SHARP-SHOOTING MANAGING INSULIN LIKE A PRO

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1 SHARP-SHOOTING MANAGING INSULIN LIKE A PRO Christine Kessler RN MN CNS ANP BC-ADM The Diabetes Institute Dept of Endocrinology & Metabolic Medicine Fort Belvoir Community Hospital, Fort Belvoir, VA Walter Reed National Military Medical Center Bethesda, MD Objectives Identify realistic A1C targets for your diabetic patients Discuss the initiation and titration of basal and bolus insulin Identify when and who should be started on insulin Discuss alternative ways to deliver insulin Describe barriers to insulin initiation There he is...sugars up meds need adjusting...now what? 1

2 Diagnostic Criteria Reminder Pre-Diabetes A1C: * Impaired Fasting Glucose: FPG: mg/dl Impaired Glucose Tolerance: 2 hr OGTT (75-gm): mg/dl Diabetes A1C: >/= 6.5* FPG: > 126 mg/dl x 2 2 hr OGTT (75-gm): > 200 mg/dl Casual: > 200 mg/dl with classic symptoms ADA. Diabetes Care. 2006; 29(suppl 1):S10-s11 What are we dealing with? Type 1 Type 2 LADA (latent autoimmune DM in adults)****** Flat bush Atypical DM Idiopathic type 1 DM Type 3 MODY type 1, 2, 3, 4, 5, 6 Clues to Diagnosis of LADA DM family history General characteristics History of autoimmune disease Hashimoto s, Graves Celiac, Addison s Vitiligo, psoriasis Lupus, pernicious anemia, AR Others 2

3 ANOTHER WAY TO LOOK AT DIABETES Antibody + Beta cell (insulin) + Classic Type I Antibody + Beta cell /insulin- Classic Type 2 Antibody Beta cell/insulin + Antibody Beta cell/insulin - ANTIBODIES: GAD, Islet Cell; INSULIN: C-peptide Plasma Glucose Natural History of Type 2 Diabetes 120 (mg/dl) Obesity IGT * Diabetes Uncontrolled Hyperglycemia Post-Meal Glucose Fasting Glucose Relative -Cell Function 100 (%) Insulin Resistance Insulin Secretion Years of Diabetes *IGT = impaired glucose tolerance. Adapted from International Diabetes Center (IDC), Minneapolis, Minnesota. What is the A1C target and blood sugars be? 3

4 ac: /140 2 hr pp: < % % 1 A1C (%) % % 1 VA/DOD ADA recommended target 3 ACE recommended target 4 Upper limit normal range 1 Saydah SH, et al. JAMA. 2004; 291: Koro, CE, et al. Diabetes Care. 2004; 27: ADA. Diabetes Care. 2006; 29(suppl 1): S10-S11 4 ACE. Endocrine Practice Ann Intern Med 154: ,

5 What about Fructosamine? A 2 week glycemic marker Used for closer monitoring or to help determine compliance Best in patients with hemoglobinopathy or anemia Normal range <290. Reasonable under 330. Generally Diabetes Drugs Increase insulin output Decrease insulin resistance Decrease glucose output Improve GI glucose metabolism Alexander GC et al. National trends in treatment of type 2 diabetes mellitus, Arch Intern Med. 2008;168: Bennett W et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Annals of internal medicine; 2011 May 3;154(9): Qaseem V et al. Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians. Annals of internal medicine; 2012 Feb 7;156(3): So What Do We Have? Biguanides Metformin Sulfonylureas Glyburide, glipizide, glimeperide Thiazolidinediones (TZDs).SIGH Pioglitizone, rosiglitazone Meglitinide analogues Repaglinide, nateglinide Glucosidase inhibitors Acarbose, miglitol 5

