Update on Diabetes Medications and Guidelines in Cardiopulmonary Rehab Setting

1
Update on Diabetes Medications and Guidelines in
Cardiopulmonary Rehab Setting

• Raja Hanania, R.Ph, CDM, CDE, BCPS
• Clinical Pharmacy Specialist
• Critical Care/Diabetes Care
• IU-Health- Bloomington Hospital
• Bloomington-Indiana

2
Objectives

• Learn about the impact of diabetes in the United
  States
• Review oral and injectable diabetes medications
  and their role in diabetes management
• Review the 2013 ADA general recommendations with
  special emphasis on physical activity and
  exercise in the cardiopulmonary rehab setting

3
National Diabetes Estimates

• 25.8 million Americans (8.3 of the US
  population)
• 7 million undiagnosed
• 79 million American adults aged 20 years or older
  qualify as being at high risk to develop diabetes
  (fasting glucose between 100 and 125)
• If the trend continues, 1-in-3 American adults
  will have diabetes by 2050
• The 7th leading cause of death in the US
• The leading cause of blindness, renal failure and
  nontraumatic amputations between the age of 20-74
• Cost U.S. national economic burden of
  pre-diabetes and diabetes reached 245 billion in
  2012, 218 billion in 2007 , 132 billion in 2002
  vs. 44 billion in 1997
• CDC National Diabetes Fact Sheet 2011.
• ADA diabetes Statistics 2013

4
Making the Diagnosis

• Fasting Plasma Glucose Test
• 99 or below Normal
• 100 to 125 Pre-diabetes (impaired fasting
  glucose (IFG))
• 126 Diabetes
• Oral Glucose Tolerance Test (OGTT)
• 2 hr plasma glucose result
• 139 and below Normal
• 140-199 Pre-diabetes (impaired glucose
  tolerance (IGT))
• 200 and above Diabetes
• Random Plasma Glucose Test
• 200 or more plus presence of symptoms
  (polydypsia/polyuria/polyphagia) Diabetes
• Results should be confirmed by repeating the test
  on another day prior to diagnosis
• A1c 6.5 (new 2010 criteria for diagnosis)

5
Classification of Diabetes

• Insulin-Dependent Diabetes Mellitus (Type I)
• High anti-beta cell antibodies
• Low plasma insulin concentration (determined by
  C-peptide levels)
• Usually lean and young patients but this trend in
  changing
• Non-Insulin-Dependent Diabetes Mellitus (Type II)
• Serum insulin levels normal or elevated but still
  have relative insulin deficiency
• Metabolism does not respond properly to insulin
  insulin resistance
• Usually obese (60-90) and older but thins trend
  is changing
• Losing weight frequently brings glucose levels
  and insulin sensitivity back under control
• Strong genetic linkage

6
Classification of Diabetes (Cont.)

• Type 1.5 Diabetes (also known as slow onset type
  I or latent autoimmune diabetes in adults)
• Patients do not immediately require insulin for
  treatment
• Little or no resistance to insulin
• Antibodies present (especially GAD65)
• Can be easily misdiagnosed as Type II since
  patients are older and respond to oral
  medications except glitazones (since little or no
  insulin resistance) usually have good C-peptide
  levels
• Gestational Diabetes (GD)
• In most cases, slender and physically fit
  patients
• Approximately 4 of all pregnancies according to
  ADA
• 5-10 of women with GD are found to have type 2
  diabetes
• Women with GD have 20-50 chance to develop
  diabetes in the next 5-10 years

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Type 3 Diabetes??

• Alzheimers can be associated with low levels of
  insulin in the brain is the reason why increasing
  numbers of researchers have taken to calling it
  Type 3 diabetes, or "Diabetes of the Brain
• In Alzheimers, the brain, especially parts that
  deal with memory and personality, become
  resistant to insulin.  Research is ongoing and
  there will be more to come on the link between
  diabetes and the brain.

8
Risk Factors

• Family History
• Obesity 20 over IBW or BMI gt 27
• Age over 45 years old
• History of impaired glucose tolerance or impaired
  fasting glucose
• Hypertension
• HDL lt 35 and/or TG gt 200
• Smoking
• Race/Ethnicity
• Pregnancy

9
Clinical Practice Recommendations

• ADA
• Begin screening at age 45
• Preprandial BG 70-130
• 2 hr postprandial lt180
• Average bedtime BG 100-140
• A1c goal lt7 for patients in general, EAG (28.7x
  A1c) - 46.7
• (6 126 mg/dl, 7 154, 8 183, 9 212, etc.)

