Group 5 Mini CAT: Ludma Delva, Laura Holmes, Andy Huang, Elishabeth Kim, Sandy Wu

 

Clinical Question:

Is Ramadan Fasting safe for Diabetic Patients?

 

PICO Question:

In a middle aged patient with well controlled NIDDM, what are the health risks associated with Ramadan fasting?

 

P=Type 2 Diabetic, Middle-aged Female

I= Ramadan Fasting

C=Not Fasting

O=Health Risks/ Outcomes

 

Search Strategy:

Searched Terms: “Diabetes Ramadan Risk”

Database and Articles Returned:

PubMed 9 (when removed risk=43)

Cochrane 11 (when removed risk=39)

Trip database 18 (PICO) (when removed risk=56)

Filters:Middle-Aged patients (45-65 y/o), within the last 10 years

Selection Methods:

Type II DM pt fasting during the month of Ramadan

Compared during Ramadan to pre-Ramadan fasting or post-Ramadan fasting

Offered measurable outcomes (hypoglycemia, weight change, biochemical data, HbA1C, etc)

Involved females in the study

 

Articles Chosen for Inclusion

• Is Ramadan fasting related to health outcomes? A review on the related evidence.
  Rouhani MH, Azadbakht L.
  J Res Med Sci. 2014 Oct;19(10):987-92. Review.
  PMID:25538785
  BACKGROUND:Fasting during Ramadan is an Islamic rule. Although previous review studies have assessed the impact of Ramadan on cardiovascular risk factors, athlete performance, diabetes and transplantation, in this study we have appraised some on these reviews by focusing on limitations and also, we have reviewed more recently published study and several recent studies, which are not reviewed till now.
  MATERIALS AND METHODS:In this article, we reviewed recently conducted studies in regarding the impact of Ramadan fasting on weight, lipid profile, diabetes, immune system and gestation. MEDLINE (http://www.pubmed.com) was searched by using “Ramadan” as keyword and the most recent articles in mentioned topics since 2009 until February 2014 were selected.
  RESULTS:Although weight has been decreased during Ramadan in the most studies, weight regain is prevalent during the following months. Meta-analysis of pre-Ramadan lipid profile in comparison to post-Ramadan values had been showed that total cholesterol and triglyceride were decreased in men and high-density lipoprotein was increased among women. In regarding diabetes and fasting, diabetic patients should be aware that medical, nutritional and physical activity consulting is necessary for individuals with diabetes who want to fast during Ramadan. Although published studies show that Ramadan fasting had no serious adverse effect on offspring, it is strongly recommended that pregnant women avoid fasting because of the limitations of studies. The effect of fasting during Ramadan on the immune system is favorable. Ramadan fasting has no impact on kidney function and urine component.
  CONCLUSION:Studies showed that Ramadan fasting has health protective effects. More precise studies should be conducted for more reliable conclusion.
  KEYWORDS: Body weight; Ramadan; diabetes; fasting; immune system; lipid profile; pregnancy

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274578/

 

