340 LONG TERM MANAGEMENT (CONT’D) reductase inhibitor (# LDL), bile acid sequestrants (# LDL), nicotinic acid (# triglycerides, # LDL, " HDL but may " glucose) DIABETIC CONTROL aim for HbA1C of less than 7.0% in all patients A target HbA1C of 6.5% may be considered in selected patients Fasting and before meals glucose should be 4.0 7.0 mmol/L [73 126 mg/dL] The h post prandial glucose ideally should be 5.0 10.0 mg/ dL [91 182 mg/dL] or 5.0 8.0 mg/dL [91 145 mg/ dL] if A1C targets are not met) Diabetes Control and Complications Trial showed that intensive gly cemic control of patients with type diabetes reduces retinopathy, nephropathy, and neuropa thy A1C correlates with complications Major side effects include 3Â " in hypoglycemia (especially previous episodes, hypoglycemia unawareness) and increased weight gain EDUCATION all patients should attend diabetes classes EXERCISE 150 per week of moderate to vig orous aerobic physical activity and resistance exer cise times per week A baseline ECG or exercise ECG is advisable prior to embarking on an exercise program EYE/NEUROLOGIC all patients with type diabetes should be referred to an ophthalmologist at the time of diagnosis and then annually Patients with type diabetes may have a baseline eye assess ment years after the diagnosis as long as they are aged 15 or greater Eye exams may be done annually after that All patients should have an annual assessment of neuropathy including the diabetic foot exam Amitriptyline, gabapentin, or pregabalin may be used for painful neuropathy Domperidone, metoclopramide, erythromycin, or cisapride (beware long QT) may be used for gastroparesis FAT REDUCTION (lose 10 kg) all patients should follow healthy eating guidelines and try to attain an ideal body weight See OBESITY ISSUES (p 403) GET GOING TO QUIT SMOKING! there are many different options for patients, including nicotine gum, nicotine inhaler, Nicoderm patch, Bupro pion SR, and varenicline Smoking cessation classes SCREENING FOR CARDIOVASCULAR DISEASE patients should have the following tests done at baseline if they meet any of the following criteria: ECG if age >40, have had diabetes for >15 years, or if they have hypertension, proteinuria, reduced pulses or vascular bruits ECG should be repeated every years in patients of high car diovascular risk Diabetes Mellitus LONG TERM MANAGEMENT (CONT’D) ECG STRESS TEST angina, atypical chest pain, dyspnea, abnormal ECG, peripheral artery disease, carotid bruits, transient ischemic attack, and stroke STRESS MIBI individuals with an abnormal ECG (LBBB or ST T wave changes) or who cannot exercise REVASCULARIZATION prompt revascularization vs medical therapy for stable ischemia seems to have similar outcomes (death and major cardiovascular events) EXERCISE ORAL HYPOGLYCEMIC AGENTS BIGUANIDES (# hepatic glucose production, " tissue sensitivity) metformin 500 850 mg PO TID; adverse effects include GI upset and lactoacidosis; contraindi cations include hypoxia, hepatic and renal failure, HF, poor LV function; hold before giving IV contrast and 48 h post contrast THIAZOLIDINEDIONES (sensitizes tissues to insulin, # hepatic glucose production) pioglitazone 15 45 mg PO daily; adverse effects include hepatotoxicity and fluid retention, contraindications include liver failure, fluid overload, HF, and CAD; avoid concurrent use of insulin and thiazolidinediones as increased fluid reten tion Recent evidence linking rosiglitazone with increased risk of myocardial infarction and cardiovas cular death; thus the decision to prescribe rosiglita zone should be done after carefully balancing the risks and benefits of treatment Rosiglitazone has been withdrawn from the European market MEGLITINIDE (" pancreatic insulin release) repagli nide 0.5 mg PO TID ac meals; adverse effects include hypoglycemia SULFONYLUREA (" pancreatic insulin release) gli clazide 80 mg PO daily to 160 mg BID; glimepiride mg PO daily, glyburide 2.5 10 mg PO BID; adverse effects include hypoglycemia a GLUCOSIDASE INHIBITOR (delays glucose absorption) acarbose 25 100 mg TID ac meals; adverse effects include bloating and diarrhea INCRETIN MIMETICS AND DIPEPTIDYL PEPTI DASE (DPP 4) INHIBITORS sitagliptin 25 100 mg PO daily Increases incretin levels, increases insulin release in response to glucose, and decreases glucagon resulting in improved postpran dial control; weight neutral; long term adverse effects are not yet known GLUCAGON LIKE PEPTIDE (GLP 1) ANALO GUES exenatide 10 mg SC BID 30 before meals Causes dose dependent and glucose depen dent insulin secretion, delays gastric emptying, pro motes weight loss, and suppresses glucagon Long term adverse effects are unknown Nausea is a com mon adverse effect and pancreatitis has been reported 341 Principles of Insulin Use Principles of Insulin Use STARTING INSULIN FOR NEW PATIENTS CALCULATE TOTAL DAILY DOSE STABLE NEW PATIENTS the total daily requirement is 0.5 units/kg of insulin per day SC in divided dosages MULTIPLE DAILY INJECTIONS all diabetic patients should be encouraged to be on this regimen to achieve good control; 20% of total insulin should be given before breakfast, lunch, and supper as rapid or regular, 40% of total insulin dose should be given as basal