Inpatient Diabetes Treatment Goals, Strategies, Safety

1
Inpatient DiabetesTreatment Goals, Strategies,
Safety

• Amish A. Dangodara, MD, FACP
• Professor of Medicine
• Internal Medicine, Hospitalist Program
• University of California, Irvine
• School of Medicine
• 2015

2
Disclosures

• None

3
Learning Objectives

• Review physiology of glucose regulation
• Describe the duration of action of various types
  of insulin
• Distinguish differences between nutritional,
  correctional, and basal insulin treatment
  strategies
• Describe appropriate action for NPO patients
• Describe appropriate prevention and treatment of
  hypoglycemia

4
Glucose Regulation
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
5
Incretin Pathway
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
6
GLP-1
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
7
DPP4

• DPP4 is an intrinsic membrane glycoprotein
  (serine exopeptidase) expressed on the surface of
  most cell types.
• antigenic enzyme that cleaves X-proline
  dipeptides from the N-terminus of polypeptides
• immune regulation, signal transduction, and
  apoptosis
• suppressor in the development of cancer and
  tumors
• Rapidly degrades incretins (GLP-1)

Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
8
Normal GI Response to Meal

• GLP-1 actions to control glucose
• Inhibits glucagon secretion
• Inhibits hepatic gluconeogenesis
• Augments glucose-induced insulin secretion
• Slows gastric emptying
• Promotes satiety

• Additional features of GLP-1 based treatment
• Restores beta-cell function
• Increases insulin synthesis
• Promotes beta-cell differentiation

Drucker, DJ. Diabetes Care. 2003 26 2929-2940.
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
9
Normal Glucose Response to Meal
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
10
Normal GI Response to Meal
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
11
Normal Pancreas Response to Meal
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
12
Diabetes, Type II
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
13
Incretin Effect in Diabetes
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
14
GLP-1 Effect in Diabetes
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
15
Pancreas Response in Diabetes
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
16
Diabetic Therapies
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
17
Case

• 63 yo M admitted with (L) foot ulcer/cellulitis,
  not responding to outpatient Abx. Weight 100 Kg.
  He 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 HgbA1c11.4, glucose 325, BUN 20,
  creatinine 0.9
• In addition to holding Metformin, what should you
  do with insulin?
• Hold 70/30 and start regular insulin sliding
  scale q4h
• Reduce 70/30 to 35 units in AM and 15 units in PM
• Change 70/30 to Lantus 25 units/d use
  corrective insulin scale q4h
• Change 70/30 to Lantus 50 units/d use
  corrective insulin scale q6h
• Continue home dose of insulin

Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
18
Whats Wrong With Sliding Scale Alone?
Glucose Units
180 - 200 2
201 - 250 4
251 - 300 6
301 - 350 8
351 - 400 10
gt400 12
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
19
Whats Wrong With Using Home Dose To Estimate
Insulin Dose?
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
20
Insulin Strategy Goal Glucose 140-180
Severe Hyperglycemia Insulin resistance or DM
Corrective Therapy
Sliding Scale Insulin
180 126 80 0
Post-prandial Hyperglycemia Insulin, GLP-1,
Incretins
Nutritional Therapy
Fasting Euglycemia Nutrition, Glycogenolysis,
Insulin
Basal Therapy
Hypoglycemia Cortisol, Epinepherine, Glucagon,
Glycogenolysis
Hypoglycemia Tx
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
21
Some Endogenous Insulin Activity
Severe Hyperglycemia Insulin resistance or DM
Corrective Insulin
180 126 80 0
Post-prandial Hyperglycemia Insulin, GLP-1,
Incretins
Nutritional Insulin
Fasting Euglycemia Nutrition, Glycogenolysis,
Insulin
Basal Insulin
Hypoglycemia Cortisol, Epinepherine, Glucagon,
Glycogenolysis
Hypoglycemia Tx
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
22
Types of Nutrition

• Bolus meal or bolus TF

• Continuous TF or TPN

Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
23
Inpatient Diabetes Treatment

• Basal-Bolus Nutritional insulin

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
Inpatient Diabetes Treatment

• Basal-Continuous Nutritional insulin

Basal insulin for fasting nutritional insulin
for meals
Long-acting
Glucose
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
25
Inpatient Diabetes Treatment

