Background: Many patients with type 2 diabetes (T2D) insist to fast the holy month Ramadan against medical advice. Aim: The aim of the study was to evaluate the effects of Ramadan fasting on diabetic nephropathy in patients with T2D. Patients and Methods: The present study was conducted on ninety patients with T2D who intended to fast Ramadan; they were divided into the following groups: Group 1: 30 patients with T2D, without albuminuria (normoalbuminuria); Group 2: 30 patients with T2D, with microalbuminuria; and Group 3: 30 patients with T2D, with macroalbuminuria. Laboratory tests including fasting plasma glucose, 2-h postprandial plasma glucose, haemoglobin A1c, serum creatinine, blood urea and urinary albumin/creatinine ratio (UACR) were measured 2 weeks before Ramadan fasting and then repeated within 2 weeks after Ramadan. Results: On comparing data before and after Ramadan, there was a significant increase in creatinine and urea levels, while there was a significant decrease in the estimated glomerular filtration rate (eGFR) and UACR in all the study groups. There was no significant difference between the study groups regarding the percentage of increase in creatinine (P = 0.204) and urea (P = 0.505), while the percentage of decrease in eGFR was significantly higher in the macroalbuminuria group (P = 0.038), and the percentage of decrease in UACR was significantly higher in the normoalbuminuria group (P = 0.001). Conclusion: Ramadan fasting has adversely affected the renal function and causes a decrease in the eGFR in type 2 diabetic patients with diabetic nephropathy. Fasting should be under close medical supervision with strict attention to fluid intake and daily activity, as well as adjustment of drug regimens.
Keywords: Diabetic nephropathy, Ramadan fasting, type 2 diabetes
|How to cite this URL:|
Mohammad MS, Aboromia MM, Ibrahim NA, Abdul Jalil NA. Effects of ramadan fasting on diabetic nephropathy in patients with type 2 diabetes. Hamdan Med J [Epub ahead of print] [cited 2022 Aug 19]. Available from: http://www.hamdanjournal.org/preprintarticle.asp?id=351962
| Introduction|| |
Fasting during the holy month of Ramadan is one of the five pillars of Islam. Muslims form about 20% of the world population and inhabit almost corners of the globe, thus clinicians need to be familiar with such spiritual obligation as well as its impact on health.,
During Ramadan, Muslims must abstain from eating, drinking, taking medications and smoking from the exact time of dawn until time of sunset, while there are no restrictions on food or fluid intake between sunset and dawn. Fasting duration ranges from 10 to 18 h daily and varies according to the season and the geographic location.
Ramadan fasting differs from other experimental fasting, as there is involvement of many psychological and sociological aspects. Despite the exemption of individuals with chronic illnesses whose health may be adversely affected from fasting,, many patients with type 2 diabetes (T2D) insist to fast against medical advice.,
During Ramadan, Muslims tend to alter their lifestyle which is one of the major and modifiable risk factors of diabetes control. Patients with diabetes mellitus who fast are prone to fluctuations of their glucose levels depending on the changes in eating times, composition as well as quantity of food, sleep pattern, regularity in medicine taking and alterations in daily physical activities.
Diabetic nephropathy is one of the major microvascular complications of diabetes, characterised by proteinuria and renal insufficiency; it is also considered one of the major causes of end-stage renal disease worldwide. Some of the previous studies demonstrated good tolerance, safety and favourable outcome of Ramadan fasting in patients with diabetic nephropathy, while others revealed that fasting during Ramadan had adversely affected kidneys, particularly in tropical climate with heat and humidity. Prolonged fasting and fluid deprivation, in addition to changes in eating habits during Ramadan, may be complicated by dehydration and hyperviscosity, predisposing to further kidney injury in patients with chronic kidney disease (CKD).
The aim of this study was to evaluate the effects of Ramadan fasting on diabetic nephropathy in patients with T2D.
| Subjects and Methods|| |
The present study was conducted on 90 patients with T2D selected from the outpatient clinic of diabetes and endocrinology, Ain Shams University Hospitals. Patients with T2D who were aged 18 years or more and expressed intention to fast the whole month of Ramadan (April–May 2021) were invited to participate in the study.