• Metabolic parameters in type 2 diabetic patients with varying degrees of glycemic control during Ramadan: An observational study.
  Siaw MY, Chew DE, Toh MP, Seah DE, Chua R, Tan J, Lee EY, Chan SY, Lee JY.
  J Diabetes Investig. 2016 Jan;7(1):70-5. doi: 10.1111/jdi.12374. Epub 2015 Jun 17.
  PMID: 26816603
  Aims/Introduction: The changes in metabolic parameters in type 2 diabetic patients who fast during Ramadan have not been studied in Singapore. This study aimed to examine the trends of glycated hemoglobin (HbA1c), systolic blood pressure, low‐density lipoprotein cholesterol, and triglycerides in diabetic patients with varying degrees of glycemic control and different types of therapeutic approaches during Ramadan.
  Methods: The present retrospective study used a national electronic database to examine the metabolic parameter of Malay patients with type 2 diabetes. Eligible patients were stratified into three groups based on their mean HbA1c control before Ramadan: group 1 (HbA1c ≥10%), group 2 (HbA1c 7.1–9.9%) and group 3 (HbA1c ≤7%). Patients with a glomerular filtration rate <15 mL/min were excluded. The trends of metabolic parameters were traced before, during and after Ramadan.
  Results: Of 13,565 patients examined, 5,172 patients (38.1%) were eligible for this study. Mean change of HbA1c varied from −1.4% to +0.2% during Ramadan, with the greatest reduction observed in group 1 (P < 0.001). A minimal systolic blood pressure reduction was observed in groups 2 and 3 (2 mmHg; P < 0.01). Low‐density lipoprotein cholesterol and triglycerides changes were insignificant. A small, 0.1%, reduction in mean HbA1c was observed in patients taking oral antidiabetic agents during Ramadan (P < 0.001).
  Conclusions: Blood glucose was most affected during Ramadan, particularly in patients with mean baseline HbA1c ≥10%. The type of antidiabetic agent used did not seem to contribute to glycemic changes.
  Keywords: Metabolic parameters, Ramadan, Type 2 diabetes

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718105/  https://www.ncbi.nlm.nih.gov/pubmed/25581456

 

• Multi-country retrospective observational study of the management and outcomes of patients with Type 2 diabetes during Ramadan in 2010 (CREED).
  Babineaux SM(1), Toaima D(2), Boye KS(1), Zagar A(1), Tahbaz A(3), Jabbar A(4),Hassanein M(5).
  Author information:
  (1)Eli Lilly and Company, Indianapolis, IN, USA. (2)Eli Lilly, Cairo, Egypt.
  (3)Lilly UK, Basingstoke, UK. (4)Eli Lilly SA, Dubai, United Arab Emirates.
  (5)Dubai Hospital, Dubai, United Arab Emirates.
  AIM: To describe the characteristics and management of patients with diabetes who
  chose to fast during Ramadan in 2010.
  METHODS: This was a multi-country, retrospective, observational study, supplemented with physician and patient questionnaires, with data captured before, during and after Ramadan. A total of 508 physicians in 13 countries enrolled 3777 patients and a total of 3394 evaluable cases were analysed. We report on the subset of patients with Type 2 diabetes, which included 3250 patients (95.8%).
  RESULTS: Oral anti-hyperglycaemic therapy was the predominant pre-Ramadan therapy for most patients (76.6%). The treatment regimen was modified before Ramadan for 39.3% of all patients (34.9% for patients on oral drugs alone, 47.1% for patients on injectable drugs alone). Almost all physicians (96.2%) reported providing fasting-specific advice to patients and 62.6% report using guidelines or recommendations for the management of diabetes during Ramadan. In all, 64% of patients reported fasting everyday of Ramadan and 94.2% fasted for at least 15 days.
  CONCLUSIONS: Physicians have increasingly adopted multiple approaches to the management of fasting during Ramadan, including the adoption of international and/or national guidelines, providing fasting-specific advice and adjusting treatment regimens, such that patients are able to fast for a greater number of days without acute complications. Additional research is needed to explore physician and patient beliefs and practices to inform the evidence-based management of diabetes while fasting, both during and outside of Ramadan, and to  identify and address barriers to the universal uptake of techniques to facilitate that management.
  © 2015 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.
  DOI: 10.1111/dme.12685
  PMID: 25581456  [Indexed for MEDLINE]

Link: http://onlinelibrary.wiley.com/doi/10.1111/dme.12685/full

• Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan.
  Bravis V1, Hui E, Salih S, Mehar S, Hassanein M, Devendra D.
  Diabet Med.2010 Mar;27(3):327-31.
  doi: 10.1111/j.1464-5491.2010.02948.x. PMID:20536496

AIM: Determine the impact of Ramadan-focused education on weight and hypoglycemic episodes during Ramadan in Type 2 diabetic Muslim population who are currently taking oral glucose-lowering medication

METHODS: Retrospective analysis of 2 groups. Group A- attended Ramadan Education and Awareness in Diabetes Program (READ), a structured program to educate on physical activity, meal planning, glucose monitoring, hypoglycemia, as well as dosage and timing of medications.  Group B- no educational program. Hypoglycemia defined as home blood glucose <3.5 mmol/l

RESULTS: Weight loss-mean weight loss of 0.7kg (1.5 lbs) in Group A, 0.6kg weight gain in group B (P<0.001).

