The Role of Vegan Diets in Lipotoxicity-Induced Beta-Cell Dysfunction in Type-2-Diabetes

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Maximilian Andreas Storz


Vegan, Diet, Fat, Saturated, Polyunsaturated, Weight, Obesity, Beta Cell, Lipotoxicity, Lipoapoptosis, Type-2-Diabetes


Type-2-diabetes is considered the new plague of the current century and both, its incidence and prevalence are rapidly increasing. Chronic insulin resistance and a progressive decline in beta-cell function are discussed as the root causes of type-2-diabetes. Both were associated with obesity and pathologically elevated concentrations of circulating free fatty acids in the blood.

The harmful effects of chronically elevated free fatty acid levels on glucose homeostasis and non-adipose tissues are referred to as lipotoxicity. Pancreatic beta-cells appear to be particularly vulnerable and both, dietary fat quantity and quality may impact beta-cell function.

Diets high in saturated fats are especially harmful to beta-cells while (poly-)unsaturated fatty acids were associated with beta-cell protective effects. This review examined how a dietary modification towards a low-fat vegan diet, which is particularly low in saturated and trans-fats, could help to prevent or reduce lipotoxicity-induced beta cell dysfunction.

Several potential mechanisms of action were identified including: (1) reduced total fat intake (fat quantity), (2) a more favorable polyunsaturated fatty acid to saturated fatty acid ratio (fat quality), (3) improved body weight and a reduction in adipose tissue mass, and finally (4) improved glycemic control. The latter appears of paramount importance in light of the accumulating evidence that lipotoxic events are tightly coupled to excess glucose levels.

All four mechanisms are likely to contribute complementarily to improved beta-cell function in individuals with type-2-diabetes and may reduce the likelihood of lipotoxic events to occur. Physicians must consider these findings when counseling patients on lifestyle and nutrition.

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1. Uusitupa M, Khan TA, Viguiliouk E, et al. Prevention of type 2 diabetes by lifestyle changes: A systematic review and meta-analysis. Nutrients. 2019 Nov;11(11):2611.
2. Zimmet PZ. Diabetes and its drivers: The largest epidemic in human history? Clin Diabetes Endocrinol. 2017 Jan 18;3(1):1. 1186/s40842-016-0039-3
3. Cederberg H, Stan?áková A, Kuusisto J, et al. Family history of type 2 diabetes increases the risk of both obesity and its complications: Is type 2 diabetes a disease of inappropriate lipid stor-age? J Intern Med. 2015;277(5):540–51. https://doi. org/10.1111/joim.12289
4. Kojta I, Chaci?ska M, B?achnio-Zabielska A. Obesity, bioactive lipids, and adipose tissue inflammation in insulin resistance. Nutrients [Internet]. 2020 May 3 [cited 2020 Jun 27];12(5). Available from: PMC7284998/
5. Standl E, Khunti K, Hansen TB, Schnell O. The global epidemics of diabetes in the 21st century: Current situation and perspectives. Eur J Prev Cardiolog. 2019 Dec 1;26(2_suppl):7–14. https://
6. Oh YS, Bae GD, Baek DJ, et al. Fatty acid-induced lipotoxicity in pancreatic beta-cells during development of type 2 diabetes. Front Endocrinol [Internet]. 2018 [cited 2020 Jun 27];9. Available from: fendo.2018.00384/full
7. Chen C, Cohrs CM, Stertmann J, et al. Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis. Mol Metab. 2017 Jul 8;6(9):943–57. molmet.2017.06.019
8. Taylor R. Pathogenesis of type 2 diabetes: Tracing the reverse route from cure to cause. Diabetologia. 2008 Oct;51(10):1781–9. s00125-008-1116-7
