Diabetes Review

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Diabetes Review

• Judy Bornais RN, BScN, MSc, CDE

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Prevalence

• More than 2 million Canadians have diabetes1
• By 2010 that number is expected to rise to 3
  million 1
• 31 rise in prevalence in Ontario since 1995 2
• Estimated that 1 in 5 individual over 45 years of
  age have diabetes and 1 in 3 over the age of 75 3
• Studies suggest that up to 30 of people with
  diabetes are undiagnosed6

3
Did You Know?

• About half of all people diagnosed with diabetes
  have already had the disease for as long as 7
  years1
• 20 - 30 of those individuals diagnosed already
  have developed complications 3

4

• Cardiovascular disease is 2-4 times more
  prevalent in patients with diabetes than in those
  without1
• Cardiovascular disease accounts for at least 60
  of the deaths in patients with diabetes2

5

• When a patient develops vascular complications
  like MI or stroke, the outcome is worse in the
  individual with diabetes3

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The Burden of Cardiovascular Disease in Diabetes
Mortality rate in patients with diabetes more
than doubled versus those without diabetes
Balkau B, et al. Lancet 1997
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Does the outcome depend on the Type of Diabetes?

• Two large studies, UKDPS and DCCT, indicate that
  both Type 1 and Type 2 can result in macro and
  microvascular complications such as
• Coronary heart disease
• Stroke
• Peripheral vascular disease
• Nephropathy
• retinopathy
• Neuropathy

8
Clinical Impact of Diabetes
The leading cause of new cases of end stage renal
disease (ESRD)
A leading cause of cardiovascular events in adults
The leading cause of new cases of blindness in
working age adults
The leading cause of non-traumatic lower
extremity amputations
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Life Expectancy

• Diabetes reduces survival by almost 12 years4

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Diabetes is a Major Health Care Issue
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How does this impact you?

• Patients with diabetes, had higher rates of
  hospitalization than the general population with
  an excess risk of about 30
• In Essex County, in 1999 there were
• 18, 982 cases of people who visited a health
  care provider for their diabetes7

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There is hope!

• Complications of diabetes can be delayed and in
  some cases avoided with tight
• glycemic control
• lifestyle modification
• vascular protection
• Health care professionals roleand the battle
  begins

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Not so long ago in a galaxy remarkably like ours
, the evil Diabetes Empire ruled over a
terror-stricken population. Striking without
warning Diabetes would leave suffering ,
mutilation and death in its wake. Diabetes had
thus ruled unopposed for generations.
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A mere 80 years ago Rebel Fighters , Banting and
Best devised a weapon to battle the Empire. The
weapon was called Insulin. While powerful ,
insulin was difficult to deliver and tricky to
use . Diabetes learned to exploit these
weaknesses over the years. The war raged on.
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To win the battle we mustUnderstand Diabetes
Management

• Diabetes management involves balancing food,
  medication, and activity to achieve blood glucose
  levels that are near the normal range
• Hormones, stress, illness, food - raises blood
  sugars
• Insulin, medications (type 2), exercise lowers
  blood sugars

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Types of Diabetes?

• You have a patient who takes Novolin 20/80 twice
  a day. What type of diabetes does your patient
  have?
• Individual can have either type 1 or type 2.
  Taking insulin does not classify the individual
  as having type 1diabetes.

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What happens in Diabetes

• Type 1 Diabetes
• The pancreas no longer produces insulin. The
  person is totally dependant on exogenous insulin

• Type 2 Diabetes
• The pancreas is not making enough insulin and/or
• the body is resistant (no longer sensitive to
  insulin)

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Treatment for Diabetes

• Type 1 Diabetes
• Insulin

• Type 2 Diabetes
• diet and exercise
• oral hypoglycemics
• oral hypoglycemics and insulin
• insulin

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The Phantom Menace Diabetes New Ally -
Hypoglycemia

• Hypoglycemia a new threat in Glucose Wars.
• No easy way to predict or treat (no glucose tabs
  or glucagon).
• Low blood sugar perceived as greater threat than
  hyperglycemia by caregivers.