• AACE
• Begin screening at age 30
• Preprandial BG 110
• 2 hr postprandial lt140
• A1c goal lt6.5

ADA American Diabetes Association AACE American
Association of Clinical Endocrinologists
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Benefits of Reducing A1c by 1

• Type I diabetes (DCCT)
• -32 decrease in risk for retinopathy
• -20 -27 decrease in risk for nephropathy
• -30 decrease in risk for neuropathy
• Type II diabetes (UKPDS)
• -10 decrease in risk in diabetes related death
• - 6 decrease in all-cause mortality
• -16 decrease in risk for MI
• -25 decrease in microvascular complications
• DCCT Diabetes Control and Complications Trial
• UKPDS United Kingdom Prospective Diabetes Study

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A1C Goals Unmet in Majority of Patients With
Diabetes
10.0
9.5
9.0
8.5
A1C ()
8.0
7.5
7.0
ACE recommended target (lt6.5)4
6.5
Upper limit of normal range (6)
6.0
5.5
1. Data from Saydah SH, et al. JAMA. 2004
291335-342 2. Calculated from Koro CE, et al.
Diabetes Care. 2004 2717-20 3. Data from ADA.
Diabetes Care. 2003 26(suppl 1)S33-S50 4. Data
from ACE. Endocrine Practice. 2002
12
Diabetes Management

• Control of A1c, fasting glucose(FG) and
  postprandial glucose levels (PPG) (DECODE study
  showed that PPG is more predictive than AIC and
  FG for CV risk)
• Hypertension-goal is lt140/80 mmHg
• Dyslipidemia (General Guidelines)
• LDLlt100 mg/dl
• HDL men gt40 mg/dl, women gt50 mg/dl
• Triglycerideslt150 mg/dl
• Diabetes Epidemiology Collaborative Analysis of
  Diagnostic Criteria in Europe (DECODE)

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Review of Oral Hypoglycemic Meds

• Sulfonylureas
• Meglitinides
• Thiazolidinediones
• Biguanides
• Alpha-Glucosidase Inhibitors
• Dipeptidyl Peptidase IV inhibitors (DPP 4
  inhibitors)
• Sodium Glucose Co-transporter 2 Inhibitor (SGLT-2
  inhibitor)
• Combination Products
• Others Welchol and Cycloset

14
Sulfonylureas

• Stimulate insulin production from pancreas
• Glyburide (Diabeta, Micronase, Glynase), max.
  dose 20 mg/day
• Glipizide (Glucotrol)-taken 30 min before
  eating, max. dose 40 mg/day, (Glucotrol XL)-may
  be taken with food, max. dose 20 mg/day
• Glimipiride (Amaryl)-taken with food, max dose 8
  mg/day
• Watch for renal dysfunction
• -Glyburide not recommended for CrCllt50 ml/min,
  contraindicated for patients with severe renal
  failure
• -Glimipiride lt 30ml/min, start with 1 mg daily
  and adjust
• -Glipizide lt 10ml/min use a conservative dose
  adjust
• Side effects-hypoglycemia, GI effects and sun
  sensitivity

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Meglitinides

• Stimulate insulin production from pancreas
• Repaglinide (Prandin)-Max. dose 4 mg tid-qid
• Nateglinide (Starlix)-Max. dose 120 mg tid
• To be taken 15-30 min before meals
• Skip doses for skipped meals
• Side effects hypoglycemia and GI effects

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Thiazolidinediones (TZDs)

• Decrease insulin resistance, promote skeletal
  muscle glucose uptake
• Rosiglitazone (Avandia)-taken with meals once or
  twice daily. Max. dose 8 mg/day
• Pioglitazone (Actos)-taken once daily. Max. dose
  45 mg/day
• Monitor LFTs every 2 months for the first year of
  therapy then periodically.
• Not recommended if LFTs gt2.5 times upper limit
  or for NYHA class III or IV CHF patients
• Side effects Edema (secondary to plasma volume
  expansion), GI effects, weight gain and back pain

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Biguanides

• Decrease production of glucose in the liver,
  decrease glucose absorption improve insulin
  sensitivity
• Metformin (Glucophage, Glucophage XR,
  Fortamet, Riomet (liquid metformin))- Max dose
  2550 mg/day
• Used first line for obese diabetics
• May also be used for polycystic ovary syndrome
  (PCOS) (Not FDA approved for that indication)
• Should be taken with food
• Contraindicated in symptomatic CHF patients and
  renal patients (SCr gt1.5 men, SCrgt1.4 women)
• Must be discontinued for 48 hrs after any IV dye
  procedure due to risk of lactic acidosis
• Side effects Nausea, diarrhea and gas that tend
  to improve with continued use

