Diabetes Type 1

Question 1

What are the effects of insulin secretion?

Answer 1

Increased:

• glucose uptake
• glycogen synthesis
• protein synthesis
• FFA and TG synthesis

Decreased:

• gluconeogenesis
• glyconeolysis
• proteolysis
• lipolysis and ketogenesis

Question 2

What are the metabolic consequences of acute insulin deficiency?

Answer 2

↓ 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

Question 3

What are the metabolic consequences of insulin excess?

Answer 3

↓ 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)

Question 4

Acute hypoinsulinaemia

Answer 4

↓ 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

Question 5

When do the symptoms of hypoglycaemia occur and what are they?

Answer 5

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

Question 6

What are the metabolic consequences of permanent insulin deficiency (T1DM)?

Answer 6

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.

Question 7

What are the causes of hypoglycaemia in diabetic patients?

Answer 7

↑ed physical activity w/ insufficient food
Consumption of alcohol
Delayed or missed meals
Errors in insulin dose
Inappropriate insulin regimens

Question 8

Treatment of hypoglycaemia in diabetic patients:

Answer 8

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.

Question 9

What is Whipple’s triad?

Answer 9

Used to diagnosis hypoglycaemia in non-diabetic patients. Absence of signs and symptoms excludes a diagnosis of hypoglycaemic disorder.
1. [Plasma glucose]

Question 10

How do you classify hypoglycaemia in adults?

Answer 10

Reactive hypoglycaemia or Fasting hypoglycaemia

Question 11

What is reactive hypoglycaemia?

Answer 11

Vague adrenergic symptoms 1-3hrs after food intake.

Question 12

What are the causes of reactive hypoglycaemia?

Answer 12

Postgastrectomy, vagotomy, pyloroplasty, early diabetes, idiopathic

Question 13

What is fasting hypoglycaemia?

Answer 13

Occurs >5hrs after food intake and is a consequence of ↓ed rate of hepatic gluconeogenesis or ↑ rate of glucose utilisation

Question 14

What are the causes of fasting hypoglycaemia?

Answer 14

Iatrogenic: insulin or oral hypoglycaemic treatment
Insulinomas
Ethanol (Inhibits gluconeogenesis)
Hypopituitarism
Liver Disease
Chronic Renal Failure
Starvation
Sepsis
Non-pancreatic neoplasms

Question 15

Pathology of hypoglycaemia in neonates, infancy and childhood:

Answer 15

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.

Question 16

What are the cause of hypoglycaemia that persists after early neonatal period?

Answer 16

Same as above, insulinomas, nesidioblastosis, extrapancreatic tumours, endocrine disorders (↓ cortisol, GH, T4, hypopituitarism), glycogen storage diseases, hereditary fructose intolerance, galactosaemia, liver disease.

Question 17

What is the paradox between maintaining euglycaemia in diabetic patients and the complications of diabetes?

Answer 17

It’s associated with ↓ risk of microvascular and neuropathic complications but a 2-3X ↑ risk of hypoglycaemia

Question 18

What is the aetilogy of Type 1 Diabetes?

Answer 18

• 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.

Question 19

What is the pathogenesis of T1DM?

Answer 19

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.

Question 20

Decribe the use of autoantibody detection as a method for predicting future progression to T1DM.

Answer 20

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.