Diabetes

1
Diabetes Ramadan

• Dr. Nizar AlbacheHead of Diabetes Research
  Unit, Aleppo UniversityPresident of Syrian
  Endocrine Society
• Carlton citadel Hotel , Aleppo, July 20th

2
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 ?

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
T2 DiabetesInsulin resistance insulinopenia
Insulin resistance
Glycemia
Insulin secretion
Time
No diabetes
Pre- diabetes
Type 2 Diabetes
5
Decline of ß-cells function determinesthe
progressive nature of T2DM
100
?
Time of diagnostic
80
60
ß-cell function (of normal by HOMA)
Pancreatic function 50 of normal
40
20
0
-12
-10
-8
-6
-4
-2
0
2
4
6
Time (years)
HOMAhomeostasis model assessment. UKPDS Group.
Diabetes 1995441249-58. Adapted from Holman RR.
Diabetes Res Clin Pract 199840(suppl 1)S21-5.
6
ADA/EASD Consensus Guidelines Treatment
Algorithm, 2006
Diagnosis
Step 1
Lifestyle intervention Metformin
HbA1c ? 7
Step 2
Add basal insulin (Most effective)
Add sulfonylurea (Least expensive)
Add glitazone (No hypoglycemia)
Additional medications insulin, sulfonylureas or
TZDs, on the top of metformin
Nathan DM, et al. Diabetes Care 2006298.
7
ADA/EASD guidelines recommend use of basal
insulin as early as the second step in type 2
diabetes management
Tier 1 well-validated core therapies
Lifestyle Metformin plusBasal insulin
Lifestyle Metformin plus Intensive insulin
At diagnosis Lifestyle Metformin
Lifestyle Metformin plus Sulfonylureaa
Check HbA1C every3 months until lt7. Change
treatment if HbA1C is 7
STEP 1
STEP 2
STEP 3
Tier 2 Less well validated therapies
Lifestyle Metformin plus Pioglitazone No
hypoglycaemia Oedema/CHF Bone loss
Lifestyle Metformin plus Pioglitazone plus
Sulfonylureaa
Lifestyle metformin plus GLP-1 agonistb No
hypoglycaemia Weight loss Nausea/vomiting
Lifestyle Metformin plus Basal insulin

• Sulfonylureas other thanGlybenclamide or
  chlorpropamide
• Insufficient clinical safety data
  CHF,congestive heart failure
• Nathan DM, et al. Diabetes Care 2008311-12.

8
Types 2 Diabetes

• Recommendations in case of oral bitherapy failure

Diet and lifestyle recommendations
Oral triple therapyMetSU GIitazones
Insulin therapy
HbA1c gt8
9
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
• Metformin as first line therapy(unless
  contraindicated)
• Sulfonylureas are the recommended second line
• Third line therapy is either a third oral agent
  or insulin (basal or premixed)
• 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

10
Considerations for Fasting During Ramadan

• Religious Considerations imposition, obligation
• Exemption of the sick

11
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12
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13
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14
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15
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16
Considerations for Fasting During Ramadan

• Religious Considerations
• Exemption of the sick
• Medical Considerations
• Need to define which diabetic is sick enough
  to be at risk and should be advised not to fast

17
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.

18
Hours of fast during the month of Ramadan
Globally
??? ????? 2011????? 3.55????? 19.44 ????15
???? ???? ??????? 44
19
Change in blood glucose profile
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.
20
Change in blood glucose with meal timing
Daily glucose profile during the month of Ramadan
21
Change in blood glucose with meal timing
Daily glucose profile for both months
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 )

22
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.

23
Dietary Change
Calorie Change
Total daily calorie intake before and during
24
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25
 
 
EPI.DIA.R EPIdemiology of DIAbetes Ramadan
1422/2001 Salti IS et al Diabetes Care 27
2306-2311, 2004
 
 
26
Number of patients by country (N 12,914)
Salti IS et al Diabetes Care 27 2306-2311, 2004
27
Repartition by type of 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 gt 1 day)
DM type 1
DM type 2
()
Overall population
DM type 1 54
DM type 2 86
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

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,
3143-145, 2004
32
RECOMMENDED RAMADAN GUIDELINES FOR PATIENTS WITH
DIABETES MELLITUS Type 2Continued

• 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 gt 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,
3143-145, 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,
3143-145, 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 gt 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,
3143-145, 2004
35
I. General considerationsII. Pre-Ramadan
medical assessment and educational
counselingIII. Management of patients with type
1 diabetesIV. Management of patients with type 2
diabetesDiet-controlled patientsInsulin
therapy OHAsInsulin aloneV. Pregnancy and
fasting during RamadanVI. Management of
hypertension and dyslipidemia
Monira Al-Arouj,, Samir Assaad-Khalil,, John
Buse, MDDiabetes Care August 2010 vol. 33 no. 8
1895-1902
36
II. Pre-Ramadan medical assessment and
educational counseling

• Medical assessment
• Educational counseling

37
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
• 5060 maintain their BMI
• 2025 gain or lose weight (gt3 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

Monira Al-Arouj,, Samir Assaad-Khalil,, John
Buse, MDDiabetes Care August 2010 vol. 33 no. 8
1895-1902
38
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.

39
I. General considerations Breaking the fast

• If hypoglycemia (blood glucose of lt60 mg/dl)
• If blood glucose reaches lt70 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 ?

40
III. Management of patients with type 1 DM

• INSULIN THERAPY
• It 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

41
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
  program2 h after the sunset meal (Tarawih)
• older age-group, often with hypertension and
  dyslipidemia, fluid restriction and dehydration
  may increase the risk of thrombotic

42
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

43
IV. Management of patients with type 2 DM

• 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

44
"Basal" Insulinsintermediate or long-acting
insulins

• Reproduce the basal insulin secretionInhibition
  of hepatic glucose productionControl 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

Insulin glargine metformin
NPH metformin
16
12
Baseline
Blood glucose (mmol/L)
p0.0047
8
p0.07
p0.0003
Weeks 25 - 36
4
Beforebreakfast
Afterbreakfast
Beforelunch
Afterlunch
Beforedinner
Afterdinner
2200
0400
Yki-Järvinen H, et al. Diabetologia
200649442-51.
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 titratedfor 24 weeks in 756 overweight
  insulin-naïve patients with T2DM

NPH
Insulin glargine
8.61
8.56
plt0.02
17.7
plt0.005
6.96
6.97
13.9
HbA1c ()
Events per patient-year
12.9
9.2
Confirmed events of 4mmol/L (72 mg/dL) Riddle
M, et al. Diabetes Care 2003263080-6.
47
Percentage of patients with HbA1c lt7 without
nocturnal hypoglycaemia

• Better response (HbA1c lt7 without nocturnal
  hypoglycaemia) in the insulin glargine group vs.
  NPH

patients
plt0.05
33
27
LANTUS
48
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

49
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

50
THANK YOU