L44, 45, 46 Diabetes and glucose regulation Flashcards
1
Q
What is metabolism?
A
Metabolism is the continuous provision, storage, and use of energy in the body. It includes energy intake from carbohydrates, lipids, and proteins, and energy storage as glycogen (short-term) and triglycerides (long-term).
2
Q
What organs are key to fuel metabolism and their functions?
A
Liver: Glycolysis, gluconeogenesis, glycogen storage/release, lipogenesis
Pancreas: Secretes insulin and glucagon
Muscle: Glucose uptake, glycogen & triglyceride storage
Adipose tissue: Glucose uptake, triglyceride storage, fatty acid release
3
Q
What are normal blood glucose ranges?
A
Fasting: 4–6 mmol/L
Post-meal: ~10 mmol/L
4
Q
What are symptoms and consequences of hyperglycaemia?
A
Symptoms: Often none early, polyuria, thirst, weight loss, fatigue
Complications: Neuropathy, nephropathy, heart disease, cataracts, diabetic coma, death
5
Q
What are symptoms and complications of hypoglycaemia?
A
Symptoms: Irritability, fatigue, cravings, dizziness, confusion
Complications: Unconsciousness, accidents, weight gain, reduced IQ, brain abnormalities
6
Q
What are the main pancreatic cells and their hormones?
A
Alpha cells (25%): Glucagon
Beta cells (70%): Insulin
Delta cells (5%): Somatostatin
7
Q
Describe insulin synthesis and structure.
A
Synthesised as pre-proinsulin → proinsulin → insulin + C-peptide
A & B chains: Linked by disulphide bonds
B chain: Binds receptor
C-peptide: Assists folding, useful marker in diabetes
8
Q
How is insulin secreted in response to glucose?
A
Glucose enters beta cells via GLUT2
Phosphorylated by hexokinase → glycolysis → ATP
ATP closes K⁺ channels → depolarisation
Ca²⁺ influx triggers insulin granule exocytosis
Biphasic secretion: Rapid (1st phase) & sustained (2nd phase)
9
Q
What are the metabolic effects of insulin?
A
Muscle: GLUT4-mediated glucose uptake, glycogenesis, LPL expression
Liver: Promotes glycogenesis, inhibits gluconeogenesis
Adipose tissue: Enhances glucose uptake, promotes fat storage
10
Q
How does glucagon counteract insulin?
A
Secreted by: Alpha cells when glucose is low
Effects on liver: Stimulates glycogenolysis, gluconeogenesis, ketogenesis
Adipose tissue: Promotes lipolysis, inhibits lipogenesis
11
Q
Which other hormones regulate blood glucose?
A
Growth hormone
Epinephrine (Adrenaline)
Glucocorticoids (e.g. cortisol)
Somatostatin
Glucagon-like peptide-1 (GLP-1)
12
Q
What is GLP-1 and how is it used in diabetes?
A
Stimulates insulin, inhibits glucagon
Analogues (e.g. Exenatide, Liraglutide) resist DPP-IV breakdown
Administered via subcutaneous injection for Type 2 diabetes
13
Q
What do SGLT2 inhibitors do?
A
Inhibit renal glucose reabsorption
Increase glucose excretion in urine
Lower blood glucose levels (e.g., in Type 2 diabetes)
14
Q
A
15
Q
What is the insulin signalling cascade in target cells?
A
- Insulin binds to its tyrosine kinase receptor on the cell surface.
- The receptor autophosphorylates and activates IRS (Insulin Receptor Substrates).
- This triggers the PI3K → Akt (Protein Kinase B) pathway.
- Akt causes GLUT4 translocation to the membrane → glucose uptake.
- Also promotes glycogen synthesis, lipid synthesis, and protein synthesis.
16
Q
What is the role of C-peptide beyond being a diagnostic marker?
A
Facilitates proper folding of proinsulin during synthesis.
Used clinically to assess endogenous insulin production (injected insulin lacks C-peptide).
May have biological roles:
- Enhances renal blood flow
- Reduces neuropathy
- May improve endothelial function
17
Q
How is glucagon secretion regulated in alpha cells?
A
Triggered by low blood glucose.
