Diabetes Mellitus and Fasting Ramadan may 2015

Fasting Ramadan & Diabetes

Do It Right

Mohammad Daoud, MDConsultant Endocrinologist

KAMC –NGHA Jeddah- Saudi Arabia

DM & Fasting Ramadan Frequently asked questions

Can a diabetic patient fast Ramadan, safely?

What are the risks & benefits ?

What about diet and exercise?

How to adjust Medications ?

Remember…

Most of the data are “Expert opinion “ based

Avoid use of the terms “indications” or “contraindications” for fasting

Focus on better risk stratification and best medical advice that can be provided to the patient

Working with patients’ “Choice to Fast ” to make their fasting as safe as possible

Sura Al-BaqaraVerse 183 /185

O you who have believed, fasting is decreed / prescribed upon you as it was decreed upon those

before you that you may become righteous (may ward off (evil)

ا� ن�و م� م�� م ذ�ي � م ٱ م�ا ن�ي م�ا �� ـ م� مي ي�ا ص� ٱل م م� ي� ي ي� ي� ت� م� م� ن�و �� م م� م� �ن �� م �م م م� ن� �ذ م م! ذ� م ذ�ي � م ٱ م�ى م# م$ ذ� ن% م&ا م% (١٨٣)

* ن,‌ م& ن- م. �م م/ م0 م1 م�2 ٱ ن� �ن ذ�� م3 ذ1 م4 م& م/ ذ�‌* م!ا م0 ن6 م م7ٱ 8� م3 ن� م ٱ م م� :; ت �� م� م. م= م7 ذ< ��ا م � م 83? ت ن@ ن� م�� م0 ن� م ٱ ذ, ذ/. Aم Bذ ن��ن ـ8 ذ� � م ٱ م� مDا م� Eم ن0 م1 ي� م4 ي�ا ي�ن ي�ض�ا ت�ي * ي� م0‌ Gم ن�� H; �يا م م�� م م� IJ ت 3� م �ذ م/ 0; ت م6 Kم �ى �م م# م7 ي� م�� �ي �م يل ٱ م م� �ت م� ت�ي مي ي!ا ي� ي� �ي م� يل ٱ م م� �ت م" # ي ٱل م� ت�ي �ى مي �م م# م, �� م ٱ ا� ن70 م م� ن� ذ م7 Iم م�3 �ذ م ٱ ا� ن�و ذ& م� ن� ذ م7

م� ن70 �ن م2 م� م� ن� �م� �م م م7 م� �ن L� م3 م@ م�ا (١٨٥)

Fasting Ramadan

Muslims are almost approaching 2 billions persons

≈ 25% of Earth’s population…increasing

Like wise …DM-type 2 prevalence is

increasing

6

A large number of Muslim patients with diabetes fast during Ramadan

1The Pew Forum on Religion & Public Life. http://www.pewforum.org/The-Future-of-the-Global-Muslim-Population.aspx (Accessed March 2013); 2Al-Arouj M et al. Diabetes Care 2010;33:1895–902; 3Salti I et al. Diabetes Care 2004;27:2306–11; 4IDF Diabetes Atlas 5th edition. www.idf.org/diabetesatlas/5e/the-global-burden (Accessed March 2013); 5Whiting DR et al. Diabetes Res Clin Pract 2011; 94: 311–21; 6Beshyah SA. Ibnosina J Med Biomed Sci 2009;1:58–60

• The global prevalence of diabetes is projected to increase in emerging economies, including those with large Muslim populations4,5

• The pattern of daytime fasting and night-time meals and use of anti-diabetic treatment increases the risk of complications, including hypoglycaemia in patients with diabetes2,3

• Although the consensus from religious and medical leaders is that Muslims with diabetes are generally not obliged to fast6 many choose to do so2,3

1.6 billion(2010)

2.2 billion(2030)

Global Muslim population1

> 50 million people with diabetes are estimated to fast during Ramadan worldwide2,3

Fasting

Occurs during the month of Ramadan

and

Voluntary fasting ( ex: 1-2 days /wk; Monday and Thursdays 13th - 15th o days of Lunar months …)

