Inpatient Glycemic Management UCI Medicine- Inpatient Mini Lecture Jodi Nagelberg, PGY2 April 2017

Learning Objectives Goals of glycemic management Blood glucose monitoring Insulin formulations Calculating insulin regimens

Goals of Glycemic Management 1 Avoid hypoglycemia 2 Avoid severe hyperglycemia 3 Ensure adequate nutrition 4 Ensure pre-discharge education Hyperglycemia is an independent factor for mortality in cardiac, septic, and respiratory failure patients ↑ LOS, delayed extubation, ↑risk of perioperative complications Glycemic control with intensive insulin therapy improves mortality and morbidity

Assessment: Criteria for Insulin Therapy Oral medications and non-insulin injectables should be held and substituted with insulin therapy while in the hospital Determine last dose of medications (oral/ injectable) Determine diet status (i.e.-NPO, TPN, TF) Contact endocrine fellow for patients with insulin pump

Clinical Considerations in Glycemic Management DM1 vs. DM2 Current blood glucose levels Prior treatment regimen Comorbidities (i.e.- renal function) Expected caloric intake

Inpatient Glycemic Target 140-180 mg/dL Critically ill: NO firmly established targets via clinical trials, however TIGHT glucose control (i.e.- 80-110 gm//dL) has NOT resulted in improved outcomes Acute MI: suboptimal glycemic control and DM and non-DM patient associated with worse outcomes after acute MI (AHA guidelines) NICE-SUGAR Study § Intensive control (81-108 mg/dL) vs. Standard control (144-180 mg/dL) §  Intensive control of hyperglycemia is difficult without risk of hypoglycemia §  Increase mortality in intensive group Finfer S et al. N Engl J Med 2009;360:1283–1297

General Approach Step 1: Stop oral hypoglycemic agents Step 2: Calculate total daily dose Step 3: Determine frequency of monitoring based on nutritional source Step 4: Determine insulin formulation (basal + nutritional + correctional) Step 5: Monitor blood sugars and adjust regimen Step 2: ACCOUNT for home dose, renal function, nutritional source/ schedule, etc.)

Step 2: Calculating Insulin Dosage Total daily dose (TDD) (Weight in Kg) x (Correctional Factor) BASAL NUTRITIONAL Breakfast Lunch Dinner 1/2 1/3 If patient is on insulin at HOME, give them 2/3 of their home dose (basal and nutritional) as they don’t eat the same foods in the hospital vs. at home EXAMPLE: 75 Kg person Standard correction: 0.4 Basal 15 Meals 5/5/5 How to calculate correctional factor comes next…

Total Daily Dose (TDD) Correctional Factor LOW = 0.3 units/kg/day: very lean patient, on hemodialysis or very sensitive to insulin (hypoglycemic risk factors) STANDARD = 0.4 unit/kg/day: patient with normal body habitus MODERATE = 0.5 units/kg/day: overweight patient AGGRESSIVE = 0.6 + units/kg/day: patient obese, on steroids, known to be insulin resistant This is a prelude to next slide, HOW TO KNOW WHICH CORRECTIONAL FACTOR TO USE

Correction for Renal Impairment GFR % Reduction in Total Daily Units of Insulin GFR>50 No correction GFR 30-50 20% reduction GFR < 30 30-50% reduction Ex: If TDD = 100 by weight and patient has a GFR of 40  TDD = 80

Step 3: Blood Glucose Monitoring Schedule Diet Schedule Oral Diet (TID meals) TID AC & QHS Bolus enteral feedings Prior to each bolus & QHS Tube feeds, TPN or NPO Q6H (or Q4H if unstable sugars) Insulin ggt Q1H

Step 4: Insulin Categories EVERY patient should have 3 insulin orders, EXCEPT CORRECTIONAL INSULIN alone is OK for: Pre-diabetics Borderline diabetic patients Patients with good glycemic control just on oral medication …because they still have enough endogenous insulin production to meet basal needs. Insulin Type Description Example Basal Background insulin provided by intermediate or long acting insulin Glargine (Lantus) Detemir Nutritional Rapid acting insulin that is given with meals to mimic the body’s mealtime insulin secretions Lispro (Humalog) Aspart (Novolog) Regular Correctional (Sliding Scale) Rapid acting insulin given at the time of blood sugar check to correct for hyperglycemia (frequently given with nutritional insulin) NUTRITIONAL and CORRECTIONAL SHOULD BE THE SAME TYPE OF INSULIN CHANGE COLOR OF SHPES AT BOTTOM Basal Nutri-tional Correctional Daily Insulin + + =

UCI Insulin Protocol: Basal+ Nutritional + Correctional ALL patients should have 3 insulin orders: basal+ nutritional + correctional (exceptions on previously slide in which case just ISS alone ok) TDD: Total insulin requirement in a 24H period This represents ONE EXAMPLE of possible insulin sliding scale Note the different sliding scale based on regimen tract