Total number of hypoglycemic events- from 9 before Ramadan to 5 during Ramadan in group A, and from 9 before Ramadan to 36 in group B (p<0.001).

Additionally, 12 months after attending READ, group A sustained HbA1C reduction.

CONCLUSIONS: Ramadan-focused education in diabetes can lead to positive lifestyle changes during Ramadan. It also reduces hypoglycemic incidence and can prevent weight gain during Ramadan.

Link: http://onlinelibrary.wiley.com/doi/10.1111/j.1464-5491.2010.02948.x/full

 

• 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

Ibrahim Salti, MD, PHD1, Eric Bénard, MD2, Bruno Detournay, MD, MBA2, Monique Bianchi-Biscay, MD3, Corinne Le Brigand4, Céline Voinet2, Abdul Jabbar, MD5 and on behalf of the EPIDIAR Study Group*

OBJECTIVE—The aim of this study was to assess the characteristics and care of patients with diabetes in countries with a sizable Muslim population and to study diabetes features during Ramadan and the effect of fasting.

RESEARCH DESIGN AND METHODS—This was a population-based, retrospective, transversal survey conducted in 13 countries. A total of 12,914 patients with diabetes were recruited using a stratified sampling method, and 12,243 were considered for the analysis.

RESULTS—Investigators recruited 1,070 (8.7%) patients with type 1 diabetes and 11,173 (91.3%) patients with type 2 diabetes. During Ramadan, 42.8% of patients with type 1 diabetes and 78.7% with type 2 diabetes fasted for at least 15 days. Less than 50% of the whole population changed their treatment dose (approximately one-fourth of patients treated with oral antidiabetic drugs [OADs] and one-third of patients using insulin). Severe hypoglycemic episodes were significantly more frequent during Ramadan compared with other months (type 1 diabetes, 0.14 vs. 0.03 episode/month, P = 0.0174; type 2 diabetes, 0.03 vs. 0.004 episode/month, P < 0.0001). Severe hypoglycemia was more frequent in subjects who changed their dose of OADs or insulin or modified their level of physical activity.

CONCLUSIONS—The large proportion of both type 1 and type 2 diabetic subjects who fast during Ramadan represent a challenge to their physicians. There is a need to provide more intensive education before fasting, to disseminate guidelines, and to propose further studies assessing the impact of fasting on morbidity and mortality.

PMID: 15451892

Link:http://care.diabetesjournals.org/content/27/10/2306

 

Summary of the Evidence:

