2/4/13. Insulin Dosing. Insulin Dosing. Insulin Dosing. Insulin Dosing. Insulin Dosing. Insulin Dosing

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1 Step 1: Determine etween Intensive Insulin Therapy or Conventional Insulin Therapy Intensive Insulin Therapy (IIT) y definition, IIT attempts to mimic the body s normal release of insulin and therefore, generally includes more than two injections per day using insulin with different action profiles. The goal of IIT is achieving near normal biochemical markers of glycemic control. Conventional Insulin Therapy (CIT) CIT involves one or two injections per day using intermediate-acting insulin with less-than-normal biochemical markers of glycemic control as a goal of therapy. The major goal of CIT is avoiding the symptoms of hyper- and hypoglycemia. Step 1: Determine etween Intensive Insulin Therapy or Conventional Insulin Therapy Candidates for Intensive Insulin Therapy (IIT) Diabetic women planning to conceive Pregnant women Poorly controlled on conventional therapy Highly motivated and compliant patients willing to test blood glucose 4 times daily and inject at least 3 doses of insulin daily Technical ability to test glucose Intellectual ability to interpret test results and adjust insulin Younger patients Step 1: Determine etween Intensive Insulin Therapy or Conventional Insulin Therapy Patients to avoid or use Intensive Insulin Therapy cautiously Counter-regulatory insufficiency (hypoglycemic unawareness) Type 1 diabetes for 15 years or more (not all patients) eta-blocker therapy (mask symptoms of hypoglycemia) Autonomic insufficiency Adrenal or pituitary insufficiency Patients with coronary or cerebral vascular disease (counterregulatory hormones may adversely affect these patients) Unreliable, noncompliant patients including those abusing alcohol or drugs and patients with psychiatric disorders Patients with severe diabetic complications Children who have not yet reached puberty Step 2: Determine Daily Insulin Requirement Diabetes Type Dosage in U/kg Actual ody Weight Type 1 Initial Dose Honeymoon Phase Type 2 Initial Dose With Insulin Resistance Step 3: Develop a Dosing Schedule (ase Dose) Number of Morning Noon Evening Injections efore efore efore Supper edtime Method 1 Injection Method 1 N Not Recommended Method 2 2 Injections N (2/3) N (1/3) N&R (2/3) N&R (1/3) Method 3 2 Injections 2:1 or 1:1* 1:1 Method 4 3 Injections N&R (2/3) 2:1 or 1:1* R (1/6) N (1/6) N&R (2/5) N&R (2/5) Method 5 3 Injections 1:1 R (1/5) 1:1 Method 6 4 Injections R (1/4) R (1/4) R (1/4) R (1/4) Method 7 4 Injections R (1/4) R (1/4) R (1/4) N (1/4) lispro/aspart/ lispro/aspart/ lispro/aspart// Glargine/Detemir Method 8 4 Injections glulisine/inhaled glulisine/inhaled glulisine/inhaled (50%) (16%) (17%) (17%) 1

2 Method 1 Method 2 L S HS L S HS Method 3 Method 4 L S HS L S HS Method 5 Method 6 L S HS L S HS 2

3 Method 7 Method 8 Glargine/Detemir Lispro/Aspart/Glulisine L S HS L S HS One Injection of asal Insulin Step 3: Develop a Dosing Schedule (ase Dose) Normal Physiologic Insulin Secretion Number of Morning Noon Evening edtime Injections efore efore efore Method Supper Method A 1 Injection Method A 2 2 Injections Method 1 Injection Glargine Method C 1 Injection Detemir Plasma Insulin Levels Method D 2 Injections Detemir *May be used in patients with Type 2 DM to increase basal insulin levels ** Often used in combination with oral agents to increase total insulinization *** Starting dose is often 5-10 units HS 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 One Injection of asal Insulin One Injection of asal Insulin Type 2 Diabetes Characterized by Reduced Insulin Secretion asal Insulin Plasma Insulin Levels Plasma Insulin Levels 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 3