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Alpha-Glucosidase Inhibitors

• Slow the digestion and absorption of
  carbohydrates
• Acarbose (Precose), Miglitol (Glyset)
• Good for lowering post-prandial glucose
• Contraindicated in patients with cirrhosis ,colon
  ulcerations, DKA, inflammatory bowel disease and
  patients with bowel obstruction
• Usual dose 25,50 or 100 mg tid
• To be taken with first bite of meal
• Side effects gas, diarrhea and abdominal pain
  (tend to improve with continued use)

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• DPP- IV inhibitors Januvia (sitagliptin),
  Onglyza (saxagliptin), Tradjenta (linagliptin)
• A relatively new class of oral antidiabetic drugs
  known as dipeptidyl peptidase-IV (DPP-IV)
  inhibitors
• The DPP-IV enzyme normally rapidly inactivates
  the gut hormone (GLP-1) so that additional
  insulin secretion is not prolonged more than
  necessary.
• Slow the inactivation of that gut hormone,
  therefore increase insulin release and decrease
  glucose release by the liver-prolong homeostasis
• May be taken with or without food
• Low sugar reactions are rare since they work in a
  glucose dependent fashion

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Invokana (canagliflozin)

• Drug Class Sodium Glucose Cotransporter 2
  Inhibitor (SGLT-2 inhibitor)
• Works by blocking the bodys reuptake of filtered
  glucose in the kidneys leading to an increased
  amount of urinary excretion of glucose
• A typical starting dose of canagliflozin is
  100mg orally once a day taken before the first
  meal

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More on Canagliflozin

• Doses can be increased to a maximum daily dose of
  300mg/day
• Most common side effects increased urination,
  and increased urinary tract infections/genital
  yeast infections in females
• May cause increased thirst, constipation and
  nausea
• Report symptoms of low blood pressure to Physician

22

• Bile Acid Sequestrants
• Welchol (colesevelam)
• Decreases blood sugar in Type II diabetics by an
  unknown mechanism. Originally used for high LDL
  cholesterol
• Main side effect is constipation. May cause
  increased triglycerides
• May interfere with absorption of other
  medications and must be separated from them by
  at least 1 hour

23
Cycloset (Bromocriptine)

• The first drug for type 2 diabetics that targets
  the bodys dopamine activity
• Mechanism of Action Generally unknown , but
  preclinical studies have shown brain dopamine
  activity to be low in metabolic disease states
  which may contribute to insulin resistance
• Indication Treatment of type 2 diabetes most
  likely in combination with all other existing
  agent
• Dosage Initial dose 0.8 mg (one tablet) taken
  within 2 hours of waking with food. Dose
  titration weekly by 0.8 mg until clinical
  effectiveness or a maximum dose of 4.8 mg is
  reached
• Contraindications Patients with syncopal
  migraines, pregnant and nursing women, use with
  other dopamine receptor agonists and pediatric
  patients

24

• Bile Acid Sequestrants
• Welchol (colesevelam)
• Decreases blood sugar in Type II diabetics by an
  unknown mechanism. Originally used for high LDL
  cholesterol
• Main side effect is constipation. May cause
  increased triglycerides
• May interfere with absorption of other
  medications and must be separated from them by
  at least 1 hour

25
Combination Products

• Glucovance Glyburide Metformin
• Metaglip Metformin Glucotrol
• Avandamet Avandia Metformin
• Actoplus Met Actos Metformin
• Avandaryl Avandia Amaryl
• Duetact Actos Amaryl
• Janumet Januvia Metformin
• Prandimet Prandin Metformin
• Kombiglyze Onglyza Metformin
• Juvisync Januvia Zocor

26
Symlin (Pramlintide)

• Symlin (pramlintide) is an injectable synthetic
  analog of human amylin, a hormone that is not
  present in diabetics.
• It slows gastric emptying, lessens after meals
  glucagon secretion and suppress appetite
• May be given as a subcutaneous injection in Type
  I and Type II diabetics as an add on therapy to
  meal time insulin
• May cause Nausea/vomiting and add to risk of
  hypoglycemia especially in type I diabetics

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• GLP-1 agonists Byetta (exenatide) , Victoza
  (liraglutide) and Bydureon (exenatide LA)
• Stimulate insulin secretion in a
  glucose-dependent fashion
• Slows the movement of food in the stomach
  (gastric emptying).
• Slows sugar (glucagon hormone) secretion during
  hyperglycemia
• May have some potential in stimulating
  regeneration of the cells that make insulin (beta
  cells)