Author (Date)	Level of Evidence	Sample/Setting(# of subjects/ studies, cohort definition etc. )	Outcome(s) studied	Key Findings	Limitations and Biases
Rouhani MH, Azadbakht L. 2014	Systematic Review	13 Studies (Searched keyword ‘Ramadan’ and chose most recent articles not already reviewed in previous studies regarding weight, lipid profile, diabetes, gestation, immune system and kidney function)   Included a total of  40 trials and articles included in meta-analysis and 44,606 people (combination of healthy, CKD, IDDM and NIDDM individuals)	Outcome of Ramadan fasting on weight, lipid profile, DM, immune system and gestation	● Risk of severe hypoglycemia for type 2 diabetics increased by seven-fold (from 0.4 to 3 events per 100 people per month) and hyperglycemia increased by five-fold (from 1 to 5 events per 100 people per month)● Hyperglycemia occurred from overeating during non-fasting hours or changes in dosage of anti-DM meds ● Decreased fasting BS by ~1 mmol/L during and after Ramadan than before Ramadan (before 8.59±3.07, during 6.91±2.03, after 7.42±3.06,p= 0.001) in Type 2 DM ● Increased serum fructosamine by ~30 µmol/L but still within suboptimal parameters  (indicator for overall glycemic control in preceding 2-3 weeks) (before 316 ±102.35, during 344.7± 92.15, after 352.6 ± 96.45, p=0.005) in Type 2 DM	●  Weak control of confounder in observational studies used in Meta Analysis● Many authors did not address confounder adjustments in the study so results may not be reliable ● Difference in results from different confounder adjustments (some reported increased weight and lipid levels, while others noted decreased) ● No set criteria for selecting the articles or does not explicitly describe method ● Short term follow-up of subjects (1 month) ● Also included IDDM, CKD and healthy pts in the study so may not be applicable to our pt but does differentiate NIDDM from IDDM
Melanie Y. L. Siaw,  Daniel E. K. Chew,  Matthias P. H. S. Toh,  Darren E. J. Seah,  Ruimin Chua,  Jielin Tan, Evonne Y. Q. Lee,  Sui Yung Chan, and Joyce Y. C. Lee 2016	Retrospective Cohort	Of 13,565 patients examined, 5,172 patients (38.1%) were eligible for this study. Stratified into three groups based on their mean HbA1c control before Ramadan: group 1 (HbA1c ≥10%), group 2 (HbA1c 7.1–9.9%) and group 3 (HbA1c ≤7%)	Impact of Ramadan fasting on HgA1C, systolic blood pressure, LDL, and triglycerides	● Blood glucose was most affected during Ramadan, particularly in patients with mean baseline HbA1c ≥10%.● Greatest reduction of HgA1C was observed in the group with HbA1c ≥10%. (p < 0.001) ● The type of antidiabetic agent used did not seem to contribute to glycemic changes. ● LDL and Triglyceride changes were insignificant ● Groups 2 and 3 showed small changes in systolic pressure (2mmHg; p <0.01)	●  Patient behavior could have contributed to changes in metabolic parameters (i.e. diet, exercise, lifestyle) since data was obtained from an electronic database.● Unable to capture incidents of acute complications (i.e. hypoglycemic events) ● Study is for Ramadan fasting in Singapore which might differ ● Missing data didn’t allow for BMI or fasting blood glucose values. ● Mean age of the groups studied were approximately  50-70 which does not include the age of our patient.
Babineaux SM et al. 2015	Retrospective Cohort Study	3777 patient(selection criteria: T1/T2 DM, medically managed, had 1 PCP visit within 3 months prior to Ramadan, older than 17 years old, Fasted during Ramadan, 1 PCP visit s/p Ramadan fast)  under 508 physicians in 13 countries were studied in this cohort study. 3250 (95.8%) of the patients had of T2DM.	Mean number of days patients fasted at different risk stratifications, number of hypoglycemic episodes during fasting period, factors associated with changes in DM treatment during Ramadan.	● Most patients were low risk (67%)● 39.3% of Patients had changes in DM management during Ramadan ● 20.4% of these changes were to pharmacotherapy, which were predominantly frequency changes ● 94% of T2DM patients fasted for at least 15 days and at 63.6% of patients fasted for the entire duration. ● 8.8% of patients had at least one episode of hypoglycemia ● Hospitalizations were rare.	● While this study consisted of a large population at 3,250 patients, there was no indication of the quality of patient data collected from medical practices.● The authors admit to the design of this studying having the possibility of recall bias which affects the validity of patient-reported hypoglycemia. ● While there are substantial numbers for each of the parameters recorded, this quantitative data does not allow for drawing causal relationships. ● There was multiple guidelines used by physicians a part of the 13 countries studied. ● There was inclusion of both T1DM and T2DM in statistical analysis of risks of fasting and changes in diabetic management. This skews the results when considering T2DM only even if the T1DM population is effectively ~4% of the T2DM population studied.
