Module ii insulin therapy

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  • The progressive nature of diabetes is associated with long-term microvascular and macrovascular complications 1-3 Microvascular complications of diabetes (those affecting the small blood vessels) include: Retinopathy – diabetic retinopathy, often associated with cataracts and glaucoma, leads to visual impairment and, potentially, blindness 3 Nephropathy – diabetic nephropathy is a common complication of diabetes and is the single leading cause of end-stage renal disease 3 Neuropathy – clinical manifestations of diabetic neuropathy can be broadly classified as those occurring due to autonomic and peripheral (sensory) neuropathy 1,2 : Autonomic neuropathy (impaired nerve signalling to internal organs) is associated with a range of clinical manifestations such as gastro-intestinal dysfunction (including slowed digestion of food in the stomach, slowed gastric emptying and diarrhoea), bladder dysfunction and sexual dysfunction. Cardiac autonomic neuropathy can lead to heat rate disturbances and postural hypotension Peripheral (sensory) dysfunction results in impaired sensation or pain in the feet or hands and a subsequent increase in the risk of wounds/infection. Diabetic foot is characterised by gangrene and ulceration that develop as a result of increased wounding/infection of the foot due to reduced sensation and also due to impaired peripheral blood supply Cognitive impairment – patients with diabetes have also been shown to have a higher risk of vascular and Alzheimer’s dementia, and elevated HbA 1c has been linked to reduced cognitive function 4 Macrovascular complications of diabetes (those affecting the larger blood vessels) include: Cerebrovascular disease – including stroke and transient ischaemic attack 2 Coronary disease – including manifestations of coronary heart disease such as chronic angina and acute myocardial infarction, usually resulting from atherosclerosis in the coronary circulation. Patients with coronary heart disease also commonly develop heart failure 2 Peripheral vascular disease – caused by poor blood supply to the lower limbs as a consequence of atherosclerotic hardening of the arteries. Gangrene can develop as a result of blockage of a large artery leading to poor blood supply to the feet 2 References: International Diabetes Foundation. Time to Act: Type 2 diabetes, the metabolic syndrome and cardiovascular disease in Europe. 2006. Available at: http://www.idf.org/webdata/docs/IDF_T2D_slides_final_aug06.ppt. Accessed April 19 , 2010. International Diabetes Federation. Time to Act. 2001. Available at: http://www.idf.org/webdata/docs/Diabetes%20and%20CVD.pdf. Accessed April 19, 2010. American Diabetes Association. Standards of medical care in diabetes—2010. Diabetes Care. 2010;33(Suppl 1):S11-S61. Seaguist, ER. The final frontier: how does diabetes affect the brain? Diabetes. 2010;59:4-6.
  • Monnier et al analyzed the daily glycemic profiles of patients with T2DM, with different levels of A1C, to determine the relative contribution of fasting and postprandial plasma glucose to hyperglycemia. Contributions of postprandial and fasting hyperglycemia to A1C shifted as T2DM progressed. The relative contribution of postprandial glucose elevations to A1C decreased progressively over quintiles of A1C; conversely, the impact of FPG increased with rising A1C level. Postprandial glucose spikes are the major determinants of hyperglycemia in patients with moderate T2DM, whereas basal glucose plays an increasing role as T2DM worsens. Relative contributions of postprandial glucose and FPG to A1C
  • This slide illustrates that in normal individuals, glucose excursions following meals are modest and kept within a very narrow range. Therefore, defense against hyperglycemia is very aggressive. In patients with type 2 diabetes who have established fasting hyperglycemia, postprandial glycemic excursions are exaggerated.
  • This slide illustrates that in normal individuals, glucose excursions following meals are modest and kept within a very narrow range. Therefore, defense against hyperglycemia is very aggressive. In patients with type 2 diabetes who have established fasting hyperglycemia, postprandial glycemic excursions are exaggerated.
  • This slide illustrates that in normal individuals, glucose excursions following meals are modest and kept within a very narrow range. Therefore, defense against hyperglycemia is very aggressive. In patients with type 2 diabetes who have established fasting hyperglycemia, postprandial glycemic excursions are exaggerated.
  • This slide illustrates that in normal individuals, glucose excursions following meals are modest and kept within a very narrow range. Therefore, defense against hyperglycemia is very aggressive. In patients with type 2 diabetes who have established fasting hyperglycemia, postprandial glycemic excursions are exaggerated.
  • Testing times Before meals Post largest meal to see how the insulin is covering the meal
  • Key Points: Elevated fasting glucose indicates need for basal insulin to suppress gluconeogenesis overnight. With basal insulin, patient needs to be on at least one oral agent to address mealtime glucose excursions Elevated post-meal glucose indicates need for bolus insulin to cover meal related carbohydrate intake. Most common starting points are Basal Insulin and Mixed Insulin but both point to Basal/Bolus regimen of increased flexibility. Note page reference (3-5) to 4 th edition Quick Guide to get people into the SDM materials. Insulin detemir is a new basal insulin that is expected to be approved by FDA by the end of 2005.
  • Key Points: Elevated fasting glucose indicates need for basal insulin to suppress gluconeogenesis overnight. With basal insulin, patient needs to be on at least one oral agent to address mealtime glucose excursions Elevated post-meal glucose indicates need for bolus insulin to cover meal related carbohydrate intake. Most common starting points are Basal Insulin and Mixed Insulin but both point to Basal/Bolus regimen of increased flexibility. Note page reference (3-5) to 4 th edition Quick Guide to get people into the SDM materials. Insulin detemir is a new basal insulin that is expected to be approved by FDA by the end of 2005.
  • Testing times Before meals Post largest meal to see how the insulin is covering the meal
  • Key Points: Elevated fasting glucose indicates need for basal insulin to suppress gluconeogenesis overnight. With basal insulin, patient needs to be on at least one oral agent to address mealtime glucose excursions Elevated post-meal glucose indicates need for bolus insulin to cover meal related carbohydrate intake. Most common starting points are Basal Insulin and Mixed Insulin but both point to Basal/Bolus regimen of increased flexibility. Note page reference (3-5) to 4 th edition Quick Guide to get people into the SDM materials. Insulin detemir is a new basal insulin that is expected to be approved by FDA by the end of 2005.
