Diabetes & Insulin Comprehensive Notes 176 lec wk 1 thursday.

Introduction to Diabetes

• Diabetes mellitus = chronic metabolic disorder characterized by elevated blood glucose (hyperglycemia) that also alters lipid & protein metabolism.
• Prevalence: ≈ 10.5 % of U.S. population; ranked 7^{th} leading disease–related cause of death.
• Morbidity spectrum: heart disease, stroke, blindness, renal failure, amputations, fatty-liver disease, gout, infections.

Pancreatic Physiology

• Exocrine portion – secretes digestive enzymes (not discussed in depth).
• Endocrine portion – islets of Langerhans contain:
– Alpha (α) cells → secrete glucagon.
– Beta (β) cells → secrete insulin.

Glucagon

• Memory aid: “When the sugar is GONE you need glucaGON.”
• Stimulus = hypoglycemia; major action = signals liver to convert stored glycogen → glucose (glycogenolysis) ↑ serum glucose.

Insulin

• “Key” that unlocks cell-membrane receptor → permits glucose entry.
• Basal secretion at rest; bolus secretion with meals.
• Multi-system effects:
– Carbohydrates: promotes cellular uptake & oxidation of glucose; stimulates glycogenesis in liver/muscle.
– Fats: inhibits lipolysis; keeps triglycerides in adipose tissue; prevents hepatic triglyceride storage (↓ fatty-liver risk when adequate).
– Proteins: promotes amino-acid uptake/protein synthesis; inhibits proteolysis.

Consequences of Insulin Deficiency

1. Glycogenolysis despite hyperglycemia → even higher glucose.

2. Lipolysis → free fatty acids + glycerol → hepatic ketone production → metabolic acidosis (DKA).

3. Proteolysis → muscle wasting, organ dysfunction, ↑ circulating amino acids → predisposition to gout (uric-acid accumulation).

4. Hyperglycemic blood becomes hypertonic ⇒• cellular dehydration • activation of thirst center (polydipsia).

5. Osmotic diuresis ⇒ polyuria → volume depletion & electrolyte loss.

6. Brain glucose starvation despite hyperglycemia triggers polyphagia.

“Three P’s” of Uncontrolled Diabetes

• Polyuria – large urinary output.
• Polydipsia – excessive thirst (hypertonic plasma).
• Polyphagia – excessive hunger (cellular glucose starvation).

Types of Diabetes Mellitus

Type 1 (T1DM)

• Autoimmune destruction of β-cells, often post-viral; abrupt onset (children, adolescents, sometimes adults).
• Endogenous insulin ≈ 0 → absolute dependence on exogenous insulin.
• Classic manifestations: three P’s, weight loss, fatigue, sudden DKA risk.

Type 2 (T2DM)

• Insulin resistance ± relative insulin deficiency ± hepatic over-production of glucose.
• Strong genetic & lifestyle links (obesity, inactivity).
• Therapy: lifestyle change, oral/GLP-1 meds, possibly insulin.

Gestational Diabetes (GDM)

• First recognized during pregnancy; should resolve by 6-wk postpartum visit.
• Management mirrors T2DM; signal of ↑ future T2DM risk → lifelong screening.

Sick-Day Rules (S I C K )

• S – Sugar: check glucose q 2–3 h (or PRN).
• I – Insulin/meds: NEVER skip doses; set alarms if sleeping.
• C – Carbs:
– Type 1 → use opposite rule: if BG high → low-carb drinks; if BG low → high-carb drinks.
– Type 2 → always low-carb fluids.
• K – Ketone testing: urine dipsticks PRN.
– Positive → follow MD protocol (extra rapid-acting insulin and/or phone call).

Insulin Pharmacology

Insulins classified by onset, peak, duration.

Rapid-Acting ("logs roll RAPIDly")

• Agents: insulin lispro, aspart, glulisine; inhaled insulin (adjunct only).
• Onset 5–15\,\text{min}; Peak \approx2\,\text{h}; Duration 3–5\,\text{h}.
• Give when meal tray is present; greatest hypoglycemia risk ≈ 2 h post-dose.

Short-Acting (Regular "R")

• Agents: regular (Humulin R, Novolin R).
• Only insulin for IV use (e.g., DKA drip, hyperkalemia).
• Onset 30–60\,\text{min}; Peak 2–3\,\text{h}; Duration 6–8\,\text{h}.

Intermediate-Acting (NPH "N")

• Only cloudy insulin.
• Onset 1–2\,\text{h}; Peak 4–12\,\text{h}; Duration 12–16\,\text{h}.

Long-Acting ("L" = Lantus/Levemir)

• Agents: insulin glargine, detemir.
• Onset 1–2\,\text{h}; NO true peak; Duration \le 24\,\text{h}.
• Provides basal coverage; fixed daily dose (not sliding-scale).
• Never mix in syringe with other insulins.