Fasting Ramadan

Time of the year ...Never the same # of hours fasted Varies greatlyClimate ; Winter Vs. Summer

2015 Ramadan ; Summer June-July about 15 hours

(Fajr 4:14 to 4:25 am …Sunset 7:10 to 7: 10 pm)

Pathophysiology of fasting in Normal Individuals

Pathophysiology of fasting in Diabetes

Fasting Ramadan

Physiologic changes:

↓ Glucose and insulin levels

↑Glucagon / Catechol-amines → ↑Gluconeo-genesis ↑ Glycogeno-lysis

Free fatty acids → Ketones(Ketones are fuel by skeletal /cardiac muscles, liver, kidney, and adipose tissue, thus sparing glucose for continued utilization by brain and RBCs)

Fasting Ramadan and DMPatho-Physiologic changes:

Defected secretion of insulin :Risk of hyperglycemia /DKA

Defected secretion of Glucagon / Catecholamines :

Risk of hypoglycemia

EPIDIAR study group Results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. , Salti Iet al -Diabetes Care 2004;27:2306–2311

EPI.DIA.R trial (EPIdemilogy DIAbetes in Ramadan)

Multi-country epidemiological study (Algeria, Bangladesh, Egypt, India, Indonesia, Jordan, Lebanon, Malaysia, Morocco, Pakistan, Saudi Arabia, Tunisia & Turkey)

12,273 diabetic patients

Individuals who fast during Ramadan showed a high rate of acute complications

Diabetes Care, volume 28, NUMBER 9, September 2005

How Many Diabetics Fast?

Type 1 DM Type 2 DM

≈ 43% ≈ 79%

Salti I, et al. EPIDIAR study. Diabetes Care 2004;27:2306

50% … did not change their lifestyle

Lifestyle changes involved :Physical activitySleep duration

Food, sugar, and fluid intake

Only 25% on OADs adjusted Rx 1/3 rd on insulin

adjusted Rx

Fasting Ramadan and DM

Risk stratification Fatwa : Is it due for a

review?

والشرع Fiqh and Medicineالطب

www.fiqhacademy.org.sa

اإلسالمي الفقه مجمعالدولي

اإلسالمي الفقه لمجمع عشرة التاسعة الدورة والتوصيات القراراتالشارقة - إمارة )الدولي المتحدة ( العربية اإلمارات دولة

26-30 ( إبريل ( األولى 1 -5- م / 2009نيسان 1430جمادى

Fiqh Islamic Academy الدولي اإلسالمي الفقه مجمع

Patients are divided into groups according to risk:

First group: Very high risk

Second group: High risk

www.fiqhacademy.org.sa

1st and 2nd groupsshould not fast

حصول إ من التأكد على مبني والثانية األولى الفئتين حكم نالطبيب يقدره ما بحسب بحصوله الظن غلبة أو البالغ الضرر

المختص،�� تنطبق الثقة الذي المريض على شرعا فيتعينفيهما الواردة الحاالت إحدى له عليه يجوز وال يفطر أن

نفسه الصيام عن للضرر درءا ، ،

( : تعالى (النساءلقوله: ( رحيما بكم كان الله إن أنفسكم تقتلوا (وال

المجمع بالصيام ويؤكد تضرره مع صام من أنصومه فإنه صحة مع يأثم

Very High Risk

High RiskDIABETES CARE, VOLUME 33, NUMBER 8, AUGUST 2010

Note: This classification is based largely on expert opinion and not on scientific data derived from clinical studies

Fiqh Islamic Academy الدولي اإلسالمي الفقه مجمع

www.fiqhacademy.org.sa

Third group: Moderate risk

Fourth group: low risk

3rd and 4th groupsshould fast

المجمع هاتين ورأى لمرضى اإلفطار جواز بعدمال الفئتين الطبية المعطيات كون إلى استنادا ،

بصحتهم ضارة مضاعفات احتمال إلى تشيرمن يستفيد قد منهم الكثير إن بل وحياتهم

وأن الحكم بهذا االلتزام األطباء داعيا ، الصيامحدة على حالة لكل المناسب العالج يقدروا

