By Eman Rushdy

عليكم ”” كتب أمنوا الذين عليكم ياأيها كتب أمنوا الذين ياأيهامن الذين على كتب كما من الصيام الذين على كتب كما الصيام

تتقون لعلكم تتقون قبلكم لعلكم ““قبلكم

“ “ O you who believe! Fasting O you who believe! Fasting has been prescribed to you has been prescribed to you as it was prescribed to those as it was prescribed to those before you so that you attain before you so that you attain Taqwa Taqwa ””

Fasting is not meant to create Fasting is not meant to create excessive hardship on the Muslim excessive hardship on the Muslim individuals. The Quran specifically individuals. The Quran specifically exempts the sick from the duty of exempts the sick from the duty of fasting. fasting.

The Prophet Mohammad said, “God The Prophet Mohammad said, “God likes his permission to be fulfilled, as likes his permission to be fulfilled, as he likes his will to be executed.”he likes his will to be executed.”

Things Happened During Things Happened During RamadanRamadan

During Ramadan, Muslims must fast from During Ramadan, Muslims must fast from dawn to sunset. dawn to sunset.

This will involve a sudden change in the This will involve a sudden change in the daily meals.daily meals.

Two meals named Two meals named Iftar Iftar and and SahurSahur.. Ramadan is a lunar-based month. Its Ramadan is a lunar-based month. Its

timing changes with respect to seasons. timing changes with respect to seasons. Depending on the geographical location Depending on the geographical location

and season, the duration of the daily fast and season, the duration of the daily fast may range from a few to more than 20 h. may range from a few to more than 20 h.

Uniqueness of Ramadan FastingUniqueness of Ramadan Fasting

It is a voluntary undertaking rather than It is a voluntary undertaking rather than being ordered by a physicianbeing ordered by a physician

There is no selective food intake i.e. There is no selective food intake i.e. protein only, juice only, fruit only , water protein only, juice only, fruit only , water only etconly etc

There is no total calorie malnutrition There is no total calorie malnutrition An exercise in self discipline i.e. from An exercise in self discipline i.e. from

constant nibbling , drinking, smoking etcconstant nibbling , drinking, smoking etc

Physiological Effects of Fasting:Physiological Effects of Fasting:

On Calorie intakeOn Calorie intake On fluid /water intakeOn fluid /water intake Effects on – Digestive SystemEffects on – Digestive System

- Kidneys- Kidneys

- Endocrine glands- Endocrine glands

- Lipid Metabolism- Lipid Metabolism

- Respiratory system- Respiratory system

- Neurological System- Neurological System

Some Facts :Some Facts : The most important metabolic fuels are glucose and fatty The most important metabolic fuels are glucose and fatty

acids.acids. In normal circumstances, glucose is the only fuel the brain In normal circumstances, glucose is the only fuel the brain

uses.uses. To ensure the continuous provision of glucose to the brain To ensure the continuous provision of glucose to the brain

and other tissues, metabolic fuels are stored.and other tissues, metabolic fuels are stored. Carbohydrates are stored as glycogen - the amount of Carbohydrates are stored as glycogen - the amount of

available glycogen stored is not large - about 75g in the available glycogen stored is not large - about 75g in the liver and little amounts in the muscles. Liver glycogen can liver and little amounts in the muscles. Liver glycogen can supply glucose for no longer than 16h.supply glucose for no longer than 16h.

To provide glucose over longer periods, the body To provide glucose over longer periods, the body transforms non-carbohydrate compounds into glucose transforms non-carbohydrate compounds into glucose (Gluconeogenesis).(Gluconeogenesis).

