Diabetes mellitus Flashcards
Define diabetts
Chronic, non-communicable disease characterised by hyperglycaemia
What is type 1 diabetes
Chronic autoimmune disease characterised by immune mediated disruption of pancreatic beta cells within islets of Langerhans
What must always be injected in type 1 diabetes
Insulin deficiency
Name 3 pieces of evidence that suggest T1D is an immune-mediated disease
- Infiltration of pancreas islets by mononuclear cells
- Almost 90% of patients possess autoantibodies against islets
- Immunosupression after diagnosis delays beta cell disruption
What % of people with diabetes have T2D
85-90%
What characterises type 2 diabetes
Abnormal insulin action adn secretion
What genes are suspected to be responsible for T2D
GKRP, PPARG
Name some risk factors for T2D
Obesity Family history Age Ethnicity Environemental factors (urbanisation)
Briefly describe how obesity is suspected to cause T2D
- Accumulation of lipids and their metabolites/ increased concentration of circulating free fatty acids
- Adipose tissue releases factors called adipokines which affect insulin resistance
- Chronic inflammation
Why does hyperinsulinaemia occur in T2D? What is the effect of this
Pancreas produces more insulin in response to the body not responding to insulin anymore
Increases lipid synthesis which worsens situation
How do levels of circulating adipokines contribute to insulin resistance
- Act as level or IRS so phosphorylate IRS in another residue
- Because its phosphorulated can’t be phosphorylated on tyrosine anymore
- Pathway is blocked at this stage
Which 2 physiological conditions is insulin resistance associated with in healthy people
Pregnancy
Body weight gain
How is physiological insulin resistance different to pathological insulin resistance
In physiological insulin resistance new beta cells can be generated so beta cells can compensate
How do islets change during insulin resistance
Increase in size (beta cells increase in size and number)
Increased beta function
How do islets change during T2D
Number of islets decrease
Signification decrease in number of beta cells per islet
What types of genes are the susceptability genes associated with T2D
Regulators of cell turover or regeneration
What happens to glucagon in diabetics
Excessive circulating levels of glucagon because theres no regulation
HYPERGLUCAGONAEMIA
Why does hyperglucagonaemia occur in T1D
No insulin in the body to regulate glucagon
Why does hyperglycagonaemia occur in T2D
Reduction of beta cells, alpha cells could also be resistant to insulin and hyperglycaemia
What is MODY
Maturity onset diabetes of the young- autosomal dominantly inherited form
Pancreatic beta cell dysfunction
What is LADA
Latent autoimmune diabetes of the adult
2 situations in which diabetes can be diagnosed
- One abnormal plasma glucose in presence of symptoms
- Two fasting venous plasma in abnormal range
What should plasma glucose be in oral glucose tolerance test in healthy person
Fasting= <6.1 2h= <7.8
What should plasma glucose be in oral glucose tolerance test in person with diabetes
Fasting>7
2h> 11.1
What are the advantages of measuring HbA1c
Reliable
Stable
Patient convenience
What is the recommended cut off point of HbA1c for diagnosing patients
48mmol/mol (6.5%)
Aims of diabetes treatment
Reduce insulin resistance or reduce hyperglycaemia
What drug is the first line treatment for treating diabetes
Metformin
Functions of metformin
Improve function of insulin receptor
Improve transport of glucose from blood into muscle
What does tzd do
Tackles insulin resistance
Resistant muscles pushed to uptake glucose as well as preventing the liver from producing glucose
Why does the liver produce glucose in diabetes
Essentially in starvation condition
Where can drug targets be to prevent excessive insulin secretion
Potassium channels
Calcium channels
Name 2 drugs that work at the level of potassium channels
Sylfonylureas and meglifinides
What is the role of GLP-1
Inhibits secretion of glucagon
Effect of metformin on GLP-1
Increases GLP-1 secretion
What drug inhibits DDP-4
Sitagliptin
What is the threshold for hypoglycaemia
<70mg/dL
<3.9mmol/L
Name 5 causes of hypoglycaemia
Alcohol excess Insulinoma Excessive exercise Reactive hypoglycaemia Type 1 diabetes
How does alcohol excess lead to hypoglycaemia
Gluconeogenesis inhibited at the level of lactate dehydrogenase
Symptoms of hypoglycaemia
- Trembling
- Palpitation
- Sweating
- Anxiety
- Hunger
- Tingling
What hormones are secreted in hypoglycaemia
Growth hormone
Cortisol
What are the consequences of prolonged hypoglycaemia
- Neuroglycopaenia
- Permenant brain damage
- Loss of cognitive function
Name 3 microvascular complications of diabetes
- Nephopathy
- Neuropathy
- Retinopathy
What pathway does glucose activate that isn’t normally activated
protein kinase C pathways
How does hypoeractivation of PKCs can damage blood vessels
- Increased permeability
- Increased occlusion
- Increased reactive oxygen species
- Increased inflammation
- Mitochondrial dysfunction
How do glycation end products mediate cellular damage
Lipids modified when they attach molecule of glucose
Products from glucose attach to the proteins leading to changes in activity
What is non proliferative diabetic retinopathy
Dilation of retina veins and microaneurysms can cause internal haemorrhaging and oedema in the retina.
Oedema in central retina is main cause of vision loss
What is proliferative diabetic retinopathy
Fragile, new blood vessels form near the optic disc and grow on vitreous chamber
Bleed, reducing vision and leads to separation and detachment of areas of retina
What characterises diabetic nephopathy
Proteinuria
Glomerular hypertrophy
Decreased GFR
Renal fibrosis
What is peripheral diabetic neuropathy
Pain or loss in feelings in hands/ arms/ feet/ legs
What is autonomic diabetic neuropathy
Changes in digestion, bowel and bladder control problems, erectile dysfunction
What is proximal diabetic neuropathy
Pain in thighs and hips
Weakness in legs
What can promote macrovascular disease
Advanced glycation end production formation
How does AGE formation promote macrovascular disease
AGE modification of oxidised LDLR leads to enhanced LDL uptake
Induces pro-inflammatory cytokine production
