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‫”ياأيها الذين أمنوا كتب عليكم الصيام كما‬
“‫كتب على الذين من قبلكم لعلكم تتقون‬
“ O you who believe! Fasting has
been prescribed to you as it was
prescribed to those before you so
that you attain Taqwa ”


Fasting is not meant to create excessive
hardship on the Muslim individuals. The
Quran specifically exempts the sick from
the duty of fasting.
The Prophet Mohammad said, “God likes
his permission to be fulfilled, as he likes
his will to be executed.”
Things Happened During Ramadan
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During Ramadan, Muslims must fast from
dawn to sunset.
This will involve a sudden change in the
daily meals.
Two meals named Iftar and Sahur.
Ramadan is a lunar-based month. Its timing
changes with respect to seasons.
Depending on the geographical location and
season, the duration of the daily fast may
range from a few to more than 20 h.
Uniqueness of Ramadan Fasting
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It is a voluntary undertaking rather than being
ordered by a physician
There is no selective food intake i.e. protein
only, juice only, fruit only , water only etc
There is no total calorie malnutrition
An exercise in self discipline i.e. from constant
nibbling , drinking, smoking etc
Physiological Effects of Fasting:
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On Calorie intake
On fluid /water intake
Effects on – Digestive System
- Kidneys
- Endocrine glands
- Lipid Metabolism
- Respiratory system
- Neurological System
Some Facts :
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The most important metabolic fuels are glucose and
fatty acids.
In normal circumstances, glucose is the only fuel the
brain uses.
To ensure the continuous provision of glucose to the
brain and other tissues, metabolic fuels are stored.
Carbohydrates are stored as glycogen - the amount of
available glycogen stored is not large - about 75g in
the liver and little amounts in the muscles. Liver
glycogen can supply glucose for no longer than 16h.
To provide glucose over longer periods, the body
transforms non-carbohydrate compounds into glucose
(Gluconeogenesis).
Insulin and Glucagon
Main determinants of glucose metabolism
Insulin&
C-peptide
Proinsulin
Proglucagon
Glucagon
Both cell types release their hormones simultaneously at a basal level.
This is augmented in response to alterations in blood glucose levels .
Blood glucose<70mg/dl
Proinsulin
--+++
Insulin&
C-peptide
+++
Proglucagon
---
Blood glucose >90mg/dl
Glucagon
Paracrine Actions of Insulin and
Glucagon
Insulin
- glucagon
Glucagon
+ Insulin
Insulin
glycogenesis
glycogenolysis
Protein
synthesis
gluconeogenesis
from aa
lipogenesis
Glucagon
lipolysis
So, insulin favors anabolic reactions and storing energy
glucagon, catabolic reactions and release of stored energy
1- 6 hours: blood glucose < 60 mg/dl
2- Lowered blood glucose ++ secretion
of glucagon& -- insulin
+++
3-Glycogenolysis
maintain blood
glucose for 12-16 hours
4- Then stimulates gluconeogenesis
5- Ketone bodies
Alanin
&lactate
glycerol
FFA
Fuel reserves are:
Triacylglycerols
& tissue proteins
So, Effects of Fasting on
Carbohydrate Metabolism
1. Slight fall in serum glucose from 9 to 11 am, but not from
11 am to 6 pm.
Serum Insulin
Serum glucagon
Growth hormone
Catecholamine
2-Slight decrease blood glucose in the first week then
normalization by day 20 ± rise in the last week
Fasting and Lipid Metabolism
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Decrease in : Total Cholesterol ,LDL and
Triglycerides in first few days then rise to pre
fasting levels (quality and quantity of food
consumed at Iftaar and Sahur)
Increase in HDL-C
Endocrine functions in Fasting
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Fall in free T3 but rise in rT3
Slight fall in total T4 (due to fall in
TBG) but normal freeT4 and TSH
Serum Testosterone, LH, FSH may be
normal or slightly low with change of
circadian pattern
-- Sexual desire during fasting
hours
Altered circadian patterns of cortisol and
testosterone, with sharper decreases
of these hormones in the morning and
later rises at night
Decrease in appetite due to
ketosis and increase in Betaendorphins
Decreased and delayed melatonin
peak
Decreased
Nocturnal sleep
Daytime alertness
Psychomotor performance
Renal Function in Fasting
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Urinary volume
Osmolality
Dehydration
Shift of fluids intracellularly
Slight increase in BUN (insignificant)
Increase in Uric acid (less in Ramadan
fasting than in prolonged fasting)
Other Effects of Fasting
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Weight loss of 1.7 - 3.8 Kg (obese lose
more weight than non obese)
Fewer suicide in Ramadan than in
other months (reported in Jordan)
Benefits of fasting:
Muslims do not fast because of medical benefits but because
they are ordered to.
1- Self -regulation and self-training
2- Concentration of all fluids within the tissues and plasma.
3-Lower of blood sugar
4-Lowering of LDL and elevation of HDL
5-Lowering of the systolic blood pressure.
6-Lowering of body weight
7-Psychological :sense of inner peace and tranquility
(Fasting Muslims realize that anger may take away the
blessings of fasting) (stress elevate blood sugar via
catecolamines)
Ramadan fasting would be an ideal recommendation for
treatment of mild to moderate stable NIDDM, obesity
and essential hypertension.
What will happen in
diabetic patient ?????????
In patients with diabetes
Insulin replacement
Insulin replacement
Glucagon secretion may fail to increase
Epinephrine secretion is also defective
due to a autonomic neuropathy .
Excessive: Glycogenolysis
Gluconeogenesis
Ketogenesis
Hypoglycemia
Hyperglycemia &
Ketosis
EPIDIAR STUDY-T2DM:
78.2% fasted >15days
Salti et al: Diabetes Care Vol 27; 10 Oct 2
Risks associated with
fasting in diabetic
patient???
Risks associated with fasting in
patients with diabetes
*
Hypoglycemia: Severe hypoglycemia
Type 1 diabetes
3 to14 events/100 people/ m
Finch GM et al, Appetite 31:2, 1998
Ghaznawi H I. et al. "The Effect of Ramadan Fasting on Body Weight." Joumalfo the
IMA, 1993
Al-Hurani HM etal, Singapore Med J. 2007 Oct;48(10):906-10
Faye J et al, Dakar Med. 2005;50(3):146-51
Type 2 diabetes
0.4 to3 events/100 people/ m.
*Hyperglycemia:
severe hyperglycemia (requiring hospitalization)
Type 1 diabetes
3 fold increase
± Ketoacidosis
Type 2 diabetes
5 fold increase
due to excessive reduction in dosages of medications
to prevent hypoglycemia
*Dehydration and thrombosis :
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if prolonged fasting
In hot and humid climates
Among individuals who perform hard physical labor
Hyperglycemia
Might lead hypovolemia and orthostatic hypotension ,
however, hospitalizations due to coronary events or
stroke were not increased
Taking the decision

