LET S TALK INSULIN THE BASICS

LET S TALK INSULIN THE BASICS

AUTHOR S DISCLOSURES Contracted for program development for Lifescan Canada Speaker for Lifescan, Lilly, BI, Consultant for Lilly, Janssen, Novo Nordisk, Lifescan Canada

OBJECTIVES After completing this workshop the participant will be able to: 1. Discuss benefits of SMBG with insulin use. 2. Practice pattern identification. 3. Identify insulin action times. 4. Discuss criteria for choosing patient specific insulin regimens. 5. Discuss action to be taken to prevent hypoglycemia.

PLAN FOR MANAGING DIABETES Insulin Activity Blood glucose Lifestyle Healthy eating

MANAGEMENT PLANS Every individual is different No one insulin plan will suit everyone Consider all factors that affect blood glucose levels. Meals: type, amount, and timing of meals Activity: type, duration, and timing of activity Insulin: type and timing of insulin Lifestyle: stress, anxiety, sleep patterns

INSULIN REGIMENS Type 1 diabetes to achieve glycemic targets use multiple daily insulin injections (MDI) or CSII (pump) Type 2 diabetes when glycemic targets are not met with lifestyle and antihyperglycemic agents insulin should be initiated -

NORMAL INSULIN SECRETION 60 Insulin 40 20 0 Time of day Breakfast Lunch Supper adapted from Owens, Zinman,& Bolli,2001

INSULIN REGIMENS: 1. Basal insulin once or twice daily. 2. Premixed insulin 2-3 x per day. 3. MDI: basal and bolus insulin 4. CSII

BASAL INSULIN Type of Insulin When It Should Be Taken Onset (starts working) Peak (working hardest) Duration Interme diateacting Novolin NPH Humulin N Longacting As prescribed 1 3 hr 5 8 hr Up to 18 hr Longacting Lantus (Glargine) Levemir (Detemir) As prescribed 90 min No peak Up to 24 hr

Type of Insulin BOLUS INSULIN When It Should Be Taken Onset (starts working) Peak (working hardest) Duration Rapidacting NovoRapid Lispro: Humalog Glulisine 15 min or less before a meal 10 15 min 60 90 min 3 5 hr Shortacting Novolin Toronto Humulin R 30 45 min before a meal 30 min 2 3 hr 6.5 hr

PREMIXED INSULINS Premix (with shortacting) Premix (with rapidacting) Type of Insulin When It Should Be Taken Novolin 30/70, 50/50 Humulin 30/70 NovoMix 30 Humulin Mix 25 30 45 min before a meal 15 min or less before a meal Action Time Premixed insulin will have the same onset, peak, and duration as the types of insulin in the premix. For example: Novolin 30/70 will have the onset, peak, and duration of both regular and NPH insulin. NovoMix 30 will have the onset, peak, and duration of rapid-acting and intermediateacting insulin.

ACTION PROFILES OF BOLUS & BASAL INSULINS Plasma Insulin levels mu/l 80 60 40 20 aspart/glulisine/lispro 3-5 hours regular 5-8 hours NPH ~14 hours Diagrammatic representation Action curves are approximations taken from different data sources. Actual patient response will vary detemir/glargine ~24 hours 0 12 24 Hours Hours

KNOW THE ACTION PROFILE It is important that patients using insulin know the type and action profile of the insulin they are on. It will help them: Know when they are at risk of hypoglycemia Decide when to check their blood glucose Decide which factors in their management plan need to be adjusted to achieve their targets

ADDITION OF BASAL? MIXED? 1. Treat-to-Target trial: N or glargine added to OHA effective 2. Janka et al: Basal versus premixed Added to SU and metformin Basal more effective 3. Raskin et al: basal versus mixed d/c SU Mixed more effective if SU d/c

BASAL /BACKGROUND INSULIN Often a good starting point for insulin use Initially targeting fasting blood glucose Options: intermediate acting insulin N or NPH Longacting insulin : detemir or glargine What is the advantage of one over the other?

