Available via license: CC BY 4.0
Content may be subject to copyright.
Journal of Advanced Zoology
ISSN: 0253-7214
Volume 44 Issue S-6 Year 2023 Page 1333:1340
________________________________________________________________________________________________________
- 1333 -
The Effect of Intermittent Fasting and Caloric Restricted Diet on Diabetic
Rats
Naeem M. Rabeh*, Omnia G. Refaat, Mayan T. Hamada
Naeem M. Rabeh, Omnia G. Refaat, Mayan T. Hamada
*Corresponding author’s: Naeem M. Rabeh
Article History
Received: 06 June 2023
Revised: 05 Sept 2023
Accepted: 30 Nov 2023
CC License
CC-BY-NC-SA 4.0
Abstract
The present study was aimed to investigate the effect of intermittent fasting and
caloric restricted diet (RD) for 8 weeks on diabetic rats. Forty-nine adult male
albino rats were divided into two main groups; the first main group was fed
only on basal diet and served as negative control group and the second main
group: diabetic rats were induced by a single intra-peritoneal injection of
freshly prepared STZ (60 mg/kg BW) then divided into 6 subgroups: Subgroup
(1) was fed only on basal diet and was served as positive cont. Subgroup (2)
was fed on RD only. Subgroups (3, 4) were fed on basal diet and were deprived
of food except water from 5 p.m. to 8 a.m. twice a week and every other day,
respectively. Subgroups (5, 6): were fed on RD and intermittent fasting twice a
week and every other day, respectively. The results indicated that RD and
intermittent fasting significantly decreased the final body weight, feed intake
and body weight gain % values as compared to the positive control rats.
Diabetic treated rats had significant increase (p<0.05) in insulin concentration
and lower glucose levels as well as an improvement in liver functions and lipid
profile as compared to the positive control group. Conclusion: the findings
suggest that intermittent fasting and caloric restricted diet could have a
potential role in managing diabetes
.
Keywords: Diabetes- Caloric restricted- Intermittent fasting- Glucose- Lipid
profile
1. Introduction
Diabetes mellitus is reported to impact more than 100 million individuals worldwide and is one of the
world's top five causes of death (Otovwe and Akpojubaro, 2020). Diabetes is a serious, long-term
condition with a major impact on the lives and well-being of individuals, families, and societies
worldwide (Saeedi et al., 2019). International Diabetes Federation (IDF) estimates that the global
prevalence of diabetes in people aged 20-79 years is estimated at 10.5% (536.6 million) in 2021, rising
to 12.2% (783.2 million) by 2045 (Sun et al., 2022)
However, current T2DM medications without lifestyle interventions lack comprehensiveness in
glycemic control (Siehler et al., 2021). In light of the limitations of available antidiabetic agents,
alternative treatments are highly recommended. In recent years, the dietary intervention has become a
hot topic of research .
Fasting is one type of calorie restriction and has been widely practiced as a type of medical application
or religious ritual. Fasting is defined as abstinence from or reduction of food, drink or both for a period
typically lasting between 12 h and 3 weeks, in short-term, long-term or intermittent patterns (Lessan
and Ali, 2019). Intermittent fasting is an umbrella term for various diets comprising a cycle of a period
of fasting and non-fasting (Harney et al., 2019). In fact, intermittent fasting has been practiced by the
Muslim population for over a thousand years in the month of Ramadan. This usually involves 12-16 h
of daily fasting by abstinence of both drink and food for one month (Ahmad and Chowdhury, 2019) .
Intermittent fasting (IF) is an approach that requires focusing only on fasting days to reduce energy
expenditure and is potentially more straightforward to implement than calorie restriction (Anastasiou
et al., 2015). It can be used as an alternative for obese individuals who have difficulty applying calorie-
restricted diets for a long time (Wegman et al., 2015) .
The Effect of Intermittent Fasting and Caloric Restricted Diet on Diabetic Rats
Available online at: https://jazindia.com - 1334 -
Intermittent fasting is a promising strategy among different approaches of fasting such as caloric
restriction (CR) and RD. It has proved to be the most fruitful approach for its ability to cope with
different diseases such as cancer, diabetes, antioxidant stress, ulcerative colitis, cardiovascular diseases,
renal diseases and hypertension (Mattson et al., 2017) .
Numerous types of intermittent fasting, including time-restricted feeding, intermittent energy
restriction, and Ramadan diurnal intermittent Ramadan fasting have recently gained considerable
attention (De Cabo and Mattson, 2019), as it reportedly provokes numerous physiological changes that
benefit human health. In the fasting period, cells enhance their innate defenses against oxidative and
metabolic stress by activating certain pathways (Mattson et al., 2017). Clifton et al., (2021) shown that
IF has a modulating function in a variety of chronic diseases, including obesity, diabetes, cardiovascular
disease, multiple sclerosis, neurodegenerative diseases of the brain, and cancer .
