What acts as a marker for insulin function?
- C PEPTIDE
- -> it is linked to insulin production
What causes T1DM ?
- destruction of Beta cells
Autoimmune destruction of islet cells
What is a histological feature of T1DM?
- there is a lot of lymphocyte infiltration of the beta cells
- -> which destroys B-cells
- -> so they can no longer release insulin
What is the importance of the autoimmune basis of T1DM?
- increased prevalence of other autoimmune disease
- risk of autoimmunity in relatives
- more complete destruction of B-cells
- autoantibodies can be useful clinically
- immune modulation offers possibility of novel treatments
What are 2 most significant marker for clinically defining someone who might have T1DM?
- Islet cell antibodies (ICA)
- Glutamic Acid Decarboxylase antibodies (GADA) –> neurotransmitter
others:
- insulin antibodies (IAA)
What are some symptoms of T1DM?
Symptoms:
- polyuria
- nocturia
- polydipsia
- blurred vision
- weight loss
- fatigue
- thrush (due to increased risk of infections)
What are signs of T1DM?
Signs:
- dehydration
- cachexia
- hyperventilation (may have metabolic acidosis)
- smell of ketones
- glycosuria
- ketonuria
What is the effect of Insulin on:
HGO:
Glucose uptake:
Proteolyic breakdown:
Glycerol release from fatty tissue:
HGO: decrease
Glucose uptake: increase
Proteolyic breakdown: decrease
Glycerol release from fatty tissue: decrease
Describe the mechanism of diabetic ketoacidosis in T1DM
- glucose = isn’t taken up into cells + utilized
so most energy = from fatty acids - if you have insulin deficiency, fatty acids come out of adipocytes –> into circulation (instead of glycerol)
- then fatty acids go to the liver
- and is converted to ketones
- there is no insulin to inhibit this process
- -> so you get ore ketone bodies produced by the liver
What are main aims of treatment of T1DM?
- reduce early mortality
- avoid acute metabolic decompensation
- identify requirement for exogenous insulin
- prevent longterm complications such as retinopathy, neuropathy, nephropathy etc.
note: increase in ketone = insulin DEFICIENCY
-
How would you control diet in T1DM?
- reduce fat
- reduce refined carbohydrate
- increase complex carbs
- increase soluble fibre
What are some treatments for T1DM?
with meals:
- short acting insulin
- human insulin
- insulin analogues e.g lispro, aspart etc
background insulin:
- long acting
- non-C bounds to zinc or protamine
- insulin analogues e.g glargine, determir, degludec
note: type + dose = dependent on how much patient eats in each meal and when they eat.
How do insulin pump act as a method of treatment for T1DM?
what are disadvantages of it?
- provides continuous insulin delivery
- has preprogrammed basal rates + bolus for meals
DSADV:
- doesn’t measure glucose
- no completion of feedback loop
How do islet cell transplants act as a method of treatment for T1DM?
what are disadvantages of it?
- islet cells = harvested/isolated/injected into liver
DSADV:
- risk of rejection
- long waiting list
note: transplant if there is severe hypoglycemia + can’t be controlled by insulin pump
How do capillary monitoring act as a method of treatment for T1DM?
what are disadvantages of it?
- prick finger tips
- capillary glucose levels
- -> reflects venous blood glucose
- patients can titrate insulin dose according to reading
Long term blood glucose control is monitored by measuring:
HbA1c
- HbA1c red cells react with glucose
- high HbA1c = high glucose level in blood
- lower HbA1c = lower risk of microvascular complication
note: not that useful in those with renal failure/ Hb Opathy
What are the major acute complications associated with T1DM? (rapid decompensation)
- hyperglycemia
- metabolic acidosis
Why would hyperglycemia occur in T1DM?
- reduced glucose utilisation in tissues –> causes increased hepatic glucose production
Why would metabolic acidosis occur in T1DM?
- increased ketone body production in liver
- causes increase in circulating acetoacetate + hydroxybutyrate
- causes osmotic dehydration _ poor tissue perfusion
Define hypoglycemia
+
severe hypoglycemia
hypoglycemia = condition when the plasma glucose level = < 3.6 mmol/L
severe hypoglycemia = hypo requiring help of another person to treat
what are some Hypoglycemia symptoms + signs?
Increased autonomic activation:
- palpitations
- tremor
- sweating
- cold extremities
- anxiety
Impaired CNS function:
- drowsiness
- confusion
- coma
How would you treat hypoglycemia orally?
- feed patient glucose as solution/ tablets
- give complex CHO
How would you treat hypoglycemia parenterally?
if consciousness = impaired:
- give IV dextrose
- 1mg Glucagon IM
What is Honeymoon phase
period of time following diabetes diagnosis when the pancreas is still able to produce amount of insulin to reduce insulin needs and aid blood glucose control.
What is the primary genetic marker of diabetes ?
in HLA chr 6
- DR3/4
note:
insulin tries to prevent glucose leaving liver
(no insulin –> increase plasma glucose
insulin can also increase glucose absorption by muscle
(no insulin –> increase plasma glucose level)
insulin prevents fatty cells from breaking up
(because glycerol from fatty cells can be used to produce glucose in liver)
-
What are some long term complication
- retinopathy
- nephropathy
- neuropathy
- vascular disease
note: basal insulin = constantly released throughout the day
-
What are the different methods of monitoring diabetes in patients?
- capillary monitoring
- continuous glucose monitor
hypoglycemia is usually associated with patients with low/high HbA1c
hypoglycemia is usually associated with patients with low HbA1c