Summary

Type 1 Diabetes (T1DM) is a chronic autoimmune condition characterized by the destruction of pancreatic beta-cells, leading to absolute insulin deficiency. Unlike Type 2, it is not primarily driven by insulin resistance or lifestyle. It is fatal without exogenous insulin replacement. The modern management landscape has shifted from "survival" to "optimisation" using technology (CGM, Pumps) and structured education (DAFNE) to mimic physiological insulin profiles.

• Key Pathophysiology: T-Cell mediated autoimmune destruction.
• Key Management: Basal-Bolus Insulin or Pump Therapy.

Clinical Summary Table

Epidemiology

• Prevalence: 0.5% of population (10% of all diabetes).
• Age: Peaks at 4-6 years and 10-14 years.
• Genetics: HLA-DR3 and HLA-DR4 confer susceptibility.
  • Drill Down: The highest risk genotype is HLA-DR3-DQ2 and HLA-DR4-DQ8 heterozygosity (Risk 1 in 20).
  • Twin Studies: Concordance is only 30-50% in identical twins (Proving Environmental trigger is crucial).
• Geography: Highest incidence in Scandinavia (Finland).

Historical Context: The Miracle of 1921

• Before 1921: T1DM was a death sentence. Treatment was the "Starvation Diet" (living a few months longer as skeletons).
• The Heroes: Frederick Banting (Surgeon) and Charles Best (Medical Student, age 22). Toronto caused University.
• The Discovery: Ligated dog pancreatic ducts to isolate the "Isletin".
• The First Patient: Leonard Thompson (Age 14). Went from near-death to living another 13 years.
• Nobel Prize: Banting and Macleod (1923). Banting shared his money with Best.

The "Spot Diagnosis"

The 4 Ts: Toilet (frequency), Thirsty (unquenchable), Tired (exhaustion), Thinner (catabolism). The Breath: Pear-drop smell (Ketones).

Red Flags (Admit Immediately)

• Vomiting: In a T1DM patient (or suspected), vomiting is DKA until proven otherwise.
• Kussmaul Breathing: Deep, sighing respiration (Respiratory compensation for acidosis).
• Confusion: Cerebral oedema or Severe Hypoglycaemia.

Regimen: Basal-Bolus (MDI)

Multiple Daily Injections. The Gold Standard for pens.

1. Basal (Background):
   • Drug: Glargine (Lantus/Abasaglar), Detemir (Levemir), Degludec (Tresiba).
   • Action: Flat profile. Covers liver glucose output.
   • Timing: Once or twice daily.
2. Bolus (Mealtime):
   • Drug: Aspart (Novorapid), Lispro (Humalog).
   • Action: Rapid onset (10-15 mins). Covers the carbs in the meal.
   • Timing: Before eating.

Pharmacology: Insulin Profiles

Drill Down: The Art of Injection

It's not just "stab and go".

• Needle Size: 4mm is the Gold Standard. 5mm, 6mm, 8mm increase risk of IM injection (painful, unpredictable absorption).
• Angle: 90 degrees. No pinch needed for 4mm.
• Sites:
  • Abdomen: Fastest absorption (Use for Bolus).
  • Thigh/Buttock: Slower absorption (Use for Basal).
• Lipohypertrophy ("Lumpy bumps"):
  • Cause: Injecting into the same spot. Fat grows (anabolic insulin).
  • Effect: Insulin is trapped in the lump -> Erratic release -> "Unexplained" highs and hypos.
  • Fix: Site Rotation. Check sites at every clinic visit.

Drill Down: Safe Sharps Disposal

• The Box: Yellow Bins (Clinical Waste). Prescription only.
• The Clipper: Devices that "clip" the needle off so the pen can be recycled.
• The Law: Never put needles in household bin. Council collection required.
• Recycling: POGO (Pen Cycle) allows huge return of plastic pens to Novo Nordisk.

Education: DAFNE Principles

Dose Adjustment For Normal Eating.

• No fixed doses: Patients match insulin to what they eat.
• Carb Counting: "1 CP (Carb Portion) = 10g carbs".
• Insulin:Carb Ratio (ICR): e.g. "1 unit for every 10g carbs".
• Correction Factor (ISF): e.g. "1 unit drops blood glucose by 3 mmol/L".

Continuous Glucose Monitoring (CGM)

• Flash (Libre): Scan arm to see glucose. Now standard of care in NHS.
• Real-Time (Dexcom): Beams data significantly to phone. Alarms for High/Low.
• Time in Range (TIR): Goal is >70% of time between 3.9 - 10.0 mmol/L.

