185b/186b/187b - Diabetes I, II, Pharm Flashcards
How will the following paramaters change with decreased weight?
- HbA1C -
- Blood pressure -
- Triglycerides -
- HDL cholesterol -
- LDL cholesterol -
- HbA1C - decrease
- Blood pressure - decrease
- Triglycerides - decrease
- HDL cholesterol (good cholesterol) - increase
- LDL cholestero (bad cholesterol)l - no change
Describe the basal/bolus insulin regimen
Glargine or detimir (long acting) before breakfast or at bedtime
+
Glulisine, aspart, or lispro (short acting) before meals
Vs. Split mixed, which is a mixture of short and long acting pre-breakfast and pre-supper
Which class of diabetes mediacation increases the transcription of insulin-sensitivity genes in muscle and adipose tissue?
Thiazolidinediones (-glitazones)
not as popular anymore
When a patient presents with DKA, what is their potassium status?
Hyperkalemia*
- *High serum K+, but low total body K+
- Intracellular stores of potassium are depleted
- Decreased pH in DKA drives H+ into the cell, K+ out
- K+ is excreted due to polyuria
- When giving insulin, must monitor K+ levels
- Begin repleting K+ as soon as serum K+ falls to normal
- (Insulin increased Na+/K+ activity, shoveling K+ into cells)
How does hyperglycemia result in microvascular damage?
(describe the pathogenesis)
- Increased oxidative stress -> metabolic consequences
- Inhibition of GAPDH
- Glucose shunted to the aldose reductase pathway
- Consumption of NADH -> reduced ability to deal with oxidative stress
-
-> Advanced glycation end products (AGEs) are formed
- Leads to release of growth factors and cytokines
- Also, accumulation of sorbital
In short
Intracellular hyperglycemia -> Oxidative stress -> AGEs and Sorbitol -> microvascular damage
Which agents work to increase endogenous insulin secretion? (4)
Can the be used for T1DM, T2DM, or both?
- Sulfonylureas (-amide, -ride)
- Meglitinides (repaglinide)
- GLP-1 analogs (-tide)*
- DPP-4 inhibitors (-gliptin)*
Used for T2DM - relies on endogenous insulin secretion
* = glucose-dependent insulin secretion; no risk of hypoglycemia
How does adipose tissue contribute to insulin resistance?
(describe the pathogenesis)
Obesity is a state of inflammed adipose tissue
- Adipocytes have outgrown their blood supply
- Secrete inflammatory cytokines in response (IL-1, IL-6, TNF-alpha)
-
Decreased storage -> excess free fatty acids
- Liver: increased gluconeogenesis
- Systemic: Decreased fast oxicdation, insulin action, glucose uptake
Describe the split-mixed insulin regimen
Pre-breakfast AND pre-supper injection of a mixture of short and long acting
- Short = glulisine, aspart, or lispro*
- Long = detemir or glargine*
- vs. basal/bolus: Glargine or detimir (long acting) before breakfast or at bedtime +Glulisine, aspart, or lispro (short acting) before meals*
What is the peak age of incidence of T1DM?
10-14
BUT important to remember 25% of T1DM is diagnosed in adulthood
How does DKA develop when insulin is absent?
(describe the pathogenesis)
- Body senses percieved lack of glucose (can’t take glucose up into cells)
- Glycerol -> gluconeogenesis
-
FFAs are metabolized via beta oxidation
- Acetyl CoA -> Acetoacetyl CoA -> Ketones
- -> Decreased pH
- DKA
Exacerbating processes:
- -> Gluconeogenesis in the liver
- But peripheral tissues cannot abosorb, excreted in urine
- -> Hyperglycemia, polyuria, dehydration
- -> Proteinolysis in the periphery
- Amino acids are substrates for gluconeogensis
Which antibodies are commonly associated with T1DM? (5)
- Islet cell autoantibodies
- Glutamic acid decarboxylase autoantibodies
- Insulinoma associated 2 antibodies
- Insulin autoantibodies
- ZnT8 autoantibodies
*presence of autoantibodies may precede disease by years, most patients have >1 when presenting with symptoms*
Which insulin preparation has a fatty acid side chain?
What is the result?
Detemir
Aggregates and binds to albumin -> longer half life
Which secretagogues are glucose-dependent?
Why is this important?
GLP-1 analogs (-tide)
DPP-4 inhibitors (-gliptin)
These drugs are safer for people who are at increased risk of hypoglycemia
What is the onset and duration of action of the short-acting insulin agents?
Onset: 5-15 min
Duration: 3-5 hr
Lispro, aspart, glulisine
Which cells mediate destruction of islet cells in T1DM?
T cells
Antibodies are a marker of destruction, but damage is T-cell mediated
(=> Type IV hypersensitivity reaction)
D - Use of pioglitazone should be avoided in patients with heart failure or acute dieases of the liver
- exenatide (GLP-1 analog) closes the K+ channel
- metformin (biguanide) activates AMPK (and inhibits glycerol-3-phosphate dehydrogenase) to decrease hepatic glucose output
- Canagliflozin (SGLT-2 inhibitor) inhibits renal sodium/glucose transporters
How does insulin release change in T2DM?
Patients with T2DM will have a decreased first phase of insulin secretion
This results in hyperglycemia
How is HbA1C formed?
Glucose irreversibly attaches to hemoglobin (glycation)
- Glycated hemoglobin is proportional to the amount of glucose in the blood over time
