Ramadaan and Diabetes : South Africa

Transcription

1 Ramadaan and Diabetes : South Africa M.A.K. Omar Dept. of Diabetes and Endocrinology Nelson R Mandela School of Medicine University of KwaZulu Natal South Africa

2 Conflict of Interest Statement - Nil Acted as a consultant for and/or received support from: Astra-Zeneca, BMS,Boehringer-Ingelheim, Eli Lilly, MSD, Medtronic, Merck, Novartis, Novo Nordisk, Pfizer,Roche,SanofiAventis,Servier

3 Section 1: Brief Introduction to Ramadan

4 The Holy Quran, Surah Al Baqarah 2:185 Ramadan is the (month) in which was sent down the Quran, as a guide to mankind, also clear (Signs) for guidance and judgment (between right and wrong). So every one of you who is present (at his home) during that month should spend it in fasting, but if any one is ill, or on a journey, the prescribed period (should be made up) by days later. Allah intends every facility for you; He does not want to put to difficulties. (He wants you) to complete the prescribed period, and to glorify Him in that He has guided you; and perchance ye shall be grateful.

5 Ramadan: Background Ramadan is a holy month in the Islamic calendar Healthy Muslims are obliged to abstain from all food, drink, and oral medications from dawn to sunset throughout the month Those exempt from fasting include children below the age of 12, individuals with illness, travelers, and women who are menstruating, pregnant, or nursing There is a significant change in meal pattern, sleep/wake cycle and spiritual and social activities. Ramadan is the ninth month of the Islamic lunar calendar Duration varies between 29 and 30 days Each year it occurs approximately 10 days earlier Every 9 years it occurs in a different season The hours spent fasting can range from only a few hours to more than 20 hours depending on geographical location and season Most people eat 2 meals a day during Ramadan Suhur (meal before dawn) and Iftar (meal after sunset)

6 Section 2: Physiological Impact of Fasting

7 Pathophysiology of Postprandial State In non-diabetic individuals: Eating stimulates insulin secretion, which promotes storage of glucose in liver and muscle as glycogen Insulin secretion suppresses glucagon secretion Increased insulin concentrations and suppressed glucagon stop hepatic glucose production In diabetic individuals: Insulin secretion is perturbed; after eating, glucagon levels remain high after a meal and glucose released by the liver continues to enter circulation, resulting in hyperglycemia Al-Arouj et al. Diabetes Care 2010;33(8): Aronoff et al. Diabetes Spectrum 2004;17(3):

8 Section 3: Clinical Implications of Fasting

9 Potential Complications of Fasting Hypoglycemia Hyperglycemia Diabetes Keto-acidosis Dehydration Thrombosis Changes in weight During Ramadan

10 Complications of Fasting: Hypoglycemia Risk increases when you decrease food intake 1 There is an increased risk of severe hypoglycemia in individuals with diabetes who fast during Ramadan fold increase in type 1 diabetes patients 7.5-fold increase in type 2 diabetes patients Patients who do not change dosages of oral medications or insulin and who have significant lifestyle changes during Ramadan are more likely to have hypoglycemia 2 1. DCCT Research Group. N Engl J Med 1993;329(14): Salti et al. Diabetes Care 2004;27(10):

11 Complications of Fasting: Hyperglycemia Several studies have shown mixed results with regard to loss of glycemic control in patients with diabetes who fast during Ramadan 1-5 The incidence of severe hyperglycemia has been shown to increase 6 3-fold in type 1 diabetes patients fasting during Ramadan 5-fold in type 2 diabetes patients fasting during Ramadan Patients with an increase in food and/or sugar intake have significantly higher rates of severe hyperglycemia 6 1. Miller et al. Arch Intern Med. 2001;161: UKPDS Group. Lancet 1998;352: Beckman et al. JAMA. 2002;287: Akhan et al. Acta Neurol Scand. 2000;101: Alghadyan et al. Ann Ophthalmol. 1993;25: Salti et al. Diabetes Care. 2004;27(10):

12 Potential Complications of Fasting: Weight Change The effect of the fasting period of Ramadan on weight is not definitive Studies have shown weight gain, loss, and no change in patients fasting during Ramadan 1-5 Variability in weight changes may be attributed to local traditions and food quality 5 1. Sari et al. Endocr Res 2004;30(2): Uysal et al. Diabetes Care 1998;21(11): Mafauzy et al. Med J Malaysia 1990;45(1): Khatib et al. Saudi Med J 2004;25(12): Rashed AH. BMJ 1992;304(6826):521-2.

