Advances in Food Technology and Nutritional Sciences

Open journal

ISSN 2377-8350

Intermittent Fasting: A Potential Effective Strategy for Preventing Obesity and Type II Diabetes Mellitus

Sam Walker, Angela M. Tacinelli, Hexirui Wu, Sarah Pendergraft, Karla Horsfall and Sami Dridi*

Sami Dridi, PhD
Center of Excellence for Poultry Science, University of Arkansas, 1260 W, Maple Street, Fayetteville AR 72701, USA; Tel. (479)-575-2583; Fax: (479)-575-7139; E-mail:


The prevalence of obesity among adults has increased significantly in the past few decades. In the US alone, one in three adults is classified as obese..1 Most commonly, obesity results from an imbalance of limited energy expenditure to compensate for excess energy intake. However, a number of factors have been identified as possible contributors towards the increasing obesity rates worldwide, therefore acting as a multifaceted problem to resolve.2 Obesity is considered a primary contributor towards the development of type 2 diabetes mellitus (T2DM).3 T2DM is characterized by the inability of pancreatic β-cells to produce a sufficient amount of insulin (insulin resistance) in response to necessary levels of glucose uptake. As a result of inhibited insulin secretion, glucose is not taken up into target tissues such as muscle and adipose tissue, leading to elevated blood glucose levels, or hyperglycemia.4,5 Hyperglycemia can subsequently lead to vascular damage and other adverse effects.6


Intermittent fasting (IF), a form of calorie restriction, has gained popularity in recent years as a methodology for combating obesity and development or progression of type 2 diabetes. IF regimes can vary in fasting durations. Common variations of IF include alternate day fasting (ADF), in which one day consists of a 75% energy restriction followed by a day of ad libitum food consumption or 16/8 IF, which includes consuming 100% of energy needs in an 8 hour time period followed by a 16 hour fast.7,8 Dysregulated insulin/glucose pathways, shown as glucose tolerance and insulin resistance, is the most frequently reported symptom of T2DM and has been discussed broadly in recent years. Studies

implementing IF have shown normal and overweight human subjects have efficacy for weight loss.9 In addition to being an effective method for weight loss, IF can also improve specific health indicators associated with chronic disease in the overweight and obese population, such as insulin resistance.10 Research on IF’s weight loss benefits is aimed at understanding its metabolic effects on many age-related diseases, including type 2 diabetes.10 However, limited research exists on assessing fasting glucose and insulin levels in patients undergoing IF.


Changes in fasting blood glucose levels have been observed in humans undergoing ADF.11,12 As much as a 6% decrease was observed between overweight patients’ fasting glucose levels after 8 to 12 weeks of an ADF versus an ad libitum diet.13 Adversely, a significant insulin reduction of approximately 20% was observed in intermittently fasted overweight and obese adults, respectively.14 Similar effects of decreased blood glucose and insulin levels resulting from IF have also been observed in human studies. This suggests effects of IF treatment on the insulin transduction pathway, as well as pathways involving cytokine-induced food intake behavior, may be responsible for improving glucose tolerance. A study involving New Zealand obese mice undergoing a calorierestricted IF diet showed improved blood insulin sensitivity in an oral glucose tolerance test, higher blood glucose clearance in insulin tolerance tests, and lower blood glucose and insulin compared to mice fed an ad libitum diet.15

Improvements in the insulin transduction pathway in response to IF may be a consequence of increased expression of sirtuins (SIRTs). SIRT1 is a protein complex involved in cellular energy sensing via the ratio of nicotinamide adenine dinucleotide (NAD+) and its reduced form nicotinamide adenine dinucleotide (NAD) + hydrogen (H) (NADH).16 The ratio between NAD+ and NADH represent overall oxidative phosphorylation capacity within the cell. Higher levels of NAD+ in response to fasting and exercise are shown to increase SIRT1 activity.17 Conversely, SIRT1 activity is reduced during periods of hyperinsulinemia.18 β-hydroxybutyrate (βOHB), a ketone body, is elevated during fasting.19 Downstream metabolism of βOHB for acetyl-CoA production requires less NAD+ consumption when compared to glucose, thus expression of SIRT1 perpetuates in parallel with the duration of the fast.In addition, βOHB and periods of intermittent fasting upregulate the expression of brain derived neurotrophic factor (BDNF).20,21 BDNF, a protein in the hypothalamus, is shown to decrease in response to T2D.22,23 Increased expression of BDNF is shown to have protective effects against the development and progression of T2D including: increased energy expenditure, decreased dietary intake, and decreased fasting blood glucose.24 Interestingly, BDNF administration is shown to reduce food intake and correct hyperglycemia in leptin receptor deficient db/db mice.25 Increased SIRT1 expression regulates energy expenditure through modulation of cellular respiration. Translation of mitochondrial biogenesis and lipid oxidation are both regulated by peroxisome proliferator-activated receptors (PPARs) and coactivator-1a (PGC-1a).26 Both of these proteins are downregulated in response to hyperinsulinemia and insulin resistance.27 Upregulating their expression through increased SIRT1 activity may serve as a novel approach in combating metabolic abnormalities observed in T2D such as intracellular fat depositions. (Figure 1)