  • Testing times Before meals Post largest meal to see how the insulin is covering the meal
  • What are some of the things that get in the way of starting a person on insulin? We need to identify those concerns a patient has, and not make assumptions as to what their concerns actually are. You may think they're afraid of giving themselves a shot when they're actually afraid of having a low blood sugar. Let me share a couple of stories with you. ACCORD patient story about giving themselves a shot and the ACCORD realtor story. I'm sure many of you have heard about the concept called motivational intervieiwing - that is, having the patient come to the decision by providing the right cues. We need to give them the information they need to make good decisions for themselves and to correct any false assumptions they've received along the way.
  • To reinforce this message, you can use these color coded insulin production gauges to help them understand where they are at in the course of their disease. We’ve taken the information from the graph that Dr. Bergenstal shared earlier with you and developed a more patient friendly approach to convey this idea. The first gauge shows normal insulin production, the 2nd gauge shows how insulin production is actually higher than a person without diabetes. This occurs at a time, when, most likely, the patient didn’t even know they had pre-diabetes. You can explain that after they were diagnosed, the pancreas continues to make insulin but can not make enough to overcome the insulin resistance and the pancreas is “wearing out” so to speak.
  • We also conducted a survey among providers like you asking them what concerns they had and, as it turned out, they had many of the same concerns that the patients did. They listed the complexity of starting and adjusting insulin, they weren’t sure what it was like to take an insulin injection, and also listed weight gain and hypoglycemia. I’m sure you may have others that we can address later in our question and answer time but right now, we are going to make sure that you don’t leave here without knowing what’s it like to actually take an insulin injection. Watch this next video.
  • The purpose of blood glucose monitoring is to improve clinical decision-making so that the physician can appropriately identify the glucose patterns of each patient and whether or not the insulin is working appropriately. It’s second purpose is to adjust insulin therapy and the patient should understand the significance of providing accurate and reliable blood glucose data so that the therapy can be adjusted. The third purpose is to evaluate whether the therapy is working appropriately to avoid hypoglycemic events and to make sure that the patient is following the regimen. It is clear that the most important and most significant purpose of blood glucose monitoring lies in the feedback that it provides the patient to know that the current therapy that the patient is utilizing is effective for managing blood glucose levels, improving control over all and making the quality of life for the patient significantly better.
  • As was previously mentioned, the minimum or recommended amount of testing should be four times per day, before each meal and before bed time. For individuals who are concerned with post-prandial blood glucose levels and are concerned that particular meals or particular times of the day the individual may be suffering from regular hypoglycemia, it is important to test two hours post-meal periodically to evaluate the effectiveness of the insulin in managing post-meal blood glucose levels. If it is necessary, modify the frequency of monitoring. This would be appropriate in individuals who are traveling and there is a change in time zone, or for whom testing becomes difficult at certain times of the day. The most important thing is to view the day as a 24-hour period and to try to fill in as many of the hours as possible over at least a months worth of testing. This excludes, of course, overnight testing which should be considered if patients are concerned with nocturnal hypoglycemia. Nocturnal hypoglycemia is usually caused by conventional or mixed insulin therapies in which the intermediate or NPH-acting insulin is peaking and causing blood glucose to become very low at about 2 to 3 a.m. in the morning. Encourage patients to maintain an accurate and reliable record of their blood glucose tests. If possible, use a reflectance meter with a memory. Ideally, this meter can be connected to a computer and the blood glucose values can be downloaded and recorded on the computer memory or printed out for the patient’s use or printed out and maintained in the record. All patient’s should maintain their own record book which would keep blood glucose values for them to review and to search for specific patterns.
  • 2006 International Diabetes Center
  • This slide demonstrates the key nutrition messages for the various insulin regimens described by Dr. Bergenstal. This information is also on Table 4 in the "Guide to Starting and Adjusting Insulin for Type 2 Diabetes". Note also on the algorithm, that on the right side-bar, there are initial nutrition messages given. For those patients put on a background insulin it helps glucose control if they control their carbohydrates throughout the day. A suggestion to get started is to tell the patient to have 3-4 carb choices per meal until they can consult with a dietitian For those patients on a premixed insulin it is important to eat meals at consistent times and consistent amount of carbs. Snacks may be needed depending on the insulin mix, for example if it's a Regular,NPH mix and patient schedule For the Background and mealtime regimen encourage the patient to start with a consistent carb intake at all meals. Generally snacks are not needed with this regimen. This regimen also allows for more flexibility in eating times and carb amounts. Once a patient is under control, you can teach what their insulin/carb ratio is which we'll adress later. This will add even more flexibility to their daily routine.
  • Titrating background insulin focus on am fasting BG. Once you reach 0.5 units/kg body weight, explain to the patient that a RA insulin will need to be added If fasting BG is in target and A1C > 7%, it means that there are other timepoints throughout the day where the patient is having higher blood sugar. Ask them to do some post meal testing. This also helps them see that they're a partner with you in taking care of their diabetes. They provide you with importnat information which in turn helps you to make the best decision for them.
  • Doses need to be titrated on a regular basis Increase equally between doses if over 200 by 0.1 unit/kg For BG readings below 100, look at Table 6 as a guide for titrating insulin
  • Shirley on 3 orals A1C 7.7% Where would you make an adjustment? Add 1 units to decrease am FPG
  • Shirley on 3 orals A1C 7.7% Where would you make an adjustment? Add 1 units to decrease am FPG
  • Titrating background insulin focus on am fasting BG. Once you reach 0.5 units/kg body weight, explain to the patient that a RA insulin will need to be added If fasting BG is in target and A1C > 7%, it means that there are other timepoints throughout the day where the patient is having higher blood sugar. Ask them to do some post meal testing. This also helps them see that they're a partner with you in taking care of their diabetes. They provide you with importnat information which in turn helps you to make the best decision for them.
