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Diabetes Treatment Practical Applications Tim Drake PharmD How to Adjust Therapy to Get The Best Control Intensive vs.. Conventional Insulin dosing Single vs.. Combination Oral Medications Fasting vs. Postprandial blood glucose values Combination of Oral and Insulin American College of Endocrinologists vs. American Diabetes Association Goals Blood Glucose Goals ACE ADA A1C 6.5 7 Fasting <110 70-130 Post prandial Bedtime <140 <180 110-150 A1C A1C (%) 6 7 8 9 10 11 12 Mean Plasma Glucose (mg/dl) 126 154 183 212 240 269 298 Fasting vs. Postprandial Fasting Reflects hepatic glucose production Postprandial hyperglycemia Carbohydrates in meal Insulin deficiency Muscle sensitivity Incretin deficiency Glucagon increased Fasting vs. Postprandial Fasting values are more important with a higher A1c Lower A1c values deal more with postprandial values Effects on fasting or postprandial? Fasting Metformin TZD’s Basal Insulin Sulfonylureas Post-Prandial Exanatide Sitigliptin Nateglinide Acarbose Short-acting insulins Miglitol Repaglinide Type 2 Case JA is a 42 year old Hispanic male with newly diagnosed type 2 diabetes. He also has hypertension and hyperlipidemia. His mother and 2 sisters have diabetes. Mother is on dialysis He is married and has 2 children. He works as a restaurant manager Labs A1c = 9.8 Glucose = 238 Urinalysis = glucose SrCr = 0.8 BMI = 33 LFTs = WNL Eye exam = WNL Foot exam = WNL What Additional Information Would You Want to Know? Dietary Information Exercise Information Current understanding of diabetes Does he know how to self monitor? Labs etc. Lipid profile Blood Pressure Albumin/creatinine ratio JA was seen by the dietician, started walking 30 minutes daily, but 2 weeks later, still has a fasting Blood Glucose of 220. What are the issues (good and bad) with starting the following medications? Glipizide 10 mg QD Metformin 500 mg BID Actos 30 mg QD Precose 25mg TID How would you counsel a patient or monitor each one of the medications? Glipizide Sulfa allergy, do not skip meals, possible hypoglycemia Metformin Self limiting GI upset, SrCr, heart failure, ALOH, surgery, potential CV benefit Actos Edema, weight gain, possible HF symptoms, caution use with insulin Precose Timing with meals, GI side effects JA is started on Metformin 500 mg BID and Actos 30mg QD and titrated to the maximal effective dose. His A1c is still 7.5% after 3 months. What would be the best to do for him? Switch to glipizide ER 20mg daily Switch to Glucovance (metformin/glyburide 500mg/2.5mg) 2 tablets BID Add exenatide 5mcg SQ BID Add sitagliptin 100mg QD What if? What if JA was diagnosed with hepatitis and had an elevated ALT of 150 (normal is 3-31)? Which anti-diabetic medications need to be changed in the presence of liver dysfunction? What if JA developed kidney failure and had a SrCr of 2.6 Which anti-diabetic medications need to be changed in the presence of kidney failure? Kidney Failure or Insufficiency Metformin Do not use with SrCr > 1.4 in women and 1.5 in men Glyburide Miglitol Acarbose Exenatide Sitagliptin Liver Dysfunction Glipizide, glyburide and glimepiride Nateglinide and repaglinide Metformin Rosiglitazone and pioglitazone DC if ALT is >3 times the ULN JA has been controlled with an A1c less than 7% on metformin/glyburide 500/2.5mg 2 BID, and actos 30 mg daily for the last 5 years. Recently his A1c has been creeping up. 1 year ago it was 6.5%, 6 months ago it was 6.9%, 3 months ago – 7.3% and now it is 7.6%. What would you recommend? Lantus insulin 10 units QHS Add Avandia 4mg QD Add Precose 25mg TID Add glipizide 10 mg QD Insulin Management Basal Insulin Metobolic needs Keeps blood glucose steady About 50% of requirement Bolus Insulin Nutrition Correct highs About 50% of requirement Pattern Management What is the target blood glucose level Get fasting blood glucose controlled first After fasting, then look at post-prandial and others Only one change at a time Small problems = small changes JA has been on metformin/glyburide 500/2.5mg 2 BID, and actos 30 mg daily with escalating A1c levels. He is placed on Lantus 25 units SQ QHS Titrate basal insulin 2 units every 2 days until fasting blood glucose is at goal Now JA is on 34 units of Lantus QHS plus oral therapy. He comes in with these readings Because of convenience, JA was switched to NPH/regular insulin He uses 24/6 units of NPH/regular at breakfast and 20/8 at dinner Breakfast 24/6 Dinner 25/8 Carbohydrate Counting More precise matching of food and insulin More food choices Potential for increased blood glucose control Fits insulin into the patient’s lifestyle Carbohydrate Exchange or “15 grams of carbohydrate equal” 1 slice of bread 6 crackers ½ cup of cereal or grains ½ cup of juice 1 small piece of fruit ¾ cup of yogurt 1 cup of milk 1 small cookie 1 Tbl jam or jelly ½ cup cooked veggies 1 cup raw veggies Labeling Look at serving size first Count total carbohydrates If dietary fibers are 5 grams or more, deduct from total carbohydrate Estimating CHO/insulin ratio Usually 1 unit rapid acting insulin/15 grams CHO Can vary from 1/(5-20) Lower insulin dose = higher ratio Lower body weight = higher ratio Estimating CHO/insulin ratio Calculate patients daily insulin requirement 450 divided by total daily insulin requirement = ratio 450/45 units = 10 1 unit of insulin for every 10 grams CHO Insulin Sensitivity Factor 1700 rule Use for rapid acting insulin 1700/total daily insulin requirement = amount of blood glucose lowering from 1 unit of rapid acting insulin 1700/34 units = 50 So for every 1 unit of insulin, you would expect a 50 unit lowering of blood glucose Fine Tuning Pick a meal for which you can easily keep a record Record the CHO from that meal and keep the CHO consistent for 7 days Record the insulin used for that meal Find 3 meals where the pre and post-prandial levels were within goal Divide the CHO by the insulin used to find your new ratio 45 grams CHO/ 3 units insulin = 15 Type 1 case Ratio of 15:1 Breakfast: 4 units aspartamine insulin (60 grams CHO) Lunch: 2 units aspartamine insulin (30 grams CHO) Dinner: 5 units aspartamine insulin (60 grams CHO + 1 unit correction factor) Takes 14 units of glargine at bedtime Add correction back into lunch dosing Decrease ratio for lunch 1:15 for breakfast 1:10 for lunch 1:15 for dinner Patient Case AS is a 37 y/o female with Diabetes Mellitus Type 1 for >30years. She has been on Multiple Dose Injection (MDI) therapy for about 5 years. She is currently prescribed glargine insulin (Lantus®) 15u at 10 PM and glulisine Insulin before each meal. The before meal Glulisine Insulin regimen is 4u before breakfast, 4u before lunch, and 7u before dinner. Her last A1C was 8.0 and BP110/75 mm Hg. The patient is complaining that her blood glucose is inadequately controlled and she is locked into eating a fixed amount for each meal. Patient Case What is recommended for her to help her adjust her eating habits? What is her CHO/insulin ratio? About 1:15 What is her insulin sensitivity factor? About 1:50 AS is taking glargine 10 units QHS and dosing glulisine according to CHO counting with a ratio of 1:15. She has a correction factor of about 1:50. Morning Lunch Dinner Before Bed 135 130 162 +1u 115 120 115 170 +1u 110 115 120 155 +1u 116 Why was the extra unit given at dinner? How should we adjust her schedule? What is the cost of therapy for AS? How much glargine will she need per month? 450u or one vial (1000u) about $100 How much glulisine will she need each month? Same, 450u at about $100 How many testing strips and lancets will she need? About 150 so about $150 What other supplies or medications might she need? Glucose monitor, syringes, etc. What is the total cost of therapy just for the diabetes? Like $400 per month DCCT trial Estimated that to use intense insulin regimens on every type 1 patient and advanced type 2 patients would cost 4 billion dollars Benefits seen would be net gains of 920,000 more years of sight, 691,000 more years of free of end stage renal disease and 678,000 more years free from amputations. Self monitoring blood glucose Is it worth it? Absolutely necessary for intense insulin regimens and to avoid serious side effects For type 2 patients, it is not as crucial One study found an A1C lowering of 0.4% while others showed no change Dawn Phenomenon Associated with increased early morning blood glucose and insulin requirements Comes from an increase in glucose production Elevation in counter regulatory hormones Depends upon stress, illness, menses, BG control Somogyi Effect Rebound hyperglycemia First hypoglycemia followed by hyperglycemia Difficult to distinguish from dawn phenomenon Need a blood glucose reading from 2-3 am to diagnose Immunizations Annual influenza vaccine Pneumococcal vaccine Once for all patients with diabetes and age 2 or older Repeat the vaccine after age 65 if they have not received the vaccine in the last 5 years Adjusting A1C goals Older adults who are functional and cognitively intact should have the same goals as younger patients For older adults who are not fully functional or have cognitive disabilities, the goals can be relaxed Screening for complications should be individualized Hypertension should be treated in all patients Anti-platelet and anti-lipid therapies should be individualized Adjusting A1C goals Even while relaxing A1C goals, care should be taken to to avoid symptoms and acute complications associated with hyperglycemia or hypoglycemia