Low glucose = ↓ ATP → K⁺ channels remain open, preventing depolarisation in beta cells (but not alpha).
Paracrine inhibition: insulin and somatostatin from neighbouring beta/delta cells suppress glucagon release.
Alpha cells detect glucose indirectly via the local environment.
18
Q
What is the process of ketogenesis and why is it important?
A
Occurs in the liver during fasting or insulin deficiency.
Fatty acids undergo β-oxidation → acetyl-CoA → ketone bodies (acetoacetate, β-hydroxybutyrate).
Provides alternative energy for the brain and muscles during prolonged fasting or in diabetes.
Excess = ketoacidosis (esp. in T1DM).
19
Q
How does lipolysis occur and what is its purpose?
A
Triggered by glucagon, adrenaline, cortisol.
Activates hormone-sensitive lipase in adipocytes.
Breaks triglycerides into glycerol and free fatty acids (NEFAs).
Glycerol → liver for gluconeogenesis
Fatty acids → energy or ketogenesis
20
Q
What are the detailed roles of other hormones in glucose regulation?
A
Growth hormone: Anti-insulin; decreases glucose uptake; increases lipolysis
Epinephrine: Increases glycogenolysis, gluconeogenesis; inhibits insulin
Cortisol (Glucocorticoid): Increases gluconeogenesis, protein breakdown, lipolysis
Somatostatin: Inhibits insulin, glucagon, and GH secretion
GLP-1: Enhances insulin, inhibits glucagon; delays gastric emptying and promotes satiety
21
Q
How does GLP-1 function, and how is it used clinically?
A
Released by L-cells in the intestine post-meal
Stimulates insulin secretion, inhibits glucagon, slows gastric emptying
Suppresses appetite
GLP-1 analogues (e.g. Exenatide, Liraglutide) resist DPP-IV degradation
Used in Type 2 Diabetes via subcutaneous injection
22
Q
What are SGLT2 inhibitors and how do they treat diabetes?
A
Inhibit SGLT2 transporters in the proximal renal tubule
Reduce renal glucose reabsorption, increase urinary glucose excretion
Lower blood glucose levels
Benefits: weight loss, blood pressure reduction
Risks: genital infections, dehydration, euglycaemic ketoacidosis
Examples: Dapagliflozin, Empagliflozin
23
Q
How does insulin resistance affect blood sugar control?
A
Target tissues (liver, muscle, fat) do not respond adequately to insulin
Less GLUT4 translocation → reduced glucose uptake
Liver continues gluconeogenesis despite high glucose
Leads to hyperglycaemia, a hallmark of Type 2 diabetes
24
Q
How does blood glucose regulation differ in Type 1 vs. Type 2 diabetes?
A
Type 1 Diabetes: Autoimmune destruction of beta cells → no insulin
Type 2 Diabetes: Insulin resistance + impaired beta cell function
T1DM: Risk of ketoacidosis, requires insulin therapy
T2DM: Managed with lifestyle, oral agents (e.g. metformin, SGLT2i), GLP-1 analogues, or insulin later
25
How is diabetes classified?
Type 1 Diabetes
Type 2 Diabetes
Monogenic Diabetes (e.g. MODY, neonatal, mitochondrial)
Other Types: Gestational, drug-induced (e.g. steroids), secondary (e.g. post-pancreatic surgery, endocrinopathies)
25
What is the pathophysiology of Type 1 diabetes?
Autoimmune destruction of pancreatic beta cells in the islets of Langerhans
Results in absolute insulin deficiency
Peak onset: 10–14 years
Can present acutely with BG > 11.1 mmol/L and ketosis
25
What is diabetes mellitus?
A group of metabolic diseases characterised by chronic hyperglycaemia, resulting from defects in insulin secretion, insulin action, or both. It is a partially inherited condition which, if untreated, leads to vascular and nerve damage.
25
What causes Type 1 diabetes?
Genetic: HLA genes (DR3, DR4-DQ8 in ~50% of cases)
Environmental: Viral infections, diet, gut microbiota
26
What are the symptoms of Type 1 diabetes?
