The acute effects of dietary carbohydrate reduction on postprandial responses of non-esterified fatty acids and triglycerides: a randomized trial

Amirsalar Samkani, Mads J Skytte, Christian Anholm, Arne Astrup, Carolyn F Deacon, Jens J Holst, Sten Madsbad, Ray Boston, Thure Krarup, Steen B Haugaard, Amirsalar Samkani, Mads J Skytte, Christian Anholm, Arne Astrup, Carolyn F Deacon, Jens J Holst, Sten Madsbad, Ray Boston, Thure Krarup, Steen B Haugaard

Abstract

Background: Postprandial non-esterified fatty acid (NEFA) and triglyceride (TG) responses are increased in subjects with type 2 diabetes mellitus (T2DM) and may impair insulin action and increase risk of cardiovascular disease and death. Dietary carbohydrate reduction has been suggested as non-pharmacological therapy for T2DM, but the acute effects on NEFA and TG during subsequent meals remain to be investigated.

Methods: Postprandial NEFA and TG responses were assessed in subjects with T2DM by comparing a carbohydrate-reduced high-protein (CRHP) diet with a conventional diabetes (CD) diet in an open-label, randomized, cross-over study. Each diet was consumed on two consecutive days, separated by a wash-out period. The iso-caloric CRHP/CD diets contained 31/54 E% from carbohydrate, 29/16 E% energy from protein and 40/30 E% from fat, respectively. Sixteen subjects with well-controlled T2DM (median HbA1c 47 mmol/mol, (37-67 mmol/mol) and BMI 30 ± 4.4 kg/m2) participated in the study. NEFA and TG were evaluated following breakfast and lunch.

Results: NEFA net area under curve (AUC) was increased by 97 ± 38 μmol/Lx270 min (p = 0.024) after breakfast but reduced by 141 ± 33 μmol/Lx180 min (p < 0.001) after lunch on the CRHP compared with CD diet. Likewise, TG net AUC was increased by 80 ± 28 μmol/Lx270 min (p = 0.012) after breakfast but reduced by 320 ± 60 μmol/Lx180 min (p < 0.001) after lunch on the CRHP compared with CD diet.

Conclusions: In well-controlled T2DM a modest reduction of dietary carbohydrate with a corresponding increase in protein and fat acutely reduced postprandial serum NEFA suppression and increased serum TG responses after a breakfast meal but had the opposite effect after a lunch meal. The mechanism behind this second-meal phenomenon of CRHP diet on important risk factors for aggravating T2DM and cardiovascular disease awaits further investigation.

Trial registration: The study was registered at clinicaltrials.gov ID: NCT02472951. https://ichgcp.net/clinical-trials-registry/NCT02472951 . Registered June 16, 2015.

Keywords: Dietary carbohydrate reduction; Non-esterified fatty acids; Postprandial triglycerides.

Conflict of interest statement

Ethics approval and consent to participate

Written informed consent was obtained from all participants prior to any study related procedures. The study protocol was approved by the Health Ethics Committee of Copenhagen in accordance with the Helsinki-II declaration, and the trial was registered at Consent for publication

Written informed consent was obtained from all participants.

Competing interests

The authors declare that they have no competing interests to declare related to the present study.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Concentration of non-esterified fatty acid (NEFA) in sixteen well-controlled patients with type 2 diabetes after intake of a carbohydrate-reduced high-protein (CRHP) or conventional diabetes (CD) breakfast (0–270 min) and lunch (270–450 min), respectively (means of 2 consecutive days on each diet). Values are presented as means with their standard errors. Bar charts show net area under curve for breakfast and lunch, respectively. *Significant difference (p < 0.05) between diets
Fig. 2
Fig. 2
Incremental concentration of triglyceride in sixteen well-controlled patients with type 2 diabetes after intake of a carbohydrate-reduced high-protein (CRHP) or conventional diabetes (CD) breakfast (0–270 min) and lunch (270–450 min), respectively (means of 2 consecutive days on each diet). Values are presented as means with their standard errors. Bar charts show net area under curve for breakfast and lunch, respectively. *Significant difference (p < 0.05) between diets
Fig. 3
Fig. 3
Concentration of insulin in sixteen well-controlled patients with type 2 diabetes after intake of a carbohydrate-reduced high-protein (CRHP) or conventional diabetes (CD) breakfast (0–270 min) and lunch (270–450 min), respectively (means of 2 consecutive days on each diet). Values are presented as means with their standard errors. Bar charts show net area under curve for breakfast and lunch, respectively. *Significant difference (p < 0.05) between diets. (Reproduced from Samkani et al., BJN, 2018, with approval from British Journal of Nutrition)