Insulin and Glucagon Insulin and Glucagon Main determinants of glucose Main determinants of glucose

metabolismmetabolism

GlucagonProglucagonInsulin&C-peptide

Proinsulin

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

Insulin&C-peptide

Proinsulin---

GlucagonProglucagon+++

Blood glucose >90mg/dl

+++ ---

Paracrine Actions of Insulin and Paracrine Actions of Insulin and GlucagonGlucagon

Insulin - glucagon Glucagon + Insulin

Insulin

glycogenesis

Protein synthesis

lipogenesis

Glucagon

glycogenolysis

gluconeogenesisfrom aa

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 bloodglucose for 12-16 hours

4- Then stimulates gluconeogenesis Fuel reserves are:Triacylglycerols & tissue proteins

Alanin &lactate glycerol

FFA5- Ketone bodies

+++

So, Effects of Fasting on So, Effects of Fasting on

Carbohydrate MetabolismCarbohydrate Metabolism

11. . Slight fall in serum glucose from 9 to 11 am, but Slight fall in serum glucose from 9 to 11 am, but not from 11 am to 6 pmnot from 11 am to 6 pm..

Serum Insulin Serum glucagon Serum Insulin Serum glucagon Growth Growth hormonehormone Catecholamine Catecholamine

2-Slight decrease blood glucose in the first week then 2-Slight decrease blood glucose in the first week then normalization by day 20 ± rise in the last weeknormalization by day 20 ± rise in the last week

Fasting and Lipid Fasting and Lipid MetabolismMetabolism

Decrease in : Total Cholesterol ,LDL and Decrease in : Total Cholesterol ,LDL and Triglycerides in first few days then rise to Triglycerides in first few days then rise to pre fasting levels (quality and quantity of pre fasting levels (quality and quantity of food consumed at Iftaar and Sahur)food consumed at Iftaar and Sahur)

Increase in HDL-CIncrease in HDL-C

Endocrine functions in FastingEndocrine functions in Fasting

Fall in free T3 but rise in rT3Fall in free T3 but rise in rT3 Slight fall in total T4 (due to fall in Slight fall in total T4 (due to fall in

TBG) but normal freeT4 and TSHTBG) but normal freeT4 and TSH Serum Testosterone, LH, FSH may Serum Testosterone, LH, FSH may

be normal or slightly low with be normal or slightly low with change of circadian pattern change of circadian pattern

-- Sexual desire during -- Sexual desire during fasting hours fasting hours

Altered circadian patterns of Altered circadian patterns of cortisol and testosteronecortisol and testosterone, with , with

sharper decreases of these sharper decreases of these hormones in the morning and hormones in the morning and

later rises at night later rises at night

Decrease in appetite due to Decrease in appetite due to ketosis and increase in ketosis and increase in

Beta-endorphinsBeta-endorphins

Decreased and delayed Decreased and delayed melatonin peakmelatonin peak

Decreased Nocturnal sleepDecreased Nocturnal sleep

Daytime alertness Daytime alertness

Psychomotor Psychomotor performance performance

Renal Function in FastingRenal Function in Fasting

Urinary volume Urinary volume OsmolalityOsmolality Shift of fluids intracellularlyShift of fluids intracellularly Slight increase in BUN (insignificant) Slight increase in BUN (insignificant) Increase in Uric acid (less in Ramadan Increase in Uric acid (less in Ramadan

fasting than in prolonged fasting)fasting than in prolonged fasting)

Dehydration

Other Effects of FastingOther Effects of Fasting

Weight loss of 1.7 - 3.8 Kg (obese Weight loss of 1.7 - 3.8 Kg (obese lose more weight than non obese)lose more weight than non obese)

Fewer suicide in Ramadan than in Fewer suicide in Ramadan than in other months (reported in Jordan)other months (reported in Jordan)

Benefits of fasting:Benefits of fasting:

Muslims do not fast because of medical benefits but because they Muslims do not fast because of medical benefits but because they are ordered to.are ordered to.