Polyuria: excessive urine
Polydipsia: excessive thirst
Fatigue
Weight loss
Glycosuria: glucose in urine
Hyperglycaemia
27
What is Diabetic Ketoacidosis (DKA)?
Occurs when lack of insulin → liver produces ketones
Ketones = alternative fuel, but excess causes metabolic acidosis
Occurs in ~1 in 4 children at diagnosis
Mortality rate: 0.15–0.3%
Requires urgent fluid replacement & insulin therapy
28
What are the epidemiological trends in Type 1 diabetes?
Most common in White Europeans (0.3–0.5%)
Rare in South/East Asia & Africa (<0.05%)
Incidence ↑ by ~3% annually
75% of new cases have no family history
29
What is the pathophysiology of Type 2 diabetes?
Combination of insulin resistance + progressive beta-cell failure
Tissues fail to respond to insulin → hyperglycaemia
Initially, beta cells compensate → eventually dysfunction
Associated with dyslipidaemia, endothelial dysfunction, CVD
30
What are the risk factors for Type 2 diabetes?
Age > 40 (White) or > 25 (South Asian, Black, Chinese)
Obesity or high waist circumference
Family history
Medical history: Hypertension, gestational diabetes, heart disease, mental illness
31
What are the clinical features of Type 2 diabetes?
Insidious onset, many asymptomatic
Often found during routine checks
Ketosis is rare due to residual insulin
Often presents with complications first
32
What are the complications of diabetes?
Microvascular:
- Neuropathy: Numbness, pain, poor wound healing
- Nephropathy: Kidney damage → dialysis
- Retinopathy: Eye damage → blindness
Macrovascular:
- CVD: Heart attack, atherosclerosis
- Stroke
- Peripheral Vascular Disease: Poor leg circulation → necrosis
32
How is diabetes diagnosed?
Blood Glucose Tests:
- Random glucose ≥ 11.1 mmol/L with symptoms
- Fasting glucose ≥ 7.0 mmol/L
- 2h OGTT glucose ≥ 11.1 mmol/L
HbA1c:
- Diabetes: ≥ 48 mmol/mol (6.5%)
- Pre-diabetes: 42–47 mmol/mol (6.0–6.4%)
32
What is the role of autoantibodies and C-peptide in diagnosis?
- Autoantibodies (Anti-GAD, IA-2A, ZnT8): Confirm Type 1
- C-peptide: Marker of endogenous insulin
Low in Type 1, retained in Type 2 or MODY
- Used to distinguish between Type 1, Type 2, and MODY
33
What are the stages of Type 1 diabetes development (Eisenbarth model)?
Stage 1: Autoantibodies present, normoglycaemic
Stage 2: Autoantibodies + dysglycaemia (abnormal OGTT or fasting glucose)
Stage 3: Symptomatic Type 1 diabetes (hyperglycaemia, clinical features)
34
What is the full pathophysiology of Diabetic Ketoacidosis (DKA)?
Insulin deficiency → unopposed glucagon
↑ Lipolysis → ↑ Free Fatty Acids → Ketogenesis (liver)
Accumulated ketone bodies (acetoacetate, β-hydroxybutyrate) → metabolic acidosis
↑ Blood glucose → osmotic diuresis → severe dehydration
Can lead to shock, cerebral oedema, death
35
What biochemical abnormalities are seen in DKA?
Hyperglycaemia (BG >11 mmol/L)
Ketonaemia or ketonuria
Metabolic acidosis (pH <7.3, bicarbonate <15 mmol/L)
Raised anion gap
Possible hyperkalaemia (despite total body K⁺ depletion)
36
What is the cellular mechanism behind insulin resistance in Type 2 diabetes?
Impaired insulin receptor signalling (post-receptor)
Dysfunction of IRS-1, PI3K, Akt → reduced GLUT4 translocation
Adipose tissue inflammation (cytokines: TNF-α, IL-6)
Ectopic fat in muscle and liver disrupts glucose uptake and storage
37
What causes beta-cell failure in Type 2 diabetes?
Chronic hyperglycaemia (glucotoxicity)
Elevated fatty acids (lipotoxicity)
Increased beta-cell workload → ER stress, oxidative damage
Leads to progressive loss of function and eventual reduced mass
38
What is MODY (Maturity-Onset Diabetes of the Young)?
