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Diabetes Mellitus (DM) Part II PHCL 442 Hadeel Al-Kofide MSc 1 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 Last lecture 2 Principles of Management Part II: A.Insulin & its Clinical Applications 3 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 Initiating Insulin Therapy Clinical Situation Insulin Dose After calculating the total daily dose (TDD) of insulin: Type 1 DM 1. Split the dose between the regular or short acting insulin & 1. Initial dose 0.5-0.8 U/kg the intermediate or long acting insulin HOW? Either 50% 2. Honeymoon phase 0.2-0.5 U/kg each, or 70% (the intermediate or long acting) & 30% (the rapid orwith short actingduring insulin) 1-1.5 U/kg 3. Patients ketosis, illnesses, during growth 2. Then it depends in which method of insulin delivery you Typewill 2 DM (insulin resistance) chose e.g. insulin pump, 0.7-1.5 MDI orU/kg conventional method 5 Methods of Insulin Therapy • Intensive insulin therapy (IIT): Insulin pump Multiple daily injections (MDI) • Conventional method • Example on different methods of insulin therapy 6 Methods of Insulin Therapy 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 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 Intensive Insulin Therapy • Two major methods used to deliver IIT: 1. Insulin pump 2. MDI 9 Methods of Insulin Therapy 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 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 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 Examples of Different Insulin Regimens Method 1 AM Why we Bedtime Why weneed needan a intermediate short acting here? --acting here? PM Lispro/NPH Noon Whywe weneed needan a Why short acting here? intermediate -- acting here? To cover lunch + --To cover breakfast basal insulin -- Lispro/NPH -- Lispro/Lente -- Lispro/Lente -- Aspart/NPH -- Aspart/NPH -- Aspart/lente -- Aspart/lente -- Reg/NPH Reg/Lente Reg/NPH Reg/Lente To Tocover coversnack dinner+ -basal insulin 13 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 1 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 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 2 This method is used to overcome disadvantages of method 1 Bedtime AM Noon PM Reg/NPH -- Reg NPH Reg/Lente -- Reg Lente Lispro/NPH -- Lispro NPH Lispro/Lente -- Lispro Lente Aspart/NPH -- Aspart NPH Aspart/Lente -- Aspart Lente 15 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 2 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 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 3 AM Noon PM Bedtime Reg Reg Reg NPH Reg Reg Reg Lente Reg Reg Reg Glargine Reg Reg Reg Ultralente 17 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 3 • 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 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 4 AM Noon PM Bedtime Lispro/NPH Lispro Lispro NPH Lispro/Lente Lispro Lispro Lente Aspart/NPH Aspart Aspart NPH Aspart/Lente Aspart Aspart Lente 19 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 4 • 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 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 5 AM Noon PM Bedtime Reg/Ultralente Reg Reg/Ultralente -- Lente/Ultralente Lispro Lente/Ultralente -- Aspart/Ultralente Aspart Aspart/Ultralente -- 21 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 5 • Why ultralente is given twice daily? • If glargine replaces ultralente give it once daily • The main disadvantage here is fasting hyperglycemia, why? 22 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 6 AM Noon PM Bedtime Reg/Ultralente Reg Reg NPH Lente/Ultralente Lispro Lente NPH Aspart/Ultralente Aspart Aspart NPH 23 Methods of Insulin Therapy Examples of Different Insulin Regimens Method 6 • It overcomes the problems in method 5, why? 24 Testing Frequency Ideally patients should test their blood glucose in the following times: • Before meals • After meals This means 8 times/day!! • Bedtime • At 2-3 am 25 Testing Frequency But at least the patient should measure blood glucose in the following times: • Before meals This means 4 times/day • Bedtime • At 2-3 am 3 times/week • 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 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 Interpreting SMBG Test Time Target Insulin Dose Target Meal/Snack Fasting (pre-breakfast) Pre-dinner/bedtime intermediate or long acting insulin Bedtime snack Pre-lunch Pre-breakfast regular insulin Breakfast Pre-dinner Pre-breakfast intermediate acting insulin or pre-lunch regular acting insulin Lunch Bedtime Pre-dinner regular insulin Dinner 3 am Pre-dinner intermediate acting Dinner/bedtime insulin snack 28 Interpreting SMBG Examples 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 preprandial 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) Time SMBG (mg/dl) 7 am 160-200 Noon 220-260 5 pm 130-180 11 pm 140-180 29 Interpreting SMBG Examples 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 Fasting Hyperglycemia • Insufficient insulin dose • Somogyi effect • Dawn phenomenon • Examples 31 Fasting Hyperglycemia 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 12 pm 5 pm 3 am 190 220 200 140 • Solution: increase the TDD of insulin 32 Fasting Hyperglycemia 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 12 pm 5 pm 3 am 190 120 100 80 33 Fasting Hyperglycemia Somogyi Effect • It occurs after severe hypoglycemia & its 2nd 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 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 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 12 pm 5 pm 3 am 180 120 110 110 36 Fasting Hyperglycemia 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 Examples • Example 1: Patient on NPH/Reg am & NPH/Reg pm 7 am 160 12 pm 130 5 pm 90 10 pm 100 3 am 60 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 38 Fasting Hyperglycemia Examples • Example 2: Patient on NPH/Reg am & NPH/Reg pm 7 am 160 12 pm 130 5 pm 90 10 pm 100 3 am 100 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 breakfast39 Fasting Hyperglycemia Examples • Example 3: Patient on NPH/Reg am, Reg pm, & NPH bedtime 7 am 100 12 pm 60 5 pm 90 10 pm 100 3 am 110 Solution: 1. Snack at morning 2. Change from regular to lispro 3. Decrease morning dose of regular insulin Post-prandial hypoglycemia 40 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 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 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 Supplemental Insulin Compensatory insulin doses • Example for algorithm for the previous patient: Blood glucose