1- Self -regulation and self-training 1- Self -regulation and self-training 2- Concentration of all fluids within the tissues and plasma. 2- Concentration of all fluids within the tissues and plasma. 3-Lower of blood sugar3-Lower of blood sugar4-Lowering of LDL and elevation of HDL 4-Lowering of LDL and elevation of HDL 5-Lowering of the systolic blood pressure.5-Lowering of the systolic blood pressure.6-Lowering of body weight6-Lowering of body weight7-Psychological :sense of inner peace and tranquility7-Psychological :sense of inner peace and tranquility (Fasting Muslims realize that anger may take away the (Fasting Muslims realize that anger may take away the

blessings of fasting) (stress elevate blood sugar via blessings of fasting) (stress elevate blood sugar via catecolamines)catecolamines)

Ramadan fasting would be an ideal recommendation for Ramadan fasting would be an ideal recommendation for treatment of mild to moderate stable NIDDM, obesity treatment of mild to moderate stable NIDDM, obesity

and essential hypertension. and essential hypertension.

What will happen in What will happen in diabetic diabetic

patient ?????????patient ?????????

In patients with In patients with diabetesdiabetes

Insulin replacement Hypoglycemia

Insulin replacement

Hyperglycemia &Ketosis

Glucagon secretion may fail to increaseGlucagon secretion may fail to increase Epinephrine secretion is also defective Epinephrine secretion is also defective

due to a autonomic neuropathy .due to a autonomic neuropathy .

Excessive: Glycogenolysis Excessive: Glycogenolysis Gluconeogenesis Gluconeogenesis

KetogenesisKetogenesis

EPIDIAR STUDY-T2DM: EPIDIAR STUDY-T2DM: 78.2% fasted >15days78.2% fasted >15days

Salti et al: Diabetes Care Vol 27; 10 Oct 2

Risks associated with Risks associated with fasting in diabetic fasting in diabetic

patient???patient???

Risks associated with Risks associated with fasting in patients with fasting in patients with diabetesdiabetes

**HypoglycemiaHypoglycemia: : Severe hypoglycemia Severe hypoglycemia

Type 1 diabetes Type 2 diabetes Type 1 diabetes Type 2 diabetes 3 to14 events/100 people/ m 0.4 to3 events/100 3 to14 events/100 people/ m 0.4 to3 events/100

people/ m. people/ m.

Finch GM et al, Appetite 31:2, 1998Ghaznawi H I. et al. "The Effect of Ramadan Fasting on Body Weight." Joumalfo the IMA, 1993Al-Hurani HM etal, Singapore Med J. 2007 Oct;48(10):906-10 Faye J et al, Dakar Med. 2005;50(3):146-51

**HyperglycemiaHyperglycemia: : severe hyperglycemia (requiring severe hyperglycemia (requiring hospitalization)hospitalization)

TyType 1 diabetespe 1 diabetes Type 2 diabetesType 2 diabetes 3 fold increase 5 3 fold increase 5 fold fold

increaseincrease ± Ketoacidosis± Ketoacidosis

due to excessive reduction in dosages of medications due to excessive reduction in dosages of medications to prevent hypoglycemia to prevent hypoglycemia

**Dehydration and thrombosisDehydration and thrombosis : :

if prolonged fastingif prolonged fasting In hot and humid climates In hot and humid climates Among individuals who perform hard physical labor Among individuals who perform hard physical labor Hyperglycemia Hyperglycemia

Might lead hypovolemia and orthostatic Might lead hypovolemia and orthostatic hypotension , however, hospitalizations due to hypotension , however, hospitalizations due to coronary events or stroke were not increasedcoronary events or stroke were not increased

Taking the decisionTaking the decision

The decision to fast is usually taken by The decision to fast is usually taken by three people: the three people: the patient , the physician patient , the physician and a religious advisor. and a religious advisor.

Ibrahim M. A. ; Managing diabetes during Ramadan; Diabetes Voice; June 2007 | Volume 52 | Issue 2

Thank YouThank You

Insulin Glargine Insulin Glargine during Ramadanduring Ramadan

Eman RushdyEman Rushdy

3232

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.