4 One Injection of asal Insulin One Injection of asal Insulin Increasing Doses of asal Insulin Increasing Doses of asal Insulin Plasma Insulin Levels Plasma Insulin Levels 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 One Injection of asal Insulin Plasma Insulin Levels Increasing Doses of asal Insulin Step 4: Adjustments to ase Insulin Dose Only adjust the base insulin dose if a pattern (similar glucose concentrations 3 or more days) is seen with a stable diet and exercise program Unless all values are > 200mg/dL, adjust one portion of insulin at a time (e.g. in the PM, etc.) Fix the Fasting First If adjustments are needed, start with the insulin component affecting fasting blood glucose (there is a saying that if you start low in the morning you will tend to stay low throughout the day) 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 If needed, adjust the base insulin dose by 1-2 units for every mg/dl above your glycemic goal Example Step 4: Adjustments to ase Insulin Dose Out of Range lood Glucose Value (Not explained by food, illness, exercise or stress) High FS Low High efore Low High efore Low Pattern Adjustment Algorithms PM or edtime N, glargine, detemir * PM or edtime N, glargine, detemir Morning Short-Acting Insulin Morning Short-Acting Insulin Morning N or time Short-Acting Insulin Morning N or time Short-Acting Insulin efore edtime High Low time Short-Acting Insulin time Short-Acting Insulin During the Night Low Evening N or Move time N to edtime * Rule out Somogyi Effect with a 2-3 AM lood Glucose Test L S HS 250 mg/dl Morning Insulin 4

5 Example Example L S HS L S HS 250 mg/dl Morning Insulin 250 mg/dl Insulin Example Example L Perform a 2 AM lood Glucose Test Insulin or Insulin S HS 250 mg/dl L S HS Insulin or Move to HS 2AM 50 mg/dl Example Step 4: Correction Insulin Dose Once the base insulin dose is stable, supplemental doses of shortacting insulin can be used to correct occasional excessive preprandial glucoses Algorithms (sliding scales) based on generalized patient response 1500 Rule: 1500/Patient s total daily dose of all insulin = *(lood glucose points) * Represents the number of points blood glucose will be lowered by adding 1 unit of R insulin to the normal pre-meal insulin dose 1800 Rule: 1800/Patient s total daily dose of all insulin = *(lood glucose points) * Represents the number of points blood glucose will be lowered by adding 1 unit of Lispro, Aspart or Glulisine insulin to the normal pre-meal insulin dose Example Step 4: Anticipated Insulin Dose The base insulin dose is increased or decreased based upon anticipated effects from diet and physical activity Insulin coverage of extra food: egin with an additional 1 unit of short-acting insulin for every grams of additional carbohydrate ingested above what is normally consumed at meals (e.g. holiday meal) Insulin-Carbohydrate ratio (500-rule): Divide 500 by the total daily dose of insulin The result is the number of grams of carbohydrate covered by 1 unit of short-acting insulin 5

6 Coordinating Insulin Injections Side Effects of Insulin Therapy Proper timing of bolus insulin administration with regards to meals is crucial to optimize the action of insulin, achieve better glycemic control and reduce the risk of adverse reactions insulin (30 minutes) Lispro/Aspart/Glulisine (given immediately (within 5-10 minutes) prior to the start of a meal) Hypoglycemia Lipohypertrophy Weight gain Hypersensitivity reactions Skin reactions Special Issues With Insulin Somogyi Effect Characterized by normoglycemia at bedtime and hypoglycemia around 2:00-3:00 AM Usually results in a rebound hyperglycemia the following morning due to excessive hepatic glucose output activated by the counterregulatory hormones (glucagons, epinephrine etc.) Often times patients have nightmares and wake in the middle of the night with profuse perspiration Special Issues With Insulin Somogyi Effect Therapeutic options: (after documenting low 3:00 AM blood glucose) Decrease the evening insulin by 2-4 units and continue to watch 3:00 AM blood glucose to see if the situation resolves Move the evening insulin from pre-dinner to bedtime This will shift the peak action of the to near breakfast time when the patient is awake and ready to eat Special Issues With Insulin Dawn Phenomenon Characterized by a rise in blood glucose occurring between 4-8 AM The rise in glucose cannot be blamed on counterregulatory hormones due to a hypoglycemic event, but may be secondary to a rise in growth hormone levels It is not consistent from day to day; it is often difficult to tell if hyperglycemia is due to insufficient (insulin waning) or the dawn phenomenon Special Issues With Insulin Dawn Phenomenon Therapeutic options: In either case, (insufficient evening or the Dawn phenomenon), the dose of evening should be increased Since it not consistent from day to day, need to continue to monitor 3 AM blood sugars to prevent nocturnal hypoglycemia 6