References

    1. Il'yasova D, Wang F, D'Agostino RB, Jr., Hanley A, Wagenknecht LE. Prospective association between fasting NEFA and type 2 diabetes: impact of post-load glucose. Diabetologia 2010;53(5):866–874.
    1. Karpe F, Dickmann JR, Frayn KN. Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes. 2011;60(10):2441–2449. doi: 10.2337/db11-0425.
    1. Poynten AM, Gan SK, Kriketos AD, Campbell LV, Chisholm DJ. Circulating fatty acids, non-high density lipoprotein cholesterol, and insulin-infused fat oxidation acutely influence whole body insulin sensitivity in nondiabetic men. J Clin Endocrinol Metab. 2005;90(2):1035–1040. doi: 10.1210/jc.2004-0943.
    1. Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab. 2004;89(2):463–478. doi: 10.1210/jc.2003-030723.
    1. Pilz S, Scharnagl H, Tiran B, Seelhorst U, Wellnitz B, Boehm BO, et al. Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease. J Clin Endocrinol Metab. 2006;91(7):2542–2547. doi: 10.1210/jc.2006-0195.
    1. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction. Eur J Clin Investig. 2002;32(Suppl 3):14–23. doi: 10.1046/j.1365-2362.32.s3.3.x.
    1. Frayn KN. Non-esterified fatty acid metabolism and postprandial lipaemia. Atherosclerosis. 1998;141(Suppl 1):S41–S46. doi: 10.1016/S0021-9150(98)00216-0.
    1. Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective Diabetes study (UKPDS: 23) BMJ. 1998;316(7134):823–828. doi: 10.1136/bmj.316.7134.823.
    1. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298(3):299–308. doi: 10.1001/jama.298.3.299.
    1. American Diabetes A 4. Lifestyle management: standards of medical Care in Diabetes−2018. Diabetes Care. 2018;41(Suppl 1):S38–S50. doi: 10.2337/dc18-S004.
    1. American Diabetes A 7. Approaches to glycemic treatment. Diabetes Care. 2016;39(Suppl 1):S52–S59.
    1. Strohacker K, McCaffery JM, MacLean PS, Wing RR. Adaptations of leptin, ghrelin or insulin during weight loss as predictors of weight regain: a review of current literature. Int J Obes. 2014;38(3):388–396. doi: 10.1038/ijo.2013.118.
    1. Evert AB, Boucher JL, Cypress M, Dunbar SA, Franz MJ, Mayer-Davis EJ, et al. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care. 2014;37(Suppl 1):S120–S143. doi: 10.2337/dc14-S120.
    1. Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, et al. Management of Hyperglycemia in type 2 Diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018.
    1. Mann JI, De Leeuw I, Hermansen K, Karamanos B, Karlstrom B, Katsilambros N, et al. Evidence-based nutritional approaches to the treatment and prevention of diabetes mellitus. Nutr Metab Cardiovasc Dis. 2004;14(6):373–394. doi: 10.1016/S0939-4753(04)80028-0.
    1. Samkani A, Skytte MJ, Kandel D, Kjaer S, Astrup A, Deacon CF, et al. A carbohydrate-reduced high-protein diet acutely decreases postprandial and diurnal glucose excursions in type 2 diabetes patients. Br J Nutr. 2018;119(8):910–917. doi: 10.1017/S0007114518000521.
    1. American Diabetes A. (2) classification and diagnosis of diabetes. Diabetes Care 2015;38 Suppl:S8-S16.
    1. Rogiers V. Stability of the long chain non-esterified fatty acid pattern in plasma and blood during different storage conditions. Clin Chim Acta. 1978;84(1–2):49–54. doi: 10.1016/0009-8981(78)90475-8.
    1. Krebs M, Stingl H, Nowotny P, Weghuber D, Bischof M, Waldhausl W, et al. Prevention of in vitro lipolysis by tetrahydrolipstatin. Clin Chem. 2000;46(7):950–954.
    1. Boden G. Obesity and free fatty acids. Endocrinol Metab Clin N Am. 2008;37(3):635–646. doi: 10.1016/j.ecl.2008.06.007.
    1. Paolisso G, Tataranni PA, Foley JE, Bogardus C, Howard BV, Ravussin E. A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia. 1995;38(10):1213–1217. doi: 10.1007/BF00422371.
    1. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. J Clin Invest. 2004;113(11):1582–1588. doi: 10.1172/JCI21047.
    1. Ruge T, Hodson L, Cheeseman J, Dennis AL, Fielding BA, Humphreys SM, et al. Fasted to fed trafficking of fatty acids in human adipose tissue reveals a novel regulatory step for enhanced fat storage. J Clin Endocrinol Metab. 2009;94(5):1781–1788. doi: 10.1210/jc.2008-2090.