Epidemiology of Diabetes and Ramadan 1422/2001 : (EPIDIAR) study

Diabetes Care2004 : 27:2306–2311

During Ramadan about During Ramadan about 60%60% of patients of patients change their antidiabetic drug intake. change their antidiabetic drug intake.

35% stop treatment35% stop treatment 8% change the dosage8% change the dosage

Importantly, this is done at the Importantly, this is done at the

patients’ own initiative without patients’ own initiative without medical supervision. 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 Sequelae of hypoglycaemiahypoglycaemia

MildMild””: Adrenergic (BG<70): Adrenergic (BG<70)– No direct serious clinical effects No direct serious clinical effects – With a rapid decline in blood glucose : tachycardia, tachypnea, With a rapid decline in blood glucose : tachycardia, tachypnea,

vomiting, and diaphoresis vomiting, and diaphoresis – May impair subsequent hypoglycaemia awarenessMay impair subsequent hypoglycaemia awareness

Severe Severe Neuroglycopenic Neuroglycopenic (BG<50) (BG<50) Usually associated with slower or prolonged hypoglycemia, Usually associated with slower or prolonged hypoglycemia,

– Stroke and transient ischaemic attacksStroke and transient ischaemic attacks– Memory loss/cognitive impairmentMemory loss/cognitive impairment– Myocardial infarctionMyocardial infarction– Convulsions Convulsions – DeathDeath

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

Recent Clinical Trial Recent Clinical Trial Findings:Findings:

Intensive glucose control in type 2 Intensive glucose control in type 2 diabetes:diabetes:

Was associated with increased mortality Was associated with increased mortality in patients with longstanding DM and in patients with longstanding DM and known CVD known CVD (ACCORD)(ACCORD)

Increases risk of severe hypoglycemia Increases risk of severe hypoglycemia (ADVANCE, ACCORD and VADT)(ADVANCE, ACCORD and VADT)

Hypoglycaemia and CV Hypoglycaemia and CV DiseaseDisease

Desouza C et al Diabetes Care 26: 1485-1489, 2003

Haematologic Responses To HypoglycaemiaHaematologic Responses To Hypoglycaemia


Wright R et al Diabetes/ Metabolism Research and Reviews , 2008

• 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

Inflammatory Responses To HypoglycaemiaInflammatory Responses To Hypoglycaemia


*p < 0.04 vs. Baseline

CRP (mg/L)

Baseline 4 Hours 24 Hours

Diabetes 0.77 0.84 2.31*

Control 0.32 ND 0.96*

Galloway P et al Diabetes Care 23: 861-862, 2000


Wright R et al Diabetes/ Metabolism Research and Reviews , 2008

Hemodynamic

Thrombotic

Inflammatory

Hypoglycaemia Ischaemia

Hypoglycemia Hypoglycemia UnawarenessUnawareness

Type 1 DM

DURATION

Autonomic neuropathy

Recurrent hypoglycemia

MIMICKING NATUREMIMICKING NATURE WITH INSULIN THERAPY WITH INSULIN THERAPY

All persons needAll persons need

both basal and mealtime insulinboth basal and mealtime insulin

to to controlcontrol glucose glucose

6-19

•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 Insulin secreted into portal circulation where 50% of it extracted circulation where 50% of it extracted by liver without reaching systemic by liver without reaching systemic circulation.circulation.

•Insulin catabolized by insulinase in Liver, Kidney, & placenta.

Regulation of Basal Regulation of Basal insulin secretioninsulin secretion

Na+

Na+

K+

K+

K+

K+

GLUT2

Ca2+

Voltage-gated Ca2+ channel

KIR

Pancreatic ß cell

PacemakerPacemakerß cellsß cells

SignalSignal

Insulin granules

Ca2+

Ca2+

Ca2+Ca2+

Vm

Mature insulin granules contracts

by exposure to high intracellular

Ca.