Moderate Risk

Low Risk

DIABETES CARE, VOLUME 33, NUMBER 8, AUGUST 2010

Note: This classification is based largely on expert opinion and not on scientific data derived from clinical studies

Fasting Ramadan Risks

Risks associated with FASTING in patients with diabetes

Diabetes Care, volume 28, NUMBER 9, September 2005

1. Hypoglycemia

2. Hyperglycemia : DKA / HHS

3. Dehydration and thrombosis

4. Hospitalizations

EPIDIAR study: fasting during Ramadan increases the risk of severe hypoglycaemia and hyperglycaemia in

patients with T2DM30

1Salti I, et al. Diabetes Care 2004;27:2306–11; 2Al-Arouj M, et al. Diabetes Care 2010;33:1895–902

Inci

denc

e (e

vent

s/10

0 pa

tien

ts/m

onth

)

Series10

1

2

3

4

0.4

3

Series10123456

1

57.5-fold increase*

5-fold increase

P<0.0001 P<0.0001

EPIDIAR = EPIdemiology of DIAbetes and Ramadan; T2DM = type 2 diabetes mellitus

11,173 patients with T2DM; 78.7% chose to fast for at least 15 days during Ramadan1

Higher risk of severe Hypoglycemic events†

in overall population during Ramadan‡1,2

Higher risk of severe Hyperglycaemic events†

in overall population during Ramadan‡1,2

Pre-Ramadan

During Ramadan†Events requiring hospitalization in overall population with T2DM; ‡compared with previous months

* There was a 7.5 fold difference of hypoglycaemia in overall population fasting during Ramadan. For patients who fasted for > 15 days difference was, 6.7 fold

Probably

Under-estim

ated

Fasting RamadanHyper- glycemia Risk

Higher risk of hospitalization in both types of DM

Type 2DM 5 X increase in incidence of severe

hyperglycemia

EPIDIAR study group / Diabetes Care 2004;27:2306–2311

Type 1 DM 3 X increase

More DKA with prior poor control

Fasting RamadanHyper- glycemia Risk

Benghazi Diabetes and Endocrine Centre (BDEC)

493 T2DM patients fasting during Ramadan

10.7% experienced hyperglycemia

Nearly 20% of SU-Treated Muslim Patients With Type 2 DM Experienced Symptomatic Hypoglycemia During

Ramadan Fasting1

Mean daily doses of SUs were: 2.8 mg for glimepiride, 129.3 mg for gliclazide, 10.7 mg for glibenclamide (glyburide), and 6.6 mg for glipizide.SU=sulfonylurea.1. Aravind SR et al. Curr Med Res Opin. 2011;27(6):1237–1242.

16.814.0

25.627.6

19.7

0

5

10

15

20

25

30

Patie

nts,

%

GlimepirideGliclazideGlibenclamideGlipizideOveralln=428 n=386 n=535 n=29 n=1378

Incidence of Symptomatic Hypoglycemia During Ramadan in 2009

by Treatment Group

6.7% of SU-Treated Muslim Patients With Type 2 DM Experienced Severe Hypoglycemia During Ramadan

Fasting1

Incidence of Severe Hypoglycemia During Ramadan in 2009by Treatment Group

SU=sulfonylurea.1. Aravind SR et al. Curr Med Res Opin. 2011;27(6):1237–1242.

5.1

2.6

10.8

6.9 6.7

0

2

4

6

8

10

12

Patie

nts,

%

GlimepirideGliclazideGlibenclamideGlipizideOverall

n=428n=386

n=535 n=29 n=1378

Dehydration Orthostatic hypotension esp. with

autonomic neuropathy Syncope, falls, injuries, and bone

fractures

-Adjust patients' BP medication -Drink sugar free / caffeine free drinks frequently

throughout the evening and before dawn. 

