Download Diabetes Mellitus

CELLULAR
REGULATION:
GLUCOSE METABOLISM
Diabetes & Antidiabetic
Medications
TWO TYPES OF DIABETES

Diabetes Insipidus:
A disorder of the pituitary gland that involved antidiuretic hormone (ADH)

Diabetes Mellitus:
A disorder of insulin production and/or glucose
utilization.
DIABETES MELLITUS





Est. 23.6 million people are diagnosed with diabetes but 5.7
million are unaware they have the disease.
Prevalence in the US:
 Approximately 5-10% of the population have Type I DM
Complications from diabetes are the 3rd leading cause of death in
the US
Rates in African Americans, Native Americans and those of
Hispanic ethnicity (in adults age 45-65) are 2-3x higher than in
Caucasians.
History:
 1500’s writings mention “honeyed urine”
 Insulin was developed by Eli Lilly in 1921
GLUCOSE
Glucose is the simplest form of carbohydrate (“sugar”)
 All of our cells require glucose as an energy source
 Glucose must be consumed through food sources
 Excess glucose is converted and stored in the body as
adipose tissue (“fat”) and as glycogen in the liver and
in the skeletal muscles
 Inadequate food intake leads to:

Glycogen stores are broken down first by the liver
 Gluconeogenesis, or the body’s production of glucose
from non-carbohydrate sources such as fat (ketones) and
muscle tissue occurs second

Diabetes mellitus is fundamentally a
disease of cellular starvation for glucose.
PHYSIOLOGY OF CELLULAR
GLUCOSE: THE HOMEOSTASIS
BLOOD SUGAR
Pancreatic cells
 Islets of Langerhans

Beta cells produce
insulin
 Alpha
 Delta
 F cells (used in digestion)

OF
ROLE OF HORMONES AND BLOOD
GLUCOSE HOMEOSTASIS
Glucose Counter-regulatory Hormones
• These increase glucose levels in the body:
• Cortisol – chronic stress (Cortisone)
• Epinephrine – sympathetic nervous system
• Human Growth hormone
• Glucagon – produced by the pancreas and
stimulates the liver to make glucose
REGULATION OF BLOOD GLUCOSE…
Food is eaten
PATHOPHYSIOLOGY AND ETIOLOGY
Diabetes mellitus is a serious chronic disease
that affects people of all ages and ethnic groups
Types:
Type I
 Type 2
 Gestational (pregnancy)
 Other
 Drug induced (e.g., Prednisone);
 Medical condition (e.g., hyperthyroidism,
pancreatitis, pancreatic cancer)

Usually resolves when underlying
condition is corrected

ETIOLOGY OF DIABETES
 Theories
link cause of DM to combination of
these factors
 Genetic
 Autoimmune
 Viral
 Environmental – obesogenic lifestyles
(Type II)
 Regardless of its cause, diabetes is primarily a
disorder of glucose metabolism related to
absent or insufficient insulin supply and/or
cell membrane resistance to available insulin.
TYPE I DIABETES MELLITUS
 Most
often occurs in people younger than 40
years of age
 Occurs more frequently in younger children
 End result of long-standing process
 Theorized to be autoimmune
 Progressive destruction of pancreatic
-cells by body’s own T cells
 Antibodies cause a reduction of
80% to 90% in normal -cell
function before manifestations
occur.
TYPE I DIABETES MELLITUS (CONT’D)
 Will
require exogenous insulin
 Clinical manifestations:
 Polyuria & polydipsia
 Polyphagia
 Weakness and fatigue
 Diabetic ketoacidosis (DKA)
 Occurs in absence of exogenous insulin
 Life-threatening condition
 Results in metabolic acidosis
PATHOPHYSIOLOGY OF DIABETIC KETOACIDOSIS
TYPE II DIABETES MELLITUS
Pre-diabetes is a precursor to diabetes
 FBS 100-140
 Characterized by insulin resistance at the cell level
and eventually reduced insulin production
 Affects adults and children
 Genetic predisposition + Environment
 Contributes to Metabolic Syndrome:
 Diabetes
 Abdominal obesity
 Hypertension – high total cholesterol, low LDL
 High triglycerides, atherosclerotic changes

