Type 1 diabetes Flashcards
What is the pathophysiology of type 1 diabetes?
-Autoimmune response against pancreatic B cells
-causes infiltration of pancreatic islets by mononuclear cells = insulitis
=absolute insulin deficiency
What is the Aetiology of type 1 diabetes?
HLA-assoc. immune-mediated organ specific disease:
- genetic susceptability is polygenic with greatest contribution from HLA region
- Auto-antibodies directed against pancreatic islet constituents appear in circulation in 1st few years of life and often predate onset for many years
- Environmental factors then act as a trigger: viral/infection/maternity/weight gain
Describe the epidemiology of T1DM?
Peak incidence around the time of puberty
- highest incidence Finland and northern european contries
- incidence increasing
What is the diagnosis of T1DM?
Diagnosis of diabetes:
Random glucose 11.1mmol/l or more
Fasting glucose 7.0mmol/l or more
and symptoms or repeat test
Diagnosis of type 1 diabetes:
- often on history and presentation alone e.g. DKA
- GAD/IA2 antibodies and C peptide may help
(discriminatory tests: GAD/anti islet cell abodys, ketones, c-peptide)
What is C-peptide
This is a biproduct of insulin synthesis and it’s level indicates insulin levels - if low =insulin is low
Describe the risk factrors and disease markers for T1DM in the:
- Foetus
- Pre-diabetes
- Clinical diabetes
Foetal risk factors (maternal factors):
- infection
- age
- ABO mismatch
- Birth order
Foetal disease markers:
-HLA or non-HLA
Pre-diabetes risk factors (autoimmune trigger factors):
- viral infection
- vit D deficiency
- Dietary factors
- environ. toxins
Pre-diabetes disease markers:
- autoantibodies
- candidate antigens
- insulitis
Clinical diabetes risk factors (accelerating factors):
- infection
- insulin resistance
- puberty
- diet/weight
- stress
Clinical diabetes disease markers:
- raised blood glucose
- ketones
- low insulin levels
- decrease in B cell mass
- decrease in C peptide
Type 1 diabetes symptoms:
- Triad?
- others?
Triad:
- polyuria (enuresis in children)
- polydipsia
- weight loss
- fatigue and somnolence
- blurred vision
- candida infection
- ketoacidosis
Describe the general management principles of Type 1 diabetes
- blood glucose and ketone monitoring
- insulin: usually basal/bolus regime
- carbohydrate estimation
- regular DSN + dietician contact
- appropriate medical clinic review
- HbA1c monitoring (ideal range is 48-58 mmol/L)
- annual review
- record severe hypoglycaemic episodes or admission with diabetic ketoacidosis
What is included in an annual diabetic review?
- weight
- BP
- bloods
- HbA1c
- Renal function
- Lipids
- Retinal screening
- foot risk assessment
insulin - What is: -humalog -humulin S -insulatard -lantus/levermir -humalog mix 25 -humulin M3 examples of?
- humalog: rapid acting
- humulin S: short acting
- insulatard: intermediate acting
- lantus/levermir: long acting
- humalog mix 25: rapid/intermediate mix
- humulin M3: short/intermediate mix
What are the blood glucose targets:
- pre-prandial
- post-prandial
Pre-prandial: 4-7mmol/L
post-prandial: <10mmol/L
What are the main aims of insulin treatment?
- prevent hyperglycaemia (too little insulin)
- avoid hypoglycaemia (too much insulin)
- reduce chronic complications
What symptoms are associated with hyperglycaemia?
- Thirst
- tiredness
- blurred vision
- weight loss
- polyuria
- nocturia
- fungal infections
What signs are associated with hyperglycaemia?
- mood state
- information processing
- working memory
What is the risk of hyperglycaemia in type 1 diabetes? What could precipitate this?
Diabetic ketoacidosis
- non-compliance with treatment
- newly diagnosed DM
- alcohol
- illicit drugs
- infection
Describe the pathogenesis of diabetic ketoacidosis in the absence of insulin?
in the absence of insulin:
- hepatic glucose production accelerates (glycogenolysis and glucneogenesis) and peripheral uptake glucose is reduced.
- rising glucose levels leads to an osmotic diuresis = loss of glucose in urine drags salt/electrolytes with it which water follows
- plasma osmolarity rises and renal perfusion falls
simultaneously:
- rapid lipolysis occurs which leads to raised levels of free fatty acids
- these are broken down in the liver = ketone bodies
This leads to:
-renal perfusion has fallen and therefore ketones can’t be excreted
= build up
=ketoacidosis
What other biochemistry is deranged in ketoacidosis?
- hyperkalaemia (insulin usually drives potassium into cells)
- Creatinine often raised
- hyponatraemia
- raised lactate common
- bicarb <10 in most severe cases
- amylase often raised
- WCC raised due to effect of acidosis on bone marrow
What symptoms are experienced in ketoacidosis?
Osmotic related:
- thirst/polyuria
- dehydration
Ketone body related:
- flushed
- vomiting
- abdo pain and tenderness
- kussmauls resp. (breathless as trying to blow off CO2)
- ketone smell
Assoc. conditions:
- gastroenteritis
- underlying sepsis
How is diabetic ketoacidosis diagnosed?
Ketonaemia >3mmol/L
Ketonuria >2+ on dipstick
Blood glucose >11mmol or known DM
Bicarbonate <15mmol/L or venous pH <7.3
What is the management of diabetic ketoacidosis?
In HDU following hospital protocol
Replace losses:
- fluid (initially 0.9% NaCl, if glucose falls to 15 use dextrose)
- insulin 0.1unit/kg/hour
- potassium
- phosphate rarely
- HCO3- almost never
Describe ketone monitoring
Ketone monitoring, this is attached to the glucometer in T1DM to prevent ketoacidosis as can allow preventative action:
Blood ketone monitoring - <0.6mmol/L normal
Urine ketone testing - indicates ketone level 2-4hrs ago
What hormone effects are seen in insulin deficiency?
Growth hormone:
-promotes lipolysis and reduces hepatic uptake glucose
Adrenaline:
-stimulates glucagon release and lipolysis
Cortisol:
-stimulates glucneogenesis in liver from amino acids, glycerol, lactate and pyruvate
Describe what symptoms are seen in hypoglycaemia?
Symptoms - typically below 3mmol/L develop over minutes:
- pallor
- sweating
- tremor
- palpitations
- confusion
- nausea
- hunger
- irritable/angry
- pounding heartbeat
- weakness/fatigue
- heachae
What signs are seen in hypoglycaemia?
- pallor
- cold sweat