BASAL /BACKGROUND USING INTERMEDIATE-ACTING INSULIN Intermediate acting Breakfast Lunch Supper

DISCUSSION Mr. Singh presents with a prescription for detemir. You note he has type 2 diabetes and is already on NPH before breakfast and before supper He says the doctor just told him to take this one Why do you think the MD has prescribed detemir? What should you ask Mr. Singh? How should Mr. Singh be switched to detemir?

BASAL/ BACKGROUND USING LONG- ACTING INSULIN glargine/levemir Breakfast Lunch Supper

VARIABILITY IN TIME-ACTION PROFILE OF BASAL INSULINS Dose at each injection: 0.4 U/kg, thigh Clamp 1 Clamp 2 Clamp 3 Clamp 4 GIR mg/(kg min) 8.0 6.0 4.0 2.0 0 NPH insulin 8.0 Insulin glargine 8.0 Insulin detemir Patient 1 6.0 Patient 2 6.0 Patient 3 0 6 12 18 24 4.0 2.0 0 0 6 12 18 24 4.0 2.0 0 6 12 18 24 Time (hours) Time (hours) Time (hours) 0 Glucose infusion rate profiles following four non-consecutive injections of identical doses (0.4U/kg, thigh) in three patients T. Heise, et al. Diabetes 2004

INSULIN GLARGINE: THE ONLY BASAL INSULIN TO PROVIDE A 24-HOUR PROFILE WITH NO PRONOUNCED PEAK Glucose utilization rate (mg/kg/min) 6 5 4 3 2 1 0 Hourly mean values Insulin Glargine (n=20) NPH Insulin (n=20) Time after SC injection (hours) SC, subcutaneous. Adapted from LANTUS (insulin glargine) Product Monograph 2005.

Glucose concentration (mg/dl) CONTROL OF POSTPRANDIAL BG NEEDED AS DIABETES PROGRESSES 270 240 210 180 150 120 90 60 30 0 Fasting (nocturnal period) Morning Period 0 2 4 6 8 10 12 14 16 18 20 Time of day (24-hour clock) Monnier L et al., Diabetes Care 2007; 30: 263 269 Postprandial (daytime period) Curve 1 (blue): A1C <6.5% Curve 2 (red): 6.5 to <7% Curve 3 (green): 7 to <8% Curve 4 (orange): 8 to 9% Curve 5 (purple): 9% 22 24 Diabetes duration (years) 11.5 10.0 8.4 4.4 0.7

DISCUSSION Mrs. Jones comes in with prescription for Insulin 30/70 15u ac breakfast and 10u ac supper. She is currently on glyburide 10 mg BID and metformin 1000 BID Should she discontinue her oral meds? When does premix insulin work? Why is she being started on premix? When should she take the insulin?

PREMIX INSULIN TWICE A DAY OR TWICE DAILY RAPID OR SHORT AND INTERMEDIATE Rapid or short acting Intermediate acting Breakfast Lunch Supper 23

PREMIX INSULIN Advantages 2 injections a day No mixing insulins leads to fewer mistakes Intermediate acting provides basal dose Intermediate may provide the bolus for lunch especially if using a premix containing short acting insulin. Disadvantages Cannot adjust for meals or activities Need for a consistent lifestyle Intermediate-acting insulin taken at supper might increase risk of hypoglycemia around 3 a.m.

PREMIXED/TWICE A DAY INSULIN 60 Insulin 40 20 0 Breakfast Lunch Supper Michener, 2004

Rapid versus short acting insulin aspart, glulisine

MOST COMMON - RAPID-ACTING MIXTURE BEFORE BREAKFAST & DINNER

BASAL PLUS CONCEPT: A1C > 7.0% Continue basal at hs (overnight BG control) Continue Oral AHA (daytime BG control) Add 1 dose of prandial insulin with the meal with the greatest impact on 2 hr pc BG OR start with largest meal SMBG pre & 2 hours post meals to determine timing of 1 st dose

BASAL PLUS Pros Step-wise transition to more physiologic insulin replacement More flexibility with meal(s) Able to correct for high BG pre main meal Less risk of lows (nocturnal) People can be taught to adjust doses based on 2hr pc BG patterns & changes in food /activity Rapid-acting are preferred over short-acting insulins. Cons Two injections. Increase SMBG 3-4. Learn more about carbohydrate amount of food.

