Insulin Initiation and Intensification

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1 Insulin Initiation and Intensification ANDREW S. RHINEHART, MD, FACP, CDE MEDICAL DIRECTOR AND DIABETOLOGIST JOHNSTON MEMORIAL DIABETES CARE CENTER Objectives Understand the pharmacodynamics and pharmacokinetics of the different insulins Know how to teach patients regarding the identification and proper treatment of hypoglycemia Decide on a dosing strategy for adding basal insulin Understand when to intensify insulin therapy. Know how to add bolus pre-meal insulin to a basal insulin regimen Insulin Pharmacodynamics and Pharmacokinetics Insulin Pharmacodynamics and Pharmacokinetics K.I.S.S. Human vs. Analogue Insulins Human insulin are less physiologic Human insulins have more intra-patient variability of action Human insulins have more hypoglycemia Onset, Peak, and Duration Onset When does the insulin start working? Peak When is the insulin doing the most work? Duration How long it the insulin working? 1

2 Insulins Split-Mixed Insulins Insulins of Convenience Basal insulin Levemir (insulin detemir) Lantus (insulin glargine) Intermediate Acting insulin Humulin N or Novolin N (NPH) Humulin R U-500 (5 times concentrated regular insulin) Short acting insulin Humulin R and Novolin R (regular insulin) Rapid acting insulin Humalog (Lispro) NovoLog (Aspart) Apidra (glulisine) Human Humulin 70/30-70% NPH (Neutral Protamine Hagedorn*) & 30% Regular Humulin 50/50-50% NPH & 50% Regular Novolin 70/30-70% NPH & 30% Regular Analogue Novolog Mix 70/30 70% NPA (Neutral Protamine Apsart) & 30% NovoLog (Aspart) Humalog Mix 75/25 75% NPL (Neutral Protamine Lispro) & 25% Humalog (Lispro) Humalog Mix 50/50 50% NPL (Neutral Protamine Lispro) & 50% Humalog (Lispro) *Hans Christian Hagedorn inventor of NPH in 1936 and founder of Nordisk Insulinlaboratorium Initiating Insulin Therapy - Basal When? Type 2 diabetes who has failed therapy with Metformin plus other therapies or possibly 2 nd line after Metformin per ADA/EASD Consensus Statement from 2009 Morning hyperglycemia A1c climbing despite adequate non-insulin therapy How? Initiate basal insulin at bedtime at either: 10 units units/kg Titrate to morning control First set morning goal ( mg/dl ADA) Increase by 1-2 units every 2-3 night until goal reached Low to High CASE 2 2

3 Case presentation Logbook Mrs. Smith is a 58 year old female referred to you regarding an A1c of 9.8% (eag = 235 mg/dl) Weight = 98 kg Current Anti-Diabetic Medications Levemir (Detemir) 40 units at bedtime Glimepiride 4 mg each morning Metformin ER 2000 mg with supper Date Breakfast Lunch Supper Bedtime 3/1/ /2/ /3/ /4/ /5/ /6/ /7/ Question? Recommendations What should you do next? Gather more data!! A1c & Self-Monitoring of Blood Glucose (SMBG) results do not correlate Test meter for accuracy Control solution Compare to office FS glucose result Consider a new meter Ask patient to SMBG 4 times daily (before meals and at bedtime) for a week and return for follow-up Consider diagnostic CGM Bring meter to follow-up for download 3

4 Follow-up Visit Question? Date Breakfast Lunch Supper Bedtime 3/8/ /9/ /10/ /11/ /12/ /13/ /14/ Treatment recommendations? Basal-Bolus Therapy Initiating Insulin Therapy - Bolus Stop Glimepiride No longer efficacious Continue Metformin ER Begin Bolus Rapid-Acting Insulin Analogue (Aspart, Lispro, or Glulisine) before each meal or one meal at a time SMBG 4-5 times daily Before meals for proper dosing Bedtime After one meal a day Overnight basal testing Going to bed at a lower glucose level may cause overnight hypoglycemia Ease in Basal plus 1 Begin 4-5 units of rapid-acting insulin before the biggest meal of the day (usually the evening meal) Titrate by 1 unit every few nights to post-prandial control (<50 mg/dl rise from pre-prandial glucose or < ) Basal plus 2 Add another pre-prandial insulin dose before breakfast or lunch Basal/Bolus therapy (Basal plus 3) Add pre-meal rapid-acting insulin before each meal Beginning here is an option ( Jump in ) 4

