Obesity - Canadian Pharmacists Association

Obesity - Canadian Pharmacists Association

Insulin Therapy 101: Using Insulin in Type 2 Diabetes Rahim Hirji, MD, MSc, CCFP Marilyn McInnes, RN, BA, MEd, CDE Inge Schabort, MB, ChB, CCFP OCFP Annual Scientific Assembly November 16, 2006 Outline Presentation Objectives Diabetes Background Information Type 2 Diabetes Targets & Complications Insulin Indications Insulin Administration & Mechanism of Action Classification of Types of Insulin Initiating Insulin Therapy Adjusting Insulin Therapy Resource Materials

Summary Why is a Discussion about Insulin Important? Mainstay treatment for all type I and many type 2 DM patients Many Family Physicians are apprehensive about initiating and adjusting insulin DM clinic not readily available in all communities Initiating and adjusting insulin can be confusing! Primary Objectives Demystify insulin therapy Add tools to your toolbox Provide a practical primary care approach to initiating and adjusting insulin therapy Type I DM

Approximately 10% of all DM patients Characterized by destruction of pancreatic beta cells Usually autoimmune Leads to absolute insulin deficiency Develop DKA if not given insulin Intensive insulin therapy (MDI) recommended Type 2 DM Most common type of DM Characterized by variable degrees of insulin deficiency and resistance Global Prevalence of DM 400 333

350 366 300 People with DM (millions) 221 250 177 200 194

Prevalence 150 100 50 0 30 1985 2000 2003 2010 2025 2030 Sources: www.who.int www.idf Zimmet P. et al Nature: 414, 13 Dec 2001 Year

Canadian Prevalence of DM 3.5 3.03 3 2.5 People with DM (millions) 2.03 2 Prevalence 1.5 1 0.5

0 2003 2025 Year Projected 50% increase in DM prevalence in Canada over next 2 decades Sources: www.who.int www.idf.org Refresher on the Targets Blood glucose: Fasting: 4-7 (4-6 if safe) 2hr.pc: 5-10 (5-8 if safe)

HbA1c: .04-.07 (.04-.06 if safe) 2003 Clinical practice guidelines for the prevention & management of diabetes in Canada UKPDS: UKPDS: decreased decreased risk risk of of diabetes-related diabetes-related complications complications associated associated with with aa 1% 1% decrease decrease in in A1c A1c

Percentage decrease in relative risk corresponding to a 1% decrease in HbA1C Observational analysis from UKPDS study data Any All diabetes- Diabetesrelated cause Myocardial related death mortality infarction endpoint 21% 21% **

** 14% 14% ** ** Peripheral Stroke vascular disease Microvascular Cataract

disease extraction 12% * 19% ** 37% Lower extremity amputation or fatal peripheral vascular disease *P = 0.035; **P < 0.0001 Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405412. 43%

** ** Do We Meet The Targets? DICE Study Diabetes in Canada Evaluation (DICE) study Objective Examine management and control of T2DM in Canada National, cross-sectional patient chart audit Each physician asked to complete two page summary for each of next 10 patients with T2DM 243 primary-care physicians completed entire study Contributed 2473 patient diaries S.B. Harris, J. ko, Y. Zdanowicz, S. Webster-Bogaert. Glycemic control and morbidity in the Canadian primary

care setting. (Results of the Diabetes In Canada Evaluation Study). Diabetes Research and Clinical Practice. DICE Study Contd DICE Study Findings Nearly half (49 per cent) of patients were not at target blood sugar levels (A1C 7 per cent) Almost one-third (32 per cent) of patients achieved sub-optimal blood sugar levels (A1C between 7% to 8.4%) Stewart Harris, 2006 Stewart Harris, 2006 Stewart Harris, 2006 Indications for Insulin in Type 2 DM

Initial therapy in cases of marked hyperglycemia Defined as A1C 9.0% (CPG, 2003) If glycemic targets not reached with oral agents If oral agents are contraindicated e.g. hepatic/renal disease when metabolic decompensation occurs At any time!! Capillary blood glucose monitoring All capable patients should do home testing Patients need to know how to make life style changes based on the numbers This helps them take charge of their diabetes How do you know the tests are

accurate ? Accuracy of monitor depends on the user Check fasting venous vs CBG: 15% variation Are recorded test results: Upside down, real /fiction, mg or mmol Correct technique, strips, date, code, Clean hands Testing on arms Testing on arms: not accurate after meals until >2 hrs Use finger tips: if hypoglycemia suspected & during pregnancy Patients can err Elderly patient stated had 2 lows since MD increased Actos 1 week ago

