Endocrinology:
Diabetes
Courses in Therapeutics and Disease State Management
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Epidemiology
• Diabetes mellitus (DM) is a metabolic disorder characterized by
hyperglycemia that affects over 29 million Americans.
• Results from defects in insulin secretion, insulin sensitivity, or
both
• Diabetes contributes to microvascular and macrovascular
complications, and is the leading cause of kidney failure in the
U.S.
• In 2012, the burden of diabetes exceeded $245 billion in direct
and indirect costs
American Diabetes Association. “FAST FACTS: Data and Statistics about Diabetes” http://professional.diabetes.org/sites/professional.diabetes.org/files/media/fast_facts_12-2015a.pdf. Updated 12-2015.
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Classification
Characteristic
Type 1 DM (5% of all cases)*
Type 2 DM (90% of all cases)*
Typical age at onset
Youth, adolescence
Adulthood
Speed of onset
Rapid
Slow
Response to lifestyle modifications
Poor
Good
Frequency of DKA
High
Low
Personal or Family history of autoimmune disease
Common
Uncommon
Body habitus
Lean
Overweight, obese, central adiposity
C-Peptide Levels
Undetectable to low
Normal to high
Evidence of β-cell autoimmunity
Present
Absent
• Gestational diabetes (GDM) and other forms make up the remaining 5% of cases.
See Table 57-1 in Pharmacotherapy for additional classifications and Table 20.1 in Patient Assessment
Triplitt CL, Repas T, Alvarez C. Chapter 57. Diabetes Mellitus. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.
http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=45310509. Accessed November 05, 2016.
Herrier RN, Apgar DA, Boyce RW, Foster SL. Diabetes Mellitus. In: Herrier RN, Apgar DA, Boyce RW, Foster SL. eds. Patient Assessment in Pharmacy. New York, NY: McGraw-Hill; 2015.
http://accesspharmacy.mhmedical.com/content.aspx?bookid=1074&Sectionid=62364511. Accessed November 05, 2016.
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Screening
• Symptomatic
• Patients presenting with Diabetic Ketoacidosis or Hyperosmolar
Hyperglycemic State
• Generally Type 1 DM or longstanding Type 2 DM
• Asymptomatic
• All adults >45 years old
• Any adult with a BMI ≥ 25kg/m2 (≥23kg/m2 for Asian Americans) with
≥1 diabetes risk factor
• Recheck at a minimum of every 3 years
Diabetes Care 2016;39(Suppl. 1):S1–S108
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Diabetes Risk Factors
• Physical inactivity
• First degree relative with diabetes
• African American, Latino, Native American, Asian American, Pacific
Islander
• Women with PCOS, a history of GDM or delivering a baby weighing
>9lbs
• Hypertension, HDL <35mg/dL, or triglycerides >250mg/dL
• A1c ≥ 5.7%, impaired glucose tolerance or impaired fasting glucose
• Conditions associated with insulin resistance
• Cardiovascular disease Diabetes Care 2016;39(Suppl. 1):S1–S108
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Diabetes Risk Factors
• Physical inactivity
• First degree relative with diabetes
• African American, Latino, Native American, Asian American, Pacific
Islander
• Women with PCOS, a history of GDM or delivering a baby weighing
>9lbs
• Hypertension, HDL <35mg/dL, or triglycerides >250mg/dL
• A1c ≥ 5.7%, impaired glucose tolerance or impaired fasting glucose
• Conditions associated with insulin resistance
• Link: Figure of acanthosis nigricans, with typical hyperpigmented
plaques on a velvet-like, verrucous surface on the neck.
• Cardiovascular disease Diabetes Care 2016;39(Suppl. 1):S1–S108
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Diagnosis
Pre-Diabetes
Diabetes
• HbA1c 5.7%-6.4%
• Fasting plasma glucose 100125mg/dL
• HbA1c ≥6.5%
• Fasting plasma glucose ≥126
mg/dL (Fasting is defined as no
caloric intake for at least 8
hours)
• 2-hour plasma glucose ≥200
mg/dL during an OGTT
• In a patient with classic
symptoms of hyperglycemia or
hyperglycemic crisis, a random
plasma glucose concentration
≥200 mg/dL
• IFG=Impaired Fasting Glucose
• 2-hour plasma glucose 140199mg/dL during an OGTT
• IGT=Impaired Glucose
Tolerance
Diabetes Care 2016;39(Suppl. 1):S1–S108
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Concept Review
• GC is 24 year-old, obese, white female seen in family medicine
clinic to establish care. She has a history of polycystic ovarian
syndrome. Her family history is unknown. She denies tobacco
and alcohol use. Endorses polydipsia with polyuria and
oligomenorrhea with moderate to heavy menstrual bleeding.