Insulin Pumps (CSII)

Continuous Subcutaneous Insulin Infusion.

• Mechanism: A cannula delivers rapid insulin continuously (Basal rate) + Large doses for meals (Bolus). No long-acting insulin used.
• Indication: Recurrent hypos, Dawn Phenomenon, Needle phobia, Pregnancy.

Hybrid Closed Loop (The "Artificial Pancreas")

• The Loop: CGM talks to Pump. Algorithm adjusts basal insulin automatically every 5 mins.
• HCL: Still requires user to input carbs for meals ("Hybrid"), but automates the background.
• Evidence: Massive improvement in TIR and reduced Hypos. NICE TA943 recommends widespread use.

Innovation: The Bionic Pancreas (iLet)

The end of carb counting?

• Concept: A fully autonomous system that needs NO meal input (just "Small/Medium/Large").
• Hormones: Uses Bi-hormonal control (Insulin AND Glucagon) to prevent hypos actively.
• Status: FDA approved. Coming to UK soon.

Innovation: Smart Pens

For those not on pumps.

• Device: NovoPen Echo Plus / Kiwik.
• Function: Records last dose and time (Memory). Uploads data to phone (NFC).
• Benefit: Prevents "Did I take my injection?" double-dosing.

Drill Down: Pump Failure Protocol

A unique emergency.

• Problem: Pumps use only rapid acting insulin. If the cannula kinks/blocks, the patient has zero insulin on board within 2 hours.
• Risk: DKA develops extremely rapidly (4-6 hours).
• Rule: If Glucose >14 on pump with Ketones:
  1. Assume the pump has failed.
  2. Take an injection of insulin via Pen immediately.
  3. Change the set/cannula.
  4. Troubleshoot later.

Physiology: The Morning Highs

Why is glucose high on waking?

1. Dawn Phenomenon:
   • Cause: Natural surge of Growth Hormone and Cortisol at 4am. These are counter-regulatory (anti-insulin).
   • Result: Liver dumps glucose. High waking blood sugar.
   • Fix: Increase basal insulin (or Pump rate) at 4am.
2. Somogyi Effect (Rare):
   • Cause: Hypo during the night (3am).
   • Result: Body panic-dumps Glucagon/Adrenaline. Rebound Hyperglycaemia on waking.
   • Fix: Reduce evening insulin or eat a snack.

• Diagnosis: 3am blood test (or CGM) distinguishes them.

Hypoglycaemia ("Hypo")

• Definition: Glucose <4.0 mmol/L.
• Symptoms: Sweating, Tremor, Palpitations (Autonomic) -> Confusion, Coma (Neuroglycopenic).
• Treatment (Rule of 15):
  • 15g fast carbs (3-4 Jelly babies, 150ml Coke).
  • Wait 15 mins. Retest.
  • severe (Unconscious): IM Glucagon or IV Dextrose.

Hypoglycaemia Awareness

• Gold: Normal symptoms at 3.5mmol/L.
• Impaired Awareness: Patient feels nothing until they collapse at 2.0mmol/L. Dangerous.
• Solution: Avoid hypos strictly (Technology) to reset the "thermostat".

Sick Day Rules

Infection increases insulin resistance. Risk of DKA.

1. NEVER STOP INSULIN: Even if not eating. You need basal to stop ketones.
2. Check Ketones: If >1.5 mmol/L -> Emergency.
3. Increase Dose: Often need 20-50% more insulin during illness.
4. Hydration: Drink sugar-free fluids. If vomiting -> A&E.

Sick Day Traffic Light System

Driving (DVLA)

• Car (Group 1): Must inform DVLA if on insulin. Blood test before driving and every 2 hours. Do not drive if <5.0 mmol/L.
• Hypo Awareness: Must be intact. "Severe hypo while driving" = Loss of licence.

Drill Down: The Peri-operative Period

Surgery is a stress test.

• Elective Surgery:
  • Place first on the list.
  • Minor (<1 meal missed): Keep basal. Omit mealtime bolus.
  • Major (>1 meal missed): Start VRIII (Sliding Scale).
• VRIII (Variable Rate Intravenous Insulin Infusion):
  • Safety: Safe but requires hourly monitoring.
  • Risk: If stopped without overlapping SC insulin -> DKA in 2 hours.
  • Rule: NEVER stop background (Levemir/Lantus) even if on VRIII (The "Basal Bridge").

Innovation: Immunotherapy

Can we stop it before it starts?