6 Newer and Newest Rx GLP-1 memetics (exenatide & LR, liraglutide ) Amylin (symlin) DPP-4 antagonists (sitaglipitin, saxagliptin, linagliptin) Bile-acid sequestrants (colesevelam) Dopamine Agonists (bromocryptine) more>? Rodbard HW, Jellinger PS, Davidson JA, Einhorn D, Garber AJ, Grunberger G, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. Sep-Oct 2009;15(6): More Recent Drugs We Have Incretin mimetics DPP-4 sitagliptin (Januvia) Saxagliptin (Onglyza) linagliptin (Tradjenta) GLP-1 Exenatide (Byetta) Byrudeon Liraglutide (Victoza) Sites of Action by Therapeutic Options Presently Available to Treat Type 2 Diabetes LIVER GLUCOSE PRODUCTION Biguanides (Thiazolidinediones) INTESTINE GLUCOSE ABSORPTION BRAIN Endocannabinoid Receptor Blockers GLP-1 Pramlinitide PANCREAS INSULIN Secretion/replacement Sulfonylureas Meglitinides GLP-1 DPP4 Inhibitors Insulin ADIPOSE TISSUE MUSCLE PERIPHERAL GLUCOSE UPTAKE Thiazolidenediones (Biguanides) STOMACH DELAYED EMPTYING GLP-1, Pramlintide alpha-glucosidase inhibitors Adapted from Sonnenberg and Kotchen. Curr Opin Nephrol Hypertens 1998;7(5):

7 Hollander P. Anti-Diabetes and Anti-Obesity Medications: Effects on Weight in People With Diabetes. Diabetes Spectrum 2007 vol. 20 no TYPE 2 DIABETES TREATMENT PARADIGM Diet and exercise Single Oral Agent Treatment Combination Oral Agent/incretin Treatment Insulin with or Without orals/ incretins Who Needs Insulin Type T1DM (? honeymoon LADA) T2DM unable to tolerate/take OHAs T2DM on max OHDs with A1C >7.5 (or 8.0) Those with glucose toxicity (ave BG >250) with wgt loss, DKA A1C >10 or AM BG >250 Pregnancy Severe infection, illness, surgery, steroids Flexible treatment desired 7

8 Kessler s Diabetes Rx Points Safety first Safe target, safe drug Can t treat blind need pt to give you data Timing is everything Always think.basal first then Prandial sugar!! All diabetes agents will affect one or both of these Know Your Insulin Types BASAL vs BOLUS (Prandial) 8

9 Insulin Types Basal (cover what we make) Intermediate Novolin, NPH Long-acting Glargine (Lantus), detemir (Levemir) Bolus/prandial (cover what we take) Short-acting Regular Rapid-acting Humalog, novolog, glulisine Consider timing, profile, ease of use! Mayfield, JA.. et al, Amer. Fam. Phys.; Aug. 2004, 70(3): 491 9

10 Type of Insulin Brand Name Generic Name Onset Peak Duration Rapid-acting NovoLog Insulin aspart 15 minutes 30 to 90 minutes 3 to 5 hours Apidra Insulin glulisine 15 minutes 30 to 90 minutes 3 to 5 hours Humalog Insulin lispro 15 minutes 30 to 90 minutes 3 to 5 hours Short-acting Humulin R Regular (R) Novolin R Intermediate-acting Humulin N NPH (N) Novolin N Long-acting Levemir Insulin detemir Lantus Insulin glargine 30 to 60 minutes 2 to 4 hours 5 to 8 hours 1 to 3 hours 8 hours 12 to 16 hours 1 hour Peakless 20 to 26 hours Pre-mixed NPH (intermediate-acting) and regular (short-acting) Humulin 70/30 Novolin 70/30 Humulin 50/50 70% NPH and 30% regular 50% NPH and 50% regular 30 to 60 minutes Varies 10 to 16 hours 30 to 60 minutes Varies 10 to 16 hours Pre-mixed insulin lispro protamine suspension (intermediate-acting) and insulin lispro (rapid-acting Humalog Mix 75/25 75% insulin lispro protamine and 25% insulin lispro 10 to 15 minutes Varies 10 to 16 hours Humalog Mix 50/50 50% insulin lispro protamine and 50% insulin lispro 10 to 15 minutes Varies 10 to 16 hours Pre-mixed insulin aspart protamine suspension (intermediate-acting) and insulin aspart NovoLog Mix 70/30 70% insulin aspart protamine and 30% insulin aspart 5 to 15 minutes Varies 10 to 16 hours Basal/Bolus Treatment Program with Rapid-acting and Long-acting Analogs Breakfast Lunch Dinner Plasma insulin Aspart Aspart Aspart Apidra Apridra Apidra Lispro Lispro Lispro Glargine or Detemir 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 Time Adapted from Bruce Bode MD, FACE Insulin Pens 10