• Height: 5 ft 7in Weight: 300lbs BMI: 47 kg/m2
• BP:
140/101
• Is GC a candidate for diabetes screening?
Herrier RN, Apgar DA, Boyce RW, Foster SL. Diabetes Mellitus. In: Herrier RN, Apgar DA, Boyce RW, Foster SL. eds. Patient Assessment in Pharmacy. New York, NY: McGraw-Hill; 2015.
http://accesspharmacy.mhmedical.com/content.aspx?bookid=1074&Sectionid=62364511. Accessed November 05, 2016.
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Concept Review
• GC is ordered screening labs based on her BMI and diabetes
risk factors.
• Her results:
• HbA1c 10.6%
• Plasma Glucose (non-fasting) 325mg/dL
• What diagnosis, if any, can be made today?
• Link: Table of a list of other assessments that should be
completed at the initial visit.
• How should we approach treatment?
Herrier RN, Apgar DA, Boyce RW, Foster SL. Diabetes Mellitus. In: Herrier RN, Apgar DA, Boyce RW, Foster SL. eds. Patient Assessment in Pharmacy. New York, NY: McGraw-Hill; 2015.
http://accesspharmacy.mhmedical.com/content.aspx?bookid=1074&Sectionid=62364511. Accessed November 05, 2016.
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Goals of Treatment
• Prevent Acute Complications
• Prevent Chronic Complications
• Alleviate Symptoms of Complications
• Minimize/Avoid Drug Related Problems
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Glycemic Control
• Self-Monitoring of Blood Glucose (SMBG)
•
•
•
•
Part of the patient’s self-management strategy
Pre-prandial is the primary target
Symptoms of hypo-/hyperglycemia
Individualized for the needs and goals of the patient
• HbA1c
•
•
•
•
Glycosylated hemoglobin on RBCs
Every 3 months
“average blood glucose”
Target to prevent complications
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
SMBG
• Measured using blood glucose meter
• Link: Video on Home Blood Glucose Monitoring
• Link: Video on Preventing Infections When Monitoring Blood
Glucose
• ADA recommendations
• Preprandial
• Goal 80-130mg/dL
• Postprandial
• Goal <180mg/dL
• Hypoglycemia
• Any value <70mg/dL
Diabetes Care 2016;39(Suppl. 1):S1–S108
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
SMBG
Patients using multiple
insulin injections per day
• Before meals and snacks
• Occasionally postprandially
• At bedtime
• Prior to exercise or
performing critical tasks
• When suspect the presence
of, and after treating
hypoglycemia
Non-intensive regimens
• Oral agents only
• Monitoring for hypoglycemia
• May help guide treatment
decisions
• Basal Insulin
• Fasting SMBG for titration of
basal insulin dose
• Monitoring for hypoglycemia
Diabetes Care 2016;39(Suppl. 1):S1–S108
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
HbA1c
• A1C is influenced by both the fasting glucose and post-prandial levels
• Estimated Average Glucose eAG= 28.7 X A1C – 46.7
• Link: eAG/A1C Conversion Calculator
• Link: Infographic on A1C Goals
• Measured every 3-6 months
• Goal for most patients is <7%
• More stringent goals (<6.5%) can be considered if:
•
•
•
•
Hypoglycemia can be avoided
Short duration of diabetes
Long life expectancy
No significant CVD
• Less stringent goals (<8%) can be considered if:
•
•
•
•
Severe hypoglycemia
Limited life expectancy
Advanced complications/Longstanding disease
Extensive comorbidities
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Concept Review
•
•
•
•
•
GC is 24 year-old, obese, white female
History of polycystic ovarian syndrome.
Family history is unknown.
Denies tobacco and alcohol use.
Endorses polydipsia with polyuria and oligomenorrhea with moderate to heavy
menstrual bleeding.
• Vitals/Labs
•
•
•
•
Height: 5 ft 7in Weight: 300lbs BMI: 47 kg/m2
BP:
140/101
HbA1c 10.6%
Plasma Glucose (non-fasting) 325mg/dL
• What glycemic targets would you recommend for GC?
