Chapter 5 - Endocrine Disorders Flashcards
What is the pathophysiology of diabetes mellitus?
• A hormonal abnormality characterized by a deficiency of the hormone of fluid storage (insulin)
• Deficiency may be absolute (type 1) or relative (type 2)
• In patients with type 2 DM, relative deficiency can be due to:
o Developed insensitivity of insulin receptors (obese type 2)
o Decrease in insulin production (non-obese type 2)
What is the role of insulin?
- Catalyzes storage of all fuel types – carbs, fats, and proteins
- Fats are lipid-soluble and can pass through cell membranes without the help of insulin
- Carbs and protein are water-soluble and require insulin to transport them across cell membranes
Complete vs. Relative Insulin Deficiency
- Complete – type 1 DM – lipids/fats are the only source of intracellular fuel
- Relative – type 2 DM – may initially be a compensatory increase in insulin secretion but eventually the beta cell dysfunction and the relative insulin deficiency occurs
Diagnostic Criteria for DM
- HgbA1c (main): A1C ≥ 6.5% with repeat A1C recommended in asymptomatic adults with glucose ≤ 200; no repeat needed if glucose is > 200
- Plasma glucose: fasting glucose (no intake for ≥ 8 hours) ≥ 126 on 2 occasions or random glucose ≥ 200 with symptoms including polyphagia, polyuria, polydipsia, and unexplained weight loss or hyperglycemic crisis
- Oral glucose tolerance test: 2-h plasma glucose ≥ 200 after a 75-g glucose load
Comparing Type 1 and Type 2 DM: Pathophysiology
- Type 1: autoimmune activated by trigger → destroy beta cells
- Type 2: relative insufficiency d/t either distended/distorted peripheral receptors or beta cell dysfunction
Comparing Type 1 and Type 2 DM: Disease Trajectory
- Type 1: relatively short, weeks to months; beta cell destruction results in absolute insulin deficiency
- Type 2: years; approximately 10 years; beta cell dysfunction gradually decreases insulin production
Comparing Type 1 and Type 2 DM: Presenting s/s
- Type 1: weight loss, muscle mass loss, dehydration, paresthesias, acetone breath, ± mental status change (cells are having to use fats as energy source)
- Type 2: subtle; vascular changes d/t chronic hyperglycemia – non-healing rashes, skin insult, hair loss in extremities
Comparing Type 1 and Type 2 DM: Lab Findings
- Type 1: serum ketones, rising BUN/creatinine, hypokalemia, high anion gap (mostly seen with DKA)
- Type 2: chronic; BUN/creatinine can rise as a result of renal insult
Comparing Type 1 and Type 2 DM: Assessment
• Complete baseline assessment to include foot exam, eye exam, ECG, and diagnostic markers for both type 1 and 2
Comparing Type 1 and Type 2 DM: Treatment
- Type 1: insulin replacement mimicking physiologic insulin production and release – basal supplemented with pre-meal short- or ultra-short-acting
- Type 2: weight loss in obese patients, oral therapy to sensitize insulin receptors, insulin to help achieve initial glycemic control (help preserve function of working beta cells)
When to use insulin – type 1 treatment
- All patients need insulin
* Basal insulin with adjustments for meals via multiple injections or pump
When to use insulin – type 2 treatment
- At time of diagnosis to help achieve initial glycemic control and preserve function of working beta cells – OR –
- When ≥ 2 standard oral agents at optimized doses are inadequate to maintain glycemic control
- Acute illness – in critically ill surgical and non-surgical patients, blood glucose should be kept 140-180
Glycemic control targets
- HgbA1c: non-diabetic < 6%; diabetic < 7%
- Fasting glucose: non-diabetic: < 100; diabetic 80-130