Monogenic, autosomal dominant diabetes
Young onset (<25), non-insulin dependent
Often misdiagnosed as Type 1 or 2
Caused by mutations (e.g. HNF1A, GCK)
C-peptide retained, autoantibodies negative
Responds well to sulfonylureas
39
How is MODY diagnosed?
Negative for islet autoantibodies
Preserved C-peptide levels
Family history of early-onset diabetes
Confirmed with genetic testing
40
How is HbA1c used and what are its limitations?
Reflects average glucose over 2–3 months
Diagnosis: ≥ 48 mmol/mol (6.5%)
Limitations:
- Unreliable in anaemia, haemoglobinopathies, pregnancy
- Doesn’t capture acute changes (e.g., rapid T1DM onset)
41
What is the oral glucose tolerance test (OGTT) interpretation?
Normal: 2h glucose < 7.8 mmol/L
Impaired glucose tolerance (IGT): 7.8–11.0 mmol/L
Diabetes: ≥ 11.1 mmol/L at 2 hours post-75g glucose
Often used to detect gestational diabetes
42
What is pre-diabetes and how is it classified?
HbA1c: 42–47 mmol/mol (6.0–6.4%)
Impaired fasting glucose (IFG): Fasting glucose 6.1–6.9 mmol/L
IGT: OGTT 2h glucose 7.8–11.0 mmol/L
Intervention: lifestyle changes to prevent progression to diabetes
43
What are the key features of diabetic foot complications?
Caused by neuropathy + ischaemia
↓ sensation + ↓ blood flow → risk of ulcers, infection, gangrene
May lead to amputation
Managed with regular foot checks, education, and multidisciplinary teams
44
How does diabetes affect mental health?
↑ Risk of depression, anxiety
Psychological distress affects treatment adherence
“Diabetes distress” is common—linked to the burden of self-management
Poor mental health worsens glycaemic control
45
What is gestational diabetes and why is it important?
Glucose intolerance with onset during pregnancy
Usually resolves after birth, but ↑ risk of future Type 2 diabetes
Risks to baby: Macrosomia, shoulder dystocia, neonatal hypoglycaemia
Diagnosed with OGTT between 24–28 weeks
46
How does NICE recommend monitoring and managing HbA1c?
Monitor every 3–6 months
Aim for HbA1c < 48 mmol/mol unless contraindicated
Avoid tight control in elderly or frail patients due to hypoglycaemia risk
47
Which of the following best defines diabetes mellitus?
A. A genetic disorder characterised by insulin overproduction
B. A metabolic disease involving chronic hypoglycaemia
C. A metabolic disorder involving chronic hyperglycaemia due to insulin defects
D. A hormonal disorder caused by glucagon overproduction
Answer: ✅ C
Explanation: Diabetes is a metabolic disease characterised by chronic hyperglycaemia due to insulin deficiency, resistance, or both.
48
Which genetic markers are most associated with Type 1 diabetes?
A. HLA-B27
B. HLA-DR3 and DR4-DQ8
C. BRCA1 and BRCA2
D. P53 and RB1
Answer: ✅ B
Explanation: The HLA-DR3 and DR4-DQ8 haplotypes are strongly linked to Type 1 diabetes susceptibility
49
Which of the following is NOT a typical symptom of Type 1 diabetes?
A. Polyuria
B. Polydipsia
C. Rapid weight gain
D. Fatigue
Answer: ✅ C
Explanation: Weight loss is a common feature of Type 1 diabetes, not weight gain.
50
A 12-year-old child presents with vomiting, confusion, and rapid breathing. Capillary blood glucose is 26 mmol/L. What is the most likely diagnosis?
A. Hypoglycaemia
B. Hyperosmolar hyperglycaemic state
C. Diabetic ketoacidosis
D. Insulinoma
Answer: ✅ C
Explanation: This is classic DKA presentation: high glucose, acidotic symptoms, ketone production.
51
Which of the following factors most strongly contributes to Type 2 diabetes pathogenesis?
A. Autoimmune beta cell destruction
B. Viral infection
C. Insulin resistance with beta-cell exhaustion
D. Mutation in HLA-DQ2
Answer: ✅ C
Explanation: Insulin resistance and progressive beta-cell failure are key in Type 2 diabetes.