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Targets Blood Sugar Ranges4
Fasting / preprandial glucose (mmol/L) 2-hour postprandial glucose (mmol/L)
Targets for most patients with diabetes
Normal range
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Targets Blood Sugar Ranges4
Fasting / preprandial glucose (mmol/L) 2-hour postprandial glucose (mmol/L)
Target for most patients 4.0 7.0 5.0 10.0
Normal range 4.0 - 6.0 5.0 8.0
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Hypoglycemia

• Blood sugars less than 4.0 mmol/L
• What are the Signs Symptoms of a low blood
  sugar?

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Signs and Symptoms of Hypoglycemia

• sweating
• shaking
• weakness
• hunger
• nausea
• irritability
• confusion

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Symptoms of Hypoglycemia5

• Neurogenic (autonomic)
• Sweating (47 84)
• Trembling (32-78)
• Palpitations (8-62)
• Hunger (39-49)
• Anxiety (10-44)
• Nausea (5-20)
• Tingling (10-39)

• Neuroglycopenic
• Difficulty concentration (31-75)
• Weakness (28-71)
• Vision change (24-60)
• Confusion (13-53)
• Tiredness (38-46)
• Difficulty speaking (7-41)
• Dizziness (11-41)
• Headache (24-36)

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SEVERITY OF HYPOGLYCEMIA4

• MILD
• Autonomic symptoms are present
• Individual is able to self-treat
• MODERATE
• Autonomic and neuroglycopenic symptoms are
  present
• Individual is able to self-treat
• SEVERE
• Individual requires assistance of another person
• Unconsciousness may occur
• Plasma glucose is typically lt 2.8 mmol/L

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How do you treat a low blood sugar?

• A) Chocolate bar?
• B) A hard candy?
• C) Juice?
• D) Glucose tabs?

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How do you treat a low blood sugar?

• A)
• B) A hard candy (2-3)
• C) Juice (3/4 cup)
• D) Glucose tabs (3 glucose tabs)

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Treatment for Hypoglycemia
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When do Hypos occur?

• Episodes of hypoglycemia most commonly occur
  before meals or when the insulin effect is
  peaking.
• Patient is on Humalog/Novorapid at breakfast eats
  less than normal when would you expect the
  hypoglycemia?
• Patient takes NPH at bedtime when are they most
  likely to have a low?

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Medications can blunt response to hypoglycemia6

• Salicylates (Aspirin in large doses gt4g/day)
• Sulfonomide antibiotics (Probenecid Benemid,
  Benuryl, Probalan)
• Tricyclic antidepressants (Amitriptyline
  Elavil Anafranil, Sinequan, Triadapin, Impril,
  Novopramine, Nortriptyline Aventyl Triptil)
• Phenylbutazone (for rheumatoid arthritis,
  osteoarthritis or gouty arthritis)
• Warfarin (Coumadin)
• Fibrates

.
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Medications can blunt response to hypoglycemia

• Pentamidine (Nebupent, Pentacarinat)
• Acetaminophen (Tylenol)
• ACE Inhibitors (Captopril, Lisinopril, Enalapril,
  Ramipril)
• Beta Blockers (Acebutolol, Carvedilol, Labetalol,
  Metoprolol)
• Celexa (antidepressant)

.
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Hyperglycemia

• Elevated blood sugars outside of the
  normal/target ranges i.e. a blood sugar over 10.0
  mmol/L (2 hours post-prandial)
• What are the Signs Symptoms of hyperglycemia?

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Signs and Symptoms of Hyperglycemia
Extreme thirst
Fatigue
Frequent urination
Weight loss
Blurred vision
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Treatment for Hyperglycemiathe forces strike back

• Obtain near normal blood sugar levels through
• Insulin,
• Medications
• Exercise

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The Phantom Menace Fatalists the Other Ally
of Diabetes

• A large faction of caregivers and individuals
  with diabetes believed that all complications
  were genetically programmed would occur no
  matter what the blood glucose levels were !
• Treated to relieve symptoms only.
• Waited for complications to show up. Fate and
  luck !

