Type 2 diabetes Flashcards

Question

Bevacizumab MOA

Answer 1

1. VEGF-A binds VEGF receptors (VEGFR-1 and 2) on endothelial cells, triggering downstream pathways that promote proliferation, survival, vasodilation and endothelial cell migration (blood vessel formation essential) 2. Bevacizumab binds VEGF-A preventing interaction with VEGF receptors, blocking signalling pathways for blood vessel formation 3. Anti-angiogenic effect useful in preventing new leaky blood vessel formation

Answer 2

Monoclonal antibody that inhibits angiogenesis by targeting vascular endothelial growth factor A Off-label diabetic macular oedema and proliferative diabetic retinopathy treatment

Answer 3

Narrowed arteries reduce blood flow to the limbs, often due to atherosclerosis

Answer 4

1. Normal Artery: Blood flows freely with no obstruction 2. Atherosclerotic Plaque Build-Up: Cholesterol and inflammatory cells accumulate, narrowing the artery 3. Plaque Blocking Blood Flow: Severe plaque formation significantly obstructs blood flow, leading to tissue damage and ischaemia

Answer 5

By causing plaque buildup in the arterial walls This plaque consists of lipids, cholesterol, inflammatory cells, and cellular debris Over time, it hardens and narrows the arteries, restricting oxygen-rich blood flow to the limbs, particularly the legs If untreated, this can lead to pain (claudication), ulcers, gangrene, and increased risk of CV events like heart attacks and strokes

Answer 6

1. Platelet: Blood cells involved in clot formation, which can contribute to blockages 2. Fibrous Cap: A tough outer layer that forms over the plaque, preventing rupture 3. Core: Contains lipids and cholesterol, forming the bulk of the plaque 4. Transformed Macrophages (Foam Cells): Immune cells that engulf cholesterol but contribute to plaque growth 5. Transformed Muscle Cells (Foam Cells): Smooth muscle cells that also take up lipids and contribute to the thickening of the artery wall

Answer 7

1. Angioplasty & Stenting – A minimally invasive procedure using a balloon and stent to open narrowed arteries 2. Bypass Graft Surgery – A surgical procedure that redirects blood flow around a blocked artery using a graft 3. Endarterectomy – A procedure to remove plaque buildup from an artery to restore blood flow.

Answer 8

Filtration process: normally waste products pass into urine but in nephropathy proteins also do Normal metabolic waste is expelled into urine

Answer 9

Chronic condition characterised by high blood glucose Due to insulin resistance and beta-cell dysfunction Leading to insufficient insulin secretion

Answer 10

1. Insulin resistance 2. Beta-cell dysfunction and death 3. Genetic predisposition 4. Environmental and lifestyle factors (e.g., obesity, poor diet, lack of exercise)

Answer 11

Fasting glucose ≥ 7 mmol/L 2-hour post-prandial glucose ≥ 11.1 mmol/L

Answer 12

1. Glutamic acid decarboxylase (GAD) antibodies 2. Age at diagnosis 3. Body Mass Index (BMI) 4. HbA1c levels 5. Insulin resistance 6. Beta-cell function

Answer 13

Obesity (most significant risk factor) Socioeconomic status (higher prevalence in deprived groups) Ethnicity (higher risk in Black, South Asian populations at lower BMI) Age (increased risk with ageing) Low birth weight (associated with future risk) Hx of gestational diabetes

Answer 14

- 30%-70% of T2DM risk is attributed to genetics - Family studies show 15% risk if one parent has T2DM, 75% risk if both parents have it - Monozygotic twin concordance ~70% - Dizygotic twin concordance ~20%-30% - GWAS studies have identified multiple diabetes susceptibility genes

Answer 15

1. Insulin Resistance – Insulin-sensitive tissues fail to respond to insulin 2. Beta-cell Dysfunction and Death – Beta cells become dysfunctional, reducing insulin secretion

