Chapter 49 Flashcards
What are the 3 main classes of drugs which affect blood glucose levels?
- Insulins
- Non-insulin antidiabetics
- Glucose-elevating agents
What is the prototype drug for the insulin class of drugs which affect blood glucose levels?
Regular Insulin
What are three drugs are that closely related to regular insulin?
- Aspart
- Lispro
- Glulisine
What is the prototype drug which is a glucose-elevating agent?
Glucagon
How many people in the US does Diabetes Mellitus affect?
- 6 million people
- 7.8% of the population
How many people have type 1 diabetes? Type 2 diabetes?
Type 1 = 5-10%
Type 2 = 90-95%
What does diabetes increase your risk of?
- cardiovascular disease (HTN, heart disease, stroke) - kidney failure - blindness - nervous system disease - extremity amputation
In 2007, what was the economic cost of diabetes?
$174 billion
What are the two major classes of oral antidiabetic drugs that are used to control type 2 diabetes?
- Sulfonylureas (anti-glycemics)
2. Non-sulfonylureas (anti-hyperglycemics)
What is the prototype sulfonylurea?
Glyburide
What is the prototype non-sulfonylurea?
Metformin
What are the three body systems that are involved in the regulation and use of glucose?
- Liver
- Pancreas
- Skeletal muscle tissue
What is the liverās role in glucose regulation?
Liver synthesizes its own glucose supply (gluconeogenesis)
- stores and releases glucose that has been converted from dietary carbohydrates
What happens in the liver when blood glucose is low? When it is high?
Low = releases its stored and synthesized glucose High = stops producing and releasing glucose
What is the exocrine function of the pancreas?
Produce digestive enzymes
What is the endocrine function of the pancreas?
Synthesize and secrete peptide hormones
What are the three peptide hormones that the pancreas secretes from the islets of Langerhans?
- Insulin
- Glucagon
- Somatostatin
What types of cells are contained in the islets of Langerhans?
- Beta cells
- Alpha cells
- Delta cells
- F cells
What do Beta cells secrete?
Hypoglycemic hormone insulin
What do Alpha cells secrete?
Hyperglycemic hormone glucagon
What do Delta cells secrete?
Somatostatin - hormone that inhibits both glucagon and insulin secretion
What do F cells synthesize and secrete?
Pancreatic polypeptides used in digestion
What kind of tissue is the target for the action of insulin?
Muscle tissue
- contains the majority of insulin receptor sites
What provides a good indication of circulating insulin levels? Why?
C peptide
- Proinsulin splits to form insulin and C peptide
- they will be in equal concentrations
What is insulin secretion most commonly triggered by?
High blood glucose levels
What is the role of insulin?
Lowers blood glucose levels by stimulating peripheral glucose uptake (especially skeletal muscle and fat)
- promotes the uptake and storage of glucose in the liver (in the form of glucagon)
Which tissues do not need insulin so that glucose can enter their cells?
- brain
- nerves
- intestine
- liver
- retina
- erythrocytes
- renal tubules
What factors can influence changes in blood glucose levels?
- stress
- secretion of insulin-antagonistic hormones (cortisol, E, growth hormone, glucagon, somatostatin)
- rates of hepatic synthesis of glucose
- presence of levels of insulin antibodies
- number of cellular insulin receptors
- use of glucose by peripheral cells or tissues
If glucagon is released, what happens in the liver?
Glucagon stimulates glycogenolysis and gluconegogenesis
- resulting in a release of glucose into the blood
What are the three types of diabetes mellitus?
- Type 1
- Type 2
- Gestational
What is diabetes insipidus?
Metabolic disorder
- high amounts of dilute urine are formed because of deficient production of ADH or inability of the kidney tubules to concentrate urine
- does not affect blood glucose levels
- is NOT treated with insulin or oral antidiabetics
What is the defining characteristic of Type 1 diabetes?
Autoimmune disorder
- destruction of insulin-secreting beta cells in the pancreas
- leading to absolute insulin deficiency
What happens if the bodyās reserve of insulin is depleted?
Results in HYPERglycemia
- circulating glucose CANNOT enter the cells
How does ketoacidosis occur?
Body is in a hyperglycemic state
- high circulating blood glucose
- glucose cannot enter cells
- body thinks there is NOT ENOUGH glucose so it starts to break down lipids and proteins for energy
- This causes an increase in ketoacids
What is the final result of Type 1 diabetes?
Destruction of pancreatic beta cells
- may occur over period of months to years
- state of absolute insulin deficiency
What is required for all cases of Type 1 diabetes?
Insulin therapy
When is the onset of Type 1 diabetes?