Intermittent fasting appears an equivalent alternative to CR to improve health. However, few trials have
considered applying meal timing during the ‘fasting’ day, which may be a limitation. Therefore, the
aim of this work was to investigate the possible effect of intermittent fasting and caloric restricted diet
on diabetic rats .
2. Materials And Methods
Diet: The present study was performed using standard (American Institute of Nutrition AIN- 93G
purified Rodent diet) and AIN-93G vitamin and minerals were purchased from El-Gomhoria Company,
Cairo, Egypt. Kits were purchased from Alkan Company for biodiagnostic Reagents, Dokki, Cairo,
Egypt. Forty-nine Adult male albino rats (Sprague- Dawly strain) weighing approximately (200 ±10 g.)
were purchased from Helwan Experimental Animals Farm were randomly housed in ventilated cage
under controlled conditions (temperature: 22 ± 2°C, humidity: 55 ± 5%)
Study design
:
Diabetic rats were induced by a single intra-peritoneal injection of freshly prepared STZ (60 mg/kg
BW). Three days later, the level of the blood glucose was assessed and the level ≥250 mg/dl was
considered as diabetes (Sarkar, et al., 1996). The experimental animals were fed on basal diet according
to (Reeves et al., 1993) and were subjected to 40% caloric restriction via the basal diet
Caloric restriction Protocol
:
This study was carried out at the Postgraduate Lab of the faculty of Home Economic, Helwan
University. Forty-nine adult male Sprague-Dawley rats were fed on standard diet for one week for
adaptation. Rats were divided into two main groups; the first main group was fed only on basal and
served as negative control group and the second main group: diabetic rats were induced by a single
intra-peritoneal injection of freshly prepared STZ (60 mg/kg BW) then divided into 6 subgroups:
Subgroup (1) was fed only on basal diet and was served as positive control group. Subgroup (2) was
fed only on RD. Subgroups (3, 4) were fed on basal diet and were deprived of food except water from
5 p.m. to 8 a.m. twice a week and every other day, respectively. Subgroups (5, 6): were fed on RD and
intermittent fasting twice a week and every other day, respectively
At the end of the experimental period (8 weeks), rats were fasted over night before sacrificing, blood
samples were collected into a centrifuge tube without any anticoagulant and were centrifuged to obtain
serum which were stored at- 20°C until used for subsequent analysis. Body weight gain percentage
(BWG %) and feed intake (FI) and Feed efficiency ratio (EFR) were calculated according to (Chapman
et al., 1959)
Statistical Analysis: The obtained results were analyzed according to SPSS program Version 20
ANOVA test was used to compare results among groups and P<0.05 was considered to be significant
(Bancroft and Stevens, 1977)
3. Results and Discussion
Table (1): Effect of intermittent fasting and caloric restricted diet on body weight status of diabetic
rats
Groups
IBW (g)
FBW (G)
BWG%
FI
(g/d/rat)
FER
Control (-ve)
187.00±1.47a
243.75±2.25a
30.37±1.63a
22.50
0.042±0.021a
Control (+ve)
188.00±1.22a
207.75±3.03c
10.55±2.32c
24.00
0.014±0.029c
Restricted diet (RD)
192.75±1.18a
198.00±1.29d
2.72±0.49d
20.00
0.004±0.008d
RD+ 2 day fasting
187.00±2.91a
195.75±3.70d
4.66±0.38d
20.50
0.007±0.007d
RD + fasting day/ day
187.50±1.25a
192.00±1.47d
2.40±0.46d
21.10
0.004±0.006d
https://jazindia.comnline at: le obilaAva - 1335 -
Basal diet + 2 day
fasting
187.75±1.65a
216.50±1.84b
15.32±0.87b
21.70
0.022±0.012b
Basal diet + fasting
day / day
187.25±1.79a
215.50±1.32b
15.12±1.48b
23.70
0.020±0.018b
Data are expressed as mean ± SE
Values in each column which have different letters are significantly different at (p<0.05)
Table (1) display the body weight of all groups during the experimental periods. There were no
significant differences of the IBW among all rats. The diabetic rats (+ve) had the lowest (P<0.05) final
body weight, BWG% and FER while the feed intake was higher as compared to the other treated rats.