13 Section 4: Epidemiology of Fasting During Ramadan

14 EPIDIAR: A Population-Based Study of Diabetes and Its Characteristics During the Fasting Month of Ramadan in 13 Countries

15 EPIDIAR: Fasting Statistics Patients fasting 15 days 42.8% of type 1 diabetes patients 78.7% of type 2 diabetes patients Inter-country differences in patients fasting 15 days Range: 9.4% in Morocco to 71.6% in Saudi Arabia among type 1 diabetes patients Range: 57.8% in Turkey to 89.8% in Malaysia and Bangladesh among type 2 diabetes patients Average number of fasting days 23 days among type 1 diabetes patients 27 days among type 2 diabetes patients Salti et al. Diabetes Care 2004;27(10):

16 EPIDIAR: Change in Weight Type 1 Diabetes N=1070 Type 2 Diabetes N=11,173 Weight changes, n (%) No change Gain Loss 562 (62.5) 161 (17.9) 176 (19.6) 5286 (54.1) 1861 (19.1) 2628 (26.9) Value of weight change, kg Overall population Patients who fasted at least 1 day Patients who reported weight gain Patients who reported weight loss 332 (0.12±3.79) 235 (-0.51±3.23) 159 (3.24±2.71) 173 (-2.74±1.92) 4367 (-0.25±3.25) 4152 (-0.32±3.08) 1811 (2.78±2.49) 2556 (2.39±1.61) Data are n (%) or n (means ± SD). Salti et al. Diabetes Care 2004;27(10):

17 EPIDIAR: Change in Medication Insulin dose, n (%) Increased Decreased Maintained Stopped OAM dose, n (%) Increased Decreased Maintained Stopped OAM = oral antihyperglycemic medication. Type 1 Diabetes N= (10.7) 237 (24.0) 637 (64.5) 8 (0.8) 5 (5.3) 14 (14.9) 74 (78.7) 1 (1.1) Type 2 Diabetes N=11, (8.2) 452 (24.7) 1174 (64.1) 55 (3.0) 415 (4.4) 1779 (18.8) 7085 (74.8) 197 (2.1) Salti et al. Diabetes Care 2004;27(10):

18 EPIDIAR: Conclusions Prevalence estimates for diabetics fasting during Ramadan were 43% for type 1 diabetes and 86% for type 2 diabetes patients Only 1 in 4 patients changed oral antihyperglycemic medication dosage during Ramadan Only 1 in 3 patients changed insulin dosage during Ramadan Severe hypoglycemia and severe hyperglycemia were more frequent during Ramadan than in the preceding year Salti et al. Diabetes Care 2004;27(10):

19 Section 5: Studies of the Effects of Available Therapy on Glycemic Control in Ramadan

20 Dietary Habits During Ramadan Daily caloric and carbohydrate intake has been shown to decrease among diabetic patients during Ramadan 1 65% of daily caloric intake occurs during Iftar (after sunset meal) 2 Considerable quantities of traditionally sweet and carbohydrate-rich foods are consumed during nonfasting hours 1 The dietary habits during non-fasting hours increase the risk of hyperglycemia and weight gain in diabetic patients 3 1. Benaji et al. Diabetes Res Clin Pract 2006;73(2): Gharbi et al. East Mediterr Health J 2003;9(1-2): Rashed. BMJ 1992;304(6826):521-2.

21 Oral Antihyperglycemic Medications During Ramadan In patients with well-controlled type 2 diabetes, oral antihyperglycemic medication (OAMs) administered at sunset meal (Iftar) and sunrise meal (Suhur) 1-3 generally: Improve or have no effect on glycemic control Do not increase hypoglycemic episodes Hyperglycemic episodes have been shown in patients who arbitrarily reduce or stop their OAMs 4 1. Mafauzy et al. Med J Malaysia 1990;45(1): Khatib et al. Saudi Med J 2004;25(12): Belkhadir et al. BMJ 1993;307(6899): Benaji et al. Diabetes Res Clin Pract 2006;73(2):

