1 Diabetes & Ramadan Dr. Nizar Albache Head of Diabetes Research Unit, Aleppo University...

1

Diabetes & Ramadan

Dr. Nizar Albache

Head of Diabetes Research Unit, Aleppo UniversityPresident of Syrian Endocrine Society

Carlton citadel Hotel , Aleppo, July 20th

Diabetes & Ramadan

Why Muslims should fast ?

When Muslims should fast ?

What are the metabolic changes during fasting and their consequences on diabetes control ?

Who should not fast ( exempted) ? Religious recommendations Medical recommendations

What are the diet advices ?

What are the therapeutic changes or recommendations ?

2

3

Diabetic Patients in the Muslim Countries

Muslims: 1.1-1.5 Billion around the world

The prevalence of type 2 diabetes in the Muslim World is very high ( 10-20 %)

What percentage of diabetic patients actually fast ?

20 %

4

TimeNo

diabetesPre-

diabetesType 2

Diabetes

T2 Diabetes:Insulin resistance + insulinopenia

Glycemia

Insulin secretion

Insulin resistance

5

Decline of ß-cells function determinesthe progressive nature of T2DM

-12 -10 -8 -6 -4 -2 0 2 4 6

0

20

40

60

80

100

Time of diagnostic

Time (years)

ß-c

ell f

unct

ion

(%of

nor

mal

by

HO

MA

) ?

HOMA=homeostasis model assessment.UKPDS Group. Diabetes 1995;44:1249-58.Adapted from Holman RR. Diabetes Res Clin Pract 1998;40(suppl 1):S21-5.

Pancreatic function = 50% of normal

6

ADA/EASD Consensus Guidelines Treatment Algorithm, 2006

Additional medications: insulin, sulfonylureas or TZDs, on the top of metformin

Diagnosis

Lifestyle intervention+ Metformin

HbA1c 7%

Add basal insulin

(Most effective)

Add sulfonylurea

(Least expensive)

Add glitazone

(No hypoglycemia)

Step 1

Step 2

Nathan DM, et al. Diabetes Care 2006;29:8.

7

ADA/EASD guidelines recommend use of basal insulin as early as the second step in type 2 diabetes management

At diagnosis:Lifestyle + Metformin

Lifestyle + Metforminplus

Basal insulin

Lifestyle + Metforminplus

Sulfonylureaa

Lifestyle + Metforminplus

Intensive insulin

Tier 1: well-validated core therapies

STEP 1 STEP 2 STEP 3

Tier 2: Less well validated therapies

Lifestyle + Metforminplus

PioglitazoneNo hypoglycaemia

Oedema/CHFBone loss

Lifestyle + metforminplus

GLP-1 agonistb

No hypoglycaemiaWeight loss

Nausea/vomiting

Lifestyle + Metforminplus Pioglitazoneplus Sulfonylureaa

Lifestyle + Metforminplus Basal insulin

a. Sulfonylureas other thanGlybenclamide or chlorpropamide

b. Insufficient clinical safety data; CHF,congestive heart failure

Nathan DM, et al. Diabetes Care 2008;31:1-12.

Check HbA1C every

3 months until <7%. Change

treatment if HbA1C is ≥7%

8

Types 2 Diabetes

Recommendations in case of oral bitherapy failure:

Diet and lifestyle recommendations

Target not reached at 6 monthsHbA1c >7%

Treatment

Met + SUMet + GlitazonesSU + Glitazones

Oral triple therapyMet+SU + GIitazones

Insulin therapy

HbA1c >8%

New IDF guidelines 2011 in type 2 diabetes:

Two key changes : A change in the HbA1c target to 7.0% (previously 6.5%) Algorithm TT :effectiveness, harm, cost and global availability

Each step of the algorithm recommends a preferred therapy and also alternative therapies:

1. Metformin as first line therapy(unless contraindicated)2. Sulfonylureas are the recommended second line 3. Third line therapy is either a third oral agent or insulin (basal or

premixed)4. Finally insulin should be used if the choice has been to use an

oral agent as the third step, or intensification of insulin therapy if insulin had been chosen in the previous step.

