Management of Diabetes Mellitus in Ramadan Fasting Month

Pradana Soewondo

Division of Endocrine and Metabolism, Department of Internal

Medicine, Medical Faculty, University of Indonesia

Surah Al-Baqarah: 183-184

• …..Observing As-Saum (the fasting) is prescribed for you as it was prescribed for those before you, ….

• ….., but if any of you is ill or on a journey, …… And as for those who can fast with difficulty, (e.g. elderly, etc),…….

PHYLOSOPHY OF FASTING

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

• Food and fluids may be consumed freely during the night, but forbidden during day time, including oral and parenteral medication.

• This will involve a sudden and major change in the daily meals.

• This include meal timing, total calories, food type and consistency.

• Prior to the month of Ramadan, people usually take 3 major meals (breakfast, lunch, dinner/supper)

• This will change to only two meal named Iftar and Sahur. Iftar will be around 6:00 pm and Sahur will be around 3:00 am.

Things Happened During Ramadan

• Eating habits change in many ways, not only do mealtimes change, but patterns of meals, the short of food eaten and caloric intake all change in a stereotyped way.

• Increased in post prandial physical activity during the nighttimes associated with Tarawih.

• Psychological changes due to the general spiritual atmosphere during Ramadan, which create a feeling of inner well-being

Physiological State of Healthy Individuals During Ramadan (Kuwait study) (1)

• Body weight decrease transiently during the first half of Ramadan, but recovered by the end.

• Respiratory and cardiovascular parameters during exercise were perturbed.

• Plasma osmolarity and protein concentration were increased during Ramadan, maybe an indication of dehydration.

Physiological State of Healthy Individuals During Ramadan (2)

• Increases in acid and pepsin secretion Increases in acid and pepsin secretion were noted with no changes in plasma were noted with no changes in plasma gastrin, mucogastrin, or the duodeno-gastrin, mucogastrin, or the duodeno-gastric reflex. (Moroccan study)gastric reflex. (Moroccan study)

• Decrease in fasting plasma glucose Decrease in fasting plasma glucose and insulin. Increase in plasma and insulin. Increase in plasma proteins. Lipid parameters were not proteins. Lipid parameters were not altered.altered. (Tunisian study)(Tunisian study)

Impact of Fasting in Diabetics During Ramadan

• Blood glucose levels triggered homeostatic

mechanism to prevent hypoglycemia. But in

diabetics, this mechanism can be disrupted, and

also perturbed by medication.

• Risk of hypoglycemia during daytime and

hyperglycemia following Iftar are 6 % and 3 %

respectively.

• Changes in timing medication are important.

Impact of Fasting in Diabetics During Ramadan

• If a proper medication regimen is followed, stable and uncomplicated patients on OHA should be able to fast without problems.

• Patients taking single dose insulin or combination therapy may be able to fast but needs to be evaluated on an individual basis.

Impact of Fasting in Diabetics During Ramadan

• In the fasting state, individual depends totally on endogenous substrates for energy.

• Fasting subject is considered in a state of catabolism since his source of energy are all decreasing.

• The liver supplies glucose by glycogenolysis.

Impact of Fasting in Diabetics During Ramadan

• Glucose oxidation in liver and muscles is spared as soon as increased quantities of FFA becomes available.

• A balance is reached at a plasma glucose level sufficient to ensure adequate brain function and at insulin and glucagon levels sufficient to prevent excessive depletion of previously stored nutrients.

• Observational study• N=60 (30 males and 30 females) • Well controlled type 2 diabetics treated with

OHA (PPG < 200 mg%)• Mean body weight 0,75 Kg • Mean Post Prandial Glucose 9,32 mg% • No correlation from both parameters.

Askandar T etal, Kopapdi V,1978.

Effect on Diabetic Controlled During Ramadan Fasting

• Observational study• Well controlled diabetics with out severe

complication • N=55; 49 on diet and 6 on diet +OHA• No Changes in BW, BG and lipid profile• There is no negative effects of fasting during

Ramadan, as long as they followed the instructions.

