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
2015
Disclosures
None
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
Glucose Regulation
1
3
2
2
3
4
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1
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Incretin Pathway
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
GLP-1
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
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
Normal GI Response to Meal
Mixed
Meal
Intestinal
GLP-1
Release
GLP-1 [7-36]
Active
GLP-1 actions to control glucose:
• Inhibits glucagon secretion
• Inhibits hepatic gluconeogenesis
• Augments glucose-induced
insulin secretion
• Slows gastric emptying
• Promotes satiety
DPP-4
Rapid Inactivation
(>80%)
Additional features of GLP-1
based treatment:
• Restores beta-cell function
• Increases insulin synthesis
• Promotes beta-cell
differentiation
GLP-1 [9-36]
Inactive
Drucker, DJ. Diabetes Care. 2003; 26: 2929-2940.
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Normal Glucose Response to Meal
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Normal GI Response to Meal
Incretins increase insulin release from Beta cells in pancreas
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Normal Pancreas Response to Meal
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Diabetes, Type II
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Incretin Effect in Diabetes
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
GLP-1 Effect in Diabetes
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Pancreas Response in Diabetes
NGT - normal glucose tolerance
T2DM - Type 2 Diabetes Mellitus
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Diabetic Therapies
Reduce gluconeogenesis and increase insulin sensitivity
Decrease insulin resistance
Decrease insulin resistance
Pancreatic Beta cells
Increase insulin secretion
Increase insulin secretion
Multiple effects
 GLP-1
Binds FFA to increase insulin secretion
Exogenous insulin
Prevents digestion of
carbohydrates
Slows gastric emptying
Na-glucose transport (SGLT); blocks
glucose reabsorption in kidney
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
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: HgbA1c=11.4, glucose 325, BUN 20, creatinine 0.9
In addition to holding Metformin, what should you do with insulin?
A.
B.
C.
D.
E.
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
Corrective Insulin Dose
What’s Wrong With Sliding Scale Alone?
Glucose
Insulin Level
241
6
264
4
223
185
2
Time q4 h
?
Units
180 - 200
2
201 - 250
4
251 - 300
6
301 - 350
8
351 - 400
10
>400
12
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
What’s Wrong With Using Home Dose To
Estimate Insulin Dose?
Home
Hospital
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Insulin Strategy: Goal Glucose = 140-180
Corrective Therapy
Severe Hyperglycemia
Insulin resistance or DM
180
Post-prandial Hyperglycemia
Nutritional Therapy
Insulin, GLP-1, Incretins
126
Fasting Euglycemia
Basal Therapy
Sliding
Scale
Insulin
Nutrition, Glycogenolysis, Insulin
80
Hypoglycemia
Hypoglycemia Tx
0
Cortisol, Epinepherine, Glucagon, Glycogenolysis
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Some Endogenous Insulin Activity
Corrective Insulin
Severe Hyperglycemia
Insulin resistance or DM
180
Post-prandial Hyperglycemia
Nutritional Insulin
126
Basal Insulin
80
Insulin, GLP-1, Incretins
Fasting Euglycemia
Nutrition, Glycogenolysis, Insulin
Hypoglycemia
Hypoglycemia Tx
0
Cortisol, Epinepherine, Glucagon, Glycogenolysis
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
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
Inpatient Diabetes Treatment
Basal-Bolus Nutritional insulin:
Basal insulin for fasting & nutritional insulin for meals
Glucose
Breakfast Lunch
Analog
Analog
Dinner
Analog
Long-acting
Time
8:00
12:00
18:00
Nutritional Insulin
21:00
Basal 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
Inpatient Diabetes Treatment
Basal-Continuous Nutritional insulin:
Basal insulin for fasting & nutritional insulin for meals
Glucose
Basal glucose
Continuous
nutrition
Time
Long-acting
4:00
Long-acting
8:00
12:00
Basal Insulin
16:00
20:00
24:00
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
Inpatient Diabetes Treatment
Basal-Continuous Nutritional insulin:
Basal insulin for fasting & nutritional insulin for meals
Glucose
Basal glucose
Continuous
nutrition
Time
Short-acting
4:00
Long-acting
8:00
12:00
Basal Insulin
16:00
20:00
24:00
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
Which Insulin Is Best For What Strategy?
Basal:
Analog Insulins:
(Glulisine)
(Lispro)
(Aspart)
GFR<30-50
-Lantus q24h
q24h
-Levemir q12h
q24h
-NPH q8h
q12h
Nutritional (Bolus):
-Analog qAC
qAC
-Regular qAC
qAC
(Glargine)
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
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 (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 <50%, 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
Basal-Nutritional Strategy
Adjust dose after 24 hours:
 If zero events of hypoglycemia in past 24h and glucose >180:
 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
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 < 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
>400 = 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
>400 = 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
>400 = 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
Mean Blood Glucose Levels During Insulin Tx
Blood Glucose Levels During Insulin Treatment
240
Blood glucose (mg/dL)
220
*
200
*
*
¶
¶
¶
¶
180
Regular ISS
160
140
Lantus + glulisine
120
100
* p<0.01
¶ p<0.05
Admit
1
2
3
4
5
6
7
8
9
10
Days of Therapy
< Day 3: P=0.06
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
Basal–Bolus Insulin Outcomes
• Treatment success
• Treatment failure
100%
75%
66%
50%
38%
25%
0%
Basal-Bolus
Sliding-Scale
Insulin
– One out of 5 patients using SSI
remained with BG >240 mg/dL and
switched to Basal-Bolus (Lantus®
+ Apidra®)
Blood Glucose (mg/dL)
with%BG <140
Patients
mg/dL,
– BG target of < 140 mg/dL was
achieved in 66% of patients on
Basal-Bolus (Lantus® + Apidra®)
and 38% regular insulin (SSI)
300
Sliding-Scale
Insulin Delivery
LANTUS® + APIDRA®
280
260
240
220
200
180
160
140
120
100
Admit 1
2
3
4
1
2
3
4
5
6
7
Days of Therapy
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
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
NPO - Hold Nutritional Insulin
Corrective Insulin
Severe Hyperglycemia
Insulin resistance or DM
180
Post-prandial Hyperglycemia
Nutritional Insulin
Insulin, GLP-1, Incretins
126
Fasting Euglycemia
Basal Insulin
Nutrition, Glycogenolysis, Insulin
80
Hypoglycemia
Hypoglycemia Tx
0
Cortisol, Epinepherine, Glucagon, Glycogenolysis
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
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) @ minimum 100 mL/h or D10 (+/- saline) @
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
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
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
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 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
Questions?