1. Inpatient Diabetes Treatment Goals, Strategies, Safety Amish A. Dangodara, MD, FACP Professor of Medicine Internal Medicine, Hospitalist Program University of California, Irvine School of Medicine 7.18.14

2. Disclosures None

3. Case Ms Dianne Beades is a 63 yo F admitted with (L) foot ulcer/cellulitis, not responding to outpatient Abx. Weight 100 Kg. She is NPO for LE angiogram. PMHx: PVD s/p (L) distal tibial artery bypass, DM II, CRI Meds: 70/30 insulin 70 units in AM, 30 units in PM, Metformin 1000 mg BID (takes after breakfast & bedtime) Labs: HgbA1c=11.4, glucose 325, BUN 20, creatinine 1.8 What is basal insulin [choose single best answer]? A.The NPH component of 70/30 insulin B.The NPH component of 70/30 insulin PM dose only C.Lantus insulin equivalent of NPH component of 70/30 insulin D.Amount of insulin required for fasting state E.The amount of insulin to which sliding scale is added Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

4. Case Ms Dianne Beades is a 63 yo F admitted with (L) foot ulcer/cellulitis, not responding to outpatient Abx. Weight 100 Kg. She is NPO for LE angiogram. PMHx: PVD s/p (L) distal tibial artery bypass, DM II, CRI Meds: 70/30 insulin 70 units in AM, 30 units in PM, Metformin 1000 mg BID (takes after breakfast & bedtime) Labs: HgbA1c=11.4, glucose 325, BUN 20, creatinine 1.8 In addition to holding Metformin, what should you do with insulin? A.Hold 70/30 and start sliding regular insulin scale q4h B.Reduce 70/30 to 35 units in AM and 15 units in PM C.Change 70/30 to Lantus 20 units/d & use corrective insulin scale q6h D.Change 70/30 to Lantus 50 units/d & use corrective insulin scale q6h E.Change to NPH 24 AM + 10PM & use corrective insulin scale q6h Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

5. Home Insulin Treatment Strategy Consolidated insulin:  Schedule AC breakfast and dinner with combined long & short-acting insulin with 2/3 total daily dose in AM and 1/3 total daily dose in PM :  Split NPH/Regular in any ratio and give mixed simultaneously  70/30 NPH/Regular  75/25 NPH/Regular  50/50 NPH/Regular Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program For consolidated strategy, 50% NPH estimates basal dose BLDHSB Reg NPH Insulin Effect Meals NPH Reg NPH treats both basal AND nutritional needs

6. Inpatient Diabetes Treatment Consolidated insulin: Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program Consolidated Insulin BreakfastLunchDinner 21:0018:0012:008:00 Time Glucose BD Reg NPH

7. Inpatient Diabetes Treatment Basal-Bolus insulin (Glargine): Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program Umpierrez GE et al. [RABBIT-2 Trial] Diabetes Care 2007;30:2181-2186. Basal insulin for fasting & nutritional insulin for meals BreakfastLunchDinner Glucose Time 18:0012:008:0021:00 Nutritional Insulin Analog Long-acting Basal Insulin

8. Inpatient Diabetes Treatment Basal-Bolus insulin compared to Consolidated insulin: Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program Basal-Bolus versus Consolidated 21:0018:00 BreakfastLunchDinner 12:008:00 Time Basal Insulin Glucose Nutritional Insulin Analog Long-acting Reg NPH

9. Inpatient Diabetes Treatment Basal-Bolus Insulin (NPH):  Dose NPH q8-12h depending on GFR = 50% TDD  Analog insulin qAC for meals = 50% TDD Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program B LDHSB Insulin Effect Meals NPH Analog

10. Match Home Treatment Strategy to Basal Home Treatment 1.Consolidated 70/30 insulin BID dosing 2.Nighttime NPH basal insulin and oral drugs 3.Basal-bolus insulin with long and short acting insulins 4.Long-acting basal insulin and oral drugs Basal Insulin A.Same dose of long-acting insulin as home dose B.Half dose of home long- acting insulin C.None of the above Basal dosing has to do with insulin STRATEGY, not the type of insulin! Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

11. What’s Wrong With Sliding Scale Alone? In addition to holding Metformin, what should you do with insulin? A.Hold 70/30 and start sliding regular insulin scale q4h Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program GlucoseUnits 180 - 2002 201 - 2504 251 - 3006 301 - 3508 351 - 40010 >40012 Corrective Insulin Dose 185 223 264 241 2 4 6 ? Time q4 h Insulin Level