CLINICAL MANIFESTATIONS OF
TYPE II DIABETES
 Nonspecific
symptoms
 May have classic symptoms of Type 1
 Common symptoms:
 Fatigue
 Recurrent infections
 Recurrent vaginal yeast infection
 Prolonged wound healing
 Visual changes
Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.
GESTATIONAL DIABETES
Occurs only during pregnancy
 Related to increased levels of natural progesterone,
cortisol and human placental lactogen.
 Associated with higher birth weight babies (more
glucose in mother = more nutrients for infant)
 Also associated with later onset of Type II diabetes in
the woman
 First screen: urine tests positive for glucose at each
office visit.
 Second screen: Glucose Tolerance Test (GTT)


A fasting glucose is drawn then high carbohydrate solution is
ingested. Blood is drawn every 30-60” for 3 hours.
CRITERIA FOR DIABETES DIAGNOSIS
 Consistent
fasting plasma glucose of 126 mg/dL
 Hemoglobin A1C level = or > 6.5%
 Clinical symptoms of diabetes and
hyperglycemia
 May include a chemical, or “fruity” breath
due to ketones
 Urine positive for:
 Albumin, Protein (muscle breakdown due to
gluconeogenesis)
 Ketones (due to fat breakdown)
 Glucose (due to excess glucose in the serum)
HEMOGLOBIN A1C TEST
Hemoglobin A1c: Normal is <6.5
 A measure of glucose bonded to hemoglobin molecules
 Used to estimate fluctuating blood sugar levels over
time
 Turnover of Hgb is about every 3-months
 Better test for looking at overall glycemic control
SERUM GLUCOSE LEVELS
TREATMENT GOAL IS TO NORMALIZE
BLOOD GLUCOSE LEVELS
 Diet
 Exercise
 Medications
Insulin
 Oral antidiabetics

 Self-care
 Chronic

infections
Glucose is a rich
environment for bacteria
 Slow
wound healing
Poor circulation due to
capillary fragility
 Dependent ulcers
 Gangrene and
amputations

 Renal
disease & renal
failure
 Visual retinopathy
leading to blindness
COMPLICATIONS OF
POORLY
MANAGED DIABETES
 Cataracts
 Peripheral
neuropathies
 Atherosclerosis
(“hardening of the
arteries”)
 Cerebrovascular
disease
 Ischemic heart
disease
DIABETIC RETINOPATHY & CATARACT
Cataract
FOOT ULCERS IN DIABETIC PATIENTS
DRUGS AFFECTING
BLOOD GLUCOSE LEVELS
ANTIDIABETIC DRUGS
Used to control or manage diabetes (not cure)
Two groups:
 Insulin


Replaces the body’s own missing insulin
Other antidiabetic agents
 Sulfonylureas: Stimulate beta cells to
release more insulin
 Non-sulfonylureas: Promote glucose
transportation into the cells & inhibit
glucagon production
 Incretin modifiers/mimetics: Increase
action of incretin hormones to release more
insulin and decrease glucagon hormones.
INSULIN



Synthetic insulin (exogenous) acts in the same manner
as endogenously (human) insulin.
Sources of exogenous insulin historically included pork
and beef pancreas, but now only recombinant DNA
technology or genetic engineering is used to create
human-like insulin.
Human-sourced insulin is considered the standard
therapy.
INSULIN



Insulin promotes the uptake of glucose, amino
acids, and fatty acids converting them into
substances that are stored in body cells.
Insulins are injected subcutaneously (subQ, or
SQ). The abdomen absorbs most
consistently. Orally will break down
and not be absorbed.
Insulin syringes are marked as
100 units per 1 mL. Insulin is
always ordered in “units” (0.1 mL)
TYPES OF INSULIN