9. Lytrivi M, Castell A-L, Poitout V, Cnop M. Recent insights into mechanisms of ?-cell lipo- and glucolipotoxicity in type 2 diabetes. J Mol Biol. 2020 Mar 6;432(5):1514–34. jmb.2019.09.016
10. Wende AR, Symons JD, Abel ED. Mechanisms of lipotoxicity in the cardiovascular system. Curr Hypertens Rep. 2012 Dec;14(6):517–31. https://doi. org/10.1007/s11906-012-0307-2
11. Estadella D, da Penha Oller do Nascimento CM, et al. Lipotoxicity: Effects of dietary saturated and transfatty acids. Mediators Inflamm [Internet]. 2013 [cited 2020 Jun 27];2013. Available from: PMC3572653/
12. Ye R, Onodera T, Scherer PE. Lipotoxicity and ? cell maintenance in obesity and type 2 diabetes. J Endocr Soc. 2019 Feb 4;3(3):617–31. https://doi. org/10.1210/js.2018-00372
13. Cunha DA, Igoillo-Esteve M, Gurzov EN, et al. Death protein 5 and p53-upregulated modulator of apoptosis mediate the endoplasmic reticulum stress–mitochondrial dialog triggering lipotoxic rodent and human ?-cell apoptosis. Diabetes. 2012 Nov;61(11):2763–75. js.2018-00372
14. Acosta-Montaño P, García-González V. Effects of dietary fatty acids in pancreatic beta cell metabolism, implications in homeostasis. Nutrients. 2018 Apr;10(4):393. https://doi. org/10.3390/nu10040393
15. Acosta-Montaño P, Rodríguez-Velázquez E, Ibarra-López E, et al. Fatty acid and lipopolysaccharide effect on beta cells proteostasis and its impact on insulin secretion. Cells. 2019 Aug;8(8):884. https://
16. Hagman DK, Hays LB, Parazzoli SD, Poitout V. Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans. J Biol Chem. 2005 Sep 16;280(37):32413–18.
17. Paul R, Choudhury A, Choudhury S, et al. Cholesterol in pancreatic ?-cell death and dysfunction: Underlying mechanisms and pathologi-cal implications. Pancreas. 2016 Mar;45(3):317–24.
18. Carrasco-Pozo C, Tan KN, Reyes-Farias M, et al. The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic ?-cells, glycemic control and inflammation: In vitro and in vivo studies. Redox Biol. 2016;9:229–43. 2016.08.007
19. Cnop M, Hannaert JC, Grupping AY, et al. Low density lipoprotein can cause death of islet beta-cells by its cellular uptake and oxidative modification. Endocrinology. 2002 Sep;143(9):3449–53.
20. Baynes HW, Mideksa S, Ambachew S. The role of polyunsaturated fatty acids (n-3 PUFAs) on the pancreatic ?-cells and insulin action. Adipocyte. 2018 Apr 3;7(2):81–7. 945.2018.1443662
21. Wang X, Chan CB. n-3 polyunsaturated fatty acids and insulin secretion. J Endocrinol. 2015 Mar 1;224(3):R97–106. JOE-14-0581
22. Muramatsu T, Yatsuya H, Toyoshima H, et al. Higher dietary intake of alpha-linolenic acid is associated with lower insulin resistance in middle-aged Japanese. Prev Med. 2010 Jun;50(5–6):272–6.
23. Westhoek H, Lesschen JP, Rood T, et al. Food choices, health and environment: Effects of cutting Europe’s meat and dairy intake. Global Environ Chang. 2014 May 1;26:196–205. https://doi. org/10.1016/j.gloenvcha.2014.02.004
24. Muralidharan J, Galiè S, Hernández-Alonso P, et al. Plant-based fat, dietary patterns rich in vegetable fat and gut microbiota modulation. Front Nutr [Internet]. 2019 Oct 11 [cited 2020 Jul 3];6. Available from: pmc/articles/PMC6797948/
25. Wanders AJ, Blom WAM, Zock PL, et al. Plant-derived polyunsaturated fatty acids and markers of glucose metabolism and insulin resistance: A meta-analysis of randomized controlled feeding trials. BMJ Open Diabetes Res Care [Internet]. 2019 Feb 8 [cited 2020 Jul 3];7(1). Available from: PMC6398820/
26. New Zealand Nutrition Foundation. Dietary Fats and Oils White Paper. 2015. Available from: files/150302%20Dietary%20Fats%20and%20 Oils%20White%20Paper.pdf (accessed on: September 23, 2020).