BASAL PLUS: HOW DOSE IT WORK? AHA Basal Basal Bolus

BASAL-BOLUS REGIMEN WITH LONG- ACTING INSULIN Rapid or short acting Long-acting insulin Breakfast Lunch Supper 31

THINK LIKE A PANCREAS. Physiological production of insulin: Basal/background insulin 50% Bolus /mealtime insulin 50%

KEY TO BETTER CONTROL Self monitoring of blood glucose

BLOOD GLUCOSE TARGETS Before Meals After Meals CDA Recommendations 2008 4.0 7.0 mmol/l 5.0 10.0 mmol/l A1C Less than or equal to 7% Individualize

SHORT OR RAPID ACTING INSULIN: WHEN TO GIVE IT AND WHEN TO CHECK BG Type of Insulin When Given When to Check Rapid-acting Novolog or Humalog Given within 15 mins of start of meals Check at peak action time, 1.5 2 hours after meal Short-acting Novolin R or Humulin R Given 30-45 mins before meals Check at peak action 2-3 hours after injection Checking before and after meals allows the person to assess if the insulin was adequate for the meal

INTERMEDIATE ACTING INSULIN: WHEN TO GIVE IT AND WHEN TO CHECK BG Type of Insulin When Given When to Check Intermediate -acting Novolin N (NPH) or Humulin N Given before breakfast Given before supper Given at bedtime Peak action 5-8 hours, check around lunch and again presupper to determine duration of action Before bed, 2 to 3 a.m. once or twice a week until stable as it may cause hypoglycemia during the night and check before breakfast 2 to 3 a.m. once or twice a week until stable as it may cause hypoglycemia during the night and check before breakfast

LONG-ACTING INSULIN; WHEN TO GIVE IT AND WHEN TO CHECK BG Type of Insulin When Given When to Check Long-acting Lantus or Levemir Given before breakfast, supper or at bedtime Background insulin efficacy can be checked fasting and pre supper

PREMIX INSULIN: WHEN TO GIVE IT AND WHEN TO CHECK BG Type of Insulin When Given When to Check Premix (with short-acting) Novolin 30/70, 50/50 Humulin 30/70 Given 30-45 mins before breakfast and supper Check at peak action 2-3 hours after injection and at 2 to 3 a.m. once or twice a week until stable as it may cause hypoglycemia during the night and check before breakfast Premix (with rapid-acting) NovoMix 30 Humulin Mix 25 Given within 15 mins before breakfast and supper Check at peak action time 1.5 2 hours after meal and at 2 to 3 a.m. once or twice a week until stable as it may cause hypoglycemia during the night and check before breakfast

TWO WAYS TO LOOK AT BG Immediate Results If the level is low, what caused it? A skipped meal or some activity? If it is high, are you feeling sick? Did you eat more than usual? Patterns of Results from Several Days Are you always low at the same time of day? Or always high at The same time of day?

SAMPLE CHECKING PATTERN: RAPID OR SHORT ACTING PRE-MEALS WITH LONG- ACTING ONCE A DAY acb pcb acl pcl acs pcs 3 am 1 2 3 4 5 6 7 After 7 or 8 days, have three sets of data for before and after each meal. A 3 a.m. check would also allow you to rule out low blood glucose at that time.

SAMPLE CHECKING PATTERN: PREMIX INSULIN TWICE A DAY acb pcb acl pcl acs pcs 3 am 1 2 3 4 5 6 7 Checking after breakfast and pre-supper will determine if the morning premix dose is working. Checking post-supper and fasting will determine if the supper dose is working. Premix insulin at supper will peak in the middle of the night so it is important to check at 3 a.m. to ensure the blood glucose is not low.

WHAT IS A BLOOD GLUCOSE PATTERN Low pattern: 2 low results, in 5 days at the same time of day High pattern: 3 high results, in 5 days at the same time of day ac B pc B ac L pc L ac S M 7.0 3.2 pc S T 6.7 6.9 3.8 9.8 W 5.8 3.6 T 6.5 7.4 4.2 F 6.2 acb pc B ac L pc L ac S M 7.9 6.2 pcs T 8.7 6.9 10.5 W 10.2 6.6 T 9.1 7.6 F 8.4 6.8

PATTERNS IDENTIFY AREAS OF CONCERN Need consistency in lifestyle, meals and activity over the period before looking for patterns. When a high or low pattern is identified, a change may be needed. in foods, activities, timing of meals or injections, or doses of insulin. These changes should be discussed with a healthcare professional. Watch results for several days before making a change. Wait several days after making a change before making another change. If too many changes are made too often, blood glucose levels might start fluctuating.