Log book : L.9 1.9 Actual reading: 6.7 6.1 ( pt. read monitor upside down) Patients can be creative Patients Logbook date 22 23 24

25 26 27 Br Lunch 7.8 7.2 8.1 7.2 7.4 7.8 7.8

7.8 7.4 7.9 7.6 7.9 supper 7.8 7.6 7.9 7.8 8 7.2 hs 7.9 7.7

7.8 7.4 7.9 8 Monitors Memory am lunch suppe r Hs 22 7.8 23 24 7.2 25 9 26 7.8 27

12. 10 14.6 Fact or Fiction All meters have memory to compare to log book If no meter suspect fiction if: Numbers neat, repeated, same ink, no blood stains Patients may not record highs/lows or they write in more tests than they actually do Reinforce that they test to see how they are managing not to please you How often to test? Once daily not enough Can test QID on BID schedule Some patients can test every other day

Encourage inclusion of 2 hrs.pc (A1c = 60%pc) Can see patterns of blood sugars-best way to adjust medication Percentage of the day in postprandial vs. fasting state 15-18 hours a day spent in post-meal state1 PPG FPG DECODE2: 2-hour postprandial glucose associated with increased risk of death independent of fasting glucose In Monnier, L. et. al., Diabetes Care, 2003, 26(3): 881-5 1. Nathan, DM. et al., Diabetes Care 24(4), 2001: 775-778. 2. The DECODE Study Group. Lancet. 1999;354(9179):617-621. 27

Increasing Contribution of PPG as A1C Improves Contribution (%) FPG PPG 30% 50% 55% 60% 70% 50% < 7.3

7.3 to 8.4 45% 8.5 to 9.2 40% 9.3 to 10.2 70% 30% > 10.2 A1C Range (%) (American Diabetes Association Diabetes Care 24(4), 2001: 775-778) Adapted from Monnier L, et al. Diabetes Care. 2003;26:881-885

Suggested Testing Schedule date B after B 12 x x 13 x 14

x 15 x L after Lunch s after Sup. bed

x x x x x x x x comments -Cell Failure is Progressive 100

75 -Cell function (%) 50 25 0 -12 -10 -6

-2 0 2 6 10 14 Diagnosis Years from diagnosis Dashed line shows extrapolation forward and backward from years 0 to 6 based on HOMA data from UKPDS. Lebovitz H. Diabetes Rev 1999;7:139153. Holman RR. Diabetes Res Clin Pract 1998;40(suppl):S21-S25.

Goals of Insulin Therapy Improve glycemic control Reduce risk of developing microvascular and macrovascular complications Improve health and well-being Advantages of Insulin No maximum or minimum dose Easy to titrate No contraindications Only two side effects Weight gain, hypoglycemia Providing insulin replaces a deficiency An old drug, proven safe & effective No serious drug interactions

Potential Mechanisms of Insulin Benefits Decrease plasma glucose Decrease FFA Rests beta cells Improves endothelial dysfunction Decreases inflammatory markers Vasodilatory and anti-thrombotic Why is Insulin not Used Early? More psychology than medicine art and science to insulin therapy Regular provider threats to use the needle Messaging use of insulin = I failed diabetes Marketing Provider anxiety/time constraints r.e. starting

insulin Fear of pain, weight gain, hypoglycemia I am doomed mother took insulin and died soon after Is there Evidence for Early Insulin vs. Pushing Oral Agents? INSIGHT Trial In people with Type 2 DM who Are treated with LSM alone, 1 agent or sub-maximal doses of 2 OHA by specialists or generalists, AND Can easily be managed without insulin, Does the addition and titration of glargine to the above mentioned regimens improve glycemic control? Results 1.7x more likely to achieve HbA1c 6.5% (20% vs. 12%)

and 7% (50% vs. 30%) no difference in hypoglycemia rates Insulin Potent primary hormone responsible for controlling uptake, utilization and storage of cellular nutrients Stimulates anabolic actions: Intracellular utilization and storage of glucose, amino acids and fatty acids Glycogen synthesis Inhibits catabolic processes e.g. glycogenolysis Insulin Sources Recombinant DNA technology Chemically identical to human insulin Insulin analogs by modifying the AA sequence of insulin molecule

