L14: An introduction to Diabetes Mellitus Flashcards
What is diabetes?
Group of metabolic disorders Chronic hyperglycaemia (elevated blood glucose concentration)--> damage to small and large blood vessels--> death
What are the two main types of diabetes?
Type 1–> autoimmune disorder–> destruction of β cells in pancreas
Type 2–> Insulin resistance, slow progressive loss of β cells
Why is diabetes a major health concern?
10% NHS budget 1/4--> kidney disease Blindness Non traumatic lower limb amputation 15% life time risk of amputation 70% deaths CVS disease LE reduced type 1--> 5-15yrs, type 2--> 5-10yrs
What is the likely cause of Type 1 diabetes?
Genetic predisposition interactive with environmental factors stimulate immune activation
Allele of HLA (human leukocyte antigen) –> HLA DR3 and HLA DR4
Seasonal variation suggesting link with viral infection–> trigger
What are the symptoms associated with diabetes type 1? (What is the normal classic case for Type 1 diabetes diagnosis?)
Young person <30yrs –> recent history of viral infection
Triad of symptoms
- Polyuria–> excess urine production, ↑ glucose in urine due to hyperglycaemia–> water follows
- Polydipsia–> Excess water loss (dehydration), osmotic effect of glucose on thirst centres
- Weight loss–> fat and protein metabolised by tissues because insulin is absent
How is diabetes diagnosed?
Blood test–> measure plasma glucose
↑ glucose as insulin not present
Presence or absence of symptoms
–> presence 1 test required
–> absence 2 tests required–> done a week apart
Random venous plasma concentration–> >11.1 mmol/L
Fasting glucose–> >7.0mmol/L
Oral tolerance test–> 2hrs post >11.1 mmol/L
HbA1c–> 6.5% >48mmol/L see if blood glucose is bound to haemoglobin–> RBC 120 lifecycle so could indicate been present for a while
What is one of the risk factors associated with diabetes type 1? Why does it occur?
Ketoacidosis
β- oxidation of FA along with low insulin/anti-insulin ratio (normally suppresses it)–> large amount of ketone bodies
–> β-hydroxybutyrate, acetone and acetoacetate
H+ associated with ketone produce a metabolic acidosis
What are the clinical feature of ketoacidosis?
Prostration (lying out), hyperventilation, nausea, vomiting, dehydration, and abdominal pain
Acetone–> volatile–> breathed out–> fruity smell on breath
What is cause of type 2 diabetes?
Obesity--> central obesity --> 85% risk Muscle and liver fat deposition Elevated circulating free fatty acids Physical inactivity Genetic influence
What are the symptoms of Type 2 diabetes?
Symptoms of hyperglycaemia
–> Polyuria, polydipsia, blurring vision and urogenital infections
Symptoms of inadequate energy utilisation
–> tiredness, weakness, lethargy, persistent infection, infections of feet, slow healing of minor skin damage etc…
How is type 1 diabetes managed?
Insulin
Subcutaneous injection several times a day
Appropriate dose needs to be given
Frequent blood glucose measurement needs to be taken–> finger prick test and measurement
Potential for hypoglycaemia (glucose too low)–> glucose given if hypoglycaemic
How is type 2 diabetes managed?
Early detection/diagnosis–> potential remission of disease–> need to loose about 10-15kg (about 15% TBW)–> very difficult
Lifestyle chanages–> increase exercise, improve diet
Non-insulin therapies–> Biguanides (metformin–> reduced gluconeogenesis), sulphonylureas (increase insulin release and reduce resistance)
Reduce other risk factors–> BP, lipids, smoking etc…
Extra drugs –> thiazolidinediones, GLP1 analogues, DPP4 inhibitors (slow inactivation and degradation of GLP-1 in gut which removes glucose), α-glucosidase inhibitors (prevent carb digestion) and SGLT2s
How can type 2 diabetes be prevented?
Control diet and exercise
- -> reduced risk by 58%
- -> Over 60s–> 71%
What are some of the metabolic consequence associated with persistant hyperglycaemia? Why do they occur?
Abnormal metabolism of glucose–> product maybe harmful to cells
Uptake of glucose into eye, peripheral nerve and the kidney doesn’t require insulin
Metabolised by the enzyme aldose reductase
Glucose+ NADPH + H+–> Sorbitol and NADP+
-Depletes NADPH stores–> increased disulphide bond formation in proteins
- Sorbitol–> osmotic damage to cells
Increased glycation of plasma proteins
–> disruption of function
Glycated haemoglobin–> HbA1c–> glucose interacts with terminal valine in Hb–> glycated haemoglobin
- -> HbA1c level good indicator of blood glucose control over last 3 months
- -> Normal 4-6% glycated
- -> Diabetic >10% glycated
What are some of the clinical complications of diabetes?
Microvascular
- -> ↑ risk of stroke
- -> ↑ risk of MI
- -> poor circulation to periphery
Macroscopic
- -> Diabetic eye disease–> retinopathy–> damage to BV in retina–> blindness
- -> Diabetic kidney disease (nephropathy)–> damage to glomeruli, poor blood supply, damage from infections to urinary tract–> sign= ↑ protein in urine (microalbuminuruia)
- -> Diabetic neuropathy–> loss of sensation, changes in function
- -> Diabetic feet–> poor blood supply, damage to nerve, increase risk of infection–> often unaware of problems–. gangrene–> foot amputation not uncommon
