1. Diabetes Mellitus (DM) Part II PHCL 442 Hadeel Al-Kofide MSc 1

2. Topics we will cover in DM Definition & Epidemiology Carbohydrate metabolism Classification Signs & symptoms Diagnosis Long term complications Monitoring parameter & test to Guide management Principles of management:  Part I: General principles  Part II: a. Insulin & its clinical applications b. Oral anti-diabetic agents Prevention & management of diabetes complications 2 Last lecture

3. Principles of Management Part II: A.Insulin & its Clinical Applications 3

4. Clinical Applications of Insulin in DM Initiating insulin therapy Methods of insulin therapy Testing frequency Interpreting SMBG Fasting hyperglycemia Supplemental insulin doses Sliding scale Sick day management 4

5. Initiating Insulin Therapy Clinical SituationInsulin Dose Type 1 DM 1. Initial dose0.5-0.8 U/kg 2. Honeymoon phase0.2-0.5 U/kg 3. Patients with ketosis, during illnesses, during growth 1-1.5 U/kg Type 2 DM (insulin resistance)0.7-1.5 U/kg 5 After calculating the total daily dose (TDD) of insulin: 1.Split the dose between the regular or short acting insulin & the intermediate or long acting insulin HOW? Either 50% each, or 70% (the intermediate or long acting) & 30% (the rapid or short acting insulin) 2.Then it depends in which method of insulin delivery you will chose e.g. insulin pump, MDI or conventional method

6. Methods of Insulin Therapy Intensive insulin therapy (IIT):  Insulin pump  Multiple daily injections (MDI) Conventional method Example on different methods of insulin therapy 6

7. Intensive Insulin Therapy Patient selection criteria: 1.Type 1 DM, healthy, >7 yr, highly motivated & compliant individuals, willing to test blood glucose 4 times/day 2.Diabetic women who plan to get pregnant 3.Pregnant diabetic patient 4.Patients poorly controlled on conventional therapy (including type 2) 5.Technical ability to test blood glucose 6.Intellectual ability to interpret blood glucose concentrations 7.Access to trained & skilled medical staff to direct treatment plan & provide supervision 7 Methods of Insulin Therapy

8. Intensive Insulin Therapy When to avoid IIT? 1.Patient with counter-regulatory insufficiency 2.Type 1 DM for more tan 15 years (not all patients) 3.On beta-blockers 4.Autonomic, pituitary or adrenal insufficiency 5.Patients with coronary or cerebral vascular disease 6.Patients who are non-compliant, unable to measure blood glucose, or patients with psychiatric disorders 8 Methods of Insulin Therapy

9. Intensive Insulin Therapy Two major methods used to deliver IIT: 1.Insulin pump 2.MDI 9 Methods of Insulin Therapy

10. Intensive Insulin Therapy Insulin pump: The most precise way to mimic normal insulin secretion Portable Delivers basal & bolus insulin doses New: Implantable insulin pumps 10 Methods of Insulin Therapy

11. Intensive Insulin Therapy Multiple daily injections: It mimics the release of insulin from the pancreas Contains both basal & bolus insulin Insulin is given 3 times or more per day There are different methods to deliver MDI of insulin 11 Methods of Insulin Therapy

12. Conventional Insulin Therapy Insulin is given twice daily It usually contains a mixture of intermediate acting & short acting insulin Not commonly used now 12 Methods of Insulin Therapy

13. Examples of Different Insulin Regimens AMNoonPMBedtime Reg/NPH--Reg/NPH-- Reg/Lente--Reg/Lente-- Lispro/NPH--Lispro/NPH-- Lispro/Lente--Lispro/Lente-- Aspart/NPH--Aspart/NPH-- Aspart/lente--Aspart/lente-- 13 Method 1 Why we need a short acting here? To cover breakfast Why we need an intermediate acting here? To cover lunch + basal insulin Why we need a short acting here? To cover dinner Why we need an intermediate acting here? To cover snack + basal insulin Methods of Insulin Therapy