  • For premixed insulin if BG over 200 increase total dose by 0.2 units Distribute evening between the two doses
  • Bernie A1C 9.4% 0.2 units bid or 19 units bid Add 0.1 unit/kg = 9.5 units or 10 units divided between 2 doses
  • Bernie A1C 9.4% 0.2 units bid or 19 units bid Add 0.1 unit/kg = 9.5 units or 10 units divided between 2 doses
  • For background mealtime regimen increased total insulin dose by 0.1 units and add half to the background and distribute other half between mealtime doses If more than 40 mg/dl add 1-3 units
  • Jackie had an A1C of 10.4% Calculate at 0.3 units for the day 24 units bid Encourage pre/post lunch readings
  • Jackie had an A1C of 10.4% Calculate at 0.3 units for the day 24 units bid Encourage pre/post lunch readings

Transcript

  • 1. SDM: Focus on Insulin Therapy
  • 2. Major microvascular and macrovascular complications of diabetes Microvascular1,2 Macrovascular1,2Cognitive impairment3 Cerebrovascular disease Diabetic retinopathy Coronary disease Coronary heart diseaseDiabetic nephropathy Diabetic neuropathy Cardiac autonomic Atherosclerosis neuropathy Skin infection Gastro-intestinal and Peripheral vascular bladder dysfunction disease Sexual dysfunction Peripheral sensory dysfunction Diabetic foot Adapted from: 1. International Diabetes Foundation. Time to Act: Type 2 diabetes, the metabolic syndrome and cardiovascular disease in Europe. 2006. 2. International Diabetes Federation. Time to Act. 2001. 3. Seaguist ER. Diabetes. 2010;59:4-6.
  • 3. UKPDS: Tight Glycaemic Control Reduces Complications Epidemiological extrapolation showing benefit of a 1% reduction in mean HbA1c Deaths related 21% to diabetes * Microvascular 37% complications e.g. HbA1c kidney disease and blindness * 1% 14% Heart attack * Amputation or fatal 43% peripheral blood * p<0.0001 vessel disease * ** p=0.035 Stroke ** 12%Stratton IM et al. UKPDS 35. BMJ 2000; 321: 405–412
  • 4. Scientific Foundation for InsulinTherapy in Type 2 Diabetes  Why is insulin needed?  When is insulin needed?  Is insulin therapy effective?  Is insulin therapy safe?
  • 5. Achieving Glycemic Control The first step is to set a glycemic target (agreed to by the patient) HbA1c target (%) ADA/EASD <7 IDF ≤6.5 NICE <6.5 AACE ≤6.5 France <6.5* Canada ≤7 Australia ≤7 Latin America <6.5Are these HbA1c targets still appropriate in light of recent clinical trials?
  • 6. Scientific Foundation for InsulinTherapy in Type 2 Diabetes  Why is insulin needed? To achieve glycemic targets  When is insulin needed?  Is insulin therapy effective?  Is insulin therapy safe?
  • 7. Clinical Inertia: “Failure to Advance Therapy When Recommended” Mean A1C at Last Visit* (%) 10 9.6% 8.9% 8.6% Combination 9 oral agents SU or Diet and metformin 8 Exercise 7ADA Goal 2.5 Years 2.9 Years 2.8 Years Initiation 8.2 Years of insulin therapy Years Elapsed Since Initial Diagnosis*Adapted from: Brown JB et al. Diabetes Care. 2004;27:1535-1540.
  • 8. Staged Diabetes Management * * Liraglutide approved in EUMazze, Strock, Simonson, Kendall, Cuddihy, Bergenstal. SDM Quick Guide 5th Edition, International Diabetes Center, 2009
  • 9. ADA/EASD Revised Algorithm for T2DM Nathan DM, et al. Diabetes Care & Diabetologia January 2009.Tier 1: well-validated therapies Lifestyle + Metformin Lifestyle + Metformin + Basal insulin + Intensive insulin At diagnosis: Lifestyle + Insulin Metformin Lifestyle + Metformin + Sulfonylureas STEP 1 STEP 2 STEP 3Tier 2: Less well validated therapies Lifestyle + Metformin + Pioglitazone Lifestyle + metformin No hypoglycaemia + Pioglitazone Oedema/CHF Bone loss + Sulfonylurea Lifestyle + metformin Lifestyle + metformin + GLP-1 agonist + Pioglitazone No hypoglycaemia Weight loss + Basal insulin Nausea/vomiting
  • 10. ADA/EASD Revised Algorithm for T2DM Nathan DM, et al. Diabetes Care & Diabetologia January 2009.Tier 1: well-validated therapies Lifestyle + Metformin Lifestyle + Metformin At diagnosis: Insulin + Basal insulin + Intensive insulin Lifestyle + Metformin Lifestyle + Metformin + Sulfonylureas STEP 1 STEP 2 STEP 3Tier 2: Less well validated therapies Lifestyle + Metformin + Pioglitazone Lifestyle + metformin No hypoglycaemia + Pioglitazone Oedema/CHF Bone loss + Sulfonylurea Lifestyle + metformin Lifestyle + metformin + GLP-1 agonist + Pioglitazone No hypoglycaemia Weight loss + Basal insulin Nausea/vomiting
  • 11. * * Liraglutide approved in EUMazze, Strock, Simonson, Kendall, Cuddihy, Bergenstal. SDM Quick Guide 5th Edition, International Diabetes Center, 2009
  • 12. Scientific Foundation for InsulinTherapy in Type 2 Diabetes Why is insulin needed? To achieve glycemic targets When is insulin needed? Earlier in the treatment plan Is insulin therapy effective? Is insulin therapy safe?
