PBL Learning Objectives Flashcards
What is the first step in the mechanism of action of insulin?
- Insulin binds to insulin receptors (members of the growth factor receptor family)
What is special about insulin receptors?
They are members of the growth factor receptor family.
-Unlike G-protein associated receptors, these span the membrane just once and acquiring signaling ability through activation of tyrosine kinase activity (intrinsic to individual receptor molecules)
What is the second step in the mechanism o faction of insulin?
Through complex signaling pathway consisting of kinases, phosphatases, and other signaling molecules there are 2 pathways insulin activates
What two pathways does insulin activate?
- Metabolic
2. Mitogenic signaling pathway
What is the function of the metabolic pathway?
- Activation of phosphatidylinositol-3-kinase leads to the activation of serine/threonine kinase Akt
- Akt activation drives the movement of glucose transporter (GLUT) 4-containg vesicles to the cell membrane, increases glycogen and lipid synthesis, and stimulates protein synthesis through the activation of mTOR.
What is the function of the mitogenic signaling pathway?
Activation of RAS initiates a cascade of activating phosphorylations via the MAP kinase pathway, leading to cell growth and proliferation
What are 7 overall insulin functions?
- Inc. transport of glucose into skeletal muscle and adipose tissue
- Inc. glycogen synthesis and storage
- Inc. triglyceride synthesis
- Inc. Na retention in kidneys
- Inc. protein synthesis
- Inc. cellular uptake of K+ and amino acids
- Dec. glucagon release
What is a primary gain from a patient inducing DKA?
Treatment of the medical condition
What is a secondary gain from a patient inducing DKA?
Getting attention from boyfriend, people at hospital, family, etc. [External motivator, exaggerating or causing symptoms]
What is another way to phrase primary gain?
Positive reasons to use treatments (take insulin/go to hospital –> not sick/acidotic)
What is another way to phrase secondary gain?
Reasons patient would want to NOT take treatment (no insulin –> attention from boyfriend and others)
Primary gain vs. Secondary online:
- Interpersonal, social or financial advantages from the conversion of emotional stress directly into illness (e.g. hysterical blindness or paralysis) –> alleviation of anxiety that results from conversion of emotional conflict to organic illness (defense mechanism)
- Interpersonal or social advantages gained indirectly from illness (e.g. assistance, attention, sympathy)
What is the inheritance pattern of Type 1 diabetes?
It’s unknown
Does Type 1 diabetes have a hereditary component?
Yes
What mutations are associated with an increased risk of developing type 1 diabetes?
Mutations in HLA-DR3 and HLA-DR4
What is the function of HLA?
HLA provides instructions for the immune system. The HLA complex helps the immune system distinguish the body’s own protein from proteins made by foreign invaders such as viruses and bacteria.
What do monozygotic twin studies indicate about Type 1 diabetes?
Cohort studies
-Onset of Type 1 diabetes by age 60 years is reported in 65% of monozygotic twins of persons with type 1 diabetes
What are non-HLA single nucleotide polymorphisms associated with?
Increased risk of developing persistent autoantibodies in children at risk for type 1 diabetes.
In a prospective cohort study where all patients had high-risk HLA genotype for development of type 1 diabetes but lacked a 1st deg. relative with type 1 diabetes, how many participants with polymorphisms developed type 1 DM?
24% of participants
What is the prevalence of Type 1 diabetes?
Prevalence of newly diagnosed type 1 diabetes per 1,000 persons:
1.93 overall (out of 1,000)
What is the prevalence of newly diagnosed type 1 diabetes per 1,000 people by race?
- 55 in whites
- 62 in blacks
- 29 in hispanics
- 35 in American indians
What are three risk factors for Type 1 diabetes?
- High birth weight
- Childhood obesity
- Increasing maternal age at birth
What are preventative care and disease-related risk management strategies are appropriate for patients with diabetes?
Disease related risk management:
- Cigarette smoking –> cessation
- Blood pressure raise HDL (no set goal)
- Prothrombotic state –> low does aspirin therapy (patients with CHD and other risk factors)
- Glucose –> A1C dec. BMI
- Exercise prescription based on patient’s status
- Nutrition
What are the main signs of DKA?
- Kussmaul respirations (rapid/deep breathing)
- N/V
- abdominal pain
- psychosis/delirium
- dehydration
- fruity breath (exhaled acetone)
What chief concerns are associated with DKA?
Polyuria, polydipsia, polyphagia, fatigue, dyspnea, abdominal pain, N/V, HA, confusion, lethargy
What are precipitating factors for DKA?
- New onset DM type 1
- Fever/signs of infection
- Reduced insulin intake/inadequate management
- Atherosclerotic disease
- Change in eating patterns/eating disorder
- Pregnancy
- Increased alcohol intake/illicit drug use
- Changes in medications
- Other stressors (trauma, pancreatitis, psychological stress)
What is Rapid acting insulin?
Ultra rapid
What is Short acting insulin?
Regular
What is Intermediate acting insulin?
NPH
What is Long acting insulin?
Insulin glargine
What is the onset of action for rapid acting/ultra rapid insulin (lispro insulin)?
0.25 hr (15 min)
What is the onset of action for short acting (regular) insulin?
0.5 hr (30 min)
What is the onset of action for intermediate acting (NPH) insulin?
2-4 hours
What is the onset of action for long acting (glargine) insulin?
1-2 hours
What is the peak of action for rapid acting/ultra rapid insulin (lispro insulin)?
0.5-1.5 hours
What is the peak of action for short acting (regular) insulin?
2-3 hours
What is the peak of action for intermediate acting (NPH) insulin?
4-12 hours
What is the peak of action for long acting (glargine) insulin?
No peak/relatively flat
What is the duration of action for rapid acting/ultra rapid insulin (lispro insulin)?
3-4 hours
What is the duration of action for short acting (regular) insulin?
4-8 hours
What is the duration of action for intermediate acting (NPH) insulin?
10-20 hours
What is the duration of action for long acting (glargine) insulin?
18-24 hours
What are the three ultra rapid/rapid acting insulins?
Insulin lispro
Insulin aspart
Insulin glulisine
What is short acting insulin?
Regular insulin
What is intermediate acting insulin?
NPH (neutral protamine hagedorn)
What is Long-acting insulin?
Insulin glargine & Insulin detemir
How does the respiratory system compensate for metabolic acid-base disorders?
- Your body wants to get rid of CO2
- In order to do this, you breathe more (Kussmaul breathing)
What is Kussmaul breathing?
Air hunger, rapid, deep, labored breathing
What is Le Chateliers Principle in relation to Kussmaul breathing?
If you breathe off CO2, it shifts the bicarb equation to the left –> this gets rid of H+, decreasing acidity caused by ketoacids
H2O + CO2 H2CO3 H+ + HCO3-