7 Special Issues With Insulin Sick Day Management Patients should be instructed to take their normal dose of insulin even if they are not eating well or have episodes of nausea and vomiting lood glucose may need to be monitored more frequently (e.g. every ½ hour) Supplemental doses of short-acting insulin may be required Test urine for ketones Drink plenty of fluids (1/4 cup/hr for adults) and maintain caloric intake (Jell-O, crackers, soup, soft drinks, etc.) Call physician if blood glucose remains greater than 240mg/dl or urine ketones remain after 2-3 doses of supplemental insulin Special Issues With Insulin Differing Work Schedules Patients may have problems with adherence when working day shifts verses night shifts The use of a basal/bolus regime may alleviate the problems associated with work schedules Work Sleep 9 AM-5 PM 10 PM-6 AM 11 PM-7 AM 12 AM-8 PM asal Insulin given at 9 PM every day and olus Insulin given during meals The Case of Ms. ottie Case #1 Ms. ottie is a 27-year-old female recently diagnosed with Type 1 diabetes. Her physician asks you to see her in the hospital to provide diabetes education. In addition, he asks you to design and implement an insulin therapy regimen for her. P: 118/76 Wt: 60kg Ht: 173cm Works as chemical engineer PMH (-) SH (-) What should be the target for glycemic control in this patient? How should we approach treating this patient intensively or conventionally? Design an insulin regimen for Ms. ottie. Step 1: Determine etween Intensive Insulin Therapy or Conventional Insulin Therapy Intensive Insulin Therapy (IIT) y definition, IIT attempts to mimic the body s normal release of insulin and therefore, generally includes more than two injections per day using insulin with different action profiles. The goal of IIT is achieving near normal biochemical markers of glycemic control. Conventional Insulin Therapy (CIT) CIT involves one or two injections per day using intermediate-acting insulin with less-than-normal biochemical markers of glycemic control as a goal of therapy. The major goal of CIT is avoiding the symptoms of hyper- and hypoglycemia. Intensive insulin therapy was chosen Type 1 DM (mimic normal physiology) Pt is younger (achieve near normal biochemical markers of glycemic control to prevent long-term complications) Highly motivated and compliant patients willing to test blood glucose 4 times daily and inject at least 3 doses of insulin daily Technical ability to test glucose Intellectual ability to interpret test results and adjust insulin 7

