🩺 Pancreas and Diabetes Mellitus Pancreas
The pancreas is an abdominal organ with dual roles:
- Exocrine → Produces digestive enzymes that break down food.
- Endocrine → Regulates blood sugar through hormones secreted by the islets of Langerhans.
Endocrine Pancreas
- Beta cells → Produce insulin, which lowers blood sugar.
- Alpha cells → Produce glucagon, which raises blood sugar.
- 👉 Think about wolfs, alphas are high and betas are low.
👉 Key Points
- Pancreas = exocrine (digestion) + endocrine (blood sugar control).
- Beta cells = insulin ↓ glucose.
- Alpha cells = glucagon ↑ glucose.
📝 Detail Information
Other islet cell types:
- Delta cells → Secrete somatostatin, which inhibits both insulin and glucagon.
- PP cells → Secrete pancreatic polypeptide, regulating enzyme secretion and gut motility.
- Epsilon cells → Produce ghrelin, influencing appetite.
These additional hormones are important in appetite regulation, GI function, and clinical research on diabetes/obesity.
Diabetes Mellitus
General Definition
A condition caused by insufficient insulin secretion or ineffective use of insulin, leading to chronically high blood sugar.
Classic Symptoms – “3 P’s”
- Polyuria → Excessive urination.
- Polydipsia → Excessive thirst.
- Polyphagia → Excessive hunger.
Let's say, Michelle is hungry (polyphagia) and of course Michelle needs to drink because she is thirsty (polydipsia) and now after that, she need to go to the restroom to pee (polyuria). Something like that.
Types of Diabetes
Type 1 Diabetes (T1D)
- Cause: Autoimmune destruction of beta cells.
- Insulin production: Absent.
- Onset: Childhood/adolescence.
- Main problem: Absolute insulin deficiency.
- Treatment: Insulin only.
- Risk: High risk of diabetic ketoacidosis (DKA).
- Pharmacology focus: Insulin dose calculations.
Type 2 Diabetes (T2D)
- Cause: Insulin resistance + relative deficiency.
- Insulin production: Present but ineffective.
- Onset: Usually adulthood, rising in youth.
- Main problem: Insulin resistance.
- Treatment: Lifestyle, oral meds, injectables, sometimes insulin.
- Risk: Lower DKA risk, but possible.
- Pharmacology focus: Oral + insulin dose calculations.
👉 Key Points
- T1D = no insulin, kids, insulin-only, high DKA.
- T2D = insulin resistance, adults, meds + lifestyle, lower DKA.
📝 Detail Information
T1D often presents with abrupt onset and weight loss; autoantibodies (GAD, IA-2, ZnT8) confirm diagnosis.
T2D progression includes impaired fasting glucose → impaired glucose tolerance → diabetes. Insulin resistance is linked to obesity, sedentary lifestyle, and genetic predisposition.
LADA (Type 1.5)
- It’s just Type 1 that presents later in life, so it get’s confused with Type 2.
- Definition: Latent autoimmune diabetes in adults, slower autoimmune beta cell destruction.
- Onset: Around age 30+.
- Presentation: Initially looks like T2D, but oral meds fail.
- Treatment: Oral meds at first, eventually insulin (like T1D).
- Key point: Often misdiagnosed as T2D.
👉 Key Points
- LADA = slow-onset Type 1.
- Misdiagnosed as T2D.
- Requires insulin eventually.
📝 Detail Information
GAD antibodies are common markers. Patients are often lean, with progressive need for insulin. Early identification prevents delays in insulin therapy and reduces complications.
Other Forms
- Gestational Diabetes → Occurs during pregnancy, may resolve postpartum, increases risk of later diabetes.
- Secondary Diabetes → Caused by drugs (glucocorticoids, thiazides, epinephrine) or endocrine disorders.
👉 Key Points
- Gestational = pregnancy-related.
- Secondary = drugs/hormones.
📝 Detail Information
Gestational diabetes is screened with oral glucose tolerance test at 24–28 weeks. Secondary diabetes is important in patients on chronic steroids or with Cushing’s disease.
Insulin Resistance = Decreased insulin sensitivity
Symptoms: Blurry vision, high blood sugar, increased hunger, tingling in extremities, fatigue, dark skin patches (acanthosis nigricans), increased thirst.
📝 Detail Information
Insulin resistance is central to metabolic syndrome (obesity, hypertension, dyslipidemia). It precedes T2D and contributes to cardiovascular risk.
Insulin Therapy
Manufacture
Modern insulin is produced using DNA recombinant technology (Humulin R, Novolin N, lispro, aspart).
Mixing Insulin
Steps:
- Roll NPH vial.
- Clean vial tops.
- Inject air into NPH.
- Inject air into Regular.
- Draw Regular (clear).
- Draw NPH (cloudy).
Rule: “Clear before cloudy” → Regular before NPH.
👉 Key Points
- Regular = clear = first.
- NPH = cloudy = second.