27. Sivakumaran S, Martell S, Huffman L. The concise New Zealand food composition tables. 9th ed., Palmerston North, New Zealand: The New Zealand Institute for Plant & Food Research Limited and Ministry of Health; 2012. Available from:
28. Craig WJ. Health effects of vegan diets. Am J Clin Nutr. 2009 May;89(5):1627S–1633S. https://doi. org/10.3945/ajcn.2009.26736N
29. Le LT, Sabaté J. Beyond meatless, the health effects of vegan diets: Findings from the Adventist cohorts. Nutrients. 2014 May 27;6(6):2131–47.
30. Storz MA. Will the plant-based movement rede-fine physicians’ understanding of chronic disease? New Bioeth. 2020 Apr 2;26(2):141–57. https://doi. org/10.1080/20502877.2020.1767921
31. Medawar E, Huhn S, Villringer A, Veronica Witte A. The effects of plant-based diets on the body and the brain: A systematic review. Transl Psychiatry. 2019 Sep 12;9(1):1–17. https://doi. org/10.1038/s41398-019-0552-0
32. Saunders AV, Davis BC, Garg ML. Omega-3 polyunsaturated fatty acids and vegetarian diets. Med J Aust. 2013 19;199(S4):S22–26. https://doi. org/10.5694/mja11.11507
33. Clarys P, Deliens T, Huybrechts I, et al. Comparison of nutritional quality of the vegan, vegetarian, semi-vegetarian, pesco-vegetarian and omnivorous diet. Nutrients. 2014 Mar 24;6(3):1318–32.
34. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-analyses: The PRISMA Statement. PLoS Med 6(7):e1000097. For more information, visit: www.prisma-statement. org
35. Nicholson AS, Sklar M, Barnard ND, et al. Toward improved management of NIDDM: A randomized, controlled, pilot intervention using a low fat, vegetarian diet. Prev Med. 1999 Aug;29(2):87–91.
36. Barnard ND, Cohen J, Jenkins DJ, et al. A low-fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: a randomized, con-trolled, 74-wk clinical trial. Am J Clin Nutr. 2009 May;89(5):1588S–1596S. ajcn.2009.26736H
37. Bunner AE, Wells CL, Gonzales J, et al. A dietary intervention for chronic diabetic neuropathy pain: A randomized controlled pilot study.
Nutr Diabetes. 2015 May 26;5:e158. https://doi. org/10.1038/nutd.2015.8
38. Lee Y-M, Kim S-A, Lee I-K, et al. Effect of a brown rice based vegan diet and conventional diabetic diet on glycemic control of patients with type 2 diabetes: A 12-week randomized clinical trial. PLoS ONE. 2016;11(6):e0155918. https://doi. org/10.1371/journal.pone.0155918
39. Ramal E, Champlin A, Bahjri K. Impact of a plant-based diet and support on mitigating type 2 diabetes mellitus in Latinos living in medically underserved areas. Am J Health Promot. 2018;32(3):753–62.
40. Barnard ND, Levin SM, Gloede L, Flores R. Turning the waiting room into a classroom: Weekly classes using a vegan or a portion-con-trolled eating plan improve diabetes control in a randomized translational study. J Acad Nutr Diet. 2018 Jun 1;118(6):1072–9. jand.2017.11.017
41. Ferdowsian HR, Barnard ND, Hoover VJ, et al. A multicomponent intervention reduces body weight and cardiovascular risk at a GEICO corporate site. Am J Health Promot. 2010 Aug;24(6):384–7.
42. Mishra S, Xu J, Agarwal U, et al. A multicenter randomized controlled trial of a plant-based nutrition program to reduce body weight and cardio-vascular risk in the corporate setting: The GEICO study. Eur J Clin Nutr. 2013 Jul;67(7):718–24.
43. Kim M-S, Hwang S-S, Park E-J, Bae J-W. Strict vegetarian diet improves the risk factors associated with metabolic diseases by modulating gut microbiota and reducing intestinal inflammation. Environ Microbiol Rep. 2013 Oct;5(5):765–75.