14. Examples of Different Insulin Regimens Disadvantages: Peak of NPH will be between 2-4 am causing nocturnal hypoglycemia & morning hyperglycemia (rebound hyperglycemia) To overcome this problem: either decrease NPH dose, or give NPH at bedtime instead of pre-dinner, why? 14 Method 1 Methods of Insulin Therapy

15. Examples of Different Insulin Regimens AMNoonPMBedtime Reg/NPH--RegNPH Reg/Lente--RegLente Lispro/NPH--LisproNPH Lispro/Lente--LisproLente Aspart/NPH--AspartNPH Aspart/Lente--AspartLente 15 Method 2 This method is used to overcome disadvantages of method 1 Methods of Insulin Therapy

16. Examples of Different Insulin Regimens How can method 2 overcome method 1 disadvantages? By shifting NPH or lente dose to bedtime the peak action will occur in early morning (5-7 am) when the patient is awake & ready to eat 16 Method 2 Methods of Insulin Therapy

17. Examples of Different Insulin Regimens AMNoonPMBedtime Reg NPH Reg Lente Reg Glargine Reg Ultralente 17 Method 3 Methods of Insulin Therapy

18. Examples of Different Insulin Regimens More flexibility in meals If regular insulin was replaced by lispro must add with it NPH, why? If glargine replaces either NPH or lente the dose should be decreased by 20% 18 Method 3 Methods of Insulin Therapy

19. Examples of Different Insulin Regimens AMNoonPMBedtime Lispro/NPHLispro NPH Lispro/LenteLispro Lente Aspart/NPHAspart NPH Aspart/LenteAspart Lente 19 Method 4 Methods of Insulin Therapy

20. Examples of Different Insulin Regimens The problem with lispro or aspart is post-prandial hyperglycemia due to short duration of action If glargine replaces either NPH or lente the dose should be decreased by 20% 20 Method 4 Methods of Insulin Therapy

21. Examples of Different Insulin Regimens AMNoonPMBedtime Reg/UltralenteRegReg/Ultralente-- Lente/UltralenteLisproLente/Ultralente-- Aspart/UltralenteAspartAspart/Ultralente-- 21 Method 5 Methods of Insulin Therapy

22. Examples of Different Insulin Regimens Why ultralente is given twice daily? If glargine replaces ultralente give it once daily The main disadvantage here is fasting hyperglycemia, why? 22 Method 5 Methods of Insulin Therapy

23. Examples of Different Insulin Regimens AMNoonPMBedtime Reg/UltralenteReg NPH Lente/UltralenteLisproLenteNPH Aspart/UltralenteAspart NPH 23 Method 6 Methods of Insulin Therapy

24. Examples of Different Insulin Regimens It overcomes the problems in method 5, why? 24 Method 6 Methods of Insulin Therapy

25. Testing Frequency Ideally patients should test their blood glucose in the following times: Before meals After meals Bedtime At 2-3 am 25 This means 8 times/day!!

26. Testing Frequency But at least the patient should measure blood glucose in the following times: Before meals Bedtime At 2-3 am Patients should evaluate blood glucose level when they are not feeling well, or in case of increased physical activity, large meal, final examinations or family crisis 26 This means 4 times/day 3 times/week

27. Testing Frequency Testing blood glucose at these times corresponds with the peak action of short & intermediate acting insulin administered at different times of the day This enables the clinician to evaluate the effect of various insulin components on meals & to identify nocturnal hypoglycemia GlucoWatch? 27

28. Interpreting SMBG Test TimeTarget Insulin DoseTarget Meal/Snack Fasting (pre-breakfast)Pre-dinner/bedtime intermediate or long acting insulin Bedtime snack Pre-lunchPre-breakfast regular insulinBreakfast Pre-dinnerPre-breakfast intermediate acting insulin or pre-lunch regular acting insulin Lunch BedtimePre-dinner regular insulinDinner 3 amPre-dinner intermediate acting insulin Dinner/bedtime snack 28