Answer 16

A reduced ability of insulin-sensitive tissues to respond to insulin 1. Decreased sensitivity and reduced responsiveness 2. Reduced maximum response-curve due to impaired insulin signalling

Answer 17

1. Loss of pulsatile insulin secretion (early feature) 2. Loss of first-phase insulin secretion 3. Reduced glucose-stimulated insulin secretion 4. Decreased insulin content 5. Increased proinsulin secretion

Answer 18

Excess fat is stored in non-adipose tissues (e.g., muscle, liver) Leads to increased fatty acid metabolites, which inhibit insulin signalling Results in lipotoxicity, contributing to insulin resistance

Answer 19

Glucolipotoxicity: High glucose and fatty acids are toxic to beta cells Beta-cell exhaustion: Increased insulin demand leads to depletion ER stress: Overproduction of insulin exceeds cellular processing capacity Amylin deposits: Accumulation of amylin damages beta cells Inflammation: Systemic and local inflammation impairs function Genetics: Determines susceptibility to stress and ability to compensate Reduced incretin effect: Incretin hormones (GLP-1, GIP) are less effective

Answer 20

1. Severe autoimmune 2. Severe insulin-deficient 3. Severe insulin-resistant 4. Mild obesity-related 5. Mild age-related

Answer 21

As age increases, weight increases Beta cells compensate for insulin-resistance by producing more insulin BUT 30% of insulin-resistant individuals B cells cannot produce enough insulin to compensate weight, increasing blood glucose

Answer 22

1. Increase function & mass leading to increase in insulin secretion - NO diabetes 2. Reduced beta cell function & mass (reduced insulin secretion) - diabetes Increased beta cell mass and function in response to increased demand

Answer 23

Regulates glucose metabolism, protein synthesis, and lipid storage Involves insulin binding to its receptor, triggering a cascade of intracellular signals that control key metabolic processes in the liver, muscle, and adipose tissues

Answer 24

1. Insulin binds to the extracellular insulin receptor, a transmembrane protein 2. This activates the tyrosine kinase domain of the receptor 3. Receptor undergoes autophosphorylation, adding phosphate groups (P) to specific tyrosine residues 4. Activated receptor recruits insulin receptor substrates (IRS-1, IRS-2, IRS-3, IRS-4)

Answer 25

1. IRS proteins activate phosphoinositide 3-kinase (PI3K) 2. PI3K converts PIP2 (phosphatidylinositol-4,5-bisphosphate) into PIP3 (phosphatidylinositol-3,4,5-trisphosphate) 3. PIP3 recruits AKT/PKB (Protein Kinase B) to the membrane 4. AKT/PKB is activated via phosphorylation, leading to various metabolic effects

Answer 26

✔️ Glycogen Synthesis: Insulin promotes glucose storage by activating glycogen synthase. ❌ Inhibits Gluconeogenesis: Insulin suppresses the production of glucose from non-carbohydrate sources by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase)

Answer 27

✔️ Protein Synthesis: Insulin stimulates protein synthesis by activating mTOR (mechanistic target of rapamycin), which enhances muscle growth ✔️ Glucose Uptake: Insulin promotes glucose uptake into muscle cells by increasing GLUT4 (glucose transporter type 4) translocation to the cell membrane

Answer 28

✔️ Lipogenesis: Insulin enhances fat storage by activating acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) ❌ Inhibits Lipolysis: Insulin suppresses fat breakdown by inhibiting hormone-sensitive lipase (HSL), preventing the release of free fatty acids

Answer 29

1. Activated Akt/PKB stimulates the translocation of GLUT4 transporters to the cell surface 2. GLUT4 facilitates the uptake of glucose into muscle and adipose cells 3. This reduces blood glucose levels, storing glucose as glycogen (muscle) or fat (adipose)

Answer 30

Reduces hepatic glucose production (gluconeogenesis & glycogenolysis). Increases insulin sensitivity in muscle and fat. Delays intestinal glucose absorption. Activates AMP-activated protein kinase (AMPK).