Stephen Colagiuri, Boden Institute, University of Sydney, Australia; MGSD CASABLANCHA 2011

9

10

Considerations for Fasting During Ramadan

Religious Considerations: imposition, obligation

Exemption of the sick

البقرة

=183 � �وا آم�ن �ذ�ين� ال �ه�ا ي� أ �ا �ام� ي الص#ي �م� �ك �ي ع�ل �ب� �ت �م�ا ك ك

�ق�ون� �ت ت �م� �ك �ع�ل ل �م� �ك �ل ق�ب م�ن �ذ�ين� ال ع�ل�ى �ب� �ت ك

=184 م�نك�م �ان� ك ف�م�ن م�ع�د�ود�ات5 �ام:ا �ي و� م�ر�يض:اأ� أ

�ذ�ين� ال و�ع�ل�ى �خ�ر� أ 5 �ام �ي أ م#ن� ف�ع�د�ة< ف�ر5 س� ع�ل�ىف�ه�و� ا �ر: ي خ� �ط�و�ع� ت ف�م�ن ك�ين5 م�س� ط�ع�ام� �ة< ف�د�ي �ه� �ط�يق�ون ي

�م�ون� �ع�ل ت �م� �نت ك �ن إ �م� �ك ل �ر< ي خ� � �ص�وم�وا ت �ن و�أ �ه� ل �ر< ي خ�

=185 ه�د:ى آن� �ق�ر� ال ف�يه� �نز�ل� أ �ذ�ي� ال م�ض�ان� ر� ه�ر� ش�ه�د� ش� ف�م�ن ق�ان� �ف�ر� و�ال �ه�د�ى ال م#ن� �ات5 #ن �ي و�ب �اس� #لن لع�ل�ى و�

� أ م�ر�يض:ا �ان� ك و�م�ن �ص�م�ه� �ي ف�ل ه�ر� الش� �م� م�نك�ر�يد� ي �خ�ر� أ 5 �ام �ي أ م#ن� ف�ع�د�ة< ف�ر5 � س� و�ال ر� �س� �ي ال �م� �ك ب �ه� الل

ر� �ع�س� ال �م� �ك ب �ر�يد� ع�ل�ى ي �ه� الل � وا #ر� �ب �ك �ت و�ل �ع�د�ة� ال � �وا �م�ل �ك �ت و�لون� �ر� ك �ش� ت �م� �ك �ع�ل و�ل �م� ه�د�اك م�ا

الدولي اإلسالمي الفقه مجمع 2010فتوى : فئات اربع إلى بالسكري المصابين تصنيف تم

: األولى الفئةذوو بالسكري جدا المصابين الكبيرة االحتماالت

مؤكدة بصورة الخطيرة :للمضاعفات

الفقدان • أو المتكرر أو الشديد السكر هبوط حدوثتسبق ) التي الثالثة األشهر خالل السكر بنقص الحس

رمضان(السكرية• الغيبوبة فرط ( حدوث أو الكيتوني الحماض

رمضان( تسبق التي الثالثة الشهور خالل التناضحللسكري• المرافقة االخرى الحادة األمراضشاقة• بدنية أعماال مضطرين يمارسون

كلى• غسيل لهم يجري

الحمل • اثناء

: الثانية الفئةالصيام نتيجة مضاعفات لحدوث كبير احتمال

وقوعها والتي األطباء ظن على :يغلب بـ وتتمثل

السكر )• ( 300-180ارتفاع السكري/ الخضاب و دسل <ملغ10%

كلوي• قصور

الكبيرة• والشرايين القلب اعتالل

عليهم• إضافية oأخطارا تضيف أخرى أمراض

بمفردهم• يسكنون الذين

أخرى• بأمراض المصابون السن كبار

العقل• على تؤثر عالجات يتلقون

الدولي اإلسالمي الفقه مجمع 2010فتوى

: والثانية األولى الفئتين حكم•

الصيام له يجوز وال يفطر ان المريض على oشرعا o فيتعين درءا ، ) ( : vةwكxل yهzالت vلwى إ yمxيكvدyيw بvأ y وا xقyلxت wالwو تعالى لقوله نفسه، عن للضرر

