The Role of Dietary Sugars and Sweeteners in Metabolic Disorders and Diabetes

Living reference work entry
Part of the Reference Series in Phytochemistry book series (RSP)


Sugar consumption has dramatically increased worldwide. A growing body of evidence suggests that sugars might have various adverse health effects. High intake of sugars may be related with an increased risk of several disorders including dental caries, obesity, cardiovascular disease, diabetes, gout, fatty liver disease, some cancers, components of the metabolic syndrome, and hyperactivity. Added sugar in processed foods are used to sweeten, to increase the flavour, to change the freezing or melting point or to protection of food spoilage. It is better to consume sugars in natural foods, since these foods provide useful micronutrients. Nowadays, there are questions as to whether excessive consumption of sugars, especially processed foods, might be correlated with metabolic syndrome or diabetes. However, insufficient study design, variety in evaluating dietary intake, contradictory findings and several definitions of sugars have inhibited definitive conclusions regarding these associations. However, limiting added sugars and monitoring carbohydrate consumption are serious strategy for keeping healthy weights and achieve glycemic control. This chapter describe different types of sweeteners in foods and beverages, as well as their effects on diabetes and metabolic disease. In addition, this chapter describes underlying mechanisms of sweeteners on health outcomes and how various types of sweeteners may threaten health.


Sweeteners Non-nutritive sweeteners Sugar sweetened beverage High-fructose corn syrup Diabetes Metabolic syndrome 



