index and content of indigestible carbohydrates on daylong glucose tolerance in healthy subjects. Am J Clin Nutr 87:645–654CrossRefGoogle Scholar
  35. 35.
    Lindgren O, Carr RD, Deacon CF, Holst JJ, Pacini G, Mari A, Ahren B (2011) Incretin hormone and insulin responses to oral versus intravenous lipid administration in humans. J Clin Endocrinol Metab 96:2519–2524CrossRefGoogle Scholar
  36. 36.
    Lindgren O, Pacini G, Tura A, Holst JJ, Deacon CF, Ahren B (2015) Incretin effect after oral amino acid ingestion in humans. J Clin Endocrinol Metab 100:1172–1176CrossRefGoogle Scholar
  37. 37.
    Lindgren O, Carr RD, Holst JJ, Deacon CF, Ahren B (2011) Dissociated incretin hormone response to protein versus fat ingestion in obese subjects. Diabetes Obes Metab 13:863–865CrossRefGoogle Scholar
  38. 38.
    Bendtsen LQ, Lorenzen JK, Bendsen NT, Rasmussen C, Astrup A (2013) Effect of dairy proteins on appetite, energy expenditure, body weight, and composition: a review of the evidence from controlled clinical trials. Adv Nutr 4:418–438CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ann Bjørnshave
    • 1
    • 2
  • Jens Juul Holst
    • 3
  • Kjeld Hermansen
    • 1
  1. 1.Department of Endocrinology and Internal MedicineAarhus University HospitalAarhus CDenmark
  2. 2.Danish Diabetes AcademyOdense CDenmark
  3. 3.NNF Centre for Basic Metabolic Research and The Department of Biomedical SciencesUniversity of CopenhagenKøbenhavn NDenmark

Personalised recommendations