8 Step 2: Determine Daily Insulin Requirement Diabetes Type Dosage in U/kg Actual ody Weight Type 1 Initial Dose Honeymoon Phase Daily insulin requirement was calculated 0.6 Units/Kg * 60 Kg (weight) = 36 Units of insulin per day Type 2 Initial Dose With Insulin Resistance Step 3: Develop a Dosing Schedule (ase Dose) Number of Morning Noon Evening Injections efore efore efore Supper edtime Method 1 Injection Method 1 N Not Recommended Method 2 2 Injections N (2/3) N (1/3) N&R (2/3) N&R (1/3) Method 3 2 Injections 2:1 or 1:1* 1:1 Method 4 3 Injections N&R (2/3) 2:1 or 1:1* R (1/6) N (1/6) N&R (2/5) N&R (2/5) Method 5 3 Injections 1:1 R (1/5) 1:1 Step 3: Develop a Dosing Schedule (ase Dose).. Number of Injections Morning efore Noon efore Evening efore Supper Method. 1 Injection. Method 1 N. Not Recommended. Method 2 2 Injections N (2/3) N (1/3). Method 3 Method 4 Method 5 2 Injections 3 Injections 3 Injections N&R (2/3) 2:1 or 1:1* N&R (1/3) 1:1 edtime N&R (2/3) 2:1 or 1:1* R (1/6) N (1/6) N&R (2/5) 1:1 R (1/5) N&R (2/5) 1:1 Method 6 4 Injections R (1/4) R (1/4) R (1/4) R (1/4) Method 7 4 Injections R (1/4) R (1/4) R (1/4) N (1/4) lispro/aspart/glulisine lispro/aspart/glulisine lispro/aspart//glulisine Glargine/Detemir Method 8 4 Injections (16%) (17%) (17%) (50%) Method 6 4 Injections R (1/4) R (1/4) R (1/4) R (1/4) Method 7 4 Injections R (1/4) R (1/4) R (1/4) N (1/4) lispro/aspart/glulisine lispro/aspart/glulisine lispro/aspart//glulisine Glargine/Detemir Method 8 4 Injections (16%) (17%) (17%) (50%) Method 4 Method 5 L S HS (15 units, 9 units R) S(6 units R) HS(6 units ).. L S HS (7 units, 7 units R) L(8 units R) S(7 units, 7 units R) 8

9 Method 6 Method 7 L S HS (9 units R) L(9 units R) S(9 units R) HS(9 units R) L S HS (9 units R) L(9 units R) S(9 units R) HS(9 units ) Method 8 Glargine/Detemir Lispro/Aspart/Glulisine Ms. ottie was placed on an intensive insulin regimen consisting of 6 units of insulin aspart with meals and 18 units of insulin detemir at bedtime. Detemir Aspart L S HS 6 units Lis/ L 6 units Lis/ S 6 units Lis/ Asp/Glu Asp/Glu Asp/Glu HS 18 units. Glargine/ Detemir L S HS (6 units Asp) L(6 units Asp) S(6 units Asp) HS(18 units Detemir) 6-25 Correction Anticipated Suppose Ms. ottie s pre-supper blood glucose is 250 mg/dl. How much additional insulin should be administered at supper to correct this situation? (Assume a target G of 100 mg/dl) Rule of /Total Daily Dose of Insulin (36 units) = represents the number of points blood glucose will be lowered by the addition of 1 unit of insulin aspart Current G - Goal G = Amt G needs to be reduced 250 mg/dl 100 mg/dl = 150 mg/dl 150 mg/dl /50 points = 3 Units An additional 3 units of insulin aspart should be added to correct the G elevation Suppose Ms. ottie wants to eat an additional 60 g of carbohydrate for her supper time meal. How much additional insulin would be required to cover the additional carbohydrate? Rule of /Total Daily Dose of Insulin (36 units) = represents the grams of carbohydrate that is covered by 1 unit of insulin aspart 60 g carbohydrate /14 = 4 units An additional 4 units of insulin aspart would be required to handle the additional 60 grams of carbohydrate 9

