Systemic complications of diabetes Lecture 12

Question 1

What is diabetes mellitus

Answer 1

A metabolic disorder of multiple aetiology, characterized by sustained hyperglycermia wih disterbances of carbohydrate, fat and protein homeostasis resulting from defects in insulin secretion, insulin action or both.

Question 2

What are the classifications of diabetes?

Answer 2

Type 1- classic autoimmune (normally develop within 15-20 years)

Type 2- acquired insulin resistance

Genetic- defects in insulin action or beta cell function

Secondary:

• drug/toxin induced,
• exocrine pancreatopathies,
• endocrine parties,
• infections

Nonclassical autoimmune - type B insulin resistance

Syndromic

Gestational - during pregnancy

Question 3

What are the clinical features of diabetes?

Answer 3

Dehydration, polyuria(excessive urine), polydipsia (excessive thirst), blurred vision

Fatigue

Weight loss (Type 1)

Recurrent infection

None (Type 2)

Question 4

Describe the management of hyperglycaemia

Answer 4

Sensitise- Biguanides, this solid in edibles

Excrete- acarbose, SGLT2 inhibitors

Replace- insulin, analogues

Secrete- sulphonylureas, meglitinides, GLP-1R agonists

Prevent with life style changes

Question 5

What are the complications of diabetes?

Answer 5

Metabolic- hyperglycaemic hyperosmolar syndrome, diabetic ketoacidosis

Micro vascular- cerebral microangiopathy, retinopathy, neuropathy, nephropathy

Macro vascular- ischaemic stroke, CV disease, peripheral vascular disease Immunoparesis/infection

Question 6

What are the microvascular complications of diabetes?

Answer 6

Microvascular complications are modifications in small bood vessels

Retinopathy:

• Main cause of blindness in working age people
• Disorder of retinal circulation leading to areas of hypoxia

Nephropathy:

• Affects glomerulus and tubular interstitium of kidney - impairs filtration of blood
• Results in end-stage renal failure

Neuropathy:

-Degeneration of peripheral nerves

Question 7

What are the macrovascular complications of diabetes?

Answer 7

Accelerated atherosclerosis:

-Due to high TGs/LDLs

Diabetic Foot:

• Due to loss of blood supply and neuropathy
• Common cause of lower limb amputation

Hypertension

Cardiovascualr disease and stroke

Question 8

What is the mechanism behind microvascular complication arising from diabetes?

Answer 8

• Increased generation of oxygen radicals in mitochondria via excess electron donors from TCA cycle
• Inhibition of glycolysis
• Shunting glycolytic intermediates towards alternative metabolic pathways:
• Polyol pathway leads to decreased antioxidant defence
• Hexosamine and PKC pathway causes detrimental gene expression profile

-Formation of “advanced glycation endproducts” that lead to altered signalling, inflammation and apoptosis

Question 9

Describe hyperglycaemic emergencies

Answer 9

Diabetic ketoacidosis- physical stress, intercurrent illness, non compliance

Hyperglycaemic + ketonaemia + metabolic acidosis

Treatment- fluid replacement, insulin therapy, correction of electrolyte disturbance

Hyperglycaemic hyperosmolar state- milder, no significant ketonaemia, similar management