    1. Taggart P, Carruthers M. Endogenous hyperlipidaemia induced by emotional stress of racing driving. Lancet. 1971;1(7695):363–366. doi: 10.1016/S0140-6736(71)92207-0.
    1. Djurhuus CB, Gravholt CH, Nielsen S, Mengel A, Christiansen JS, Schmitz OE, et al. Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans. Am J Physiol Endocrinol Metab. 2002;283(1):E172–E177. doi: 10.1152/ajpendo.00544.2001.
    1. Boden G, Chen X, Desantis RA, Kendrick Z. Effects of insulin on fatty acid reesterification in healthy subjects. Diabetes. 1993;42(11):1588–1593. doi: 10.2337/diab.42.11.1588.
    1. Campbell PJ, Carlson MG, Hill JO, Nurjhan N. Regulation of free fatty acid metabolism by insulin in humans: role of lipolysis and reesterification. Am J Phys. 1992;263(6 Pt 1):E1063–E1069.
    1. Sadur CN, Eckel RH. Insulin stimulation of adipose tissue lipoprotein lipase. Use of the euglycemic clamp technique. J Clin Invest. 1982;69(5):1119–1125. doi: 10.1172/JCI110547.
    1. Evans K, Burdge GC, Wootton SA, Clark ML, Frayn KN. Regulation of dietary fatty acid entrapment in subcutaneous adipose tissue and skeletal muscle. Diabetes. 2002;51(9):2684–2690. doi: 10.2337/diabetes.51.9.2684.
    1. Pollare T, Vessby B, Lithell H. Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. Arterioscler Thromb. 1991;11(5):1192–1203. doi: 10.1161/01.ATV.11.5.1192.
    1. Miles JM, Nelson RH. Contribution of triglyceride-rich lipoproteins to plasma free fatty acids. Horm Metab Res. 2007;39(10):726–729. doi: 10.1055/s-2007-990273.
    1. Samkani A, Skytte MJ, Thomsen MN, Astrup A, Deacon CF, Holst JJ, et al. Acute effects of dietary carbohydrate restriction on Glycemia, Lipemia and appetite regulating hormones in Normal-weight to obese subjects. Nutrients. 2018;10(9).
    1. Belfort R, Mandarino L, Kashyap S, Wirfel K, Pratipanawatr T, Berria R, et al. Dose-response effect of elevated plasma free fatty acid on insulin signaling. Diabetes. 2005;54(6):1640–1648. doi: 10.2337/diabetes.54.6.1640.
    1. Hue L, Taegtmeyer H. The Randle cycle revisited: a new head for an old hat. Am J Physiol Endocrinol Metab. 2009;297(3):E578–E591. doi: 10.1152/ajpendo.00093.2009.
    1. Frayn KN. The glucose-fatty acid cycle: a physiological perspective. Biochem Soc Trans. 2003;31(Pt 6):1115–1119.
    1. Chen YD, Coulston AM, Zhou MY, Hollenbeck CB, Reaven GM. Why do low-fat high-carbohydrate diets accentuate postprandial lipemia in patients with NIDDM? Diabetes Care. 1995;18(1):10–16. doi: 10.2337/diacare.18.1.10.
    1. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005;115(5):1343–1351. doi: 10.1172/JCI23621.
    1. Wilson DE, Chan IF, Buchi KN, Horton SC. Postchallenge plasma lipoprotein retinoids: chylomicron remnants in endogenous hypertriglyceridemia. Metabolism. 1985;34(6):551–558. doi: 10.1016/0026-0495(85)90193-3.
    1. Jeppesen J, Chen YI, Zhou MY, Schaaf P, Coulston A, Reaven GM. Postprandial triglyceride and retinyl ester responses to oral fat: effects of fructose. Am J Clin Nutr. 1995;61(4):787–791. doi: 10.1093/ajcn/61.4.787.
    1. Huntriss R, Campbell M, Bedwell C. The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Eur J Clin Nutr. 2018;72(3):311–325. doi: 10.1038/s41430-017-0019-4.
    1. Widjaja A, Morris RJ, Levy JC, Frayn KN, Manley SE, Turner RC. Within- and between-subject variation in commonly measured anthropometric and biochemical variables. Clin Chem. 1999;45(4):561–566.
    1. Magkos F, Patterson BW, Mittendorfer B. Reproducibility of stable isotope-labeled tracer measures of VLDL-triglyceride and VLDL-apolipoprotein B-100 kinetics. J Lipid Res. 2007;48(5):1204–1211. doi: 10.1194/jlr.D600048-JLR200.
    1. Hodson L, Harnden KE, Roberts R, Dennis AL, Frayn KN. Does the DASH diet lower blood pressure by altering peripheral vascular function? J Hum Hypertens. 2010;24(5):312–319. doi: 10.1038/jhh.2009.65.

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