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Review of Complications of Diabetes

• Neuropathy
• Retinopathy
• Nephropathy
• Macro vascular complications
• Foot Problems (ulcers amputations)
• Dental Skin Problems

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A New Hope The DCCT

• 1993 New England J. of Medicine
• Glucose hypothesis proven to be true
• Never too late to improve control
• Any improvement in control is beneficial
• A powerful way to employ insulin (medications) in
  the battle with Diabetes

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Summary DCCT

• 69 reduction in Neuropathy
• Trend toward reduction in risk of heart disease

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Improved Insulin and Delivery

• 1985 modernization of insulin by genetic
  engineering to produce Human insulin
  Humulin Novolin
• 1995 Introduction of insulin analogues Lispro
  Humalog Aspart - Novorapide
• 2005 Introduction of new long acting insulin
• Glarzine Lantus
• 2006 Another long acting insulin
• Levermir (expected to be available in Jan./06)

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Challenge of Insulin

• To mimic the pancreas
• 2 patterns
• a basal secretion of insulin
• intermittent bolus of insulin in response to food

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Goals of Insulin Therapy

• To control blood glucose levels
• Prevent the development and progression of
  long-term complications from hyperglycemia
• Minimize effects of hypoglycemia
• Mimic endogenous insulin

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Insulins are divided into 5 main types

• Rapid-acting
• Short-acting
• Intermediate-acting
• Long-acting
• Premixed

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Rapid-Acting Insulin (new analogues)

• Insulin Lispro (Humalog)
• Insulin Aspart (Novorapid)

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Insulin lispro (Humalog) Insulin aspart
(Novorapid)

• May be taken before or after meals
• appearance clear
• onset 10 -15 min
• peak 45 min - 3 hrs
• duration 3 - 5 hrs
• Take WITH meals

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Short-acting or Regular (R) Insulin

• Novolin ge Toronto (R) or Humulin R
• appearance clear
• onset 1/2 hr - 1 hr
• peak 2 - 5 hrs
• duration 6 - 8 hrs
• Take 30 minutes before meals

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Intermediate-acting or NPH/Lente

• Novolin NPH or Humulin N
• Novolin Lente or Humulin L
• appearance cloudy
• onset 1 - 3 hrs
• peak 4 - 12 hrs
• duration 18 - 24 hrs

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Long-acting Two types

• Ultra Lente
• Novolin Ultra Lente or Humulin U
• appearance cloudy
• onset 4 - 6 hrs
• peak 8 - 20 hrs
• duration 24 gt

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Long-acting Two types

• Glargine (Lantus) NEW!
• Levemir
• appearance clear
• onset 3-4 hrs
• peak no peak
• duration 24 hrs
• acts like basal insulin
• Can not be mixed with any other insulin

55
Example profiles interstitial glucose
fluctuations from the mean
Glucose
25
450
Patient 1 NPH insulin
20
360
15
270
(mg/dl)
(mmol/l)
10
180
5
90
0
0
Glucose
0600
0800
1000
1200
1400
1600
1800
2000
2200
0000
0200
0400
0600
25
450
Patient 2 Insulin detemir
20
360
15
270
(mmol/l)
(mg/dl)
10
180
5
90
0
0800
1000
1200
1400
1600
1800
2000
2200
0000
0200
0400
0600
0600
CGMS profiles
Russell-Jones D et al. Clinical Therapeutics
200426724-36
Time
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Hypoglycaemia Relative Risk (Insulin detemir
vs. NPH)
Insulin detemir
NPH insulin
10

1.2


18
39
16
50
Baseline
1
8
Relative risk
0.8
6
0.6
HbA1c
4
0.4
2
0.2
0
0
All
Major
Minor
All nocturnal
Between-group difference, plt 0.05
Kolendorf et al. Diabetes 200453(Suppl. 2)A130.
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Action Times of Insulin
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Premixed 10/90, 20/80, 30/70, 40/60, 50/50

• 20/80
• Intermediate or NPH insulin
• Acts as the background insulin throughout the day
  or night

• Example
• 20/80
• Short-acting or Regular insulin
• Works on the meal you take it with

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When is the ideal time to give a patient their
premixed 30/70 insulin?

• a) 30 minutes before their meal
• b) With their meal
• c) After their meal

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PremixedHumalog Mix 25Novomix 30

• Example
• 25/75
• Fast acting insulin
• Works on the meal you take it with

• 25/75
• Intermediate or NPH insulin
• Acts as the background insulin throughout the day
  or night

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When is the ideal time to give a patient their
premixed Humalog Mix 25 insulin?