• Link: Table on Treatment Goals for Adults with Diabetes
Herrier RN, Apgar DA, Boyce RW, Foster SL. Diabetes Mellitus. In: Herrier RN, Apgar DA, Boyce RW, Foster SL. eds. Patient Assessment in Pharmacy. New York, NY: McGraw-Hill; 2015.
http://accesspharmacy.mhmedical.com/content.aspx?bookid=1074&Sectionid=62364511. Accessed November 05, 2016.
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Comprehensive Assessment
• Link: Table of Guidelines on for Ongoing, Comprehensive
Medical Care for Patients with Diabetes
• Medical History
• Physical Exam
• Laboratory Evaluation
• Referrals
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Acute Complications
Symptoms of Hyperglycemia
• Include:
•
•
•
•
•
•
•
Polyuria
Polydipsia
Polyphagia
Dry Skin
Nausea
Fatigue/Drowsiness
Blurred vision
• May be caused by:
• Too much food
• Too little insulin/medication
• Illness, stress
• Drugs that cause hyperglycemia
•
•
•
•
•
Corticosteroids
Niacin
Atypical Antipsychotics
Protease inhibitors
Sympathomimetics
• Treatment
• Additional insulin
• Moderation of carbohydrate intake
• Physical activity
• Link: Table on Medications that may
Affect Glycemic Control
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Acute Complications
Impaired Wound Healing and Infection
• Impaired wound healing
• Skin infections
• Foot Infections
• Treatment
• Prevention through foot care
• Glycemic control
• Referral to podiatry
• Link: Video on Diabetic Foot Exam
• Link: Algorithm covering pathophysiology of
the diabetic foot
• Infection
• Skin
• Oral
• Genitourinary
• Vaginal candidiasis
• Urinary tract
• Causes
• Increased susceptibility
• Decreased healing
• Treatment
• Prevention
• Immunizations
•
•
•
•
Influenza-yearly
Pneumococcal
Tetanus
Hepatitis B vaccine
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Hyperglycemic Crises
Diabetic ketoacidosis
(DKA)
• Causes
• Decreased insulin
• Increased counter-regulatory
hormone
• Release of free fatty acids (lipolysis)
that are oxidized to ketone bodies
• Results in metabolic acidosis
• Presentation
Hyperosmolar
hyperglycemic state
(HHS)
• Causes
• Inadequate insulin levels to utilize
glucose
• Enough insulin to prevent lipolysis
• Glycosuria leads to osmotic
diuresis
• Presentation
• Acute presentation (<24 hours)
• Evolves over several days to
• Can occur with BG >250
weeks
• Usually Type 1 DM, can be
• Occurs with BG >600
precipitated in Type 2 by
infection/stress
drugs
Author: Autumn
Stewart, PharmD, BCACP, or
CTTS;
Associate Professor of Pharmacy Practice; Duquesne
Pharmacy
• University
TypeSchool
2 ofDM
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Hyperglycemic Crises
• Symptoms
•
•
•
•
•
•
•
•
•
•
Hyperglycemia
Vomiting
Weight loss
Dehydration
Weakness
Clouding of sensorial
Coma
Tachycardia
Hypotension
Abdominal pain (DKA only)
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Chronic Complications
Microvascular
• Retinopathy
• Leading cause of new blindness
• Edema
• Non-proliferative diabetic retinopathy-microaneurysms, hemorrhages
• Proliferative diabetic retinopathy-growth of new blood vessels into optic nerve and
macula; hemorrhage, retinal detachment
• Prevention
• Glycemic control
• Blood pressure control
• Fundoscopic Eye Exam
• Type 1- initial exam or within 5 years after disease onset, annually thereafter
• Type 2- initial exam shortly after the diagnosis of diabetes, annually thereafter
• Laser treatment to prevent vision loss, intravitreal anti-VEGF agents
• Link: Figure of a patient has neovascular vessels proliferating from
the optic disc
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Chronic Complications
Microvascular
• Nephropathy
• Leading cause of ESRD
• Link: Algorithm for screening for microalbuminuria
• Annual urine microalbumin/creatinine ratio
• Annual serum creatinine (even patients without kidney damage)
• Prevention
• Glycemic control
• Blood pressure control
• Compelling indication for use of ACEI or ARB
• Treatment
• ACEI prevents CVD events AND slows the decline in renal function
• ARB prevents progression of albuminuria