  • 13. Type 2 Diabetes Master DecisionPath METFORMIN Titrate to clinically effective dose Advance if not at target in 3 months TWO DRUG THERAPY Add SU Add DPP4-I Add GLP-1 Agonist Add TZD THREE DRUG THERAPY Add Background Insulin Add Background Insulin or Add Background Insulin or TZD, DPP-4, GLP1 Or TZD, SU SU, DPP-4, GLP1A1C >11%FPG >300 mg/dL Titrate to clinically effective dose Advance if not at target in 3 monthsRPG >350 mg/dL Start Insulin (Multi-Dose MULTI-DOSE INSULIN THERAPY Insulin therapy preferred) Background & Mealtime Premixed Insulin (main meal) + Oral Agent(s)* + Sensitizers* 2 meals Background & Mealtime (all meals) + Sensitizers* * Limited published data for use of insulin plus either DPP-4 inhibitor or GLP-1 agonist Mazze, Strock, Simonson, Kendall, Cuddihy, Bergenstal. SDM Quick Guide 5th Edition, International Diabetes Center, 2009
  • 14. Relative contributions of postprandial glucose and FPG to A1C 100 80 60 Contribution (%) 40 20 0 <7.3 7.3–8.4 8.5–9.2 9.3–10.2 >10.2 A1C quintiles (%) Fasting plasma glucose Postprandial plasma glucose Monnier L et al. Diabetes Care. 2003;26:881-5.
  • 15. Plasma Glucose Normally Maintainedin Narrow Range Diabetes 400 No diabetes Plasma Glucose (mg/dL) control 300 200 Fix fasting first 100 0 6 AM 10 AM 2 PM 6 PM 10 PM 2 AM Time of Day Adapted from Polonsky KS, et al. N Engl J Med. 1988;318:1231-1239.
  • 16. Plasma Glucose Normally Maintainedin Narrow Range Diabetes 400 No diabetes Plasma Glucose (mg/dL) control 300 200 Fix fasting first 100 0 6 AM 10 AM 2 PM 6 PM 10 PM 2 AM Time of Day Adapted from Polonsky KS, et al. N Engl J Med. 1988;318:1231-1239.
  • 17. Insulin Glargine vs. NPH in Treat-to- Target Trial: HbA1c and Hypoglycemia Randomized to NPH or Glargine + OAD with target HbA1c <7% 16 21% risk reduction Events per patient per year p <0.02 9.0 14 NPH + OAD Insulin glargine + OAD 12 8.5 10HbA1c (%) 8.0 42% risk 8 reduction p <0.01 7.5 6 7.0 4 6.5 2 0 0 4 8 12 16 20 24 Overall Nocturnal Weeks Hypoglycemia Riddle et al. Diabetes Care 2003;26:3080-6.
  • 18. Insulin Detemir vs. NPH in Treat-to-Target Trial: HbA1c and Hypoglycemia 18 9.0 16 Events per patient per year NPH + OAD Insulin detemir + OAD 14 47% risk reduction 8.5 p < 0.001 12HbA1c (%) 8.0 10 7.5 8 7.0 6 55% risk reduction 6.5 4 p < 0.001 2 -2 0 12 24 0 Weeks Overall Nocturnal Hermansen et al. Diabetes Care 29:1269, 2006 Hypoglycaemia
  • 19. Using Insulin Effectively Physiologic Insulin Replacement Sensitizers Sulfonylurea / GLP-1 A / DPP-4 I 50 Long-ActingInsulin Levels 40 30 20 10 Long-acting 0 0 2 4 6 8 10 12 14 16 18 20 22 24 Time of Day Adapted from Polonsky. N Engl J Med. 1996;334:777-783. Kendall DM. N Engl J Med 322: 898-903, 1990.
  • 20. Using Insulin Effectively Physiologic Insulin Replacement Sensitizers Sulfonylurea / GLP-1 A / DPP-4 I 50 Long-ActingInsulin Levels 40 30 20 10 Long-acting 0 0 2 4 6 8 10 12 14 16 18 20 22 24 Time of Day Adapted from Polonsky. N Engl J Med. 1996;334:777-783. Kendall DM. N Engl J Med 322: 898-903, 1990.
  • 21. 24-Hour Plasma Glucose CurveNormal and People with Type 2 Diabetes Fix Fasting First 400 300 Glucose (mg/dL) 200 100 Meal Meal Meal Normal 0 0600 1000 1400 1800 2200 0200 0600 Time of Day Adapted from Polonsky et al, N Engl J Med 1988.
  • 22. 24-Hour Plasma Glucose CurveNormal and People with Type 2 Diabetes Fix Fasting First 400 300 Glucose (mg/dL) 200 100 Meal Meal Meal Normal 0 0600 1000 1400 1800 2200 0200 0600 Time of Day Adapted from Polonsky et al, N Engl J Med 1988.
  • 23. Premixed Regimen with Rapid-actingInsulin Premixed: 75/25 with lispro, 70/30 with aspart, 50/50 with lispro
  • 24. Background / Mealtime (Basal / Bolus)Insulin Regimen Rapid-acting insulin at meals Long-acting insulin at bed
  • 25. Improvement in HbA1c with Basal – Bolus InsulinRegimen (Glargine / Glulisine) in Type 2 Diabetes Simple algorithm CHO counting The majority of patients achieved HbA1c <7.0% • Simple algorithm: 73.0% p = NS • CHO counting: 69.2% Bergenstal RM, Johnson M, Powers M et al. Diabetes Care 2008;31:1305–10.
  • 26. Scientific Foundation for InsulinTherapy in Type 2 Diabetes Why is insulin needed? To achieve glycemic targets When is insulin needed? Earlier in the treatment plan Yes – if regimen is Is insulin therapy effective? matched to patient’s glucose profile and lifestyle Is insulin therapy safe?