📝 Detail Information
Incorrect order contaminates Regular insulin with NPH, altering action profile. Insulin pens and premixed insulins simplify administration.
Insulin Types
Insulin Type | Examples | Onset | Peak | Duration | Notes |
Rapid-acting | Lispro, Aspart, Glulisine | 10–30 min | 30–60 min | 2–4 hrs | Give when meal ready. 5 min before meal. |
Short-acting (Regular) | Humulin R, Novolin R | 30–60 min (IV 15) | 2–3 hrs | 3–4 hrs | Only type IV |
Intermediate-acting | NPH (Humulin N, Novolin N) | 1.5 hrs | 4–12 hrs | 18–24 hrs | Cloudy |
Long-acting | Glargine, Detemir | ~1 hr | Minimal | ~24 hrs | Don’t mix |
🧪 Insulin Interactions
Drugs that ↓ Blood Glucose (Hypoglycemia Risk)
- Oral anticoagulants, Aspirin
- Alcohol
- Oral hypoglycemics
- ACE inhibitors (ACEIs)
- ARBs
- Beta blockers
- Tricyclic antidepressants (TCAs)
- MAO inhibitors
- Tetracyclines
Drugs that ↑ Blood Glucose (Hyperglycemia Risk)
- Thiazides
- Glucocorticoids
- Oral contraceptives
- Thyroid drugs
- Smoking
- Furosemide
- Fluoroquinolones
- Green tea
👉 Key Points
- Certain drugs enhance insulin’s effect → risk of hypoglycemia.
- Others antagonize insulin → risk of hyperglycemia.
- Infection temporarily increases the need for insulin.
- Insuline steps:
- (1) Verify the doctor’s ordered dosage.
- (2) Draw up the insulin.
- (3) Clean the skin with alcohol.
- (4) Pinch the skin.
- (5) Insert the needle.
- (6) Inject the medication.
- (7) Count to five.
- (8) Remove the needle.
📝 Detail Information
Beta blockers may mask hypoglycemia symptoms (tachycardia, tremor), making monitoring critical. Glucocorticoids cause significant insulin resistance, a major issue in hospitalized patients.
🌙 Insulin-Related Phenomena (hyperglycemia)
- Somogyi Effect → Rebound hyperglycemia caused by nighttime hypoglycemia (due to too much evening insulin).
- Low at 2–3 AM, then high in the morning
- Dawn Phenomenon → Early morning hyperglycemia from normal hormone release (growth hormone, cortisol).
- Normal or high at 2–3 AM, then high in the morning.
👉 Key Points
- Dawn = morning hyperglycemia from hormones.
- Somogyi = rebound hyperglycemia.
📝 Detail Information
Checking 3 AM blood glucose helps differentiate:
- Low at 3 AM → Somogyi.
- Normal/high at 3 AM → Dawn.
Management differs: Somogyi requires evening insulin adjustment; Dawn may need increased basal insulin.
⚠️ Insulin Complications
- Insulin Shock (Hypoglycemia) → Very low blood sugar, caused by too much insulin.
- Diabetic Ketoacidosis (DKA) → Severe complication of insulin deficiency. 👉 So: High sugar → ketones → blood too acidic → Kussmaul breathing to get rid of acid.
- Early symptoms: excessive thirst, frequent urination.
- Severe symptoms: Kussmaul breathing, fruity breath, abdominal pain, fatigue, nausea/vomiting.
Symptoms: sweating, tremors, confusion, headache, seizures, coma.
Always remember to check glucose before and after insulin treatments, and teach that also to the pts.
👉 Key Points
- Hypoglycemia → “Cold & clammy, need some candy.”
- Hyperglycemia → “Hot & dry, sugar is high.”
- DKA = high glucose + ketones, dehydration, acidosis.
📝 Detail Information
DKA is more common in T1D but can occur in insulin-deficient T2D.
Hyperosmolar Hyperglycemic State (HHS) occurs in T2D: severe hyperglycemia, dehydration, minimal ketosis.
💉 Insulin Administration
Methods
- Pump (carb counting + bolus before meals)
- Pen injector
- Jet injector
- Subcutaneous (SubQ)
- IV (Regular only)
Injection Sites
- Abdomen, thighs, upper arms, buttocks.
- Rotate sites to prevent lipodystrophy.
Sliding-Scale Insulin
- Dose based on blood glucose.
- Usually before meals and bedtime.
- Uses rapid- or short-acting insulin.
Storage
- Refrigerate until opened.
- At room temp → 1 month.
- In fridge → 3 months.
- Avoid heat and sunlight.
👉 Key Points
- Regular insulin = only IV type.
- Rotate sites → prevent lipodystrophy.
- Store properly → maintain potency.
📝 Detail Information
Continuous SubQ infusion via insulin pumps mimics physiologic basal-bolus secretion. Lipohypertrophy from repeated injections can alter absorption kinetics. Insulin should never be frozen.