Fasting Ramadanother risks

Thrombosis ? Volume contraction / Increased blood viscosity

may exacerbate the hyper- coagulable state **

Increased incidence of retinal vein occlusion #

No data concerning the effect of fasting on mortality

Fasting RamadanOther risks

**24Akhan G, Kutluhan S, Koyuncuoglu HR. Is there any change in stroke incidence during Ramadan? Acta Neurol Scandin 2000;101:259–261#25 Alghadyan AA. Retinal vein occlusion in Saudi Arabia: possible role of dehydration.Ann Ophthalmol 1993;25:394–398@Temizhan A, et al B. Is there any effect of Ramadan fasting on acute coronary heart disease events? Int J Cardiol 1999;70:149–153

DM and Fasting RamadanManagement

Pre Ramadan assessment Individualization Frequent monitoring of glycemia Nutrition & Exercise Breaking the fast Medications adjustment

Diabetes Care, volume 28, NUMBER 9, September 2005

Pre-RAMADAN assessment

Medical Assessment:1-3 months before RAMADANSpecific attention to the:

Well-being of the patientGlycemia, BP and lipids

Specific medical advice for those who wish to fast against medical recommendations

Necessary changes in the diet or medication regimen should be made

Diabetes Care, volume 28, NUMBER 9, September 2005

Pre-RAMADAN assessment

Educational Counseling: Educate the patient and his family on:

Signs & symptoms of hypoglycemiaBG monitoring ; risk of

hypoglycemia,even not fasting !!?Meal planningPhysical activityMedication administrationManagement of acute complications

DM and FastingManagement

-Decide on fasting Vs. non fasting

-Diet: assess pattern / amounts of food intake /habits ; to be able to match with a good Rx plan

Pre Ramadan fasting experience / prior Rx plan success

DM and FastingTrial fast in pre-Ramadan period

For 3 consecutive days before Ramadan should be advisedEx: Fasting the 13th, 14th, and 15th day of Shaban.

Can assess the risks of hypo- and hyper glycemia

Can help as a guide for medications adjustments

DM and FastingBGM

Frequent monitoring of glycemia: esp. in the first few days esp. with Insulin use or insulin secretagogues

To verify Safe DM control:Early morning , noon ,late afternoon , before sunset

To verify Adequate DM control:After Iftar , late night and before Sohour

BGM for high risk groups

Consider BGM done at the following times

1. Pre-Suhur2. 2 hours post-Suhur3. Midday4. Pre-Iftar5. 2 hours post-Iftar6. Whenever symptoms of hypoglycemia occur7- Midnight blood glucose if needed Management of Type 2 diabetes in Ramadan: Low-ratio premix insulin working group practical advice

NutritionAim to not overeat

-Healthy and balanced diet-Avoid large quantities of fried foods and CHO-meals

- Sohour (pre-dawn meal): - Delay as late as possible - Use “complex” carbohydrates

-Aim at maintaining a constant body mass

- Plenty of fluid during non-fasting hours

Dietary Patterns & Glycemic Control and Compliance

to Dietary Advice Among Fasting Patients With DM During Ramadan

Positive pattern CHO intake < 50 % of energy;

Distributed (i.e:3-4 meals)= Effective diet assuring

normoglycemia

= Better DM control

Diabetes Care 2014;37:e47–e48 | DOI: 10.2337/dc13-2063

Dietary Patterns & Glycemic Control and Compliance

to Dietary Advice Among Fasting Patients With DM During Ramadan

Diabetes Care 2014;37:e47–e48 | DOI: 10.2337/dc13-2063

Activity/Exercise

-Maintain Normal levels of physical activity/ safe timing

-Avoid Excessive physical activity : Higher risk of hypoglycemia (especially before Iftar)-Avoid late daytime (close to Iftar time) sleeping

-High risk of hyperglycemia in poorly controlled DM 1

-Prayer activity is generally safe including Ishaa’ and Taraweeh

- BG ≤ 60 mg/dl [3.3 mmol/l])

- BG < 70 mg/dl (3.9 mmol/l) early in the day

Stop fasting even if the hypoglycemia occurs close to the time of Iftar

- BG > 300 mg/dl ( 16.7 mmol/l) ; esp. Type 1 DM

ketones in blood or urine should be checked

- Sick days / Unusual symptoms (Vomiting, SOB,…)

Frequent Monitoring KeyBreak the Fast if Necessary

DM and Fasting Adjustment of Medications

DM and FastingDM Type 1

Don’t Fast ?