WHAT PATTERN TO WORK ON FIRST When finding more than one kind of pattern, focus on addressing the patterns one at a time in this order: 1. Low pattern at any time 2. High before breakfast (fasting) pattern 3. High before other meals 4. High after meal pattern

PATTERN IDENTIFICATION Day Before Breakfa st After Breakfa st Before Lunch After Lunch Before Supper After Supper Mon 7.0 3.2 Tues 6.7 6.9 3.8 9.8 Wed 5.8 3.6 Thurs 6.5 7.9 4.2 Fri 6.2 Sat 7.6 Sun 6.8

POSSIBLE CAUSES OF LOW PATTERNS Possible causes Potential Action Not enough carbohydrates in your previous meal or snack You ve been more active than usual Your meal times have changed with more time between meals Too much insulin Alcohol intake Plan consistent meals and snacks Might need to increase snacks when active or reduce insulin Might need a snack between meals May need to reduce insulin dose Eat carbs when drinking

HIGH PATTERN BEFORE BREAKFAST Possible Causes Your supper time insulin is not lasting long enough or the dose you took is not enough Your supper time insulin is causing you to drop too low around 3 a.m., resulting in a rebound high before breakfast or the dose you took was too much You forgot your evening dose of insulin or the dose you took was not sufficient You had a larger meal than usual or had a late snack Potential Action Change timing of insulin or increase dose Move supper basal insulin to bedtime Remember to take all doses of insulin; may need to increase dose May need to eat earlier or reduce after supper snacks

HIGH PATTERNS AT TIMES OTHER THAN BEFORE BREAKFAST The pre-meal insulin did not cover the food consumed Your basal dose of insulin is not enough to keep your levels at target throughout the day The timing of your insulin is off in relation to the meal Check if you ate the appropriate amount of food or check with your diabetes care team about changing your insulin dose Discuss this with your diabetes care team Try to be consistent with meal times and when you take your insulin Your insulin dose may not be meeting your needs and should be adjusted by your healthcare professional

SUSANNE 56 years old, type 2 diabetes for 15 years Currently on glyburide 10 mg BID, metformin 1000 mg BID Comes to pharmacy with prescription for long-acting insulin to be taken at bedtime. Susanne asks you to show her how to take it and to go over the instructions she got from the doctor

HOW WILL YOU MAKE TIME TO DO THIS? Book her to come in later in the day? Ask someone to cover and take her into the consult room immediately? Teach her over the counter? Call the Diabetes Education centre and get her an appointment? Ask your Pharmacy Tech to do the teaching?

PLAN OF ACTION Evaluation Needs Assessment Implementation Plan Development

WHERE TO START?? 1 ST ASSESSMENT Ask her how she feels about giving insulin Ask her if she knows anyone else on insulin and what has been their experience Ask her if she has ever done an injection Ask her if she knows why the doctor has prescribed insulin

ATTITUDES TO INSULIN (POLANSKY 2003) Factor Description Frequency Perceived loss of control over life Poor self esteem Personal failure Perceived disease severity Restrict life, eat out, Travel, cannot stop Decisions time and dose, complicated Punishment gluttony, Sloth Causes problems, more dangerous 61.4% 40-50% 50% Hisp 72.2% Non Hisp 8.1% Injection Anxiety True phobia rare 50% Perceived lack of positive gain Disbelief/unaware of benefits 90%

2 ND PLAN WHAT SHE WANTS TO KNOW AND WHAT SHE NEEDS TO KNOW Reason for insulin at this stage of diabetes Action of insulin in relation to oral meds she is on Timing of injection How to prepare syringe or pen How to inject Possible side effects hypoglycemia, cause, S & S and treatment Storage of insulin Checking blood glucose when Titrating dose as per doctor s order