• Teplizumab (Tzield): Anti-CD3 antibody.
• Evidence: Delays onset of Stage 3 T1DM by approx 2 years in high-risk relatives.
• FDA Approved: 2022. First ever disease-modifying therapy for T1DM.
• Future: Stem Cell islets (Vertex VX-880). Meaningful cure?

Alcohol: The Delayed Hypo

The most common cause of "Morning after" admission.

• Mechanism: Alcohol blocks gluconeogenesis in the liver.
• Problem: When eating stops (sleep), the liver normally releases glucose. If blocked by alcohol -> Hypoglycaemia.
• Glucagon: DOES NOT WORK (Liver is occupied).
• Advice: Eat carbs before sleep. Do not bolus for alcohol.

Pregnancy

High stakes. Tightest control required.

• Pre-conception: Folic Acid 5mg (High dose). Target HbA1c <48.
• Risks: Macrosomia (Big baby), Pre-eclampsia, Congenital malformations (Sacral agenesis).
• Targets: Fasting <5.3, 1-hour post-meal <7.8.
• Delivery: Often induced at 38 weeks. Sliding scale in labour.

Physiology: Pregnancy Insulin Requirements

The Rollercoaster.

1. First Trimester (0-12 weeks):
   • Risk: Hypoglycaemia. Nausea reduces intake. Fetus drains glucose.
   • Action: Often need to reduce insulin by 10-20%.
2. Second/Third Trimester (13-40 weeks):
   • Mechanism: Placental hormones (HPL, Cortisol, Progesterone) cause massive insulin resistance.
   • Action: Insulin requirements Triple.
3. Post-Partum (Immedately after delivery):
   • Mechanism: Placenta is delivered. Resistance vanishes instantly.
   • Action: Halve the dose immediately to prevent severe hypo. Breastfeeding lowers glucose further.

The Variant: LADA (Type 1.5)

Latent Autoimmune Diabetes in Adults.

• Scenario: 40-year-old diagnosed with "Type 2". Not obese. Metformin works for 6 months, then fails rapidly.
• Clue: Weight loss. No insulin resistance features.
• Diagnosis: Positive GAD Antibodies.
• Treatment: Needs insulin. Sulfonylureas consume remaining beta cells (Avoid).

Drill Down: The Science of Sport

Why does blood sugar go Crazy?

• Aerobic Exercise (Running, Cycling):
  • Uses glucose. Increases insulin sensitivity.
  • Result: Hypoglycaemia.
  • Action: Reduce bolus by 25-50% with pre-exercise meal. Reduce basal.
• Anaerobic Exercise (Weights, Sprinting):
  • Stress response -> Adrenaline release.
  • Result: Hyperglycaemia (initially), then delayed Hypo hours later.
  • Action: May need a small insulin correction correction after.

Drill Down: Travel Medicine

• Time Zones:
  • West (USA): Day is longer. Need more basal. (Inject basal, then top up 4 hrs later).
  • East (Asia): Day is shorter. Need less basal. (Inject basal earlier).
• Storage:
  • Insulin dies if frozen in the hold (Checked luggage). Always carry in Hand Luggage.
  • Frio Bags: Keep insulin cool without a fridge (evaporative cooling). Essential for backpacking.
• Customs:
  • Carry a letter. Do not let technology go through X-ray.

Psychology: Diabetes Distress

• Burnout: The relentless burden of calculating every meal.
• Diabulimia: Omission of insulin to lose weight (Eating Disorder). Extremely high mortality.

The Silent Destroyers. Driven by Glycation (HbA1c).

1. Microvascular (Small vessel)

A. Retinopathy (The Eyes)

• Mechanism: Hyperglycaemia damages pericytes -> Capillary leakage -> Ischaemia -> VEGF release -> New, fragile vessels (Proliferative).
• Stages: Background (Dots/Blots) -> Pre-proliferative (Cotton wool spots) -> Proliferative (New vessels).
• Treatment: Laser Photocoagulation (burns retina to reduce O2 demand) or Anti-VEGF injections.

B. Nephropathy (The Kidneys)

• Screening: Urinary Albumin:Creatinine Ratio (ACR). Protein leaks before filtration drops.
• Stages: Microalbuminuria (Reversible) -> Macroalbuminuria -> Nephrotic Syndrome -> ESKD.
• Treatment: ACE-Inhibitor (Ramipril) even if BP normal (renoprotective).