They were divided into the following groups: Group 1: 30 patients with T2D, without albuminuria (normoalbuminuria); Group 2: 30 patients with T2D and microalbuminuria; and Group 3: 30 patients with T2D and macroalbuminuria.
Patients with end-stage kidney disease, type 1 diabetes, pregnant or lactating women and other systemic diseases such as liver cell failure, heart failure, malignancy or autoimmune kidney disease were excluded from the study.
All enrolled individuals were subjected to medical history taking emphasising on symptoms, duration and treatment of T2D as well as exclusion of other systemic disorders. Anthropometric parameters were obtained while participants were standing erect and barefoot. Height and weight were determined using standardised conventional methods. Body mass index (BMI) was calculated as weight in kilograms divided by height in squared meters. Systolic blood pressure and diastolic blood pressure were measured with a mercury sphygmomanometer with patients in the sitting position.
The study protocol was approved by the Institutional Ethics Committee, and all participants provided written informed consent before participating in the study.
Early morning ≥8-h fasting blood samples were collected from the participants. About 10 ml of venous blood sample was obtained from each patient in two visits; 4 ml was taken in two tubes with heparin and the rest in a biochemical tube. Samples were immediately transferred to the laboratory in a cool box at +4°C. Serum was obtained from samples collected in biochemical tubes by centrifuging blood samples at 3000 rpm for 15 min at 4°C; then, samples were stored at −20°C until analysed. Furthermore, the second-morning urine samples were collected in serialised urine containers determining albuminuria.
Laboratory tests including fasting plasma glucose (FPG), 2-h postprandial plasma glucose (2-h PPG), haemoglobin A1c (HbA1c), serum creatinine, blood urea and urinary albumin/creatinine ratio (UACR) were measured 2 weeks before Ramadan fasting and then repeated within 2 weeks after Ramadan.
Estimation of the biochemical parameters was done in the clinical biochemistry laboratory using commercial kits adapted to autoanalyser. Plasma glucose was carried out by glucose oxidase and peroxidase method. Serum urea was estimated by Berthelot's method while creatinine was determined by alkaline Jaffe's Picrate method; the normal levels of creatinine were considered 0.8–1.4 mg/dL and for urea 10–45 mg/dL. HbA1c of all subjects in the study was estimated by ion exchange resin method using the diagnostic HbA1c kits of Asritha Diatech as per the guidelines provided.
Urine microalbumin was measured by radioimmunoassay using the DPC Coat-A-Count kit (Diagnostic Products Corp., Los Angeles, CA, USA). Urine creatinine was determined by the alkaline picrate method. UACR was calculated and classified as either normal (albumin/creatinine ratio <30 μg/mg) or microalbuminuria (albumin/creatinine ratio from 30 μg/mg to 300 μg/mg) and macroalbuminuria (albumin/creatinine ratio >300 μg/mg).
Estimated glomerular filtration rate (eGFR) was calculated by Modification of Diet in Renal Disease (MDRD) equation; eGFR =186 x (Plasma Creatinine)-1.154 x (age)-0.203 x (0.742 if female) x (1.210 if African American).
All the patients were seen twice during the study: 2 weeks before Ramadan and within 2 weeks after Ramadan fasting. Clinical, demographic and laboratory data were collected from all patients in the two visits.
Statistical evaluation was carried out by using SPSS programme version 21.0 (SPSS Inc., Chicago, IL, USA). Numerical data were presented as mean ± standard deviation and categorical data were presented as number and percentage of total. Comparison between more than two independent groups with quantitative data was done by using one-way analysis of variance. Chi-square test was used to compare qualitative data. Post hoc test (Tukey's) was used to identify the least significant difference amongst the studied groups. Probability (P < 0.05) was considered statistically significant.
| Results|| |
All recruited patients managed to fast at least 25 days during the month of Ramadan. Fasting time was around 14 h and the atmosphere temperature was from 28°C to 34°C. None of the patients suffered acute illness during Ramadan, and none of them displayed any new clinical symptoms or signs.