Intervention with caloric restricted diet with or without intermitting fasting significantly decreased the
FBW, BWG% and FER and feed intake as compared to the +ve control group. There were a significant
difference (P<0.05) in the FBW, BWG% and FER between the diabetic groups fed RD with intermitting
fasting as compared to the diabetic groups fed basal diet with intermitting fasting. There were a
significant difference between the groups fed RD with 2day fasting or fasting day/day, the same trend
was observed between the groups fed on basal diet. The most body weight improvement was observed
at the diabetic rats fed on basal diet with 2 days fasting. The FBW, BWG% and FER of all the treated
rats still significantly lowered than those of the -ve control group
Ramadan fasting studies have shown mixed effects on health. Some studies found reduction in body
weight (Kul et al., 2014) while others report minimal change (Sadeghirad et al., 2014). Similar
inconsistencies are reported for the lipid profile and blood glucose levels as well. One explanation could
be the confounding variables such as the fasting duration, medications, dietary habits, cultural norms
and physical activity (Trepanowski and Bloomer, 2010). Other factors may include methodological
differences, seasonal changes, geographical location, daylight exposures etc
IF (4–24 weeks) induces body weight reductions of 4% to 10% in overweight individuals (Catenacci et
al., 2016). The varying degree of body weight reduction depends on the dietary pattern, dietary duration,
diet composition, sex, and genetic response. Although some studies have shown greater body fat
reductions with IF than with CR (Alhamdan et al., 2016), the majority of these studies have shown
equivalent effects on reductions in body weight and fat mass following IF or CR in overweight or obese
individuals (Rynders et al., 2019)
Many studies have indicated that IF is an effective and acceptable intervention in obese subjects,
including obese adolescents (Jebeile et al., 2019 and Sundfør et al., 2018), in addition, regular IF
decreased fat-free mass more than CR (Roman et al., 2019). Recently, IF has appeared as an alternative
dietary intervention to CR because dieters feel that IF is a more tolerable method than CR (Duregon et
al., 2021)
Weight reduction may be associated with the shift from glucose to fatty acid metabolism resulting from
the fasting-induced elevation in fat mobilization and utilization (De Cabo et al., 2019). The reduction
in insulin, an anabolic hormone, by IF may also be responsible for the reduction in body fat mass
(Zubrzycki et al., 2018)
Table (2): Effect of intermittent fasting and caloric restricted diet on blood glucose and insulin
hormone of diabetic rats
Parameters
Groups
Glucose
(mg/dl)
Glucose reduction
(%)
Insulin
Insulin increment
(%)
Control (-ve)
75.91±1.18g
-
1.20±0.008a
-
Control (+ve)
232.20±1.30a
-
0.336±0.012f
-
Restricted diet (RD)
130.73±1.57d
43.69
0.620±0.017d
84.52
RD+ 2 day fasting
123.59±0.88e
46.77
0.736±0.016c
119.04
RD + fasting day/ day
115.75±0.90f
50.15
0.900±0.020b
167.85
Basal diet + 2 day fasting
143.90±1.32b
38.02
0.516±0.008e
53.57
Basal diet + fasting day /
day
136.10±1.00c
41.38
0.606±0.006d
80.35
Data are expressed as mean ± SE
Values in each column which have different letters are significantly different at (p<0.05)
Data at table (2) revealed that, serum glucose of untreated diabetic rats was significantly higher (p<0.05)
than the negative control rats. RD significantly decreased the glucose concentrations by (43.69%) when
compared to the +ve control group. Moreover, RD with different intermitting fasting (2 day fasting and
The Effect of Intermittent Fasting and Caloric Restricted Diet on Diabetic Rats
Available online at: https://jazindia.com - 1336 -
fasting day/day) lowered serum glucose as compared to the rats fed on RD only by 46.77 and 50.15%,
respectively. The fasting day/day model was more effective in lowering glucose than the 2-day fasting.