البقرة

عليهم، • الصيام خطورة لهم يبين ان المعالج الطبيب على يتعين كماغالب - في تكون قد بمضاعفات إلصابتهم الكبيرة واالحتماالت

حياتهم- أو صحتهم على خطيرة الظن

الدولي اإلسالمي الفقه مجمع 2010فتوى

: الثالثة الفئةالصيام نتيجة للمضاعفات للتعرض المتوسطة االحتماالت ذوو

المستقرة الحاالت ذوي بالسكري المصابين ذلك ويشملبالـ عليها .S.Uوالمسيطر

: الرابعة الفئةالصيام نتيجة للمضاعفات للتعرض المنخفضة االحتماالت ذوو

المستقرة الحاالت ذوي بالسكري المصابين ذلك ويشملالعالجات بتناول أو الحمية بمجرد عليها .METFوالمسيطر

: والرابعة الثالثة الفئتين حكم

ال الطبية المعطيات الن اإلفطار، الفئتين هاتين لمرضى يجوز الالكثير ان بل وحياتهم بصحتهم ضارة مضاعفات احتمال إلى تشير

. الصيام من يستفيد قد الحكم منهم بهذا االلتزام الطبيب وعلى. حدة على حالة لكل المناسب العالج يقدر وان

الدولي اإلسالمي الفقه مجمع 2010فتوى

Duration of Fast

• There is variation in the number of days:

Depends on the moon sighting.

• There is variation in the number Fasting hours:

Depends on the season.

• There is variation in the Temperature:

• Effect on total body fluid.

17

Hours of fast during the month of Ramadan Globally

18

Day hours 24

22

20

18

16

14

12

10

8

6

4

2

0

Winter in the lower pale and in the summer upper pale for the year

رمضان :2011حلب3.55إمساك 19.44إفطار

ساعة 15صيام=

الحرارة 44درجة

Change in blood glucose profile

19

0

5

10

15

20

12 6 12 6 12

Daily glucose profile during the month of Shawal

Patients were asked to test their blood sugar every two hours with a glucometer for one day during the month of Shawal as part of diet change study regardless of their diabetes management. There are three peaks for serum blood glucose following meals. The highest been following lunch and the lowest following breakfast with a mean daily glucose at 10.2 mmol/L.

Change in blood glucose with meal timing

20

Daily glucose profile during the month of Ramadan

Change in blood glucose with meal timing

21

Risk of hypoglycemia

– The change in meal time will affect the glucose level through the day.– There will be a prolonged period of fasting with risk of hypoglycemia.– Sever hyperglycemia occur following the main meal ( ie: Eftar ).

Ramadan Diabetes Study ( unpublished data )

Daily glucose profile for both months

Biochemistry of Fasting

Carbohydrate metabolism

In normal subjects fasting will:

• Decrease in serum glucose to 3.3 - 3.9 mmol ( 60-70 mg/dl ).

• Gluconeogenesis by liver will stop further drop of blood glucose.

• Insulin secretion will decrease but glucagon will increase.

• In diabetic subjects fasting will:

• Blood glucose fell within physiological limits if properly controled.