The decision to fast is usually taken by three
people: the patient , the physician and a religious
advisor.
Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2
Thank You
Insulin Glargine during
Ramadan
Eman Rushdy
Epidemiology of Diabetes and Ramadan
1422/2001 : (EPIDIAR) study
12,243 people with diabetes from
13 Islamic countries about 43% of
patients with type 1 diabetes and
78% of patients with type 2 diabetes
fast during Ramadan.
32
Diabetes Care2004 : 27:2306–2311
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During Ramadan about 60% of patients change
their antidiabetic drug intake.
35% stop treatment
8% change the dosage
Importantly, this is done at the patients’
own initiative without medical supervision.
Salti I, Benard E, Detournay B et al. A population-based study of diabetes and its characteristics during the fasting
month of Ramadan in 13 countries. Diabetes Care 2004; 27: 2306–11.
Aslam M, Healey MA. Compliance and drug therapy in Moslem patients. J Clin Hosp Pharm 1986; 11: 321–5.
Aslam M, Assad A. Drug regimens and fasting during Ramadan: a survey in Kuwait. Public Health 1986; 100: 49–53.
Results in
Sequelae of
hypoglycaemia
 Mild”:
Adrenergic (BG<70)
– No direct serious clinical effects
– With a rapid decline in blood glucose :
tachycardia, tachypnea, vomiting, and
diaphoresis
– May impair subsequent hypoglycaemia
awareness
 Severe