3 RD IMPLEMENTATION HOW TO DO THE TEACHING Explain that people with type 2 diabetes eventually run out of insulin Explain action of long acting insulin using flip chart Demonstrate preparation of syringe or pen Have her redemonstrate back to you Discuss sites and have her put needle into skin without injecting insulin

3 RD IMPLEMENTATION HOW TO DO THE TEACHING CONT D Explain hypoglycemia, use handouts to illustrate S & S and treatment Discuss timing of blood glucose checks and recording in logbook Discuss titrating insulin dose: need for follow-up

Target before meals Target after meals

HYPOGLYCEMIA MILD MODERATE SEVERE Trembling, Palpitations, Sweating, Anxiety, Hunger, Nausea, Tingling 3.4 4.0 mmol/l Difficulty concentrating, Confusion, Weakness, Drowsiness, Vision Changes, Difficulty speaking, Headache, Dizziness, Tiredness 2.8 3.3 mmol/ L Need assistance, either conscious or unconscious < 2.8 mmol/l

TREATMENT OF HYPOGLYCEMIA: 3.4 4.0 mmol/l 2.8 3.3 mmol/l < 2.8 mmol/l MILD MODERATE SEVERE 15 gms carbohydrate; ¾ cup regular pop ¾ cup juice 7-8 lifesavers 3 glucose tabs 4 dextrosols 3 tsp sugar, jam, or honey 20 gms carbohydrate 1 cup regular pop 1 cup juice 10-11 lifesavers 4 glucose tabs 4 tsp sugar, jam or honey Glucagon kit, IV glucose, nothing by mouth Re-test in 15 minutes, if still < 4.0 mmol/l, retreat with: Another 15 gms of carbohydrate.

4 TH EVALUATING CAN SHE DO IT AT HOME? Watch her prepare syringe or pen Watch her put needle into skin Ask her what she might feel like if blood glucose went too low Ask her what she would do about it Ask her what time she will give insulin Ask where she will keep her insulin and where she will give it DO NOT ask her if she understands!!!

ROBERT 60 years old, type 2 diabetes for 20 years Current meds, metformin 1000 mg BID, sitagliptin 50 mg BID, A1C 8.5% Eats healthy, active lifestyle Brings a prescription to pharmacy for rapid acting insulin ac meals, long acting at bedtime

DISCUSSION Why is he being started on Insulin? What other options are there? Advantages Disadvantages

THE DIABETES TEAM Diabetes is not managed by any one discipline Diabetes is managed by a team consisting of The person with diabetes Family physician Diabetes educator Nurse Dietitian Pharmacist Endocrinologist Other health professionals Communication is the responsibility of all members of the team!

ONE WEEK LATER Robert has been to the Diabetes Education Centre and started insulin 1 week ago He comes to the Pharmacy to buy more test strips He shows you his log book

ROBERT acb pcb acl pcl acs pcs 3 am Mon 7.2 3.5 Tues 8.4 6.8 4.2 15.5 Wed 6.9 4.1 Thurs 7.6 7.6 3.6 11.4 Fri 14.0 Sat 8.5 8.2 3.2 12.6

HYPOS BEFORE SUPPER What might be the cause? Need to look at lifestyle issues before medication Timing of meals, activity in afternoon etc. How has he been treating them? Is treatment appropriate? Is he checking 15 minutes later? Should he have alcohol with super after a low? How can he prevent them?

WHAT ABOUT THE OTHER PATTERNS? Highs before breakfast Might be better when the lows before supper are gone Are you worried about the one that is 14??? Highs after supper May be partly rebound from the lows May be overtreating the low May be a supper that is too large Can t do anything about them until hypos are fixed

Insulin is only as good as its titration.

SUMMARY Discuss with clients Action of the insulin they are taking When to check blood glucose How to record blood glucose results How to look for patterns How to trouble-shoot results that are out of target Possible actions to improve blood glucose results

Key Planning Points for insulin initiation Insulin Regimen Injection technique Basal Mixed MDI Pen use Injection Hypoglycemia S/S Treatment

TAKE HOME MESSAGE one size does not fit all Individualize treatment Treat to target early Titrate according to SMBG