INTERNAL MEDICINE RESIDENTS NOON

CONFERENCE:

INPATIENT GLYCEMIC CONTROL

Presented by: Leyda Callejas

PGY5 Endocrinology , Diabetes and Metabolism

Acknowledgements:

Dr. P Orlander

Dr. V Lavis

Dr. N Shah

DEFINITIONS OF GLUCOSE

ABNORMALITIES

• Hypoglycemia is defined a BG level <70 mg/dL

• Mild to moderate hypoglycemia is when BG levels are

between 40 and 69 mg/dL.

• Severe hypoglycemia is when BG is <40 mg/dL.

AACE/ ADA Consensus: Inpatient Hyperglycemia, Endocr Pract. 2009;15(No. 4)

DEFINITIONS OF GLUCOSE

ABNORMALITIES

• Hyperglycemia is defined as any blood glucose (BG) value

>140 mg/dL.

• In patients without a previous diagnosis of diabetes mellitus

(DM) and Hemoglobin A1c (HbA1c) values of < 6.5%

elevated BG may be due to stress hyperglycemia.

• HbA1c values of >6.5% suggest that DM preceded

hospitalization.

AACE/ ADA Consensus: Inpatient Hyperglycemia, Endocr Pract.

2009;15(No. 4)

HYPERGLYCEMIA IN HOSPITALIZED PATIENTS

• Irrespective of its cause, hyperglycemia associated with

adverse outcomes

• Hyperglycemia occurs in patients with known or undiagnosed

diabetes, or it occurs during acute illness in those with

previously normal glucose tolerance (“stress hyperglycemia”)

• Possible connections between hyperglycemia and

complications:

• Impaired collagen synthesis

• Impaired WBC function

• Increased production of free radicals and activation of

inflammatory markers

Stress Hyperglycemia

Dungan et al, Lancet 2009 1789-807

SCOPE OF THE PROBLEM OF HYPERGLYCEMIA

IN HOSPITALIZED PATIENTS

• 12 % admissions‐ previously unrecognized DM

or stress hyperglycemia

• 26 % of admissions‐ known DM

• 70 % ‐ non diabetic patients having cardiac

surgery become hyperglycemic( BG > 150)

Umpierrez, JCEM 87:978, 2002

Leibowitz ANN Thor Surg 90:1825, 2010

DIABETES DISADVANTAGE

Retrospective analysis in 3184 pts admitted to Emory University Hospital for non cardiac

surgery

A Frisch et al Diabetes Care 33:1783, 2010

RELATION BETWEEN GLUCOSE VALUES

AND OUTCOMES

CAUSES OF GLUCOSE INSTABILITY IN

HOSPITALIZED PATIENTS

• Changes in nutrition (NPO, enteral, parenteral feedings)

• Changes in clinical status/meds (pressors,

glucocorticoids)

• Prolonged use of SSI as monotherapy

• Failure of clinician to make adjustments

• Poor coordination of BG testing and administration of

insulin

• Poor communication during times of transfer of care

• Poor understanding of when insulin can be held and

when it should be given (DM-1 vs DM-2, long acting vs

short acting)

• Insulin errors (writing and transcription)

TREATMENT OF HYPERGLYCEMIA IN

CRITICALLY ILL PATIENTS

HYPERGLYCEMIA IS ASSOCIATED WITH INCREASED MORTALITY IN ICU PATIENTS, INDEPENDENT OF SEVERITY OF ILLNESS

Hyperglycemia is associated with increased mortality in ICU patients, independent of severity of illness

Mortality risk increases with mean glucose across the entire cohort (n = 259,040) starting at mild hyperglycemia (p < 0.0001). Odds ratios for mortality after adjustment for severity of illness are represented as point estimates with 95% confidence intervals for each mean glucose category; exclusion of unity represents a significant association.

Crit Care Med. Dec 2009; 37(12): 3001–3009.

DOES TREATING HYPERGLYCEMIA

IMPROVE OUTCOMES?

Insulin infusion protocol reduces `rates of wound infections. Furnary AP Starr et al, 1999, ANN Thor Surg 67:352-63

Deep Sternal Wound Infection rate decreased from 3.8% to 0.8% after starting insulin protocol

THE NORMOGLYCEMIA IN INTENSIVE CARE

EVALUATION AND SURVIVING USING

GLUCOSE ALGORITHM REGULATION (NICE-

SUGAR) TRIAL

Intensive versus Conventional Glucose Control in Critically Ill Patients

international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose

target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. N Engl J Med 2009;

360:1283-1297

TREATMENT OF HYPERGLYCEMIA IN

CRITICALLY ILL PATIENTS

• Insulin infusion should be used to control hyperglycemia

in the majority of critically ill patients in the ICU setting,

with a starting threshold of no higher than 180 mg/dL.