It was clear that, the rats fed on RD with or without different intermitting fasting model had lower
glucose concentration than the rats fed on basal diet with different intermitting fasting model. The
lowest glucose concentration among all the tested groups was observed at the rats fed on RD with
intermitting fasting day/day by
Regarding to insulin hormone, the amount of insulin secretion was significantly (P<0.05) decreased as
compared to the -ve control group. In addition, Intervention with RD improved the insulin concentration
by (84.52%) when compared to the +ve control rats. It was obviously that, intervention with RD with
different intermitting fasting significantly increased insulin levels as compared to the +ve group by
119.04 and 167.85, respectively. Moreover, diabetic rats fed on basal diet with different intermitting
fasting increased Insulin concentration by 53.57 and 80.35%. The highest insulin concentration was
observed at the group fed on RD with fasting day/day by
Intermittent fasting plus early time-restricted eating provided modest benefit for postprandial glycemia
in response to mixed-meal tolerance test compared with daily CR without timing advice in adults at
elevated risk of type 2 diabetes after 6 months. This study adds to the growing body of evidence to
indicate that meal timing and fasting advice might be influential in clinical practice (Teong et al., 2023)
IF, in any form, leads to significant weight loss and reduction in the whole body and visceral fat (Carter
et al., 2018) and both weight and visceral fat gain are associated with an increased risk of T2DM
(Neeland et al., 2012). Previous studies on people with T2DM have shown that IF can result in
comparable weight loss and glycated haemoglobin (HbA1c) reduction as traditional dietary
recommendations (Parvaresh et al., 2019)
Intermittent fasting diets have certain therapeutic effects on blood glucose and lipids in patients with
metabolic syndrome and significantly improve insulin resistance (Yuan, et al., 2022). Since IF
intervention, patients with T2DM have experienced improvements in glycemic parameters and partial
reductions in medication intake. IF could improve patient motivation and compliance and reduce
medication side effects. As no severe hypoglycemic events and other adverse events have been reported,
IF can be considered a relatively safe dietary intervention for T2DM patients (CHEN et al., 2023)
Table (3): Effect of intermittent fasting and caloric restricted diet of serum lipid profile of
diabetic rats Parameters
Parameters
Groups
Total
Cholesterol
Triglyceride
HDL-C
LDL-C
VLDL-C
(mg/dl)
Control (-ve)
119.13±1.71g
73.53±1.37g
62.46±0.93a
41.96±1.84g
14.70±0.27g
Control (+ve)
171.20±2.73a
134.60±1.49a
25.60±0.96e
118.68±3.34a
26.92±0.29a
Restricted diet (RD)
143.73±1.12d
116.33±1.48d
44.93±0.81c
75.53±1.33d
23.26±0.29d
RD+ 2 day fasting
128.76±0.67f
108.60±1.15e
47.60±0.92b
66.58±0.30e
21.72±0.23e
RD + fasting day/ day
135.90±0.80e
98.56±1.31f
50.13±1.46b
58.92±1.99f
19.71±0.26f
Basal diet + 2 day fasting
161.00±1.19b
125.86±1.11b
36.43±0.34d
99.39±1.27b
25.17±0.22b
Basal diet + fasting day /
day
155.90±1.05c
120.93±1.03c
39.06±0.41d
92.64±0.57c
24.18±0.20c
Data are expressed as mean ± SE
Values in each column which have different letters are significantly different at (p<0.05)
Table (3) showed the lipid profile of all groups. Significant variations were detected between the +ve
control groups and the -ve control group. All the treated rats with RD or basal diet with or without
intermitting fasting had lower lipid profile (TC, TG, LDL-c and VLDL-c) and higher HDL-c compared
to the +ve control group. In terms with RD groups, the rats fed on RD with 2 day fasting had a greater
lipid profile reduction than those of the groups treated with RD. In addition, diabetic rats fed on basal
diet with 2 days fasting had lower lipid profile and greater HDL-c than the group fed on basal diet with
fasting day/day. Also, the RD model was more effective in lowering lipid profile than those fed on basal
diet. The highest lipid profile reduction and highest HDL-c concentration were seen at the diabetic rats
fed on RD and 2 days fasting compared to the other treated rats
Harvie et al., (2013) found that 3 months on an IF diet significantly reduced the blood lipid levels of
patients with impaired glucose and lipid metabolism. In addition, Moro et al., (2016) observed lipid
profile enhancement (increased HDL-c and decreased LDL-c) in a 2-month trial of IF in healthy men.