Time-Activity Profile Post-prandial insulin secretion in normal subjects generally biphasic Phase 1 Rapid rise in insulin secretion after meal peak after 1-2 minutes Phase 2 Delayed onset and longer duration Storage of insulin Most insulins are stable once opened for 30 days (at room temperature) and for 3 months (if refrigerated) Exceptions: Glargine: 28 days (even if refrigerated) Levemir: 42 days Never leave in the car or freeze extreme temperatures could render it ineffective

Insulin not in use should be refrigerated good unopened until expiry date Route of Administration Long-term treatment relies predominantly on subcutaneous (SC) injection Can be administered IV or IM if necessary Insulin Administration Options Syringe Pen Pump Insulin Injection Sites Sites abdomen, thighs, arms abdomen has best absorption Note: avoid 2 inches around the navel

Rotate sites 1-2 inches apart over use of sites produces lipohypertrophy and affects absorption Inspect injection sites to avoid lipohypertrophy Factors influencing insulin absorption Insulin preparation Dose (concentration & volume) Physical status (solution or suspension) Mechanism of protraction Self association

Precipitation Albumin binding Injection site factors Region of injection Depth of injection Lipodystrophy Blood flow changes e.g. temperature, exercise, hypoglycaemia, ketoacidosis Insulin types and action Rapi d Short Humulin R NovolinToron to

Intermediate Humulin N Novolin NPH Long : Humulin U Lantus Humalog & Novo-rapid Action Profiles of Insulins lispro/aspart 46 hours Plasma Insulin levels regular 6-10 hours

BOLUS INSULINS BASAL INSULINS NPH 1220 hours levemir ~ 6-23 hours glargine ~ 10-26 hours Hours Note: action curves are approximations for illustrative purposes. Actual patient response will vary. Mayfield, JA.. et al, Amer. Fam. Phys.; Aug. 2004, 70(3): 491 Plank, J. et.al. Diabetes Care, May 2005; 28(5): 1107-12 Types of Insulin

Action Rapid Name Starts Peaks Lasts (hours) (hours (hours) ) Humalog (Lispro) 0.1-0.4 1-2.5 3-5 Novo-rapid (Aspart) Short Humulin R

Novolin Toronto Intermediat Humulin N e Novolin NPH Long Lantus (glargine) Long Levemir 0.5-1 2-4.5 5-8 1-3

4-12 18-24 1.5 1.5 None None 10-24 6-23 Pre-mixed Insulin Type 30/70

Content Onset (hours ) 30% R /Toronto 0.5 70% N / NPH Humalo 25 % Humalog g Mix 75% NPL 25 0.10.4 Peak Lasts

2-12 18-24 1-12 18-24 ANY QUESTIONS? Case #1 Mr. M 60 y.o. male, type 2 x 14 years, wt = 90 Kg , Day FBS PC BF

Mn 9.0 11.3 Tu 10.3 We 9.6 Th 11

Hx NSTEMI AC lunc h PC lunch AC dinner PC dinn er HS

Metformin 2gm/day, Glyburide 20 mg/day FBS 9-11 mmol/L CBS range 9-16 mmol/L A1c 0.092 Symptomatic Patient not willing to add more oral agents WHAT NEXT? 11.6 12 11 16.0 13

HS Insulin NPH or glargine can be added HS without discontinuing oral agents suppresses nocturnal hepatic glycogenolysis - prevents fasting hyperglycemia Less weight gain with HS insulin especially in combination with metformin Riddle,M.,Rosenstock,J.Gerich,J., Treat to Target Trial Diabetes Care26.3080-86 2003 American Diabetes Association (mg/kg/min) Glucose utilization rate Insulin Glargine: The Only Basal Insulin to Provide a 24-Hour Profile with no Pronounced Peak

6 5 4 3 2 1 0 Hourly mean values Insulin Glargine (n=20) NPH Insulin (n=20) End of observation period 0

