23) Diabetes Flashcards
The endocrine pancreas in the adult human consists of
- Approximately 1 million islets of Langerhans
Within the islets, at least five hormone-producing cells are present. The hormone products related to diabetes include:
- Insulin
- Islet amyloid polypeptide (IAPP, or amylin)
- Glucagon
Insulin
- Storage and anabolic hormone of the body
Islet amyloid polypeptide (IAPP, or amylin)
- Also secreted by β-cells
- Modulates appetite, gastric emptying, and glucagon/insulin secretion
Glucagon
- Hyperglycemic factor that mobilizes glycogen stores
Diabetes mellitus
- Elevated blood glucose associated with absent or inadequate pancreatic insulin secretion
- With or without concurrent impairment of insulin action
The disease states underlying the diagnosis of diabetes mellitus are now classified into four categories
- Type 1
- Type 2
- Other
- Gestational
Pre-diabetes glucose test values
- A1C = 5.7-6.4%
- Fasting = 100-125 mg/dL
- 2 hour OGTT 140-199 mg/dL
Confirmation diagnostic glucose test values
- A1C = >6.5%
- Fasting = >126 mg/dL
- 2 hour OGTT = >200 mg/dL (or random > 200 with classic symptoms)
GDM (1-step strategy) glucose values
- A1C = N/A
- Fasting = ≥92 mg/dL
- 1 hr: ≥180 mg/dL
- 2 hr: ≥153 mg/dL
OGTT
- Oral glucose tolerance test (75g glucose)
Types of drugs used in diabetes mellitus
- Insulins
- Non-insulin drugs
Types of insulin used in diabetes
- Rapid, short acting
- Intermediate acting
- Slow, long-acting
Rapid, short acting insulin drugs
- Lispro, regular
Intermediate acting insulin drugs
- NPH
- Lente
Slow, long acting insulin drugs
- Glargine
Types of non-insulin drugs used in diabetes
- Insulin secretagogues
- Biguanides
- Alpha-glucosidase inhibitors
- Thiazodinediones
- Amylin analogs
- Incretin modulators
- SGLT2 inhibitors
Insulin secretagogues
- Glipizide
Biguanides
- Merformin
Alpha-glucosidase inhibitors
- Acarbose
Thiazolidinediones
- Pioglitazone
Amylin analogs
- Pramlintide
Incretin modulators
- GLP-1 analog (exenatide)
- DPP-4 inhibitor (sitagliptin)
SGLT2 inhibitors
- Canalgiflozin
Insulin is a small protein or peptide i.e. it cannot be taken orally because
- Digestive enzymes will break the peptide or protein into basic unit amino acids
- Therefore insulin is given as an injection (except for the new Afrezza®)
Insulin is secreted in response to
- All insulin secretagogues
Insulin is classified based on
- How quickly they take effect (onset of action)
- How long they work for (duration of action)
Basal-bolus strategy
- Taking a longer acting form of insulin to keep blood glucose levels stable through periods of fasting
- Take separate injections of shorter acting insulin to prevent rises in blood glucose levels resulting from meals
The goal of subcutaneous insulin therapy
- Replicate normal physiologic insulin secretion
- Replace the background or basal (overnight, fasting, and between-meal) as well as bolus or prandial (mealtime) insulin
_____ % of the exogenous insulin is cleared by the _____ and ____ % is removed by the _____
- 60% by kidneys
- 30-40% by liver
Four principle types of injected insulin
- Rapid
- Short
- Intermediate
- Long
Rapid acting has a very fast onset and short duration of action, and also contains
- Small amount of zinc to improve the stability
Short acting has a fast onset of action, and also contains
- Small amount of zinc to improve the stability
Intermediate acting insulin
- Neutral protamine Hagedorn [NPH] insulin
Rapid acting insulin injection schedule
- Should be taken immediately before the meal
- Insulin lispro, aspart and glulisine DOA: 4-5 h i.e. decrease the risk of post-meal hypoglycemia
Rapid acting insulin brand/generic names (LAAG)
- Humalog (insulin lispro)
- Novolog (insulin aspart)
- Apidra (insulin glulisine)
- Afrezza (oral inhalation)
Humalog, novolog, apidra OAA/peak/DOA
- OAA = 5-15 min
- Peaks = 1 h
