Intensifying Insulin In Type 2 Diabetes
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1 Intensifying Insulin In Type 2 Diabetes Eric L. Johnson, M.D. Associate Professor Department of Family and Community Medicine University of North Dakota School of Medicine and Health Sciences Assistant Medical Director Altru Diabetes Center Grand Forks, North Dakota
2
3 Objectives Review use of current guideline based diabetes medication management Assess patients with type 2 diabetes requiring more intensive glycemic management Describe the use of intensive insulin management in appropriate patients in a clinical setting
4 ADA/EASD Type 2 Medication Guideline April 2012
5 Intensifying Insulin Management in Type 2 Diabetes
6 Role of Basal Insulin in Type 2 Diabetes Beta-cell function declines as Type 2 diabetes progresses 100 Beta-cell function (%) IGT Postprandial 25 Type 2 Diabetes Hyperglycemia Diagnosis Beta-cell decline exceeds 50% by time of diagnosis Insulin initiation Years from diagnosis Lebovitz H. Diabetes Rev 1999;7:
7 Long-Acting Insulin Detemir (Levemir) Glargine (Lantus) (Human NPH (N) ) Taken 1 or 2 times daily Basal insulin
8 Rapid Acting Insulin Aspart (Novolog) Lispro (Humalog) Glulisine (Apidra) (Human Regular) Taken with meals and snacks Bolus insulin
9 Basal Insulin in Type 2 Diabetes Glargine (Lantus), Detemir (Levemir) (NPH) Good, potent add-on for improved A1C Second line agent for some patients A1C >9, diabetes longer than 5 to 7 years
10 What do we do when basal insulin + other meds aren t enough? Practical Clinical Approaches
11 Recall Insulin Types Basal (long acting) insulin often given once daily (sometimes twice daily) Bolus (rapid acting) insulin often given with meals and maybe snacks
12 Adding Bolus Insulin for Meals in Type 2 Diabetes Lispro (Humalog) Aspart (Novolog) Glulisine (Apidra) Why might bolus insulin be important in some Type 2 patients?
13 Contribution (%) Fasting and Postprandial Glycemic Excursions as a Function of A1C 80 Postprandial hyperglycemia Fasting hyperglycemia (<7.3) 2 ( ) 3 ( ) 4 ( ) 5 (>10.2) Monnier L et al. Diabetes Care. 2003;26: A1C (%) Quintiles
14 3 Ways to Intensify Insulin In Type 2 Diabetes Simple: 90/10: 2 injection program 1 basal, 1 bolus (w/biggest meal) Advanced: Non-Carb Counting 1 basal, 3 boluses estimated dosing based on meal size Sophisticated: Carb-counting 1 basal, 3 boluses (+ maybe snack boluses) calculated on carb intake
15 Moving Toward Multiple Daily Injections (MDI) As type 2 patients take larger doses of basal insulin, temptation is to split basal dose and give BID If going to 2 injection program, better to keep basal once daily and add a rapid acting insulin injection with largest meal (90/10 rule)
16 Insulin Effect Basal/Bolus Injection 2 injection program Rapid (Lispro,Glulisine, Aspart) Long (Detemir,Glargine) Hours adapted from R. Bergenstal, IDC
17 Initiate 2 Injection Program 90/10 rule (90% basal, 10% bolus) for 2 injection regimen Start with largest meal of the day Often stop TZD, always stop SU, need to consider dosing of other meds
18 90/10 Rule For Initiating MDI For example: Patient on 50 units of basal (long acting) (Glargine or Detemir) Want to add bolus (rapid acting) (aspart, lispro, glulisine) with largest meal of the day
19 90/10 Rule Reduce basal insulin by 10% to 45 units Add that 5 units of bolus insulin to largest meal 45 units basal (glargine or detemir) 5 units bolus(aspart, lispro, glulisine)
20 Basal/Bolus Insulin Multiple Daily Injections (MDI) Many patients will accept a 2 injections program as first step in advancing to MDI (90/10 rule) Many patients will resist going from a 1 injection daily regimen to a 4 injections daily regimen (Basal + mealtime insulin) Eventually some will need 4 injections daily