Post prandial insulin Post prandial insulin secretionsecretion

Glucokinase

Glucose

K

Ca

Physiologic Insulin Secretion:Physiologic Insulin Secretion:Basal/Prandial Concept Basal/Prandial Concept

Breakfast Lunch Supper

Insu

lin

(µU

/mL

)

Glu

cose

(mg

/dL

)

Basal Glucose

150

100

50

07 8 9 101112 1 2 3 4 5 6 7 8 9

A.M. P.M.

Time of Day

Basal Insulin

50

25

0

Nutritional Glucose

Nutritional (Prandial) Insulin

Basal Insulin

*Suppresses Glucose Production Between Meals & Overnight

*Nearly constant levels 40- 50% of daily needs

Prandial Insulin *Limits hyperglycemia after meals *Immediate rise and sharp peak *10% to 20% of total daily insulin

requirement at each meal

Good Good

70/30 premixed insulin twice 70/30 premixed insulin twice daily, ….Use the usual morning daily, ….Use the usual morning dose at the sunset meal (Iftar) dose at the sunset meal (Iftar) and half the usual evening dose and half the usual evening dose at predawn (Suhur), at predawn (Suhur),

e.g., 30 units in morning and 20 e.g., 30 units in morning and 20 units in evening…e.g., 70/30 units in evening…e.g., 70/30 premixed insulin, 30 units in Iftar premixed insulin, 30 units in Iftar and 10 units in Suhur .and 10 units in Suhur .

The best: The best:

Consider changing premixed Consider changing premixed insulin preparations to insulin preparations to Glargine or Dtemir Glargine or Dtemir plus plus Lispro, Glulisine or Aspart .Lispro, Glulisine or Aspart .

4848Diabetes Care

September 2005 , pages 2305-11

49

Types of basal insulinTypes of basal insulin

Intermediate-Acting

(e.g. NPH, lente)

Long-Acting Analogues

(glargine, detemir)

Onset 1-3 hr(s) 1.5-3 hrs

Peak 5-8 hrs

No peak with glargine, dose-

dependent peak with detemir

Duration Up to 18 hrs9-24 hrs (detemir); 20-24 hrs (glargine)

Rossetti P, et al. Arch Physiol Biochem 2008;114(1): 3 – 10.

Ideal Basal Insulin:Ideal Basal Insulin:

SafeSafe Effective Effective Less glucose excurtionsLess glucose excurtions

Why GlargineWhy Glargine

5252

Insulin Glargine has less intra-patient variation & has a relatively constant, longer 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 action profile with no pronounced peak in contrast to the peak and intermediate

activity of NPH insulinactivity of NPH insulin

Glu

cose u

tiliza

tion

rate

mg

/kg

/min

0 8 16 24

6

5

4

3

2

1

0

Insulin Glargine

NPH

Time

Insulin Glargine Peakless with 24hour Insulin Glargine Peakless with 24hour Release Release

Janka HU, et al. Diabetes Care 2005;28(2):254–259

LAPTOP: lower incidence of LAPTOP: lower incidence of hypoglycaemia with Insulin hypoglycaemia with Insulin Glargine versus premixGlargine versus premix

54

Less hypoglycemia with glargine Less hypoglycemia with glargine vs NPH vs NPH

Adapted from Mullins P, et al. Clin Ther 2007;29:1607-1619.

p=0.021

NPH insulin

Insulin glargine

Rat

e o

f H

ypo

glyc

em

ia(E

vent

s/10

0 P

atie

nt-Y

ears

)

200

150

100

50

0

6 7 8 9 10

HbA1c (%)

Meta-Regression Analysis

11 randomized controlled trials; n=3,083

Insulin glargine consistently Insulin glargine consistently achieves HbAachieves HbA1C1C ≤ 7% ≤ 7%

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.