Manaf A. etal, Kopapdi V, 1981

Effect of Ramadan Fasting on Well Controlled Diabetic Patients

• Observational study • N=22; controlled diabetic• Diet and medication were maintain • Blood glucose levels from 8 to 11 am at the

first and last week of fasting month, but not from 11 am to 6 pm.

• Hypoglycemia should be anticipated when good controlled diabetics are going to fast.

Soegondo S etal, AOCE

Blood Glucose Responses Of Diabetics During the Fasting Month Ramadan

• Observational study

• N=41 type 2 diabetics (9 on diet, 12 on single OHA,

and 20 on combined OHA)

• Number of symptomatic hypoglycemic periods,

which were not biochemically verified, increased in

eight of patients (19,5%) during Ramadan. None of

the patients, however, experienced severe

hypoglycemia or neuroglycopenic symptoms

Ali Riza etal, Univ of Ankara

Ali Riza etal, Univ of Ankara

In conclusion:

• type 2 diabetic is not a contraindication to fasting

in Ramadan

• Patients on single or combination OHA could

observe Ramadan fasting with appropriate

instruction about meals and OHA use.

• However some patients may still experience an

increased number of hypoglycemic episodes

Treatment regimen and HbA1C level in 8 type 2 Treatment regimen and HbA1C level in 8 type 2 Diabetics, whose Hypoglycemic Events Were More Diabetics, whose Hypoglycemic Events Were More Frequent During Ramadan FastingFrequent During Ramadan Fasting

HyHypoglycemic events poglycemic events HbA1c level (%) HbA1c level (%) Patient before during Treatment before after after Patient before during Treatment before after after number number regimen regimen 3 weeks 8 weeks 3 weeks 8 weeks

1 1 2 Diet only1 1 2 Diet only 6.6 6.6 6.7 6.6 6.7 6.6 2 1 4 Gliclazide2 1 4 Gliclazide 7.5 7.3 7.2 7.5 7.3 7.2 3 1 4 Gliclazide3 1 4 Gliclazide 7.6 7.2 7.4 7.6 7.2 7.4 4 1 3 Glybornuride 7.6 7.3 7.34 1 3 Glybornuride 7.6 7.3 7.3 5 1 3 Gliclazide, MF 5.6 5.8 5.95 1 3 Gliclazide, MF 5.6 5.8 5.9 6 1 9 Glybori,MF 7.5 7.6 7.5 6 1 9 Glybori,MF 7.5 7.6 7.5 7 1 37 1 3 Glyburi,MF,AC 8.2 8.6 8.7 Glyburi,MF,AC 8.2 8.6 8.7 8 1 8 Glipizide, MF,AC 9.5 9.6 9.28 1 8 Glipizide, MF,AC 9.5 9.6 9.2

AC=acarbose; MF=metforminAC=acarbose; MF=metformin

Mafauzy et al., 1990

• N=22; carried out in Malaysia.• No evidence of hypoglycemia was obtained.• Total caloric and carbohydrate intake both

during Ramadan compared with Shaban, although the proportion of simple carbohydrate consumed from 8,4% to 14%

• No changes in FBG or cholesterol level.• But fructosamine level from 6.6 to 4.3 mM.

An Observational Survey of the Impact of Ramadan fasting on Diabetes

Muslims with NIDDM Fasting During Ramadan: Treatment with Glibenclamide • Setting of study university hospital, private hospital,

private clinic in Casablanca and Rabat, Morocco

• n = 591 diabetic patients (198 men, 391 women and two unspecified) with similar duration of illness, length and amount of glibenclamide treatment.

• To compare the efficacy of two glibenclamide regimen in NIDDM who were fasting and regular dose in non fasting group.

Belkhadir et al., 1993

• Non randomized non fasting control group >< two groups of patients who fasted randomized equally two one of two regimen

• Take their usual morning dose of glibenclamide in the evening and their

usual evening dose before dawn; or to follow this pattern but to reduce the total dose by a quarter.