29. Interpreting SMBG Case 1: J.F is a 20 year old female recently diagnosed with type I DM, she was prescribed NPH insulin twice daily: 16 units am & 8 units PM. Her initial goal of therapy was to achieve a pre- prandial blood glucose concentration <180 mg/dl. After being on this regimen for 1 week, trends in her blood glucose concentrations were: (occasional 3 am tests was 160 mg/dl) 29 Examples TimeSMBG (mg/dl) 7 am160-200 Noon220-260 5 pm130-180 11 pm140-180

30. Interpreting SMBG How to solve case 1? Increase TDD because her overall control is poor (increase dose to 0.6 U/kg) Split this dose to provide 2/3 in the morning & 1/3 at evening Add regular insulin to her regimen by 2:1 ratio, how? 30 Examples

31. Fasting Hyperglycemia Insufficient insulin dose Somogyi effect Dawn phenomenon Examples 31

32. Insufficient Insulin Dose In which there is at least 3 reading values of blood glucose are high The 3 am value must be high or normal (not low), why? Example: 7 am 190 12 pm 220 5 pm 200 3 am 140 Solution: increase the TDD of insulin 32 Fasting Hyperglycemia

33. Somogyi Effect Also called rebound hyperglycemia; posthypoglycemic hyperglycemia Fasting hyperglycemia but normal blood glucose at bedtime, low at 3 am with symptoms of hypoglycemia (nightmares, sweating, hunger & morning headache) Example: 7 am 190 12 pm 120 5 pm 100 3 am 80 33 Fasting Hyperglycemia

34. Somogyi Effect It occurs after severe hypoglycemia & its 2 nd to excessive increase in glucose production by the liver that is activated by counter regulatory hormones The evening dose of NPH is responsible for this effect It is the cause of morning hyperglycemia in >10% of diabetic patients 34 Fasting Hyperglycemia

35. Somogyi Effect Solutions: Decrease NPH dose by 2-3 units, or Shift the pre-dinner NPH dose to bedtime (preferred than twice daily injection) Switch NPH to glargine, give it at bedtime & decrease the dose by 20% (remember glargine cannot be mixed with regular insulin) 35 Fasting Hyperglycemia

36. Dawn Phenomenon A rise in blood glucose concentration that occurs between 4-8 am It is due to natural increase in growth hormone levels in the early morning (not rebound effect) Example: 7 am 180 12 pm 120 5 pm 110 3 am 110 36 Fasting Hyperglycemia

37. Dawn Phenomenon Solutions: Increase evening NPH by 1-2 units If patient on glargine switch to something with peak as NPH or lente Decrease bedtime snack 37 Fasting Hyperglycemia

38. Examples Example 1: Patient on NPH/Reg am & NPH/Reg pm 38 Fasting Hyperglycemia 7 am160 12 pm130 5 pm90 10 pm100 3 am60 Somogyi effect Solution: 1.Decrease evening NPH by 1-2 units 2.Give NPH at bedtime 3.Give a snack Solution: Increase regular insulin in breakfast

39. Examples Example 2: Patient on NPH/Reg am & NPH/Reg pm 39 Fasting Hyperglycemia 7 am160 12 pm130 5 pm90 10 pm100 3 am100 Down phenomenon Solution: 1.Increase evening NPH by 1-2 units 2.Decrease amount of dinner or bedtime snack Solution: 1.May not need to do anything, why? 2.Increase regular insulin in breakfast

40. Examples Example 3: Patient on NPH/Reg am, Reg pm, & NPH bedtime 40 Fasting Hyperglycemia 7 am100 12 pm60 5 pm90 10 pm100 3 am110 Post-prandial hypoglycemia Solution: 1.Snack at morning 2.Change from regular to lispro 3.Decrease morning dose of regular insulin

41. Supplemental Insulin After establishing the basic dose of insulin, each patient must be educated on supplemental insulin in case of increase or decrease in blood glucose level according to SMBG Two methods 1.Compensatory insulin doses 2.Anticipatory insulin doses 41

42. Supplemental Insulin Compensatory insulin doses These doses are used to compensate for high blood glucose levels It assumes that there is no unusual changes in patient’s overall diet & exercise patterns Given as regular or short acting insulin (lispro & aspart are preferred due to shorter duration of action) 42