Baseline Study end

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.09.5

T-T-T1

(n = 367)INSIGHT2

(n = 206)APOLLO3

(n = 174)INITIATE4

(n = 58)

Schreiber5

(n = 12,216)

Hb

A1

C (

%) 8.6 8.6 8.7 8.78.8

7.0 7.0 7.0 6.8 7.0

5656

Janka HU, et al. Diabetes Care 2005;28(2):254–259

LAPTOP: once-daily Insulin Glargine + oral LAPTOP: once-daily Insulin Glargine + oral antidiabetic drug antidiabetic drug therapy is better than two premixes when therapy is better than two premixes when initiating initiating insulin in Type 2 diabetesinsulin 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 weeksInsulin Glargine + OADs is more efficient in lowering HbA1c, with less hypoglycaemia

5757

Porcellati F, et al. Diabetes Care 2007;30(10):2447–2452

PK/PD: Insulin Glargine has a longer PK/PD: Insulin Glargine has a longer duration of action than detemirduration 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

5858

– FBG at or close to targetFBG at or close to target (90–130 mg/dl) (90–130 mg/dl) but HbA1c ≥but HbA1c ≥7%17%1

– FBG controlled but PPBG consistently highFBG controlled but PPBG consistently high

– Basal insulin dose > 0.5U/KgBasal insulin dose > 0.5U/Kg

The need for prandial insulin despite The need for prandial insulin despite optimal titration of basal insulin is optimal titration of basal insulin is indicated by:indicated by:

Fasting and Insulin Fasting and Insulin Glargine inGlargine inIndividuals With Type 1 Individuals With Type 1 DiabetesDiabetes

Fasting during Fasting during Ramadan in T2DM Ramadan in T2DM patients with insulin patients with insulin GlargineGlargine

Breaking the fastBreaking the fast

Diabetic patients must end their fast Diabetic patients must end their fast immediately in the following cases: immediately in the following cases:

if blood glucose levels drop dramatically to if blood glucose levels drop dramatically to 60 mg/dl60 mg/dl or lower or lower if blood glucose reaches if blood glucose reaches 70 mg/dl in the first few hours70 mg/dl in the first few hours after after

the start of the fast, especially if insulin, sulfonylureas, or the start of the fast, especially if insulin, sulfonylureas, or meglitinides are taken at the pre-dawn meal meglitinides are taken at the pre-dawn meal

if blood glucose levels rise excessively to if blood glucose levels rise excessively to 300 mg/dl.300 mg/dl.


THANK YOUTHANK YOU

People with type 1 diabetesPeople with type 1 diabetes In general, people with type 1 diabetes are at very In general, people with type 1 diabetes are at very

high risk of developing severe complications, and high risk of developing severe complications, and should be strongly should be strongly advised to not fast during advised to not fast during Ramadan.Ramadan.

Management:


Management:Management:

To be Discussed later in the To be Discussed later in the following sessionsfollowing sessions

Two daily injections of NPH intermediate-Two daily injections of NPH intermediate-acting insulin in combination with a short-acting insulin in combination with a short-acting insulin acting insulin

administered the usual dose before Iftar administered the usual dose before Iftar and half the dose before Sahour, However, and half the dose before Sahour, However, there is an increased risk of hypoglycaemia there is an increased risk of hypoglycaemia around midday around midday

Another option : use one daily injection of Another option : use one daily injection of the long-acting insulin analogue, glargine; the long-acting insulin analogue, glargine; or detemir along with pre-meal rapid-acting or detemir along with pre-meal rapid-acting insulin analogues.insulin analogues.

ManagementManagement

People with type 2 diabetesPeople with type 2 diabetesLifestyle and nutritionLifestyle and nutrition In people who manage their diabetes with diet and physical In people who manage their diabetes with diet and physical

activity, the risks associated with fasting are quite low. activity, the risks associated with fasting are quite low. However, if people eat excessively, a potential risk of post-meal However, if people eat excessively, a potential risk of post-meal

hyperglycaemia . hyperglycaemia . Distributing energy intake over two to three smaller meals during Distributing energy intake over two to three smaller meals during

the non-fasting interval may help. the non-fasting interval may help. A person’s regular daily exercise programme should be modified A person’s regular daily exercise programme should be modified

in its intensity and timing to avoid episodes of hypoglycaemiain its intensity and timing to avoid episodes of hypoglycaemia..