Characteristics of Patients on Admission to Study, Value are Means (standard deviations) unless Stated Otherwise

Groups of patients*

Control(n = 194)

56137

57.2 (9.0)64.9 (11.3)25.9 (3.9)8.53 (6.2)11.7 (3.5)383 (84)

14.2 (3.3)

No of menNo of womenAge (years)†Weight (kg)‡Body mass index (kg/m2) ‡Duration of diabetes (years)§Usual daily dose of glibenclamide (mg)llSerum concentration of fructosamine (mol)§Glycated hemoglobin (%)§

Full doseof glibenclamide

(n = 199)

75123

54.9 (9.3)68.6 (10.3)26.7 (3.8)7.03 (5.5)10.7 (3.1)366 (85)

13.7 (3.4)

Reduced doseof glibenclamide

(n = 198)

67131

54.8 (9.7)67.9 (11.4)26.7 (4.2)

7.05 (5.35)10.7 (3.5)352 (82)

13.2 (3.6)

p Value

NS0.180.020.010.060.020.020.01

0.01

Data missing for † 10 cases, ‡ 4 cases, § 13 cases, and II 30 cases

Characteristics of the 542 Who Completed the Study at The End of Ramadan. Figures are Means (standard deviations)

Groups of patients*

Control(n = 177)

396 (91)400 (102)

14.3 (3.6)14.7 (3.2)

65.2 (11.4)65.7 (11.4)

Fructosamine concentration (µmol/l): At start of Ramadan At end of RamadanGlycated hemoglobin (%): At start of Ramadan At end of RamadanBody weight (kg) At start of Ramadan At end of Ramadan

Full doseof

glibenclamide(n = 183)

367 (80)381 (96)

13.6 (3.5)14.0 (2.9)

68.2 (10.0)69.2 (10.0)

Reduced doseof

glibenclamide(n = 182)

359 (82)376 (98)

13.2 (3.6)13.6 (3.2)

68.2 (82) 68.7 (10.8)

Number of Hypoglycemia Events (number of affected patients) Reported During Study

Duringrun in

16 (15)

19 (13)

18 (15)

Control

Full dose of glibenclamide

Reduced dose of

glibenclamide

DuringRamadan

11 (9)

14 (10)

10 (9)

Duringfollow up

8 (6)

16 (12)

8 (6)

Total

35 (30)

49 (35)

36 (30)

Groups of patients*

Result

At the end of Ramadan there were no significant differences between the groups in fructosamine concentration, HbA1c and number of hypoglycemic event.

Conclusion

Glibenclamide is effective and safe for patients with non-insulin dependent diabetes who fast during Ramadan. The easiest regimen is taking the normal morning dose at sunset and any evening dose before dawn

HYPOGLYCAEMIC EVENT AMONG TYPE 2 DIABETICS ON HYPOGLYCAEMIC EVENT AMONG TYPE 2 DIABETICS ON GLIMEPIRIDE AND OTHER SULFONILUREAS DURING RAMADHAN GLIMEPIRIDE AND OTHER SULFONILUREAS DURING RAMADHAN

Soewondo P et al. RSCM, Jakarta 1999.Soewondo P et al. RSCM, Jakarta 1999.

METHODMETHOD

•To observe the occurrence of hypoglycaemic event on type 2 To observe the occurrence of hypoglycaemic event on type 2 Diabetics on glimipiride and other sulfonilureas during fasting Diabetics on glimipiride and other sulfonilureas during fasting monthmonth

•To describe the nutrition intake and metabolic changes on type 2 To describe the nutrition intake and metabolic changes on type 2 diabetic who were fasting during Ramadhan monthdiabetic who were fasting during Ramadhan month

OBJECTIVEOBJECTIVE

•Hospital based, observational study, enrolliring controlled type 2 Hospital based, observational study, enrolliring controlled type 2 diabetics who want to fast Ramadhandiabetics who want to fast Ramadhan