Fasting at Ramadan carries a very highrisk for people with type 1 diabetes

Still with the new safer formulation of insulin ; Fasting maybe possible but

with possible compromise of inadequate control

DM Type 1

If the patient Insists on fasting :Basal-bolus regimen

(or Insulin pump) is the preferred protocol of

management

Tends to be safer, with fewer episodes of hyper- and hypoglycemia

Lispro Compared with Regular Human Insulin During Ramadan

Kadiri A et al. Diabetes Metab (Paris) 2001;27:482-6.

0

3

5

4

1

2

Fasting 1-h 2-hPostprandial time

*

HumalogRegular insulin

* P = 0.026

0

3

5

4

1

2

Fasting 1- 2-Postprandial time

*

HumalogRegular insulin

* P = 0.026

Postprandial Blood GlucoseB

lood

glu

cose

exc

ursi

on (m

mol

/L)

Lispro Compared with Regular Human Insulin During Ramadan

Kadiri A et al. Diabetes Metab (Paris) 2001;27:482-6.

Epi

sode

s of

hyp

ogly

cem

ia

Hypoglycemia by Time of Day

0

5

10

15

20

000

Insulin LisproRegular insulin

Sunrise meal

Sunrise meal

Sunset meal

2-h 6-h 2-h 6-h

27

5

12

27

11

5

2

43

0

5

10

15

20

000

Regular insulin

Sunrise meal

Sunrise meal

Sunset meal

2-h 6-h 2-h 6-h

27

5

12

27

11

5

2

43

Premix analogue (Vs. human premix insulin)

Better average glycemic control

Better meal time flexibility

Less likely to cause post-prandial hypoglycemia

DM and FastingType 2 DM

Diet-controlled / Metformin Low risk of Hypoglycemia

Fasting is of benefit /Safe

Change dosing schedule to after sunset meal (2/3) and before dawn meal (1/3)Or Full dose at Iftar (ex:Metfromin XR)No need to decrease dose if Solo

Type 2 DMSulfonylureas

Risk of hypoglycemia If well adjusted …can fast with least possible

risk

Avoid use of Chlorpropamide ,Glyburide /Glibenclamide

Gliclazide, Glimepiride and Glipizidehave lower risk

Short-Acting Insulin Secretagogues

Repaglinide and Nateglinide

Taken twice daily before the sunset and predawn meals.

Repaglinide Vs Glibenclamide : less hypoglycemia *

*Mafauzy M. Repaglinide versus glibenclamide treatment of type 2 diabetes during Ramadan fasting. Diabetes Res Clin Pract 2002;58:45–53

Type 2 DMSafer New Choices

Glitazones ;PioglitazoneGlucosidase inhibitors

Acarbose,miglitol, and voglibose Bromocriptine

GLP-1 Agonists : Exenatide and Liraglutide,… DPP-4 -I : Sitagliptin, Linagliptin ,…

No hypoglycemia on its own Provides an excellent choice in

Ramadan

DPP-4 I vs SU

Patients (1066) on SU (with or without Metformin) Randomized just before Ramadan to:

Sitagliptin Vs SU Hypoglycemia:

4.8 %: Sitagliptin group 14.3 %: SU group

Had to break fast: 6.3 %: Sitagliptin group 10.3 %: SU group

Al Sifiri S, et al. Int J Clin Pract. 2011;65:1132

Incidence of symptomatic hypoglycemia in Muslim patients with Type 2 DM (Ramadan)

The International Journal of Clinical Practice ,November

2011,65,11,1132-1143 Sitagliptin

Gliclazide MR

Conclusions: Among > 1000 patients

The incidence of Hypoglycemiawas lower with Gliclazide relative to the other sulphonylurea agents and similar

to that observed with Sitagliptin

Before Ramadan During RamadanPatients on “Diet and Exercise”

- No change- Modify time /intensity of exercise- Ensure adequate fluid intake

Metformin -Iftar: 1,000 mg-Sohour: 500 -1000 mg

DPP4 inhibitor As usual at night

Glitazone As usual at nightGlinide As usual at night

Treatment Recommendations

Before Ramadan During RamadanSulfonylurea Once Daily: Morning dose.e.g., Gliclazide MR

Iftar: Full Morning Dose May cut down by 20-30%

Sulfonylurea Twice Daily: Morning & Evening dose.e.g., Gliclazide 80-160 mg BD

-Iftar: Full Morning Dose-Sohour: ½ Evening Dose (or skip ?)