Figure 1. Anti-diabetic Effects of Intermittent Fasting via SIRT1 Signaling



As IF elicits similar effects as calorie restriction, it is worthwhile to test if the expression of adipocyte-specific glucose transporter 4 (GLUT4) is increased as shown in obese mice undergoing calorie-restriction.28 It is believed that IF could induce the secretion of leptin in adipose tissue through up-regulating GLUT4 expression in T2D. The role of the GLUT4 transporter serves as a mediator for improved glucose disposal in response to altered nutrition status. GLUT4 transcription is shown to be tightly regulated in response to energy sensing within the cell. In response to prolonged exercise and calorie restriction, 5’ AMP activated protein kinase (AMPK) activity increases and promotes translocation of GLUT4 to the cell membrane surface. However, the potential of IF influencing this interaction has led to noncorrelative results in both human and animal studies.29

Contrastingly, in 2014, Dorighello et al. Reported that wild type mice under IF regimen developed symptoms of diabetes including elevated blood glucose and insulin levels, glucose intolerance, and insulin resistance while reduced food intake was observed. Mechanistic understanding the effects of IF can be beneficial towards attenuating or preventing the increasing prevalence of chronic diseases such as obesity and T2D. However, due to the contradicting evidence in current literature, further research is still needed for understanding the mechanisms of IF on various biomarker responses and appetite control.


The authors declare that they have no conflicts of interest.

1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA. 2010; 303(3): 235-241. doi: 10.1001/jama.2009.2014

2. Wright SM, Aronne LJ. Causes of obesity. Abdominal Imaging. 2012; 37(5): 730-732. doi: 10.1007/s00261-012-9862-x

3. Charles J, Pollack A, Britt H. Type 2 diabetes and obesity in young adults. Aust Fam Physician, 2015; 44(5): 269-270.

4. Whitmore C. Type 2 diabetes and obesity in adults. Br J Nurs. 2010; 19(4): 880-886. doi: 10.12968/bjon.2010.19.14.49041

5. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011; 11(2): 98-107. doi: 10.1038/nri2925

6. Giugliano D, Ceriello A, Esposito K. Glucose metabolism and hyperglycemia. Am J Clin Nutr. 2008; 87(1): 217S-222S. doi: 10.1093/ajcn/87.1.217S

7. Barnosky AR, Hoddy KK, Unterman TG, Varady KA. Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: A review of human findings. Transl Res. 2014; 164(4): 302-311. doi: 10.1016/j.trsl.2014.05.013

8. Moro T, Tinsley G, Bianco A, et al. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. Journal of Translational Medicine. 2016; 14(1). doi: 10.1186/s12967-016-1044-0

9. Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev. 2017; 39: 46-58. doi: 10.1016/j.arr.2016.10.005

10. Baumeier C, Kaiser D, Heeren J, et al. Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice. Biochim Biophys Acta, 2015; 1851(5): 566-576. doi: 10.1016/j.bbalip.2015.01.013

11. Eshghinia S, Mohammadzadeh F. The effects of modified alternate-day fasting diet on weight loss and CAD risk factors in overweight and obese women. J Diabetes Metab Disord. 2013; 12(1): 4. doi: 10.1186/2251-6581-12-4

12. Johnson JB, Summer W, Cutler RG, et al. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med. 2007; 42(5): 665-674. doi: 10.1016/j freeradbiomed.2006.12.005

13. Varady KA, Bhutani S, Church EC, Klempel MC. Short-term modified alternate-day fasting: A novel dietary strategy for weight loss and cardioprotection in obese adults. Am J Clin Nutr. 2009; 90(5): 1138-1143. doi: 10.3945/ajcn.2009.28380

14. Klempel, MC, Kroeger CM, Bhutani S, et al. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutr J. 2012; 11: 98. doi: 10.1186/1475-2891-11-98

15. Li X. SIRT1 and energy metabolism. Acta Biochim Biophys Sin (Shanghai). 2013; 45(1): 51-60. doi: 10.1093/abbs/gms108

16. Zhu Y, Yan Y, Gius DR, Vassilopoulos A. Metabolic regulation of Sirtuins upon fasting and the implication for cancer. Curr Opin Oncol. 2013; 25(6): 630-636. doi: 10.1097/01.cco.0000432527.49984. a3

