GHM PBL 3

Question 1

State the clinical definition of diabetes Mellitus (DM)

Answer 1

Chronic metabolic disease
Characterised by elevated levels of blood glucose
Leads to damage to HEART, KIDNEY, BLOOD VESSELS, EYES, NERVES

Question 2

Describe the pathognesis of Type 1 and Type 2 Diabetes

Answer 2

TYPE 1: Destruction of pancreatic beta cells (due to AUTOIMMUNE response to virus, as virus has similar antigens to beta cells). Therefore, no insulin produced

TYPE 2: Problem with insulin receptors or insulin signalling pathway (could be caused by obesity), leading to body becoming resistant to insulin

Question 3

Describe the crirteria for diagnosis of DM

Answer 3

Glucose prick test - 2 hour post-prandial (eating) / random blood sample

Non-fasting venous plasma concentration <6.1 mmol/L is normal, if _> if more than 11.1 mmol/L = DM
if between 6.1-11.1 should be followed by fasting test

Fasting Venous plasma glucose concentration <6.1 mmol/L is normal, if _>7.0 mmol/L DM

BETWEEN THESE LEVELS, OGTT (oral glucose tolerance test) can confirm the degree of glucose intolerance

HbA1c: Measures ammount of blood glucose attached to haemoglobin - _>48 mmol/L = DM

C-peptide test: insulin overdose

Question 4

Describe the macro and microvascular complications of poorly controlled DM - include neuropathy, nephropathy, retinopathy, heart disease

Answer 4

RETINOPATHY:
-microvascular
-high BP causes damage to endothelial lining of blood vessels in retina
-because high blood glucose blocks vessels going to retina
-inflammatory cytokines upregulated during diabetes, causes chronic inflammation + endothelial damage, increases vascular permeability of blood vessels
-Resultant fluid (protein exudates) leak into the retina + deposit under the macula. - it can rupture the eye, causing bleeding
-Therefore, new blood vessels may also form (proliferative retinopathy). These vessels are weak + easilu bleed

DIABETIC HEART DISEASE
-endothelium damaged by free fatty acids forming atherosclerotic plaque
-the plaque can obstruct blood flow
-glucose damages endothelium + reduces nitric oxide production (vasodilator)
-heart cannot dilate

NEPHROPATHY
High glucose, increases ROS, casues oxidative stress
Overactivates RAAS system
Activated RAAS increases BP
Damage to glomerular filtration system
Increase permeability to the filtration membrane + leakage of proteins (albumin) in urine
Can lead to CKD + ESKD (end stage kidney disease) - requires dialysis / kidney transplantation

NEUROPATHY (MACROVASCULAR)
Hyperglycemia (increase blood glucose) - damages nerve in PNS
Pain, numbness, loss of sensatiion. - feet wounds may go undetected, get infected, lead to gangrene (limbs start rotting) - lack of blood supply cause tissue to die
NEUROPATHY (MICROVASCULAR): prolonged hyperglycemia causes polyol pathway to occur - damage to nerve blood vessels because SORBITOL + FRUCTOSE accumulate in Schwann cells, this causes:
-OXIDATIVE STRESS -> dysfunction of nerve cells
-Protein kinase C pathway - nerve damage
-Osmotic stress

THIS ALL ALTERS THE FUCNTION OF SCHWANN CELLS, WHICH PRODUCE MYELIN. THIS LEADS TO AXONAL DEGENRATION, DEMYELINATION, + impaired nerve conductions

Question 5

Describe the typical urine + blood test result from a diabetc patient

Answer 5

Urine:
-Glucose HIGH
-Ketones HIGH

Blood test:
-Sodium LOW
-Potassium HIGH
-Glucose VERY HIGH
-Bicarbonate LOW
-Urea HIGH

Arterial Blood gases:
-pH - LOW
-pO2 - FINE
-pCO2 - low
-HCO3 - LOW

Question 6

Signs and symptoms associated with DM and their underlying causes

Question 7

Describe the management of patients with DM (pharmacological + dietry)

Answer 7

PHARMACOLOGICAL:

TYPE 1 DM:
-Insulin therapy (multiple injections daily) or continuous subcutinous insulin infusion (insulin pump)
-Dosage / type depends on individuals needs + lifestyle factors
- Adjunctive therapies include PRAMLINTIDE or GLP-1 receptor agonist, to improve glycemic control + reduce risk of hypoglcyemia

TYPE 2 DM:
-Metformin: improves insulin sensitivity, reduces hepatic glucose production
-Oral antidiabetic agents including DPP-4 inhibitors, GLP-1 receptor agonists, SGL2-inhibitors
-Insulin therapy may be required

(for type 2, lifestyle changes including weight loss, physical activity + diet is the main treatment, if these do not work then we result to pharmacological)

DIETRY MANAGEMENT:
-Carbohydrates: Consume complex carbs (whole grains, legumes, fruits, vegetables) and limit simple carbs (sugat, sweet, refined grains)
-Proteins - intake moderate, not excessive, excessive leads to glucose production
-Fats- intake moderate, balance between saturated and unsaturated fats. Patients should limit intake of trans fat and cholestrol
-Fibre: Intake is beneficial for control of glucose levels, lipid metabolism. (fruit, veg, whole grain, legumes

Question 8

Describe the various metabolic actions of insulin

Answer 8

1. Glycogen synthesis turned on
   (GS activated by dephosphoryation by PP1)
2. Glycogen degradation turned off
   (GP inactivated by dephosphorylation by PP1)
3. Fatty acid synthesis turned on because:
   (ACC activated by dephos

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Question 9

Outline the significance of HbA1c monitoring in clincal management of DM

Answer 9

Measures amount of blood sugar (glucose) attached to haemoglobin.

DIAGNOSTIC THRESHOLD FOR DIABETES> _48mmol/L