28
Over The counter Medications of Concern with
Diabetes

• Vitamins Minerals
• Calcium 1000 - 1500 mg Vitamin D daily
• Approximately 3 glasses of milk
• Multivitamin or additional supplements as needed
  to balance diet
• Decongestants (pseudoephedrine) - prolonged use
  can increase blood pressure and decrease
  circulation
• Watch for sugar and alcohol content (especially
  in cough syrups)
• Many products are available sugar free and
  alcohol free- Diabetic Tussin Codimal DM

29
Herbals and Nutraceuticals

• Consult doctor prior to use
• Check glucose before and after you take,
  routinely for first few weeks, then periodically
• Use caution with all herbals, especially
• Ginseng
• Ma Huang or Ephedra
• Glucosamine
• Ginger
• Nettle
• Garlic

30
Cholesterol Medications

• Total cholesterol goal is lt 200, LDLlt100, HDL for
  mengt45, for womengt55 and triglycerides lt150
• Have been shown to cut down on the incidence of
  heart attacks and strokes in diabetics
• May delay the initiation of insulin in Type II
  diabetics
• Take at bedtime and avoid grapefruit and
  grapefruit Juice
• Monitor liver function tests
• Side effects to tell the doctor about include
  muscle weakness, skin rash, nausea, vomiting,
  diarrhea and loss of appetite

31
Cholesterol Medications (Cont.)

• Statins (Crestor, Zocor, Lipitor, etc.)
• raise HDL lower LDL
• Niacin lowers LDL increases HDL
• Bile Acid Resins (Questran, Welchol) lower LDL
• Fibrates (Lopid, Tricor) lower
• triglycerides increase HDL
• Ezetimibe (Zetia) lowers LDL

32

• Blood Pressure Medications
• Blood pressure goal is 140/80 for diabetics (New
  2013 goal ! (lower for some)
• Blood pressure control has shown to decrease
  cardiovascular disease, stroke, and kidney damage
  in diabetics
• Lifestyle changes may be adequate for some
• Some diabetics are started on blood pressure
  medications called ACE Inhibitors or Angiotensin
  Receptor Blockers which offer kidney protection
  as well
• There are many different classes of blood
  pressures medications for your doctor to choose
  from

33
2012 ADA/EASD Guidelines for T2DM Management
Algorithm
34
AACE/ACE Consensus Statement Endocrine Practice
2009 15 (No. 6)
35
What to do when OADs fail to maintain control in
Type 2 diabetes

• Reemphasize that diet and exercise can produce at
  most a 1 reduction from baseline maximum effect
  is at 3 months
• If on 2 first-line oral therapies, a third oral
  agent will result in a further reduction of A1c
  levels of only 1 or less
• Do not add a third oral agent if A1cgt 9 since
  most patients will not reach target level. It is
  time to consider insulin!

36
Insulin Fundamentals

• Think about insulin therapy as having three
  components
• Basal insulin what you need when not
  eating(between meals)
• Prandial insulin to cover food
• Correction insulin to fix abnormal glucose
  levels

37
Characteristics of Insulin

• Rapid acting Insulin such as Novolog, Humalog
  or Apidra
• Onset 10-15 min Peak 30-90 min
  Duration 6-8 hrs
• Fast acting Insulin such as Novolin R or Humulin
  R
• Onset 30 min Peak 2-4 hrs
  Duration 8-12 hrs
• Intermediate Acting Insulin such as Novolin N or
  Humulin N
• Onset 1-2 hrs Peak 4-12 hrs
  Duration 18-24 hrs
• Basal (long acting Insulin) such as Lantus or
  Levemir
• Onset 1-2 hrs No Peak
  Duration Up to 24 hrs
• Mixed Insulin such as Humulin or Novolin 70/30,
  Novolog Mix 70/30,
• Humalog 75/25, Humalog 50/50

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• Treatment of Hypoglycemia
• Things to inform patients
• What is an insulin reaction (hypoglycemia) and
  how is it treated??
• Blood glucose becomes too low (below 70 mg/dl for
  most people)
• Signs - cold sweat, dizziness, fatigue, nausea,
  hunger, vision changes, rapid heart rate
• Treatments - glucose tablets (3-4), glass of
  milk, juice (1/2 cup), soft drink (1/2 can)
• Test your glucose again after 15 minutes, and
  repeat treatment if still below 70 mg/dl
• Notify your physician!!