• Link: Figure on time course of development of diabetic nephropathy
• Can use either ACEI or ARB in normotensive patients with elevated urinary albumin
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Chronic Complications
Microvascular
• Neuropathy
• Autonomic
• Erectile Dysfunction
• Link: Chapter on ED on AccessPharmacy
• Cardiac
• Resting tachycardia
• Orthostasis
• Gastroparesis
• Link: Chapter on Nausea and Vomiting on
AccessPharmacy
• Sensory
• Diabetic Peripheral Neuropathy
• Numbness, tingling, burning, loss of
sensation esp. in extremities
• Screening
• Foot exam at each visit
• Link: Video on Diabetic Foot Exam
• Pulses (dorsal pedal and post tibial)
• Monofilament testing (loss of protective
sensation)
• Vibration using 128-Hz tuning fork, OR,
pinprick sensation, OR ankle reflexes, OR
vibration perception
• Orthostatic BP measurements
• A fall in systolic blood pressure >20
mmHg upon standing without an
appropriate heart rate response
• Heart rate measurements (>100bpm)
• Treatment
• Erectile dysfunction
• Link: Algorithm for selecting treatment for erectile
dysfunction
• phosphodiesterase type 5 inhibitors
• intracorporeal or intraurethral
prostaglandins
• vacuum devices
• Gastroparesis
• Erythromycin
• Metoclopramide
• Diabetic Peripheral Neuropathy (DPN)
• Link: Table on Pharmacologic Management of Chronic
Noncancer Pain
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Chronic Complications
Macrovascular
• Blood Pressure
• Checked at each visit
• Link: Table on Blood Pressure Technique
ADA 2016 Standards
Systolic Goal
JNC8
<140mmHg (<130mmHg may be appropriate in younger patients; those with
albuminuria; additional ASCVD risk factors. If achieved without undue
<140mmHg
treatment burden.)
Diastolic Goal
<90mmHg (< 80mmHg may be appropriate in younger patients; those with
albuminuria; additional ASCVD risk factors. If achieved without undue
< 90mmHg
treatment burden.)
Drug Therapy
ACEI or ARB for all patients with diabetes
Administer 1 or more antihypertensive meds at HS
Add on amlodipine, HCTZ or chlorthalidone
CKD: ACEI or ARB
Nonblack persons: ACEI, ARB, Thiazide, or
CCB
Black persons: Thiazide or CCB
James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2013.
doi:10.1001/jama.2013.284427.
Diabetes Care 2016;39(Suppl. 1):S1–S108
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Chronic Complications
Macrovascular
• Lipids
• Lipid panel at least annually
• Link: Figure on Four Major Statin Benefit Groups
• Moderate intensity statin if age 40-75 with diabetes (Level of evidence: A)
• High intensity statin if age 40-75 with diabetes and a ≥7.5% 10 year ASCVD risk. (Level of
evidence: E)
• Evaluate benefit vs risk in patients <40 and >75 with diabetes (Level of evidence: E)
• 10-Year Risk can be calculated using the ASCVD Pooled Cohort Equations CV Risk Calculator
• Link: Algorithm covering major recommendations for statin therapy for atherosclerotic
cardiovascular disease (ASCVD) prevention
• Link: Figure on intensity levels of statins
Stone NJ, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines. Circulation. 2013;00:000–000
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Chronic Complications
Macrovascular
• Antiplatelet therapy
• Aspirin 75-162 mg/day
• Primary Prevention
• MEN and WOMEN > 50 with at least 1 additional major risk factor
• family history of CVD, hypertension, smoking, dyslipidemia, albuminuria
• Secondary prevention
• Recommended for ALL patients with previous MI or stroke
• Smoking Cessation
• Pharmacotherapy and Support programs—“The 5 A’s”
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Medical Nutrition Therapy
Carbohydrates in diabetes management
• The carbohydrate amount in meals and available insulin are usually the most important
factors influencing glycemic response after eating and should be considered when
developing the eating plan.
• Includes carbohydrate from fruits, vegetables, whole grains, legumes, and low-fat milk
(sucrose-containing foods in place of other carbohydrates should not displace nutrient
dense food choices.