  • 27. Scientific Foundation for Insulin Therapy in Type 2 Diabetes Why is insulin needed? To achieve glycemic targets When is insulin needed? Earlier in the treatment plan Is insulin therapy effective? Yes – if regimen matched to patient’s glucose profile and lifestyle Is insulin therapy safe? Used effectively – the benefits of glycemic control out weight risks Weight Gain Minimize by lifestyle advice & matching glycemic profile Hypoglycemia Minimize by lifestyle advice & matching glycemic profile Cancer Not clear risk of exogenous insulin and cancer established – likely some increased risk of cancer with diabetes
  • 28. Starting and Adjusting Insulin inType 2 Diabetes
  • 29. Steps for Starting Insulin Therapyin Type 2 Diabetes 1. Set a target or goal for glucose control • HbA1c and self-monitored blood glucose 2. Use an algorithm to advance therapy Apply a consistent approach with timelines to reach goal 3. Determine the appropriate insulin regimen 4. Calculate the starting insulin dose 5. Educate patient and family
  • 30. Steps for Starting Insulin Therapyin Type 2 Diabetes 1. Set a target or goal for glucose control • HbA1c and self-monitored blood glucose 2. Use an algorithm to advance therapy Apply a consistent approach with timelines to reach goal 3. Determine the appropriate insulin regimen 4. Calculate the starting insulin dose 5. Educate patient and family
  • 31. Glycemic Targets for Type 2 Diabetes* IDF ADA IDC/SDM HbA1c <6.5% <7% <7% Fasting <100 mg/dL 90 -130 mg/dL 70-120 mg/dL and 5.5 mmol/l 6.0-7.2 mmol/l 3.9-6.7 mmol/l Premeal 2 hour <140 mg/dL <180 mg/dL <160 mg/dL Postmeal 7.8 mmol/l <10 mmol/l 8.9 mmol/l * non-pregnant adults Diabetes Care 33 Supp1, Jan 2010 Insulin BASICS 2nd ed 2008:p25, © International Diabetes Center
  • 32. Steps for Starting Insulin Therapyin Type 2 Diabetes 1. Set a target or goal for glucose control • HbA1c and self-monitored blood glucose 2. Use an algorithm to advance therapy Apply a consistent approach with timelines to reach goal 3. Determine the appropriate insulin regimen 4. Calculate the starting insulin dose 5. Educate patient and family
  • 33. Staged DiabetesManagement at IDC *Mazze, Strock, Simonson, Kendall, Cuddihy, Bergenstal. SDM Quick Guide 5th Edition, International Diabetes Center, 2009
  • 34. Steps for Starting Insulin Therapyin Type 2 Diabetes 1. Set a target or goal for glucose control • HbA1c and self-monitored blood glucose 2. Use an algorithm to advance therapy Apply a consistent approach with timelines to reach goal  Determine the appropriate insulin regimen  Calculate the starting insulin dose  Educate patient and family
  • 35. Preparing for Insulin in Type 2 DiabetesClinical IndicatorsInitiate insulin if: HbA1c above target for >3 months and on maximum effective dose of 2 or more glucose- lowering agents HbA1c >11% and/or symptomatic and blood glucose >300 mg/dL – If clinically stable and high intake of sweetened beverages (>36 oz or 3 cans/day), eliminate sweetened beverages and re-evaluate need for insulin in 1-2 weeks SDM Quick Guide 5th Edition, 2009 International Diabetes Center, Park Nicollet Institute
  • 36. Using Insulin Effectively Physiologic Insulin Replacement Meal Meal Meal 50 Mealtime (bolus) 40 insulin needs = 50% Insulin Levels 30 20 10 Basal (background) insulin needs = 50% 0 0 2 4 6 8 10 12 14 16 18 20 22 24 Time of DayAdapted from Polonsky. N Engl J Med. 1996;334:777-783.Kendall DM. N Engl J Med 322: 898-903, 1990.
  • 37. Insulin Time Action Curves Rapid-Acting: Lispro (Humalog®), Aspart (NovoLog®), Glulisine (Apidra®) Relative Insulin Effect Short-Acting: Regular (Humulin® R, Novolin® R) Intermediate: NPH (Humulin® N, Novolin® N) Long-Acting: Glargine (Lantus®) Detemir (Levemir®) 0 2 4 6 8 10 12 14 16 18 20 Time (Hours)Bergenstal, “Effective insulin therapy,” International Textbook of Diabetes Mellitusvol 1. 3rd ed, Chichester NY, John Wiley and Sons, Inc., 2004:995-1015.
  • 38. Selecting an Insulin Regimen Background Background and Premixed Insulin (Basal) Insulin Mealtime Insulin ± Sensitizer(s) + 2 Drugs ± Sensitizer(s)Glycemic  Elevated FPG  Elevated fasting  Elevated PPGFactors and/or post-meal  Increasing daytime BG  Stable daytime BG  HbA1c >11%  HbA1c >11%  Intensive controlPatient  Overwhelmed  More flexibility  Decreased dexterityFactors  Desire single injection  Erratic schedule or visual acuity  Regular schedule
  • 39. Case Study: Khalida  73 year-old woman  Glycemic factors Diabetes for 7 years Taking metformin 1000 BID; and 10 mg glyburide BID Current HbA1c 7.9% SMBG in morning and evening are high  Patient factors Very Fearful of injections
  • 40. Background (Basal) Insulin Options  Glargine (Lantus®) and Detemir (Levemir®) – No significant peak; lasts up to 24 hours – Twice daily dosing may be required – Decreases risk of nocturnal hypoglycemia  NPH (Humulin® N and Novolin® N) – Less expensive – Twice daily dosing requiredRiddle et al. Diabetes Care. 26:3080-3086; 2003Raskin et al Diabetes Care. 28:260-265; 2005