The mechanisms of improving cardiovascular disease risks by IF may result from obesity control,
https://jazindia.comnline at: le obilaAva - 1337 -
improved lipid profiles, elevated adiponectin levels (Bhutani et al., 2010), and a suppressed
inflammatory state (Fothergill et al., 2016). Additionally, increased hepatic fatty acid oxidation in the
fasting state results in reduced hepatic accumulation of triglycerides, which sequentially decreases the
hepatic production of VLDL and plasma levels of VLDL (Grajower and Horne, 2019)
Santos et al., (2018) have compiled data from different trials and concluded that different types of IF
can increase HDL by 1–14 mg/dl, decrease LDL by 1–47 mg/ dl, decrease TC by 5–88 mg/dl and
decrease TG by 3–64 mg/dl. Previously conducted trials have mentioned that intermittent fasting of 12–
36 h results in a metabolic switch (Anton et al., 2018) leading to a breakdown of triglycerides into fatty
acids and glycerol and conversion of fatty acids to ketone bodies in the liver (De Cabo and Mattson,
2019). During fasting, fatty acids and ketone bodies provide energy to cells and tissues (Malinowski et
al., 2019). Intermittent fasting (12 h during daytime, three times per week for 6 weeks) may protect
cardiovascular health by improving the lipid profile and raising the sub-optimal HDL. Intermittent
fasting may be adopted as a lifestyle intervention for the prevention, management, and treatment of
cardiovascular disorders (Ahmed et al., 2020)
Table (4): Effect of intermittent fasting and caloric restricted diet on serum liver functions of diabetic
rats
Parameters
Groups
ALT
AST
µ/L
Control (-ve)
46.46 1.00ᵉ
32.70 1.26ᵉ
Control (+ve)
131.42 1.16ᵃ
106.50 1.337ᵃ
Restricted diet (RD)
113.10 0.25ᶜ
57.00 1.47ᶜ
RD+ 2 day fasting
113.10 0.75ᶜ
53.73 0.81ᵈ
RD + fasting day/ day
110.60 0.88ᵈ
47.73 0.81ᵈ
Basal diet + 2 day fasting
117.26 0.69ᵇ
63.76 1.49ᵇ
Basal diet + fasting day / day
117.20 0.63ᵇ
58.90 3.62ᵇᶜ
Data are expressed as mean ± SE
Values in each column which have different letters are significantly different at (p<0.05)
The effect of intermittent fasting and caloric restricted diet on serum liver functions of diabetic rats was
shown at table (4). Injection with STZ caused a significant increase in liver functions (ALT and AST)
as compared to the -ve control group. Rats fed on RD with or without intermitting fasting had lower
serum ALT and AST compared to the +ve control group. Moreover, rats fed on basal diet with
intermitting fasting showed reduced liver functions as compared to the +ve control group. Notably, the
most common improvement in liver functions was clearly observed at the diabetic rats fed on RD with
fasting day/day
The role of fasting therapy on liver enzymes, among healthy persons was verified (Naveen et al., 2014).
It was observed that excessive caloric intake, as well as food consumption throughout the day, can
influence liver lipid accumulation (Koopman et al., 2014). The altered levels of liver enzymes may be
associated with variations in cytokine levels and alterations in circadian rhythms of hormones as a result
of Ramadan fasting (Nasiri et al., 2016)
This is partially similar to that reported by Pirmadah et al., (2020) in patients who mentioned that IF
might positively affect liver function in diseased patients. It was also concluded that daily 12 h of
intermittent fasting for one month significantly reduced the liver weight of mice, which is associated
with enhanced liver metabolism (Jianbo et al., 2021)
Various researchers have reported that fasting may lead to improvements in liver function, potentially
indicating a reduction in liver fat accumulation or inflammation (Badran et al., 2022). Additionally, IF
can affect the gut microbiota, leading to changes in bile acid metabolism, which can impact lipid
metabolism and hepatic steatosis (Khan et al., 2022). Moreover, Ramadan fasting model can induce
positive metabolic changes and improve alterations associated with NAFLD, including weight gain,
lipid profile, liver enzymes, and hepatic steatosis (Alasmari et al., 2023)
4. Conclusion
The Effect of Intermittent Fasting and Caloric Restricted Diet on Diabetic Rats
Available online at: https://jazindia.com - 1338 -
In conclusion, the data present the evidence demonstrating the beneficial effects of restricted diet with
intermitting fasting in a rat model with diabetes, suggesting that restricted diet with intermitting fasting
exerts potential hypoglycemic, hepatoprotective, hypolipidemic effects
References:
1. Ahmad S and Chowdhury TA. Fasting during Ramadan in people with chronic kidney disease: A review of
the literature. Ther Adv Endocrinol Metab. 2019;10
2. Ahmed N.; Farooq J.; Siddiqi H.; Ayoub Meo S.; Kulsoom B.; Laghari A.; Jamshed H and Pasha F.(2020):
Impact of Intermittent Fasting on Lipid Profile–A Quasi-Randomized Clinical Trial. Front Nutr. 2020;
7: 596787
3. Alasmari A.; Al-Khalifah A.; BaHammam A.; Alshiban N.; Almnaizel A.; Alodah H and Alhussain M. (2023):
Ramadan Fasting Model Exerts Hepatoprotective, Anti-obesity, and Anti-Hyperlipidemic Effects in an
Experimentally-induced Nonalcoholic Fatty Liver in Rats. The Saudi Journal of Gastroenterology,
29:1-33
4. Alhamdan BA.; Garcia-Alvarez A.; Alzahrnai AH.; Karanxha J.; Stretchberry DR.; Contrera KJ.; et al.
Alternate-day versus daily energy restriction diets: which is more effective for weight loss? A
systematic review and meta-analysis. Obes Sci Pract 2016;2: 293–302
5. Anastasiou CA.; Karfopoulou E and Yannakoulia M. Weight regaining: from statistics and behaviors to
physiology and metabolism. Metabolism. 2015;64(11):1395-407
6. Anton SD.; Moehl K.; Donahoo WT.; Marosi K.; Lee SA.; Mainous AG.; et al.. Flipping the metabolic switch:
understanding and applying the health benefits of fasting. Obesity. (2018) 26:254–68.