10 20 Time after SC injection (hours) SC, subcutaneous. Adapted from LANTUS (insulin glargine) Product Monograph 2005. 30 NPH vs. Lantus (Glargine) New long acting clear insulin ( cannot be mixed with any insulin) Onset 90 minutes, no peak, lasts 24 hours Studies comparing NPH and glargine: type 2s : both equal for euglycemia

increased hypoglycemia with NPH type 1s: lower A1c, lower fasting glucose and less hypoglycemia in glargine group Porcellati et al., (2003) Garg, S K., Paul, J. M., Karsten, J. I., Meditto, l., Gottlieb, P. A. (2004). Reduced severe hypoglycaemia with insulin glargine in intensively treated adults with type 1 diabetes. Diabetes Technology and Therapeutics, 6 (5), 589-595 Rosenstock, Schwartz, Clarke et al. 2001 Fonesca, V., Bell, D., Berger, S., Thomson, S., Mecca, T. (2004). A comparison of bedtime insulin glargine with NPH in patients with type 2 diabetes a subgroup analysis of patients taking once daily insulin in a multicenter randomized parallel group study. American Journal of Medical Sciences, 328(5), 274-279. How to Initiate HS Insulin Reinforce lifestyle modifications Ensure capillary tests are accurate Continue oral agents and add: 5-10 units of NPH/glargine qHS

add 2-4 units q 4th night until FBS @ target Insulin Nave Patients May feel poor (i.e. hypoglycemic) when blood glucose decreases to 7-9 This feeling will pass with time Eye/vision changes as blood glucose changing Advise not to change prescription eyeglasses until blood glucose normalizes Case #1 Contd Mr. M. started on 10 units NPH Hs with minimal improvement in CBG NPH titrated up by 4 units

q 4days for 2 weeks Pt on 22 units NPH; FBS 6.1-6.8 mmol/L, PC meals 9.9-12.3 mmol/L, qHS 12.7-14.0 mmol/L WHAT NEXT? Day FBS PC BF Mon

6.8 9.9 Tues 6.3 Wed 6.1 Thurs 6.5 AC PC

AC lunch lunch dinner PC dinner 12.3 11.1 qHS 14.0 11.8 12.0 12.7

Control Poor with qHS NPH? Can (and should!) continue metformin Discontinue insulin secretagogues (e.g. glyburide, gluconorm, diamicron) To avoid hypoglycemia Commence BID insulin Initiating BID Insulin Start with the following units of NPH per kg body weight: 0.1- 0.2 (thin) 0.2-0.3 (normal weight) 0.3-0.5 (obese) Give 2/3 total daily dose in am & 1/3 HS Case #1 Contd

Consider insulin BID d/c insulin secretagogue- glyburide & continue metformin Patient wt = 90 Kg (BMI 31) Insulin start NPH 0.3 units / Kg = 27 units 2/3 of insulin in a.m. (18 units) 1/3 HS (9 units) Patient returns in 2 weeks; CBS range 7.4-13 mmol/l WHAT NEXT? Day FBS PC BF

Mon 7.4 9.1 Tues 7.8 Wed 7.5 Thurs 7.9

AC PC AC lunch lunch dinner PC dinner qHS 13.0 8.5 10.2 9.2 11.4

Adjusting Insulin (1/3) Reinforce lifestyle modifications Ensure Capillary tests are accurate Make one change at a time Increase by 5-10 % (2-4 units) every 4th day until at target Adjusting Insulin (2/3) Adjust to decrease hypoglycemia risk first Base changes on patterns of glucose tests taken at different times over a few days e.g. patterns of food, exercise, and CBS Never react to a single test i.e. fasting venous (a moment in time) or just A1C

Adjusting Insulin (3/3) Pre- and post-prandial PG checks If diff of 2 mmol/l pre and post amount of insulin with meal is sufficient If diff of >2 mmol/l pre and post need more insulin with meal Note: if patient on Regular/R insulin Make sure insulin administered 30 minutes before meal! Case #1 Contd Recall patients insulin regimen was: NPH 18 units qAM, 9 units

qHS Dose increased by patient every 4th day Patient now on NPH 34 units qAM, 16 units qHS CBS range 6.3-12 CBS range ac lunch 9-12 mmol/l WHAT NEXT? Day FBS PC