• Drug induced hypoglycemia is the commonest complications.22

Dietary Change

23

28002950

2500

2600

2700

2800

2900

3000

SHABAN RAMADAN

Calorie ChangeTotal daily calorie intake before and

during

24

25

   EPI.DIA.REPI.DIA.R EPIEPIdemiologydemiology ofof DIAbetesDIAbetes

Ramadan 1422/2001Ramadan 1422/2001

Salti IS et al Diabetes Care 27: 2306-2311, 2004

26

Number of patients by country )N = 12,914(

994

889

981

871

827

1,066

837

927

1,089

1,000

1,370

1,007

1,056

0 200 400 600 800 1000 1200 1400 1600

Turkey

Tunisia

Saudi Arabia

Pakistan

Morocco

Malaysia

Lebanon

Jordan

Indonesia

India

Egypt

Bangladesh

Algeria

Overallpatientswith DM

Salti IS et al Diabetes Care 27: 2306-2311, 2004

27

Repartition by type of DM

27

13

15

10

10

8

8

7

6

4

4

2

1

2

10

5

8

7

7

5

4

3

71

78

80

83

83

81

86

88

91

92

94

97

93

11

1

6

2

0 20 40 60 80 100

Saudi Arabia

Morocco

Egypt

Jordan

Tunisia

Algeria

Pakistan

Lebanon

Turkey

Malaysia

India

Bangladesh

Indonesia

type 1 DM

DMunclassifiable

type 2 DM

)%(type 1 DM = 1,070 patients )8.3%(

type 2 DM = 11,173 patients )86.5%(DM unclassifiable = 671 patients )5.2%(

Salti IS et al Diabetes Care 27: 2306-2311, 2004

28

Fasting during Ramadan )1( )% of patients who fast > 1 day(

49

24

77

55

12

92

52

45

70

58

6152

80

0 20 40 60 80 100

Turkey

Tunisia

Saudi Arabia

Pakistan

Morocco

Malaysia

Lebanon

Jordan

Indonesia

India

Egypt

Bangladesh

Algeria

73

73

89

77

83

95

78

88

83

91

9592

91

0 20 40 60 80 100

Turkey

TunisiaSaudi Arabia

Pakistan

MoroccoMalaysia

Lebanon

JordanIndonesia

India

EgyptBangladesh

Algeria

DM type 1 DM type 2

)%(

DM type 1 = 54% DM type 2 = 86%Overall population

29

Results

Hyperglycemia 3-fold increase in T1D 5-fold in T2D (from 1 to 5 events/100pts/month)

Excessive reduction in insulin doses (1/3-1/4 of patients change their insulin dose or OHAs)

Increase in food intake (sugar)

Severe Hypoglycemia 4-fold increase in type 1 diabetes 7-fold increase in type 2 diabetes

Salti IS et al Diabetes Care 27: 2306-2311, 2004

30

The need for guidelines for physicians and patients

The Diabetes and Ramadan Advisory Board

(supported by Aventis Intercontinental)

Chairmen:

Ibrahim SALTI, Lebanon; Abdul JABBAR, Pakistan

Members:

Kamel Ajlouni, Jordan; Khalid AL-RUBEAAN, Saudi Arabia;

Fahmy AMARA, Egypt; Mohamed BELHADJ, Algeria; Jamalleddine BELKHADIR, Morocco;

Aissa BOUDIBA, Algeria; Said Nouou DIOP, Senegal; Ugur GORPE, Turkey;

Farid HAKKOU, Morocco; Ak.Azad KHAN, Bangladesh;

Adrien Lohourignon LOKROU, Ivory Coast; Jean-claude MBANYA, Cameroon;

NAGATI, Tunisia; Nadim RAIS, India;

Pradana SOEWONDO, Indonesia; W.Mohamed WAN BEBAKER, Malysia

31

RECOMMENDATIONS OF THE ADVISORY GROUP

In principle, all patients with type 1 should not fast.

However, if a patient insists against medical advice, please consider the following:

Absolute Contra-indications:

Brittle DM (as defined by the American Diabetes Association)

Patients on insulin pump Patients on multiple insulin injections per day Ketoacidosis or severe hypoglycemia in the last 3 months

before Ramadan People living alone Advanced micro- or macro-vascular complications Pregnancy and lactation

Salti IS et al for the Diabetes and Ramadan Advisory Board. International Medical Recommendations for Muslim Subjects with Diabetes Mellitus Who Fast During the Month of Ramadan. Clinical Diabetes- Middle East, 3:143-145, 2004

32

RECOMMENDED RAMADAN GUIDELINES FOR PATIENTS WITH DIABETES MELLITUS Type 2:Continued

Patients with one or more of the following are advised not to fast:

Physiological conditions: Lactation

Co-existing major medical conditions such as:

Acute peptic ulcer Pulmonary Tuberculosis and uncontrolled infections Severe bronchial asthma People prone to urinary stones formation with frequent