- Obtain A1C at least 2x/year in patients with stable glycemic control; 4x/year in patients whose therapy has changed or who are not meeting glycemic goals
Pharmacologic interventions for type 2 DM: Biguanides
• Examples: Metformin (Glucophage)
• A1C reduction: 1-2%
• FIRST LINE MEDICATION UNLESS CONTRAINDICATED
• MOA: insulin sensitizer
• Hypoglycemia risk: no
• Side effects/comments:
o Renal function impairment – with conditions that alter hydration (surgery, contrast), hold for day of and 48 hours after, reinitiate once hydration status and renal function have been established
o Lactic acidosis (rare) – in those with hepatic impairment, hypovolemia, HF, advanced age
o Vitamin B12 deficiency – increased risk
Pharmacologic interventions for type 2 DM: Thiazolidinedione (TZD, glitazones)
• Examples: Pioglitazone (Actos)
• A1C reduction: 1-2%
• MOA: insulin sensitizer
• Hypoglycemia risk: none when used as solo product
• Side effects/comments:
o Edema – especially when used with insulin or SU. Do not start in HF patients
o MI – increased risk in patients taking insulin or nitrates
Pharmacologic interventions for type 2 DM: Sulfonylurea (SU)
• Examples: Glipizide (Glucotrol), Glyburide (DiaBeta)
• A1C reduction: 1-2%
• OFTEN CONSIDERED, IN ADDITION TO METFORMIN, WHEN A SECOND MEDICATION IS NEEDED
• MOA: increases insulin release
• Hypoglycemia risk: yes, especially in the elderly and those with renal impairment
• Side effects/comments:
o Hypoglycemia – elderly and those with renal impairment
Pharmacologic interventions for type 2 DM: Dipeptidyl peptidase-4 (DDP-4) inhibitor
• Example: Sitagliptin (Januvia) • A1C reduction: 0.6-1.4% • MOA: increases insulin release • Hypoglycemia risk: no • Side effects/comments: o Pancreatitis – FDA advisory o Unexplained joint aches
Pharmacologic interventions for type 2 DM: GLP-1 antagonist
• Example: Liraglutide (Victoza), Exenaide (Byetta)
• A1C reduction: 1-2%
• INJECTION ONLY
• MOA: increases insulin release
• Hypoglycemia risk: little
• Side effects/comments:
o Nausea/vomiting – improves with dose adjustment and continued use, contraindicated in gastroparesis
o Pancreatitis – rare, discontinue if develops
o Slows gastric emptying, often leads to appetite suppression and weight loss
Pharmacologic interventions for type 2 DM: Sodium glucose cotransporter-2 (SGLT-2) inhibitor
• Example: Canaglifozin (Invokana), dapaglifozin (Farxiga)
• A1C reduction: 0.7-1%
• MOA: lowers plasma glucose levels by increasing the amount of glucose excreted in urine
• Hypoglycemia risk: yes, risk increases when used with insulin
• Side effects/comments:
o Genital mycotic infection, UTI, increased urination
o Modest weight loss, greater with higher dose
o Renal impairment – adjust dose d/t risk of electrolyte imbalance
o DKA and urosepsis risk – FDA advisory
Insulin Types: Short-acting, rapid onset
- Examples: Lispro (Humalog), Aspart (NovoLog), regular (Humulin R)
- Onset of action: 15-30 minutes, give right around time of meals
- Peak: 1-3 hours
- Duration of action: 3-6 hours
Insulin Types: Intermediate-acting
- Example: NPH (Humulin N)
- Onset of action: 1-2 hours
- Peak: 6-14 hours
- Duration of action: 16-24 hours
Insulin Types: Long-acting – Glargine (Lantus)
- Onset of action: 1 hour
- Peak: none
- Duration of action: ≥ 24 hour
Insulin Types: Long-acting – Detemir (Levemir)
- Onset of action: 1-2 hours
- Peak: 6-8 (minimal)
- Duration of action: dose-dependent, 12 hours at 0.2 units/kg, 20 hours at 0.4 units/kg
Hyperglycemic control in the acute care setting: possible reversible causes
- Dietary changes
- Dextrose-containing IV fluids
- Glucocorticoids
- Post-op