•23 controlled type 2 diabetics who was treated with single dose sulfonilurea were enrolled

RESULTSRESULTS

23 type 2 DM

2 drop out21 completed the study

12 on glimepiride 9 other Sulfonilurea (glibenclamide, glicazide,

gliquidone, glipizide)

125

119

111

105

128132

126 126

909498

102106110114118122126130134138

I II III IVWeek

mg

/dl

Glimepirid

other Sulfonilurea

Average Blood Average Blood Glucose Glucose Level before dawn in Type 2 Level before dawn in Type 2 Diabetic Patients During Ramadan Fasting MonthDiabetic Patients During Ramadan Fasting Month

Average Blood Average Blood Glucose Glucose Level before breakLevel before breakIn Type 2 Diabetic Patients During Ramadan Fasting MonthIn Type 2 Diabetic Patients During Ramadan Fasting Month

106

96 9698

100

104

100

104

90

95

100

105

110

I II III IV

Week

mg

/dl

Glimepirid

Other Sulfonilurea

Average Energy Intake in Type 2 Diabetic patients Average Energy Intake in Type 2 Diabetic patients during Ramadan Fasting Monthduring Ramadan Fasting Month

1000,00

1100,00

1200,00

1300,00

1400,00

1500,00

1600,00

1700,00

1 2 3 4 5 6

Visit

En

erg

y(ca

l)

Victim GroupVictim Group

GlimGlimeepiridpiridee Other Sulfonilurea Other Sulfonilureass

(n=12)(n=12) (n=9) (n=9) PP

MenMen 2 2 4 4WomenWomen 10 10 5 5 0.3310.331Old (year)Old (year) 49.8 (49.8 (++ 13.4) 13.4) 58.1 58.1 ((++ 8.4) 8.4) 0.1210.121Lama DM (month)Lama DM (month) 33.9 (33.9 (++ 34.2) 34.2) 74.2 ( 74.2 (++ 45.0) 45.0) 0.0480.048Fasting Glucose (mg/dl)Fasting Glucose (mg/dl) 124.0 (124.0 (++ 30.7) 30.7) 129.8 ( 129.8 (++ 21.9) 21.9) 0.6370.637Post PrandialPost Prandial 185.8 (185.8 (++ 68.9) 68.9) 183.0 ( 183.0 (++ 45.4) 45.4) 0.6440.644HbA1c (%)HbA1c (%) 7.4 ( 7.4 (++1.3)1.3) 7.8 ( 7.8 (++1.3)1.3) 0.4700.470IMT (kg/mIMT (kg/m22)) 23.3 23.3 23.623.6Dose (mg)Dose (mg) 2.6 ( 2.6 (++1.3)1.3) Glibenklamid 4 (Glibenklamid 4 (++1.4)1.4)

GliklazGliklaziiddee 80 80GlipisidGlipisid 5 5Glikuidon 22.5 (Glikuidon 22.5 (++ 10.6) 10.6)

Subject Characteristics Subject Characteristics

GroupGroup

GlimepirideGlimepiride OtherOther SulfonilureaSulfonilurea

BMIBMI (kg/m2) (kg/m2)

Before Before 23.3 23.3 23.6 23.6

After After 23.2 23.2 23.223.2

HbA1c (%)HbA1c (%)

Before Before 7.4 ( 7.4 (++1.3)1.3) 7.8 ( 7.8 (++1.3)1.3)

After After 7.2 ( 7.2 (++1.2)1.2) 7.3 ( 7.3 (++1.7) 1.7)

Body Mass Index and HbA1c Level in Type 2 Diabetic Patient Body Mass Index and HbA1c Level in Type 2 Diabetic Patient Before and After Ramadan Fasting MonthBefore and After Ramadan Fasting Month

Parameter \ GroupParameter \ Group GlimGlimeepiridpiridee Other SulfonilureaOther Sulfonilurea

Total cholesterol Total cholesterol (mg/dl)(mg/dl)Before Before 214 ( 214 (++36)36) 230 (230 (++70)70)After After 218 (218 (++38)38) 225 (225 (++53)53)