• Once therapy has been initiated, the glucose level should

be maintained between 140 and 180 mg/dL.

• Targets less than 110 mg/dL are not recommended.

AACE/ ADA Consensus: Inpatient Hyperglycemia, Endocr Pract. 2009;15(No. 4)

ADVANTAGES & DISADVANTAGES OF

INSULIN INFUSION

• Advantages:

• Easily adjustable

• Lower risk for hypoglycemia with higher goals

• Disadvantages:

• Intensive nursing monitoring

• Hourly glucose checks

• Do not address prandial needs

TRANSITION FROM DRIP TO

SUBCUTANEOUS (SC) INSULIN

• Patients with Type 1 and Type 2 DM should receive

first dose of scheduled SC insulin 1-2 hrs before

discontinuing the insulin drip.

• Patients with out a diagnosis of DM but who are

requiring at least 2 units/ hr on the insulin drip should

also be converted to SC insulin

TRANSITION FROM DRIP TO

SUBCUTANEOUS (SC) INSULIN

• In order to calculate insulin requirements you can:

• Review requirements on insulin drip (75-80%)

• Use weight based dosing

• Use home insulin dose as a guide

TREATMENT OF HYPERGLYCEMIA IN

NON-CRITICALLY ILL PATIENTS

TREATMENT OF HYPERGLYCEMIA IN NON-

CRITICALLY ILL PATIENTS

• There is no RCT data for establishing specific

guidelines in non-critically ill patients.

• For the majority of patients on insulin, premeal

glucose targets should generally be <140 mg/ dL in

conjunction with random BG values <180 mg/dL .

TREATMENT OF HYPERGLYCEMIA IN NON-

CRITICALLY ILL PATIENTS

• For avoidance of hypoglycemia, if BG levels decline

below 100 mg/dL see if any changes can be done.

• Modification of the regimen is necessary when BG

values are <70 mg/dL, unless the event is easily

explained by other factors (such as a missed meal)

TREATMENT OF HYPERGLYCEMIA IN NON-

CRITICALLY ILL PATIENTS • Scheduled subcutaneous administration of insulin is the

preferred method for achieving and maintaining glucose

control in non-ICU patients with diabetes or stress

hyperglycemia.

• Non-insulin agents are inappropriate in most hospitalized

patients.

• The recommended components of inpatient subcutaneous

insulin regimens are a basal, a nutritional, and a

supplemental (correction) element

• Should avoid overuse of sliding scale insulin (SSI) for

management of hyperglycemia.

INSULIN THERAPY

PHYSIOLOGIC INSULIN SECRETION

Insulin is secreted into portal system

• Fasting or Basal‐

Low level constantly secreted to decrease hepatic

production of glucose from breakdown of muscle

• Prandial or Bolus‐

Spike in insulin to lower glucose absorbed from food

PHARMACOKINETICS OF SC INSULIN

PREPARATIONS

Onset Peak Duration

Rapid-acting

analogs 5-15 min 1-2 h 4–6 h

Regular 30-60 min 2-3 h 6-10 h

NPH 2-4 h 4-10 h 12-18h

Glargine 2 h none 20-24h

Detemir 2h none 12-24h

INSULIN PROFILES

COMPONENTS OF MULTIPLE DOSE INSULIN

REGIMEN • Basal‐ Glargine ,NPH, Detemir

•Circulates between feedings

•Restrains glucose production, and catabolism of stored fuels

•Defends against ketoacidosis

•About 50% of daily insulin requirement

•Nutritional / Bolus insulin -Aspart, Glulisine, Lispro, Regular)

•Mimics rapid secretion of insulin in response to feeding

•Promotes assimilation of ingested nutrients

•Moderates post-prandial hyperglycemia

•Correction doses

•Single doses of short or rapid-acting insulin, for short-term adjustment of the

blood sugar over the next few hours

•Usually given in conjunction with meals, as a positive or negative adjustment of

the dose of prandial insulin

ENDOGENOUS INSULIN VERSUS

MULTIDOSE INJECTION REGIMEN

ADVANTAGES OF MULTIDOSE INJECTION

REGIMEN

• Mimics physiological insulinemia

• More opportunities for dosage adjustment

• Can adjust basal & nutritional insulin independently

• Reduced risk of hypoglycemia

RANDOMIZED STUDY OF BASAL-BOLUS INSULIN THERAPY IN THE INPATIENT MANAGEMENT OF PATIENTS WITH TYPE 2 DIABETES (RABBIT 2 TRIAL).