Rapid-acting


Must be given within 5 minutes of eating
Humalog (insulin lispro)
NovaLog (insulin aspart)
Short-acting
Onset 30”-1 hr, Peak 2-4 hrs., Duration 6-8 hrs.
 Can be given 30” before meals
 Only Regular Insulin can be given IV (all others SQ
only)

*Regular

Insulin
Intermediate-acting



Onset 1-2 hrs.
Peak 6-12 hrs.
Duration 18-24 hrs.
Lente, NPH and Humulin N
TYPES OF INSULIN (CONT’D)
 Long-acting
Available in prefilled, 3-mL cartridges “OptiPen One” insulin
pen devices or via traditional injections
Levemir (insulin detmir)
 Duration 12-24 hrs.
*Lantus (insulin glargine)
 Duration 24 hrs.
 Given once a day, usually at HS
Combination – commercial mixes. Example:
Humulin 70/30 (70% NPH and 30% Regular)
 Available in vials or prefilled syringe “pens”


Prototypes:
Regular Insulin and Insulin Glargine (Lantus)
INSULIN
THERAPY
REGULAR INSULIN: CORE DRUG KNOWLEDGE
 Pharmacotherapeutics
All types of diabetes mellitus
 Pharmacokinetics
 Administered: SC or IV
 Pharmacodynamics
 Injected insulin mimics the effect of
endogenous insulin

REGULAR INSULIN: CORE DRUG KNOWLEDGE (CONT.)
Contraindications and precautions
 Hypoglycemia
 Side effects and/or Adverse effects
 Hypoglycemia and lipoatrophy
 Patient and family education
 Discuss how to administer insulin properly.
 Discuss storage of insulin.
 Discuss side effects of therapy.
 Ongoing assessment and evaluation
 Evaluate ability to administer insulin.
 Monitor fasting blood glucose daily and hemoglobin
A1C levels every few months.

STORAGE OF INSULIN
Refrigerate unopened vials until needed
 Once opened:

Room temperature for 1 month; or
 Refrigerator for 3 months

Less tissue irritation if at room temperature
 Roll the vials to mix contents before withdrawing
(roll the Pens before injecting)
 Pre-filled syringes should be stored in the
refrigerator and used within 1-2 weeks

SLIDING SCALE INSULIN COVERAGE
Insulin may be given in varying doses dependent
on the patients glucose levels
 Glucose testing is performed several times a day,
and insulin dose is given based on those test
results
Example:

ADVERSE REACTIONS TO INSULIN
 Hypoglycemic
reaction (Insulin shock)
 Nervousness, trembling, lack of coordination
 Cold and clammy skin
 Headache, dizziness
 Slurred speech
 Mental confusion, agitation, combativeness
 Seizures (Coma and Death may occur)
Hypoglycemia symptoms are treated by
administering glucose in any form - preferably
oral
ADVERSE REACTIONS TO INSULIN
 Hypokalemia
(↓ K) – palpitations,
arrhythmias
 Somogyi
Effect
 Hypoglycemia between 2:00-4:00 am
 Dawn
Phenomenon
 Hyperglycemia on wakening. Sxs are a
headache on waking, night sweats, and
nightmares
INSULIN PUMPS

Implantable
Surgically implanted into the abdomen
 Delivers basal insulin and boluses of insulin with
meals either intraperitoneal or IV


Portable





Continuous subQ insulin infusion (CSII)
Battery operated device outside of the body that
stores Regular insulin with wires that enter the body
placed subQ in the location that the patient prefers
About the size of a cell phone
Delivers basal and bolus insulin
Doses are programmed by the patient – pushes a
button to deliver the insulin
EXAMPLES OF INSULIN PUMPS
QUESTION
Which of the following SC site provides the most
rapid absorption of insulin therapy?
A. Arm
B. Abdomen
C. Buttocks
D. Thigh
QUESTION
Which of the following SC site provides the most rapid
absorption of insulin therapy?
A. Arm
B. Abdomen
C. Buttocks
D. Thigh
B. Abdomen
Rationale: The most rapid absorption occurs when
administration is into the abdominal SC layer (as much
as 50% faster than other routes).
The next most rapid is into the arm, followed by the
thigh, and finally the buttocks.
ORAL HYPOGLYCEMICS - SULFONYLUREAS
Sulfonylureas
Stimulate the beta cells to secrete insulin plus
increase tissue response to insulin and decrease
glucose production by the liver
 Only for Type II Diabetes
 Chemically related to sulfonamides but no
antibacterial properties