Answer 31

- Oral, immediate-release (IR) or extended-release (ER). - Unchanged in urine (renal clearance). - GI upset, nausea, diarrhea. - Renal impairment (risk of lactic acidosis).

Answer 32

Binds to PPAR-γ receptor, increasing insulin sensitivity. Enhances glucose and fatty acid uptake.

Answer 33

- Oral. - Weight gain, fluid retention, increased risk of fractures. - Cardiovascular risk (Rosiglitazone withdrawn).

Answer 34

Inhibits SGLT2 in kidney tubules, preventing glucose reabsorption. Increases glucose excretion via urine.

Answer 35

- Oral. - Weight loss, cardiovascular protection. - Increased risk of UTIs, dehydration, ketoacidosis.

Answer 36

Stimulates insulin secretion from pancreatic β-cells. Closes ATP-sensitive potassium channels, leading to calcium influx and insulin release.

Answer 37

- Oral (once/twice daily). - Hypoglycemia, weight gain. - Renal or hepatic impairment, elderly (higher hypoglycemia risk).

Answer 38

Inhibits DPP-4 enzyme, prolonging GLP-1 action. Enhances insulin release and suppresses glucagon.

Answer 39

- Oral. - Nasopharyngitis, headache, pancreatitis (rare). - Severe renal impairment (dose adjustment needed)

Answer 40

Mimics GLP-1 hormone, stimulating insulin secretion. Suppresses glucagon release. Delays gastric emptying, promotes satiety.

Answer 41

- Subcutaneous injection. - Weight loss, cardiovascular protection. - Nausea, vomiting, pancreatitis risk.

Answer 42

- Used when oral agents fail. - Rapid-acting, short-acting, intermediate, long-acting (e.g., Lantus, Levemir). - Directly replaces insulin, lowering blood glucose. - Subcutaneous injection. - Hypoglycemia, weight gain.

Answer 43

- Sensitizes cells to insulin, reduces hepatic glucose production, increases glucose uptake. - Weight neutral, no hypoglycaemia risk, proven cardiovascular benefits, inexpensive. - GI side effects, lactic acidosis risk, B12 deficiency. - Renal function, Vitamin B12 levels.

Answer 44

- Stimulates insulin secretion. - Effective, quick glucose reduction, useful in steroid-induced hyperglycaemia. - Hypoglycaemia risk, weight gain, β-cell exhaustion, cardiovascular risks. - Blood glucose, risk of falls in elderly patients.

Answer 45

- Increases insulin sensitivity by activating PPAR-γ. - No hypoglycaemia risk, HbA1C reduction, useful in NASH. - Weight gain, oedema, fracture risk, bladder cancer risk. - Liver function, heart failure symptoms.

Answer 46

- Delays carbohydrate absorption by inhibiting α-glucosidase. - No hypoglycaemia risk, weight neutral. - GI side effects, minimal HbA1C effect. - Liver function tests (LFTs).

Answer 47

- Enhances incretin effects to increase insulin secretion and decrease glucagon. - Weight neutral, no hypoglycaemia risk, once-daily dosing. - Risk of pancreatitis, potential heart failure risk (Saxagliptin). - Symptoms of pancreatitis, renal function.

Answer 48

- Enhances glucose-dependent insulin secretion, slows gastric emptying. - Weight loss, cardiovascular and renal benefits (Semaglutide), alternative to insulin. - Expensive, GI side effects, retinopathy risk. - GI symptoms, retinopathy signs.

Answer 49

- Inhibits glucose reabsorption in kidneys, increasing glucose excretion. - Weight loss, cardiovascular and renal protective effects, low hypoglycaemia risk. - UTIs, dehydration, euglycaemic DKA risk, Fournier’s gangrene. - Kidney function, infection signs, hydration status.

Answer 50

Monitor CBG; intervene if >12 mmol/L. Use Gliclazide 40mg OM, titrate up as needed. Consider evening gliclazide or basal insulin if persistent.