21 Basal/Bolus Insulin Multiple Daily Injections (MDI) Basal (long acting)insulin daily + bolus (rapid acting) insulin with each meal 2 strategies: 1) Non-carb counting Simple 2) Carb counting Calculated dose based on carb intake Diabetes Care July :
22 Insulin Effect Basal/Bolus Injection Rapid (Lispro,Glulisine, Aspart) Hours Long (Detemir,Glargine) adapted from R. Bergenstal, IDC
23 Basal/Bolus Insulin in Type 2 Diabetes: Non-Carb Counting
24 Non-Carb Counting Fixed dose of basal (long acting) insulin Mealtime bolus (rapid acting) insulin is split evenly per meals or estimated roughly on meal size
25 Basal/Bolus Non-Carb Counting Of total daily dose, ~50% basal (long acting) insulin ~50% bolus (rapid acting) insulin
26 Basal/Bolus Non-carb Counting Adding Bolus (rapid acting) Insulin: First, consider reducing basal (long acting) (glargine or detemir) by 50% at initiation of bolus insulin
27 Basal/Bolus Insulin Add mealtime rapid acting insulin (bolus) (aspart,lispro,glulisine) which will be the other 50% of total daily dose So, 50% of total daily dose will be basal, and 50% of total daily dose will be bolus
28 Basal/Bolus Insulin Example: Patient currently on 50 units of glargine or detemir once daily -cut glargine or detemir by 50% So, down to 25 units daily Then, calculate bolus insulin..
29 Basal/Bolus Insulin Add mealtime bolus (rapid acting) insulin -25 total units daily (bolus- 50% of total daily insulin dose) Can split up into 3 equal doses with meals - 8 units/meal Or.
30 Basal/Bolus Insulin Split up bolus (rapid acting) insulin based roughly on meal size: ~50% with largest meal 13 units ~33% with next largest meal 8 units ~17% with smallest meal 4 units
31 Basal/Bolus Insulin Non-carb counting So, our patient finishes this consult with: Basal (long acting) (~50% of daily total) 25 units once daily Bolus (rapid acting) 8 units with each meal (~50% of daily total) Or split up by approx meal size: 13 units large meal 8 units medium meal 4 units small meal
32 Basal/Bolus Insulin in Type 2 Diabetes: Carb Counting
33 Basal/Bolus Insulin Carb-Counting Reduce basal (long acting) 30-40% when starting bolus (rapid acting) insulin Bolus (rapid acting) ~2u/15 gram carb Correction (sensitivity factor) ~1 u to drop blood sugar 30 points Need to know pre-meal blood sugar
34 Calculating Bolus (rapid acting) with Carb Counting and Correction Example: Blood sugar pre-meal was 200, target gram carb meal= 2u/15gram= 8 units Correction insulin 1u/30pts=3 units (90pts) Meal (carb) 8 units + correction 3 units= 11 units for this meal
35 Case Study
36 Case Study 54 y/o white male Diagnosed with type 2 diabetes after 2 fasting blood sugars of 154 and 142 and A1C of 6.8% Also has high blood pressure and cholesterol disease (common in type 2)
37 Case Study Metformin 500 mg prescribed twice daily, titrated to 1000mg BID ASA 81 mg daily Lisinopril 10 mg daily Simvistatin 40 mg daily Fish Oil 1000mg BID
38 Case Study Referred to Diabetes Educator and Dietician Recommend developing graduated exercise plan (exercise prescription) Six months after diagnosis, A1C = 6.8% (target <7%)
39 Case Study Three years later, patient s A1C has risen to 8.4% (target <7%) Blood pressure and cholesterol effectively treated Now what?
40 Case Study Choices include Adding a basal insulin once daily Adding any other oral agent Adding exenatide twice daily (or weekly) or liraglutide once daily Any of these are good choices Choice may be made on individual factors
41 Case Study Patient chose additional oral agent (sitagliptin), but others would be OK A1C: 6 months later = 7.4% (target <7%) 3 years later = 8.1% (target <7%) Now what?
