Diabetes Review and Update on New

Therapies

John G. Morrow III, M.D.

Emory University School of Medicine

Atlanta, Georgia

Understanding Southern Y’All

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Conflict of Interest

There are no industry or other financial relationships to disclose

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Goals and Objectives

• Review of Diabetes physiology

• Insulin – old and new

• Recent studies

• Recommendations for Outpatient surgery

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What is Diabetes?

The body does not make or properly use insulin:

no insulin production

insufficient insulin production

resistance to insulin’s effects

All body cells need energy and glucose (blood sugar) is the body’s main source of energy.

Insulin, produced by the pancreas, allows the body to move blood sugar (glucose) into cells, where it fuels the body.

Without insulin to move sugar from blood into cells blood sugar rises (hyperglycemia) and the cells starve.

How the Body Uses Food as Fuel

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I

GLUCOSE

Blood Stream Cell

G

G

G

G G

G

Digestion of

Macronutrients

(CHO, FAT, PRO)

Pancreas

(Insulin) I I

I

I

I Insulin

Type 1 or Type 2?

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Type 1 Diabetes

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• Auto immune disorder

• Insulin deficient; insulin producing cells destroyed

• Daily insulin replacement necessary

• Age of onset: usually childhood, young adulthood

• Most prevalent type of diabetes in children and

adolescents

Type 1 Diabetes: Insulin Deficiency

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Glucose

Blood Stream Cell

G

G

G

Pancreas

(Insulin) XXXXX

Type 2 Diabetes

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Not auto immune disorder

Insulin resistance/insufficiency

May be treated with diet, oral medication or insulin

Most common in adults, but increasingly more

common in children

90% of the 18 million Americans living with

diabetes are Type 2

Type 2 Diabetes: Insulin Resistance

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I

GLUCOSE

Blood Stream Cell

G

G

G

Pancreas

(Insulin) I I

I

I

I Insulin I

Hgb A1C

• % of Hgb which has been “glycosylated” by glucose

• Good indicator of BG control over the previous 3 months

• Normal 4-6%

• Recommended by ADA <7% to <8.5% depending on age

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Insulin

• First discovered in 1921 by Charles Best

• The only way to administer insulin is by injection or pump

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Insulin Action

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Normal insulin delivery

This is a 24 hour representation of the insulin profile for

someone who does not have diabetes. The pancreas

releases insulin for each meal, but there is always a

constant background or basal amount present that has

nothing to do with food.

Insulin regimens

• Split/Mixed (old way)

• Basal/Bolus (new way)

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Split/Mixed regimen Two or three injections/day

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• The breakfast injection combines a short-acting insulin

which covers just that meal.

• The intermediate-acting insulin, mixed in the same

injection, covers lunch and the hours until supper.

• The supper injection covers the evening meal and the

nighttime hours.

Physiologic Insulin Regimen (Basal/Bolus Regimens)

• These regimens most closely mimic a normally-functioning pancreas

• Majority of people with Type 1 will be on one of two types of physiologic regimens:

– Lantus(glargine) and pre-meal short acting insulin

– Insulin Pump

• More people with Type 2 are being put on these regimens

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Basal Insulin

– Basal insulin maintains blood sugar in the absence of food

– Basal insulin can be given via a pump or once a day injection of Lantus insulin

– Basal rates in pumps are programmed to be delivered automatically

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Types of Insulin

Intermediate and Long Acting Insulins

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Type Onset Peak Duration

NPH

(N)

1-3

hours

6-8

hours

10-12

hours

Lantus

(Glargine)

2-4

hours

No

pronounced

peak

24 +

hours

Levemir

(Detemir)

2-4

hours

No

pronounced

peak

12-18

hours

Bolus Insulin

• Type of bolus insulin: Humalog (H), Novolog (A), Apidra (P) and Regular (R)

• This is a “burst” of insulin either programmed into a pump or given as an injection prior to a meal.

• The bolus is determined by the amount of carbohydrates to be consumed and the level of blood sugar at the time.

• If blood sugar is elevated at meal time, then a correction amount is included to cover the high blood sugar.

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Types of Insulin:

Very Short Acting and Short Acting Insulins

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Type Onset Peak Duration

Humalog

(Lispro)

5-15

minutes

1-2

hours

2 -4

hours

Apidra

(glulisine)

5-15

minutes

1-2

hours

2-4

hours

Novolog

(aspart)

5-15

minutes

1-2

hours

2-4

hours

Regular

(R)

30

minutes

2-4

hours

6-8

hours

WARNING: LA-SA DRUGS

• Novolin R

• Novolin N

• Humulin R

• Humulin N

• Novolog

• Humalog

• **Novolin and Humulin are Brands

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Basal/Bolus Regimens (also known as physiologic regimens)

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This shows the basal/bolus regimen with the background or

basal insulin as the thick black line at the bottom. Meal or

bolus doses are delivered in varying amounts and times

according to meals.

Insulin Action

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Normal insulin delivery

This is a 24 hour representation of the insulin profile for

someone who does not have diabetes. The pancreas

releases insulin for each meal, but there is always a

constant background or basal amount present that has

nothing to do with food.

Ways to Give Insulin- Injections

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Insulin can be injected with a standard

vial and syringe or by using a pre-filled

insulin pen.

Ways to Give Insulin- Insulin Pumps

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• Insulin pumps are computers that deliver

insulin continuously instead of taking

multiple injections.