Glucose Glucose absorptionabsorption

Hepatic glucoseHepatic glucoseoverproductionoverproduction

Beta-cellBeta-celldysfunctiondysfunction

InsulinInsulinresistanceresistance

Major Targeted Sites of Oral Drug Major Targeted Sites of Oral Drug ClassesClasses

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.

Pancreas

↓Glucose level

Muscle and fatLiver

Biguanides

TZDs Biguanides

Sulfonylureas

Meglitinides

TZDs

Alpha-glucosidase inhibitors

Gut

The glucose-dependent mechanism of DPP-4 inhibitors targets 2 key defects: insulin release and unsuppressed hepatic glucose production.

DPP-4 inhibitorsGLP-1

DPP-4 inhibitors

Biguanides

Source of hyperglycemia during Source of hyperglycemia during fasting hours:fasting hours:

1- Dietary 1- Dietary

2- Insulin deficiency2- Insulin deficiency

3- Hepatic glucose output 3- Hepatic glucose output

4- Non of the above.4- Non of the above.

An Ideal Oral Agent Should You An Ideal Oral Agent Should You

Select during fasting..?Select during fasting..?

Achieve A1c TargetAchieve A1c Target

Has lower hypoglycemic eventsHas lower hypoglycemic events

Promotes weight lossPromotes weight loss

In general, medications that act by increasing insulin sensitivity In general, medications that act by increasing insulin sensitivity

are associated with a significantly lower risk of hypoglycaemia are associated with a significantly lower risk of hypoglycaemia

than insulin secretagoguesthan insulin secretagogues

Glucose Glucose absorptionabsorption

Hepatic glucoseHepatic glucoseoverproductionoverproduction

Beta-cellBeta-celldysfunctiondysfunction

InsulinInsulinresistanceresistance

Major Targeted Sites of Oral Drug Major Targeted Sites of Oral Drug ClassesClasses

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.

Pancreas

↓Glucose level

Muscle and fatLiver

Biguanides

TZDs Biguanides

Sulfonylureas

Meglitinides

TZDs

Alpha-glucosidase inhibitors

Gut

The glucose-dependent mechanism of DPP-4 inhibitors targets 2 key defects: insulin release and unsuppressed hepatic glucose production.

DPP-4 inhibitorsGLP-1

DPP-4 inhibitors

Biguanides

ManagementManagement

Oral medicationsOral medications MetformineMetformine: two thirds of the total daily dose to : two thirds of the total daily dose to

be taken after the sunset meal, with the other be taken after the sunset meal, with the other third taken after the pre-dawn meal.third taken after the pre-dawn meal.

Rosiglitazone and PioglitazoneRosiglitazone and Pioglitazone: have a low risk of : have a low risk of hypoglycemia. Usually no change in dose is hypoglycemia. Usually no change in dose is required.required.


SulfonylureasSulfonylureas are believed to be unsuitable for are believed to be unsuitable for use during fasting because of the inherent risk of use during fasting because of the inherent risk of hypoglycemia; they should be used with caution hypoglycemia; they should be used with caution and select the safest SU (glimipride). and select the safest SU (glimipride).

MeglitinidesMeglitinides are superior to SU as long as they are superior to SU as long as they could control hyperglycemia.could control hyperglycemia.

ChlorpropamideChlorpropamide is absolutely contraindicated is absolutely contraindicated during Ramadan because of the high possibility of during Ramadan because of the high possibility of prolonged and unpredictable hypoglycemia. prolonged and unpredictable hypoglycemia.


InsulinInsulin The aim should be to maintain necessary levels of basal The aim should be to maintain necessary levels of basal

insulin to suppress output of glucose from the liver to near-insulin to suppress output of glucose from the liver to near-normal levels during fasting. normal levels during fasting.

