Development of Diabetes Flashcards
1
Q
What is the normal ranges for blood glucose?
A
- normal = 4-6mM
- hyperglycaemia = >11mM
2
Q
What is the development of type 1 diabetes?
A
- genetic predisposition or exposure to enviro trigger (eg. viral infection)
- causes pancreatic beta-cell destruction leading to absolute insulin deficiency
- most patients present with life-threatening DKA
3
Q
Describe the clinical course of type I diabetes
A
Characterised by rapid onset of osmotic symptoms - polyuria - polydipsia - weight-loss - fatigue - slow wound healing (signs of hyperglycaemia)
4
Q
Describe the course of DKA
A
- uncontrolled diabetes leads to low insulin signalling
- normal process of glucose storage as glycogen reverses leading to increased lipolysis and decreased re-esterification
- causes hydrolysis of triacylglycerol into glycerol and increase in release of free fatty acids in plasma
- glycerol used for gluconeogenesis in liver resulting in further hyperglycaemia
- in absence of insulin liver transports fatty acids into mitochondria to generate large amounts of Acetyl-CoA which is used in peripheral tissues as ketone bodies (acetone, acetoacetic acid, beta-hydroxybutaric acid) which lowers the blood pH (acidosis)
5
Q
Describe the development of type II diabetes
A
- genetic predisposition and progressive loss of insulin sensitivity and defective insulin receptor signalling
- often due to impaired insulin receptor signalling leading to insufficient transport of glucose into tissues
- can be associated with metabolic syndrome (energy imbalance, high food consumption, low energy expenditure)
- fatty deposits in organs cause defective insulin signalling, resistance and beta cell damage
6
Q
Describe the progression of pre-diabetes to type II diabetes
A
- disruption of ability to metabolise glucose
- lower insulin sensitivity resulting in hyperinsulinaemia
- diabetes progresses when beta cells are failing causing low insulin secretion with low insulin sensitivity
7
Q
Describe the development of gestational diabetes
A
- occurs when pregnancy adaptations dont take place on a background of chronic insulin resistance
- when local, foetal and placental hormones promote a state of insulin resistance
- raises blood glucose which is readily transported across placenta to fuel foetal growth
- maternal compensation through hypertrophy and hyperplasia of pancreatic beta cells and glucose stimulated insulin secretion
- maternal insulin sensitivity returns to normal after a few days after delivery
8
Q
What are the risks of GDM?
A
maternal risks: miscarriage, CVD, pre-eclampsia and type II diabetes
foetal: macrosomia (large birth-weight), perinatal mortality, birth complications
9
Q
What factors increase the risk of GDM?
A
- ethnic minority background
- prior pregnancy in which baby weight more than 4.5kg
- BMI over 30
10
Q
Describe glucose monitoring in diabetes
A
- self-monitoring through finger prick capillary blood test
- type 1: test at least 4 times a day (before each meal and at bedtime)
- continuous glucose monitoring systems that measure interstitial glucose every few minutes (recommended for type 1 with frequent severe hypoglycaemia)
11
Q
What test can be done to diagnose diabetes?
A
- Hb1A1c test (glycated haemoglobin)
- 6-6.4% = pre-diabetes
- > 6.5% = diabetes
12
Q
Describe the diagnosis of diabetes
A
diabetes symptoms plus:
- random venous plasma glucose conc >11.1mmol or
- fasting plasma glucose conc >7mmol/l or
- 2 hr plasma glucose conc of >11.1 2 hr after 75g glucose in oral glucose tolerance test
- HbA1c > 6.5%
13
Q
Describe the long term effects of diabetes
A
- increased fat mobilisation
- increased plasma FFA/TG/cholesterol
- hyperglycaemia causing increased glycation and glycoxidation of proteins, and lipoproteins
- modification of extracellular structural proteins in arteries and arterioles (causing damage/loss of vascular endothelium)
- loss of vascular compliance
- atherosclerosis, hypertension
- CVD (angina, arrhythmias, renal disease)