10 Putting it all together Correction Dose +3 units Normal Meal Dose +6 units Anticipated Dose +4 units Total insulin administered at supper = 13 units Case #2 Detemir Aspart L S HS (6 units Asp) L(6 units Asp) S(6 units Asp) HS(18 units Detemir) 6-25 The Case of Mr. Martin The Case of Mr. Martin HPI: MM is a 58 y/o obese man with T2DM of 5 years duration. The diabetes had been controlled by diet and exercise for 2 years. Approximately 3 years ago sulfonylurea therapy was started and adequate control was maintained up until 1 year a go when metformin was added to his therapy. MM has heard the recent reports about Actos and bladder cancer and states, I don t want Actos or any other drug like it. PMH: HTN x 18 yrs Hyperlipidemia x 10 yrs Type 2 DM FH: DM present in mother SH: Stopped smoking 5 years ago. MEDS: Lisinopril 10 mg QD Atorvastatin 20 mg QD Glyburide 20 mg QD Metformin 1000 mg ID ALL: NKA ROS: Occasional polydipsia, polyphagia, fatigue, weakness and blurred vision VS: P 124/76, P 80, RR 26, Wt 93kg, Ht 64, MI 35.3 kg/m2 SKIN: Dry with poor turgor HEENT: PERRLA, EOMI, fundi were not examined LAS: Random plasma glucose 264 mg/dl A1C 9.4% Na 140 meq/l Mg 1.2 meq/l Chol 180 mg/dl UN 20 mg/dl K 4 meq/l AST 21 IU/L HDL 42 mg/dl SCr 0.7 mg/dl Cl 95 meq/l ALT 15 IU/L LDL 98 mg/dl Ca 9.9 mg/dl Alk phos 45 IU/L Trigs 131 mg/dl Review of SMG reveals Avg AM 234 mg/dl & Avg 2-hr PPG 280 mg/dl Therapeutic Dilemma Starting Insulin Therapy Sulfonylurea + Metformin Start Insulin Therapy What do we use? When do we use it? How do we use it? What do we use? Considerations: A1c < Target (7%) A1c is comprised of FG & 2-hr PPG Head into a meal with an elevated FG little chance of a 2-hr PPG being within target FFF Fix the Fasting First What insulin is responsible for keeping G levels normalized overnight? (Influences FG) asal Insulin Secretion Glargine Detemir 10

11 Step 3: Develop a Dosing Schedule (ase Dose) The Ideal asal Insulin Mimics normal pancreatic basal insulin secretion Method Number of Injections Morning efore Noon efore Evening efore Supper edtime Insulin Characteristics Detemir Glargine 1 Injection Method A 2 Injections Method A 2 Method 1 Injection Glargine Method C 1 Injection Detemir Method D 2 Injections Detemir *May be used in patients with Type 2 DM to increase basal insulin levels ** Often used in combination with oral agents to increase total insulinization Smooth, peakless profile 24-hour duration of action Reproducible & predictable effects Reduced risk of nocturnal hypoglycemia Once-daily administration *** Starting dose is often 5-10 units HS Starting Insulin Therapy Starting Insulin Therapy When do we use it? How do we use it? Any of the Day Administration Patient ease 1 injection per day no mixing Not overwhelming to the patient Insulin pen available Low dosages Limited weight gain Reduced risk of hypoglycemia Slow, safe, simple titration Effective improvement in glycemic control Insulin Glargine Start with 10 units QD Maintain existing oral therapy while starting basal insulin Titrate the dose of insulin until FG is at target level Advance the dose of Glargine by 1-2 units, but no more than 4-5 units every 2-3 days until FG is at goal Starting Insulin Therapy Over the course of the next 2 months MM was titrated to 28 units of insulin glargine QD. The following readings are obtained from his glucose monitor. SMG reveals: Avg AM 87 mg/dl Are We Done? A. Yes. No Starting Insulin Therapy Over the course of the next 2 months MM was titrated to 28 units of insulin glargine QD. The following readings are obtained from his glucose monitor. SMG reveals: Avg AM 87 mg/dl Are We Done? Once FG is at goal, evaluate the need for oral therapy/full insulin therapy Monitor 2-hour postprandial glucose level PPG < 100 mg/dl PPG < Target ( ) PG > Target ( ) dose of SU Maintain dose of SU Change SU to bolus insulin Avg 2-hr PPG 132 mg/dl 11