Pump Facts

Pumps :

• Are pager sized “mini-computers”

• Do not measure glucose levels

• Deliver programmed (bolus) insulin

• Deliver pre-programmed insulin

delivery (basal)

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Pump Sites

• Pump sites are changed every 2-3 days

• Pumps can be disconnected

for activities and/or showers

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Catheter- small plastic tube that remains under the skin.

Literature Review

Intensive insulin therapy in critically ill patients

• 2001 NEJM Van der Berghe, et al

– Randomized control trial

– >1500 surgical ICU pts

– Intensive insulin therapy (IIT)(BG 80-110) vs

Standard insulin therapy (BG 180-200)

– Reduced in-hosp mortality by 34%

– Reduced morbidities including infections, ARF, transfusions

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Cardiac surgery

• 2005 Anesthesiology “Poor intraoperative blood glucose control is associated

with worsened hospital outcome after cardiac surgery” • 2005 Mayo Clin Proc “Intraoperative hyperglycemia and perioperative

outcomes in cardiac surgery patients” • 2005 J Thorac Cardiovasc Surg “Hyperglycemia during cardiopulmonary bypass is an

independent risk factor for mortality in patients undergoing cardiac surgery”

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Neurosurgery

• 2007 J Neurosurg Anesthesiol

“The effect of IIT on infection rate, vasospasm, neurologic outcome and mortality in ICU after intracranial aneurysm clipping in pts w/ SAH”

• 2007 Annals of Internal Medicine

“Intraoperative IIT vs. conventional glucose management during cardiac surgery”

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Benefits and Risks of Tight Glucose Control in Critically Ill Patients

• 2008 JAMA

• Meta-analysis

• 34 randomized trials

• Conclusion: In critically ill patients, tight glucose control is not associated with significantly reduced mortality but is associated with an increased risk of severe hypoglycemia

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Review Article: Perioperative Glycemic Control

• 2009 Anesthesiology

• Comprehensive review of all studies

• Conclusions:

– Insufficient evidence to support routine use of tight gycemic control (80-110)

– Some patients may benefit but who they are and what the BG target should be have not clearly been identified

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Perioperative Management

• 2005 Anesth Analg Rhodes, et al

– Algorithm developed at Children’s Hospital Boston

– Type 1 or Type 2

– In-patients and Out-patients

– Correction of hyperglycemia with rapid-acting insulins using correction formulas

– Pump management

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Case report: Preoperative Hypoglycemia in a Patient Receiving Insulin Detemir

• 2009 Anesthesia and Analgesia Olson, et al

– Pt with Type 2

– Recently changed from 70/30 to Detemir/Apidra

– Took 45 units Detemir am of surgery

– BG 68 required multiple glucose infusions IV to maintain BG above 100

– Beware of potential for hypoglycemia in patients on long acting insulin

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SAMBA guidelines for Diabetes Management in out-patients

• Anesthesia and Analgesia December 2010 Volume 111 Number 6

• Literature review and attempt to answer 13 specific questions

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Recommendations: Night Before Surgery

• Oral agents

– Continue all oral agents except metformin (glucophage), which has very long half-life and should be stopped 24hrs before surgery

• Injectable agents

– Insulin

• Basal- take 75% of basal insulin evening or night before surgery if normally taken in evening

• Bolus – take normal dose of short acting insulin

• Continue Insulin pump at normal rates

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Recommendations: Day of Surgery

• Oral Agents – hold all oral agents especially metformin (Glucophage)

• Check BG at home

• Injectable Agents

– Basal insulin – If BG > 100, take 75% of basal insulin if normally taken in morning

– Bolus insulin – If BG < 200, do not take any short acting insulin

– Byetta (exenatide) /Symlin (pramlintide) – HOLD DOS

– BRING insulin and other meds DOS

– Continue insulin pump at normal rates

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Recommendations: Day of Surgery

• Schedule surgery as early as possible

• Treatment of low blood sugars:

– Without IV: 4 oz of sugar containing clear liquid – recheck BG in 15 minutes, retreat if necessary until BG > 100

– With IV:

• Asymptomatic – infuse 250ccs D5W – recheck in 15 minutes, retreat is BG still <100

• Symptomatic – push 12.5 grams (25 cc) D50 followed with D5W infusion, recheck in 15 minutes

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Recommendations: Day of Surgery

• Treatment of High Blood Sugars:

– BG < 200: No treatment

– BG > 200:

• Did patient receive their basal insulin last night or morning of surgery? If not, give 100% of their basal insulin.

• If patient received basal or is not on basal insulin, consider correction dose of short acting insulin based on correction formula

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Recommendations: Day of Surgery

Correction formula: (BG – 150)/sensitivity = # units of short-acting insulin to be given

• Consider using rapid-acting insulin SQ for faster action and shorter duration especially if pt already uses Novolog or Humalog

• Recheck BG every hour if short-acting insulin is given • Do not “stack” doses of Regular insulin – remember it lasts for

6-8 hours • Only Regular (R) insulin can be given IV • Target BG range 120-200

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Recommendations Day of Surgery

• Patients on insulin pumps:

– Leave pump on

– If BG< 120 – give D5W IV, recheck until >120

– If BG> 200 – give correction dose of insulin based on pts correction formula

– If BG> 300 – site is probably not working, give insulin by injection

– Know how to suspend or disconnect pump

– Q2h Blood sugars, especially if under GA

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Review

• Review of Diabetes physiology

• Insulin – old and new

• Recent studies

• Recommendations for Out-patient surgery

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