Demographic and laboratory data of the study groups before Ramadan revealed no significant difference between the study groups regarding age, gender, BMI, blood pressure, treatment, FPG and HbA1c, while there was a significant difference between the study groups regarding duration of diabetes, 2-h PPG, serum creatinine, blood urea, UACR and eGFR, as shown in [Table 1].
After Ramadan fasting, there was no significant difference between the study groups regarding BMI, blood pressure, FPG, 2-h PPG and HbA1c while there was a significant difference between the study groups regarding serum creatinine, blood urea, UACR and eGFR, as shown in [Table 2].
On comparing demographic and laboratory data before and after Ramadan fasting in each study group, the results showed a significant increase in creatinine and urea levels, while there was a significant decrease in eGFR and UACR in all the study groups. Otherwise, no significant differences were found regarding the other studied parameters, as shown in [Table 3] and [Figure 1] and [Figure 2].
|Table 3: Comparison of anthropometric measures and laboratory parameters before and after Ramadan of each study group|
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|Figure 1: Estimated glomerular filtration rate of the study groups before and after Ramadan|
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|Figure 2: Urinary albumin/creatinine ratio of the study groups before and after Ramadan|
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There was no significant difference between the study groups regarding the percentage of increase in creatinine and urea, while the percentage of decrease in eGFR was significantly higher in the macroalbuminuria group, and the percentage of decrease in UACR was significantly higher in the normoalbuminuric group, as shown in [Table 4] and [Figure 3].
|Table 4: Comparison between the study groups regarding the percentage of change in renal function tests before and after Ramadan|
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|Figure 3: Percentage of change in renal function tests of the study groups before and after Ramadan|
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| Discussion|| |
Annually, endocrinologists around the world must face their sociomedical duties towards Muslim diabetic patients who wish to fast during the holy month of Ramadan and fulfil their religious obligation. One of the major concerns for CKD patients regarding fasting is the possibility of dehydration and its deleterious consequences on renal functions. In the present study, we evaluated the effects of Ramadan fasting on diabetic nephropathy in patients with T2D.
The results showed no significant change in BMI of the three study groups after Ramadan fasting. This was agreed with Yeoh et al. who revealed no significant change in BMI when compared after and before Ramadan. Furthermore, Jaleel et al. and Kara et al. demonstrated that diabetic patients who fasted during Ramadan had no significant change in their body weight. On the other hand, Sadiya et al. showed that the body weight was significantly decreased after Ramadan fasting; this was in line with Khaled et al. and Mafauzy et al. who observed a decrease in body weight after fasting in Algerian and Malaysian diabetic population, respectively, while Kamar et al. reported a significant increase in body weight. This could be attributed to the variations in sample size as well as eating pattern of different communities included in these studies.
In the present study, there was no significant change in both systolic and diastolic blood pressure of all the study groups after Ramadan fasting, this was agreed with Sandhya et al. who reported no statistically significant change in the systolic blood pressure. The increase in the dietary fibre and rehydration in the evening could have a role in maintaining the blood pressure in the pre-fasting level. Moreover, Bernieh et al. revealed no statistically significant reduction in systolic and diastolic blood pressure at the end of Ramadan fasting compared to values before fasting. Furthermore, Sahin et al. showed that the blood pressure was unchanged in patients who fasted during Ramadan. On the contrary, Bener and Yousafzai reported that systolic and diastolic blood pressures were significantly lowered after as compared with before Ramadan. Furthermore, Samad et al. revealed a significant improvement of systemic blood pressure after Ramadan.