Food and agriculture organization


Glycaemic index


Glycemic load


Glucagon-like peptide-1


Sodium-glucose transport proteins


High fructose corn syrup


Health professionals follow-up study


Inosine monophosphate




Nurses’ health study


Non-nutritive sweeteners


Natural sweeteners


Sugar-sweetened beverages


Taste receptors type 1


Xanthine oxidase


  1. 1.
    Cummings J, Stephen A (2007) Carbohydrate terminology and classification. Eur J Clin Nutr 61(Suppl 1):S5–S18CrossRefGoogle Scholar
  2. 2.
    Davies G, Williams S (2016) Carbohydrate-active enzymes: sequences, shapes, contortions and cells. Biochem Soc Trans 44(1):79–87CrossRefGoogle Scholar
  3. 3.
    Gil-Campos M, San Jose Gonzalez M, Diaz Martin J (2015) Use of sugars and sweeteners in children’s diets. Recommendations of the Nutrition Committee of the Spanish Paediatric Association. An Pediatr (Barc) 83(5):353e1–353e7CrossRefGoogle Scholar
  4. 4.
    Welsh J, Cunningham S (2011) The role of added sugars in pediatric obesity. Pediatr Clin North Am 58(6):1455–1466CrossRefGoogle Scholar
  5. 5.
    Lustig R, Schmidt L, Brindis C (2012) Public health: the toxic truth about sugar. Nature 482(7383):27–29CrossRefGoogle Scholar
  6. 6.
    Duffey K, Popkin B (2008) High-fructose corn syrup: is this what’s for dinner? Am J Clin Nutr 88(6):1722S–1732SCrossRefGoogle Scholar
  7. 7.
    Karalius V, Shoham D (2013) Dietary sugar and artificial sweetener intake and chronic kidney disease: a review. Adv Chronic Kidney Dis 20(2):157–164CrossRefGoogle Scholar
  8. 8.
    Malik V, Hu F (2012) Sweeteners and risk of obesity and type 2 diabetes: the role of sugar-sweetened beverages. Curr Diab Rep 12:195 [Epub ahead of print]CrossRefGoogle Scholar
  9. 9.
    Johnson R, Segal M, Sautin Y, Nakagawa T, Feig D, Kang D, Gersch MS, Benner S, Sánchez-Lozada LG (2007) Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr 86(4):899–906Google Scholar
  10. 10.
    van Baak M, Astrup A (2009) Consumption of sugars and body weight. Obes Rev 10(Suppl 1):9–23CrossRefGoogle Scholar
  11. 11.
    Burt B, Pai S (2001) Sugar consumption and caries risk: a systematic review. J Dent Educ 65(10):1017–1023Google Scholar
  12. 12.
    Gross L, Li L, Ford E, Liu S (2004) Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment. Am J Clin Nutr 79(5):774–779Google Scholar
  13. 13.
    Te Morenga L, Mallard S, Mann J (2013) Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. BMJ 346:e7492CrossRefGoogle Scholar
  14. 14.
    Coss-Bu J, Sunehag A, Haymond M (2009) Contribution of galactose and fructose to glucose homeostasis. Metabolism 58(8):1050–1058CrossRefGoogle Scholar
  15. 15.
    American Dietetic Association (2004) Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners. J Am Diet Assoc 104(2):255–275CrossRefGoogle Scholar
  16. 16.
    Mace O, Affleck J, Patel N, Kellett G (2007) Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2. J Physiol 582(Pt 1):379–392CrossRefGoogle Scholar
  17. 17.
    Margolskee R, Dyer J, Kokrashvili Z, Salmon K, Ilegems E, Daly K, Maillet EL, Ninomiya Y, Mosinger B, Shirazi-Beechey SP (2007) T1R3 and gustducin in gut sense sugars to regulate expression of Na + −glucose cotransporter 1. Proc Natl Acad Sci U S A 104(38):15075–15080CrossRefGoogle Scholar
  18. 18.
    Zheng Y, Sarr M (2013) Effect of the artificial sweetener, acesulfame potassium, a sweet taste receptor agonist, on glucose uptake in small intestinal cell lines. J Gastrointest Surg 17(1):153–158CrossRefGoogle Scholar
  19. 19.
    Araujo J, Martel F, Keating E (2014) Exposure to non-nutritive sweeteners during pregnancy and lactation: impact in programming of metabolic diseases in the progeny later in life. Reprod Toxicol 49:196–201CrossRefGoogle Scholar
  20. 20.
    Sylvetsky A, Welsh J, Brown R, Vos M (2012) Low-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr 96(3):640–646CrossRefGoogle Scholar
  21. 21.
    Shankar P, Ahuja S, Sriram K (2013) Non-nutritive sweeteners: review and update. Nutrition 29(11–12):1293–1299CrossRefGoogle Scholar
  22. 22.
    Gardner C, Wylie-Rosett J, Gidding S, Steffen L, Johnson R, Reader D, Lichtenstein AH (2012) Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 35(8):1798–1808CrossRefGoogle Scholar
  23. 23.
    Garcia-Almeida J, Casado Fdez G, Garcia Aleman J (2013) A current and global review of sweeteners. Regulatory aspects. Nutr Hosp 28(Suppl 4):17–31Google Scholar
  24. 24.
    Ferrer I, Thurman E (2010) Analysis of sucralose and other sweeteners in water and beverage samples by liquid chromatography/time-of-flight mass spectrometry. J Chromatogr A 1217(25):4127–4134CrossRefGoogle Scholar
  25. 25.
    Pepino M (2015) Metabolic effects of non-nutritive sweeteners. Physiol Behav 152(Pt B):450–455CrossRefGoogle Scholar
  26. 26.
    Swithers S (2015) Artificial sweeteners are not the answer to childhood obesity. Appetite 93:85–90CrossRefGoogle Scholar
  27. 27.