Prototype Drug: Glipizide
(Glucotrol, Glucotrol XL)
GLIPIZIDE: CORE DRUG KNOWLEDGE
 Pharmacotherapeutics
Adjunctive treatment to lower blood
glucose levels in diabetes mellitus
Type 2
 Pharmacokinetics
 Administered: oral. Metabolism: liver.
Excreted: urine and feces. Onset: 2
hours. Protein bound.
 Pharmacodynamics
 Hypoglycemic action results from the
stimulation of pancreatic beta cells
causing them to release more insulin.

GLIPIZIDE: CORE DRUG KNOWLEDGE (CONT.)
 Contraindications
and precautions
 Hypersensitivity, Sulfa allergy
 Side effects
 Anorexia, nausea, vomiting, heartburn,
and a metallic taste in the mouth
 Adverse
effects
Hypoglycemia
 Drug interactions
 Drug interactions are possible because
these drugs are metabolized by the
CYP3A3/4 system.

GLIPIZIDE: CORE DRUG KNOWLEDGE (CONT.)
 Patient
and family education
 Administer before breakfast or the first
main meal of the day.
 Teach about diabetes management.
Diet
 Exercise
 Conditions that can increase blood glucose


Teach patients and families the signs
and symptoms of hypoglycemia.
QUESTION
The mechanism of action of glyburide is the
decreased production of insulin by the liver,
which results in decreased blood glucose
levels.
A. True
B. False
QUESTION
The mechanism of action of glyburide is the
decreased production of insulin by the liver,
which results in decreased blood glucose
levels.
B. False
Rationale: The mechanism of action of
glyburide is stimulation of the beta cells
in the pancreas. Hypoglycemic action of
glyburide results from the stimulation of
pancreatic beta cells.
ORAL HYPOGLYCEMICS
Nonsulfonylureas
Prototype: Metformin (Glucophage)





Decreases liver production of glucose from
stored glycogen
Decreases the absorption of glucose from the
small intestine
Increases insulin sensitivity and uptake at the
cells
Does not cause hypoglycemia
May be combined with other antidiabetic
medications
METFORMIN: CORE DRUG KNOWLEDGE
 Pharmacotherapeutics
Lower blood glucose in type 2 diabetes
 Pharmacokinetics
 Administered: oral. Metabolism: liver.
Excreted: kidneys.
 Pharmacodynamics
 Decreases hepatic glucose production,
decreases intestinal absorption of glucose, and
improves insulin sensitivity by increasing
peripheral glucose uptake.

METFORMIN: CORE DRUG KNOWLEDGE (CONT.)
Contraindications and precautions
 Hepatic disease
 Side effects
 Anorexia, nausea and vomiting, weight loss,
abdominal discomfort, dyspepsia, flatulence,
diarrhea, and a metallic taste sensation
 Diarrhea is the biggest problem!
 Adverse effects
 No significant adverse effects. Will not cause
hypoglycemia
 Drug interactions
 May react with contrast media used for radiographic
procedures