44. Campbell EK, Fidahusain M, Campbell Ii TM. Evaluation of an eight-week whole-food plant-based lifestyle modification program. Nutrients. 2019 Sep 3;11(9):2068. nu11092068
45. Shah B, Newman JD, Woolf K, et al. Anti-inflammatory effects of a vegan diet versus the American heart association-recommended diet in coronary artery disease trial. J Am Heart Assoc. 2018 Apr;7(23):e011367. JAHA.118.011367
46. Wright N, Wilson L, Smith M, et al. The BROAD study: A randomised controlled trial using a whole food plant-based diet in the community for obesity, ischaemic heart disease or diabetes. Nutr Diabetes. 2017 20;7(3):e256.
47. Qaseem A, Wilt TJ, Kansagara D, et al. Hemoglobin A1c targets for glycemic control with pharmacologic therapy for nonpregnant adults with type 2 diabetes mellitus: A guidance statement update from the American college of physicians. Ann Internal Med. 2018 Mar 6;168(8):569–76. https://
48. Chehregosha H, Khamseh ME, Malek M, et al. A view beyond HbA1c: Role of continuous glucose monitoring. Diabetes Ther. 2019 Jun 1;10(3):853– 63.
49. Poitout V, Amyot J, Semache M, et al. Glucolipotoxicity of the pancreatic beta cell. Biochimica et Biophysica Acta (BBA) –Molecular and Cell Biology of Lipids. 2010 Mar 1;1801(3): 289–98.
50. Ferdowsian HR, Barnard ND. Effects of plant-based diets on plasma lipids. Am J Cardiol. 2009 Oct 1; 104(7):947–56. 2009.05.032
51. Yokoyama Y, Levin SM, Barnard ND. Association between plant-based diets and plasma lipids: A systematic review and meta-analysis. Nutr Rev. 2017 Sep 1;75(9):683–98.
52. Palomer X, Pizarro-Delgado J, Barroso E, Vázquez-Carrera M. Palmitic and oleic acid: The Yin and Yang of fatty acids in type 2 diabetes mellitus. Trends Endocrinol Metab. 2018;29(3):178– 90.
53. Kahleova H, Hlozkova A, Fleeman R, et al. Fat quantity and quality, as part of a low-fat, vegan diet, are associated with changes in body compo-sition, insulin resistance, and insulin secretion. A 16-week randomized controlled trial. Nutrients. 2019 Mar 13;11(3):615. nu11030615
54. Kahleova H, Matoulek M, Malinska, H et al. Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes. Diabet Med. 2011;28(5):549–59. j.1464-5491.2010.03209.x
55. Kristensen NB, Madsen ML, Hansen TH, et al. Intake of macro- and micronutrients in Danish vegans. Nutrition J. 2015 Oct 30;14(1):115. https://
56. Vessby B, Uusitupa M, Hermansen K, et al. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. Diabetologia. 2001 Mar;44(3):312–19. s001250051620
57. Page KA, Reisman T. Interventions to pre-serve beta-cell function in the management and prevention of type 2 diabetes. Curr Diab Rep. 2013 Apr;13(2):252–60. s11892-013-0363-2
58. Mazza AD, Pratley RE, Smith SR. Beta-cell preservation…Is weight loss the answer? Rev Diabet Stud. 2011;8(4):446–53. RDS.2011.8.446
59. Arner P, Rydén M. Fatty acids, obesity and insulin resistance. OFA. 2015;8(2):147–55. https://doi. org/10.1159/000381224
60. Boden G. Obesity and free fatty acids. Endocrinol Metab Clin North Am. 2008;37(3):635-ix. https://
61. Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev. 2002 Apr;23(2):201–29. https://
62. Barnard N, Kahleova H, Levin S. The use of plant-based diets for obesity treatment. IJDRP. 2019;1(1):12 pp. Retrieved from index.php/ijdrp/article/view/11
63. Gupta S, Hawk T, Aggarwal A, Drewnowski A. Characterizing ultra-processed foods by energy density, nutrient density, and cost. Front Nutr [Internet]. 2019 May 28 [cited 2020 Jul 4];6. Available from: pmc/articles/PMC6558394/
64. Hall KD, Ayuketah A, Brychta R et al. Ultra-processed diets cause excess calorie intake and weight gain: An inpatient randomized controlled trial of ad libitum food intake. Cell Metab. 2019 Feb; 30(1):67–77.e3. 05.008
65. Berkow SE, Barnard N. Vegetarian diets and weight status. Nutr Rev. 2006 Apr;64(4):175–88.
66. Jakše B, Pinter S, Jakše B, et al. Effects of an ad libitum consumed low-fat plant-based diet supplemented with plant-based meal replacements on body composition indices [Internet]. Vol. 2017. Hindawi: BioMed Research International; 2017 [cited 2020 Jul 6]. p. e9626390. Available from: https://www.