Pharmacokinetics of Insulin Formulations Here one can see the relative peak and durations of various insulin formulations Adapted from www.diabetesincontrol.com Hirsch, IB: Insulin Analogues. N Engl J Med 352:174–183; table on 177, 2005

Step 5: Monitor Blood Sugars and Adjust If glucose >180 at any time (without risk of hypoglycemia), increase TDD by 10-20% If glucose consistently >180-200, increase TDD by 30% If ANY hypoglycemia (BS<70 mg/dL), start D5 ½ NSS and reduce TDD by 20% If glucose >180, can also take the total daily dose from the day before INCLUDING THE REQUIRED INSULIN SLIDING SCALE and redistribute this to with meals and basal so the TDD includes the ISS

Type of Insulin and Monitoring by Nutrition Source Monitoring Interval Insulin Type Oral diet (TID meals) AC + QHS Basal: Long or intermediate Nutritional: Short acting ISS: Short acting Bolus enteral feeds Prior to each bolus + QHS Continuous tube feeds/ TPN Q6H (or Q4H if unstable sugars) Basal: Long or intermediate acting Nutritional: Regular Insulin ISS: Regular Insulin NPO (on D5/ D10) Basal: long or intermediate acting Nutritional: None Insulin ggt Q1H Regular insulin only

Putting it all together… Step 1: Discontinue oral hypoglycemic agents Step 2: Calculate Total Daily Dose (TDD) Step 3: Determine the distribution of the TDD calculated above based on the nutritional regimen Eating or Bolus TF 1) Monitor: AC+QHS 2) Basal: Long acting 3) Nutritional: Short acting in 3 doses with each meal 4) Correctional: Short acting, AC Continuous Infusion/ TPN 1) Monitor: Q6H 2) Basal: Long acting 3) Nutritional: Regular insulin 4) Correctional: Regular insulin NPO (or nearly- CLD) 1) Monitor: Q6H Low dose dextrose: (D5 1/2NS) 2) Basal: Long acting 3) Nutritional: none 4) Correctional: Short acting Step 4: Re-evaluate and adjust TDD daily based on prior 24H If glucose >180 at any time (without risk of hypoglycemia), increase TDD by 10-20% If glucose consistently >180-200, increase TDD by 30% If ANY hypoglycemia (BS<70 mg/dL), start D5 ½ NSS and reduce TDD by 20% Journal of Hospital Medicine Volume 4, Issue 1, pages 3-15, 12 JAN 2009 DOI: 10.1002/jhm.391 http://onlinelibrary.wiley.com/doi/10.1002/jhm.391/full#fig2

CASE 1 Tom has Type 2 DM, weighs 88kg and is admitted for diabetic foot ulcer. He takes Metformin 1g bid, glipizide 10mg daily at home. He has a normal GFR. His HbA1c is 10% and his blood sugars since admission have ranged 250-300. How do you manage his DM?

Case 1 Step 1: STOP his metformin and glipizide Step 2: Calculate his TDD (can use correctional factor of 0.5 for overweight patient) 0.5 x 88kg = 44 units daily (normal GFR, no add’l reduction) 44 x 0.5 (or 0.4, consider comordibities) = 22 units basal and 22 units for meals 22/3 = ~7 units with each meal Step 3: Frequency of monitoring based on his nutritional source TID meals  check before meals (AC) + QHS Step 4: Insulin formulation Basal: 22u Glargine Nutritional: 7u Lispro TID ISS: Lispro TID + QHS Step 5: Monitor for 24H period and increase or decrease TDD accordingly Each order will have 2 types of insulin: Basal: provides continuous insulin coverage to diminish BS swings Nutritional: treats the anticipated BS increase with meals Correctional: corrects current BS level Nutritional and Correctional coverage should be the same type of insulin (both Lispro or both Regular) Correction insulin is designed to be given independent of nutritional intake. Also remember, studies have shown that the long acting insulins (glargine or levemir) plus the rapid acting insulins (aspart or lispro) mimic physiologic production of insulin better then any other combination (such as NPH, 70/30 combos).