V. Bravis, et al. 2010	Retrospective case-control	111 Muslim patients with T2 DM were referred (self or by GP) to READ program. Group A (N=57)- attended 2 hour education program. Group B (N=54)- did not attend READ.Group A&B comparable in terms of sex, race, mean age, pre-Ramadan HbA1c, mean weight, # of hypoglycemic episodes, type of oral glucose lowering agents prescribed.	Establish mean weight before and after Ramadan as well as hypoglycemic episodes (self-monitored BG readings <3.5mmol/l with or without symptoms). Also compared HbA1c levels before Ramadan and 12 months later to assess sustainability of program.GraphPad Prism statistical package used for data analysis. All results reported with 95% CI.	Group A: mean weight reduction of 0.7kg (p<0.001, 95% CI 0.34-0.86).● Hypoglycemic events- 9 pre-Ramadan to 5 during Ramadan. ● 12 months after program- no HbA1c change in comparison to baseline (mean HbA1c diff: -0.13%, p=0.07, 95% CI -0.29-0.03) ● ARR in hypoglycemic events of 58.2% (p<0.001, 95% CI 55.6-63.7%)   Group B: mean weight gain of 0.6kg (p<0.001, 95% CI 0.34 to 0.86) ● Fourfold increase in hypoglycemic events from 9 pre-Ramadan to 36 during Ramadan (p<0.001) ● Mean HbA1c increase of 0.33% (P=0.03, 95% CI 0.1-0.59)	● Study done in London not US● Small population selection ● Selection bias (many participants were self-enrolled, may have had attributes that predispose them to better glycemic control and a greater effort at weight management)
Ibrahim Salti et al, 2004	Population-based retrospective transversal survey	In this study, 13 countries with predominantly Muslim population were selected, where 100 practitioners (endocrinologist & internist ) were chosen from each countries. A cluster sampling method was used to select a study population of 12,914 volunteers and eligible patient. In this group of patient, 8.7% with type 1 DM and 91.3 % type 2 DM.	This study try to determine the characteristics of patients with diabetes and assess their care in counties with sizable Muslim population. It also look at the presentation of diabetic patient during the holy month of Ramadan and the potential effect of fasting on patient well-being and on diabetes management.	● Frequency of hypoglycemic episodes per month and per patient significantly higher during Ramadan than during the preceding year for patient with type 2 diabetes● Severe incidence of hypoglycemia were observed in patient who changed their oral antidiabetic dose and insulin dose ● Hypoglycemic events is low in patient who did not change their lifestyle during Ramadan ● Severe hypoglycemia is frequent during Ramadan more than preceding year when their is a change in treatment regimen and physical activities during Ramadan	●This study was done 13 years ago new guidelines and research is probably available for better management of DM type 2 during ramadan period●Patient recruited reside in Urban area may not be representative of all diabetics ramadan observer patient ●The standard of care of these countries may not be representative of all countries with Muslim patient observing ramadan ●Majority of patients in this study are women, with  physical activity restricted to housework and who might not  have no tradition of sport

 

 

Conclusion(s):

Risks include severe hypoglycemia (x7) and hyperglycemia (x5), usually from overeating during non-fasting hours as well as change in dosage of medication. Small changes in SBP (2 mmHg) were reported in well controlled NIDDM. No significant changes in LDL and triglycerides decreased fasting BS and increased serum fructosamine was noted. Reduction of HbA1C was seen (specifically HbAIC ≥10%). To decrease risks associated Ramadan fasting, structured guidelines and patient education regarding diet, complications of fasting, effects of glucose monitoring (correlates with decreased hypoglycemic events and HbA1C from READ program), and medication timing has shown to be effective. Anti-diabetic medication and dosage should not be changed because it is associated with hyperglycemia and hypoglycemia. Additionally, varying types of anti-diabetic medications did not have significant changes in glycemia.

 

 

Clinical Bottom Line:

Type 2 diabetic patients may fast during Ramadan, but should be aware of its associated risks such as severe hypoglycemia and hyperglycemia. With proper education, healthcare and structured guidelines, these risks may be greatly decreased. Anti-diabetic medication and dosage should not be changed because it is associated with hyperglycemia and hypoglycemia and type of anti-diabetic med did not have significant changes in glycemia.