Diabetes Type 1 Flashcards
What are the effects of insulin secretion?
Increased:
- glucose uptake
- glycogen synthesis
- protein synthesis
- FFA and TG synthesis
Decreased:
- gluconeogenesis
- glyconeolysis
- proteolysis
- lipolysis and ketogenesis
What are the metabolic consequences of acute insulin deficiency?
↓ rate of glucose utilisation
↑ rate of glucose production
↑ protein and fat mobilisation (break down)
A shift from using glucose to using FFAs and ketone bodies
What are the metabolic consequences of insulin excess?
↓ plasma glucose which could threaten brain function.
↓ insulin secretion (if glucose between 4-6), ↑ glucagon, adrenaline, GH and cortisol (at threshold of ~3.8mmol/L)
Acute hypoinsulinaemia
↓ insulin → migration of glucose transporters back into cells → ↑ cAMP ↑ cAMP: -In the liver: ↑ glycogenolysis + gluconeogenesis → ↑ blood glucose -In adipose tissue: ↑ FFAs + glycerol → fatty B-oxidation → inhibition of PDH complexes → conversion of pyruvate to lactate → to liver for gluconeogenesis
When do the symptoms of hypoglycaemia occur and what are they?
Glucose of ~3.0mmol/L
SNS symptoms: tremor, tachycardia, palpitations,sweating, weakness and awreness of hypoglycamia
CNS symptoms if plasma glucose continues to ↓: headaches, altered mental status, visual disturbances, neuro deficit and seizures
Cognitive dysfunction @ ~2.7mmol/L
Coma
Death
What are the metabolic consequences of permanent insulin deficiency (T1DM)?
As conc of glucose rises above 10mmol/L → glycosuria
Uncontrolled lipolysis and proteolysis → FFAs and AA in blood → formation of ketone bodies and gluconeogenesis in liver. → acidosis (ketones, lactate)
Ketone bodies and FFAs inhibit utilisation of glucose by inhibiting the PDH complex → exacerbated hyperglycaemia and glycosuria
Hyperglycaemia → cellular dehydration → polydipsia + polyuria
Rapid weight loss d/t massive breakdown of body fuel stores.
What are the causes of hypoglycaemia in diabetic patients?
↑ed physical activity w/ insufficient food
Consumption of alcohol
Delayed or missed meals
Errors in insulin dose
Inappropriate insulin regimens
Treatment of hypoglycaemia in diabetic patients:
Ingestion of 15-50g oral glucose (150ml Coke) followed by a complex carb (slice of rye bread)
if patient is unconcious or unable to swallow: IV glucose (50%) or IM glucagon, followed by ingestion of complex carb as soon as pt regains consciousness.
What is Whipple’s triad?
Used to diagnosis hypoglycaemia in non-diabetic patients. Absence of signs and symptoms excludes a diagnosis of hypoglycaemic disorder.
1. [Plasma glucose]
How do you classify hypoglycaemia in adults?
Reactive hypoglycaemia or Fasting hypoglycaemia
What is reactive hypoglycaemia?
Vague adrenergic symptoms 1-3hrs after food intake.
What are the causes of reactive hypoglycaemia?
Postgastrectomy, vagotomy, pyloroplasty, early diabetes, idiopathic
What is fasting hypoglycaemia?
Occurs >5hrs after food intake and is a consequence of ↓ed rate of hepatic gluconeogenesis or ↑ rate of glucose utilisation
What are the causes of fasting hypoglycaemia?
Iatrogenic: insulin or oral hypoglycaemic treatment Insulinomas Ethanol (Inhibits gluconeogenesis) Hypopituitarism Liver Disease Chronic Renal Failure Starvation Sepsis Non-pancreatic neoplasms
Pathology of hypoglycaemia in neonates, infancy and childhood:
Common within first 72hr after birth & esp premature and SGA (small for gestational age) babies.
d/t low glycogen stores and/or delayed feeding.
Precipitating factors: hypothermia, hypoxia, infection and poorly controlled maternal diabetes.
What are the cause of hypoglycaemia that persists after early neonatal period?
Same as above, insulinomas, nesidioblastosis, extrapancreatic tumours, endocrine disorders (↓ cortisol, GH, T4, hypopituitarism), glycogen storage diseases, hereditary fructose intolerance, galactosaemia, liver disease.
What is the paradox between maintaining euglycaemia in diabetic patients and the complications of diabetes?
It’s associated with ↓ risk of microvascular and neuropathic complications but a 2-3X ↑ risk of hypoglycaemia
What is the aetilogy of Type 1 Diabetes?
- Genetic: Polymorphisms primarily in the HLA Class 2 region ↑ susceptibility to development of T1DM. (95% of T1DM pts carry a polymorphism but 45% non-diabetics carry the same polymorphisms)
- Environment: Viruses: Coxsackie B and congenital rubella may lead to development of T1DM later in life.
What is the pathogenesis of T1DM?
It’s an autoimmune disorder against beta cell proteins.
The autoantigens implicated are: insulin, GAD and protein tyrosine phosphatase-2 (IA-2)
However, T-cells infiltrate islets early in the disease (insulinitis), they are the major destroyers of islet beta cells.
There is both a humoral and cellular response against these autoantigens.
Hypothesis: HLA gene polymorphisms allow HLA molecules to bind either a beta cell peptide or a viral peptide that has similar amino acid sequence to the beta cell peptide.
Decribe the use of autoantibody detection as a method for predicting future progression to T1DM.
Autoantibodies apper in the circulation years before any clinical symptoms are detected and at least 70% of the beta cell mass of the pancreas is destroyed before any clinical symptoms arise.
Screening needs to be of the general population and not only those w/ a family history of diabetes.