• Monitoring carbohydrate, whether by carbohydrate counting, exchanges, or experiencedbased estimation, remains a key strategy in achieving glycemic control.
• For example: 200 grams of carbohydrates per day 45-60 grams per meal; 15-20 grams
for snacks
• Avoid excess calories (adjust to maintain desirable weight or prevent weight gain)
• Consume a variety of fiber containing foods (20-30 grams of dietary fiber per day)
• People with diabetes or pre-diabetes should limit/avoid intake of sugar-sweetened
beverages to reduce risk for weight gain and worsening of cardio-metabolic risk.
• Sugar alcohols and nonnutritive sweeteners are safe within recommended daily intake
levels
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Medical Nutrition Therapy
Fat and cholesterol in diabetes management
• Limit saturated fat to <7% of total calories
• Minimize intake of trans fat and reduce dietary cholesterol to <200
mg/day
• Two or more servings of fish per week provide n-3 polyunsaturated
fatty acids
Protein in diabetes management
• If normal renal function, no need to restrict usual protein intake
• Protein should not be used to treat acute or prevent nighttime
hypoglycemia
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Medical Nutrition Therapy
Alcohol in diabetes management
• Limit daily intake to one drink per day or less for women and two drinks
per day or less for men
• Alcohol may increase risk for hypoglycemia, especially if taking insulin
or insulin secretagogues
Sodium
• Reduce sodium to < 2,300 mg/day; for individuals with both diabetes
and hypertension, further reduction in sodium intake should be
individualized
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
http://accesspharmacy.mhmedical.com/qa.aspx#tab6
Copyright © 2017 McGraw-Hill Education. All rights reserved
Insulin
Intermediate
NPH (Humulin N®, and
Novolin N®)
Can be dosed QD at dinner
or HS; or
BID (at breakfast and
dinner or HS)
Cloudy
Can be mixed with R or
Rapid acting insulin by
patient or premixed
Basal (Background Insulin)
Long acting
Glargine UGlargine U100
Detemir
300
(Lantus®,
(Levemir®)
(Toujeo®)
Basaglar®)
Can be dosed
QD at dinner
Daily at same time
or HS; or
BID (at
breakfast and
dinner or HS)
Clear
Ultra Long Acting
Degludec (Tresiba®)
100units/ml and
200units/ml
Dosed once daily at any
time of day (must
separate by >8 hours)
Cannot be mixed with other insulin
Link: Table on Available Injectable and Insulin Preparations
Link: Table on Pharmacokinetics of Various Insulins
Administered Subcutaneously
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Insulin
Bolus (Mealtime Insulin)
Short acting
Regular (Humulin R®, Novolin R®)
Rapid acting
Lispro (Humalog®)
Clear
Humulin 70/30®; Novolin 70/30®
(70% NPH; 30% Regular)
Aspart (Novolog®)
Glulisine
(Apidra®)
Clear
Humalog Mix 50/50®
(50% NPH; 50% Lispro);
Humalog Mix 75/25®
(75% NPH; 25% Lispro)
NovoLog Mix 70/30®
(70% NPH; 30%
Aspart); Ryzodeg®
(70% degludec/30%
Aspart),
Link: Graphic on insulin action
Link: Table on Available Injectable and Insulin Preparations
Link: Table on Pharmacokinetics of Various Insulins
Administered Subcutaneously
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Can be
mixed with
NPH
Injecting Insulin
• Link: Video on Drawing and
Preparation of Diabetic
Injections
• Subcutaneous Injection sites
•
•
•
•
•
Abdomen (most predictable)
Outer upper arm
Buttocks
Hip
Front and side of the thigh
(most likely affected by
exercise
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Pharmacotherapy in Type 1 Diabetes
• Intermediate or Long-acting Basal Insulin AND Pre-meal Rapid
or Short Acting Insulin
• Continuous Subcutaneous Insulin Infusion (CSII) aka “Insulin
Pump”
• Link: Figure on relationship between insulin and glucose over
the course of a day and how various insulin and amylinomimetic
regimens could be given.
• Link: Chapter on Pancreatic Hormones & Antidiabetic Drugs
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Insulin Regimen Profiles
Commonly used insulin regimens.
Panel A shows administration of a long-acting insulin like
glargine (detemir could also be used but often requires
twice-daily administration) to provide basal insulin and a
pre-meal short-acting insulin analog.