Ultra-Long-Acting

• Agent: insulin degludec (Tresiba).
• Onset 1–2\,\text{h}; NO peak; Duration \approx48\,\text{h}.

Memory Grid (simplified)

Sliding-Scale Protocol (Example)

• Physician orders insulin‐type + correction scale table.
• Locate BG row → read across to dose.
Example row: BG 200–249 → 8\,\text{units} regular insulin.

\text{Peak\;time}_{\text{regular}} = 2\,\text{h} \;\Rightarrow\;\text{observe for hypoglycemia at }07{:}30+2\text{h}=09{:}30

Mixing Insulins in One Syringe

Sequence mnemonic “Nancy Reagan, RN” (N R R N):

1. Air → NPH (cloudy) vial.

2. Air → Regular (clear) vial.

3. Draw dose from Regular (clear).

4. Draw dose from NPH (cloudy).
   • NEVER push insulin back into cloudy vial after clear has entered.
   • Long-acting insulins are NOT mixable.

Injection Sites & Technique

• Preferred Sub-Q areas: posterior upper arm, lower abdomen (≥1 – 2 in from umbilicus), anterior thigh.
• Rotate within one anatomic region to maintain absorption consistency.
• Avoid: lipohypertrophy (lumps) & lipoatrophy (dents) by rotating and using room-temperature insulin.
• Exercise/heat/massage ↑ absorption rate.

Storage & Stability

• Unopened vials/pens: refrigerator ≈ 4^{\circ}\text{C}; never freeze.
• In-use vial/pen: room T° for 30 days max; label date opened or date-to-discard.
• Protect from direct heat/sunlight (inactivates protein).

Insulin Delivery Technologies

• Pens: pre-filled, dial-a-dose; useful for mixed insulin (e.g., 70/30).
• Continuous Sub-Q Insulin Infusion (CSII) pumps: deliver programmable basal + on-demand bolus; use rapid-acting insulin only.
– Tubing kinks, catheter dislodgement, site infection, or needle fold-over can interrupt delivery → hyperglycemia/DKA.
• Continuous Glucose Monitors (CGM): transdermal sensor transmits BG q 1–5 min to phone/pump; can trigger alarms & automate dosing.

Exercise Guidelines

• Benefits: insulin-independent glucose uptake by muscle; ↓ insulin requirement.
• T1DM must check BG pre-, intra- (if prolonged), & post-workout; may need CHO snack to prevent hypoglycemia.

Diabetic Ketoacidosis (DKA) Pathway (Type 1)

1. ↓/absent insulin → cellular starvation despite hyperglycemia.

2. Counter-regulatory hormones (catecholamines, cortisol) trigger gluconeogenesis + lipolysis.

3. Ketone accumulation → metabolic acidosis (HCO$_3^-$ ↓, anion-gap ↑).

4. Respiratory compensation → Kussmaul respirations (deep, rapid).

5. Severe dehydration from osmotic diuresis.

6. Immediate threats: acidosis & hypovolemia (treat with isotonic IVFs, then IV regular insulin, electrolyte repletion).

Practice Q&A Highlights

• Glargine once daily at same time; some regimens split AM + HS for tight control.
• Intermediate insulin at 07:00 possesses greatest hypoglycemia risk late afternoon (4–12 h peak) → watch for “cold, clammy, needs candy.”
• Sliding-scale insulin orders apply to rapid/short/intermediate; NOT to long/ultra-long which are fixed doses.
• Rapid-acting insulin must coincide with meal delivery (onset 10 – 30 min).
• Regular insulin = only IV option.

Ethical & Practical Implications

• Technology (CGM, pumps) improves safety but may create access inequities; advocate insurance coverage.
• Education essential: myths (“sugar causes T1DM”; “only sugar-free foods”) dispelled—focus on carb counting + insulin matching.
• Psychological facet: adolescents may omit insulin for weight control → dangerous DKA risk; requires compassionate counseling.

Key Numbers & Formulas

• Hypertonicity concept: when plasma [glucose] ↑, effective serum osmolarity rises \Rightarrow water shifts from ICF → ECF.
• Basal–bolus goal:
\text{Total Daily Dose (TDD)} \approx 0.5\;\text{to}\;1\,\text{unit·kg}^{-1} (individualized).
• Renal threshold for glucosuria ≈ 180\,\text{mg·dL}^{-1}.

High-Yield Memory Aids

• "Logs roll rapidly; R’s are regular; N is Not fast; L=Lasts all day; Ultra = 2 days."
• Mixing order: NRRN = Nancy Reagan, RN.
• Hypoglycemia S/S: "Cold & Clammy need some candy"; hyperglycemia: "Hot & Dry sugar high."