43. Supplemental Insulin Compensatory insulin doses Usually for each 30-50 mg/dl elevation above the target level 1-2 units of supplemental insulin is required To be more accurate must determine the supplemental dose of insulin by using the sensitivity factor Sensitivity factor is determined by using the 1500 or 1800 rule 1500/TDD = sensitivity factor If TDD is 30: 1500/30 = 50 mg/dl (each unit of insulin will decrease blood glucose level by 50 mg/dl) 43

44. Supplemental Insulin Compensatory insulin doses Example for algorithm for the previous patient: 44 Blood glucose mg/dlRegular insulin <801 unit less 80-120Usual dose 120-1701 unit extra 170-2202 units extra 220-2703 units extra 270-3204 units extra

45. Supplemental Insulin Compensatory insulin doses If the patient requires more than 4 units must seek medical advice Also in case of ketones in urine must go to hospital If supplemental doses of insulin are required for ≥3 days, insulin dose should be adjusted Example: if patients is usually taking lispro before meals and NPH at bedtime, and 3 days in a row he required 2 units of lispro before lunch, so increase lispro morning dose by 2 units 45

46. Supplemental Insulin Anticipated insulin doses Prescribed in anticipation of an immediate event that is likely to alter a patient’s response to insulin This include an unusual large or small meal or exercise Increase lispro, aspart or regular insulin by 1 unit for each additional 15 g of carbohydrates Decrease lispro, aspart or regular insulin by 1 unit for smaller meals 46

47. Sliding Scale Algorithmic method for adjusting doses of short or regular acting insulin according to blood glucose test results Used for hospitalized patients in which their insulin requirements may vary significantly due to stress (infection, surgery or acute illnesses), inactivity or variable caloric intake Blood glucose levels are measured every 4 hours if given SC, & every hour if given IV Sliding scale should be individualized by using each patient sensitivity factor 47

48. Sliding Scale If sensitivity factor is not use the alternate method is for each 30-50 mg/dl elevation above the target level 1-2 units of insulin is given After sliding scale or upon hospital discharge what to do? 48

49. Sick Day Management 1.Continue insulin even if food intake is decreased 2.Maintain fluid intake 3.Test blood glucose every 4 hours at a minimum 4.Test urine for ketones 5.Administer supplemental dose of insulin according to a prescribed algorithm (ex. 1-2 units for every 30-50 mg/dl over 120 mg/dl) 6.Seek medical attention if : Urine ketones, blood glucose > 300 mg/dl or mental status changes 49

50. Principles of Management Part II: B. Oral anti-diabetic agents 50

51. Oral Anti-Diabetic Agents 1.Alpha – glucosidase inhibitors 2.Biguanides 3.Non-sulfonylurea insulin secretagogues (Meglitindes) 4.Sulfonylureas 5.Thiazolidnediones 51

52. α – Glucosidase Inhibitors Acarbose – precose® & Miglitol – Glyset ® Mechanism of action Competitive reversible inhibition of intestinal α – glucosidase Delays glucose absorption & lower postprandial hyperglycemia Dose not enhance insulin secretion No effect on weight or lipids 52

53. α – Glucosidase Inhibitors Adverse effects GI: flatulence, diarrhea & abdominal pain. Can decrease this side effect by slow titration in dose Elevated liver function test: monitor liver enzyme every 3 months for 1 st year of therapy then periodically. Because miglitol is not metabolized through liver there is no liver toxicity 53

54. α – Glucosidase Inhibitors Contraindications & precautions GI conditions: not recommended for patients with malabsorption, or inflammatory bowel disease Renal impairment: not studied in sever renal impairment so should be avoided 54

55. α – Glucosidase Inhibitors Drug interactions May decrease the bioavailability of digoxin Miglitol decreases the bioavailability of ranitidine & propranolol Charcoal decreases the absorption of these drugs 55

56. α – Glucosidase Inhibitors Dosing & clinical application As an adjunct to diet and exercise in type 2 diabetes In combination Titrate the dose:  25 mg QD with meal for first 7-14 days  25mg BID week 3-4  25mg TID week 5-12  50mg TID (max dose if wt < 60 kg)  100mg TID (max it wt > 60 kg) 56