Neuroglycopenic (BG<50)
Usually associated with slower or prolonged
hypoglycemia,
– Stroke and transient ischaemic attacks
– Memory loss/cognitive impairment
Recent Clinical Trial
Findings:
Intensive glucose control in type 2
diabetes:
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Was associated with increased mortality in
patients with longstanding DM and known CVD
(ACCORD)
Increases risk of severe hypoglycemia
(ADVANCE, ACCORD and VADT)
ACCORD: N Engl J Med 2008; 358(24):2545-59. ADVANCE: N Engl J Med 2008; 358 (24): 2560-72.
VADT: J Diabetes Complications 2003; 17 (6): 314-22
Hypoglycaemia and CV Disease
Desouza C et al Diabetes Care 26: 1485-1489, 2003
Hypoglycaemia and CV Disease
Haematologic Responses To
Hypoglycaemia
• Increased RBCs Leading To Increased Blood Viscosity
• Enhanced Platelet Aggregation
• Increased Platelet Factor 4
• Increased Thromboglobulin
• Increased Coagulation Factor VIII
• Increased Von Willebrand Factor
• Increased Thrombin Generation
Wright R et al Diabetes/ Metabolism Research and Reviews , 2008
Hypoglycaemia and CV Disease
Inflammatory Responses To
Hypoglycaemia
CRP (mg/L)
Diabetes
Control
Baseline
4 Hours
24 Hours
0.77
0.32
0.84
ND
2.31*
0.96*
*p < 0.04 vs. Baseline
Galloway P et al Diabetes Care 23: 861-862, 2000
Hypoglycaemia and CV Disease
Hemodynamic
Hypoglycaemia
Thrombotic
Ischaemia
Inflammatory
Wright R et al Diabetes/ Metabolism Research and Reviews , 2008
Hypoglycemia Unawareness
Type 1 DM
DURATION
Autonomic neuropathy
Recurrent hypoglycemia
MIMICKING NATURE
WITH INSULIN THERAPY
All persons need
both basal and mealtime
insulin
to control glucose
6-
•The normal human pancreas has a
basal insulin secretory rate of 1-2 U
per hr, with post prandial rates
increasing to 4-6 U / hr.
in two phases (early & Late phase).
•Insulin secreted into portal
circulation where 50% of it extracted
by liver without reaching systemic
circulation.
•Insulin catabolized by insulinase in
Liver, Kidney, & placenta.
Regulation of Basal insulin
secretion
Na+
GLUT2
Na+
Pacemaker
ß cells
K+
Signal
KIR
K+
K+
Vm
K+
Voltage-gated
Ca2+ channel
Ca2+
Ca2+
Pancreatic
ß cell
Ca2+
Ca2+
Insulin granules
Mature insulin
granules contracts
by exposure to high
intracellular Ca.
Post prandial insulin secretion
Glucose
Glucokinase
Ca
K
Physiologic Insulin Secretion:
Basal/Prandial Concept
Nutritional (Prandial) Insulin
Insulin
(µU/mL)
50
Basal Insulin
25
Basal Insulin
0
Breakfast
Glucose
(mg/dL)
150
Lunch
Supper
Nutritional Glucose
*Suppresses Glucose
Production Between
Meals & Overnight
*Nearly constant levels
40- 50% of daily needs
100
50
0
Basal Glucose
7 8 9 1011 12 1 2 3 4 5 6 7 8 9
A.M.
P.M.
Time of Day
Prandial Insulin
*Limits hyperglycemia after meals
*Immediate rise and sharp peak
*10% to 20% of total daily insulin
requirement at each meal
Good
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70/30 premixed insulin twice daily,
….Use the usual morning dose at the
sunset meal (Iftar) and half the usual
evening dose at predawn (Suhur),
e.g., 30 units in morning and 20 units
in evening…e.g., 70/30 premixed
insulin, 30 units in Iftar and 10 units in
Suhur .
The best:

Consider changing premixed
insulin preparations to Glargine or
Dtemir plus Lispro, Glulisine or
Aspart .
Diabetes Care
September 2005 , pages 2305-11
48
Types of basal insulin
Onset
Peak
Duration
IntermediateActing
(e.g. NPH, lente)
Long-Acting
Analogues
(glargine, detemir)
1-3 hr(s)
1.5-3 hrs
5-8 hrs
No peak with
glargine, dosedependent peak with
detemir
Up to 18 hrs
9-24 hrs (detemir);
20-24 hrs (glargine)
Rossetti P, et al. Arch Physiol Biochem 2008;114(1): 3 – 10.
49
Ideal Basal Insulin:
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Safe
Effective
Less glucose excurtions
Why Glargine
6
mg/kg/min
Glucose utilization rate
Insulin Glargine Peakless with 24hour Release
5
4
NPH
3
2
Insulin Glargine
1
Time
0
0
8
16
24
Insulin Glargine has less intra-patient variation & has a relatively constant,
longer action profile with no pronounced peak in contrast to the peak and
intermediate activity of NPH insulin
52
LAPTOP: lower incidence of
hypoglycaemia with Insulin Glargine
versus premix
Janka HU, et al. Diabetes Care 2005;28(2):254–259
Meta-Regression Analysis
Less hypoglycemia with glargine vs
NPH
11 randomized controlled trials; n=3,083
Rate of Hypoglycemia
(Events/100 Patient-Years)
200
p=0.021
150
NPH insulin
100
50
Insulin glargine
0
6
7
8
9
10
HbA1c (%)
Adapted from Mullins P, et al. Clin Ther 2007;29:1607-1619.
54
Insulin glargine consistently achieves
HbA1C ≤ 7%
Baseline
HbA1C (%)
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
8.6
8.7
8.6
7.0
T-T-T1
(n = 367)
Study end
7.0
INSIGHT2
(n = 206)
7.0
8.8
8.7
6.8
APOLLO3 INITIATE4
(n = 174)
(n = 58)
7.0
Schreiber5
(n = 12,216)
1. Riddle M, et al. Diabetes Care 2003;26:3080–6. 2. Gerstein HC, et al. Diabetes Med 2006;23:736–42. 3. Bretzel RG, et al. Lancet
2008;371:1073–84. 4. Yki-Järvinen H, et al. Diabetes Care 2007;30:1364–9. 5. Schreiber SA, et al. Diabetes Obes Metab
2007;9:31–8.
LAPTOP: once-daily Insulin Glargine + oral
antidiabetic drug
therapy is better than two premixes when initiating
insulin in Type 2 diabetes
Randomized study in 371 insulin-naïve subjects with T2DM, who received Insulin
Glargine or premix (70% NPH/30% regular) insulin for 24 weeks
Insulin Glargine + OADs is more efficient in lowering HbA1c, with less
hypoglycaemia
56
Janka HU, et al. Diabetes Care 2005;28(2):254–259
PK/PD: Insulin Glargine has a longer
duration of action than detemir
Randomized study comparing the pharmacokinetics and
pharmacodynamics of Insulin Glargine with that of detemir in 24 subjects
with T1DM who were naïve to Insulin Glargine and detemir
57
Porcellati F, et al. Diabetes Care 2007;30(10):2447–2452
The need for prandial insulin despite
optimal titration of basal insulin is indicated by:
– FBG at or close to target (90–130 mg/dl) but
HbA1c ≥7%1
– FBG controlled but PPBG consistently high
– Basal insulin dose > 0.5U/Kg
58
Fasting and Insulin Glargine in
Individuals With Type 1
Diabetes
Fasting during Ramadan in
T2DM patients with insulin
Glargine
Breaking the fast
Diabetic patients must end their fast immediately in
the following cases:
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if blood glucose levels drop dramatically to 60 mg/dl or lower
if blood glucose reaches 70 mg/dl in the first few hours after the start
of the fast, especially if insulin, sulfonylureas, or meglitinides are taken
at the pre-dawn meal
if blood glucose levels rise excessively to 300 mg/dl.
Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2
THANK YOU
Management:
People with type 1 diabetes