12. What’s Wrong With Using Home Dose To Estimate Basal Dose? Medication: 70/30 insulin 70 units in AM, 30 units in PM In addition to holding Metformin, what should you do with insulin? A.Hold 70/30 and start sliding regular insulin scale q4h B.Reduce 70/30 to 35 units in AM and 15 units in PM C.Change 70/30 to Lantus 20 units/d & use corrective insulin scale q6h D.Change 70/30 to Lantus 50 units/d & use corrective insulin scale q6h E.Change to NPH 24 AM + 10PM & use corrective insulin scale q6h Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program HomeHospital

13. Glucose Regulation Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program 1 2 3 4 1 2 2 3

14. Normal Glucose Response to Meal Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

15. Normal Pancreas Response to Meal Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

16. Diabetes, Type II Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program NGT - normal glucose tolerance T2DM - Type 2 Diabetes Mellitus

17. Insulin Strategy: Goal Glucose = 140-180 Hypoglycemia Cortisol, Epinepherine, Glucagon, Glycogenolysis 180 126 80 0 Fasting Euglycemia Nutrition, Glycogenolysis, Insulin Post-prandial Hyperglycemia Insulin, GLP, Incretins Severe Hyperglycemia Insulin resistance or DM Basal Insulin Nutritional Insulin Corrective Insulin Hypoglycemia Tx Sliding Scale Insulin

18. Basal-Bolus (Basal-Nutritional) Strategy  D/C all home diabetic therapy  Estimate initial Total Daily Dose (TDD):  TDD = Weight (Kg) x 0.3 units/d for DM I  TDD = Weight (Kg) x 0.4 units/d for controlled DM II (FBS<200)  TDD = Weight (Kg) x 0.5 units/d for uncontrolled DM II  Correct for renal clearance (adjusted TDD):  GFR >50%, no change in TDD  GFR 30 - 50%, reduce initial estimated TDD by 20-30%  GFR <30%, reduce initial estimated TDD by 30-50%  Basal-Bolus (Nutritional) dosing:  Basal dose = 50% adjusted TDD (not needed if endogenous insulin ok)  Nutritional dose = 50% adjusted TDD  Bolus dose per meal = (Nutritional Dose)/(meals/d) Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

19. Basal-Bolus (Basal-Nutritional) Strategy Adjust dose after 24 hours:  If zero events of hypoglycemia in past 24h and glucose >180:  Increase adjusted TDD by 20%  If one or more events hypoglycemia in past 24h:  Decrease adjusted TDD by 20% and consider holding nutritional insulin  Evaluate nutrition intake  Assess for nutrition-insulin mismatch  Assess for improving insulin resistance as acute illness improves  Assess for worsening renal function Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

20. Inpatient Diabetes Treatment Corrective insulin sliding scale:  Schedule qAC & qHS if eating or q4 hrs if NPO or q6 hrs if NPO with GFR < 30 using short-acting insulin: aspart, glulisine, humalog, regular Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program Insulin sensitive/Type 1: Glucose at treatment goal = 0 units Glucose >goal - 180 = 2U 181 - 220 = 4 units 221 - 260 = 6 units 261 - 300 = 8 units 301 - 350 = 10 units 351 - 400 = 12 units >400 = 14 units Usual treatment/Type 2: Glucose at treatment goal = 0 units Glucose >goal - 180 = 4U 181 - 220 = 6 units 221 - 260 = 8 units 261 - 300 = 10 units 301 - 350 = 12 units 351 - 400 = 14 units >400 = 16 units Insulin resistant: Glucose at treatment goal = 0 units Glucose >goal - 180 = 6U 181 - 220 = 8 units 221 - 260 = 10 units 261 - 300 = 12 units 301 - 350 = 14 units 351 - 400 = 16 units >400 = 18 units Umpierrez GE et al. [RABBIT-2 Trial] Diabetes Care 2007;30:2181-2186.

21. Mean Blood Glucose Levels During Insulin Tx Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program Umpierrez GE et al. [RABBIT-2 Trial] Diabetes Care 2007;30:2181-2186.