C. Neuropathy (The Nerves)

• Peripheral: "Glove and Stocking" numbness/pain. Risk of undetected foot ulcers (Charcot Foot).
• Autonomic: Gastroparesis (vomiting), Erectile Dysfunction, Postural Hypotension.
• Treatment: Amitriptyline, Duloxetine, Gabapentin.

Drill Down: The Charcot Foot

The "Bag of Bones".

• Mechanism: Loss of sensation + Autonomic vasodilation (High flow). Bones wash out (Osteopenia). Minor trauma causes collapse.
• Signs: Red, Hot, Swollen Foot. Often painless.
• Differentiation: Often misdiagnosed as Cellulitis. (In Charcot, elevation reduces redness).
• Diagnosis: MRI.
• Treatment: Total Contact Cast (Offloading) for 6-12 months. Bisphosphonates? Surgery (last resort).

Drill Down: Autonomic Neuropathy

• Gastroparesis: Vagus nerve damage. Stomach doesn't empty.
  • Symptom: Vomiting undigested food. Erratic glucose (mismatch with insulin).
  • Treatment: Small meals. Domperidone. Erythromycin. Botox?
• Erectile Dysfunction: Viagra (Sildenafil).
• Gustatory Sweating: Sweating on face when eating cheese/spicy food.

2. Macrovascular (Large vessel)

Accelerated Atherosclerosis.

• Risk: MI and Stroke risk is 2-4x higher than population.
• Management: Statin (Atorvastatin 20mg) for all >40 years or >10 years duration. Strict BP control.

• Cost: T1DM costs the NHS £1 billion/year (mostly treating complications).
• Access: The "Postcode Lottery" for insulin pumps and CGM is ending with NICE TA943, but roll-out is slow.
• Employment: Protected characteristic (Equality Act 2010). However, some jobs (Armed Forces, Pilots) have restrictions.

Special Populations: Transition Care (The "Lost Tribe")

Age 16-25 is the danger zone.

• Problem: Moving from Paediatrics (Parent-led, strict) to Adult Care (Self-directed).
• Dropout: 30% of young adults disengage from clinic ("Diabetes Burnout"). HbA1c spikes.
• Solution: "Young Adult Clinics" with joint Paediatric/Adult consultants. Text support.

Special Populations: End of Life Care

When targets change.

• Goal: Comfort. Avoid Hypos (confusion) and symptomatic Hyperglycaemia (thirst).
• Insulin: Usually switch from Basal-Bolus to Once Daily Basal (if eating little).
• Monitoring: Reduce to once daily or when symptomatic. Stop CGM if annoying.
• Medication: Stop Statins and ACE Inhibitors (No long-term benefit).
• Steroids: Often used in palliative care (e.g. for brain tumours). Will cause massive hyperglycaemia. Needs increased insulin.

Life with Type 1 Diabetes

You control it. It doesn't control you.

FAQs

Q: Can I still eat sugar? A: Yes. But you must match it with insulin. "Diabetic Chocolate" is laxative and unnecessary. Eat normal food.

Q: Can I play sport? A: Yes. Steve Redgrave (Olympic Rower) has T1DM. You usually need less insulin for exercise (reduce basal by 20-50% beforehand).

Q: What about travel? A: Airport Security: Do NOT put your Pump or Libre through the X-Ray machine (conveyor belt). It can wipe the software. Ask for a hand-search. Carry a letter from your doctor.

Q: Can I drink alcohol? A: Yes, but eat carbs before bed. Beware the "Morning After Hypo".

Q: Sex? A: You can disconnect your pump for up to 1 hour. Reconnect afterwards.

Red Flags to Return

• Vomiting (Risk of DKA).
• Ketones >1.5 mmol/L.
• Hypos you cannot treat yourself.

Landmark Trials

1. DCCT (1993): Diabetes Control and Complications Trial.

   • Finding: Intensive insulin therapy (Basal-Bolus) reduced retinopathy, nephropathy, and neuropathy by ~60% compared to conventional therapy.
   • Cost: 3x higher risk of severe hypoglycaemia.
   • Legacy: Established HbA1c control as the gold standard.

2. EDIC (2005): Epidemiology of Diabetes Interventions and Complications.

   • Finding: A "Metabolic Memory" exists. Early good control provides protection decades later, even if control subsequently deteriorates.

3. CONCEPTT (2017):

   • Finding: CGM in pregnancy significantly improves neonatal outcomes.
   • Impact: Led to universal funding for CGM in pregnancy (NHS).

Guidelines

• NICE NG17 (UK): Focuses on structured education (DAFNE) and widespread technology adoption.
• ADA (USA): Standards of Medical Care.