Childhood or puberty
- however it CAN develop at any age
What is Type 2 diabetes characterized by?
Insulin RESISTANCE by the tissues
- usually a decrease in insulin production
What is Type 2 diabetes closely linked with?
- obesity
- sedentary lifestyle
- lack of physical exercise
What happens to insulin levels in Type 2 diabetes?
Normal or increased
- may be increased because the pancreas tries to overcome the resistance by producing more insulin
- b/c the peripheral tissue is resistant to insulin, insulin does not enter the cells but stays in the bloodstream
When is Type 2 diabetes most prevalent?
Later years in life
- but we are seeing it younger and younger (as children get fatter and fatter)
What is considered the primary defect in Type 2 diabetes?
Insulin resistance
What is the metabolic syndrome?
An insulin-resistance syndrome
- a precursor to the development of type 2 diabetes
What is the age of onset of Type 1 diabetes? Type 2?
Type 1 = usually before 20 yrs
Type 2 = usually after 40 yrs
What is the incidence of Type 1 diabetes? Type 2?
Type 1 = 5 - 10%
Type 2 = 90 - 95%
What is the body weight of a person with Type 1 diabetes? Type 2 diabetes?
Type 1 = Thin or underweight
Type 2 = Overweight or obese
What are the clinical s/s of Type 1 diabetes?
Hyperglycemia Polyphagia Polydipsia Polyuria Weight loss
What are the clinical s/s of Type 2 diabetes?
Hyperglycemia Fatigue Weakness Mild 3 P's Fungal infections Blurred vision
Typically when is ketoacidosis seen? (Type 1 or Type 2)
Type 1
What are the three ways that we can manage Type 1 diabetes (3) ?
- Insulin injections
- Dietary controls
- Exercise regimen
What are the ways that we can manage Type 2 diabetes (5) ?
- Weight reduction
- Dietary controls
- Exercise regimen
- Oral drug therapy
- Insulin
Metabolic syndrome is a combination of which conditions?
- Insulin resistance
- Compensatory hyperinsulinemia (to maintain glucose homeostasis)
- Obesity
If a patient is undiagnosed with Type 2 diabetes, what are they are increased risk for?
- coronary artery disease
- stroke
- peripheral vascular disease
How does Gestational diabetes mellitus occur?
When a womanās pancreatic function is not sufficient to overcome the insulin resistance created by the anti-insulin hormones secreted by the placenta
What are some examples of anti-insulin hormones that are secreted by the placenta?
- Estrogen
- Prolactin
- Cortisol
- Progesterone
What can happen if gestational diabetes goes undiagnosed?
- Preeclampsia
- Fetal macrosomia (large infants)
- birth trauma
- perinatal mortality
What are some endogenous sources which may produce diabetes?
- genetic defects in beta cell function, insulin action or diseases of the pancreas (cystic fibrosis)
What are some exogenous sources which may produce diabetes?
- surgical removal of pancreas, ingestion of certain drugs/chemicals (glucocorticoid steroids)
What are the 4 criteria that are used to diagnose diabetes?
- Plasma glucose = 126 mg/dL after fasting for 8 hours
- Plasma glucose = 200 mg/dL during an oral glucose tolerance test
- A1C level of > 6.5%
- Symptoms of diabetes and hyperglycemia or hyperglycemic crisis at any time of the day (regardless of last meal)
What is an oral glucose tolerance test?
75 g of glucose is dissolved in water is ingested
How does the A1C test measure the average blood glucose level from the last 2-3 months?
Hemoglobin molecules react with glucose ā> glycosylated hemoglobin
- it will last the lifespan of the RBC to determine the patientās blood glucose level over time
What are the classic signs of hyperglycemia?
- excessive urination
- excessive thirst
- fatigue
- dry or itchy skin
- poor wound healing
- vision changes
At what value is a blood glucose level considered hyperglycemic?
> 126 mg/dL
What is the dawn phenomenon?
Blood glucose levels are at their highest between 5am and 6am
- release of growth hormone overnight is believed to produce this increase in blood glucose
How do we treat dawn phenomenon?
Providing larger doses of intermediate-acting insulin at bedtime
What is the Somogyi effect?
Produces early morning hyperglycemia
- precipitating factor is actually a HYPOglycemic event sometime after midnight
- body compensates by releasing glucose from the liver
- when the body overcompensates ā> REBOUND HYPERGLYCEMIA occurs
How do we treat the Somogyi effect?
- lowering the insulin dose
- increasing dietary intake at bedtime
- or both
What are the chronic complications of diabetes usually classified as?
- Microvascular
- Macrovascular
- according to the type of blood vessel damaged
What are some of the macrovascular complications?
