Hypoglycemia in the Hospital Sara Alexanian, MD Director, Inpatient Diabetes Program Department of Endocrinology, Diabetes and Nutrition

Agenda  Glycemic goals  Physiology  Epidemiology and risks of hypoglycemia  Preventing and avoiding hypoglycemia

Hyperglycemia in the Hospital: the Facts  Hyperglycemia is noted in 20-40% of hospitalized patients.  Hyperglycemia, irrespective of it’s cause, is unequivocally associated with adverse clinical outcomes.  Intervention studies directed at BG control have resulted in improved outcomes in some, but not all studies.  Insulin therapy, in particular (“intensive glycemic control”) carries a risk of hypoglycemia.

What are the recommendations for glucose control in the hospital?

AACE/ADA Target Glucose Levels in Non–ICU Patients  Non–ICU setting: –Premeal glucose targets <140 mg/dL –Random BG <180 mg/dL –To avoid hypoglycemia, reassess insulin regimen if BG levels fall below 100 mg/dL –Occasional patients may be maintained with a glucose range below and/or above these cut-points

AACE/ADA Target Glucose Level in ICU Patients  ICU setting: –Starting threshold of no higher than 180 mg/dL –Once IV insulin is started, the glucose level should be maintained between 140 and 180 mg/dL –Lower glucose targets ( mg/dL) may be appropriate in selected patients –Lower glucose targets ( mg/dL) may be appropriate in selected patients –Targets 180 mg/dL are not recommended Recommended Acceptable Not recommended <110 Not recommended >180 Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4).

Case #1   60 year-old female with a history of COPD admitted with respiratory failure, intubated, and started on tube feeds in the ICU.   The patient is started on an insulin drip to control glucose. After returning from a CT during which tube feeds were discontinued, her glucose is noted to be 55 mg/dL. The patient is asymptomatic, she is treated with dextrose and tube feeds are restarted. Question: What, if anything, does this low glucose mean for the patients’ prognosis?

Hypoglycemia: what and what is happening

Background mg/dL glucagon Glucose insulin “fed” state “post-absorptive” state G G G G G G G G

Defining Hypoglycemia  Symptomatic hypoglycemia: symptoms and BG <70 mg/dL  Severe hypoglycemia: event requiring assistance from another person to administer treatment  Relative hypoglycemia: symptoms and BG >70 mg/dL in patient with chronically poorly controlled DM  Limited utility in studies <80<60<50<40<70

normal Counterregulatory hormone release Adrenergic symptoms Neuroglycopenic symptoms lethargy coma seizure Hypoglycemia Symptoms

Chronic and Recurrent hypoglycemia

Hypoglycemia in Diabetes

Proposed mechanism of increased mortality  Prolonged, profound hypoglycemia can cause brain death.  Most deaths are presumed to be due to arrhythmia: –Hypokalemia –Sympathoadrenal activation –Prolonged QT

Potential mechanism of iatrogenic hypoglycemia- induced hypoglycemia-associated autonomic failure (HAAF) mediated sudden death in diabetes Cryer. Am J Med 24: , 2011

Inpatient Hypoglycemia: Frequency Hospital LocationFrequency SICU <40 mg/dL 1 5.1% MICU <40 mg/dL % SICU/MICU <40 mg/dL % ICU <40 mg/dL 3 16% ICU <45 mg/dL 4 6.8% ICU <81 mg/dL % Wards ≤50 mg/dL 6 7.7% 1. Van den Berge G et al, Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes 2006;55(11): Krinsley JS et al, The effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clinic Proc 2004;79( ). 3. Arabi YM et al, Hypoglycemia with intensive insulin therapy in critically ill patients. Crit Care Med 2009;37(9): Vriesendorp TM et al, Evaluation of short term consequences of hypoglycemia in an ICU. Crit Care Med 2006;34(11) Bagshaw SM et al, the impact of early hypoglycemia and blood glucose variability on outcomes in critical illness. Crit Care Med 2009;13(3):R Turchin A et al, Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward. Diabetes Care 2009;32(7):

Inpatient Hypoglycemia: Mortality 1. Egi M et al, Hypoglycemia and outcomes in critically ill patients. Mayo Clin Proc 2010;85(3): Bagshaw SM et al, the impact of early hypoglycemia and blood glucose variability on outcomes in critical illness. Crit Care Med 2009;13(3):R91 3. Van den Berge et al, Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes 2006;55(11): Kosiborod M et al, Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. JAMA 2009;301(15): Turchin A et al, Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward. Diabetes Care 2009;32(7): Hospital LocationNo hyposHypos ICU (<81 mg/dL) %36.6% ICU (<81 mg/dL) %25.6% ICU (≤40 mg/dL) 3 23%52% AMI (<60 mg/dl) 4 9.6%12.7% Wards (≤50 mg/dL) %2.96%

Bagshaw SM et al, the impact of early hypoglycemia and blood glucose variability on outcomes in critical illness. Crit Care Med 2009;13(3):R91 <36 mg/dL ≥80

We hold these truths to be self- evident… is all hypoglycemia equal?