  • 41. Starting Background (Basal) Insulin HbA1c <9% HbA1c ≥9% Background Insulin 0.1 units/kg 0.2 units/kg Dose  Start with single dose of long-acting insulin (glargine or detemir) or intermediate-acting insulin (NPH) at bedtime if cost is a concern.  Maintain oral agents: 1-2 of them - SU, Metformin, (maybe TZD), NOTE: DPP-4 Inhibitors and/or GLP-1 mimetic with insulin is “off-label”
  • 42. Starting Background (Basal) Insulin Example: Khalida with HbA1c of 7.9% Determine weight in kg 222 100 Weight in lbs _____ ÷ 2.2 = _____ kg Calculate initial dose of background insulin 100 0.1 10 Weight in kg ______ x units/kg _____ = _____units AM Noon PM Bed Plan LA - 10
  • 43. Selecting an Insulin Regimen Background Background and Premixed Insulin (Basal) Insulin Mealtime Insulin + 2 Drugs ± Sensitizer(s) ± Sensitizer(s)Glycemic  Elevated FPG  Elevated fasting  Elevated PPGFactors  Stable daytime BG and/or post-meal  Increasing daytime BG HbA1c >11%  HbA1c >11%  Intensive controlPatient  Overwhelmed  More flexibility  Decreased dexterity  Desire single injection  Erratic schedule or visual acuityFactors  Regular schedule
  • 44. Premixed Insulin Human Insulin Begins to Works Stops Work Hardest Working 75/25 with Lispro Humalog Mix 75/25 50/50 with Lispro 5-15 min 1-2 hrs 10-16 hrs Humalog Mix 50/50 70/30 with Aspart NovoLog Mix 70/30 70/30 with Reg Humulin 70/30 30-45 min 4-8 / 2-3 hrs 10-16 hrs Novolin 70/30Based on package insert data
  • 45. Case Study: Saleem Ahmad 63-year-old Glycemic factors Came to the Emergency Room with a foot infection HbA1c 11.8% Patient factors Fatigued, thirsty, dehydrated, +family history of diabetes but surprised he got diabetes and he is scared
  • 46. Starting Premixed Insulin HbA1c < 9% HbA1c ≥ 9% Premixed 0.1 units/kg 0.2 units/kg Insulin Dose (2 times/day) (2 times/day) 0.2 units/kg 0.4 units/kg total total  Start with two doses; before breakfast and dinner  Consider adding insulin sensitizer (metformin) Guide to Starting and Adjusting Insulin for Types 2 Diabetes © 2008 International Diabetes Center, Park Nicollet
  • 47. Premixed regimen with rapid-actinginsulin Premixed: 75/25 with lispro, 70/30 with aspart, 50/50 with lispro © 2007 International Diabetes Center, Minneapolis, MN All rights reserved. .
  • 48. Selecting an Insulin Regimen Background Background and Premixed Insulin (Basal) Insulin Mealtime Insulin ± Sensitizer(s) + 2 Drugs ± Sensitizer(s)Glycemic  Elevated FPG  Elevated fasting  Elevated PPGFactors  Stable daytime BG and/or post-meal  Increasing daytime BG  HbA1c >11%  HbA1c >11%  Intensive controlPatient  Overwhelmed  More flexibility  Decreased dexterity  Desire single injection  Erratic schedule or visual acuityFactors  Regular schedule
  • 49. Case Study: A Qudoos 58 year old male Glycemic factors Diabetes for 14 years Sitagliptin/metformin (Janumet™) 50/1000 BID and 30 mg pioglitazone (Actos®) Current HbA1c 9.4%, elevated fasting and post-meal glucose Patient factors Eats healthy diet, exercises regularly Desire flexible schedule for work
  • 50. Starting Background (Basal) and Mealtime(Bolus) Insulin HbA1c <9% HbA1c ≥9% Background 0.1 units/kg 0.2 units/kg Insulin Dose (once daily) (once daily) Mealtime 0.1 units/kg 0.2 units/kg Insulin Dose (divided evenly (divided evenly between meals) between meals) Total Insulin 0.2 units/kg 0.4 units/kg Dose  Stop meal related therapy (Janumet™) and begin metformin 1000 mg BID.  Consider pros and cons of maintaining pioglitazone (Actos®).
  • 51. Background (Basal) and Mealtime (Bolus)Insulin Regimen RA = rapid-acting insulin: Lispro, aspart, glulisine Rapid-acting insulin at meals Long-acting insulin at bed
  • 52. Steps for Starting Insulin Therapyin Type 2 Diabetes 1. Set a target or goal for glucose control • HbA1c and self-monitored blood glucose 2. Use an algorithm to advance therapy Apply a consistent approach with timelines to reach goal  Determine the appropriate insulin regimen  Calculate the starting insulin dose  Educate patient and family
  • 53. Team Approach to Starting Insulin
  • 54. What Gets in the Way of Starting Insulin?Patient Concerns1. Injections (Shots) 4. Inconvenient2. Diabetes more 5. Sense of failure serious 6. Hypoglycemia3. Complicated Bergenstal Chapter 53, International Textbook of Diabetes Mellitus 3rd Edition, 2004 John Wiley & Sons and International Diabetes Center, unpublished survey data
  • 55. How does diabetes change over the years? Insulin Resistance Insulin Level Pre Diabetes Metabolic Syndrome Impaired Incretin Action -15 -10 -5 0 5 10 15 20 25 30 Years© From Let’ s Talk About Insulin 2008, © International Diabetes Center
  • 56. What Gets in the Way of Starting Insulin? Doctor Concerns 1. Complexity of starting and adjusting insulin 2. Not sure what it is like to take an insulin injection 3. Weight gain 4. Hypoglycemia 5. Other concerns? Bergenstal Chapter 53, International Textbook of Diabetes Mellitus 3rd Edition, 2004 John Wiley & Sons; Jeavons D et al. Postgrad Med J 2006; 82:347-350.
  • 57. Begin with a practice injection (saline) Can help to allay apprehension about injections Information that follows may be better heard You try it!