In general, people with type 1 diabetes are at very high risk
of developing severe complications, and should be strongly
advised to not fast during Ramadan.
Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2
Management:

To be Discussed later in the following
sessions
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Two daily injections of NPH intermediate-acting
insulin in combination with a short-acting insulin
administered the usual dose before Iftar and
half the dose before Sahour, However, there is
an increased risk of hypoglycaemia around
midday
Another option : use one daily injection of the
long-acting insulin analogue, glargine; or
detemir along with pre-meal rapid-acting insulin
analogues.
Management
People with type 2 diabetes
Lifestyle and nutrition
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In people who manage their diabetes with diet and physical activity, the
risks associated with fasting are quite low.
However, if people eat excessively, a potential risk of post-meal
hyperglycaemia .
Distributing energy intake over two to three smaller meals during the nonfasting interval may help.
A person’s regular daily exercise programme should be modified in its
intensity and timing to avoid episodes of hypoglycaemia.
Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2
Major Targeted Sites of Oral Drug
Classes
Pancreas
The glucose-dependent mechanism of
DPP-4 inhibitors targets 2 key defects:
insulin release and unsuppressed
hepatic glucose production.
Liver
Beta-cell
dysfunction
Sulfonylureas
Meglitinides
Muscle
and fat
DPP-4 inhibitors
GLP-1
Hepatic glucose
overproduction
Biguanides
↓Glucose level
Insulin
resistance
Gut
TZDs
TZDs
Biguanides
DPP-4 inhibitors
Glucose
absorption
Alphaglucosidase
inhibitors
Biguanides
DPP-4=dipeptidyl peptidase-4; TZDs=thiazolidinediones.
DeFronzo RA. Ann Intern Med. 1999;131:281–303.
Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:1427–1483.

Source of hyperglycemia during
fasting hours:
1- Dietary
2- Insulin deficiency
3- Hepatic glucose output
4- Non of the above.
An Ideal Oral Agent Should You
Select during fasting..?

Achieve A1c Target

Has lower hypoglycemic events

Promotes weight loss
In general, medications that act by increasing insulin sensitivity
are associated with a significantly lower risk of hypoglycaemia
than insulin secretagogues
Major Targeted Sites of Oral Drug
Classes
Pancreas
The glucose-dependent mechanism of
DPP-4 inhibitors targets 2 key defects:
insulin release and unsuppressed
hepatic glucose production.
Liver
Beta-cell
dysfunction
Sulfonylureas
Meglitinides
Muscle
and fat
DPP-4 inhibitors
GLP-1
Hepatic glucose
overproduction
Biguanides
↓Glucose level
Insulin
resistance
Gut
TZDs
TZDs
Biguanides
DPP-4 inhibitors
Glucose
absorption
Alphaglucosidase
inhibitors
Biguanides
DPP-4=dipeptidyl peptidase-4; TZDs=thiazolidinediones.
DeFronzo RA. Ann Intern Med. 1999;131:281–303.
Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:1427–1483.
Management
Oral medications
 Metformine: two thirds of the total daily dose to be
taken after the sunset meal, with the other third taken
after the pre-dawn meal.
 Rosiglitazone and Pioglitazone: have a low risk of
hypoglycemia. Usually no change in dose is required.
Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2
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Sulfonylureas are believed to be unsuitable for use
during fasting because of the inherent risk of
hypoglycemia; they should be used with caution and
select the safest SU (glimipride).
Meglitinides are superior to SU as long as they could
control hyperglycemia.
Chlorpropamide is absolutely contraindicated during
Ramadan because of the high possibility of prolonged
and unpredictable hypoglycemia.
Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2
Insulin