💊 Oral Antidiabetic Drugs
Main Classes
- Sulfonylureas
- Biguanides
- Thiazolidinediones (TZDs)
- Alpha-glucosidase inhibitors
- Meglitinides
- Incretin enhancers (DPP-4 inhibitors, GLP-1 agonists)
- Amylin analogues
- Miscellaneous agents
Biguanides (Metformin)
- ↓ hepatic glucose production.
- ↓ intestinal absorption of glucose.
- ↑ insulin sensitivity.
- Side effects: N/V, diarrhea, anorexia, dizziness, fatigue, lactic acidosis, metallic taste.
- Interactions: Green tea ↑ hypoglycemia risk.
- MRI/CT contrast dye (iodinated contrast) can sometimes cause acute kidney injury (AKI).
- If the kidneys suddenly don’t work well, metformin can build up in the body.
- At the same time, the kidneys also can’t clear lactic acid effectively.
- Together → this raises the risk of metformin-associated lactic acidosis (MALA).
- Patients on metformin are usually told to pause metformin before and after getting IV contrast (like for an MRI or CT scan).
👉 lactic acidosis Simple chain:
Muscle makes lactate → liver usually recycles it → Metformin blocks this → lactate accumulates → lactic acidosis risk.
FUN FACT:
🧲 Metformin & MRI Contrast Dye
⚠️ Clinical Rule
Sulfonylureas (-ide)
- Mechanism: Stimulate beta cells → ↑ insulin release.
- Examples: Glipizide, Glyburide, Glimepiride.
- Generations:
- First: Tolbutamide, Tolazamide, Chlorpropamide.
- Second: Glimepiride, Glyburide, Glipizide.
- Side effects: Hypoglycemia, disulfiram-like reaction with alcohol.
- Contraindications: Kidney/liver dysfunction, DKA.
- Interactions:
- ↓ Glucose: beta blockers, aspirin, azoles, anticoagulants.
- ↑ Glucose: oral contraceptives, steroids, thiazides, anticonvulsants.
Alpha-Glucosidase Inhibitors
- Acarbose, Miglitol.
- Delay carb absorption in small intestine.
- Side effects: GI upset.
- Do not cause hypoglycemia unless combined with other meds.
Thiazolidinediones (-glitazone)
- Pioglitazone, Rosiglitazone.
- ↑ insulin sensitivity.
- Contraindicated in CHF.
- Rosiglitazone → ↑ heart attack risk.
Meglitinides (-glinide)
- Repaglinide, Nateglinide.
- Stimulate rapid insulin release.
- Short-acting; given with meals.
- Avoid in liver dysfunction.
Incretin-Based Therapies
- DPP-4 inhibitors (-gliptin) → Sitagliptin, Saxagliptin. ↑ incretin hormones → ↑ insulin, ↓ glucagon.
- GLP-1 agonists (-tide) → Exenatide, Liraglutide. Enhance insulin, suppress glucagon, slow gastric emptying, increase satiety.
Amylin Analogue
- Pramlintide → Slows gastric emptying, suppresses glucagon, increases satiety.
- Used in both T1D and T2D with insulin.
Hyperglycemic Drugs
- Glucagon → Rescue for hypoglycemia; raises glucose via glycogenolysis.
- Diazoxide → Inhibits insulin release; used in chronic hyperinsulinism.
👉 Key Points
- Sulfonylureas = stimulate insulin release.
- Metformin = ↓ hepatic glucose, no hypoglycemia.
- TZDs = avoid in CHF.
- GLP-1 agonists = slow gastric emptying, satiety.
- Glucagon = hypoglycemia rescue.
📝 Detail Information
Metformin is first-line in T2D due to weight neutrality and cardiovascular safety. TZDs improve insulin sensitivity but cause fluid retention. GLP-1 agonists and SGLT2 inhibitors (not listed in your flashcards) are now front-line options due to cardiovascular and renal benefits.
✅ Oral Therapy Criteria
Best candidates for oral therapy:
- Age ≥ 40
- Diabetes < 5 years
- Not underweight
- Fasting glucose ≤ 200
- < 40 units insulin/day
- Normal renal/hepatic function
👉 Final Key Points (Overall)
- Pancreas = dual function organ; endocrine = insulin + glucagon (and more).
- T1D = no insulin, autoimmune, high DKA.
- T2D = insulin resistance, gradual onset, lifestyle + meds.
- LADA = adult-onset autoimmune, often misdiagnosed.
- Insulin types differ by onset, peak, duration.
- Complications = hypoglycemia, DKA, Somogyi, Dawn.
- Oral drugs classified by mechanism; Metformin = first-line.
📝 Detail Information (Overall Expansion)
- SGLT2 inhibitors (empagliflozin, dapagliflozin) were not in your flashcards but are now guideline-recommended for T2D with cardiovascular/renal disease.
- Insulin therapy should be individualized, considering basal-bolus vs premixed regimens.
- Diabetes care is multidisciplinary: diet, exercise, pharmacology, and education all play critical roles.