BF Mon 6.9 9.1 Tues 6.7 Wed 6.3 Thurs

6.8 AC PC lunch lunch AC dinner PC dinner qHS 12.0 8.5 7.8

11.6 11.0 8.1 Switching to MDI Superior glycemic control with MDI* Switching from BID insulin to MDI 60% of insulin during meals Distribute based on meal size Rapid or fast acting insulin 40% of insulin qHS long or intermediate acting *2003 CDA Clinical Practice Guidelines Expert committee Basal-bolus therapy attempts to recreate physiological insulin secretion Predicted plasma insulin concentration

profile (mU/l) Rapid-acting insulin Basal insulin Total Time of day Case #1 Contd Consider MDI Recall patients insulin regimen was: NPH 34 units q.am, 16 units qHs = 50 units Mealtime insulin 50 units x 60% = 30 units of Lispro 8 units with breakfast 10 units with lunch 12 units with dinner

Bedtime insulin 50 units x 40% = 20 units of NPH Table of Suggestions for Insulin Adjustment LOW GLUCOSE DECREASE FASTING Hs insulin HIGH

( If not Somogyi) INCREASE Hs insulin HIGH consider adding: rapid or fast acting at supper Before LUNCH

rapid or shortacting at breakfast rapid or shortincrease % of R or acting at breakfast Toronto in pre mix i.e. 20/80 to 30/70 Before SUPPER breakfast intermediate or long-acting , or lunch rapid or short-acting breakfast intermediate or

long-acting, or lunchtime rapid or short-acting fast or rapid acting at lunch or intermediate at breakfast bedtime supper short or rapid-acting supper short or rapid-acting supper short or rapidacting

2. hrs pc meal time rapid meal time rapid Reference: McInnes M, M Wheeler. Managing Type 2 Diabetes (an evidence-based tool), sept/04. Types of Insulin Action Rapid Name Starts Peaks Lasts

(hours) (hours (hours) ) Humalog (Lispro) 0.1-0.4 1-2.5 3-5 Novo-rapid (Aspart) Short Humulin R Novolin Toronto Intermediat Humulin N e Novolin NPH Long Lantus (glargine) Long

Levemir 0.5-1 2-4.5 5-8 1-3 4-12 18-24 1.5 1.5 None

None 20-24 Dose depende nt 6-23 Case #2 Mr. B Mr. B, 47 y.o. male, type 2 x 5 years Insulin regimen 10 units Humalog and 32 units NPH in a.m. 8 units Humalog at supper, 12 units NPH at bedtime Table of Mr.Bs CBGS Day Mon 7.a.m.

4.8 Noon 6.0 6 p.m. 12.9 8 p.m. 4.2 Tues Wed 5.2 8.6 8.0

7.2 14.5 16.0 6.9 5.0 ADJUSTMENT Thurs 6.9 6.3 What was the adjustment?

6.2 Case #2 Contd Issue is high pre-prandial CBS at dinnertime Mr. B increased a.m. NPH by 3 units Recall: NPH peak activity is in 8-10 hrs Successful: CBS at 6pm 6.2 mmol/L post-adjustment Suppertime Humalog decreased by 2 units to avoid hypoglycemia Another choice: Humalog at each meal and discontinue Humulin N in am Case #3 Mrs. S 54 y.o. female, type 2 x 2 years Insulin regimen: TID injections with 3 types of insulin 14 units 30/70 in a.m.

Day 8 units R at suppertime 10 units NPH at bedtime qHS BS 4.5-7 mmol/L, but fasting BS 9-18 mmol/L over past week WHAT NEXT? FBS PC BF Mon 9.0 9..4

Tues 10.3 Wed 12.0 Thurs 18 AC PC AC lunch lunch dinn er

PC dinn er 10 8.1 qHS 5.7 8.8 5.2 6

4.5 Case #3 Contd Increases NPH at bedtime to 12 units x 3 days no improvement in a.m. fasting CBS Increases to 14 units x 3 days Again, no improvement in a.m. fasting CBS ANY THOUGHTS? What if tests are high fasting? is there insufficient HS insulin? Is it the Somogyi Phenomenon? Somogyi Phenomenon