Panel B shows a less intensive insulin regimen with BID
injection of NPH insulin providing basal insulin and regular
insulin or an insulin analog providing meal-time insulin
coverage. Only 1 type of shorting-acting insulin would be
used.
Panel C shows the insulin level attained following
subcutaneous insulin (short-acting insulin analog) by an
insulin pump programmed to deliver different basal rates. At
each meal, an insulin bolus is delivered. B, breakfast; L,
lunch; S, supper; HS, bedtime. Upward arrow shows insulin
administration at mealtime.
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Initiating Insulin in Type 1 Diabetes
• Use an empiric dose (best “estimate” based on actual weight)
• Initial 0.5-0.7 U/kg/day [Total Daily Dose (TDD)]
• May drop to 0.2-0.5 U/kg/day during “honeymoon phase” as glucose toxicity
resolves
• May increase to 1-1.5 U/kg/day during illness or growth
• Since patients with Type 1 diabetes need a regimen of BASAL and
BOLUS insulin, the TDD needs to be split. Usually start with a
Basal-to-Bolus ratio of 50:50.
• Newly diagnosed Type 1 diabetic weighing 114 lbs. What is a
reasonable initial total daily dose (TDD) of insulin?
• Using the TDD calculated above, what doses of basal and bolus
insulin would the patient be started on?
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Initiating Insulin in Type 1 Diabetes
• 114 lbs ÷ 2.2 lbs/kg = 52 kg
• TDD = 0.5-0.7 U/kg/day = 26-36 units
• Using 26 units as the TDD
• 50% Basal = ~14 units QD
• 50% Bolus = 3 units breakfast, lunch, 4 units dinner
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Adjusting Insulin Doses
• Fixed Dose Approach
• Look for patterns/trends in SMBG and patient characteristics to adjust and provide patient
with a fixed prandial insulin dose.
• Dose adjustments by 1-2 units every few days
• Patient must be consistent in carbohydrate amounts at each meal
• Flexible Meal Dosing Approach
• Patients can have more flexibility from meal to meal by injecting per sliding scale to
correct an elevation (correction dose) and provide coverage for carbohydrates in the
meal.
• Amount of insulin to inject depends on insulin sensitivity and amount of carbs in the meal
• Correction dose calculated from patient’s insulin sensitivity (ranges from 1 U per 25mg/dL
to 1 U per >60mg/dL). A conservative correction factor is 1 U per 50mg/dL.
• (measured blood glucose mg/dL – goal blood glucose mg/dL) ÷ Correction factor mg/dL/U =
Correction dose
• Patients will also estimate pre-meal insulin requirements based on anticipated
carbohydrates in meal (ranges 1 U for every 6 g of CHO up to 20 g of CHO).
• 1 U per 15 g CHO is good starting place
• Carbohydrates in meal g ÷ insulin:carb ratio = Units of insulin
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Pharmacotherapy in Type 2 Diabetes
• Lifestyle modifications
• Oral agents
• Non-insulin injectables
• Insulin
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Pharmacotherapy in Type 2 Diabetes
Link: Infographic from the ADA 2017 Guidelines covering general
recommendations for Antihyperglycemic therapy in Type 2
Diabetes.
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Metformin
• Biguanide
• Primarily decreases hepatic glucose production; also increases
peripheral insulin sensitivity
• Initial dose 500mg QD-BID with food. Titrated to maximum
effective daily dose of 2000mg.
• Contraindicated at eGFR<30ml/min; not recommended to start
when eGFR 30-45ml/min.
• Hold for 48 hours following iodinated contrast imaging if
eGFR<60ml/min, or if liver disease, alcoholism, or heart failure
U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function
http://www.fda.gov/Drugs/DrugSafety/ucm493244.htm. Accessed November 12, 2016.
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Metformin
• Monitoring
• Diarrhea and abdominal cramping
• Lactic acidosis (rare)
• CBC/B12 levels Initial dose 500mg QD-BID with food. Titrated to
maximum effective daily dose of 2000mg.
• Advantages
•
•
•
•
•
Low risk for hypoglycemia as monotherapy
Weight loss/weight neutral
Long term safety record
Low cost
Efficacious
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Concept Review
• GC is 24 year-old, obese, white female with a new diagnosis of
Type 2 Diabetes and a history of polycystic ovarian syndrome.
Her family history is unknown. She denies tobacco and alcohol
use.