Treatment RecommendationsMajority of our type 2 diabetic patients are treated

with Sulfonylurea & Metformin

Patients Treated With Insulin

-RAI analog Vs. Regular Insulin Less hypoglycemia and smaller postprandial glucose excursions

-Long acting Basal insulin (Glargine ) with RAI analog at Iftar and RAI analog at Sohour

Before Ramadan During RamadanPremixed insulin 30 Morning: (ex: 30 U)Dinner: (ex :20 U)

Iftar: Full Morning Dose (30 U)Sohour: ½ Dinner Dose (10 U) (? 50% reduction at Sohour ?)

Consider switching patients who are on either:

Mixed or intermediate-acting insulins to basal insulin

Split Mixed (R+N)R+0+RN+0+N

R+0+50 % of RN+0+50% of N (50% reduction at Sohour)

R+R+R0+0+N

R+R+50% of R0+0+50% of N (50% reduction at Sohour)

Treatment Recommendations

Before Ramadan

During Ramadan

Rapid-acting insulin;Ex: Aspart

Usual dose of should be taken with sunset meal

RAA insulin can work immediately after meals.Decrease predawn dose in half (?omit )

Basal AnalogueEx: Glargine

At the same time Up to 20-40 % dose reduction

Treatment Recommendations

DM and Fasting RamadanCONCLUSIONS

Fasting carries a risk for many patients

(DM 1 > DM 2)

Commonest concerns :Hypoglycemic and Hyperglycemic

Risk assessment = Advice who

should be exempted /shouldn’t fast

DM and Fasting RamadanCONCLUSIONS

Fasting Can Be Accomplished, but Care Must Be Taken

-Majority of DM patients can fast safely -If patients insist on fasting ;Work with

them -Adjusting medications is an Art >>

Science-Certain agents provide safer control

( ex: Incretins; GLP-1 R agonists and DPPr i ,MFN, Acarbose ,Glinides)

DM and FastingCONCLUSIONS

Education

Diet control

Daily activity

Drug regimen adjustment

Conclusion

Until guidelines are available, the most important management strategy for

health-care providers is

IndividualizedStructured education

Before and during Ramadan

Ramadan Kareem

References 1-Recommendations for Management of Diabetes During Ramadan , DIABETES CARE, VOLUME 33, NUMBER 8, AUGUST 2010

2-Recommendations for Management of Diabetes During Ramadan DIABETES CARE, VOLUME 28, NUMBER 9, SEPTEMBER 2005 2305

3-Dietary Patterns and Glycemic Control and Compliance to Dietary Advice Among Fasting Patients With Diabetes During Ramadan Diabetes Care 2014;37:e47–e48 | DOI: 10.2337/dc13-2063

4-Incidence if hypoglycemia among Muslims fasting Ramadan : SU vs Sitagliptin ,Al Sifiri S, et al. Int J Clin Pract. 2011;65:1132

5- Long-acting oral hypoglycemic agents (OHA) must be used more caution Hassan Chamsi-Pasha and Khalid S. Aljabri. Avicenna J Med. 2014 Apr- Jun; 4(2): 29–33

References 6- 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

7- Karamat MA, Syed A, Hanif W. Review of diabetes management and guidelines during Ramadan. J R Soc Med. 2010;103:139–47

8- Management of Type 2 diabetes in Ramadan: Low-ratio premix insulin working group practical advice ,Indian J Endocrinol Metab. 2014 Nov-Dec; 18(6): 794–799.Mohamed Hassanein, Mohamed Belhadj,1 Khalifa Abdallah,2 Arpan D. Bhattacharya,3 Awadhesh K. Singh,4 Khaled Tayeb,5 Monira Al-Arouj,6 Awad Elghweiry,7 Hinde Iraqi,8 Mohamed Nazeer,9 Henda Jamoussi,10 Mouna Mnif,11Abdulrazzaq Al-Madani,12 Hossam Al-Ali,13 and Robert Ligthelm