57. Biguanides Metformin ( Glucophage C. ®) Mechanism of action Antihyperglycemic agent Improve insulin sensitivity (they do not stimulate insulin release from pancreas & they do not cause hypoglycemia) Increase tissue uptake & utilization of glucose by muscle Decrease hepatic production of glucose 57

58. Biguanides Advantages Useful in obese patients because decreases insulin resistance Improves lipid profile Produces some weight loss No hypoglycemia 58

59. Biguanides Adverse effects GI: diarrhea, abdominal discomfort, metallic taste, nausea & anorexia. Can decrease this side effect by slow titration in dose & by giving it with meals Lactic acidosis: it may decrease conversion of lactate to glucose & increase lactate production in gut & liver. Symptoms include weakness, malaise, myalgias, abdominal distress & heavy labored breathing Lactic acidosis only happen in patients with predisposing factors 59

60. Biguanides Contraindications & precautions (For lactic acidosis) Renal impairment (not recommended if CrCl <60 ml/min) Hepatic disease CHF Alcoholic Shock Dehydration Surgery Chronic metabolic acidosis or a history of lactic acidosis 60

61. Biguanides Drug interactions Cimetidin, nifedipine, furosemide – all can increase metaformin levels 61

62. Biguanides Dosing & clinical application As an adjunct to diet in type 2 patient that are uncontrolled In combination Initial dose is 500 mg po BID or 850mg Po QD, with meals to decrease side effects Titrate dose weekly and increase by 250-500mg Maximum dose 2550 mg OD or 850 mg TID 62

63. Non-Sulfonylurea Insulin Secretagogues Meglitindes ( Repaglinide – Prandin ® and Netaglinide – Starlix ®) Mechanism of action Stimulates release of insulin from the pancreatic beta cells (like sulfonyurea) The advantage over sulfonyurea is that they have rapid onset & shorter duration of action 63

64. Non-Sulfonylurea Insulin Secretagogues Adverse effects Mild hypoglycemia Weight gain (mild) 64

65. Non-Sulfonylurea Insulin Secretagogues Contraindications & precautions Not given in patients with no pancreas (or type 1) Caution in liver dysfunction No dose adjustment is required in renal impairment 65

66. Non-Sulfonylurea Insulin Secretagogues Drug interactions CYP450 3A4 Metabolism, so potential for interactions exist 66

67. Non-Sulfonylurea Insulin Secretagogues Dosing & clinical application As an adjunct to diet & exercise to patients with uncontrolled type 2 diabetes In combination (not with sulfonylurea, why?) Rapid Onset & short duration of action, so given with meals to enhance postprandial glucose utilization 67

68. Non-Sulfonylurea Insulin Secretagogues Dosing & clinical application If HgbAIC is < 8 % start 0.5 mg repaglinide or 60 mg netaglainide If HgbAIC is > 8 % start 1-2 mg or 120 mg netaglinide Adjust doses at weekly intervals Take 15-30 minutes prior to each meal Instruct patients who skip a meal to skip a dose Instruct patient who eat an extra meal to add a dose 68

69. Sulfonylureas First generation Acetohexamide, chlorpropamid, tolazamide, & tolbutamide Not used commonly today duo to increase adverse effects, active metabolites, some prolonged half lives, & increase drug interaction Second generation Glyburide, glipizde, & glimepiride 100 times more potent than first generation 69

70. Sulfonylureas Mechanism of action Stimulate insulin release from pancereatic beta cells Normalize hepatic glucose production & partially reverse insulin resistance 70

71. Sulfonylureas Adverse effects Hypoglycemia & weight gain  Renal/hepatic insufficiency patients  Elderly or malnourished patients  Concurrent hypoglycemic drugs Hypothyroidism GI disturbances Hematologic Allergic skin reactions/photosensitivity Hepatotoxicity (Increase liver enzymes) 71