22 Patients, % Nearly 20% of SU-Treated Muslim Patients With Type 2 Diabetes Experienced Symptomatic Hypoglycemia During Ramadan Fasting 1 Incidence of Symptomatic Hypoglycemia During Ramadan in 2009 by Treatment Group Glimepiride Gliclazide Glibenclamide 10 Glipizide Overall 5 0 n=428 n=386 n=535 n=29 n= occurred among the 271 patients who recorded 1 symptomatic hypoglycemic event Most common symptoms reported were: headache (14.5%), sweating (10.2%), tremor (8.5%), and palpitations (7.0%) Mean daily doses of SUs were: 2.8 mg for glimepiride, mg for gliclazide, 10.7 mg for glibenclamide (glyburide), and 6.6 mg for glipizide. SU=sulfonylurea. 1. Aravind SR et al. Curr Med Res Opin. 2011;27(6):

23 Patients, % 6.7% of SU-Treated Muslim Patients With Type 2 Diabetes Experienced Severe Hypoglycemia During Ramadan Fasting 1 Incidence of Severe Hypoglycemia During Ramadan in 2009 by Treatment Group Glimepiride Gliclazide Glibenclamide Glipizide Overall 2 0 n=428 n=386 n=535 n=29 n=1378 No marked differences in the incidence of severe hypoglycemia between treatment groups The incidence of severe hypoglycemia requiring medical assistance was 3.7% for the entire patient cohort 1.2% of patients experienced a serious hypoglycemia-related complications during Ramadan 1. Aravind SR et al. Curr Med Res Opin. 2011;27(6):

24 Patients, % Switching to Sitagliptin Treatment Was Associated With a Significantly Lower Incidence of Symptomatic Hypoglycemia Compared With Remaining on Sulfonylurea Treatment 1 Primary End Point (APaT Population): Incidence of Symptomatic Hypoglycemia (Proportion of Patients With 1 Events) RRR (95% CI) = 0.51 (0.34, 0.75); P < Sitagliptin 100 mg qd ± metformin (n=507) SU ± metformin (n=514) symptomatic hypoglycemic events were reported by 68 patients in the SU group compared with 128 events in 34 patients for the sitagliptin group Most common symptoms were headache, sweating, dizziness, hunger, and tremor Mean doses of SUs were: 3.5 mg in the morning and 3.1 mg in the evening for glimepiride; 71.9 mg and 89.0 mg for gliclazide; and 6.1 mg and 5.9 mg for glibenclamide (glyburide). APaT=all patients as treated; CI=confidence interval; qd=once daily; RRR=relative risk ratio; SU=sulfonylurea. 1. Current Medical Research & Opinion Vol. 28, No. 8, 2012,

25 Vildagliptine During Ramadan study 52 patients preparing for Ramadan Currently poorly controlled (HbA 1 c >8.5%) Minimum Metformin 2g/day Randomised to receive Gliclazide 160mg bd Vildagliptin 50mg bd Results: Hypos were more common in gliclazide group 61.5 vs 7.7% (p < 0.001) One Severe hypo in gliclazide arm HbA1c Similar reductions Devendra et al Int J Clin Pract, 2009

26 Patients treated with insulin. Judicious use of intermediate- or long acting insulin preparations plus a short acting insulin administered before meals. Rapid acting insulin analogs are associated with less PP excursions and less risk of hypoglycaemia Diabet Med 1999;16: Diabetes Res Clin Pract 2003; 59:

27 Insulin Lispro Mix 50 (LM50) vs. Human Insulin 30/70 During Ramadan Enrollment Lead-in Ramadan Human Insulin Mixture 30/70 Human Insulin Mixture 30/70 n=79 Type 2 diabetes patients already taking Human Insulin Mixture 30/70 BID Human Insulin Mixture 30/70 QAM; LM50 QPM Human Insulin Mixture 30/70 QAM; LM50 QPM n= Weeks BID = twice daily; LM50 = 50% insulin lispro protamine suspension; 50% insulin lispro; QAM = once in the morning; QPM = once in the evening. 6 Hui et al. Int J Clin Pract 2010;64(8):

28 Insulin Lispro Mix 50 (LM50) vs. Human Insulin 30/70 During Ramadan: HbA1c LM50 50/50 p= difference in change between groups Hui et al. Int J Clin Pract 2010;64(8):

29 Insulin Lispro Mix 50 (LM50) vs. Human Insulin 30/70 During Ramadan: Frequency of Hypoglycemia LM50 50/50 p=0.36 difference in change between groups Hui et al. Int J Clin Pract 2010;64(8):