52
Which of the following patients is at highest risk of developing Type 2 diabetes?
A. 23-year-old White female with normal BMI
B. 35-year-old Black male with central obesity
C. 42-year-old Asian female with no family history
D. 15-year-old White male with HLA-DR3
Answer: ✅ B
Explanation: Ethnicity, age >25 for Black individuals, and central obesity are significant Type 2 risk factors.
53
What would you expect to find in MODY (Maturity-Onset Diabetes of the Young)?
A. Positive autoantibodies
B. Obesity and insulin resistance
C. Onset after 50 years
D. Retained C-peptide and negative autoantibodies
Answer: ✅ D
Explanation: MODY is a monogenic form, often misdiagnosed. Typically: young onset, no insulin dependence, negative antibodies.
54
A patient with Type 2 diabetes has an HbA1c of 75 mmol/mol. What is the most appropriate next step?
A. Repeat HbA1c in 12 months
B. No action required
C. Add or intensify antidiabetic therapy
D. Test for anti-GAD antibodies
Answer: ✅ C
Explanation: HbA1c ≥ 48 mmol/mol = diagnostic. 75 mmol/mol indicates poor control, and treatment should be stepped up.
55
Which of the following is a microvascular complication of diabetes?
A. Stroke
B. Peripheral artery disease
C. Diabetic nephropathy
D. Myocardial infarction
Answer: ✅ C
Explanation: Microvascular = retinopathy, neuropathy, nephropathy. Stroke/MI are macrovascular.
56
Which of the following most accurately describes the action of C-peptide?
A. Stimulates ketone production
B. Is a synthetic insulin substitute
C. Connects insulin A and B chains and serves as a marker of endogenous insulin
D. Inhibits glucagon
Answer: ✅ C
Explanation: C-peptide is cleaved from proinsulin and reflects endogenous insulin secretion.
57
Which statement about the oral glucose tolerance test (OGTT) is TRUE?
A. It's used only for diagnosing Type 1 diabetes
B. A 2-hour glucose of 7.5 mmol/L indicates diabetes
C. A value ≥ 11.1 mmol/L at 2 hours confirms diabetes
D. It measures HbA1c directly
Answer: ✅ C
Explanation: OGTT 2h plasma glucose ≥11.1 mmol/L = diabetes.
58
In which situation is HbA1c not a reliable diagnostic tool?
A. Gestational diabetes
B. Long-standing Type 2 diabetes
C. Type 2 diabetes with stable glycaemic control
D. Newly diagnosed MODY
Answer: ✅ A
Explanation: HbA1c is unreliable in pregnancy due to altered red cell lifespan—OGTT is preferred.
59
Which diabetes complication is associated with slow-healing foot ulcers?
A. Diabetic retinopathy
B. Diabetic neuropathy with peripheral vascular disease
C. Nephropathy
D. Ketoacidosis
Answer: ✅ B
Explanation: Neuropathy → loss of sensation; PVD → poor circulation = foot ulcers, infection risk.
60
What causes Type 1 DM?
Genetic predisposition (e.g., HLA haplotypes) + environmental triggers
Triggers immune activation → autoantibodies and immune cells destroy β-cells
Results in absolute insulin deficiency
61
What causes Type 2 DM?
Insulin resistance in peripheral tissues
β-cell dysfunction (progressive insulin secretion loss)
Contributing factors: genetics, obesity, increased lipolysis, increased hepatic glucose output
62
What are the pancreatic islet cell types and their secretions?
α-cells: Glucagon
β-cells: Insulin (converted from pro-insulin)
δ-cells: Somatostatin
PP-cells: Pancreatic polypeptide
ε-cells: Ghrelin
63
What stimulates insulin secretion from β-cells?
Glucose via GLUT2
GLP-1 (incretin hormone)
Amino acids and fatty acids
Parasympathetic nervous input
64
What are the characteristics of regular human insulin?
Subcutaneous or IV (IV only in emergencies)
Onset: 30–45 mins
Duration: 4–6 hours
Rarely used in the UK
Examples: Actrapid®, Humulin S®, Insuman® Rapid
65
What are rapid-acting insulin analogues?