Rebound hyperglycemia from hypoglycemia Thought to involve counter-regulatory hormones, which stimulate gluconeogenesis and glycogenolysis Nocturnal hypoglycemia can be caused by: too much bedtime insulin premix (30/70) or NPH insulin at supper Yale,J.,Begg,I.,Gerstein,H.C.,Houlden, R., Jones, H., Maheuz,P., Pacaud, D. 2001 Canadian Diabetes Assoc. Clinical practice Guidelines for the Prevention and Management of Hypoglycemia in diabetes. Canadian Journal of Diabetes /26:1 Symptoms of Somogyi in night Nightmares Waking up with wet pillow from sweating Waking up with headache Restless sleep High fasting blood sugar Diagnosis & Treatment

Have patient test at 0300 hrs 2-3 nights in a row If low, then decrease Hs insulin if on premix insulin at suppertime break it up Give fast or rapid-acting at supper and move NPH to q HS but decrease dose by 10 % Can also decrease am 30/70 by 10-15 % as NPH will overlap am insulin 2001 recommendations for treating hypoglycemia3 Mild <4 : oral ingestion of 15 grams of glucose preferably glucose or sucrose tablets Severe:< 2.8 in a conscious person use 20 grams Retest in 15 minutes and retreat with 15 grams if <4 Follow with ingestion of starch and protein or next meal In unconscious home patient use glucagon: adult 1mg, child 0.5 mg

Yale,J.,Begg,I.,Gerstein,H.C.,Houlden, R.,Jones, H., Maheuz,P., Pacaud,D. 2001 Canadian Diabetes Assoc. Clinical practice Guidelines for the Prevention and Management of Hypoglycemia in diabetes. Canadian Journal of Diabetes /26:1 Hypoglycemia Prevention Instruct patients to Follow food and insulin plan Test blood glucose regularly Carry carbohydrate Wear medical identification Teach others how to inject glucagon Case #4 Mr. S Male age 45, type 2 x 4 years Occupation : Dofasco shift worker (12 hr shifts) Meals irregular, often skipped Current insulin regimen: Humulin N 15 units Q12 H at 6 am and 6 pm

but often forgets second injection at 6pm and takes it at midnight Humalog 10-15 units at each meal CBSs vary from 3-18 Suggestions? Case #4 The Issues Increased risk for nocturnal hypoglycemia with Humulin N given at 6pm Humulin N could peak at the same time as Humalog when given irregularly, especially if patient working nights Inconsistent timing increases the risk of hypoglycemia and hyperglycemia Missing insulin changes basal amount Suggestions?

Case #4 Mr.S. Change basal insulin to Lantus & give HS Decrease by 20% at first N 15 & 15 =30 units - 20%=24 units of Lantus qHS Continue with Humalog at each meal Adjust by 5-10% every 4th day until at target Case #5:Mrs. Chemo Mrs .Chemo: 54 yrs old, wt=100kg type 2 X10 years Medications: glyburide10 mg BID metformin 1000 mg BID CBS: were all 6-8, HbA1c 5.9 Started chemotherapy with decadron 4 mg q am CBSs after treatment initiated: fasting: 8, Lunch: 20, supper 25, Hs 16

Suggestions? Case #5 The Issues Steroids cause insulin resistance and increased catecholamines Result in hyperglycemia Effect decreased as steroid action wanes often overnight Glucose levels often low fasting higher at noon and supper lower Hs Need to address rising glucose in the day Glyburide not maintaining euglycemia Suggestions? Case # 5: Mrs.Chemo

Stop glyburide Continue metformin Initiate insulin @ 0.3 units/kg 30/70 10 units in am Short (Toronto / R) or rapid (Lispro / Aspart) 10 units at lunch 10 units at supper No insulin Hs (yet) morning glucose lowest Note: when change steroid dose, reassess Cbs May be able to switch back to oral hypoglycemics How glucocorticoids cause hyperglycemia Enter cell nucleus & bind to DNA causing: Increased hepatic glycogenolysis Increased lipolysis Muscle catabolism