Careful use of intermediate or Careful use of intermediate or long-acting insulins plus a long-acting insulins plus a short-acting insulin administered before mealsshort-acting insulin administered before meals would be an would be an effective strategy.effective strategy.


Recommended changes to treatment Recommended changes to treatment regimen in patients with type 2 diabetes regimen in patients with type 2 diabetes who fast during Ramadwho fast during Ramadanan

(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

47 years old male , accountant47 years old male , accountant Sedentary lifestyleSedentary lifestyle BMI 32BMI 32 Diabetic 5 years on Glimipride 4 mg /day Diabetic 5 years on Glimipride 4 mg /day

and metformin 500 mg 3 times dailyand metformin 500 mg 3 times daily

Case #1

Glimipride adjusted dose (2 or 3 mg) Glimipride adjusted dose (2 or 3 mg) before Iftar and metformin 1000 mg after before Iftar and metformin 1000 mg after

Iftar and 500mg after SahourIftar and 500mg after Sahour

51 year old male 51 year old male Type 2 diabetes currently treated with Type 2 diabetes currently treated with

Metformin 1500 mg Metformin 1500 mg Serum creatinin 1.9 mg/dlSerum creatinin 1.9 mg/dl

Case #2

Not to fast Shift to Insulin Sensitizers

48 years old male 48 years old male BMI 28BMI 28 Diabetic 11 years controlled on mixed Diabetic 11 years controlled on mixed

Insulin 60 U breakfast &40 U dinner Insulin 60 U breakfast &40 U dinner

and metformin 850mg after lunchand metformin 850mg after lunch

Case #1

Basal Insulin 40 U & Short acing (better Basal Insulin 40 U & Short acing (better ultra short analogues) 30 U Iftar & 10 U ultra short analogues) 30 U Iftar & 10 U

SahourSahour

60 U Iftar and 20 U Sahour

Patient Care and Patient Care and Management !!!Management !!!

Frequent monitoringFrequent monitoring This is especially critical in people who require insulinThis is especially critical in people who require insulin

Medical assessmentMedical assessment This should take place one to two months before Ramadan. This should take place one to two months before Ramadan. Specific attention should be paid to people’s overall well-being and to the Specific attention should be paid to people’s overall well-being and to the

control of their blood glucose levels, blood pressure, and lipids. control of their blood glucose levels, blood pressure, and lipids.


NutritionNutrition People should maintain a healthy and balanced diet during People should maintain a healthy and balanced diet during

Ramadan. Ramadan.

The common practice of ingesting large amounts of foods that The common practice of ingesting large amounts of foods that are high in fat and carbohydrates, should be avoidedare high in fat and carbohydrates, should be avoided

It is recommended that non-caloric fluid intake be increased It is recommended that non-caloric fluid intake be increased during the non-fasting hours. during the non-fasting hours.

The Sahour meal should be taken as late as possible before the The Sahour meal should be taken as late as possible before the start of the daily fast.start of the daily fast.


x

Physical activityPhysical activity

Normal levels of physical activity can be maintained.Normal levels of physical activity can be maintained. However, However, excessive physical activityexcessive physical activity may lead to may lead to

higher risk of hypoglycaemia and should be avoided. higher risk of hypoglycaemia and should be avoided. x

If TarawihIf Tarawih prayers (multiple prayers after the sunset prayers (multiple prayers after the sunset meal) are performed, they should be meal) are performed, they should be considered a considered a part of a person’s daily physical activity programmepart of a person’s daily physical activity programme..


Diabetics should not fast Diabetics should not fast if :if :

Uncontrolled (no defined figure)Uncontrolled (no defined figure) Recurrent hypoglycemic attacks Recurrent hypoglycemic attacks Hypoglycemia unawareness.Hypoglycemia unawareness. A history of Diabetic Ketoacidosis · A history of Diabetic Ketoacidosis · Recent infectionsRecent infections Kidney disease Kidney disease Unstable ischemic heart disease.Unstable ischemic heart disease.

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By Eman Rushdy