  • 58. Saline Injection Demonstration1. Remove cap from the end 2. Remove the needle cap 3. Pull back on plunger 4. Insert needle andof the syringe to the amount calculated push air into the vial (e.g. 10 units) 5. Pull back on the 6. To remove air bubbles, 7. Pull back on the plunger to plunger to measure the push plunger back in. measure the correct amount correct amount (e.g. 10 (e.g. 10 units). Remove needle units) from vial You are ready to give the injection
  • 59. Saline Injection Demonstration8. Hold the syringe 9. Administer the injection into 10. Throw away thein your hand as the abdomen. Remove needle used syringe inshown (like holding and cover area with your a sharps containera pen) finger for a few seconds. (do not re-cap)
  • 60. Important Education Topics for StartingInsulin Therapy  Diabetes overview  Insulin administration  Glucose monitoring  Simple eating guidelines  Hypoglycemia
  • 61. Examples of Insulin PensPre-filled (Disposable) FlexPen ® SoloStar (sanofi aventis) ®Re-usable (uses insulin cartridges) HumaPen ® NovoPen® 4
  • 62. Sites for Insulin Administration Abdomen preferred Insulin BASICS 2 nd ed 2008:p19, © International Diabetes Center
  • 63. Insulin storageCheck package insert for specific instructions  Keep unopened insulin in refrigerator or cool temperature  Insulin in use can be stored at room temperature Range is from 10 days to 42 days depending on insulin Check package insert for specific instructions  Keep above freezing and below 86°F ( 30°C) Insulin BASICS 2 nd ed 2008:p110, © International Diabetes Center
  • 64. Important Education Topics for StartingInsulin Therapy  Diabetes overview  Insulin administration  Glucose monitoring  Simple eating guidelines  Hypoglycemia
  • 65. Blood Glucose Monitoring  To improve clinical decision-making  To evaluate efficacy of the therapy  To pin point problems  To support adherence to regimen  Feedback for the patient
  • 66. Glycemic Targets for Type 2 Diabetes* IDF ADA IDC HbA1c <6.5% <7% <7.0% Fasting <100 mg/dL 70 -130 mg/dL 70-120 mg/dL and 5.5 mmol/l 3.9-7.2 mmol/l 3.9-6.7 mmol/l Premeal 2 hour <140 mg/dL <180 mg/dL <160 mg/dL Postmeal 7.8 mmol/l <10 mmol/l 8.9 mmol/l * non-pregnant adults Diabetes Care 29(8), Aug 2006 Diabetes Care 32 Supp1, Jan 2009 Insulin BASICS 2 nd ed 2008:p25, © International Diabetes Center
  • 67. Ideal Testing FrequencyPatients Taking Insulin Minimum four times/day recommended Glucose testing: – Before each meal and before bedtime – Consider pre-meal and 30-90 minutes post meal to evaluate effect of insulin on post-meal glucose Modify frequency of monitoring if necessary Encourage patients to record values in a record book Use meter with a memory for verified data Modify based on individual patient circumstances; vary the times of testing to build a profile
  • 68. Important Education Topics for StartingInsulin Therapy  Diabetes overview  Insulin administration  Glucose monitoring  Simple eating guidelines  Hypoglycemia 2009 International Diabetes Center
  • 69. Quick Start: Healthy Eating Guidelines 1. Eat 3 meals per day 2. Choose a variety of foods  Small to moderately sized  Eat fewer or smaller portions of portions sweetened foods or beverages  Similar portions from day to (soft drinks, juices, day at a given meal time desserts, candy)  Consistent meal times  Include carbohydrate at each (initially for all insulin meal regimens)  Avoid alcohol for now  Include small snacks, if  Choose healthy foods when desired possible  Replace, reduce, restrictInsulin BASICS 2 nd ed 2008:p34, © International Diabetes Center
  • 70. Important Education Topics for StartingInsulin Therapy  Diabetes overview  Insulin administration  Glucose monitoring  Simple eating guidelines  Hypoglycemia
  • 71. Hypoglycemia Common Symptoms  Weak, shaky, lightheaded BG  Sweaty, clammy  Irritability  Tingling or numb lips Below  Confusion  Hungry 70 mg/dL(3.9 mmol/L) Insulin BASICS 2 nd ed 2008:p30, © International Diabetes Center
  • 72. Treatment of Hypoglycemia(Routine 15) Test blood glucose if possible Treat with 15 gm carbohydrate if <70 mg/dL (3.8 mol/L) – 3-4 glucose tablets or 1/2 cup juice or soda pop – ↑ BG ~50-60 mg/dL (3 mmol/L) – Have carbohydrate readily available – Avoid high-fat carbohydrates (slower absorption) Wait 15 minutes Test and treat again if glucose below target Insulin BASICS 2 nd edition 2008: p 31, © International Diabetes Center
  • 73. Treatment of Severe HypoglycemiaRequires assistance to treatNote: Severe hypoglycemia is rare in type 2 diabetesUnable to swallow safelyNeeds injection of glucagon – Hormone that releases stored glycogen (glucose) – Given intramuscular or subcutaneous – Standard dose: 1.0 mg adults; 0.5 mg for childrenPrecautions – May cause nausea/vomiting/headache – Increase fluids following injectionCall for emergency assistance Insulin BASICS 2 nd edition 2008: p 77, © International Diabetes Center
  • 74. Hypoglycemia Prevention  Follow food/insulin plan  Test BG daily  Be prepared and carry carbohydrate  Keep records  Wear medical ID  Inform family, friends, co-workers how to recognize and treat lows  Inform doctor of low glucose patterns  Check BG before driving Insulin BASICS 2 nd edition 2008, © International Diabetes Center
  • 75. Steps for Starting Insulin Therapy inType 2 Diabetes 1. Set a target or goal for glucose control HbA1c and self-monitored blood glucose 2. Use an algorithm to advance therapy Apply a consistent approach with timelines to reach goal 3. Determine the appropriate insulin regimen 4. Calculate the starting insulin dose 5. Educate patient and family
  • 76. Fine-Tuning Glycemic Control
  • 77. Overview  Nutrition Messages  Insulin Adjustments  Glucose Data  Treating Hypoglycemia
  • 78. Nutrition Messages Insulin Meals Snacks Regimen Background Control carbohydrate Not needed 3-4 carb choice*/meal Pre-Mixed Eat at consistent times May be needed with consistent carb depending on schedule & insulin Background Start with consistent Not needed and Mealtime carb if snack is eaten, add RA insulin to cover *One carb choice = 15 grams of carbohydrate
  • 79. Titrating Insulin for Background RegimenIf most AM fasting BG Titrate until fasting glucose at>120 mg/dL target BGIf most AM fasting BG Test pre dinner and bedtime (or 2-<120 mg/dL and HbA1c hour post dinner) and considerremains above target need for mealtime insulin Guide to Starting and Adjusting Insulin for Types 2 Diabetes © 2008 International Diabetes Center, Park Nicollet
  • 80. Titration Guide (Table 6)If most BG <200 mg/dL<70 mg/dL Decrease by 1-3 units70-120 mg/dL No change121-200 mg/dL Increase by 1-3 units>200 mg/dL Increase by 3-5 units or 10% SDM Quick Guide, 2009, IDC Guide to Starting and Adjusting Insulin for Types 2 Diabetes © 2008 International Diabetes Center, Park Nicollet
  • 81. What adjustments would youmake for Khalida? Pre- Ins- Post Pre Ins- Pt Pre- Ins Post HS Bkfst Med Med Din Mon 155 Met. 121 Met. 148 10 1000 1000 LA Glyb. Glyb. 10 10 Tue 163 142 199 10 LA Wed 143 112 143 10 LA Thur 133 96 116 12 LA Started at 0.1 units/kg x 100 kg (220#) =10 units
  • 82. After Insulin Adjustment Pre- Ins- Post Pre Ins- Pt Pre- Ins Post HS Bkfst Med Med DinMon 137 Met. 111 Met. 147 12 1000 1000 LA Glyb. Glyb. 10 10Tue 140 125 165 12 LAWed 122 102 137 12 LAThur 148 114 156 ?
