By Eman Rushdy

1. Fasting diabetic patient By Eman Rushdy

2. ”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 ”

3. 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.”

4. Things Happened During Ramadan • 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.

5. Uniqueness of Ramadan Fasting • 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

6. Physiological Effects of Fasting: • On Calorie intake • On fluid /water intake • Effects on – Digestive System - Kidneys - Endocrine glands - Lipid Metabolism - Respiratory system - Neurological System

7. Some Facts : • 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).

8. Insulin and Glucagon Main determinants of glucose metabolism

9. 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 +++ --- Insulin& C-peptide Proinsulin Proglucagon Glucagon --- +++ Blood glucose >90mg/dl

10. Paracrine Actions of Insulin and Glucagon Glucagon + Insulin Insulin - glucagon

11. glycogenesis glycogenolysis gluconeogenesis from aa Protein synthesis Glucagon Insulin lipogenesis lipolysis So, insulin favors anabolic reactions and storing energy glucagon, catabolic reactions and release of stored energy

12. 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 Alanin &lactate glycerol Fuel reserves are: Triacylglycerols & tissue proteins 4- Then stimulates gluconeogenesis 5- Ketone bodies FFA

13. 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

14. Fasting and Lipid Metabolism • 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

15. Endocrine functions in Fasting • 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

16. -- 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

17. Decrease in appetite due to ketosis and increase in Beta-endorphins

18. Decreased and delayed melatonin peak Decreased Nocturnal sleep Daytime alertness Psychomotor performance

19. Renal Function in Fasting • Urinary volume • Osmolality • Shift of fluids intracellularly • Slight increase in BUN (insignificant) • Increase in Uric acid (less in Ramadan fasting than in prolonged fasting) Dehydration

20. Other Effects of Fasting • 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)

21. 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. 

22. What will happen in diabetic patient ?????????

23. In patients with diabetes Glucagon secretion may fail to increase Epinephrine secretion is also defective due to a autonomic neuropathy . Hypoglycemia Insulin replacement Hyperglycemia & Ketosis Excessive: Glycogenolysis Gluconeogenesis Ketogenesis Insulin replacement

24. EPIDIAR STUDY-T2DM: 78.2% fasted >15days Salti et al: Diabetes Care Vol 27; 10 Oct 2

25. Risks associated with fasting in diabetic patient???

26. Risks associated with fasting in patients with diabetes *Hypoglycemia: Severe hypoglycemia Type 1 diabetes Type 2 diabetes 3 to14 events/100 people/ m 0.4 to3 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

27. *Hyperglycemia: severe hyperglycemia (requiring hospitalization) Type 1 diabetesType 2 diabetes 3 fold increase 5 fold increase ± Ketoacidosis due to excessive reduction in dosages of medications to prevent hypoglycemia

28. *Dehydration and thrombosis : 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

29. 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

30. Thank You

31. Insulin Glargine during Ramadan EmanRushdy

32. 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 duringRamadan. Diabetes Care2004 : 27:2306–2311

33. 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.

34. Results in

35. 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 Myocardial infarction Convulsions Death

36. Recent Clinical Trial Findings: Intensive glucose control in type 2 diabetes: • 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

37. Hypoglycaemia and CV Disease Desouza C et al Diabetes Care 26: 1485-1489, 2003

38. 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

39. Hypoglycaemia and CV Disease Inflammatory Responses To Hypoglycaemia CRP (mg/L) Baseline 4 Hours 24 Hours Diabetes 0.77 0.84 2.31* Control 0.32 ND 0.96* *p < 0.04 vs. Baseline Galloway P et al Diabetes Care 23: 861-862, 2000

40. Hypoglycaemia and CV Disease Hemodynamic Thrombotic Ischaemia Hypoglycaemia Inflammatory Wright R et al Diabetes/ Metabolism Research and Reviews , 2008

41. Hypoglycemia Unawareness Type 1 DM DURATION Autonomic neuropathy Recurrent hypoglycemia

42. All persons need both basal and mealtime insulin to control glucose MIMICKING NATURE WITH INSULIN THERAPY 6-19

43. 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.

44. Regulation of Basal insulin secretion Pacemaker ß cells Na+ GLUT2 K+ Signal K+ KIR Na+ K+ Vm K+ Voltage-gated Ca2+ channel Ca2+ Ca2+ Ca2+ Pancreatic ß cell Mature insulin granules contracts by exposure to high intracellular Ca. Ca2+ Ca2+ Insulin granules

45. Glucokinase Glucose K Ca Post prandial insulin secretion

46. Physiologic Insulin Secretion: Basal/Prandial Concept Nutritional (Prandial) Insulin 50 Insulin (µU/mL) Basal Insulin *Suppresses Glucose Production Between Meals & Overnight 25 0 Basal Insulin Breakfast Lunch Supper • *Nearly constant levels • 40- 50% of daily needs 150 Nutritional Glucose 100 Glucose (mg/dL) 50 • Prandial Insulin • *Limits hyperglycemia after meals • *Immediate rise and sharp peak • *10% to 20% of total daily insulin • requirement at each meal Basal Glucose 0 7 8 9 10 11 1 2 3 4 5 6 7 8 9 12 A.M. P.M. Time of Day

47. Good • 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 .

48. The best: • Consider changing premixed insulin preparations to Glargine or Dtemirplus Lispro, Glulisine or Aspart . Diabetes Care September 2005 , pages 2305-11

49. Types of basal insulin 49 Rossetti P, et al. Arch Physiol Biochem 2008;114(1): 3 – 10.

50. Ideal Basal Insulin: • Safe • Effective • Less glucose excurtions