- atherosclerotic vascular disease
- myocardial infarction
- cerebrovascular accident
What are some of the microvascular complications?
- cataracts, glaucoma, and blindness from retinopathy
- lower extremity infections and gangrene
- foot ulcers
- Charcot joints
- renal failure
- sexual dysfunction
What can severe hypoglycemia result in?
- coma
- altered consciousness
What is Basal insulin?
The continuous secretion that maintains glucose homeostasis
bodyās baseline level of insulin
What is Prandial insulin?
Insulin secretion stimulated in response to meals
What is the non-physiologic regimen of diabetic therapy?
Does not mimic normal beta-cell secretion
- ideal for those newly diagnosed (those who still produce some endogenous insulin)
What is the physiologic regimen of diabetic therapy?
Used in complete beta-cell failure when glucose control cannot be achieved with the non-physiologic regimen
What is correctional (or supplemental) insulin used for?
Patients with diabetes who are hospitalized (or ill), may require doses of insulin to correct any elevations in blood glucose
What are the 4 kinds (types) of insulin?
- rapid
- short (regular)
- intermediate
- long-acting
What is the prototype insulin?
Short-acting insulin
What are the trades names for Regular insulin?
- Novolin-R
- Humulin-R
When is insulin indicated for Type 1 diabetics? Type 2?
Type 1 = for all patients
Type 2 = for patients that cannot control their hyperglycemia with diet and exercise, weight reduction, oral antidiabetic drugs
What is regular insulin used to control?
To correct a current glucose elevation or an expected rise after eating
- not for use all day due to itās short duration
Why can regular insulin NOT be given orally?
It is destroyed by gastric acids
Which SC injection site provides the most rapid absorption?
Abdominal SC layer
- next is arm
- then thigh
- finally buttocks
How long does insulin remain stable at room temperature for?
1 month
- for longer storage, place in refrigerator
Where is insulin filtered and where is it reabsorbed?
Filtered in glomerulus
Reabsorbed in proximal renal tubule (98%)
How does renal impairment affect diabetic patients?
It reduces the amount of insulin excreted, thus reducing the amount of insulin required
- renal function impairment occurs commonly in diabetic patients b/c of vascular insufficiency
When is insulin contraindicated?
In times of hypoglycemia
What are the earliest signs of hypoglycemia?
- fatigue and malaise
- trembling
- irritability
- headache
- nausea
- numbness
- paresthesias
- muscle weakness
How can lipodystrophy be caused?
By repetitive SC injections into the same injection site
= disturbances in fat metabolism
With insulin, why do we rotate WITHIN the site, and not simply change injection sites?
It would substantially change the absorption of insulin and the blood glucose levels of the patient
If a patient has a low hematocrit, what will this do to the blood glucose reading?
Create a falsely HIGHER reading
If a patient has a high hematocrit, what will this do to the blood glucose reading?
Create a falsely LOWER reading
If a patient is experiencing shock or dehyration, what will this do to the blood glucose reading?
Create a falsely LOWER reading
What can you give your patient if they are hypoglycemic?
- 4 oz juice or non-diet soda
- 4 oz water with 4 tsp of sugar
- 8 oz non fat milk
When mixing types of insulin, which one do you draw up first?
Short-acting drawn into the syringe first
What are the three rapid-acting insulins?
- Aspart (NovoLog)
- Lispro (Humalog)
- Glulisine (Apidra)
What does protamine do when it is added to insulin?
Prolongs the action of the insulin
What are the separate parts of NovoLog Mix 70/30?
- 70% Aspart protamine
2. 30% Aspart
What does NPH stand for?
Neutral Protamine Hagedorn
What does the āNā signify on insulin? Is it clear or cloudy?
Intermediate acting
- cloudy in appearance
When is the onset, peak and duration of NPH?
Onset: 1 - 1.5 hours
Peak: 4 - 12 hours
Duration: up to 24 hours
What is Detemir (Levemir)? (Rapid, short, intermediate or long acting)
Long acting insulin
- clear insulin
What are the two main classes of oral anti-diabetic medications?
- Sulfonylureas
2. Non-sulfonylureas
How are second generation different than first generation drugs?
Second generation contain fewer drug interactions
What is Glyburide?
Potent second generation oral sulfonylurea
How is Glyburide absorbed? Metabolized?
Excreted?
Absorbed: In the GI tract
Metabolized: Liver
Excreted: urine and feces
Why is Glyburide ineffective on Type 1 diabetes?
Because there is no endogenous release of insulin
- cannot stimulate the beta cells to produce insulin
Why should Glyburide be used cautiously in patients with know hepatic or renal disease?
May elevate drug blood levels
- increase the risk of hypoglycemic reactions