Case 1: Learning Points Hold oral DM meds when inpatient (minimize hypoglycemia, improve glycemic control) DO NOT place diabetic patients only on Correctional Insulin (unless as specified elsewhere) Use weight based method to get accurate insulin requirement Adjust insulin dose for GFR: GFR > 50, no correction GFR 30-50, 20% reduction GFR < 30, 30-50% reduction Its ok to only use Correctional insulin for pre-diabetics or borderline diabetic patients bc they still have enough endogenous insulin production to meet basal needs; or in patients with good glycemic control just on oral medications

Case 2 Tom has Type 2 DM and was admitted for diabetic foot ulcer. Today is hospital day 3 and his blood sugars have been stable with Lantus 22u QHS, Lispro 7u TID and Lispro Correctional. Tomorrow he is having a L foot amputation. How should his insulin regimen be adjusted? Meaning he will need to be made NPO

Case 2: Insulin Management in NPO Patient Basal: Continue evening Lantus dose Nutritional: Stop Lispro for nutritional insulin because patient is NPO START IVFs (carbohydrate source): D5 or D10 (consider volume status and comorbidities, i.e.- CHF, ESRD) ISS: Continue Lispro correctional coverage …Remember though, Type I DM requires insulin AND carb source (D5 or D10) at all times (even when NPO, to prevent DKA). So if Type I diabetic is NPO, DO NOT hold basal insulin and DO start D5 or D10 Typically patients require 3 types of insulin orders: basal + nutritional + ISS HOWEVER, when NPO, patient STILL REQUIRES basal AND a dextrose source AND ISS Start D5 or D10 if carb source is interrupted (NPO). The infusion rate will have to take into account the patient’s general condition (CHF, cirrhosis) Do not hold basal insulin if long acting (levemir or glargine) 1 L of D5 1/2NS provides less calories than a small candy bar (170 calories per L)

Case 3 Tom has Type 2 DM and was admitted for diabetic foot ulcer. Today is hospital day 3 and his blood sugars have been stable with NPH 22 units bid and Regular Correctional. Tomorrow he is having a L foot amputation. How should his insulin regimen be adjusted? Same Tom, different regimen HOW TO USE NPH/ REGULAR

Pharmacokinetics of Insulin Formulations Here one can see the relative peak and durations of various insulin formulations See NPH is NOT as long lasting as glargine Adapted from www.diabetesincontrol.com Hirsch, IB: Insulin Analogues. N Engl J Med 352:174–183; table on 177, 2005

Case 3: Management of NPH/ Regular in NPO Setting Basal: Continue evening NPH dose Half morning NPH dose START IVF (carbohydrate source): D5 or D10 Correctional: Continue Correctional insulin Alternatively, On admission, change from NPH to Lantus for better glycemic control NPH is intermediate acting  CONTINUE THE BASAL INSULIN SOURCE WHILE NPO Regular: short acting

Case 4 Tom has Type 2 DM, admitted for diabetic foot ulcer and today is hospital day 3. He is treated with Humalog 7u TID & Lantus 22u nits QHS. Tom has pre- meal BS of 65 before lunch, but does not have any symptoms of hypoglycemia. What should you do?

Case 4: Management of Hypoglycemia First: Treat hypoglycemia If possible, give PO 1st (juice) Treat SYMPTOMS, not just the number 15-15 rule Treat with 15 grams of carbs and Recheck every 15 minutes, until blood glucose > 75 mg/dL 4 oz of juice/ 8 oz fat free milk = 15 grams of carbs Second: Lower TDD of insulin Tom has low pre-meal BG readings: confirm he ate breakfast Decrease pre-meal regimen form 7 to 5 u TID (~10-20%) Multiple different ways to change insulin regimen to manage hypoglycemia and prevent further -One way is to lower TDD by 20%, or determine where specifically he has low BG and just lower the insulin reigmen affecting that low reading -For example, a low pre-lunch lunch reading can be from a high pre-breakfast insulin dosing (see pharmacokinetics graph)

Case 5 Jerry is a 65 yo male who is receiving continuous TPN. He has a h/o DM, weighs 80kg and is on continuous TPN. His blood glucose readings have ranged 250- 300, how do you manage his DM and hyperglycemia?

Case 5: TPN Management Monitoring: Q6H Insulin regimen: Basal: Lantus 12u QHS Nutritional: Regular 5u Q6H Correctional: Regular insulin Q6H Learning Points For continuous feeds (TPN), check blood glucose levels Q6H Regular correctional insulin preferred over rapid acting (Aspart/Lispro) because patient is not taking food in orally and regular lasts longer then rapid acting Use weight based method. He weighs 80kg and 0.4 units/kg/day = 32 units total daily dose You can do 40% long acting and use 60% as short acti

Inpatient Diabetes Management: Pearls HOLD all oral DM meds and noninsulin injectable meds on admission If patient is on insulin, give them 2/3 of their home dose (basal and nutritional) as they eat less inpatient vs. at home Always account for renal function When NPO, always give carb source (D5 D10 depending on overall fluid state) Pt should be on same insulin for nutritional and correctional Monitor daily and adjust as needed

References Scott, Shruti. Inpatient Glycemic Management. UCI Mini-Lecture. 2013 American Diabetes Association. Diabetes Care 2016 Jan; 39(Supplement 1): S99-S104. https://doi.org/10.2337/dc16-S016