22. Treatment success –BG target of < 140 mg/dL was achieved in 66% of patients on Basal-Bolus (Lantus® + Apidra®) and 38% regular insulin (SSI) Treatment failure –One out of 5 patients using SSI remained with BG >240 mg/dL and switched to Basal-Bolus (Lantus® + Apidra®) Basal–Bolus Insulin in Non-critically Ill Patients Days of Therapy Blood Glucose (mg/dL) 100 120 140 160 180 200 220 240 Admit 1 2 3 4 1 2 3 4 5 6 7 Sliding-Scale Insulin Delivery LANTUS ® + APIDRA ® 260 280 300 Sliding-Scale Insulin Basal-Bolus 66% 38% 0% 25% 50% 75% 100% Patients with BG <140 mg/dL, % Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program Adapted from: Umpierrez GE et al. [RABBIT-2 Trial] Diabetes Care 2007;30:2181-2186.

23. Hypoglycemia Basal Bolus Group: –1,005 BG readings –Two patients (3%) had BG < 60 mg/dL –Four BG readings (0.4%) < 60 mg/dL –No BG < 40 mg/dL Regular ISS: –1,021 BG readings –Two patients (3%) had BG < 60 mg/dL –Two BG readings (0.2%) < 60 mg/dL –No BG < 40 mg/dL None of the episodes of hypoglycemia in either group were associated with adverse outcomes Umpierrez GE et al. [RABBIT-2 Trial] Diabetes Care 2007;30:2181-2186. Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

24. Which Insulin Is Best For What Strategy? Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program Basal: GFR<30 -Lantus q24h q24h -Levemir q12h q12h -NPH q8h q12h Nutritional (Bolus): -Analog qAC qAC -Regular qAC qAC Nutritional (Continuous): -Regular q4h q6h -Analog q4h q6h Corrective and/or NPO: -Same as nutritional! Analog Insulins: (Lispro) (Glulisine) (Aspart) (Glargine)

25. NPO (No Nutrition) Treatment  Hold nutritional insulin  Continue basal insulin  Continue corrective insulin  If no other carbohydrate (CHO) source:  Start D5 (+/- saline) @ minimum 100 mL/h or D10 (+/- saline) @ minimum 50 mL/h  Equivalent to 17 KCal/h or 408 Kcal/d  Order prn hypoglycemia therapy

26. NPO - Hold Nutritional Insulin Hypoglycemia Cortisol, Epinepherine, Glucagon, Glycogenolysis 180 126 80 0 Fasting Euglycemia Nutrition, Glycogenolysis, Insulin Post-prandial Hyperglycemia Insulin, GLP, Incretins Severe Hyperglycemia Insulin resistance or DM Basal Insulin Nutritional Insulin Corrective Insulin Hypoglycemia Tx

27. Inpatient Diabetes Safety Hypoglycemia:  Definition <80 :  Glucose lower than desired treatment goal  Clinically insignificant: Glucose 60 - 80  Associated with either mild or no symptoms of hypoglycemia  This level can be occasionally tolerated  Clinically significant: <60  Confirm with serum blood test  Glucose 40 - 60, usually associated with significant symptoms of hypoglycemia, including confusion and lethargy; avoid if possible  Glucose <40, associated with lethargy, coma, possible permanent parkinsonian dementia with extrapyramidal symptoms, and increased mortality; goal would be to avoid 100% of the time Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

28. Inpatient Diabetes Safety Hypoglycemia Treatment:  Clinically stable:  Glucose 40 - 80, give meal first, then recheck q15 minutes until >70  Give D50 IVP or glucagon if unable to take PO, start D5 or D10 until >70  Reduce nutritional insulin dose and corrective sliding scale dose by 20+ %  Clinically significant:  Glucose <40, give D50 IVP and start D5 or D10-IVF  Hold all diabetic medications.  Once >70, use insulin sensitive corrective sliding scale @ >200  If corrective scale needed >2 times/24h, restart basal insulin at lower dose Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

29. Basal-Bolus (Basal-Nutritional) Strategy  Remember this!:  Inpatient goal: glucose 140 - 180  I, II, rII, 0.3, 0.4, 0.5 (DM I, II, resistant II, use 0.3, 0.4, 0.5 units/Kg/d as TDD)  GFR <50, adjustment 20-50% reduction of TDD  50/50 basal to nutritional (50% TDD = Basal, 50% TDD = nutritional)  D5 @100 mL/h or D10 @ 50 mL/h if no nutrition source  Forget this:  Insulin sliding scale  Estimating inpatient requirement based on home therapy  Using last 24h IV insulin dose to estimate SQ insulin dose Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program

30. Questions?