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
What is the major side effect of insulin?
Hypoglycemia
(This is the single limiting factor in the treatment of idabetes)
How does insulin release change in T2DM?
Patients with T2DM will have a decreased first phase of insulin secretion
This results in hyperglycemia
Define insulin resistance
Decreased ability of insulin to lower circulating glucose concentrations
Results in:
- Impaired stimulation of glucose utilization by muscle and fat
- Imparied suppression of glucose production by the liver
What is the most serious side effect of the SGLT-2 inhibitors?
Increased risk of amputation
Other side effects include vaginal candidiasis, UTI, frequent urination, dehydration, hyperkalemia
Which diabetes medication is a bile binding resin?
Colesevelam
Why is glargine insulin long-acting?
(Mechanism of extended duration)
Forms microprecipitates in the subcutaneous tissue
Which HLA types are assoicated with increased risk of T1DM? (2)
HLA DR3
HLA DR4
What is the first line medication for the management of T2DM?
Metformin