  • 83. Titrating Insulin for Background RegimenIf most AM fasting BG Titrate until fasting glucose at>120 mg/dL target BG If dose reaches 0.5-0.7 units/kg body weight, consider adding mealtime insulinIf most AM fasting BG Test pre dinner and bedtime (or 2-<120 mg/dL and HbA1c hour post dinner) and considerremains above target need for mealtime insulin Guide to Starting and Adjusting Insulin for Types 2 Diabetes © 2008 International Diabetes Center, Park Nicollet
  • 84. Step-wise Transition from Backgroundto Background & Mealtime Regimen Start with single injection rapid-acting insulin before largest meal (most carb. choices) – 0.1 units/kg rapid-acting (RA) insulin Subtract 0.1 units/kg from background insulin dose Consider maintaining oral agents Example 100 kg patient on 60 units background insulinNew dose: 100 kg x 0.1 units/kg = 10 units RA before largest meal 60 units – (0.1 units/kg) = 50 units background insulin Staged Diabetes Management Quick Guide © 2007 International Diabetes Center, Park Nicollet
  • 85. Titrating Insulin for Premixed RegimenIf most BG >200 mg/dL Increase total insulin by 0.1 units/kg Distribute equally between dosesIf most BG <200 mg/dL Use titration guide to adjust AM FBG: adjust pre-dinner insulin dose Pre-dinner: adjust pre-breakfast insulin
  • 86. How would you adjust Saleem Ahmad dose of Mix 75/25? Pre- Ins Post Pre Ins Post Pre- Ins Post HS Bkfst DinMon 265 19 201 19 236Tue 244 19 198 19 254Wed 254 19 205 19 215Thur 195 24 206 227 24 Started at 0.2 units/kg x 95 kg (209#) = 19 units AM and PM 0.1 units/kg x 95 kg (209#) = 9.5 units
  • 87. After Insulin Adjustment Pre- Ins Post Pre Ins Post Pre- Ins Post HS Bkfst DinMon 184 24 162 24 210Tue 193 24 182 24 219Wed 174 24 158 24 183Thur 160 26 155 26 194 Use titration guide to adjust
  • 88. Titrating Insulin for Background &Mealtime RegimenIf most BG >200 mg/dL Increase total insulin by 0.1 units/kg Add half to background Distribute remaining half between mealtime dosesIf most BG <200 mg/dL Use titration guide to adjust AM FBG: adjust background Pre-lunch/dinner: adjust previous mealtime insulin If more than 40 mg/dL pre- to 2 hr. postmeal rise, increase RA 1-3 units
  • 89. What adjustment would you make to A. Qudoos insulin doses? Pre- Ins Post Pre Ins Post Pre- Ins Post HS Bkfst DinMon 133 5 244 5 115 6 156 16 RA RA RA LATue 125 5 201 5 124 6 170 16 RA RA RA LAWed 114 5 199 5 117 6 187 16 RA LA RA RAThur 139 7 5 8 16 RA RA RA LA Started at 0.2 units/kg x 80 kg (176#) = 16 units LA and 16 units RA divided between 3 meals
  • 90. After Insulin Adjustment 3 carbs for breakfast - 2 carbs for lunch 4 carbs for dinner Pre- Ins Post Pre Ins Post Pre- Ins Post HS Bkfst DinMon 105 7 142 5 RA 78 72 8 RA 139 16 RA LATue 112 7 151 5 RA 85 70 8 RA 125 16 LA RAWed 98 7 125 5 66 69 8 RA 98 16 LA RA RAThur 110 132 74 65 112 7 5 8 16 RA RA RA LA
  • 91. Starting vs. Final Insulin Dose Typical Regimen Starting Dose Common Patient (units) Final Dose(Type 2 DM) (units) Background 0.2 units/kg 0.5-0.7 units/kg Insulin (20 units) (50-70 units) Premixed 0.2 units/kg BID 1.0-1.2 units/kg Insulin (40 units total) (100-120 units) 220 lbs (100 kg) Background & 0.2 units/kg background 1.0-1.2 units/kgHbA1c 9% Mealtime 0.2 units/kg mealtime (100-120 units) Insulin (40 units total)Average dose for type 1 diabetes is 0.7 units/kg
  • 92. Follow-up and Summary Recommended follow-up – Every 1-2 weeks while adjusting dose – Every 3 months once dose established Have patient monitor BG more extensively 1-2 weeks prior to visit to have recent data for adjusting Use a team approach when starting insulin Consider enabling patients to make adjustments to their insulin regimen
  • 93. Case Studies