Diabetes

Question 1

What are the classifications of diabetes?

Answer 1

Type 1- classic autoimmune
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
Syndromic
Gestational

Question 2

What are the clinical features of diabetes?

Answer 2

Dehydration, polyuria, polydipsia, blurred vision
Fatigue
Weight loss (T1)
Recurrent infection
None (T2)

Question 3

Describe the management of hyperglycaemia

Answer 3

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 4

What are the complications of diabetes?

Answer 4

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 5

What’s the pathophysiology of vascular complications?

Answer 5

Haemodynamics, metabolic and genetic factors induced cellular changes, increases immune cell recruitment, and cell dysfunction death
Hyperglycaemic➡ DAG➡ PKC➡ 
Decrease NOS➡ blood flow abnormalities
Increase VEGF➡ angiogenesis
Increase NF-kappaB➡ pro inflammatory
Increase NADPH oxidases➡ ROS

Question 6

Describe hyperglycaemic emergencies

Answer 6

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

Question 7

Describe the insulin receptor

Answer 7

liver muscle and fat
Multisubunit protein- 2x alpha- extracellular bindng site, 2x beta- transmembrane tyrosine receptor–> phosphorylation of insulin receptor substrate proteins (IRS proteins)
–> enzyme activation and gene transcription–> glucose uptake (GLUT4 expression), increase synthesis and decrease breakdown of glycogen

Question 8

Describe insulin therapy

Answer 8

Type 1 treatment
Achieve 48mmol/mol
Human recombinant DNA
Short acting- soluble insulin or lispro, onset 30mins peak 2-4hrs
Intermediate/long- insulin complexes, insulin glargine
SE- hypoglycaemia, allergy, lipodystrophy

Question 9

Describe some oral hypoglycaemic agents

Answer 9

Sulphonylureas-
Tolbutamide- short, glibenclamide- long, gliclazide
binds to SU receptors in Beta cellls, closes K(ATP) channel–> depolarisation–> insulin release
Increases tissue sensitivity to insulin
Repaglinide- no sulphonylurea moiety- more selective for the K(ATP) channels in beta cells, shorter duration
SE- hypoglycaemia (less with repaglinide), stimulate appetite, contraindicated in pregnancy

Question 10

Describe biguanide

Answer 10

Metformin
requires insulin
decrease gluconeogenesis- activates AMP-activated protein kinase–> decreases gene expression
Increases glucose uptake in the muscle
SE- no hypoglycaemia, no increased appetite, lactic acidosis
Used for obese diabetes, combination therapy

Question 11

Describe thiazolidinediones

Answer 11

Pioglitazone
Bind TF–> decreases hepatic glucose production, increase glucose uptake in muscle, increase lipogenesis (weight gain)
SE- fluid retention
Used with sulphonylureas or metformin

Question 12

Describe Acarbose

Answer 12

alpha-glucosidase inhibitor–> decrease ketone absorption
used for obese diabetics
Alone or with metformation

Question 13

Describe drugs that manipulate incretins

Answer 13

Incretins stimulates insulin secretion
1. Increase endogenous incretin
Sitaglandins- dipeptidyl peptidase-4 inhibitor–> blocks breakdown of incretins
2. Incretin agonist
Exenatide
GLP-1 agonist- subcutaneous injection, slow gastric emptying
Combined with metformin