Regarding the effect of Ramadan fasting on FPG, 2-h PPG and HbA1c, the present study showed no significant change in all the study groups. In line with our findings, Sahin et al. reported that FPG, 2-h PPG and HbA1c were unchanged in patients who fasted during Ramadan. Moreover, Sandhya et al. revealed no significant decrease in the fasting blood sugar while the parameters such as postprandial blood sugar, mean blood glucose and HbA1c did not alter. Furthermore, Kamar et al. observed that there was no significant change in the mean fasting blood glucose which indicates that Ramadan fasting did not significantly alter glycaemic control. On the other hand, Bener and Yousafzai reported a significant reduction in HbA1c after fasting, while Bernieh et al. showed a significant increase in HbA1c levels after Ramadan fasting.
The results of the present study revealed a significant increase in serum creatinine and urea levels, as well as a significant decrease in eGFR across all the study groups after Ramadan fasting. Our findings agreed with Abushady et al. who reported a significant elevation of serum creatinine and a significant decline in eGFR in patients with T2D who have normal kidney functions, with and without albuminuria after Ramadan fasting. Similarly, Sandhya et al. concluded that the increase in renal function markers including urea, creatinine and uric acid seen in their study was possibly due to a hypohydration resulted from the reduced fluid intake during day time which was reinforced by the osmotic dieresis that was presented in patients with diabetes mellitus. Moreover, Bakhit et al. reported that 33% of CKD patients developed worsening of renal functions during or within 3 months after Ramadan.
On the contrary, El-Wakil et al. observed that serum creatinine did not change significantly after Ramadan and no significant change in GFR of CKD patients during Ramadan fasting. Furthermore, Bernieh et al. showed no significant change in serum creatinine, as well as a significant improvement in the eGFR during and after Ramadan fasting. Moreover, Kara et al. have investigated patients with Stage 3 or higher CKD and divided the patients into fasting and non-fasting groups, and they concluded that Ramadan fasting was not associated with increased risk of decline in renal functions in patients with Stage 3–5 CKD, except for elderly patients who may still be under a higher risk.
In the present study, UACR was significantly decreased after Ramadan fasting in all the study groups. The percentage of change in UACR was significantly lower in the micro- and macroalbuminuria groups when compared to the normoalbuminuric group, as well as in the macroalbuminuria group when compared to the microalbuminuria group. In agreement with our findings, Sahin et al. showed a significant decrease of microalbuminuria during Ramadan. Furthermore, Sandhya et al. reported that microalbuminuria was improved after fasting which indicates that glomerular membrane health was not harmfully affected by Ramadan fasting. Moreover, El-Gendy et al. showed no significant change of UACR in patients with T2D after Ramadan fasting, and it remained low 6 weeks after Ramadan.
Contrary to our findings, Abushady et al. showed that UACR was significantly increased in patients with micro- and macroalbuminuria. Furthermore, Kamar et al. reported that UACR had increased significantly after Ramadan, concluding that fasting had an adverse effect on albuminuria in diabetic patients.
Our results can be explained by the limitation of fluid intake during Ramadan fasting, which causes dehydration as well as decreased renal perfusion. Excessive perspiration in hot and humid climates may result in dehydration, especially amongst individuals who perform hard physical labour. Moreover, the osmotic diuresis caused by hyperglycaemia contributed to further volume and electrolyte depletion. The haemodynamic effects of fasting during Ramadan that can result in impaired renal functions are different across studies; such factors may include exercise duration, the amount of perspiration, the time that participants stayed outdoor under sun exposure or the type of work that they undertook., In addition, the duration of fasting in Ramadan changes from 1 year to another, and according to the geographic location, therefore, the results of various studies may not be generalised.
Future studies involving larger sample sizes will be useful to confirm our findings and elucidate the determinants of these changes in body composition and metabolic profile as well as gender differences. It is tempting to speculate that these differences may be attributable to changes in circadian rhythm and physical activity with intensive prayer activity performed during the month of Ramadan. Clinical practice recommendations of this study include promoting the provision of structured education for Muslims who intend to fast during the month of Ramadan; they should be advised regarding adequate hydration and dietary modification during pre-Ramadan healthcare education.
| Conclusion|| |
Ramadan fasting has adversely affected the renal function and causes a decrease in the eGFR in type 2 diabetic patients with diabetic nephropathy. Consecutively, fasting should be under close medical supervision with strict attention to fluid intake, daily activity and adjustment of drug regimens.