- DOA = 4-5 h
Afrezza OAA/peak/DOA
- OAA = 15 min
- Peaks = 1 h
- DOA = 3 h
Short acting insulin injection schedule
- Administered 30-45 min before mealtime
- Only type that should be administered IV
Short acting insulin is useful for
- Management of diabetic ketoacidosis
- Insulin requirement after a surgery
Short acting insulin brand/generic names
- Humulin R U500 (regular)
- Novolin R (regular)
Short acting insulin (Humulin R U500 and Novolin R) OAA/peak/DOA
- OAA = 30 min
- Peak = 2 h
- DOA = 5-8 h
Long acting insulins characteristics
- Soluble, peakless, long acting insulin analogue
- Usually given once a day
Intermediate acting insulins brand/generic names
- Humulin N (NPH)
- Novolin N (NPH)
Intermediate acting insulins OAA/DOA
- OAA = 1-3 h
- DOA = 4-12 h
Long acting insulins brand/generic names
- Levemir (Insulin detemir)
- Lantus, Toujeo, Basalgar (Insulin glargine)
- Tresiba U200 (Insulin degludec)
Levemir (long acting insulin) OAA/DOA
- OAA = 3 h
- DOA = 24 h
Lantus, Toujeo, Basalgar (long acting insulin) OAA/DOA
- OAA = 3 h
- DOA = 24 h
Tresiba U200 (long acting insulin) OAA/DOA
- OAA = 1 h
- DOA = 24 h
Hypoglycemia signs/symptoms
- Sympathetic: tachycardia, palpitations, sweating
- Parasympathetic: nausea and hunger
- Severe hypoglycemia may lead to coma
Treatment for hypoglycemia
- Glucose administration
Side effects of insulin
- Hypoglycemia
- Insulin allergy
- Atrophy of subcutaneous tissue at injection site, redness, itching, edema
- Hunger and nausea
- Potassium shift
Insulin allergy is usually reduced with
- Human analogue insulin
Potassium shift from insulin administration
- Extra to intracellular space
- Decreasing serum potassium concentration
Afrezza side effects
- Cough, pulmonary function should be monitored
- Caution in smokers and patients with COPD
Drugs that primarily stimulate insulin release by binding to the sulfonylurea (SU) receptor
- First generation SU
- Second generation SU
- Meglitinide analogues
- Drugs that mimic incretin and amylin
Drugs that primarily lower glucose levels by their actions on the liver, muscle and adipose tissue
- Biguanides
- Thiazolidinediones
Drugs that affect absorption of glucose
- α-glucosidase inhibitors
Drugs that mimic incretin effect or prolong incretin action
- Glucagon-like peptide 1 (GLP-1)
- Dipeptidyl peptidase-4 (DPP-4) inhibitors
Other hypoglycemic drugs
- Amylin mimetic
- Bile acid sequestrant
- Dopamine-2 agonist
Oral anti-diabetic drug options/actions
- Drugs that primarily stimulate insulin release by binding to the sulfonylurea (SU) receptor
- Drugs that primarily lower glucose levels by their actions on the liver, muscle and adipose tissue
- Drugs that affect absorption of glucose
- Drugs that mimic incretin effect or prolong incretin action
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors
- Other hypoglycemic drugs
Sulfonylureas (SU) MOA
- SU binds to SU receptor that is associated with a beta-cell inward rectifier ATP-sensitive potassium channel
- Binding of a SU inhibits the efflux of potassium ions through the channel
- Results in depolarization which opens a voltage-gated calcium channel
- Results in calcium influx and the release of preformed insulin
SU metabolism
- Metabolized in the liver to inactive metabolites
- Metabolites are excreted in the kidney
- 2nd generation has metabolites partly excreted in the bile
Advantages of 2nd generation SU
- Greater affinity to receptor which lower effective doses and plasma levels
- 100 times more potent
- Have shown less hypoglycemic side effects
2nd generation SU generic names
- Glyburide
- Glipizide
- Glimepiried
Glyburide (2nd generation SU) brand names/DOA
- Diabeta
- Miconase
- Glynase
- DOA = 10-24 h
Glipizide (2nd generation SU) brand names/DOA
- Glucotrol
- Glucotrol XL
- DOA = 10-24 h
Glimepiride (2nd generation SU) brand names/DOA
- Amaryl
- DOA = 12-24 h