• Basal-Continuous Nutritional insulin

Basal insulin for fasting nutritional insulin
for meals
Glucose
Long-acting
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
26
Which Insulin Is Best For What Strategy?
Basal GFRlt30-50 -Lantus q24h
q24h -Levemir q12h q24h -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!
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
27
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 or
  non-diabetic hyperglycemia
• TDD Weight (Kg) x 0.4 units/d for controlled DM
  II (FBSlt200)
• TDD Weight (Kg) x 0.5 units/d for uncontrolled
  DM II
• Correct for renal clearance (adjusted TDD)
• GFR gt50, no change in TDD
• GFR lt50, reduce initial estimated TDD by 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
28
Basal-Nutritional Strategy

• Adjust dose after 24 hours
• If zero events of hypoglycemia in past 24h and
  glucose gt180
• Increase adjusted TDD by up to 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
29
RaBBIT-2 Trial

• Corrective insulin sliding scale vs basal-bolus
  insulin trial
• Schedule qAC qHS if eating or q4 hrs if NPO or
  q6 hrs if NPO with GFR lt 30 using short-acting
  insulin aspart, glulisine, humalog, regular

Insulin sensitive/Type 1 Glucose at treatment goal 0 units 141 - 180 2 units 181 - 220 4 units 221 - 260 6 units 261 - 300 8 units 301 - 350 10 units 351 - 400 12 units gt400 14 units Usual treatment/Type 2 Glucose at treatment goal 0 units 141 - 180 4 units 181 - 220 6 units 221 - 260 8 units 261 - 300 10 units 301 - 350 12 units 351 - 400 14 units gt400 16 units Insulin resistant Glucose at treatment goal 0 units 141 - 180 6 units 181 - 220 8 units 221 - 260 10 units 261 - 300 12 units 301 - 350 14 units 351 - 400 16 units gt400 18 units
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
30
Mean Blood Glucose Levels During Insulin Tx
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
31
BasalBolus Insulin Outcomes

• Treatment success
• BG target of lt 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
  gt240 mg/dL and switched to Basal-Bolus (Lantus
  Apidra)

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
32
Hypoglycemia

• Basal Bolus Group
• 1,005 BG readings
• Two patients (3) had BG lt 60 mg/dL
• Four BG readings (0.4) lt 60 mg/dL
• No BG lt 40 mg/dL
• Regular ISS
• 1,021 BG readings
• Two patients (3) had BG lt 60 mg/dL
• Two BG readings (0.2) lt 60 mg/dL
• No BG lt 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
33
NPO - Hold Nutritional Insulin
Severe Hyperglycemia Insulin resistance or DM
Corrective Insulin
180 126 80 0
Post-prandial Hyperglycemia Insulin, GLP-1,
Incretins
Nutritional Insulin
Fasting Euglycemia Nutrition, Glycogenolysis,
Insulin
Basal Insulin
Hypoglycemia Cortisol, Epinepherine, Glucagon,
Glycogenolysis
Hypoglycemia Tx
Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
34
NPO (No Nutrition) Treatment

• Hold nutritional insulin
• Continue basal insulin (reduce to 0.15 0.25
  units/Kg/day)
• Continue corrective insulin
• If no other carbohydrate (CHO) source
• Start D5 (/- saline) _at_ minimum 100 mL/h or D10
  (/- saline) _at_ minimum 50 mL/h
• Equivalent to 17 KCal/h or 408 Kcal/d
• Order prn hypoglycemia therapy

Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
35
Inpatient Diabetes Safety

• Hypoglycemia
• Definition lt80
• 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 lt60
• Confirm with serum blood test
• Glucose 40 - 60, usually associated with
  significant symptoms of hypoglycemia, including
  confusion and lethargy avoid if possible
• Glucose lt40, 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
36
Inpatient Diabetes Safety

• Hypoglycemia Treatment
• Clinically stable
• Glucose 40 - 80, give meal first, then recheck
  q15 minutes until gt70
• Give D50 IVP or glucagon if unable to take PO,
  start D5 or D10 until gt70
• Reduce nutritional insulin dose and corrective
  sliding scale dose by 20
• Clinically significant
• Glucose lt40, give D50 IVP and start D5 or D10-IVF
• Hold all diabetic medications.
• Once gt70, use insulin sensitive corrective
  sliding scale _at_ gt200
• If corrective scale needed gt2 times/24h, restart
  basal insulin at lower dose

Amish A Dangodara, MD, University of California,
Irvine School of Medicine, Hospitalist Program
37
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 lt50, adjustment 50 reduction of TDD
• 50/50 basal to nutritional
• (50 TDD Basal, 50 TDD nutritional)
• D5 _at_100 mL/h or D10 _at_ 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
38
Questions?