67. Barnard ND, Levin SM, Yokoyama Y. A system-atic review and meta-analysis of changes in body weight in clinical trials of vegetarian diets. J Acad Nutr Diet. 2015 Jun;115(6):954–69. https://doi. org/10.1016/j.jand.2014.11.016
68. Kahleova H, Fleeman R, Hlozkova A, et al. A plant-based diet in overweight individuals in a 16-week randomized clinical trial: Metabolic benefits of plant protein. Nutr Diabetes. 2018 Feb;8(1):58.
69. Turner-McGrievy GM, Davidson CR, Wingard EE, et al. Comparative effectiveness of plant-based diets for weight loss: A randomized controlled trial of five different diets. Nutrition. 2015 Feb 1;31(2): 350–8.
70. Najjar RS, Feresin RG. Plant-based diets in the reduction of body fat: Physiological effects and bio-chemical insights. Nutrients [Internet]. 2019 Nov 8 [cited 2020 Jul 6];11(11). Available from: https://
71. Dubé JJ, Amati F, Toledo FGS, Stefanovic-Racic M, et al. Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglyc-erol, diacylglycerol and ceramide. Diabetologia. 2011 May 1;54(5):1147–56. s00125-011-2065-0
72. Li Y, Xu S, Zhang X, Yi Z, Cichello S. Skeletal intramyocellular lipid metabolism and insulin resistance. Biophys Rep. 2015;1:90–8. https://doi. org/10.1007/s41048-015-0013-0
73. Muoio DM. Revisiting the connection between intramyocellular lipids and insulin resistance: a long and winding road. Diabetologia. 2012 Oct 1; 55(10):2551–4.
74. Michael N, Gupta V, Sadananthan SA, et al. Determinants of intramyocellular lipid accumulation in early childhood. Int J Obes. 2020 May;44(5):1141–51.
75. Barnard ND, Cohen J, Jenkins DJA, et al. A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes. Diabetes Care. 2006 Aug 1;29(8):1777–83. dc06-0606
76. Garbarino J, Sturley SL. Saturated with fat: New perspectives on lipotoxicity. Curr Opin Clin Nutr Metab Care. 2009 Mar;12(2):110–16. https://doi. org/10.1097/MCO.0b013e32832182ee
77. Prentki M, Corkey BE. Are the ?-cell signaling molecules malonyl-CoA and cystolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM? Diabetes. 1996 Mar 1;45(3):273–83.
78. Poitout V, Robertson RP. Glucolipotoxicity: Fuel excess and ?-cell dysfunction. Endocr Rev. 2008 May;29(3):351–66. er.2007-0023
79. Gartlehner G, Affengruber L, Titscher V, et al. Single-reviewer abstract screening missed 13 percent of relevant studies: A crowd-based, randomized controlled trial. J Clin Epidemiol. 2020 May 1;121:20–8. jclinepi.2020.01.005
80. Kahleova H, Tura A, Hill M, Holubkov R, Barnard ND. A plant-based dietary intervention improves beta-cell function and insulin resistance in over-weight adults: A 16-week randomized clinical trial. Nutrients. 2018 Feb 9;10(2):189. https:// PMID: 29425120; PMCID: PMC5852765.
81. Cersosimo E, Solis-Herrera C, Trautmann ME, et al. Assessment of pancreatic ?-cell function: Review of methods and clinical applications. Curr Diabetes Rev. 2014 Jan;10(1):2–42. 10.2174/1573399810666140214093600
82. Belongie KJ, Ferrannini E, Johnson K, et al. Identification of novel biomarkers to monitor ?-cell function and enable early detection of type 2 diabetes risk. PLoS One [Internet]. 2017 Aug 28 [cited 2020 Sep 3];12(8). Available from: https://www.