• Height: 5 ft 7in Weight: 300lbs BMI: 47 kg/m2
•
•
•
•
BP:
140/101
HbA1c 10.6%
Plasma Glucose (non-fasting) 325mg/dL
Creatinine 0.8mg/dL
• How should we approach treatment?
Herrier RN, Apgar DA, Boyce RW, Foster SL. Diabetes Mellitus. In: Herrier RN, Apgar DA, Boyce RW, Foster SL. eds. Patient Assessment in Pharmacy. New York, NY: McGraw-Hill; 2015.
http://accesspharmacy.mhmedical.com/content.aspx?bookid=1074&Sectionid=62364511. Accessed November 05, 2016.
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Selecting Add-on Therapy
•
•
•
•
Efficacy
Mechanism of action
Cost
Safety
Link: Table on Oral Agents for the Treatment of
Type 2 Diabetes Mellitus
• Contraindications
• Adverse effect profile
• Risk for hypoglycemia
• Extraglycemic effects
• Lipids
• Weight
• Blood pressure
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Patient Centered Considerations
Avoiding Hypoglycemia
Metformin
Thiazolidinediones
SGLT-2 Inhibitors
GLP-1 Agonists
DPP-IV Inhibitors
Avoiding Weight Gain
Metformin
SGLT-2 Inhibitors
GLP-1 Agonists
DPP-IV Inhibitors
Lower Costs
Metformin
Sulfonylureas
Thiazolidinediones
Basal Insulin (NPH)
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Sulfonylureas
• Enhance insulin secretion
• Glimepiride (Amaryl®)
• Initial: 1-2mg QD with breakfast; then 1-4mg QD. Max: 8mg QD
• Glipizide (Glucotrol®, Glucotrol XL®)
• Initial: 5mg QD 30 minutes before breakfast and titrate by 2.5-5mg Max:
20mg BID
• XL Initial: 5mg QD with breakfast. Max: 20mg QD
• Glyburide (Diabeta®, Micronase®) +metformin (Glucovance®)
• Initial: 2.5mg QD with breakfast and titrate by 2.5mg q week. Max: 20mg
QD;
• Do not use in eGFR below 60ml/min
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Sulfonylureas
• Interact with CYP2C9 inducers and inhibitors
• Monitoring
• Hypoglycemia
• Weight gain
• Advantages
• Long term safety record
• Low cost
• Efficacious
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Meglitinides
• Stimulate insulin secretion
• Repaglinide (Prandin®)
• Initial: 0.5mg TID within 15-30 minutes before the start of each meal.
Titrate by doubling dose every week Max: 16mg a day
• Nateglinide (Starlix®)
• 120mg TID within 30 minutes before the start of each meal
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Meglitinides
• Interact with CYP2C8 and CYP3A4 inducers and inhibitors
• Monitoring
• Hypoglycemia
• Weight gain
• Advantages
• More flexible dosing and less hypoglycemia compared to sulfonylureas
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Thiazolidinediones
• Increase peripheral insulin sensitivity; decrease hepatic glucose
• Pioglitazone (Actos®) +metformin (ActosPlusMet®)
• Initial: 15-30mg QD; titrate to 45mg QD in 3-4 weeks Max: 45mg QD
• Interact with CYP2C8 and CYP3A4 inducers and inhibitors
• Monitoring
•
•
•
•
Weight gain/edema
AST/ALT
Heart Failure
Fractures
• Advantages
• No hypoglycemia
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
DPP-IV Inhibitors
• Reduce glucagon and improve insulin response to hyperglycemia
• Sitagliptin (Januvia®) +metformin (JanuMET®)
• Initial/typical: 100mg QD; Renal dosing: CrCl 30-50ml/min: 50mg QD; CrCl
<30ml/min:25mg
• Saxagliptin (Onglyza®) +metformin (Kombiglyze®)
• Initial/typical: 2.5-5 mg once daily; Renal dosing: CrCl <50ml/min: 2.5mg;
CYP3A4/5 (-): 2.5mg
• Linagliptin (Tradjenta®) +metformin (Jentadueto®)
• Initial/typical: 5 mg QD
• Alogliptin (Nesina®) +metformin (Kazano®)
• Initial/typical: 25 mg QD Renal dose: CrCl 30-60 ml/min: 12.5mg; <30
ml/min: 6.25mg
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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DPP-IV Inhibitors
• Monitoring
•
•
•
•
Urticaria
Angioedema
Pancreatitis
Worsening of heart failure
• Advantages
• Low risk for hypoglycemia
• Weight neutral
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
SGLT2 Inhibitors
• Increase urinary excretion of glucose