Modified to prevent hexamer formation → faster absorption
Onset: ~15 mins
Used around mealtime for flexibility
Examples: Lispro (Humalog®), Aspart (NovoRapid®), Glulisine (Apidra®)
66
What is intermediate-acting insulin (NPH)?
Delayed absorption via protamine complex (insoluble)
Duration: 8–12 hours
Uneven absorption profile → risk of hypoglycaemia and late hyperglycaemia
Examples: Insuman® Basal, Huminsulin® Basal
67
What are the approaches to insulin therapy?
Intensive therapy: Multiple daily injections (basal + bolus); flexible, reduces complications
Conventional therapy: Fixed-dose regimens; easier but less effective
Other: Insulin pumps, islet transplants, closed-loop/artificial pancreas systems
68
What factors should be considered in T1DM management?
Patient education (patient, family, staff)
Patient-specific factors: Age, motivation, cognition, vision, dexterity, pregnancy, comorbidities, lifestyle
69
What are the actions and benefits of Metformin (Biguanides)?
First-line therapy (esp. in overweight patients)
Actions:
↓ Hepatic gluconeogenesis
↑ Glucose uptake in muscles
Activates AMP-kinase
Benefits: No hypoglycaemia, weight loss
Side Effects: GI upset, lactic acidosis (rare), caution in kidney disease
70
How do Sulfonylureas and Meglitinides (Glinides) work?
Close KATP channels on β-cells → ↑ insulin release
Fast-acting, effective early in T2DM
Side Effects: Hypoglycaemia, weight gain, ineffective when β-cell function is lost
Example: Gliclazide
71
What are incretin-based therapies and how do they work?
GLP-1 analogues: Exenatide, Liraglutide (injectable)
DPP-4 inhibitors ("gliptins"): Sitagliptin, Vildagliptin
Mechanism:
- Enhance glucose-dependent insulin release
- Reduce appetite
- Possible β-cell preservation
Side Effects: GI upset, pancreatitis
GLP-1 analogues require self-injection
72
How do Thiazolidinediones (TZDs) work?
Activate PPAR-γ → modifies gene transcription
Improve insulin sensitivity
Side Effects: Weight gain, fluid retention, fracture risk, bladder cancer
Example: Pioglitazone (less used now)
73
What do SGLT2 inhibitors (Gliflozins) do?
Inhibit renal glucose reabsorption (proximal tubule)
Promote urinary glucose excretion
Cardio-renal protective effects
Side Effects: UTIs, dehydration, low BP, risk of ketoacidosis
Example: Dapagliflozin
74
What supportive management should be considered in diabetes?
BP and lipid control
Aspirin in selected patients for CVD prevention
Smoking cessation
Lifestyle: Diet, exercise, home glucose diary
75
What is Teplizumab and why is it important?
Anti-CD3 monoclonal antibody
FDA-approved in 2022
Delays progression from Stage 2 to Stage 3 T1DM by up to 2 years
Targets individuals with high risk of developing symptomatic T1DM
76
How do insulin preparations differ in their pharmacokinetics?
Rapid-acting (Lispro, Aspart, Glulisine): Onset ~15 min, peak ~1 hour, duration 3–5 hrs
Regular human insulin: Onset 30–45 min, duration 4–6 hrs
Intermediate (NPH): Onset 1–2 hrs, peak 4–6 hrs, duration 8–12 hrs
Long-acting (Detemir, Glargine): Flat profile, duration 14–24+ hrs
Ultra-long-acting (Degludec): Duration ~48 hrs, minimal peak
77
How does sulfonylurea stimulate insulin secretion at the molecular level?
Binds the SUR1 subunit of the KATP channel on pancreatic β-cells
Closes the channel → cell depolarisation
Opens voltage-gated Ca²⁺ channels → insulin granule exocytosis
78
What are α-glucosidase inhibitors and how do they work?
Example: Acarbose
Mechanism: Inhibits α-glucosidase enzyme in small intestine → delays carbohydrate digestion and glucose absorption
Use: Mild HbA1c reduction (0.5%), alternative when others are unsuitable
Side Effects: Bloating, flatulence, diarrhoea
79
What are the oral antidiabetic classes ranked by HbA1c reduction effect?