• a) 30 minutes before their meal
• b) With their meal
• c) After their meal

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Giving Insulin

• Vial and syringe
• Which insulin do you draw up first if you are
  mixing insulins?
• Clear then cloudy to avoid contaminating the
  clear insulin
• Insulin Pens

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Site Selection Where can I give my injections?

• 4 major areas
• upper outer area of arm
• abdomen - avoid 1 inch area around navel
• front and sides of thighs
• upper outer surfaces of the buttocks

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Site Selection Do you rub the site after
injection?

• Note do not rub the site after injection,
• just apply light pressure to stop the
• bleeding if necessary

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Case study

• You have a 19 year old female who has Type 1
  diabetes who receives Novolin 30/70 before
  breakfast and supper. She is late awakening and
  doesnt eat her breakfast and is going to
  university to return home for lunch. What do you
  do?

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Types of oral hypoglycemics

• Biguanides Decrease glucose release in the liver
  and decrease insulin resistance in muscles
• Metformin (Glucophage) take with meals
• duration of action 8-12 hours
• Key No risk for hypoglycemia when taken alone
  and at the recommended dose
• Contraindicated in patients with renal or
  hepatic dysfunction or cardiac failure
• Alcohol not recommended

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Types of oral hypoglycemics

• Insulin Secretagogues Sulfonylureas increase
  insulin secretion and potentiate insulin action
  on liver and peripheral tissues
• Glyburide (Diabeta) lasts 18-24 hours
• Gliclazide (Diamicron) last 12 -24 hours
  (Diamicron MR) last 24 hours
• Glimepiride (Amaryl) lasts 24 hours
• KEY cannot skip meals - risk of hypoglycemia

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Types of oral hypoglycemics

• Insulin Secretagogues Non sulfonylureas
• (Meglitidines) increase insulin secretion
• Repaglinide (GlucoNorm) lasts approx 3 hours
• Nateglinide (Starlix) lasts approx.1.5-3 hours
• KEY Less risk of hypoglycemia in the context of
  missed meals

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Types of oral hypoglycemics

• Alpha glucosidase inhibitors slow
• absorption of carbohydrates
• Acarbose (Prandase) lasts to cover the meal
• Decrease CHO digestion / prolongs uptake of CHO
• Key Treat hypoglycemia ONLY with dextrose
  tablets, milk or honey

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Types of oral hypoglycemics

• Thiazolidinediones decrease insulin resistance
• Pioglitazone (Actose) lasts 16-24 hours
• Rosiglitazone (Avandia) lasts 15-20 hours
• Insulin sensitizers
• Increase peripheral utilization of insulin (at
  the tissue level)
• Modify lipoproteins (increase HDLs)
• Contraindicated in renal, hepatic and CHF
  patients

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Challenge of Diabetes

• Imagine as an adult having to check your blood
  sugar on average 5-6 times a day more often
  during periods of illness or stress
• Imagine having to carry your glucometer/insulin/me
  ds with you at all times
• Imagine Having to give yourself insulin at a
  restaurant before eating

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Issues of Cost

• Blood Glucose strips average 1/strip
• Lancets 10
• Box Insulin Pen needles 25-35
• Cost of insulin cartridge 40-69
• _ vials 27-39
• Total 300/month

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The Empire Strikes Back

• Insurers ODB , Green Shield , and others
  - Barriers to treatment LU for
  Humalog Section 8 for NovoRapide (Pen 3
  Jr.) Decreased coverage for insulin
  
  pumps/pump supplies Restricted coverage for
  Glucagon (96 per single injection kit)

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Attack of the Clones

• Improved delivery systems Pen
  injectors Ultrafine needles Jet
  injectors
• Improved glucose surveillance systems Improved
  glucose meters Computer downloading of
  results Ultrafine lancets Dorsal arm testing

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Diagnosis - grieving

• May newly diagnosed patients and/or their
  families experience cycle through
• Denial
• Anger
• Bargaining
• acceptance

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Sick Day Management

• Minor illnesses cold, flu, gastroenteritis
  impair glucose control
• Stress on the body
• Cause an increase in blood sugar levels for 2
  reasons
• - an increase in hormones that cause the liver
  to pump out glucose into the blood
• - hormones also increase the resistance of
  cells to insulin

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Sick Day Management

• MONITORING
• Patients should be testing their blood sugar
  before meals and/or every 4 hours around the
  clock, until no longer sick or as directed by
  their physician or Nurse practitioner
• Urine should be tested for ketones (Type 1)
  presence means a serious situation.