10.1002/oby.22065
7. Badran H.; Elsabaawy M.; Sakr A,; et al. Impact of Intermittent fasting on laboratory, radiological, and
anthropometric parameters in NAFLD patients. Clin Exp Hepatol. 2022;8(2):118
8. Bancroft J.D. and A. Stevens (1977): Theory and Practice of Histological Techniques. Edinburgh, Churchill-
Livingstone, New York, P 740
9. Bhutani S.; Klempel MC.; Berger RA and Varady KA. Improvements in coronary heart disease risk indicators
by alternate-day fasting involve adipose tissue modulations. Obesity (Silver Spring) 2010;18:2152–9
10. Carter S.; Clifton PM and Keogh JB. Effect of Intermittent Compared With Continuous Energy Restricted
Diet on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Noninferiority Trial.
JAMA Netw Open 2018; 1: e180756
11. Catenacci VA.; Pan Z.; Ostendorf D.; Brannon S.; Gozansky WS.; Mattson MP.; et al. A randomized pilot
study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity.
Obesity (Silver Spring) 2016;24:1874–83
12. Chapman D.G., Castilla R and Campbell J.A. Evaluation of Protein in Food. I. A method for the deterinination
of protein efficiency ration. Can. J. Biochem. Phosiol. 1959;37:679–686
13. CHEN L.; TIAN F.; HU X., WU J., XU W., and HUANG Q. (2023): Intermittent fasting in type 2 diabetes:
from fundamental science to clinical applications. European Review for Medical and Pharmacological
Sciences. 2023; 27: 333-351
14. Clifton KK.; Ma CX.; Fontana L and Peterson LL. Intermittent fasting in the prevention and treatment of
cancer. CA Cancer J Clin 2021; 71: 527-546
15. de Cabo R and Mattson MP. Effects of intermittent fasting on health, aging, and disease. N Engl J Med. (2019)
381:2541–51. 10.1056/NEJMra1905136
16. Duregon E.; Pomatto-Watson L.; Bernier M.; Price NL and de Cabo R. Intermittent fasting: from calories to
time restriction. Geroscience 2021;43:1083–92
17. Ebrahimie M.; Bahmani M.; Shirzad H.; Rafieian-Kopaei M and Saki K. A review study on the effect of
Iranian herbal medicines on opioid withdrawal syndrome. Journal of evidence-based complementary
& alternative medicine. 2015 Oct;20(4):302-9
18. Faris M.; Jahrami H.; Abdelrahim D.; Bragazzi N and BaHammam A. (2021): The effects of Ramadan
intermittent fasting on liver function in healthy adults: A systematic review, meta-analysis, and meta-
regression. Diabetes Res Clin Pract; 178:108951
19. Fothergill E.; Guo J.; Howard L.; Kerns J.C; Knuth N.D.; Brychta R. and et al., (2016): Persistent metabolic
adaptation 6 years after "The Biggest Loser" competition. Obesity (Silver Spring);24:1612–9
20. Furmli et al., (2018) found that IF reversed and/or reduced insulin resistance while significantly reducing body
weight, waist circumference, and HbA1c
21. Grajower MM and Horne BD. (2019): Clinical management of intermittent fasting in patients with diabetes
mellitus. Nutrients;11: 873
22. Harney DJ.; Hutchison AT.; Hatchwell L.; Humphrey SJ.; James DE.; Hocking S.; Heilbronn LK and Larance
M. Proteomic analysis of human plasma during intermittent fasting. J Proteome Res. 2019;18:2228–
2240
23. Harvie. M,; C. Wright.; M. Pegington et al., “/e effect of intermittent energy and carbohydrate restrictionv:
daily energy restriction on weight loss and metabolic disease risk markers in overweight women,”
British Journal of Nutrition, vol. 110, no. 8, pp. 1534–1547, 2013
24. Jebeile H.; Gow ML.; Lister NB.; Mosalman Haghighi M.; Ayer J.; Cowell CT.; et al. Intermittent energy