mg/dl Regular insulin <80 1 unit less 80-120 Usual dose 120-170 1 unit extra 170-220 2 units extra 220-270 3 units extra 270-320 4 units extra 44 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 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 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 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 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 Principles of Management Part II: B. Oral anti-diabetic agents 50 Oral Anti-Diabetic Agents 1. Alpha – glucosidase inhibitors 2. Biguanides 3. Non-sulfonylurea insulin secretagogues (Meglitindes) 4. Sulfonylureas 5. Thiazolidnediones 51 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 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 1st year of therapy then periodically. Because miglitol is not metabolized through liver there is no liver toxicity 53 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 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 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 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 Biguanides Advantages • Useful in obese patients because decreases insulin resistance • Improves lipid profile • Produces some weight loss • No hypoglycemia 58 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 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 Biguanides Drug interactions • Cimetidin , nifedipine , furosemide – all can increase metaformin levels 61 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 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 Non-Sulfonylurea Insulin Secretagogues Adverse effects • Mild hypoglycemia • Weight gain (mild) 64 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 Non-Sulfonylurea Insulin Secretagogues Drug interactions • CYP450 3A4 Metabolism , so potential for interactions exist 66 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 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 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 Sulfonylureas Mechanism of action • Stimulate insulin release from pancereatic beta cells • Normalize hepatic glucose production & partially reverse insulin resistance 70 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 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 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 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 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 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 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 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 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 Thiazolidinediones Adverse effects • Hematologic effects Decrease hemoglobin & hematocrit • Cardiovascular effects Can cause edema • Weight gain Fluid & fat accumulation 80 Thiazolidinediones Contraindications & precautions • Type 1 DM • Hepatic disease • Severe CHF • History of hypersensitivity to TZD 81 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 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 Pharmacological Effects of Anti-Diabetic Agents Therapeutic Class Increases peripheral glucose uptake Decrease hepatic glucose secretion Increase insulin secretion a-glucosidase Delay CHO absorption Target Organ x GIT Biguanide x x Liver & intestine Thiazolidinediones x x Muscle, adipose tissue & liver Sulfonylureas x x Meglitinide x Islet cells of pancreas x Islet cells of pancreas 84 Combination Products • Glucovance ® : glyburide / metformin • Metaglip ® : glipizide / metformin • Advadamet ® : rosiglitazone / metaformin 85 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 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 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 Prevention & Management of Diabetes Complications 89 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 Complication of DM Goal Endpoint Assessment Blood pressure < 130/80 mmHg Every visit Lipid control LDL < 70 mg/dl TG < 150 mg/dl HDL > 45 mg/dl Yearly Urine protein Microalbuminuria < 30 mg/24 hours Yearly 91 Principles of Management Treatment Algorithm for DM 92 1. Diagnose Your Patient 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 93 2. Type 1 or Type 2 Type 1 DM Type 2 DM Young Obese PPPs Strong family history Thin Fatigue 94 3. Set Your Goals A1C < 7% Preprandial plasma glucose 70–130 mg/dl (3.9–7.2 mmol/l) Peak postprandial plasma glucose <180 mg/dl (<10.0 mmol/l) 95 4. Start Treatment for Type 1 DM Chose your initial dose 0.5 U/kg 70:30 or 50:50 Chose types of insulin to be used Other things to remember when your dealing with a type 1 patient: Honeymoon Split the dose between phase? both insulin types Remember you will need 1 Acute1. illness? short/regular acting & 1 simogyi effect & Fasting hyperglycemia (including intermediate/long acting dawn phenomenon) Tellguidelines him the frequency of to ADA MDI is the Remember the 2.According Insulin sliding scale monitoring the goals he has method of&therapy method of preferred achieve remember to see istoyour calculation 3. But Sick day management patient is welling to take MDI (insulin sensitivity Supplemental insulin factor) doses if patient is not meeting his goal Chose the method of insulin delivery Educate your patient on interpreting SBGM 96 5. Start Treatment for Type 2 DM Life style interventions This includes diet & exercise specially for obese patients Obese patient: metformin Lean patient: sulfonylurea Check HgbA1C <7% Continue on same mode of therapy >7% Add metformin or sulfonylurea Check HgbA1C If goals not achieved switch to combination 97 5. Start Treatment for Type 2 DM Use combination of metformin of the followings: • When prandial rapid+ one acting insulin is added, • Rosiglitazone or pioglitazone sulfonylureas or glinides should be DC • Sulfonylurea • Basal insulin (bedtime intermediate acting or bedtime or morning long-acting) • Consider insulin as initial therapy (with lifestyle modification) in patients with fasting glucose >250 <7% mg/dL or HbA1C Continue >10% oronthose with ketonuria or same mode symptoms of hyperglycemia of therapy Check HgbA1C • WhenAdd initiating start with a bedtime dose of an glitazoneinsulin, or sulfonylurea or insulin intermediate-acting or once-daily Or intensify insulin for those on long-acting insulin • Initiate with 0.2 units/kg >7% HgbA1C >7% In patients not yet receiving insulin, add basal insulin or • Monitor HgbA1c every 3 months intensify insulin in those receiving insulin 98 6. Educate Your Patient • Group discussion 99 Thank you 100