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Sick Day Management

• MEDICATION
• Patients should continue to take their insulin,
  even if they are vomiting
• If the patient uses Humalog or Novorapid and they
  are nauseated, consider giving the injection
  AFTER they eat determine carbohydrates and
  insulin dose.
• Patients may require additional doses of short or
  rapid acting insulin - notify the physician if
  your patient requires insulin and has been
  vomiting.

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Sick Day Management Contd

• LIQUIDS
• If a patient is losing fluids due to diarrhea,
  fever, or vomiting , or they are drinking less
  than usual or urinating more than usual, they are
  at risk for dehydration.
• They should drink 8 oz of liquid every hour
  (avoid caffeine)

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Case Study 2

• You have a patient with the stomach flu who has a
  temperature of 38.3 C and unable to eat.
• A) What should you do?
• B) Do you still give her insulin?

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Diabetic Ketoacidosis (DKA)

• Can be caused by
• Too little insulin and increased food intake
• Physical or emotional stress
• Undiagnosed diabetes

.
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DKA Signs Symptoms

• Abdominal pain
• Nausea and vomiting
• Dehydration
• Blurred Vision
• Fruity smelling ketone breath
• Excessive Thirst
• Frequent urination ketones present
• Dry mouth
• Restlessness, confusion
• Flushed feeling
• Rapid breathing or heart beat
• Sleepiness, difficulty staying awake

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Ketones What Are They?

• Normally, our bodies turns the food you eat into
  sugar (glucose)
• Sugar is the bodies main source of energy
• Without insulin, body cells cannot use sugar
  present in the blood
• The body receives a message to use energy from
  fat
• The body uses the fat for energy by changing it
  into sugar

.
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Ketones What Are They?

• When fat is broken down, KETONES are made
• KETONES are acid chemicals which are harmful to
  the body
• The body tries to filter them from the
  bloodstream into the urine

.
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DKA What happens?

• Not enough insulin
• ?
• Sugar not being used for energy
• ?
• Break down fat for energy
• ?
• Production of ketones
• ?
• Ketones (acid chemicals) cause altered pH and
  acidosis
• ?
• Ketonuria (to try and get rid of them)
• ?
• Dehydration and Loss of Electrolytes

.
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DKA Treatment?

• Replacement of fluid losses
• Correction of hyperglycemia.
• With low dose IV insulin (to prevent cerebral
  edema
• Replacement of electrolyte losses (Na and K)
• Detection of cause and prevention of future
  episodes ketone testing

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What do all these tests mean?

• Fasting blood sugar
• Creatinine
• Albumin to
• Creatinine ratio
• Blood Pressure
• A1C

• Lipids
• Cholesterol//HDL ratio
• HDL cholesterol
• LDL cholesterol
• Triglyceride

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Fasting Blood Sugar (FBS)

• Measures the amount of sugar in the blood after
  fasting for 8 hrs
• Usually done just before breakfast
• Target Current goal is between 4 7 mmol/L CDA
  guidelines (2003)

.
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Creatinine

• A blood test to check kidney function
• Creatinine clearance - is an estimate of the
  kidneys ability to filter toxins from the blood
• Target 20 - 120 umol/L
• Should be checked every year
• Patients may remain asymptomatic until as much as
  75 of renal function is lost8
• The older and smaller the patient, the lower
  their creatinine should be

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Albumin to Creatinine Ratio

• A urine test to catch early signs of kidney
  damage
• Detection of microalbuminuria identifies
  individuals at high risk of progressing to later
  stages of renal disease9-10, those at risk for
  cardiovascular events and death4, 11
• Target lt 2.0 mg/mmol for men4 lt 2.8
  mg/mmol for women4
• Prevention

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Blood Pressure (review)

• The pressure blood puts on the wall of the blood
  vessel
• Measures systolic pressure (heart contracts)
• diastolic pressure (heart relaxes)
• Target 130/80
• Research from HOT and
• UKPDS 38 trials