11 So how do you initiate insulin? (Let me count the ways ) Initiating Insulin Basal first! Continue current OHDs if no contraindications Cut back a bit on the sulfonylurea dose Easy 10 units glargine pm (adjust as needed) If obese pt with likely insulin resistance start with 20 units Consider AM dose of glargine or detemir only if there appears to be nocturnal hypoglycemia risk Initiating Insulin Up titration (can use varied dosing chart or ) Increase by 3 units q 3 days until AM FBG <120 (+/-) ( or 2 units q 2 days) If AM FBG > 180 increase by 5-6 units (+/-) Have pt stay at the dose once AM sugars at target 11

12 Next Step Need for b.i.d. basal insulin? If there appears to be a glargine wear-out Sugars go higher near time for next dose Can bid each glargine, detemir or NPH Consider hypoglycemic potholes If on correct dose of basal insulin (except NPH) will not go low! Use this to adjust basal doses Other Considerations If starting NPH take at HS Consider detemir if weight gain concern or shorter basal action needed Follow up in 1 week (phone or office visit) Another Next Step Converting NPH dosing to Lantus/Levemir If on NPH once a day use unit per unit If NPH b.i.d. use 80% of total NPH dose If fasting glucose reaches target but postprandial sugars remain high (over 180) start multiple dose insulin (MDI) Bolus insulin starting at largest meal Use rapid acting insulin (use regular insulin in patient with gastroparesis) 12

13 How to Start MDI Insulin Determine total amount of insulin being used 0.2 or 0.3 units/kg/day for patients who are lean, on hemodialysis, frail and elderly, insulin-sensitive, or at risk for hypoglycemia; 0.4 units/kg/day for a patient at normal weight; 0.5 units/kg/day for overweight patients; and 0.6 units/kg/day or more for patients who are obese, on high-dose steroids or insulinresistant. Initiating MDI in 100 kg patient Starting total dose = 0.5 x wgt. in kg Wt. is 100 kg; 0.5 x 100 = 50 units Basal dose (glargine) = 50% of starting dose at HS 0.5 x 50 = 25 units at HS Bolus doses (rapid analog) = 50% of starting dose 0.5 x 50 = 25 divided by 3 = ~8 units pc (tid) 13

14 Correction doses of bolus insulin? Determine Insulin Sensitivity Ratio Use this to correct high sugar Take with dose for carb coverage Determine carbohydrate coverage (insulin:carb coverage) For Prandial Insulin Dosing Calculate Insulin Sensitivity Calculate the patient s Insulin Sensitivity* (IS) by compiling their Total Daily Insulin Requirement (TDI) and dividing this total into 1500 or 1700 Type 2: 1500 / TDI = Insulin Sensitivity Type 1: 1700 /TDI = Insulin Sensitivity (* The IS is the incremental fall in blood sugar that can be expected from each unit of insulin) Use IS to construct a tailored BOLUS sliding scale. EXAMPLE OF INSULIN SENSITIVITY RATIO Patient has a current total daily insulin requirement of 50 Units. His ISR is 1500 / 50 = approx. 30 mg/dl The sliding scale would then be constructed in 30 mg/dl increments per 1 U of insulin, starting at capillary blood glucose values of 120 mg/dl: Blood Glucose Insulin dose mg/dl 1 U mg/dl 2 U mg/dl 3 U mg/dl 4 U mg/dl 5 U mg/dl 6 U >300 mg/dl 7 U Add carb coverage 14

15 What About Dietary Coverage? Type 1: give one unit per 15 grams of carbs Type 2: give one unit per 10 grams of carbs Or rule of 500 is 500/TDI = grams CHO3 per 1 unit What about those mixed insulins? PRE-MIXED INSULINS Humulin 70/30 30 min. 2-4 hours hours Novolin 70/30 30 min hours Up to 24 hours These products are generally taken twice a day before mealtime. Novolog 70/ min. 1-4 hours Up to 24 hours Humulin 50/50 30 min. 2-5 hours hours Humalog mix 75/25 15 min. 30 min.-2½ hours hours *Premixed insulins are a combination of specific proportions of intermediate-acting and shortacting insulin in one bottle or insulin pen (the numbers following the brand name indicate the percentage of each type of insulin). 15