72. Sulfonylureas Contraindications & precautions Type 1 DM Pregnancy & breast-feeding except glyburide Documented hypersensitivity to sulfonylurea Severe hepatic or renal dysfunction Severe, acute intercurrent illness (e.g. infection or MI), surgery, or other stressful conditions 72

73. Sulfonylureas Drug interactions Increased hypoglycemic effect Warfarin, azole antifungals, gemfibrozil, clofibrate, sulfonamides, MAOIs, tricyclic antidepressant, alcohol, cimetidine, aspirin & concomitant agents for diabetes Decreased hypoglycemic effect beta – blockers, CCBs, cholestyramine, Glucocorticoides, phenytoin, oral contraceptives, rifampin, thiazides, niacin 73

74. Sulfonylureas Dosing & clinical application Adjunct to diet and exercise in type 2 patients Used in combination therapy with insulin, metformin, thiazolidinediones or alpha – glucosidase inhibitors 74

75. Sulfonylureas Dosing & clinical application Start at low end of the dosing range, especially in the elderly Increase dose every 1-2 weeks until maximum dosage Exceeding the maximum dosage increases side effects, but does not decrease blood glucose Use cautiously in patients with increase risk of hypoglycemia 75

76. Sulfonylureas Treatment failure 15 % will have primary failure (poor blood sugar control after a trial of 6-12 weeks on medication & diet) After 5 years, ~ 50 % may experience secondary failure (failure of medicine to work after initial good glycemic control) 76

77. Sulfonylureas Glipizde: Dose 10 mg/day (maximum 40 mg/day) If not respond to 10 mg/d give combination not increase dose Glyburide: Maximum dose 20 mg/d (maximum effect occur at 10 mg/d) Advantage over others is that food does not delay extent of absorption (can be given without relation to meal) Glimepiride : Has the advantage of once daily dosing 77

78. Thiazolidinediones Rosiglitazone – Avandia ® & Pioglitazone – Actos ® Mechanism of action Improves cellular response to insulin W/O increasing pancreatic insulin secretion Decrease insulin resistance Decreases hepatic glucose production Results in reduction in exogenous insulin dosage when used in combination May have favorable effect on HDL 78

79. Thiazolidinediones Adverse effects Hepatotoxicity  Troglitazone pulled from the market secondary to hepatic fatalities  Do not start therapy in patients with baseline LFTs> 2.5x  Check LFTs every 2 months for the first year  Monitor nausea vomiting, abdominal pain, fatigue, anorexia, dark urine 79

80. Thiazolidinediones Adverse effects Hematologic effects  Decrease hemoglobin & hematocrit Cardiovascular effects  Can cause edema Weight gain  Fluid & fat accumulation 80

81. Thiazolidinediones Contraindications & precautions Type 1 DM Hepatic disease Severe CHF History of hypersensitivity to TZD 81

82. Thiazolidinediones Drug interactions Pioglitazone induces the hepatic enzyme CYP 3A4, may affect the following drugs: estrogen, cyclosporine, tacrolimus & HMG-CoA reductase inhibitors Rosiglitazone does not appear to inhibit any CYP enzymes 82

83. Thiazolidinediones Dosing & clinical application As an adjunct to diet and exercise In combination Dose: Rosiglitazone 4-8 mg/day Pioglitazone 15-30 mg/day 83

84. Pharmacological Effects of Anti-Diabetic Agents Therapeutic ClassIncreases peripheral glucose uptake Decrease hepatic glucose secretion Increase insulin secretion Delay CHO absorption Target Organ a-glucosidasexGIT BiguanidexxLiver & intestine ThiazolidinedionesxxMuscle, adipose tissue & liver SulfonylureasxxxIslet cells of pancreas MeglitinidexIslet cells of pancreas 84

85. Combination Products Glucovance ® : glyburide / metformin Metaglip ® : glipizide / metformin Advadamet ® : rosiglitazone / metaformin 85

86. Type 2 DM Under Special Circumstance Patients with decreased renal function: Consider: glipizide, glimerpiride, insulin, repaglinide, thiazolidinediones Avoid: first generation SUs, glyburide, metformin, acarbose 86

