Hypoglycemia Among Type 2 Diabetics Fasting Ramadan Dr. Khaled Tayeb tayebkhaled@hotmail.com To Fast during the month of Ramadan-Prayer and supplication to God-Discipline to be observed during the month-Rights of property to be respected الصيام َكَما ُكتِب َعلَ الَّ ِ )(183يا أَيُّ َها الَّ ِذين آمنُواْ ُكتِ ين ِمن ََ ْْلِ ُك ْم لَ َعلَّ ُك ْم تَ تَّ ُقو َن ذ م ك ي ل ع ب َ ِّ ُ َ ْ ُ َ َ َ َ َ َ َ َ ُ ات فََمن َكا َن ِ ضا أَو َعلَ س َف ٍر فَ ِع َّدةٌ ِّمن أَيَّ ٍام أُ َخر و َعلَ الَّ ِ ود ٍ ِ ين ذ ي ر م م ك ن م َّ ُ ً ( )184أَيَّ ًاما َّم ْع ُد َ َ ْ ْ َ َ َ َ ي ِطي ُقونَه فِ ْديةٌ طَعام ِ ِ َّ ٍ ومواْ َخ ْي ٌر لَّ ُك ْم ِن ُكنتُ ْم تَ ْعلَ َُمو َن ص ت َن أ و ه ل ر ي خ و ه ف ا ر ي خ ع و ط ت ن َم ف ن ي ك س م َ َ َ َّ َ َ َ َ َ ًْ َُ ٌْ ُ َ ُ ُ َ ُ ُ َ َُ ْ ِِ (َ )185ش ْهر رم َ َّ ِ ات ِّمن ال ُْه َدى والْ ُفرََ ِ اس وب يِّ نَ ٍ ان فَ ََمن َش ِه َد ُ ََ ي أُن ِز َل فيه الْ ُق ْرآ ُن ُه ًدى لِّلنَّ ِ َ َ َ ْ َ ضا َن الذ َ ِمن ُك ُم َّ ضا أ َْو َعلَ َس َف ٍر فَ ِع َّدةٌ ِّم ْن أَيَّ ٍام أُ َخ َر يُ ِري ُد اللّهُ بِ ُك ُم الْيُ ْس َر َوالَ ص َْمهُ َوَمن َكا َن َم ِري ً الش ْه َر فَ لْيَ ُ يُ ِري ُد بِ ُك ُم ال ُْع ْس َر َولِتُ ْك َِملُواْ ال ِْع َّد َة َولِتُ َكِّْ ُرواْ اللّهَ َعلَ َما َه َدا ُك ْم َولَ َعلَّ ُك ْم تَ ْش ُك ُرو َن Recommendations for Management of Diabetes During Ramadan Diabetes Care Volume 33, Number 8, August 2010 Major risk associated with fasting in patients with diabetes 1. Hypoglycemia 2. Hyperglycemia 3. Diabetic ketoacidosis 4. Dehydration and thrombosis Recommendations for Diabetic Individuals during Ramadan, Diabetes Care , vol 33, num. 8, August2010 Hypoglycaemia • 2 – 4% of mortality in patients with type 1 diabetes. • Rates of hypoglycaemia are some several-fold lower in patients with type 2 compared with type 1 diabetes • Rates being lower in patients with type 2 diabetes treated with oral agents. Recommendations for Diabetic Individuals during Ramadan, Diabetes Care , vol 33, num. 8, August2010 Categories of risks in patients with type 1 or type 2 diabetes who fast during Ramadan 1. Very high risk • Severe hypoglycaemia within the last 3 months prior to Ramadan. • A history of recurrent hypoglycaemia. • Hypoglycaemia unawareness. • Sustained poor glycemic control. • Ketoacidosis within the last 3 months prior to Ramadan. Recommendations for Diabetic Individuals during Ramadan, Diabetes Care , vol 33, num. 8, August2010 Breaking the Fast All patients must always and immediately end their fast if: 1. Hypoglycaemia (blood glucose of <60mg/dl). 2. Blood glucose reaches <70 mg in the first few hours after the start of the fast, especially if insulin, sulfonylurea drugs, or neglitinide are taken at predawn. 3. Blood glucose exceeds 300 mg with symptoms of hyperglycaemia. Recommendations for Diabetic Individuals during Ramadan, Diabetes Care , vol 33, num. 8, August2010 (4.7 fold) (7.5 fold) Change in outcome measures during Ramadan in participants receiving both gliclazide and metformin1 Hypoglycaemia in study control group on Metfromin + Gliclazide Ramadan 2008 9.25 8.95 0.92 8.75 HbA1c (%) Pre-Ramadan Post-Ramadan 8.25 7.75 7.75 7.25 6.75 Hypoglycaemic Events per person 1 0.9 0.8 0.7 0.6 0.5 0.4 0.27 0.3 0.2 0.1 0 Int J Clin Pract 2009; 63: 1446–50 10 Hypoglycemia in SulphonylureaTreated Subjects with Type 2 Diabetes Undergoing Ramadan Fasting: A Five-Country Observational Study Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Objectives • To determine the incidence of hypoglycemia during Ramadan in Muslim subjects with type 2 diabetes treated with a sulphonylurea. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Subjects & Methods • Eligible subjects • Muslim patients with type 2 diabetes treated with Sulphonylureas( Glimiperide, Glyclazide , or Glibenclamide) • With or without Metformin • Age ≥ 18 years old • Excluded subjects • Patients with Type 1 diabetes • Patients with Insulin treated type 2 diabetes Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Subjects & Methods • Subjects were recruited from 5 countries. • 300 subjects were selected per country. • Diabetes Center in Holy Makkah and other centers from (UAE, India, Malaysia, and occupied Palestine ). Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Subjects & Methods Patients were given a daily dairy card to record .. • any hypoglycemic symptoms and complications • The time from the start of hypoglycemic symptoms and the last meal and medications • Self monitor blood glucose • Need for assistance to treat hypos. • The fasting was broken or not. • Cards to be filled daily regardless of symptoms Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Subjects & Methods • The hypoglycemic events were further classified into.. - Symptomatic : (headache, sweating, tremors, palpitation, etc..) - Documented: symptomatic with BG ≤ 70 mg/dl. - Severe: requiring medical or non- medical assistance. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Patients Characteristic in the Study Glimepiride (n=428) Gliclazide (n=386) Glibenclamide (n=535) Glipizide (n=29) Overall (N=1378) Gender M 229 (54 %) 225 (58 %) 263 (49 %) 12 (41 %) 729 (53 %) Age at baseline, yrs 51.4 ± 10.1 53.7 ± 9.2 55.5 ± 10.0 58.1± 9.8 53.8 ± 10.0 BMI, kg/m2 28.4 ± 5.2 29.0 ± 5.3 29.4 ± 10.0 45.0 ± 18.5 46.6 ± 9.9 Age at diabetes diagnosis, yrs 45.3 ± 9.6 46.9 ± 8.9 47.5 ± 10.0 45.0 ± 18.5 46.6± 9.9 Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Sulponylurea use by country in the study Country Glimepiride (n=428) Gliclazide (n=386) Glibenclamide (n=535) Glipizide (n=29) Overall (N=1378) India 239 (56%) 50 (13%) 107 (20%) 0 (0%) 396 (29%) Occupied Palestine 48 (11%) 0 (0%) 170 (32%) 29 (100%) 247 (18%) Malaysia 29 (7%) 182 (47%) 144 (27%) 0 (0%) 355 (26%) 108 (25%) 141 (37%) 114 (37%) 0 (0%) 363 (26%) 4 (1%) 13 (3%) 0 (0%) 0 (0%) 17 (1%) Saudi Arabia UAE Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Results • The daily dairy card were returned by 1378 patients from total 1397 patients. • Symptomatic hypoglycemia was 40% in occupied Palestine and 10% in Saudi Arabia • Over all symptomatic hypoglycemic events were recorded in 271 subjects (19.7%) • Headache represent 14.5%, sweating 10.2%, tremors 8.5% and palpitation 7%. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Incidence of symptomatic hypoglycemia during Ramadan by countries Countries N of Patients Occupied Palestine 40% Malaysia 24% United Arab Emirates 18% India 13% Saudi Arabia 10% Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Incidence of hypoglycemia during Ramadan by type Type of hypoglycemia Percentage (%) Symptomatic hypoglycemic events 86 Documented hypoglycemic events 3.6 Severe hypoglycemic events 3.7 Severe hypoglycemic events requiring medical assistance Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 6.7 Incidence of hypoglycemia during Ramadan by type 100 80 60 86% 40 20 0 3.6% Symptomatic hypoglycemic events Documented hypoglycemic events 3.7% Severe hypoglycemic events Type of hypoglycemia 6.7% Severe hypoglycemic events requiring medical assistance Incidence of hypoglycemia during Ramadan by types of drug N of patients (%) Glimepiride (n=428) Gliclazide (n=386) Glibenclamide (n=535) Glipizide (n=29) Overall (N=1378) Symptomatic hypoglycemic events 72 (16.8%) 54 (14 %) 137 (25.6%) 8 (27.6%) 271 19.7% Documented hypoglycemic events 17 (4.0%) 11 (2.8%) 21 (3.9%) 0 (0.0%) 49 3.6% Severe hypoglycemic events 22 (5.1%) 10 (2.6%) 58 (10.8%) 2 (6.9%) 92 6.7% Severe hypoglycemic events requiring medical assistance 10 (2.3%) 6 (1.6%) 36 (6.5%) 0 (0.0%) 51 3.7% Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Results • Symptomatic hypoglycemia events 1095 • Documented hypoglycemic events were similar across all sulphonylurea groups 3.6%, . • Events not requiring medical assistance 3.7% • Events requiring assistance 6.7% . • Subjects experienced a serious complication 1.2% . Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Discussion • The incidence of severe hypoglycemia requiring medical or non medical assistance or hospitalization were less than other studies. • In the EPIDAR study, 2% of patients hospitalized in comparison to 0.5% in this study. (Diabetes Care 2004; 2306-11) • Health care resources utilization, was less in this study. The less severe hypoglycemia events or better education regarding the symptoms could explain this. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 The incidence of Hypoglycaemia in Muslim Type 2 Diabetics treated with Sitagliptin or a Sulphoylurea during Ramadan. Aim • To compare the incidence of symptomatic hypoglycaemia with Sitagliptin or A Sulphonylurea during Ramadan. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Patients and study design • A prospective, open-label, randomised study. • 6 countries, 43 clinical sites. • 1243 patients of whom 1066 randomized to treatment. • Muslim Type 2 diabetics willing to fast Ramadan. • Age : > 18 Yrs. • Treated with a sulphonylurea for at least 3 months before study with or without metformin and had HbA1c < 10%. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Pre-Randomization Treatment Sitagliptin ( n = 507 ) Sulphonylurea ( n = 514 ) Glibenclamide 158 (31%) 181 (35%) Glimepiride 189 (37%) 178 (35%) Glicalazide 159 (32%) 152 (30%) 41 (8%) 41 (8%) Monotherapy Dual ( SU + MET ), n (%) 465 (92%) 471 (92%) 4.0 4.0 Duration of SU Therapy* yrs Experienced hypoglycaemia in 3 M before Ramadan 81 (16%) 76 (15%) Data are expressed as frequency, n(%) or mean ± standard deviation unless otherwise indicated. *median Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Results • 1066 patients randomised, • 1021 enrolled in the study as they returned at least one complete diary. • Incidence of symptomatic hypoglycaemic events - Sitagliptin group (5.1%) - Sulphonylurea group (11.9). Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 Results *n/N (%) Sitagliptin 25 *n/N (%) Sulphonylurea 22.1% 20 21.2% 20.0% 20.0% 18.6% 15 11.9% 10.3% 9.9% 10 6.7% 5.1% 7.1% 5 0% 0 Overall Egypt 0.5% Palestien Jordan Lebanon Saudi Arabia *no of patients experiencing event /N overall or in each country by treatment. (%) Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 0.5% UAE Results Sitagliptin ( n = 507 ) n ( %) of patients Experiencing event Symptomatic or asymptomatic hypoglycemic events 35 Severe hypoglycemic events Hypoglycemic events requiring non-medical assistance Hypoglycemic events requiring medical assistance ( 6.9% ) Sulphonylurea ( n = 514 ) n (%) of patients Experiencing event 84 0 1 ( 0.2% ) 0 * Types of hypoglycemic event defined in Methods Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242 ( 16.3% ) 0 3 ( 0.6% ) 0 Fear of hypoglycemia is a major concern for patients Male Female Severe hypoglycemia Male Female Mild hypoglycemia Male Female Kidney problems Male Female Blindness Blindness Not worried Very worried 1. Pramming S et al. Diabet Med 1991;8:217–222 Hypoglycaemic Events 36 40 35 X4 increase 30 25 20 15 9 9 5 10 5 0 Education No education Pre-Ramadan HE • • • Main aim • To determine the incidence of hypoglycaemic events in 100 Muslim patients with T2D fasting during Ramadan, who are treated with dual therapy of metformin plus vildagliptin or metformin plus sulphonylurea (SU) Primary objectives • the incidence of hypoglycaemic events defined as: • Any reported symptoms by the patient and/or any blood glucose measurement of less than 3.9 mmol/L (also defined as mild or Grade 1 hypoglycaemia) • The need for third party assistance (also defined as severe or Grade 2 hypoglycaemia); Secondary objectives • the change in weight; • the change in HbA1c levels; and • the treatment adherence during Ramadan. VECTOR: Results - Hypoglycaemic events (HE) Mean between-group difference in patients who experienced at least one HE was –41·7% (p = 0·0002) VECTOR: HbA1c The between group difference was −0·6% (p = 0·0262) (7·7% to 7·2%) (7·2% vs 7·3%) :Adherence Only 1 patient in the Vildagliptin group missed at least one dose, compared with 10 patients in the SU group. p = 0·0204 * There are an estimated 325,000 Muslims with type 2 diabetes in the UK ** Hypoglycemic event (defined as blood glucose < 3.5 mmol ⁄ l with or without symptoms) References: 1. Devendra D et al. Vildagliptin therapy and hypoglycaemia in Muslim type 2 diabetes patients during Ramadan. Int J Clin Pract, October 2009, 63, 10, 1446–1450. How to Help Patients Fast Safely • Patient Education Program. • Select more safe drugs. • Adjust dose if needed • Ensure good non – sugar fluid intake. • Avoid heavy physical exercise at afternoon. • Ensure good calorie distribution. استشارة مجانية في شهر رمضان جــوال 0590440882 :