“Spontaneous” Hypoglycemia  Hypoglycemia occurring without prior insulin or anti-hyperglycemic therapy.  Increased in critical illness: mechanical ventilation, sepsis, renal insufficiency, higher APACHE II score.  Frequency: –26% of all ICU pts with hypoglycemia 1 –28% of patients admitted with acute MI 2 1. Krinsley JS et al, The effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clinic Proc 2004;79( ). 2. Kosiborod M et al, Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. JAMA 2009;301(15):

Risk of therapy or marker of illness?  Treated with insulin?: AMI –Mortality with spontaneous hypoglycemia: 18.4%( increased from control) –Mortality of insulin-associated hypoglycemia: 10.4% (NO increase from control) Kosiborod M et al, Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. JAMA 2009;301(15):

Risk of therapy or marker of illness?  Correct for comorbid illness: –Study #1: case control correcting for age, sex, duration of ICU stay, APACHE II score: no association with incidental hypoglycemia and death (41% vs. 27%, not significant) 1. –Study #2: case control correcting for diagnosis, APACHE II, age diabetes history: Increase mortality associated with hypoglycemia (55.9% vs. 39.5%) Vriesendorp TM et al, Evaluation of short term consequences of hypoglycemia in an ICU. Crit Care Med 2006;34(11) Krinsley JS et al, The effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clinic Proc 2004;79( ).

…but  Time from hypoglycemic episode to death: –221 hours ( hours) 1 –152 hours ( hours) 1 –11 days (0-204 days) 2 1. Van den Berghe, Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes 2006;55(11): Vriesendorp TM et al, Evaluation of short term consequences of hypoglycemia in an ICU. Crit Care Med 2006;34(11)

Case #1   60 year-old female with a history of COPD admitted with respiratory failure, intubated, and started on tube feeds in the ICU.   The patient is started on an insulin drip to control glucose. After returning from a CT during which tube feeds were discontinued, her glucose is noted to be 55 mg/dL. The patient is asymptomatic, she is treated with dextrose and tube feeds are restarted. Question: What, if anything, does this low glucose mean for the patients’ prognosis? ?????

So…hypoglycemia is bad. However there is confounding from illness, and spontaneous hypoglycema. However, we should avoid it. So what can I do?

Know the Risk Factors  Advanced age  Slender and or longstanding diabetes  Malnutrition  Active cancer  Renal disease  Liver disease  Congestive heart failure  History of heavy alcohol intake  Chronic pancreatitis  Critical illness

Know who is at most risk to suffer adverse consequences  Inability to recognize or communicate hypoglycemic symptoms  Stroke patients  Dementia  Altered Mental Status: sedation, intubated, previous hypoglycemia

Treating your patients’ hyperglycemia  Always use weight-based insulin  Do not simply order a patients’ outpatient regimen if it does not appear safe. Beware of programs > 1 unit/kg/day.  Review your patients glucose levels at least twice per day  Consider a change if a glucose is <100.  Ask yourself, why is my patient low? Why is my patient high?

Case #2  76 yo M with DM2 on admitted from NH when found confused, BG 58 mg/dL.  Patient with prior CVA, CKD, HTN.  Labs on admit: BG 121, Cr 2.72 mg/dL, normal LFTs.  Weight: 98 kg.

Case #2  Outpatient program: glargine 45 units at HS, novolog 35 units prebreakfast and presupper.  Per NH, FS run  Most recent A1c 1 month ago 5.1%.

Case #2  What are the red flags here? –High outpatient dose –Low A1c –Dementia –CKD –Advanced age

What insulin program do YOU recommend? Average insulin need: 0.5 u/kg/day Advance age: -0.1 u/kg/day Renal insufficiency: u/kg/day Initial TDD : 0.3 u/kg/day 50% basal 15 units of glargine 50% nutritional 5 units lispro TID Correction CF 1:50, start at 200 HS 98 kg x 0.3 = apx 30 u/day

How did he do?  Fasting Bg on chemistry: 99 mg/dL  2 POC: 127 mg/dL, 157 mg/dL

Case #3  23 yo M with type 1 diabetes.  Weight: 58 kg  Inpatient insulin program: 16 units of glargine at HS, lispro 5 TID with meals, lispro SS. TDD: 30 units.

Case #3 C7 287 lunch 313 supper 330 Bedtime 257 MN >600 5:40 AM 30 Meal insulin and SS Lispro 9 SS Lispro 10 X 1 2:45 AM 405 Lispro 10 X 1 TDD 30 units/day

Truth and Consequences  Hyperglycemia is a common problem that requires treatment.  Insulin treatment carries a risk of hypoglycemia (even just “sliding scale”).  Both hyper- and hypoglycemia are associated with an increase in hospital mortality, hospital cost, and increase LOS.  Frequency of hypoglycemia can be mitigated by following current guidelines for BG targets, tailoring insulin programs, and being active in assessing your insulin program.

What can you do?  Critically evaluate your patients insulin program, on admission and daily.  Tailor your program to your patient  Be aware of insulin “stacking” and appropriate correction insulin doses  Always re-evaluate a program if the BG is low, and reconsider if <100.  Take the time to figure out what is happening.  Consult the GLUC or NP service if you need help.

Thanks!

What do i do for an insulin program?

Remaining Questions  What cutoffs should define hypoglycemia in studies?  How do we sort out the risk of iatrogenic hypoglycemia from hypoglycemia as a marker of disease?  How does hypoglycemia increase mortality?

Hypoglycemia in Patients with Diabetes: contributing factors  Medication/iatrogenic: insulin, sulfonylureas, meglitinides  Abnormal hormonal counter- regulation  Hypoglycemic unawareness  autonomic dysregulation  exercise

Hypoglycemia in patients with Diabetes: contributing factors  Medications/iatrogenic: insulin, sulfonylureas, meglitinides  Abnormal hormonal counter-regulation  Hypoglycemic unawareness  Renal and hepatic dysfunction  Autonomic dysregulation  Age  Exercise  Alcohol