17. Stefanowicz M, Nikołajuk A, Matulewicz N, Karczewskakupczewska M. Adipose tissue, but not skeletal muscle, sirtuin 1 expression is decreased in obesity and related to insulin sensitivity. Endocrine. 2018; 60(2): 263-271. doi: 10.1007/s12020-018-1544-1

18. Newman JC, Verdin E. β-hydroxybutyrate: Much more than a metabolite. Diabetes Res Clin Pract. 2014; 106(2): 173-181. doi: 10.1016/j.diabres.2014.08.009

19. Marosi K, Kim SW, Moehl K, et al. 3-Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons. J Neurochem. 2016; 139(5): 769-781. doi: 10.1111/ jnc.13868

20. Bastani A, Rajabi S, Kianimarkani F. The effects of fasting during ramadan on the concentration of serotonin, dopamine, brainderived neurotrophic factor and nerve growth factor. Neurol Int. 2017; 9(2): 7043. doi: 10.4081/ni.2017.7043

21. Fujinami A, Ohta K, Obayashi H, et al. Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance. Clin Biochem. 2008; 41(10-11): 812-817. doi: 10.1016/j. clinbiochem.2008.03.003

22. Araki S, Yamamoto Y, Dobashi K, et al. Decreased plasma levels of brain-derived neurotrophic factor and its relationship with obesity and birth weight in obese Japanese children. Obes Res Clin Pract. 2014; 8(1): e63-e69. doi: 10.1016/j.orcp.2012.07.003

23. Eyileten C, Kaplon-cieslicka A, Mirowska-Guzel D, et al. Antidiabetic effect of brain-derived neurotrophic factor and its association with Inflammation in Type 2 Diabetes Mellitus. J Diabetes Res. 2017; 2017: doi: 10.1155/2017/2823671

24. Rothman SM, Griffioen KJ, Wan R, Mattson MP. Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health. Ann N Y Acad Sci. 2012; 1264: 49-63. doi: 10.1111/j.1749-6632.2012.06525.x

25. Jornayvaz FR, Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem. 2010; 47: 69-84. doi: 10.1042/bse0470069

26. Hammarstedt A, Jansson PA, Wesslau C, et al. Reduced expression of PGC-1 and insulin-signaling molecules in adipose tissue is associated with insulin resistance. Biochem Biophys Res Commun. 2003; 301(2): 578-82. doi: 10.1016/S0006-291X(03)00014-

27. Park SK, Prolla TA. Lessons learned from gene expression profile studies of aging and caloric restriction. Ageing Res Rev. 2005; 4(1): 55-65. doi: 10.1016/j.arr.2004.09.003

28. Dohm GL. Invited review: Regulation of skeletal muscle GLUT-4 expression by exercise. J Appl Physiol. 2002; 93(2): 782-7. doi: 10.1152/japplphysiol.01266.2001

29. Dorighello GG, Rovani JC, Luhman CJ, et al. Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hyper cholesterolaemic mice. Br J Nutr. 2014; 111(6) :979-86. doi: 10.1017/ S0007114513003383


Practical Pointers for Drug Development and Medical Affairs

Gerald L. Klein*, Roger E. Morgan, Shabnam Vaezzadeh, Burak Pakkal and Pavle Vukojevic



Prevalence and Risk Factors of Subclinical Mastitis of Goats in Banadir Region, Somalia

Omar M. Salah*, Yasin H. Sh-Hassan, Moktar O. S. Mohamed, Mohamed A. Yusuf and Abas S. A. Jimale


Use of Black Soldier Fly (Hermetia illucens) Prepupae Reared on Organic Waste

Maggot Debridement Therapy: A Natural Solution for Wound Healing

Isayas A. Kebede*, Haben F. Gebremeskel and Gelan D. Dahesa,


The Impact of Family Dynamics on Palliative Care at the End-of-Life

Neil A. Nijhawan*, Rasha Mustafa and Aqeela Sheikh


Long-Term Follow-Up After Laparoscopic Radical Prostatectomy for Localized and Locally Advanced Prostate Cancer

Shrenik J. Shah*, Abhishek Jha, Chirag Davara, Rushi Mistry and Kapil Kachhadiya




Pie Chart Showing Overall Proportions of Diagnostic Category of FNAC, JUMC

Retrospective Study

2024 Apr

Abel Tefera*, Lemlem Terefe and Kitesa Biresa
Prevalence (%) of Types of Anthropometric Failure among Previous and Present Studied Tribal Children

Original Research, peer reviewed

2024 Apr

Biswajit Mahapatra and Kaushik Bose*


2024 Apr

Gerald L. Klein*, Roger E. Morgan, Shabnam Vaezzadeh, Burak Pakkal and Pavle Vukojevic