We wish to express our gratitude to the Department of Clinical Pathology, Ain Shams University, for being abundantly helpful and offering invaluable assistance, support and guidance. Deepest gratitude is to the Department of Public Health, Ain Shams University, for the invaluable consultations in biostatistical analysis.
The study was approved by Research Ethical Committee (REC), Ain Shams University, Faculty of Medicine, FWA 00006444.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
The Holy Quran; Suraht Al Baquarah. Chapter 2, Versus 183-5.
Al-Arouj M, Assaad-Khalil S, Buse J, Fahdil I, Fahmy M, Hafez S, et al.
Recommendations for management of diabetes during Ramadan: Update 2010. Diabetes Care 2010;33:1895-902.
The Holy Quran; Suraht Al Baquarah. Chapter 2, Versus 187.
Berbari AE, Daouk NA, Mallat SG, Jurjus AR. Ramadan fasting in health and disease. In: Berbari AE, Mancia G, editors. Special Issues in Hypertension. Milan, Italy: Springer-Verlag; 2012.
The Holy Quran; Suraht AN-NISAA. Chapter 4, Versus 29.
Salti I, Bénard E, Detournay B, Bianchi-Biscay M, Le Brigand C, Voinet C, et al.
A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: Results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care 2004;27:2306-11.
Sahin SB, Ayaz T, Ozyurt N, Ilkkilic K, Kirvar A, Sezgin H. The impact of fasting during Ramadan on the glycemic control of patients with type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2013;121:531-4.
Risérus U, Willett WC, Hu FB. Dietary fats and prevention of type 2 diabetes. Prog Lipid Res 2009;48:44-51.
Azizi F, Siahkolah B. Ramadan fasting and diabetes mellitus. Arch Iran Med 2003;6:237-42.
Ritz E, Zeng XX, Rychlík I. Clinical manifestation and natural history of diabetic nephropathy. Contrib Nephrol 2011;170:19-27.
Bernieh B, Al Hakim MR, Boobes Y, Abu Zidan FM. Fasting Ramadan in chronic kidney disease patients: Clinical and biochemical effects. Saudi J Kidney Dis Transpl 2010;21:898-902.
] [Full text]
Gupta A, Lal C, Khaira A, Agarwal SK, Tiwari SC. R2 syndrome: Religion and renal failure. J Assoc Physicians India 2010;58:201.
Aktürk IF, Bıyık I, Koşaş C, Yalçın AA, Ertürk M, Uzun F. Effects of Ramadan fasting on blood pressure control, lipid profile, brain batriuretic peptide, renal functions and electrolyte levels in hypertensive patients taking combination therapy. Nobel Med 2013;9:43-6.
Berthelot M. Berthelot's reaction mechanism. Rep Chim Appl 1859;6:284.
Owen JA, Iggo B, Scandrett FJ, Stewart CP. The determination of creatinine in plasma or serum, and in urine; a critical examination. Biochem J 1954;58:426-37.
Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR, et al.
Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 2003;63:225-32.
Nathan DM, Singer DE, Hurxthal K, Goodson JD. The clinical information value of the glycosylated hemoglobin assay. N Engl J Med 1984;310:341-6.
Teitz NM, Trunder P. Estimation of blood glucose. In: Clinical Guide to Laboratory Test. Philadelphia, PA: WB Sanders; 1976. p. 238.
Shihabi ZK, Konen JC, O'Connor ML. Albuminuria vs. urinary total protein for detecting chronic renal disorders. Clin Chem 1991;37:621-4.
Woodhouse S, Batten W, Hendrick H, Malek PA. The glomerular filtration rate: An important test for diagnosis, staging and treatment of chronic kidney disease. Lab Med 2006;37:244-7.