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Tips to Lower Blood Pressure Health Promotion

• Reach/keep a healthy weight
• Be more active
• Drink less alcohol/eat less salt
• Stop smoking
• Take blood pressure medicine (as prescribed by
  your doctor or nurse practitioner)

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LIPIDS Important

• 1. Cholesterol/HDL Ratio
• The ratio describes how much HDL (good)
  cholesterol is part of the total cholesterol
• It is a better measure of risk for heart disease
  than Total Cholesterol alone
• Target less than 4.0 for most individuals with
  diabetes

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How to lower the cholesterol/HDL ratio and
triglycerides Health Promotion

• Reach and keep a healthy weight
• Be active!
• Choose lower fat foods
• Reach and keep good blood glucose control
• Reduce OR stop smoking
• See their MD to have levels rechecked in 3 months
• Take medication as prescribed

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2. HDL Cholesterol (High Density Lipoprotein)

• Healthy Cholesterol
• measures good cholesterol levels
• called good because it carries extra
  cholesterol out of the blood vessels
• a LOW level is a risk factor for heart disease
  (elevated plasma apo B4 )
• Lowering triglycerides helps improve HDL levels

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3. LDL Cholesterol (Low Density Lipoprotein)

• Unhealthy cholesterol
• measures bad cholesterol because it tends to
  collect in artery walls, and can speed hardening
  of the arteries
• Target lt 2.5mmol/L for most individuals with
  diabetes

.
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Tips to Lower LDL Health Promotion

• Decrease intake of foods high in cholesterol,
  saturated fats and trans fats
• Eat more soluble fibre (beans, oats, barley and
  some fruits and vegetables)

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4. Triglycerides

• Measures another type of fat that moves in the
  blood along with cholesterol
• High levels often appear with other well-known
  risk factors for heart disease, such as obesity
  and diabetes
• Optimal lt 1.5 mmol/L

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More Tips to Lower Triglycerides

• Eat fewer sweets
• Drink less alcohol
• Lower your blood sugar

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LIPID TARGETS BASED ON RISK OF A VASCULAR EVENT4
Risk LDL-C (mmol/L) TC HDL-C
High (most DM) lt 2.5 and lt 4.0
Moderate lt 3.5 and lt 5.0

• Moderate risk younger age with short duration
  of DM, no complications and no other CVD risks.
• TG are not indicated as a target because almost
  all individuals with hyper-triglyceridemia can be
  identified as having an elevated TCHDL-C.
• Optimal TG is lt 1.5 mmol/L. Optimal apo B lt 0.9
  g/L for high-risk individuals, and 1.05 g/L for
  moderate-risk individuals

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Glycosylated Hemoglobin OR Hemoglobin A1C (A1C)

• A check of long term control
• Average blood sugar over 3 months
• Do not need to fast for this test
• Goal is less than 7

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WHEN WILL THE BATTLE END?

• NOT TILL THE CURE IS FOUND
• MANY DEDICATED SCIENTISTS AND PHYSICIANS WORKING
  DILIGENTLY
• THE COMPLETION OF THE HUMAN GENOME PROJECT BRINGS
  US ONE STEP CLOSER TO VICTORY
• NOT UNTIL PREVENTION OF TYPE 2 OCCURS

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Are you at Risk for Diabetes?

• Age ? 40 years
• First-degree relative with diabetes
• Member of high-risk population (people of
  Aboriginal, Hispanic, South Asian, Asian or
  African descent)
• History of IGT or IFG
• Presence of complications associated with
  diabetes
• Vascular disease
• History of gestational diabetes or macrosomic
  infant
• Hypertension, dyslipidemia, overweight or
  abdominal obesity
• Polycystic ovarian syndrome
• Acanthosis nigricans
• Schizophrenia

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BUT !!! , TILL THEN

• THE BATTLE MUST STILL BE WAGED
• HELP YOUR DIABETES PATIENTS RECEIVE THE BEST
  POSSIBLE CARE
• TILL THE FINAL VICTORY , WHEN TYPE 1 DIABETES
  WILL FADE INTO HISTORY
• TILL TYPE 2 DIABETES IS PREVENTED