Biguanides, Sulfonylureas, Incretin therapies: ↓ HbA1c by 1.5–2.0%
TZDs: ↓ by 1.0–1.2%
SGLT2 inhibitors, DPP-4 inhibitors: ↓ by 0.5–1.0%
α-glucosidase inhibitors: ↓ by 0.5%
80
Which drug classes help with weight loss and which cause gain?
Class Effect on Body Weight
GLP-1 analogues, Metformin, SGLT2 inhibitors Weight ↓
Sulfonylureas, TZDs Weight ↑
DPP-4 inhibitors, α-glucosidase inhibitors Weight neutral (=)
81
How do SGLT2 inhibitors exert cardio-renal protection?
Reduce glucose and sodium reabsorption → natriuresis
↓ BP and volume overload
↓ Glomerular hyperfiltration (protecting kidney)
May improve heart failure outcomes
Independent of their glycaemic effect
82
What is the role of the closed-loop insulin delivery system (artificial pancreas)?
Integrates a Continuous Glucose Monitor (CGM) with an insulin pump
Uses algorithms to adjust insulin delivery automatically
Mimics real pancreatic function
Especially useful in T1DM for improved glucose control and reduced hypoglycaemia risk
83
What is the significance of Zn²⁺ in insulin formulations?
Stabilises insulin hexamers in regular and intermediate formulations
Delays absorption
Rapid-acting analogues avoid Zn²⁺-mediated hexamer formation for faster onset
84
What other key considerations are involved in diabetes pharmacological care?
BP Management: Target <140/90 mmHg (or <130/80 in high risk)
Lipid Control: Statins for all diabetics >40 years or with CV risk
Aspirin: Considered in patients with established CVD
Lifestyle: Smoking cessation, weight management, glucose monitoring
85
Which pancreatic cells secrete insulin?
A. Alpha cells
B. Beta cells
C. Delta cells
D. PP cells
Answer: ✅ B
Explanation: Beta cells in the islets of Langerhans produce insulin.
86
What stimulates insulin secretion most directly in β-cells?
A. Sodium influx
B. Calcium efflux
C. ATP closing KATP channels → depolarisation → Ca²⁺ influx
D. Glucagon release
Answer: ✅ C
Explanation: Glucose metabolism raises ATP, closing KATP channels → depolarisation → Ca²⁺ influx triggers insulin release.
87
Which process is inhibited by insulin in the liver?
A. Glycogenesis
B. Gluconeogenesis
C. Lipogenesis
D. Glycolysis
Answer: ✅ B
Explanation: Insulin inhibits gluconeogenesis and promotes glycogenesis and lipogenesis.
88
Which of the following is NOT a symptom of hypoglycaemia?
A. Confusion
B. Polyuria
C. Irritability
D. Dizziness
Answer: ✅ B
Explanation: Polyuria is a sign of hyperglycaemia, not hypoglycaemia.
89
What is the main effect of glucagon in adipose tissue?
A. Increases lipogenesis
B. Inhibits glycolysis
C. Promotes lipolysis
D. Inhibits lipolysis
Answer: ✅ C
Explanation: Glucagon promotes fat breakdown (lipolysis) to raise blood glucose via fatty acid mobilisation.
90
. Which hormone enhances insulin secretion and inhibits glucagon?
A. Somatostatin
B. Growth hormone
C. GLP-1
D. Adrenaline
Answer: ✅ C
Explanation: GLP-1 is an incretin that enhances insulin and inhibits glucagon in a glucose-dependent manner.
91
What is the diagnostic utility of C-peptide?
A. It measures dietary sugar
B. It reflects endogenous insulin production
C. It indicates kidney function
D. It determines glucose absorption
Answer: ✅ B
Explanation: C-peptide is cleaved from proinsulin and reflects internal insulin production (not present in injected insulin).
92
Which insulin preparation has the longest duration of action?
A. Regular human insulin
B. Lispro
C. Glargine
D. Degludec
Answer: ✅ D
Explanation: Degludec (Tresiba®) has a duration of ~48 hours.