39
RecommendationsMedical Nutrition Therapy (MNT)

• Individuals who have prediabetes or diabetes
  should receive individualized MNT as needed to
  achieve treatment goals, preferably provided by a
  registered dietitian familiar with the components
  of diabetes MNT
• In general,
• Carbs 45-65of total daily calories
• Fats 25-35 of total daily calories (lt7
  saturated)
• Protein 12-20 (kidney disease lt10)
• Lose weight if body mass index (BMI)gt25

ADA. V. Diabetes Care. Diabetes Care
201235(suppl 1)S21.
40
ADA Recommendations Physical Activity

• Advise people with diabetes to perform at least
  150 min/week of moderate-intensity aerobic
  physical activity (5070 of maximum heart rate),
  spread over at least 3 days per week with no more
  than 2 consecutive days without exercise
• In absence of contraindications, people with type
  2 diabetes should be encouraged to perform
  resistance training at least twice per week

ADA. V. Diabetes Care. Diabetes Care
201235(suppl 1)S25.
41
Why Exercise?

• ? maximal O2 uptake
• ? cardiac output
• ? resting heart rate
• ? blood pressure
• ? metabolism
• ? muscle mass
• ? capillary density of muscle
• ? mitochondrial density of muscle
• ? HDL cholesterol
• ? muscle strength
• ? endorphins
• ? self esteem
• ? shortness of Breath
• ? risk of heart disease stroke
• ? insulin sensitivity
• ? glucose uptake
• Benefits

42
Challenges!!

• HEALTH CARE LOGIC!!

43
Process and Assessment

• Cardiac Rehab
• Patient enters certified facility via physician
  referral
• Graded Exercise Test (optional)
• Assessment
• Cardiovascular anatomy, physiology, physiology
• Physical examination
• Risk factor profile / risk reduction options
• Learning preferences, barriers, individual goals
• 
  
• Diabetes Self Management
• Education (DSME)
• Patient enters certified facility via
• provider referral

44
Interventions

• Cardiac Rehab
• Monitored exercise training/
• physical activity
• Self management skills
• Blood pressure
• Lipids
• Tobacco cessation
• Weight control
• Diabetes
• Psychological social issues
• Counseling
• Psychosocial
• Nutrition
• DSME
• AADE 7 self care behaviors
• Eating Healthy
• Being Active
• Taking medications

45
Diabetes Complications. and Cardiac Rehab

• People with DM are 2-4 times more likely to have
  CV disease, hypertension and dyslipidemia
• People with DM are susceptible to autonomic
  neuropathy so may be less likely to have symptoms
  during exercise (such as angina to reflect
  myocardial ischemia)
• People with DM may have developed long-term
  complications that may make rehab more
  challenging such as peripheral vascular disease
  and significant claudication

46
Glucose Monitoring in Cardiac Rehab

• No evidence-based guideline on a specific
  number of times
• blood glucose should be measured in the CPR
  setting
• Glucose monitoring establishes patterns for
  glucose response and
• potentially prevent hypoglycemia
• Glucose monitoring determines how often a
  individual should
• tests BG based on his/her medications,
  co-morbid conditions,
• medical history, meal plan, time of exercise,
  and history of
• hyperglycemia and hypoglycemia
• Glucose monitoring assess patients knowledge
  and ability to
• perform accurate blood glucose checks

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Pre Exercise Hypoglycemia Care
Journal of Cardiopulmonary Rehabilitation and
Prevention 201132101-112
48
Post Exercise Hypoglycemia Care
Journal of Cardiopulmonary Rehabilitation and
Prevention 201132101-112
49
Pre Exercise Hyperglycemia for Patients with Type
1 Diabetes
Journal of Cardiopulmonary Rehabilitation and
Prevention 201132101-112
50
Pre Exercise Hyperglycemia for Patients with Type
2 Diabetes
Journal of Cardiopulmonary Rehabilitation and
Prevention 201132101-112
51
Post Exercise Hyperglycemia Care
Journal of Cardiopulmonary Rehabilitation and
Prevention 201132101-112
52
In Summary

• Regular exercise helps maintain appropriate BG
  levels and is a primary indication in the
  management of DM
• The cardiopulmonary rehab setting represents an
  excellent opportunity for health care providers
  to monitor and manage DM
• Aerobic and strength training exercise may
  trigger hypoglycemia in people with DM
• Collaboration between health care providers is
  key for success!!

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THANK YOU!

• QUESTIONS???
• Rhanania1_at_iuhealth.org