restriction is a feasible, effective, and acceptable intervention to treat adolescents with obesity. J Nutr
2019;149:1189–97
https://jazindia.comnline at: le obilaAva - 1339 -
25. Jianbo Ma.; Yan Cheng.; Qiang Su.; Wen Ai.; Ling Gong.; Yueying Wang.; Linhao Li.; Zhongren Ma.; Qiuwei
Pan.; Zilin Qiao and Kan Chen(2021): Effects of intermittent fasting on liver physiology and
metabolism in mice. Exp Ther Med. 22(3); 950 2021
26. Keogh JB,; Pedersen E.; Petersen KS and Clifton PM. Effects of intermittent compared to continuous energy
restriction on short-term weight loss and long-term weight loss maintenance. Clin Obesity. (2014)
4:150–6. 10.1111/cob.12052
27. Khan MN.; Khan SI.; Rana MI.; Ayyaz A.; Khan MY and Imran M. Intermittent fasting positively modulates
human gut microbial diversity and ameliorates blood lipid profile. Front Microbiol. 2022;13:2931
28. Koopman K.E.; Caan M.W.; Nederveen A.J.; Pels A.; Ackermans M.T.; Fliers E. and et al., (2014):
Hypercaloric diets with increased meal frequency, but not meal size, increase intrahepatic triglycerides:
A randomized controlled trial. Hepatology; 60:545-53
29. Kul S.; Savaş E.; Öztürk ZA and Karadag G. Does ramadan fasting alter body weight and blood lipids and
fasting blood glucose in a healthy population? A meta-analysis. J Religion Health. (2014) 53:929–42.
10.1007/s10943-013-9687-0
30. Lessan N and Ali T. Energy metabolism and intermittent fasting: The Ramadan perspective. Nutrients.
2019;11
31. Malinowski B.; Zalewska K.; Wesierska A.; Sokołowska MM.; Socha M,; Liczner G, et al.. Intermittent
fasting in cardiovascular disorders—an overview. Nutrients. (2019) 11:673. 10.3390/nu11030673
32. Mattson M.P.; Longo V.D. and Harvie M. (2017): Impact of intermittent fasting on health and disease
processes. Ageing Res Rev;39:46-58
33. Mitchell SJ.; Bernier M.; Mattison JA.; Aon MA.; Kaiser TA.; Anson RM.; Ikeno Y.; Anderson RM.; Ingram
DK and de Cabo R. Daily fasting improves health and survival in male mice independent of diet
composition and calories. Cell Metab. 2019;29:221–228.e3
34. Moro T.; Tinsley G.; Bianco A.; Marcolin G.; Pacelli QF.; Battaglia G.; 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. J Transl Med 2016;14:290
35. Nasiri J.; Kheiri S.; Khoshdel A and Boroujeni AJ. Effect of Ramadan Fast on Liver Function Tests. Iran J
Med Sci 2016;41(5):459–60
36. Naveen GH.; Shetty P.; Goutham M P.; Ganesh P B.; ChethanR and Sangram P. Effect of Naturopathic Based
Fasting Therapy on Liver Enzymes, Electrolytes, Fasting Blood Glucose, Weight And Perceived Stress
Among Healthy Individuals -A Randomized Controlled Trial. International Journal of Yoga and Allied
Sciences 2014; 3
37. Neeland IJ.; Turer AT.; Ayers CR.; Powell-Wiley TM.; Vega GL.; Farzaneh-Far R.; Grundy SM.; Khera A.;
McGuire DK and de Lemos JA. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes
in obese adults. JAMA 2012; 308: 1150-1159
38. Otovwe, A. and Akpojubaro, E. H. (2020). Diabetes mellitus in primary and secondary schools in Africa: An
exploratory review. Alexandria Journal of Medicine, 56(1), 166–172.
10.1080/20905068.2020.1833278
39. Parvaresh A.; Razavi R.; Abbasi B.; et al. Modified alternate-dayfasting vs. calorie restriction in the treatment
of patients withmetabolic syndrome: A randomized clinical trial. ComplementTher Med.
2019;47:102187
40. Pirmadah , F.; N. Ramezani-Jolfaie .; M. Mohammadi .; N. Talenezhad .; C.C. Clark and A. Salehi-Abargouei
(2020): Does L-carnitine supplementation affect serum levels of enzymes mainly produced by liver?.