30 Pharmacotherapy During Ramadan for Treatment of Type 2 Diabetes Metformin Acarbose Outcomes Associated with Use During Ramadan No data are available for patients fasting for long periods while taking only metformin No data are available for patients fasting for long periods while taking only acarbose 2 Risk of Hypoglycemia During Ramadan Unknown (risk is 0-21% in nonfasting patients) 1 Risk of hypoglycemia is low in non-fasting patients 2 Sulfonylurea (glimiperide) Rapid-acting insulin secretagogue (repaglinide) Switching once daily dose to be taken with Iftar vs. Suhur showed no change in glycemic control or hypoglycemia 3 Improved glycemic control vs. glibenclamide 5 No differences in glycemic control or body weight vs. glimiperide or gliclazide 6 No difference vs. repaglinide during fasting 4 Fewer hypoglycemic events vs. glibenclamide during fasting 6 1. Bolen et al. Ann Intern Med 2007;147(6): Pan et al. Diabet Med 2008;25(4): Glimiperide in Ramadan (GLIRA) Study Group. Diabetes Care 2005;28(2): Anwar et al. Med J Malaysia 2006;61(1): Mafauzy et al. Diabetes Res Clin Pract 2002;58(1): Sari et al. Endocr Res 2004;30(2):

31 Pharmacotherapy During Ramadan for Treatment of Type 2 Diabetes TZDs (pioglitazone) DPP-4 Inhibitors (Vildagliptin, Sitagliptin) Outcomes Associated with Use During Ramadan Improved glucose control with vildagliptin+metformin vs. gliclazide+metformin 2 -- Risk of Hypoglycemia During Ramadan No increase if hypoglycemic events vs. placebo during fasting 1 Reduced incidence of hypoglycemia with vildagliptin+metformin vs. gliclazide+metformin 2 GLP-1 (exenatide) Audit findings suggest no dose adjustments needed during Ramadan, though other agents taken with GLP-1 (such as SUs) may need to be reduced 3 Hypoglycemia occurs in patients taking GLP-1 mimetics with SUs in non-fasting patients 4 TZD = thiazolidinedione; DPP-4 = dipeptidyl-peptidase 4; GLP-1 = glucagon-like peptide-1; SU = sulfonylurea. 1. Vasan et al. International J Diabetes Dev Countries. 2006;26: Devandra et al. Int J Clin Pract 2009;63: Norris et al. Diabetes Medicine. 2009;26: Bravis et al. Diabeteic Medicine 2010;27(suppl 1):130.

32 Section 6: Guidelines for Treating Patients with Diabetes During Ramadan

33 Fasting During The month of Ramadan For People With Diabetes: Medicine and Fiqh United at Last. SA Beshyah Ibnosina Journal of Medicine and Biomedical Sciences 2009, 1(2):58-60 This article is available from: Fasting during the lunar month of Ramadan is a religious obligation for all adult Moslems. Under certain circumstances, a few groups are exempt from fasting such as being sick as judged by an experienced doctor. Recent collaboration between the International Islamic Fiqh Academy and The Islamic Organization for Medical Sciences produced a comprehensive guidance based on extensive review of the evidence of possible risk to diabetic patients if they observe fasting.

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35 The new guidance categorized people with diabetes into 4 groups according to their risk. Group 1 and 2 are exempted from fasting as they have risk from fasting. These included patients with poor glycemic control or with complications and serious coexisting illnesses in addition to type 1 patients and pregnant women with diabetes. Patients in groups 3 and 4 are those with moderate to low risk of harm from fasting. These are exemplified by uncomplicated patients with stable control on oral drugs not associated with excess risk of hypoglycemia. These groups of patients have no harm but may even benefit from fasting. Doctors and religious scholars have a joint responsibility to properly assess and advise patients to choose to fast or not to fast in line with these recommendations. Ibnosina Journal of Medicine and Biomedical Sciences 2009, 1(2):58-60

36 Recommendations by Risk Stratification Very High Risk and High Risk Advised not to fast as it can lead to worsened control and may result in severe hypoglycemia and diabetic ketoacidosis Moderate Risk Advised to see healthcare provider several months prior to fasting to adjust their diabetes treatment Low Risk Can fast without healthcare advice Hui et al. BMJ 2010;340:

37 Risk Stratification for Patients With Diabetes Who Fast During Ramadan: Very High Risk : Advised NOT to fast Classification of Risk Very High Risk Risk Factors Severe hypoglycemia within 3 months, recurrent hypoglycemia, and/or unawareness of hypoglycemia Poor glycemic control Ketoacidosis within 3 months Type 1 diabetes Acute illness Hyperosmolar hyperglycemic coma within 3 months Performing intense physical labor Pregnancy Al-Arouj et al. Diabetes Care 2010;33(8): Hui et al. BMJ 2010;340:

38 Risk Stratification for Patients With Diabetes Who Fast During Ramadan: High Risk: May fast with conditions Classification of Risk Risk Factors High Risk Moderate hyperglycemia (average blood glucose, mg/dl [8-16mmol/l] or HbA1c %) Comorbidities such as advanced macrovascular complications, renal disease on dialysis, cognitive dysfunction, or uncontrolled epilepsy Comorbid conditions that present additional risk factors Living alone and treated with insulin or sulfonylureas Elderly with ill health Al-Arouj et al. Diabetes Care 2010;33(8): Hui et al. BMJ 2010;340:

39 Risk Stratification for Patients With Diabetes Who Fast During Ramadan: Moderate or Low Risk: Can fast Classification of Risk Moderate Risk Low Risk Risk Factors Well-controlled diabetes treated with short-acting insulin secretagogues, sulfonylurea, insulin, or taking combination oral or oral plus insulin treatment Well-controlled diabetes treated with lifestyle therapy, metformin, DPP-4 inhibitors, thiazoladinediones, and/or incretin-based therapies in otherwise healthy individuals Al-Arouj et al. Diabetes Care 2010;33(8): Hui et al. BMJ 2010;340:

40 Medical Assessment 1 to 2 months before Ramadan Specific attention to overall well-being, control of glycemia, blood pressure, and lipids Appropriate blood studies should be ordered and evaluated Specific medical advice should be given to each individual, even if fasting against medical advice Necessary changes in diet and medication regimen should be made to patients who initiate fasting while on a stable and effective program Al-Arouj et al. Diabetes Care 2010;33(8):

41 Educating Patients Who Fast During Ramadan The role of structured education is well-established in the management of diabetes Structured instruction should be extended to Ramadan-focused diabetes education Education programs should ideally include: Awareness campaign for individuals with diabetes, healthcare professionals, and religious and community leaders Ramadan-focused structured education for healthcare professionals Ramadan-focused structured education for individuals with diabetes Al-Arouj et al. Diabetes Care 2010;33(8):

42 Ramadaan-focused Education Meal plan Appropriate exercise Blood glucose monitoring Finger prick or venesection does not break fast Recognition and management of hypoglycaemia and other acute complications Individualise treatment

43 Recommended Dietary Interventions During Ramadan Development of an individual dietary plan based on metabolic, nutritional, and lifestyle requirements 10 to 20% of caloric needs = protein 80 to 90% of caloric needs = fat and carbohydrates (<10% saturated fat) Distribution of fat and carbohydrates should be individualized based on nutrition and treatment objectives Benaji et al. Diabetes Res Clin Pract 2006;73(2):

44 Ramadan and Diabetes:DIET Split the daily calorie intake over two to three smaller meals during the non-fasting interval. Eat complex carbohydrates (e.g. oatmeal, bran,low GI rice) at Suhur (pre-dawn meal), and simple carbohydrates at Iftaar (sunset meal). Avoid foods with high sugar and fat content. Ensure adequate fluid intake during the nonfasting period.

45 METFORMIN The daily doses should be modified as follows: Two thirds after Iftaar (Eve.) One third at Suhur(Predawn) If the patient is taking modified-release metformin once daily, the dose should be taken after Iftaar rather than at Suhur

46 Management of Type 2 Diabetes in Patients Fasting During Ramadan: Oral Agents 1 Sulfonylureas Should be used with caution due to risk of hypoglycemia, although severe or fatal hypoglycemia is rare Glyburide or glibenclamide may be associated with higher risk of hypoglycemia than other second generation sulfonylureas e.g. gliclazide, glimepiride Studies have shown that repaglinide might be a safer alternative 2 1. Al-Arouj et al. Diabetes Care 2010;33(8): Sari et al. Endocr Res 2004;30(2):