Inhibition of glucose uptake in muscles and fat Suppressed insulin release from pancreas Nahaczewski,A.,Fowler,B., Haritharan,S., J neurosci nsg 2004 :36(6) 340-43 Hirsch,I.,Endocrinology and Metabolism clinics ,Vol 26 (3) Sept 1997 Diabetes and cancer Patients with hyperglycemia &/or diabetes higher mortality and recurrence rates of cancer People with diabetes 13% higher risk of dying from cancer than those without insulin resistance increases risk of dying from cancer Achieving good glycemic control leads to better

outcomes Richardson,L.,Pollock L., Nat Clin Pract Oncol .2005;2 (1)48-53 Saydah,Sh et al.,(2003) Am J.Epidemiology 157:1092-1100 Effects of hyperglycemia on the injured brain Hyperglycemia in critically ill patients described as toxic metabolic milieu that slowly results in increased morbidity and mortality Study of 656 patients with acute ischemic stroke Patients with hyperglycemia on admission longer hospital stays higher risk of death within 30 days, at 1 year and at 6 years post-stroke Effects of hyperglycemia on neurological outcome in stroke patients .Paolino,A, Garner,K. Journal of Neuroscience Nursing June 2005. vol 37 # 3

Adjusting for Exercise & Activity Can increase carbohydrate consumption Can decrease insulin in anticipation of increased activity 10% for light exercise 20% for moderate 30-40% for vigorous Should monitor CBS to determine if successful in achieving balance between food/exercise/insulin Note: hypoglycemia can occur up to 24-30 hours after exercise

Adjusting for Special Occasions Extra rapid or short-acting insulin before Or after within 15 minutes of the meal Approximately 1 unit of extra insulin per 10-15 grams of extra carbohydrate On the Horizon Oral insulin Very early in development Minimal evidence r.e. efficacy at this stage Inhaled Insulin - Adults only: type 1 (along with basal insulin) type 2 monotherapy or combination Inhaled insulin: Exubera Dry powder 1 or 3 mg dose blisters inserted into inhalation device size of eye glass case

Administered 10 minutes ac Onset similar to rapid insulin (10-15 mins) Peak 30-90 min Lasts similar to regular insulin 1-4 hrs) Contraindications: smoking , C.O.P.D. Lung spirometry at baseline / 6 months /1 year Side effects:dyspsnea, cough, hypo, sore throat dry mouth Sample Prescriptions Humulin N insulin __ units qhs ( or as directed) 3ml penfills Humalog __ units TID ac (or as directed) 3 ml penfills needles for pen (6 mm thin, 8mm obese ,12.7 very obese) 100 Lancets, 100 strips for glucometer.________ 3 months supply

Sample Prescription: Lantus Lantus pen: 24 unit size or 48 unit size Lantus pen cartridges Needles for lantus pen Take as directed (or specific instructions) or Lantus 10 ml vial Insulin syringes: 100 units /1 ml size 0.5 ml size , 0.3 ml. size Sample prescription: Novolin Novolin Levemir 3 ml penfills Novo rapid 3 ml penfills Needles for pen OR Novolin NPH,(or novo rapid) 10 ml vial Syringes 1 ml, 0.5 ml, 0.3 ml

Summary (1 of 4) Diabetes is increasing exponentially Family Physicians provide most DM care Not very successful achieving targets (DICE Study) Significant decrease in DM related complications with 1% improvement in HbA1c (UKPDS) Summary (2 of 4) Capillary blood glucose monitoring should be accurate & appropriately scheduled Insulin therapy efficacious (CPG, INSIGHT Trial), but often underutilized Many insulin preparations available Insulin therapy regimen can mimic physiologic insulin activity profile

Summary (3 of 4) Initiating insulin therapy Start with 5-10 units of glargine/detemir/N/NPH at bedtime adjust by 2-4 units q4 days until at target Switching to BID insulin therapy Approximately 0.3-0.5 units/kg 2/3 qAM & 1/3 qHS Switching to MDI insulin therapy 50-60% of insulin during meals Distribute based on meal size Rapid or fast acting insulin 40-50% of insulin qHS long or intermediate acting Summary (4 of 4)

Hypoglycemia diagnosis, management and prevention Somogyi phenomenon Examine suppertime and bedtime insulin type and dose Adjust to address hypoglycemia before hyperglycemia Effects of steroid therapy Hyperglycemia from insulin resistance & increased catecholamines Enhance control through switch to insulin therapy Effects of exercise Aim to achieve balance between food/exercise/insulin hypoglycemia can occur up to 24-30 hours after exercise

On the horizon Exubera Oral insulin? Conclusion You CAN initiate and adjust insulin therapy in the primary care setting!! References Diabetes Websites www.diabetes.ca http://care.diabetesjournals.org www.diabetesclinic.ca www.diabetes.org www.diabetesmonitor.com

www.diabeticgourmet.ca Thank you! Questions ?

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