inpatient diabetes treatment goals, strategies, safety amish a. dangodara, md, facp professor of...
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Inpatient DiabetesTreatment Goals, Strategies, Safety
Amish A. Dangodara, MD, FACPProfessor 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
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
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2
3
4
1
2
2
3
Incretin Pathway
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish 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 ProgramAmish 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 ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Normal GI Response to Meal
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Intestinal GLP-1 Release
GLP-1 [9-36] Inactive
GLP-1 [7-36] Active
DPP-4
Rapid Inactivation (>80%)
Mixed 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.
Normal Glucose Response to Meal
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Normal GI Response to Meal
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Incretins increase insulin release from Beta cells in pancreas
Normal Pancreas Response to Meal
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish 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 ProgramAmish 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 ProgramAmish 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 ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Pancreas Response in Diabetes
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
NGT - normal glucose toleranceT2DM - Type 2 Diabetes Mellitus
Diabetic Therapies
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Na-glucose transport (SGLT); blocks glucose reabsorption in kidney
Prevents digestion of carbohydrates
Slows gastric emptying
Reduce gluconeogenesis and increase insulin sensitivity
Decrease insulin resistance
Increase insulin secretion
Binds FFA to increase insulin secretion
Exogenous insulin
Increase insulin secretion
Pancreatic Beta cells
Multiple effects
GLP-1
Decrease insulin resistance
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, CRIMeds: 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. Hold 70/30 and start regular insulin sliding scale q4hB. Reduce 70/30 to 35 units in AM and 15 units in PMC. Change 70/30 to Lantus 25 units/d & use corrective insulin scale q4hD. Change 70/30 to Lantus 50 units/d & use corrective insulin scale q6hE. Continue home dose of insulin
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
What’s Wrong With Sliding Scale Alone?
Glucose Units
180 - 200 2
201 - 250 4
251 - 300 6
301 - 350 8
351 - 400 10
>400 12
Cor
rect
ive
Insu
lin
Dos
e
185
223
264
241
2
4
6
?
Time q4 h
Insulin Level
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish 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 ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Insulin Strategy: Goal Glucose = 140-180
Hypoglycemia
Cortisol, Epinepherine, Glucagon, Glycogenolysis
180
126
80
0
Fasting EuglycemiaNutrition, Glycogenolysis, Insulin
Post-prandial Hyperglycemia
Insulin, GLP-1, Incretins
Severe HyperglycemiaInsulin resistance or DM
Basal Therapy
Nutritional Therapy
Corrective Therapy
Hypoglycemia Tx
Sliding Scale Insulin
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Some Endogenous Insulin Activity
Hypoglycemia
Cortisol, Epinepherine, Glucagon, Glycogenolysis
180
126
80
0
Fasting Euglycemia
Nutrition, Glycogenolysis, Insulin
Post-prandial Hyperglycemia
Insulin, GLP-1, Incretins
Severe Hyperglycemia
Insulin resistance or DM
Basal Insulin
Nutritional Insulin
Corrective Insulin
Hypoglycemia Tx
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish 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 ProgramAmish 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
Breakfast Lunch Dinner
Glu
cose
Time 18:0012:008:00 21:00
Nutritional Insulin
AnalogAnalog Analog
Long-acting
Basal Insulin
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish 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.
Inpatient Diabetes Treatment
Basal-Continuous Nutritional insulin:
Basal insulin for fasting & nutritional insulin for meals
Glu
cose
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Time 16:0012:008:00 20:004:00 24:00Long-acting
Basal InsulinNutritional Insulin
Long-acting
Basal glucoseContinuous nutrition
Umpierrez GE et al. [RaBBIT-2 Trial] Diabetes Care, 2007; 30: 2181-2186.
Inpatient Diabetes Treatment
Basal-Continuous Nutritional insulin:
Umpierrez GE et al. [RaBBIT-2 Trial] Diabetes Care, 2007; 30: 2181-2186.
Basal insulin for fasting & nutritional insulin for meals
Glu
cose
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Long-actingTime 16:0012:008:00 20:004:00 24:00
Nutritional InsulinBasal Insulin
Short-acting
Basal glucoseContinuous nutrition
Which Insulin Is Best For What Strategy?
Basal: GFR<30-50
-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!
Analog Insulins:
(Lispro)
(Glulisine)
(Aspart)
(Glargine)
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish 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 ProgramAmish 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 ProgramAmish 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 ProgramAmish 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
Days of Therapy
Bloo
d glucose (m
g/dL)
100
120
140
160
180
200
220
240
Admit 1 2 3 4 5 6 7 8 9 10
Regular ISS
Lantus + glulisine
* p<0.01
¶ p<0.05
¶* * *
¶ ¶ ¶
< Day 3: P=0.06
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish 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.
• 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 Outcomes
Days of Therapy
Blo
od
Glu
cose
(m
g/dL
)
100
120
140
160
180
200
220
240
Admit 1 2 3 4 1 2 3 4 5 6 7
Sliding-ScaleInsulin Delivery
LANTUS® + APIDRA®
260
280
300
Sliding-ScaleInsulin
Basal-Bolus
66%
38%
0%
25%
50%
75%
100%
Pa
tie
nts
wit
h B
G <
14
0
mg
/dL
, %
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish 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.
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
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish 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.
NPO - Hold Nutritional Insulin
Hypoglycemia
Cortisol, Epinepherine, Glucagon, Glycogenolysis
180
126
80
0
Fasting EuglycemiaNutrition, Glycogenolysis, Insulin
Post-prandial Hyperglycemia
Insulin, GLP-1, Incretins
Severe HyperglycemiaInsulin resistance or DM
Basal Insulin
Nutritional Insulin
Corrective Insulin
Hypoglycemia Tx
Amish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist ProgramAmish 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 ProgramAmish 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 ProgramAmish 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 ProgramAmish 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 ProgramAmish A Dangodara, MD, University of California, Irvine School of Medicine, Hospitalist Program
Questions?