Urinary Tract Infections Cancer Overt cardiovascular diseases (recent MI, unstable

angina) Severe psychiatric conditions Hepatic dysfunction (liver enzymes > 2 x ULN)

Salti IS et al for the Diabetes and Ramadan Advisory Board. International Medical Recommendations for Muslim Subjects with Diabetes Mellitus Who Fast During the Month of Ramadan. Clinical Diabetes- Middle East, 3:143-145, 2004

33

RECOMMENDATIONS OF THE Advisory Group-2

Relative Contra-indications (fast with risk):

Well controlled type1 DM patients No diabetes keto-acidosis (DKA) No recent hypoglycemia Not more than 2 insulin injections per day

Salti IS et al for the Diabetes and Ramadan Advisory Board. International Medical Recommendations for Muslim Subjects with Diabetes Mellitus Who Fast During the Month of Ramadan. Clinical Diabetes- Middle East, 3:143-145, 2004

34

RECOMMENDED RAMADAN GUIDELINES FOR PATIENTS WITH DIABETES MELLITUS Type 2:

Patients with one or more of the following are advised not to fast:

Conditions related to diabetes:

Nephropathy with serum creatinine more than 1.5 mg/dL

Severe retinopathy

Autonomic neuropathy: gastroparesis, postural hypotension

Hypoglycemia unawareness

Major macrovascular complications: coronary and cerebrovascular

Poorly controlled diabetes (Mean Random BG > 300) Multiple insulin injections per day

Salti IS et al for the Diabetes and Ramadan Advisory Board. International Medical Recommendations for Muslim Subjects with Diabetes Mellitus Who Fast During the Month of Ramadan. Clinical Diabetes- Middle East, 3:143-145, 2004

I. General considerations

II. Pre-Ramadan medical assessment and educational

counseling

III. Management of patients with type 1 diabetes

IV. Management of patients with type 2 diabetes:

Diet-controlled patients

Insulin therapy +OHAs

Insulin alone

V. Pregnancy and fasting during Ramadan

VI. Management of hypertension and dyslipidemia 35

Monira Al-Arouj,, Samir Assaad-Khalil,, John Buse, MDDiabetes Care August 2010 vol. 33 no. 8 1895-1902

II. Pre-Ramadan medical assessment and educational counseling

Medical assessment

Educational counseling

36

I. General considerations: Nutrition

The diet during Ramadan should not differ significantly from a healthy and balanced diet

It should aim at maintaining a constant body mass : 50–60% maintain their BMI 20–25% gain or lose weight (>3 kg)

Avoid the ingesting of large amounts of foods rich in carbohydrate and fat

Advise the ingestion of foods containing “complex” carbohydrates at the predawn meal

Advise Simple carbohydrates at the sunset meal

Fluid intake be increased during non fasting hours

37

Monira Al-Arouj,, Samir Assaad-Khalil,, John Buse, MDDiabetes Care August 2010 vol. 33 no. 8 1895-1902

I. General considerations: Exercise:

Normal levels of physical activity may be maintained

Excessive physical activity may lead to higher risk of hypoglycemia and should be avoided particularly before the sunset meal

Tarawaih prayer should be considered a part of the daily exercise program

In some patients with poorly controlled type 1 diabetes, exercise may lead to extreme hyperglycemia.

38

I. General considerations; Breaking the fast

If hypoglycemia (blood glucose of <60 mg/dl)

If blood glucose reaches <70 mg/dl (3.9 mmol/l) in the first few hours after the start of the fast especially if insulin, sulfonylurea drugs, or meglitinide are taken at predawn fast

if blood glucose exceeds 300 mg/dl

Typical or atypical symptoms of hypoglycemia ?39

III. Management of patients with type 1 DM

INSULIN THERAPYIt is unlikely that one injection of intermediate- or long-acting insulin administered before the evening meal would provide adequate insulin coverage for 24 h:

Less flexible ( fixe dose) Hypoglycemic risk Timing during Ramadan

Another option could be to use: one daily injection of the long-acting insulin analog Glargine or twice-daily injections of the insulin analog Detemir with premeal

rapid-acting insulin analogs

40

IV. Management of patients with type 2 DM

DIET-CONTROLLED PATIENTS:the risk associated with fasting is quite low

there is still a potential risk for occurrence of postprandial hyperglycemia after the predawn and sunset meals

combine this with a regular daily exercise program 2 h after the sunset ∼meal (Tarawih)

older age-group, often with hypertension and dyslipidemia, fluid restriction and dehydration may increase the risk of thrombotic

41

IV. Management of patients with type 2 DM

PATIENTS TREATED WITH ORAL AGENTS:

Metformin: two thirds of the total daily dose be administered immediately before the sunset meal

Glitazones no change

Sulfonylureas unsuitable for use during fasting because of the inherent risk of hypoglycemia utilized with caution Use of chlorpropamide is absolutely contraindicated(gliclazide MR or glimepiride) have been shown to be effective

Sulfonylureas Short-acting insulin secretagogues: repaglinide might be safer than use of

42

PATIENTS TREATED WITH INSULIN

(similar to those with type 1 diabetes)

Use of intermediate- or long-acting insulin preparations plus a short-acting, or premixed insulin administered before meals hypoglycemia is still a risk

Using one injection of a long-acting insulin analog, such as insulin Glargine

or two injections of NPH, Lente, Detemir insulin

The dosage of each injection should appropriately individualized

Very elderly patients may be at high risk

43

IV. Management of patients with type 2 DM

44

"Basal" Insulins:intermediate or long-acting insulins

Reproduce the basal insulin secretion

Inhibition of hepatic glucose production

Control of FBG

45

LANMET: Insulin glargine or NPH insulin with metformin

9-month, comparative study of insulin glargine + metformin versus NPH + metformin in 110 patients with T2DM

4

8

12

16

Beforebreakfast

Afterbreakfast

Beforelunch

Afterlunch

Beforedinner

Afterdinner

22:00 04:00

Insulin glargine + metformin

NPH + metformin

Baseline

Weeks 25 - 36

Blo

od g

luco

se (

mm

ol/L

)

p=0.0003

p=0.0047p=0.07

Yki-Järvinen H, et al. Diabetologia 2006;49:442-51.

46

Insulin glargine + OHAs achieves glycaemic control with low risk of hypoglycaemia

Treat-to-Target is a pivotal landmark trial: Randomized comparison of OHAs + insulin glargine or NPH titrated

for 24 weeks in 756 overweight insulin-naïve patients with T2DM

5

6

7

8

9

Baseline Study end

5

10

15

20

25

Symptomatichypoglycaemia

Confirmedhypoglycaemia*

* Confirmed events of ≤4mmol/L (72 mg/dL)Riddle M, et al. Diabetes Care 2003;26:3080-6.

Hb

A1

c )

%(

Eve

nts

per

pat

ien

t-ye

ar

8.56 8.61

6.96 6.97

17.7

13.912.9

9.2

NPH

Insulin glargine

p<0.02

p<0.005

47

Percentage of patients with HbA1c <7 % without nocturnal hypoglycaemia

Better response (HbA1c <7% without nocturnal hypoglycaemia) in the insulin glargine group vs. NPH

NPHLANTUS®

33%

27%

% patients p<0.05

V. Pregnancy and fasting during Ramadan

controversy :

pregnant Muslim women are exempt from fasting

some with known diabetes (type 1, type 2, or gestational) insist on fasting during Ramadan

These women constitute a high-risk group, and their management requires intensive care

Women with pregestational or gestational diabetes should be strongly advised to not fast during Ramadan

if they insist on fasting: special attention should be given to their care

Pre-Ramadan evaluation of their medical condition is essential

48

VI. Management of hypertension and dyslipidemia

Dehydration, volume depletion

A tendency toward hypotension may occur with fasting

medications antihypertensive perspiration may need to be adjusted to prevent hypotension

Dyslipidemia should be checked during Ramadan

49

50

THANK YOUTHANK YOU