HDL HDL Cholesterol (mg/dl)Cholesterol (mg/dl)Before Before 56 ( 56 (++6)6) 48 (48 (++8)8)After After 56 ( 56 (++6)6) 51 (51 (++8) 8)

LDL LDL Cholesterol (mg/dl)Cholesterol (mg/dl)Before Before 115 ( 115 (++61)61) 141 (141 (++50)50)After After 133 ( 133 (++37)37) 141 (141 (++46)46)

Triglycerida (mg/dl)Triglycerida (mg/dl)Before Before 213 (213 (++24)24) 205 (205 (++14)14)After After 146 (146 (++45)45) 1166 (66 (++49) 49)

Ureum (mg/dl)Ureum (mg/dl)Before Before 32 (32 (++4)4) 37 (37 (++10)10)After After 52 (52 (++66)66) 41 (41 (++24)24)

Creatinine (mg/dl)Creatinine (mg/dl)Before Before 0.9 (0.9 (++0.2)0.2) 1.1 (1.1 (++0.5)0.5)After After 0.8 (0.8 (++0.2)0.2) 1.3 (1.3 (++1.1)1.1)

Lipid profile and kidney function in Type 2 Diabetic Lipid profile and kidney function in Type 2 Diabetic Patient Before and After Ramadan Fasting Month Patient Before and After Ramadan Fasting Month

CONCLUSION

There was no hypoglycemic event were reported in both groups in this study

Changes in caloric and nutrient intake were noted and should be considered for diet consultation as well as treatment adjustment

Recommendations on The Management of Diabetes During Ramadan

• Put forward at a Consensus Meeting held in Casablanca, Morocco in 1995

• These covered:

– criteria allowing for or exempting from fasting and recommendations for monitoring.

– Other topic covered included community education programmers, treatment regimens

– methodology and content for the future research programs

CURRENT RECOMENDATIONS

• Permitted to fasting :

NIDDM patients treated with biguanides or sulphonyureas, who are stable and do not have any complicating progressive co morbid pathology.

• Exempted from fasting :

IDDM, unstable disease, co-morbid degenerative disease, pregnancy, elderly.

CURRENT RECOMENDATIONS

• Monitoring was recommended before, during and after Ramadan, include diabetic symptoms and glucose control, psycho- logical state and co morbidity.

• Education programs directed at patients and their families. should focus on condition in which fasting is contraindicated, modifying the regimen, dietary considerations, and the importance of monitoring.

HOW TO IMPROVE THE MANAGEMENT

1. Guidelines

The existence of clear guidelines on the management of diabetes during Ramadan are indispensable in ensuring safe and rewarding fasting in patients treated in primary care away from specialist clinic.

2. Education Programs

3. Research

Contraindications

Four contraindications in which patient should be exempted from fasting :

• Patients treated with insulin (NIDDM or IDDM)

• Brittle and decompensated diabetes (history of episodes of DKA or NKHO)

• Pregnancy• Patients with potentially life-threatening

acute complications

• Ramadan provides and excellent opportunity to initiate healthy lifestyle changes.

• Motivation for self improvement is high at this time of year, the switch in eating pattern breaks previous habits, and weight lose goals

• Meals time should be fixed, with the principal meal in the evening, and the lesser meal before sunrise.

Lifestyle

Lifestyle

• Patient should be encouraged to eat a proper.

• Eating snacks between two meals should be avoided

• Ensure that an appropriate level of physical activity is maintained, whether formal exercise programs or associated with fulfilling religious obligations.

MEDICATION

• In principle, any efficacious medication upon which patients is stabilized can be used during Ramadan.

• An abrupt change in the nature of medication given should be avoided.

• Medications regimen during Ramadan need to be modified in timing and possibly dose, and should be tailored for each individual patient.

Monitoring

• Important to be done to ensure adequate blood sugar control in spite of changes in eating habits and treatment protocols.