16 Mixed Insulin Use Advantages: Relatively easy to use Good for the shot-shy Fairly good coverage Disadvantages: Not accurate replication of physiological pattern Harder to finesse Post-prandial sugars are a big target! Barriers to Insulin Provider factors Fear Pt anger How to dose hypoglycemia Compliance concerns Time-consuming Weight gain Patient factors Fear Insulin addiction Needles/shots Weight gain Getting sicker hypoglycemia Lifestyle changes Feelings of failure 16

17 Sweet Sally 56 y/o AA woman new onset DM A1C 11.2, 13 lb wgt loss past 3 months HLD, HTN, obesity, fibromyalgia, mild CKD, carpal tunnel, BMI 33, wgt 80 kg On statin, HCTZ, ACEi, ASA Strong family Hx of DM What is your impression of Sally? How would you treat her right now? Sour Sam 60 y/o with DM x 8 years A1C 9.1 Rx diet, exercise, metformin 2000 mg, liraglutide 180 mcg, glipizide 10 mg pm. Hx of HTN, BPH, gout, hypothyroidism, BMI 32 What do you do next? Low Joe 72 y/o with T2DM x 22 years HLD, HTN, prostate cancer, FLD, CKD, neuropathy Lantus 80 u bid, glipizide xl 10 mg bid, TZD 15 mg, statin, ACEi, ASA, ARB, gabapentin, BB A1c 6.3, AM sugars >200, rest of AC BG , 2 hr pp BG >200. What does his A1C indicate? What changes would you make? 17

18 Pregnant Polly 24 y/o woman T1DM with A1C weeks gestation Sugars ranging On glargine and MDI novolog TDI 35 units (13 basal, 22 bolus divided doses) Onset DM age 11, DKA x 2 What should her sugar targets be? Is glargine andnovolog okay in pregnancy? What would you suggest to help her get in control? Why Unexplained High Sugar? Glucometer or glucostrip problem Underlying illness Endogenous insulin downturn Insulin degraded (switch out every days!) Lipodystrophy If only FBG suddenly higher Nocturnal lows? Symogyi? Disturbed sleep Help Insure Success Up front, inform pt of possible insulin use and it s benefits Use insulin pens if possible Be flexible with blood glucose checks Once a week, once a day, 2-4 x a day Rotate sugars Use PAIRED TESTING 1-3 x a week Accurate blood glucose data Equipment failure Fiction? Knowing risks of poor blood glucose control doses NOT insure success! Use the technology 18

19 V-Go Disposable Insulin Delivery Device Glucose monitoring Glucose Sensors 19

20 Fingerstick Blood Glucoses Glucose (mg/dl) Glucose measurement Insulin bolus Target Range 0 12:00 AM 6:00 AM 12:00 6:00 PM 12:00 AM Continuous Glucose Monitoring Provides More Comprehensive Picture of Glycemic Patterns Glucose (mg/dl) Glucose measurement Insulin bolus Target Range 0 12:00 AM 6:00 AM 12:00 6:00 PM 12:00 AM 20

21 Hypoglycemia Treatment of Hypoglycemia Patient alert : 15of carbs ( 4 oz of juice, glucose tablets/gels) 30 gm if sugars <50 Non alert patient : glucagon IM (repeat q 15 min ) RULE OF THUMB : 15 gm of carbs will increased glucose levels mg/dl Do Not Hold Insulin When BG Normal References American Diabetes Association Professional Practice Committee. American Diabetes Association clinical practice recommendations: Diabetes Care. January 2013;36 (suppl 1):S1-S110 Diagnosis and classification of diabetes mellitus. Diabetes Care. Jan 2010;33 Suppl 1:S62-9. Dluhy RG, McMahon GT. Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl J Med. Jun ;358(24): Endocrine Society. Management of Hyperglycemia in Hospitalized Patients in Non- Critical Care Setting: An Endocrine Society Clinical Practice Guideline. January Accessed February 18, 2013 Hirsch, I. Insulin analogues. The New England Journal of Medicine,2012, 352 (2), International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. Jul 2009;32(7): Keller DM. New EASD/ADA Position Paper Shifts Diabetes Treatment Goals. Medscape Medical News Available at Vaddiraju S, Burgess DJ, Tomazos I, Jain FC, Papadimitrakopoulos F. Technologies for continuous glucose monitoring: current problems and future promises. J Diabetes Sci Technol 2010;4(6): No worries I m done! ckessler@maranatha.net 21