Diabetes - Pathophysiology

Question 1

What is diabetes?

Answer 1

a group of metabolic disorders
- persistently high blood glucose levels due to problems with insulin
= normal range is 4-6 mmol/l

lack of insulin production = T1DM/IDDM
resistance to insulin = T2DM/NIDDM

Question 2

What are the types of diabetes and their causes?

Answer 2

type 1 diabetes - lack of insulin production = most common in younger patients, is polygenic with HLA links, autoimmune

type 2 diabetes - resistance to insulin = common in older patients, polygenic but no HLA links

gestational diabetes - occurs in pregnant women who have not previously had DM

maturity onset diabetes of the young (MODY) - mutation in a single gene, autosomal dominant

secondary diabetes - as a result of another condition

type 3C - pancreatic insufficiency

Question 3

What are the clinical symptoms associated with diabetes?

Answer 3

increased hunger
increased thirst - polydipsia
hyperglycaemia
dizziness
sexual disorder
increased urination - polyuria, nocturia (at night)
hypertension
numb hands and feet
candida - thrush, UTIs
eye damage/blurry vision
weight gain
weight loss - initially in T1DM
fatigue

Question 4

What investigations would be done to diagnose diabetes?

Answer 4

blood pressure
heart rate
respiratory rate
oxygen saturation
blood glucose
urine dip - glucose, protein (proteinuria), ketones

haemoglobin A1c - blood glucose over 3 months, should be <48mmol/L
fasting glucose - should be <7mmol/L
random glucose - should be <11.1mmol/L
OGTT - should be <11.1mmol/L

Question 5

What are the types of non-pharmacological and pharmacological treatments?

Answer 5

non-pharmacological
- smoking cessation, support group, diet, exercise, eye check up, feet check up, medicine review/GP

pharmacological
- blood glucose control
- blood pressure control
- lowering cholesterol

Question 6

How is type 1 diabetes mellitus managed?

Answer 6

all are managed with insulin
- basal bolus = rapid acting and long acting insulin
- bd regimen = intermediate insulin with short or rapid acting insulin
- bd regimen = intermediate insulin only
- continuous SC insulin infusion
- long acting insulin = T2DM only

Question 7

What is the mechanism of action of insulin?

Answer 7

Stimulates glucose uptake from circulation to tissues
- adipose and muscle tissue
Stimulates
- glycolysis = break down of glucose
- glycogenesis = formation of glycogen
- lipid synthesis
- protein synthesis

Inhibits
- gluconeogenesis
- glycogenolysis
- ketogenesis
- lipolysis
- proteolysis

Question 8

What are the adverse effects of insulin use and the cautions advised?

Answer 8

adverse effects
- weight gain = lipid synthesis, increased glucose uptake into tissues
- hypoglycaemia = glycolysis, gluconeogenesis
- lipohypertropy = growth of fat tissue under skin due to repeated injections into the same site

cautions
- injectable = may not be suitable for all
- hypoglycaemia
- driving restrictions may apply = must be controlled, minimum of 5 mmol/L before driving

Question 9

What are the drug classes for type 2 diabetes mellitus treatment?

Answer 9

biguanides - metformin
sulphonylureas - gliclazide, tolbutamide
DPP-4 (gliptins) - linagliptin, sitagliptin
GLP-1 agonists - exenatide, liraglutide
thiazolidinediones - pioglitazone
SGLT-2 (flozins) - dapagliflozin, canaglipflozin

alpha glycosidase inhibitors - acarbose
post prandial regulators/meglitinide - repaglinide
= rarely used