• Canagliflozin (Invokana®); +metformin (Invokamet®)
• Initial/typical: 100mg QAM, titrate 300mg QD
• Renal dose 100mg eGFR<60. Do not use below 45ml/min
• Dapagliflozin (Farxiga®); +metformin (Xigduo XR®)
• Initial/typical: 5mg QAM, titrate 10mg QD
• Do not use in eGFR below 60ml/min
• Empagliflozin (Jardiance®); +metformin (Synjardy®); +linagliptin (Glyxambi®)
• Initial/typical: 10mg QAM, titrated to 25mg QAM
• Do not use in eGFR below 60ml/min
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
SGLT2 Inhibitors
• Monitoring
•
•
•
•
Genital mycotic infections
Urinary tract infections
Orthostatic hypotension
DKA
• Advantages
• No hypoglycemia
• Weight loss
• Convenient, daily dosing, in the morning
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
GLP-1 Agonists
• Enhance insulin secretion (glucose-dependent), reduce postprandial
glucagon secretion and increase satiety and slow gastric emptying
• Exenatide (Byetta®)
• Initial: 5mcg BID, 10mcg BID after 1 month. Give 60min before meals
• Exenatide ER (Bydureon®)
• Initial: 2mg SQ weekly
• Liraglutide (Victoza®)
• Initial: 0.6 mg QD AC for 1 week; then 1.2 mg QD; Max: 1.8 mg QD
• Dulaglutide (Trulicity®)
• Initial: 0.75mg SQ weekly, can increase to 1.5mg
• Albiglutide (Tanzeum®)
• Initial: 30mg SQ weekly, can increase to 50mg
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
GLP-1 Agonists
• Monitoring
•
•
•
•
GI upset (contraindicated in gastroparesis)
Injection site reactions
Gall bladder disease
Pancreatitis
• Advantages
• No hypoglycemia
• Weight loss
• Efficacious
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Basal insulin
• Most effective add-on therapy
• Titrated to bring AM fasting SMBG in range
• Mealtime bolus insulin added if A1c not at goal and/or as TDD
approaches 0.5 units/kg/day
• Link: Insulin algorithm for type 2 diabetes mellitus in children
and adults; initiation of once-daily therapy
• Hypoglycemia and injection site reactions
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Concept Review
• GC returns for a follow-up 3 months later and is tolerating metformin
at 1000mg BID. Blood glucose readings after dinner 180-240’s. Has
not met with dietician yet, but plans to in near future. Prior to
appointment, patient has labs drawn: HbA1c 8.3% Glucose (non
fasting) 192mg/dL
• What options are available as add-on therapy for GC’s diabetes
management?
• How would the options change if she:
•
•
•
•
•
Was 74 with an eGFR < 50ml/min?
Was an uncircumcised male with a history of balanitis?
Had a history of irritable bowel syndrome?
Was 65 with an ejection fraction of 35% on diuretics?
Had difficulty affording her medications?
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Treatment Pre-Diabetes
• Patients with IGT, IFG, or an A1c 5.7-6.4%
• Intensive lifestyle modification is most effective (~58% reduction in 3 years)
• 7% weight loss
• 150 min/week of moderate intensity physical activity
• Drug therapy (not as effective as lifestyle)
• Metformin
• Those with BMI >35kg/m2
• Aged less than 60 years old
• Women with history of GDM
• Assessment and management of cardiovascular risk factors
•
•
•
•
Obesity
Hypertension
Hyperlipidemia
Smoking cessation
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved
Preventing and Avoiding Drug Related
Problems
• Hypoglycemia
•
•
•
•
Regular assessment
Identify causes
Education
Appropriate treatment
• Medication Safety
•
•
•
•
•
Heart failure
Impaired renal function
Gastrointestinal disease
Pancreatitis
Genitourinary symptoms
• Patient education on side effects
• Anticipated side effects
• How to manage/prevent
• When to report
Author: Autumn Stewart, PharmD, BCACP, CTTS; Associate Professor of Pharmacy Practice; Duquesne University School of Pharmacy
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Copyright © 2017 McGraw-Hill Education. All rights reserved