Answer 51

First-line: Intermediate basal insulin (e.g., Humulin I). Short-acting insulin may be added if glucose remains high. Monitor glucose pre-feed and every 4-6 hours during feeding.

Answer 52

Minimize interventions that cause distress. Consider stopping non-essential diabetes medications.

Answer 53

Continue glucose monitoring. Maintain hydration and carbohydrate intake. Avoid stopping insulin unless instructed.

Answer 54

- Check every 3-6 months, individualize targets. - Key for Metformin, SGLT2 inhibitors, DPP-4 inhibitors. - Pioglitazone, Acarbose. - Monitor BP, lipid profile, weight changes.

Answer 55

Annual monitoring of HbA1C (3-6 months) BP (annual, intervene at 140/90) Cholesterol (annual lipid profile) Renal function (serum creatinine and albumin:creatinine ratio annually) Foot health (risk stratification) BMI Smoking status Emotional health Medication review (retinal screening yearly)

Answer 56

On insulin or sulphonylureas. Operating heavy machinery (e.g., HGV drivers). Pregnant.

Answer 57

Check blood glucose before driving and every 2 hours. Keep glucose levels >5 mmol/L before driving. Carry fast-acting carbohydrates in the vehicle.

Answer 58

Patient factors (age, comorbidities, occupational risks) Non-diabetic range: <42 mmol/mol. Well-controlled diabetes: 48-58 mmol/mol. Requires intervention: >74 mmol/mol. Emergency intervention: >103 mmol/mol.

Answer 59

BP Threshold for Intervention: >140/90 mmHg. Confirm hypertension with second measurement (white coat effect possible). 1st Line: ACE inhibitors (or ARBs if not tolerated). 2nd Line: Add calcium channel blocker or thiazide-like diuretic. 3rd Line: Combination of ACEi/ARB + CCB + thiazide. 4th Line: Add spironolactone (monitor electrolytes).

Answer 60

Total cholesterol (TC), Low-density lipoprotein (LDL), High-density lipoprotein (HDL), Triglycerides (TG) LDL: <2.0 mmol/L. Total cholesterol: <4.0 mmol/L. Triglycerides: <2.3 mmol/L. - Primary Prevention (No CVD): Atorvastatin 20mg OD if 10-year CVD risk >10%. - Secondary Prevention (CVD Present): Atorvastatin 80mg OD. - Consider ezetimibe, fibrates, PCSK9 inhibitors for uncontrolled cases.

Answer 61

Re-challenge with different statins (e.g., rosuvastatin weekly, then increase gradually). Hydrophilic statins (rosuvastatin, pravastatin) have lower muscle side effect risk. Monitor creatine kinase (CK) levels if myalgia occurs.

Answer 62

Any pain, numbness, skin breakdown? Nail health, calluses, deformities. Vascular (pulses), Neurological (monofilament test).

Answer 63

Low Risk: Annual check. Moderate Risk: Every 3-6 months. High Risk: Every 1-2 months. Active Problem (Ulcer/Infection): Weekly or emergency care.

Answer 64

Annual ACR & Serum Creatinine Measurement. D: ACR >30 mg/g, Creatinine Clearance (CrCl) <60 ml/min, 95% of T1DM nephropathy patients also have retinopathy → Check eyes! P: Optimize glycaemic control, BP, cholesterol.

Answer 65

5-10% body weight. Regular, sustained weight loss over time. Avoid ‘diabetic’ processed foods (often high in fat). Reinforce lifestyle improvements positively.

Answer 66

Nicotine replacement therapy, varenicline, bupropion, behavioral support. Use person-first language (e.g., ‘person with diabetes’ instead of ‘diabetic’). Acknowledge emotional struggles linked to diabetes. Encourage engagement without blame (avoid “non-compliant” language).

Type 2 diabetes Flashcards

Overview, aetiology & pathophysiology, molecular action (90 cards)