47 SULPHONYLUREA S Reduce the morning dose if taking the drug twice daily. For example, change a twice-daily dose of gliclazide 80 mg to 80 mg at Iftaar(Eve.) and 40 mg at Suhur(Predawn) consider timing adjustment. For example, if taking a qd dose, switch it to Iftaar(Eve) Switch from glibenclamide to gliclazide, glimepiride or glinide to reduce risk of hypoglycaemia

48 OTHER ORAL AGENTS DPP-4 inhibiturs: No dose adjustment needed They are an alternative to sulphonylureas if the risk of hypoglycaemia is high. Thiazolidinediones: No adjustment necessary. Acarbose: To be taken at Suhur (AM)and Iftaar(PM) Oral short-acting betacell secretagogues The glinides (e.g. repaglinide) are short acting and can be taken twice daily, at Suhur and Iftaar

49 Diabetes and Fasting GLP-1 analogues No dose adjustment of GLP-1 analogue BUT if combined with sulphonylurea,reduce dose of the sulphonylurea

50 Management of Type 2 Diabetes in Patients Fasting During Ramadan: Insulin Treatment goals and complications similar to type 1 diabetes, except hypoglycemia risk is lower Option 1 Option 2 Option 3 Judicious use of intermediate- or long-acting insulin plus a short-acting insulin before predawn and sunset meals Use of long-acting or immediate-acting insulin once daily may provide adequate coverage in some patients. Dosage should be individualized Insulin pump: continuous insulin delivery with self-administered boluses at meals. Most will need to reduce basal infusion rate and increase bolus doses to cover predawn and sunset meals Hypoglycemia is still a risk, especially in patients who have required insulin therapy for a number of years or in whom insulin deficiency predominates, and in very elderly patients Most patients will require rapid- or short-acting insulin at both meals an d basal insulin at bedtime or if on premixed insulin ½ the usual eve dose AM and the usual AM dose PM Frequent glucose monitoring is required. Failure at pump or infusion site can cause severe deterioration of control over a few hours Al-Arouj et al. Diabetes Care 2010;33(8):

51 DIABETES AND FASTING Type 2 diabetics on Insulin 1. Basal/bolus Regime : ideal choice. Basal insulin at bedtime + rapid acting insulin at Suhur(AM) and Iftaar (PM) 2. Premixed insulin Give usual breakfast dose at Iftaar and 50 % of evening dose at Suhur N.B. Premixed 50/50 preferable at Iftaar for better post prandial control. 3. Bedtime Basal insulin + Oral agents Continue basal insulin but reduce the morning dose of oral agents

52 Fasting and Type 1 Diabetes Type 1 Diabetic patients should be advised NOT to fast However, some will insist on fasting. Such patients should be referred to a diabetologist who is well versed in the field of diabetes and Ramadaan

53 Recommended Changes to Treatment Regimens in Type 2 Diabetes Patients Fasting During Ramadan Before Ramadan Diet and exercise control Oral hypoglycemic agents Biguanide, metformin 500 mg TID During Ramadan Modify time and intensity of exercise. Ensure adequate fluid intake Ensure adequate fluid intake Metformin, 1000 mg at sunset meal, 500 mg at predawn meal TZDs, AGIs, or incretin-based therapies SUs QD SUs BID Insulin Premixed or intermediate-acting insulin BID No change needed Dose should be given before the sunset meal; adjust the dose based on glycemic control and risk of hypoglycemia Use half the usual morning dose at predawn meal and usual dose at sunset meal Ensure adequate fluid intake Consider switching to long-acting or intermediate insulin in evening and short or rapid-acting insulin with meals; or take usual dose at sunset meal and half usual dose at predawn meal AGI = α-glucosidase inhibitor; BID = twice daily; QD = once daily; SU = sulfonylurea; TID = thrice daily; TZD = thiazoladinedione. Al-Arouj et al. Diabetes Care 2010;33(8):

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55 Fasting and Type 1 Diabetes : Recommendations 1.Control must be good Should be on basal/bolusinsulin regime, Short-acting Analogues preferred as bolus 2.Reduce total dose by 50 % 3.Give 60 % as basal 4.Give 40 % as bolus between the 2 meal 15 % at Suhur and 25 % at Iftaar 5.Insulin Pump(CSII) promising.