12 Monitoring Diabetes Normal A1C < 6.0% A1C = PPG + FPG As Patients Get Closer to A1C Goal, the Need to Manage PPG Significantly Increases The Need to Manage PPG Significantly Increases as A1C Improves Increasing Contribution of PPG as A1C Improves % Contribution A1C Range (%) CDC. National Diabetes Fact Sheet. 2003; Atlanta, GA. US Dept. HHS, Center for Disease Control and Prevention Adapted from Monnier L, Lapinski H, Collette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of Type 2 diabetic patients: variations with increasing levels of HA(1c). Diabetes Care. 2003;26: Importance of Postprandial Glucose DECODE 1999 High blood glucose concentrations 2 hours after load is associated with an increased risk of death, independently of fasting blood glucose Funagata Diabetes Study 1999 Impaired Glucose Tolerance (IGT) but not Impaired Fasting Glucose (IFG) is a risk factor for cardiovascular disease Paris Prospective Study 1998 Death rates for CHD increase with increasing 2-hour post-prandial glucose levels Decode Study Group. Diabetologia. 1999;42: Tominaya M, et al. Diabetes Care. 1999;22: alkou, et al. Diabetes Care. 1998;21: Honolulu Heart Study Effect of PPG Levels on Risk of CHD CHD risk per 1, n=8,006 men p<0.001 Donahue R, et al. Diabetes. 1987;36: p<0.01 Fatal CHD Total CHD mg/dl mg/dl mg/dl mg/dl mg/dl Postprandial Glycemic Quintiles Relative Risk for Death Increases with 2-hr G Regardless of the FPG Level Relative Risk of Death* < 110 *Adjusted for age, sex, study center > >140 < 140 Fasting Plasma Glucose (mg/ dl) Adapted from DECODE Study Group. Lancet. 1999;354: h Postprandial Glucose (mg/dl) Two Years Later Labs: FG 94 mg/dl A1C 7.7% What is the Problem? What are our options? MM 58 y/o male CC: Frequent episodes of morning hypoglycemia Medications: Insulin glargine 45 units QD Glyburide 20 mg QD Metformin 1000mg ID Atorvastatin 40mg QD Irbesartan-HCTZ 300/12.5mg QD Tylenol 1000mg QID Aspirin 81mg QD 12

13 Two Years Later What is the Problem? Patient not compliant with diet PPG may not be within goal Patient prescribed too much insulin glargine All of the above None of the above Two Years Later What are our options? olus insulin Review MNT with an emphasis on carb counting Reduce the dose of basal insulin oth A & C All of the above Lack of Coverage of PPG With asal Insulin Therapy Alone Patient Not Meeting Current ADA Guidelines What is the Problem? Self Monitoring of lood Glucose Reveals: AVG -- FG 81 mg/dl AVG -- 2-hr PPG 235 mg/dl Plasma Insulin Levels asal insulin 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Theoretical representation of profile of basal insulin profile 8:00 Review Medical Nutrition Therapy MNT Patient was given a 1500-calorie diet and instructed on carbohydrate counting 50 grams of CHO for 65 grams of CHO for Sample meals 75 grams of CHO for Supper were calculated olus Insulin Therapy (regular, lispro, aspart, glulisine) olus insulin ase Dose/Supplemental Dose Select 1 meal to begin bolus insulin therapy 1 unit of short-acting insulin covers approximately grams of carbohydrate (Supper 75 gm CHO = 5-7 units insulin lispro) Once the base insulin dose is stable, supplemental doses of short-acting insulin can be used to correct occasional excessive pre-prandial glucoses Algorithms (correction scales) based on generalized patient response 1800 Rule: 1800/Patient s total daily dose of all insulin = * (lood glucose points) * Represents the number of points blood glucose will be lowered by adding 1unit of analog bolus insulin to the normal pre-meal insulin dose 13

14 asal/olus Concepts: Mimicking Natural Physiology Plasma insulin 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Rapid-Acting and Long-Acting Insulin Lispro Glargine 8:00 Today Labs: FG 101 mg/dl A1C 6.8% MM Sulfonylurea discontinued Insulin glargine dose reduced 58 y/o male CC: Routine appointment Medications: Insulin glargine 30 units QD Insulin lispro 4 units at breakfast 6 units at lunch 10 units at supper Metformin 1000mg ID Atorvastatin 40mg QD Irbesartan-HCTZ 300/12.5mg QD Tylenol 1000mg QID Aspirin 81mg QD 14