METFORMIN: PLANNING AND INTERVENTIONS
 Maximizing
therapeutic effects
 Administer metformin twice a day with
the morning and evening meal.
 Adherence with the recommended
diabetic diet and daily exercise help in
the control of type 2 diabetes.
 Minimizing adverse effects
 Taking the drug at mealtimes and using
gradual dosage increments minimize
side effects.
QUESTION
Metformin is contraindicated in which patients?
A. Type 2 diabetics with open skin lesion
B. Type 2 diabetics with chronic obstructive
pulmonary disease
C. Type 2 diabetics with coronary artery disease
D. Type 2 diabetics with cirrhosis
QUESTION
Metformin is contraindicated in which patients?
A. Type 2 diabetics with open skin lesion
B. Type 2 diabetics with chronic obstructive
pulmonary disease
C. Type 2 diabetics with coronary artery disease
D. Type 2 diabetics with cirrhosis
D. Type 2 diabetics with cirrhosis
Rationale: Metformin is contraindicated in
patients with chronic liver disease.
ORAL HYPOGLYCEMICS
Incretin Modifiers
Incretin is a hormone that stimulates insulin
secretion in response to meals.
 Drugs act to slow the inactivation of incretin
hormones, increase insulin secretion, and suppress
glucagon secretion to reduce glucose production
 Used in combination with diet & exercise in Type
II diabetes

Prototype:
Sitagliptin (Januvia)
ORAL HYPOGLYCEMICS
Incretin Mimetics
Act to improve beta cell responsiveness, enhance
insulin secretion, suppress glucagon secretion,
slow gastric emptying and reduce food intake
promoting weight loss.
 Not a substitute for insulin – not used for Type I
DM
 Also approved as a weight loss drug

Prototype:
Liraglutide (Victoza)
LIRAGLUTIDE: CORE DRUG KNOWLEDGE
Pharmacotherapeutics
 Type II diabetes
 Weight loss
 Administration
 Given once daily
 Given subcutaneously using pre-filled pen
syringe
 Side effects
 Nausea, bloating, delayed gastric emptying,
decreased appetite
 Adverse effects
 Possible thyroid tumors, including cancer

HYPERGLYCEMIC DRUG USED TO RAISE BLOOD SUGAR
IN AN EMERGENCY
Prototype: Glucagon





Hormone secreted by alpha cells in the
pancreas
Stimulates glycogenolysis (breakdown of
glucose)
Available for subQ, IM and IV use
Indicated to treat insulin-induced
hypoglycemia in the patient who is semiconscious or unconscious
Glucose levels increases in 5-20 minutes after
dosing
GLUCAGON: CORE DRUG KNOWLEDGE
 Pharmacotherapeutics
Hypoglycemia
 Pharmacokinetics
 T½: 3 to 10 minutes
 Pharmacodynamics
 Increases blood glucose levels by
stimulating glycogenolysis in the
peripheral tissues

GLUCAGON: CORE DRUG KNOWLEDGE (CONT.)
 Contraindications
and precautions
Hypersensitivity
 Adverse effects
 Hypotension, respiratory distress,
nausea and vomiting
 Drug interactions
 Oral anticoagulants
 Minimizing adverse effects
 Administer supplemental carbohydrates
as soon as possible once consciousness
has been achieved.

CASE STUDY
Maria is a 67-yo, retired woman who states that
she has nocturia 3-7x each night and increased
hunger and thirst for the past 2 weeks. She is
distressed that she may need additional
medications to control her blood sugar. Her past
medical history includes type 2 diabetes mellitus
(diagnosed 15 years ago) which has been dietcontrolled, hypertension and hyperlipidemia.
Data obtained from the nursing assessment
include the following:
 Weight: 215 pounds
Height: 5 feet, 4 inches
 Vital Signs: 152/82 – 88 – 16
T-98.2 F
 Labs: Glucose: 361 mg/dL (fasting);
HgbA1C: 13.2 Cholesterol 315, Triglycerides 218
CASE STUDY
The patient’s current medication therapy includes
the following: Glucophage (Metformin) 1000 mg
PO bid
1. What is the mechanism of action of metformin?
2. What are the common side effects of metformin?
3. Identify one other medication that she might be
prescribed, its mechanism of action and its
common side effects.
4. What core patient-specific variables are
important to consider in doing patient
education?