185b/186b/187b - Diabetes I, II, Pharm Flashcards

1
Q

How will the following paramaters change with decreased weight?

  • HbA1C -
  • Blood pressure -
  • Triglycerides -
  • HDL cholesterol -
  • LDL cholesterol -
A
  • HbA1C - decrease
  • Blood pressure - decrease
  • Triglycerides - decrease
  • HDL cholesterol - increase
  • LDL cholesterol - no change
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2
Q

Describe the basal/bolus insulin regimen

A

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

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3
Q

Which class of diabetes mediations increses the transcriction of insulin-sensitivity genes in muscle and adipose tissue?

A

Thiazolidinediones (-glitazones)

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4
Q

When a patient presents with DKA, what is their potassium status?

A

Hyperkalemia*

  • *High serum K+, but low total body K+
    • 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)
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5
Q

How does hyperglycemia result in microvascular damage?

(describe the pathogenesis)

A
  • 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

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6
Q

Which agents work to increase endogenous insulin secretion? (4)

Can the be used for T1DM, T2DM, or both?

A
  • 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

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7
Q

How does adipose tissue contribute to insulin resistance?

(describe the pathogenesis)

A

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
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8
Q

Describe the split-mixed insulin regimen

A

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*
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9
Q

What is the peak age fo incidence of T1DM?

A

10-14

BUT important to remember 25% of T1DM is diagnosed in adulthood

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10
Q

How does DKA develop when insulin is absent?

(describe the pathogenesis)

A
  • Body senses percieved lack of glucose
  • -> Lipolysis in the perhiphery -> glycerol + FFAs
    • 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
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11
Q

Which antibodies are commonly associated with T1DM? (5)

A
  • Islet cell autoantibodies
  • Glutamic acid decarboxylase autoantibodies
  • Insulinoma associated 2 antibodies
  • Insulin autoantibodies
  • ZnT8 autoantibodies
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12
Q

Which insulin preparation has a fatty acid side chain?

What is the result?

A

Detemir

Aggregates and binds to albumin -> longer half life

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13
Q

Which secretagogues are glucose-dependent?

Why is this important?

A

GLP-1 analogs (-tide)

DPP-4 inhibitors (-gliptin)

These drugs are safer for people who are at increased risk of hypoglycemia

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14
Q

What is the onset and duration of action of the short-acting insulin agents?

A

Onset: 5-15 min

Duration: 3-5 hr

Lispro, aspart, glulisine

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15
Q

Which cells mediate destruction of islet cells in T1DM?

A

T cells

Antibodies are a marker of destruction, but damage is T-cell mediated

(=> Type IV hypersensitivity reaction)

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16
Q
A

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
17
Q

What is the major side effect of insulin?

A

Hypoglycemia

(This is the single limiting factor in the treatment of idabetes)

18
Q

How does insulin release change in T2DM?

A

Patients with T2DM will have a decreased first phase of insulin secretion

This results in hyperglycemia

19
Q

Define insulin resistance

A

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
20
Q

What is the most serious side effect of the SGLT-2 inhibitors?

A

Increased risk of amputation

Other side effects include vaginal candidiasis, UTI, frequent urination, dehydration, hyperkalemia

21
Q

Which diabetes medication is a bile binding resin?

A

Colesevelam

22
Q

Why is glargine insulin long-acting?

(Mechanism of extended duration)

A

Forms microprecipitates in the subcutaneous tissue

23
Q

Which HLA types are assoicated with increased risk of T1DM? (2)

A

HLA DR3

HLA DR4

24
Q

What is the first line medication for the management of T2DM?

A

Metformin

25
Q

Which class of diabetes medication increses renal glucose excretion?

A

SGLT-2 inhibitors (-flozins)

SGLT-2 is found in the proximal tubule of the kidney

26
Q

Which class of diabetes medications suppresses hepatic glucose production?

A

Biguanides (metformin)

27
Q

Describe the pathogenesis of Type 1 diabetes melitus

A
  • Some *event* in the islet
  • Immune cells enter
  • Antigens trigger T cell activation
  • T cells infiltrate the islet, destroy the beta cells

=> destruction of beta cells is T-cell mediated

28
Q

Which classes of diabetes medications work to decrease glucose absorption from the GI tract? (3)

A
  • Alpha-glucosidase inhibitors (acarbose, miglitol)
  • Amylin analog (pramlintide)
  • Colesevelam
29
Q

What is the role of islet cell antibodies in T1DM?

A

Marker of autoimmunity - correlates with presence of disease

NOT causative of islet cell damag

Damage to islet cells is mediated by T-cells

30
Q

How is HbA1C formed?

A

Glucose irreversibly attaches to hemoglobin (glycation)

  • Glycated hemoglobin is proportional to the amount of glucose in the blood over time
31
Q

What kind of receptor does insulin have?

A

Tyrosine kinase

(membrane associated)

32
Q

Is T1DM or T2DM more likely to present with DKA?

A

T1DM

33
Q

Is T1DM or T2DM more likely to cluster in famlilies?

A

T2DM

(Except MODY, which is type 1 but monogenic)