    Xu H, Staszewski L, Tang H, Adler E, Zoller M, Li X (2004) Different functional roles of T1R subunits in the heteromeric taste receptors. Proc Natl Acad Sci U S A 101(39):14258–14263CrossRefGoogle Scholar
  28. 28.
    Burke M, Small D (2015) Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism. Physiol Behav 152(Pt B):381–388CrossRefGoogle Scholar
  29. 29.
    Mattes R, Popkin B (2009) Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. Am J Clin Nutr 89(1):1–14CrossRefGoogle Scholar
  30. 30.
    Swithers S (2013) Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab 24(9):431–441CrossRefGoogle Scholar
  31. 31.
    Ludwig D, Peterson K, Gortmaker S (2001) Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Lancet 357(9255):505–508CrossRefGoogle Scholar
  32. 32.
    Schulze M, Manson J, Ludwig D, Colditz G, Stampfer M, Willett W, Hu FB (2004) Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. JAMA 292(8):927–934CrossRefGoogle Scholar
  33. 33.
    Fernstrom J (2015) Non-nutritive sweeteners and obesity. Annu Rev Food Sci Technol 6:119–136CrossRefGoogle Scholar
  34. 34.
    Fowler S, Williams K, Resendez R, Hunt K, Hazuda H, Stern M (2008) Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain. Obesity 16(8):1894–1900CrossRefGoogle Scholar
  35. 35.
    Renwick A, Molinary S (2010) Sweet-taste receptors, low-energy sweeteners, glucose absorption and insulin release. Br J Nutr 104(10):1415–1420CrossRefGoogle Scholar
  36. 36.
    Swithers S, Sample C, Davidson T (2013) Adverse effects of high-intensity sweeteners on energy intake and weight control in male and obesity-prone female rats. Behav Neurosci 127(2):262–274CrossRefGoogle Scholar
  37. 37.
    Swithers S, Laboy A, Clark K, Cooper S, Davidson T (2012) Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats. Behav Brain Res 233(1):1–14CrossRefGoogle Scholar
  38. 38.
    Mitsutomi K, Masaki T, Shimasaki T, Gotoh K, Chiba S, Kakuma T, Shibata H (2014) Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity. Metabolism 63(1):69–78CrossRefGoogle Scholar
  39. 39.
    Moran A, Al-Rammahi M, Zhang C, Bravo D, Calsamiglia S, Shirazi-Beechey S (2014) Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption. J Dairy Sci 97(8):4955–4972CrossRefGoogle Scholar
  40. 40.
    Sivertsen J, Rosenmeier J, Holst J, Vilsboll T (2012) The effect of glucagon-like peptide 1 on cardiovascular risk. Nat Rev Cardiol 9(4):209–222CrossRefGoogle Scholar
  41. 41.
    Abou-Donia M, El-Masry E, Abdel-Rahman A, McLendon R, Schiffman S (2008) Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A 71(21):1415–1429CrossRefGoogle Scholar
  42. 42.
    Larsen N, Vogensen F, van den Berg F, Nielsen D, Andreasen A, Pedersen B, Al-Soud WA, Sørensen SJ, Hansen LH, Jakobsen M (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5(2):e9085CrossRefGoogle Scholar
  43. 43.
    Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss C, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E (2014) Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514(7521):181–186Google Scholar
  44. 44.
    Chung S, Ha K, Lee H, Kim C, Joung H, Paik H, Song Y (2015) Soft drink consumption is positively associated with metabolic syndrome risk factors only in Korean women: data from the 2007–2011 Korea National Health and Nutrition Examination Survey. Metabolism 64(11):1477–1484CrossRefGoogle Scholar
  45. 45.
    Kumar G, Pan L, Park S, Lee-Kwan S, Onufrak S, Blanck H (2014) Sugar-sweetened beverage consumption among adults – 18 states, 2012. Morb Mortal Wkly Rep 63(32):686–690Google Scholar
  46. 46.
    Malik V, Popkin B, Bray G, Despres J, Willett W, Hu F (2010) Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Diabetes Care 33(11):2477–2483CrossRefGoogle Scholar
  47. 47.
    Malik V, Pan A, Willett W, Hu F (2013) Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis. Am J Clin Nutr 98(4):1084–1102CrossRefGoogle Scholar
  48. 48.
    Huang C, Huang J, Tian Y, Yang X, Gu D (2014) Sugar sweetened beverages consumption and risk of coronary heart disease: a meta-analysis of prospective studies. Atherosclerosis 234(1):11–16CrossRefGoogle Scholar
  49. 49.
    Hu F (2013) Resolved: there is sufficient scientific evidence that decreasing sugar-sweetened beverage consumption will reduce the prevalence of obesity and obesity-related diseases. Obes Rev 14(8):606–619CrossRefGoogle Scholar
  50. 50.
    Swithers S, Martin A, Davidson T (2010) High-intensity sweeteners and energy balance. Physiol Behav 100(1):55–62CrossRefGoogle Scholar
  51. 51.
    Miller P, Perez V (2014) Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. Am J Clin Nutr 100(3):765–777CrossRefGoogle Scholar
  52. 52.
    Malik A, Akram Y, Shetty S, Malik S, Yanchou Njike V (2014) Impact of sugar-sweetened beverages on blood pressure. Am J Cardiol 113(9):1574–1580CrossRefGoogle Scholar
  53. 53.