insulin at bedtime using NPH, Lantus, or Leve mir If using rapid ac meals, a small dose of basal insulin will be necessary in the morning as well TWO-THIRDS, ONE-THIRD RULE if a patient is unable to multiple daily injections, consider the two thirds, one third rule, which establishes a baseline for insulin administration using the two main types of insulin (intermediate acting and fast acting) AM dose (given before breakfast) = 2/3 of total daily insulin (2/3=N, 1/3=R), supper dose = 1/3 of total daily insulin (2/3=N, 1/3=R) BEDTIME INSULIN patients with type diabetes who are on maximum oral hypoglycemic agents may be started on bedtime insulin at 0.1 units/kg to improve control using either NPH, Lantus, or Levemir SPECIAL CONSIDERATIONS DELAY DOSE patients may need to delay their insulin intake at times (e.g if they were NPO for procedures) For every hour delay in giving NPH, subtract 10% of dose RENAL FAILURE insulin is renally excreted, thus its dose must be reduced in patients with renal failure METFORMIN AND INSULIN consider the use of met formin in conjunction with insulin in type dia betics to increase insulin sensitivity and decrease insulin requirements THIAZOLIDINEDIONES AND INSULIN avoid using thia zolidinediones (e.g rosiglitazone) in combination with insulin as both medications promote fluid retention b-BLOCKERS USE IN DIABETICS non selective b blockers may mask signs and symptoms of hypo glycemia Consider use of cardioselective b blocker agents in diabetics NEJM 2005 352:2 REGULAR INSULIN DOSE ADJUSTMENT PRINCIPLES INSULIN ADJUSTMENTS understanding the phar macokinetics of different insulin types is essential for fine adjustments of insulin regimen Blood sugar is checked times/day, before meals and at bedtime HIGH AM BLOOD SUGAR check AM glucose first to see if there is nocturnal hypoglycemia The bed time basal insulin would have to be decreased If the AM glucose is high, then increase the bed time basal insulin HIGH LUNCH TIME BLOOD SUGAR should increase breakfast insulin R dose HIGH SUPPER TIME BLOOD SUGAR should increase noon insulin R dose or morning basal dose HIGH BEDTIME BLOOD SUGAR should increase sup per insulin R dose TYPES OF INSULIN Insulin type/action Rapid acting (clear) Onset: 10 15 Peak: 1.5 h Duration: h Short acting (clear) Onset: 30 Peak: h Duration: 6.5 h Intermediate acting (cloudy) Onset: h Peak: h Duration: up to 18 h Long acting basal insulin analogues (clear) Onset: 90 Duration: up to 24 h Premixed Premixed regular insulin NPH (cloudy) Premixed insulin analogues (cloudy) Trade names Humalog (insulin lispro) NovoRapid (insulin aspart) Humulin R Novolin ge Toronto Humulin N Novolin ge NPH Insulin detemir (Levemir) Insulin glargine (Lantus) Humulin 30/70 Novolin ge 30/70 Novolin ge 40/60 Novolin ge 50/50 Humalog Mix 25 Humalog Mix 50 Novo Mix 30 Canadian Diabetes Association Guidelines 2008 342 Hypoglycemia SAMPLE SLIDING SCALE TEMPLATE INSULIN SLIDING SCALE Glucometer QID with insulin SC QID Blood sugar Regular or rapid insulin SC TID ac meals NPH or basal insulin SC qhs 0–4 give juice, call MD give juice, call MD 4.1–6 6.1–8 8.1–10 Individualized Individualized 10.1–12 dosing dosing 12.1–16 16.1–18 18.1–20 >20 Notify MD Notify MD NOTE: dose of insulin varies depending on individual patient For insulin requiring patients, total daily dose is 0.5 units/kg/day; 20% of this dose to be given as regular or Rapid with meals and 40% to be given as bedtime NPH or basal insulin TREATMENT ISSUES LOCAL COMPLICATIONS OF INSULIN INJECTION lipoatrophy (human insulin), lipohypertrophy (animal insulin), edema, itching, pain or warmth at injection site, scar tissue TREATMENT ISSUES (CONT’D) LONG TERM COMPLICATIONS OF INSULIN USE weight gain and risk of hypoglycemia Possible asso ciation between long acting insulin and malignancy has been raised; however, further studies are required Hypoglycemia DIFFERENTIAL DIAGNOSIS # GLUCOSE, # INSULIN, AND # C PEPTIDE alco holism, sepsis, adrenal insufficiency, panhypopitui tarism, liver failure, HF, renal failure, anorexia, inborn errors of metabolism, drugs (b blockers, salicylates, haloperidol) # GLUCOSE, " INSULIN, AND # C PEPTIDE exo genous insulin, insulin autoantibodies # GLUCOSE, " INSULIN, AND " C PEPTIDE drugs (sulfonylurea, meglitinide, pentamidine, quinine) b cell tumor (insulinoma, islet cell hyperplasia nesidioblastosis) PATHOPHYSIOLOGY DEFINITION OF HYPOGLYCEMIA glucose 2Â size)’’ JAMA 1995 273:10 INVESTIGATIONS BASIC TSH, fT4, fT3, TSH receptor antibody (Graves’), anti TPO antibody (Hashimoto’s, Graves’), thyroglobulin (# if factitious), ESR (" in thyroiditis), CBCD, ALT, AST, ALP, bili LABS ... low due to decreased conversion of free T4 to free T3 AUTOIMMUNE DISEASES Hashimoto’s, Graves’ dis ease, type diabetes, myasthenia gravis, Addison’s, Sjogren’s, pernicious anemia, autoimmune... symptoms The presence of thyrotoxicosis along with dysfunction in of sys tems qualifies as thyroid storm PATHOPHYSIOLOGY GRAVES’ DISEASE circulating IgG that binds to and activates the TSH receptor,... should be encouraged to be on this regimen to achieve good control; 20% of total insulin should be given before breakfast, lunch, and supper as rapid or regular, 40% of total insulin dose should