The aim should be to maintain necessary levels of basal insulin to
suppress output of glucose from the liver to near-normal levels
during fasting.
Careful use of intermediate or long-acting insulins plus a shortacting insulin administered before meals would be an effective
strategy.
Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2
Recommended changes to treatment regimen in
patients with type 2 diabetes who fast during
Ramadan
(MONIRA AL-AROUJ, MD. RADHIA BOUGUERRA, MD. JOHN BUSE, MD, PHD. SHERIF HAFEZ, MD, FACP. MOHAMED HASSANEIN, FRCP. MAHMOUD ASHRAF IBRAHIM, MD.
FARAMARZ ISMAIL-BEIGI, MD, PHD. IMAD EL-KEBBI, MD. OUSSAMA KHATIB, MD, PHD. SUHAIL KISHAWI, MD. ABDULRAZZAQ AL-MADANI, MD. ALY A. MISHAL, MD, FACP.
MASOUD AL-MASKARI, MD, PHD. ABDALLA BEN NAKHI, MD. KHALED AL-RUBEAN, MD)
Recommendations for Management of Diabetes During Ramadan; Reviews / Commentaries / ADA Statements ADA WORK GROUP REPORT; DIABETES CARE, VOLUME 28, NUMBER
9: 2305-2311, SEPTEMBER 2005
Case #1

47 years old male , accountant

Sedentary lifestyle

BMI 32

Diabetic 5 years on Glimipride 4 mg /day
and metformin 500 mg 3 times daily
Glimipride adjusted dose (2 or 3 mg) before
Iftar and metformin 1000 mg after Iftar and
500mg after Sahour
Case #2



51 year old male
Type 2 diabetes currently treated with
Metformin 1500 mg
Serum creatinin 1.9 mg/dl
Not to fast
Shift to Insulin Sensitizers
Case #1

48 years old male

BMI 28

Diabetic 11 years controlled on mixed Insulin
60 U breakfast &40 U dinner and metformin
850mg after lunch
60 U Iftar and 20 U Sahour
Basal Insulin 40 U & Short acing (better ultra
short analogues) 30 U Iftar & 10 U Sahour
Patient Care and Management !!!
Frequent monitoring

This is especially critical in people who require insulin
Medical assessment


This should take place one to two months before Ramadan.
Specific attention should be paid to people’s overall well-being and
to the control of their blood glucose levels, blood pressure, and
lipids.
Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2
Nutrition




People should maintain a healthy and balanced diet during
Ramadan.
The common practice of ingesting large amounts of foods that are
high in fat and carbohydrates, should be avoided x
It is recommended that non-caloric fluid intake be increased during
the non-fasting hours.
The Sahour meal should be taken as late as possible before the
start of the daily fast.
Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2
Physical activity



Normal levels of physical activity can be maintained.
However, excessive physical activity may lead to higher
risk of hypoglycaemia and should be avoided. x
If Tarawih prayers (multiple prayers after the sunset
meal) are performed, they should be considered a part
of a person’s daily physical activity programme.
Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2
Diabetics should not fast if :

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
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
Uncontrolled (no defined figure)
Recurrent hypoglycemic attacks
Hypoglycemia unawareness.
A history of Diabetic Ketoacidosis ·
Recent infections
Kidney disease
Unstable ischemic heart disease.