93
Which insulin type forms subcutaneous precipitates due to reduced solubility at neutral pH?
A. Aspart
B. Lispro
C. Glargine
D. Detemir
Answer: ✅ C
Explanation: Glargine’s positively charged amino acids cause precipitation in subcutaneous tissue.
94
Which oral agent inhibits hepatic gluconeogenesis and activates AMP-kinase?
A. Sulfonylureas
B. Metformin
C. Pioglitazone
D. Sitagliptin
Answer: ✅ B
Explanation: Metformin blocks gluconeogenesis and activates AMPK in peripheral tissues.
95
Which drug class is most associated with hypoglycaemia and weight gain?
A. GLP-1 analogues
B. SGLT2 inhibitors
C. Sulfonylureas
D. DPP-4 inhibitors
Answer: ✅ C
Explanation: Sulfonylureas stimulate insulin release regardless of glucose → hypoglycaemia risk and weight gain.
96
How do SGLT2 inhibitors lower blood glucose?
A. Increase insulin secretion
B. Inhibit glucose absorption in the gut
C. Inhibit renal glucose reabsorption
D. Increase insulin sensitivity
Answer: ✅ C
Explanation: SGLT2 inhibitors promote urinary glucose excretion by blocking reabsorption in the proximal tubule.
97
What is a major concern with thiazolidinediones (e.g. pioglitazone)?
A. Severe hypoglycaemia
B. Pancreatitis
C. Fluid retention and fracture risk
D. Autoimmune hepatitis
Answer: ✅ C
Explanation: Pioglitazone can cause fluid retention, weight gain, fractures, and possibly bladder cancer.
98
Which of the following requires self-injection and promotes weight loss?
A. Sulfonylureas
B. GLP-1 analogues
C. DPP-4 inhibitors
D. Metformin
Answer: ✅ B
Explanation: GLP-1 analogues (e.g. Liraglutide) are injectable, promote satiety, and aid in weight loss.
99
What feature distinguishes DPP-4 inhibitors from GLP-1 analogues?
A. Weight gain
B. Must be injected
C. Inhibit breakdown of GLP-1
D. Stimulate glucagon release
Answer: ✅ C
Explanation: DPP-4 inhibitors stop incretin degradation, prolonging endogenous GLP-1 action.
100
Which agent delays carbohydrate digestion in the small intestine?
A. Acarbose
B. Glargine
C. Dapagliflozin
D. Sitagliptin
Answer: ✅ A
Explanation: Acarbose is an α-glucosidase inhibitor that delays carbohydrate absorption.
101
Which medication has proven benefit in delaying onset of clinical Type 1 DM?
A. Metformin
B. Teplizumab
C. Sulfonylureas
D. Pioglitazone
Answer: ✅ B
Explanation: Teplizumab (anti-CD3 monoclonal antibody) delays progression from Stage 2 to Stage 3 Type 1 DM.
102
A 52-year-old overweight man with a new diagnosis of Type 2 DM has an HbA1c of 59 mmol/mol. He has no significant comorbidities. What is the most appropriate first-line treatment?
A. Gliclazide
B. Metformin
C. Sitagliptin
D. Insulin glargine
Answer: ✅ B
Explanation: Metformin is first-line for most patients with T2DM, especially if overweight. It improves insulin sensitivity and promotes weight loss.
103
A 14-year-old girl presents with polyuria, polydipsia, fatigue, and weight loss. Her blood glucose is 27 mmol/L, ketones are positive, and she is acidotic. What is the most likely diagnosis?
A. Type 2 DM
B. Type 1 DM with DKA
C. Hyperosmolar Hyperglycaemic State
D. MODY
Answer: ✅ B
Explanation: These are classic features of new-onset T1DM with Diabetic Ketoacidosis (DKA).
104
A 65-year-old man with T2DM and chronic kidney disease (eGFR 32 mL/min) is struggling with high post-meal glucose. Which medication should be avoided?
A. Sitagliptin
B. Metformin
C. Gliclazide
D. Liraglutide
Answer: ✅ B
Explanation: Metformin is contraindicated in moderate-to-severe renal impairment due to the risk of lactic acidosis.