42 Case Study Sitgliptin, metformin continued Basal insulin started with titration Eventually added bolus insulin with largest meal (90/10 rule) Likely will add bolus with other meals over time- non-carb counting strategy or carb counting strategy
43 3 Ways to Intensify Insulin In Type 2 Diabetes Simple: 90/10: 2 injection program 1 basal, 1 bolus (w/biggest meal) Advanced: Non-Carb Counting 1 basal, 3 boluses equal split or estimate based on meal size Sophisticated: Carb-counting 1 basal, 3 boluses (+ maybe snack boluses) calculated on carb intake+ glucose value
44 Premix 70/30, 75/25, 50/50 Other Insulins Combine R or rapid acting with NPH or an NPH-like component Certain applications may be appropriate 1, 2, or 3 times daily Limitation: change 2 insulins at once U-500 Sometimes in severe insulin resistance
45 Severely Insulin Resistant units total daily dose Obesity Lipodystrophies Genetic Syndromes Garg NEJM 2004 Semple et al Clin Endocrinol. 2010
46 Severely Insulin Resistant Consider occult infections (UTI, abcess, sinus, etc) Consider other inflammatory conditions (periodontal disease, etc)
47 Options: U-500 Severely Insulin Resistant Add Symlin Add GLP-1 Change/add insulin sensitizing agents Bariatric Surgery Sometimes pump- better absorption, maybe lower daily dose Some new insulins may be U-200
48 Pumps and Sensors: Considerations in Type 2 Diabetes for Intensification of Insulin Management
49 Pumps and Sensors Pump: Continuous Subcutaneous Insulin Infusion (CSII) Sensor: Continuous Glucose Monitoring System (CGMS)
50 Pumps-Basic Components
51 Animas
52 Omnipod pump with remote Not shown- patch pumps Investigational Navigator CGMS
53 Medtronic Minimed
54 Pumps and Sensors Interfaced devices developed last 3 to 4 years Still not closed loop Patient gets info, has to act on it High/low alarms, trends alarm (more rapid rise or decline)
55 Logbook Data
56 Basal/Bolus Insulin With injections: 2 different insulins Long-acting insulin basal Rapid-acting insulin bolus With pump: Only use rapid acting insulin Some delivered continuously basal Some delivered as bolus
57 Insulin Effect Basal/Bolus Injection Rapid (Lispro,Glulisine, Aspart) Hours Long (Detemir,Glargine) adapted from R. Bergenstal, IDC
58 Insulin Needs Basal / Bolus Therapy Insulin Pump Bolus Insulin Basal Insulin -Variable basals (not fixed) -Bolus-Immediate, Square, Dual Wave Time of Day
59 Advanced Features Dual wave/square wave insulin delivery Variable basal/temporary basal rates Neither of these can be replicated with injections To get full benefit, should be using these features
60 Pump/Sensors in Type 2 Diabetes Younger patients typically Technologically savvy Like type 1, those requiring more intensive management, not meeting goals on MDI
61 Wrap It Up Dr. J.. Home of the Chicago Cubs
62 Typical Type 2 Timeline Metformin at diagnosis or soon after Add something else Consider insulin if: -Duration >5-7 years -A1C>9 Multiple daily injections (or pump?) for appropriate type 2 patients
63 Review For many patients, a simple basal insulin or basal insulin + 1 bolus is a good fit For some select patients, basal insulin + multiple daily bolus or a pump may be a good fit Choice depends on individual factors and resources
64 Summary Diabetes is common Consider individual factors and goals Lots of choices, but nearly all will need insulin eventually, many will be good with basal + other meds, maybe MDI or pump
65 Acknowledgements Silvio Inzucchi, M.D. Yale University School of Medicine American Diabetes Association Primary Care Committee M. Sue Kirkman, M.D. American Diabetes Association James Brosseau, M.D., M.P.H. Altru Diabetes Center William Zaks, M.D., Ph.D., Altru Diabetes Center Altru Diabetes Center Team Melissa Gardner, Department of Family and Community Medicine, UNDSMHS
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