5 Case Presentation Too Much of a Good Thing CASE 1 Mr. Mullins is a 68 year old male who is self referred regarding his type 2 diabetes Last A1c = 7.5% (eag = 169) Weight = 109 kg Current Anti-Diabetic Medications Lantus (Glargine) 50 units at bedtime 70/30 Split-Mixed insulin 30 units before breakfast and supper Sitagliptin 100 mg daily Metformin 1000 mg twice daily Questions? Answers? Mr. Mullins complains of waking once or twice weekly either in the middle of the night or first thing in the morning with a cold clammy sweat that is relieved with juice. Would you like other data? Do you have any questions for Mr. Mullins? Date Breakfast Lunch Supper Bedtime 3/8/ /9/ /10/ /11/ /12/ /13/ /14/

6 Questions? Basal/Bolus Insulin Therapy Ratio Treatment recommendations? Total Daily Dose (TDD) Often 1-2 units/kg in insulin resistant patients Lantus (glargine) 50 units 70/30 Split-Mixed insulin 60 units TDD = 110 units Basal & Intermediate-Acting Insulin Lantus (glargine) = 50 units 70/30 Split-Mixed insulin = 60 x 0.7 = 42 units Total Basal = 92 units (84% of TDD) Bolus Insulin 70/30 Split-Mixed insulin = 60 x 0.3 = 18 units (16% of TDD) Treatment Recommendations Basal Bolus Insulin Therapy Stop Sitagliptin Likely contributing little to glycemic control but much to cost Overnight basal testing or diagnostic Continuous Glucose Monitoring (CGM) Test bedtime, 2:00-3:00 AM, and fasting morning glucose Identify asymptomatic overnight hypoglycemia Stop 70/30 Split-Mixed insulin Patient is receiving too much basal insulin and not enough bolus insulin with meals Basal - Continue current Lantus (glargine) dose (50 units at bedtime) and titrate to morning control Bolus - Begin Rapid-Acting Insulin Analogue before each meal 50% Basal Insulin (50 units) & 50% Bolus Insulin (50 units) Divide bolus insulin dose equally for each of the three meals 17 units before each meal 6

7 Bolus Insulin Dosing Meal (Nutrition Dose) Equal dose for each meal consistent carbohydrate diet Variable dose Meal size 10 units for a small meal 15 units for a normal meal 20 units for a large meal Insulin to Carbohydrate Ratio dosing 450/TDD (450/100 = 4.5) 1 unit for every 5 grams of carbohydrates Correction Dose Added to meal dose 1700/TDD = Insulin Sensitivity Factor (ISF) ISF = mg/dl drop in glucose for each unit of insulin given 1700/100 = 17 3 units for every 50 mg/dl above 150 mg/dl of glucose Correction dose = Glucose-target/ISF (Example: /17 = 7 units) On a Need to Know Basis CASE 3 Treatment Goal & SMBG Hypoglycemia SMBG 3-4 times daily at a minimum Before, 2 hours after meals, and/or bedtime Before and after exercise Overnight basal testing intermittently and with basal insulin dose changes Goals Individualize ADA Fasting = Peak 1-2 hour after eating = 180 Bedtime = A1c < 7% Common causes Too much basal insulin Eating less than usual Eating less than expected Eating later than usual Skipping a meal Being more active than usual Best cures / remedies Overnight basal testing Learn to carbohydrate count Dose after eating if dieting Carry a snack with you Avoid this & carry a snack Anticipate Take less insulin prior to activity Consume grams of carbohydrates every minutes during activity 7

8 Hypoglycemia Sick Day Rules Expect hypoglycemia when well controlled but be prepared to treat it Carry a rapid acting high-glycemic index carbohydrate at all times glucose tablets or gel Glucose mg/dl 15 grams of carbohydrates and recheck glucose in 15 minutes 3-4 glucose tables 4 oz. soda or juice 6-8 hard candies (chewed) Retreat if still <70 mg/dl If >70 mg/dl consume next meal (take normal bolus insulin dose) or a snack if between meals Glucose <50 mg/dl 30 grams of carbohydrates and recheck glucose in 15 minutes Monitor glucose every 4-6 hours Continue basal insulin Correction doses of bolus insulin every 4-6 hours Consume 8 ounces of non-caloric liquids every few hours Consume grams of carbohydrates every few hours Call provider if glucose >100 mg/dl higher than usual high glucose Type 1 Diabetes Urine ketones every 4 hours and call provider or go to ER if moderate to high ketones Questions? 8

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