87. Type 2 DM Under Special Circumstance Patients with decreased hepatic function: Consider: insulin, repaglinide (cautious dosing), miglitol Avoid: thiazolidinediones, metformin, acarbose, glyburide, first generation sulfonylurea 87

88. Type 2 DM Under Special Circumstance Obese patients: Consider: metformin, acarbose, miglitol Avoid: SUs, insulin (unless you are at the end stage of disease), repaglinide, thiazolidinediones Patients experiencing hypoglycemia due to irregular eating patterns Avoid: insulin & long acting SUs 88

89. Prevention & Management of Diabetes Complications 89

90. Complication of DM CVD 1.Hypertension/blood pressure control 2.Dyslipidemia/lipid management 3.Antiplatelet agents 4.Smoking cessation 5.CHD screening and treatment Nephropathy Retinopathy screening & treatment Neuropathy screening & treatment Foot care 90

91. Complication of DM GoalEndpointAssessment Blood pressure< 130/80 mmHgEvery visit Lipid controlLDL < 70 mg/dl TG < 150 mg/dl HDL > 45 mg/dl Yearly Urine proteinMicroalbuminuria < 30 mg/24 hours Yearly 91

92. Principles of Management Treatment Algorithm for DM 92

93. 1. Diagnose Your Patient 93 Criteria for the diagnosis of diabetes 1 FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h OR 2 Symptoms of hyperglycemia & a casual plasma glucose 200 mg/dl (11.1 mmol/l). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of hyperglycemia include polyuria, polydipsia, & unexplained weight loss OR 3 2-h plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water

94. 2. Type 1 or Type 2 Type 1 DM YoungPPPsThin Type 2 DM ObeseStrong family historyFatigue 94

95. 3. Set Your Goals 95 A1C< 7% Preprandial plasma glucose70–130 mg/dl (3.9–7.2 mmol/l) Peak postprandial plasma glucose <180 mg/dl (<10.0 mmol/l)

96. 4. Start Treatment for Type 1 DM 96 Chose your initial dose 0.5 U/kg Chose types of insulin to be used Honeymoon phase? Acute illness? Remember you will need 1 short/regular acting & 1 intermediate/long acting Split the dose between both insulin types 70:30 or 50:50 Chose the method of insulin delivery According to ADA guidelines MDI is the preferred method of therapy But remember to see is your patient is welling to take MDI Educate your patient on interpreting SBGM Tell him the frequency of monitoring & the goals he has to achieve Supplemental insulin doses if patient is not meeting his goal Remember the method of calculation (insulin sensitivity factor) Other things to remember when your dealing with a type 1 patient: 1.Fasting hyperglycemia (including simogyi effect & dawn phenomenon) 2.Insulin sliding scale 3.Sick day management

97. 5. Start Treatment for Type 2 DM 97 Life style interventions Check HgbA1C This includes diet & exercise specially for obese patients >7% Add metformin or sulfonylurea Obese patient: metformin Lean patient: sulfonylurea If goals not achieved switch to combination <7% Continue on same mode of therapy Check HgbA1C

98. 5. Start Treatment for Type 2 DM 98 Use combination of metformin + one of the followings: Rosiglitazone or pioglitazone Sulfonylurea Basal insulin (bedtime intermediate acting or bedtime or morning long-acting) >7% Check HgbA1C <7% Continue on same mode of therapy Add glitazone or sulfonylurea or insulin Or intensify insulin for those on insulin HgbA1C >7% In patients not yet receiving insulin, add basal insulin or intensify insulin in those receiving insulin When prandial rapid acting insulin is added, sulfonylureas or glinides should be DC Consider insulin as initial therapy (with lifestyle modification) in patients with fasting glucose >250 mg/dL or HbA1C >10% or those with ketonuria or symptoms of hyperglycemia When initiating insulin, start with a bedtime dose of an intermediate-acting or once-daily long-acting Initiate with 0.2 units/kg Monitor HgbA1c every 3 months

99. 6. Educate Your Patient Group discussion 99

100. Thank you 100