Changes in blood glucose concentrations in patients treated with glargine plus glulisine (•) and with SSI (○). *P < 0.01; P < 0.05. Umpierrez G E et al. Dia Care 2007;30:2181-2186

Basal Bolus versus SSRI – non-ICU

INSULIN REGIMENS

• Calculate total daily dose of insulin (TDD)

• 0.4 units / kg if BG concentration is 140-200 mg/dl

• 0.5 units / kg if BG is between 201-400 mg/dl

• 0.3 units / kg if elderly / impaired renal function

• Give one-half of total daily dose as basal and one-half

as bolus

Umpierrez et al, Diabetes Care 2007; JCEM 2009; Diabetes Care 2011

INSULIN REGIMENS

• Total daily dose (TDD)

• 1500‐1700 rule

• ISF ( insulin sensitivity factor) = 1500/TDD

• ISF/3 =Insulin to Carbohydrate Ratio

INSULIN REGIMENS

• Give supplemental short acting insulin “sliding-scale” protocol

for blood glucose >150 mg/dl before meals if tolerating PO

and if unable to eat, give scale every 6 h (6–12–6–12).

• Supplemental/sliding scale

• Low dose for TDD < 40 units/ day

• Medium dose for TDD 40‐ 80 units/ day

• High for TDD > 80 units/ day

• Reassess glucose control daily and adjust basal bolus as

indicated (20% change)

BASAL -PLUS INSULIN TRIAL

SPECIAL

CONSIDERATIONS

STEROID INDUCED HYPERGLYCEMIA

• Elevated postprandial BG , which are disproportionate to

fasting BG levels

• NPH‐ given at time of prednisone administration (0.1

units/kg/day for every 10 mg of prednisone)

• Glargine‐ if using dexamethasone or twice daily

prednisone

CONTINUOUS NUTRITION • TPN

• Add regular insulin to TPN 1unit:10 grams of

carbs

• Can administer correctional insulin Q6H (regular)

• At times the patient might require a basal dose as

well

• Continuous tube feeds

• NPH Q12H for basal needs & regular insulin Q6H

• 70/30 insulin every 6‐8H with SSI

NPO STATUS FOR PROCEDURES

• For a type 1 diabetic do not hold evening dose night

prior to procedure. The patient needs to receive basal

insulin. Can give 1/2 dose prior to procedure and give

dextrose containing IVF and administer a correction

dose after procedure.

• For a type 2 diabetic do not hold evening dose night

prior to procedure. You can omit AM insulin, give 1/2

dose prior to procedure or full dose after procedure

HYPOGLYCEMIA IN HOSPITALIZED

PATIENTS

• The key predictors of hypoglycemic events in

hospitalized patients include older age, greater illness

severity (presence of septic shock, mechanical

ventilation, renal failure, malignancy, and

malnutrition), diabetes, and the use of oral glucose

lowering medications and insulin

HYPOGLYCEMIA AND NEGATIVE

OUTCOMES • Hypoglycemia is associated with an increased risk of

mortality.

• Hypoglycemia is also associated with a prolonged

hospital length of stay .

• Patients with spontaneous hypoglycemia were noted to

have higher rates of in-hospital death (18.4 vs. 9.2% in

those without hypoglycemia; P < 0.001), mortality was

not increased in insulin-treated patients with iatrogenic

hypoglycemia (10.4 vs. 10.2% in those without

hypoglycemia; P = 0.92).

LOWEST BLOOD GLUCOSE AND PATIENT

MORTALITY

STRATEGIES FOR TREATING

HYPOGLYCEMIA • For treatment of BG below 70 mg/dl in a patient who is alert and

able to eat and drink, administer 15–20 g of rapid-acting

carbohydrate such as:

• one–15–30 g tube glucose gel or 4 (4 g) glucose tabs

(preferred for patients with ESRD.

• 4–6 ounces orange or apple juice.

• 6 ounces “regular” sugar sweetened soda.

• 8 ounces skim milk.

• For treatment of BG below 70 mg/dl in an alert and awake

patient who is NPO or unable to swallow, administer 20 ml

dextrose 50% solution and consider starting IV dextrose 5% in

water

STRATEGIES FOR TREATING

HYPOGLYCEMIA

• For treatment of BG below 70 mg/dl in a patient with an

altered level of consciousness, administer 25 ml dextrose

50% (1/2 amp) and consider starting IV dextrose 5% in

water

• In a patient with an altered level of consciousness and no

available IV access, give glucagon 1 mg IM Limit, two

times.

• Recheck BG and repeat treatment every 15 min until

glucose level is at least 80 mg/dl.

INSULIN SUBQ ORDERS FOR PATIENTS ON

PARENTERAL/ENTERAL NUTRITION OR

NPO

INSULIN SUBQ ORDERS FOR PATIENTS ON

ORAL NUTRITION

Thank you!