Eur. J. Nutr.; 59(5):1767- 1783
41. Reeves G.; Nielsen H. and Fahey, C. (1993): AIN-93 purified diets for laboratory rodents: final report of the
American institute of nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent
diet. J. Nutr. 123:1939–1951
42. Roman YM.; Dominguez MC.; Easow TM.; Pasupuleti V.; White CM and Hernandez AV. Effects of
intermittent versus continuous dieting on weight and body composition in obese and overweight people:
a systematic review and meta-analysis of randomized controlled trials. Int J Obes (Lond) 2019;4
43. Rynders CA.; Thomas EA.; Zaman A.; Pan Z.; Catenacci VA and Melanson EL. Effectiveness of intermittent
fasting and time-restricted feeding compared to continuous energy restriction for weight loss. Nutrients
2019;11:2442
44. S. Furmli.; R. Elmasry.; M. Ramos and J. Fung, “/erapeutic use of intermittent fasting for people with type 2
diabetes as an alternative to insulin,” BMJ Case Reports, vol. 2018, 2018
45. Sadeghirad B.; Motaghipisheh S.; Kolahdooz F.; Zahedi MJ and Haghdoost AA. Islamic fasting and weight
loss: a systematic review and meta-analysis. Pub Health Nutrit. (2014) 17:396–406.
10.1017/S1368980012005046
46. Saeedi P.; Petersohn I.; Salpea P.; Malanda B.; Karuranga S.; Unwin N.; Colagiuri S.; Guariguata L.; Motala
AA.; Ogurtsova K and Shaw JE. Global and regional diabetes prevalence estimates for 2019 and
projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas.
Diabetes research and clinical practice. 2019 Nov 1;157:107843
47. Santos HO and Macedo RCO. Impact of intermittent fasting on the lipid profile: assessment associated with
diet and weight loss. Clin Nutrit ESPEN. (2018) 24:14–21. 10.1016/j.clnesp.2018.01.002
48. Sarkar, S., Pranava, M. and Marita, R., 1996. Demonstration of the hypoglycemioc action of Momordica
charantia in a validate animal model of diabetes. Pharmacol. Res. 33: 1-4
The Effect of Intermittent Fasting and Caloric Restricted Diet on Diabetic Rats
Available online at: https://jazindia.com - 1340 -
49. Siehler J.; Blöchinger AK.; Meier M and Lickert H. Engineering islets from stem cells for advanced therapies
of diabetes. Nat Rev Drug Discov 2021; 20: 920-940
50. Stockman M-C.; Thomas D.; Burke J and Apovian CM. Intermittent fasting: is the wait worth the weight?
Curr Obes Rep. (2018) 7:172–85. 10.1007/s13679-018-0308-9
51. Sun H.; Saeedi P.; Karuranga S.; Pinkepank M.; Ogurtsova K.; Duncan BB.; Stein C.; Basit A.; Chan JCN.;
Mbanya JC.; Pavkov ME.; Ramachandaran A.; Wild SH.; James S.; Herman WH.; Zhang P.; Bommer
C.; Kuo S.; Boyko EJ and Magliano DJ. IDF Diabetes Atlas: Global, regional and country-level
diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 2022; 183:
109119
52. Sundfør TM.; Svendsen M and Tonstad S. Intermittent calorie restriction-a more effective approach to weight
loss? Am J Clin Nutr 2018;108:909–10
53. Teong X.; Liu K.; Vincent A.; Bensalem J.; Liu B.; Hattersley K.; et al., (2023): Intermittent fasting plus
early time restricted eating versus calorie restriction and standard care in adults at risk of type 2
diabetes: a randomized controlled trial. Nature Medicine, 29:963–972
54. Trepanowski JF and Bloomer RJ. The impact of religious fasting on human health. Nutrit J. (2010) 9:57.
10.1186/1475-2891-9-57
55. Wegman MP.; Guo MH .; Bennion DM .;Shankar MN.; Chrzanowski SM.; Goldberg LA, et al. Practicality of
intermittent fasting in humans and its effect on oxidative stress and genes related to aging and
metabolism. Rejuvenation Res. 2015;18(2):162-72
56. Yuan X.; Wang J.; Yang S.; Gao M.; Cao L.; Xumei L.; Hong D.; Tian S. and Sun C.( 2022): Effect of
Intermittent Fasting Diet on Glucose and Lipid Metabolism and Insulin Resistance in Patients with
Impaired Glucose and Lipid Metabolism: A Systematic Review and Meta-Analysis. International
Journal of Endocrinology Volume 2022, Article ID 6999907, 9 pages
57. Zubrzycki A.; Cierpka-Kmiec K.; Kmiec Z and Wronska A. The role of low-calorie diets and intermittent
fasting in the treatment of obesity and type-2 diabetes. J Physiol Pharmacol 2018;69:663- 83
STZ
p<0.05