Macedo E, Mehta RL. Prerenal failure: From old concepts to new paradigms. Curr Opin Crit Care 2009;15:467-73.
Yeoh EC, Zainudin SB, Loh WN, Chua CL, Fun S, Subramaniam T, et al.
Fasting during Ramadan and associated changes in glycaemia, caloric intake and body composition with gender differences in Singapore. Ann Acad Med Singap 2015;44:202-6.
Jaleel MA, Raza SA, Fathima FN, Jaleel BN. Ramadan and diabetes: As-Saum (The fasting). Indian J Endocrinol Metab 2011;15:268-73.
Kara E, Sahin OZ, Kizilkaya B, Ozturk B, Pusuroglu G, Yildirim S, et al
. Fasting in Ramadan is not associated with deterioration of chronic kidney disease: A prospective observational study. Saudi J Kidney Dis Transpl 2017;28:68-75.
] [Full text]
Sadiya A, Ahmed S, Siddieg HH, Babas IJ, Carlsson M. Effect of Ramadan fasting on metabolic markers, body composition, and dietary intake in Emiratis of Ajman (UAE) with metabolic syndrome. Diabetes Metab Syndr Obes 2011;4:409-16.
Khaled BM, Bendahmane M, Belbraouet S. Ramadan fasting induces modifications of certain serum components in obese women with type 2 diabetes. Saudi Med J 2006;27:23-6.
Mafauzy M, Mohammed WB, Anum MY, Zulkifli A, Ruhani AH. A study of the fasting diabetic patients during the month of Ramadan. Med J Malaysia 1990;45:14-7.
Kamar ME, Orabi AA, Salem IM, EL-Shabrawy AM. Effect of Ramadan fasting on diabetic micro-vascular complication. Zagazig Univ Med J 2015;20:193-205.
Sandhya AM, Suresh Kumar P, Mukkadan JK. Effect of Ramadan fasting on anthropometric, hematological and biochemical paramters of type 2 diabetic patients – A study on Indian male diabetic patients. Int J Adv Res 2016;4:732-7.
Bener A, Yousafzai MT. Effect of Ramadan fasting on diabetes mellitus: A population-based study in Qatar. J Egypt Public Health Assoc 2014;89:47-52.
Samad F, Qazi F, Pervaiz MB, Kella DK, Mansoor M, Osmani BZ, et al.
Effects of Ramadan fasting on blood pressure in normotensive males. J Ayub Med Coll Abbottabad 2015;27:338-42.
Abushady MM, Samy M, Bekhet M, Abdullah A. Effect of Ramadan fasting on renal function in patients with type 2 diabetes. Diabetes Res Clin Pract 2019;153:176-83.
Bakhit AA, Kurdi AM, Wadera JJ, Alsuwaida AO. Effects of Ramadan fasting on moderate to severe chronic kidney disease. A prospective observational study. Saudi Med J 2017;38:48-52.
El-Wakil HS, Desoky I, Lotfy N, Adam AG. Fasting the month of Ramadan by Muslims: Could it be injurious to their kidneys? Saudi J Kidney Dis Transpl 2007;18:349-54.
] [Full text]
El-Gendy OA, Rokaya M, El-Batae HE, Tawfeek S. Ramadan fasting improves kidney functions and ameliorates oxidative stress in diabetic patients. World J Med Sci 2012;7:38-48.
Trabelsi K, Stannard SR, Maughan RJ, Jammoussi K, Zeghal K, Hakim A. Effect of resistance training during Ramadan on body composition and markers of renal function, metabolism, inflammation, and immunity in recreational bodybuilders. Int J Sport Nutr Exerc Metab 2012;22:267-75.
Trabelsi K, El Abed K, Trepanowski JF, Stannard SR, Ghlissi Z, Ghozzi H, et al.
Effects of Ramadan fasting on biochemical and anthropometric parameters in physically active men. Asian J Sports Med 2011;2:134-44.
Nesma Ali Ibrahim,
Department of Internal Medicine, Ain Shams University, Cairo
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]