    Jayalath V, Sievenpiper J, de Souza R, Ha V, Mirrahimi A, Santaren I, Blanco Mejia S, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, Jenkins DJ (2014) Total fructose intake and risk of hypertension: a systematic review and meta-analysis of prospective cohorts. J Am Coll Nutr 33(4):328–339CrossRefGoogle Scholar
  54. 54.
    Nguyen S, Choi H, Lustig R, Hsu C (2009) Sugar-sweetened beverages, serum uric acid, and blood pressure in adolescents. J Pediatr 154(6):807–813CrossRefGoogle Scholar
  55. 55.
    Kim Y, Abris G, Sung M, Lee J (2012) Consumption of sugar-sweetened beverages and blood pressure in the United States: the national health and nutrition examination survey 2003–2006. Clin Nutr Res 1(1):85–93CrossRefGoogle Scholar
  56. 56.
    Brown I, Stamler J, Van Horn L, Robertson C, Chan Q, Dyer A, Huang CC, Rodriguez BL, Zhao L, Daviglus ML, Ueshima H, Elliott P (2011) Sugar-sweetened beverage, sugar intake of individuals, and their blood pressure: international study of macro/micronutrients and blood pressure. Hypertension 57(4):695–701CrossRefGoogle Scholar
  57. 57.
    Greenwood D, Threapleton D, Evans C, Cleghorn C, Nykjaer C, Woodhead C, Burley VJ (2014) Association between sugar-sweetened and artificially sweetened soft drinks and type 2 diabetes: systematic review and dose–response meta-analysis of prospective studies. Br J Nutr 112(5):725–734CrossRefGoogle Scholar
  58. 58.
    Rabie E, Heeba G, Abouzied M, Khalifa M (2015) Comparative effects of Aliskiren and Telmisartan in high fructose diet-induced metabolic syndrome in rats. Eur J Pharmacol 760:145–153CrossRefGoogle Scholar
  59. 59.
    Dhingra R, Sullivan L, Jacques P, Wang T, Fox C, Meigs J, D’Agostino RB, Gaziano JM, Vasan RS (2007) Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation 116(5):480–488CrossRefGoogle Scholar
  60. 60.
    Hu F, Malik V (2010) Sugar-sweetened beverages and risk of obesity and type 2 diabetes: epidemiologic evidence. Physiol Behav 100(1):47–54CrossRefGoogle Scholar
  61. 61.
    Chan T, Lin W, Huang H, Lee C, Wu P, Chiu Y, Huang CC, Tsai S, Lin CL, Lee CH (2014) Consumption of sugar-sweetened beverages is associated with components of the metabolic syndrome in adolescents. Nutrients 6(5):2088–2103CrossRefGoogle Scholar
  62. 62.
    Baik I, Lee M, Jun N, Lee J, Shin C (2013) A healthy dietary pattern consisting of a variety of food choices is inversely associated with the development of metabolic syndrome. Nutr Res Pract 7(3):233–241CrossRefGoogle Scholar
  63. 63.
    Stanhope K, Havel P (2010) Fructose consumption: recent results and their potential implications. Ann N Y Acad Sci 1190:15–24CrossRefGoogle Scholar
  64. 64.
    Dolan L, Potter S, Burdock G (2010) Evidence-based review on the effect of normal dietary consumption of fructose on development of hyperlipidemia and obesity in healthy, normal weight individuals. Crit Rev Food Sci Nutr 50(1):53–84CrossRefGoogle Scholar
  65. 65.
    Tappy L, Le K, Tran C, Paquot N (2010) Fructose and metabolic diseases: new findings, new questions. Nutrition 26(11–12):1044–1049CrossRefGoogle Scholar
  66. 66.
    Khitan Z, Kim D (2013) Fructose: a key factor in the development of metabolic syndrome and hypertension. J Nutr Metab 2013:682673CrossRefGoogle Scholar
  67. 67.
    Basciano H, Federico L, Adeli K (2005) Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond) 2(1):5CrossRefGoogle Scholar
  68. 68.
    Sayon-Orea C, Martinez-Gonzalez M, Gea A, Alonso A, Pimenta A, Bes-Rastrollo M (2015) Baseline consumption and changes in sugar-sweetened beverage consumption and the incidence of hypertension: the SUN project. Clin Nutr 34(6):1133–1140CrossRefGoogle Scholar
  69. 69.
    Dekker M, Su Q, Baker C, Rutledge A, Adeli K (2010) Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome. Am J Physiol Endocrinol Metab 299(5):E685–E694CrossRefGoogle Scholar
  70. 70.
    Johnson R, Nakagawa T, Sanchez-Lozada L, Shafiu M, Sundaram S, Le M, Ishimoto T, Sautin YY, Lanaspa MA (2013) Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes 62(10):3307–3315CrossRefGoogle Scholar
  71. 71.
    Reungjui S, Roncal CA, Mu W, Srinivas TR, Sirivongs D, Johnson RJ, Nakagawa T (2007) Thiazide diuretics exacerbate fructose-induced metabolic syndrome. J Am Soc Nephrol 18:2724–2731CrossRefGoogle Scholar
  72. 72.
    Johnson RJ, Perez-Pozo SE, Sautin YY, Manitius J, Sanchez-Lozada LG, Feig DI et al (2009) Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes. Endocr Rev 30(1):96–116CrossRefGoogle Scholar
  73. 73.
    Bray G (2012) Fructose and risk of cardiometabolic disease. Curr Atheroscler Rep 14(6):570–578CrossRefGoogle Scholar
  74. 74.
    Murphy S (2009) The state of the science on dietary sweeteners containing fructose: summary and issues to be resolved. J Nutr 139(6):1269S–1270SCrossRefGoogle Scholar

Authors and Affiliations

  1. 1.Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non Communicable DiseaseIsfahan University of Medical SciencesIsfahanIran

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