Type I Diabetes Flashcards
What is Type 1 diabetes?
Type I diabetes mellitus is characterised by an autoimmune condition in which pancreatic beta-cells of the Islets of Langerhans are dysfunctional.
What is the long-term treatment for partial or complete insulin production in T1DM?
Chronic insulin treatment
What is LADA?
Autoimmune diabetes leading to insulin deficiency can present later in life = latent autoimmune diabetes in adults (LADA).
Which metabolic feature is characteristic of T1DM?
Diabetic ketoacidosis
What is the relationship between pancreatic B-cell function and age in those with a genetic predisposition to T1DM?
• The number of pancreatic beta-cells progressively decrease with age, resulting in a decline in insulin output and glucose control.
What is the cleavage product of pro-insulin?
C-peptide
What is C-peptide used for?
C-peptide is the cleavage product of pro-insulin Used as a marker of insulin concentrations and beta-cell function.
What is the pathoimmunology underlying T1DM?
autoreactive CD4+ T-lymphocyte by antigen-presenting cells.
• CD4+ cells activate CD8+ T lymphocytes.
• CD8+ cells travel to islets and lyse beta cells expressing autoantigen (travel via lymph nodes)
• Release of pro-inflammatory species and reactive oxygen species (Granzyme and perforin are released from cytotoxic granules).
Defects in which type of tolerance is evident in T1DM pathoimmunology?
Peripheral tolerance (Impaired regulatory T-cells)
Which allele identified in GWAS is implicated in T1DM?
HLA-DR allele
What are the environmental factors implicated in T1DM?
Environmental factors Multiple factors implicated Causality not established. • Enteroviral infections • Cow’s milk protein exposure • Seasonal variation • Changes in microbiota.
What are the common pancreatic auto-antibodies involved in T1DM?
- Glutamic acid decarboxylase (GADA) – widespread neurotransmitter
- Insulin antibodies (IAA)
- Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc transporter 8 (ZnT8).
What is the clinical presentation of type 1 diabetes?
- Polyuria – excessive urination
- Polydipsia – excessive thirst
- Blurring of vision – Diabetic nephropathy
- Recurrent infections e.g thrush
- Weight loss
- Fatigue- Catabolic muscle breakdown (proteolysis considering to produce both glucogenic and ketogenic amino acids).
What are the clinical signs of type 1 diabetes?
- Dehydration
- Cachexia – Catabolic catabolism increases to provide alternative substrate including amino acids gluconeogenesis and ketone body formation.
- Hyperventilation – diabetic ketoacidosis (Respiratory compensation to remove carbon dioxide)
- Smell of ketones
- Glycosuria
- Ketonuria
Why does hyperventilation occur in T1DM?
Diabetic ketoacidosis (Respiratory compensation to remove carbon dioxide)
Why does cachexia occur in T1DM?
Catabolic catabolism increases to provide alternative substrate including amino acids gluconeogenesis and ketone body formation.
What is the fate of non-esterified fatty acids in a hyperglycaemic state?
Non-esterified fatty acids undergo beta-oxidation resulting in the production of fatty Acyl-CoA.
• Carnitine shuttle facilitates the transport of fatty acids through the mitochondrial membrane.
• Insulin exerts an inhibitory effect on the shuttle –> Downregulates ketone body formation.
• Glucagon potentiates the rate at which fatty-acyl-CoA undergoes ketogenesis to synthesise ketone bodies.
What are the treatment aims for a patient with T1DM?
Insulin dependent for life (Patients with T1DM) + dietary support.
Aim:
• Maintain glucose levels without excessive hypoglycaemia
• Restore a close to physiological insulin profile
• Prevent acute metabolic decompensation
• Prevent microvascular and macrovascular complications.
What are the three chronic microvascular complications with T1DM?
- Retinopathy
- Neuropathy
- Nephropathy
What are the three macrovascular complications with T1DM?
- Ischaemic heart disease
- Cerebrovascular disease
- Peripheral vascular disease
What is first phase insulin release?
Prandial peak of significant exocrine release of preformed insulin into circulation
How many phases are associated with prandial insulin release?
First phase insulin release and second phase (2)
What is the second insulin release phase associated with?
Second phase is dependent on pancreatic B-cell function
What are the two forms of quick acting insulin?
Human insulin
insulin analogue
What are the two forms of long-acting basal insulin?
Bound to zinc or protamine
Insulin analogue
What is the typical basal bolus regime?
Injected 15 minutes pre-prandially short acting
What is insulin pump therapy?
- Continuous delivery of short-acting insulin analogue e.g: Novorapid via pump.
- Delivery of insulin into subcutaneous space
- Programme the device to deliver fixed units/hour throughout the day (basal)
- Actively bolus for meals.
What is the available dietary advice for diabetes?
Dose adjustment for carbohydrate content of food.
• Patients receive training for carbohydrate counting.
• Substitute refined carbohydrate containing goods (high glycaemic index) with complex carbohydrates (starchy/low glycaemic index).
NICE Guidelines (NG17) for type I diabetes
• Structured Education Programme
• DAFNE
• 5-day course on skills and training in self-management.
Why are starch and complex carbohydrates a better substitute than refined carbohydrates?
Complex carbohydrates have a low glycemic index
What is the aim for simultaneous pancreas and kidney transplant?
Aim: Restore physiological insulin production to the extent that administered insulin can stop.
• Incomplete –> Results in better control.
What are the limitations with a pancreas and kidney transplant?
Limitations: Availability of donors, complications of life-long immunosuppression
What is glycated haemoglobin?
- HbA1c represents 3 months of glycaemia (red blood lifespan).
- Biased to the 30 days preceding measurement
Which amino acid terminal is glucose associated with in HbA1C?
Glycated not glycosylated (enzymatic) Glucose is associated with the N-terminal valine residue of the B-chain.
• Linear relationship
• Irreversible reaction
What are the four limitations to using HbA1c as a marker?
- Erythropoiesis
Increased HbA1c: Iron, vitamin B12 deficiency, decreased erythropoiesis
Decreased HbA1c: Administration of erythropoietin, iron, vitamin B12, reticulocytosis, chronic liver disease.
- Altered Haemoglobin
Genetic or chemical alterations in haemoglobin: Haemoglobinopathies, HbF, methaemoglobin, may increase or decrease HbA1c. - Glycation
Increased HbA1c: Alcoholism, chronic renal failure, decreased intra-electrolyte pH
Decreased HbA1c: Aspirin, Vitamin C and E, certain haemoglobinopathies, increased intra-erythrocyte pH.
Variable HbA1c: Genetic determinants.
- Erythrocyte destruction
Increased HbA1c: Increased erythrocyte lifespan: Splenectomy
Decreased HbA1c: Decreased erythrocyte lifespan: Haemoglobinopathies, splenomegaly, rheumatoid arthritis or drugs such as antiretrovirals, ribavirin and dapsone.
What is the diagnosis for diabetic ketoacidosis?
Diabetic ketoacidosis diagnosis
• pH <7.3, ketones increased (urine of capillary blood)
• HCO3- <15mmol/L and glucose >11mmol/L.
What is the risk of type 1 diabetes?
Complications
1) Diabetic ketoacidosis
2) Uncontrolled hyperglycaemia
3) Hypoglycaemia
What is the diagnostic parameter for hypoglycaemia?
<3.6mmol/L Hypoglycaemia
What are the risks of hypoglycaemia?
Hypoglycaemia problems • Excessive frequency • Impaired awareness (unable to detect low blood glucose) • Nocturnal hypoglycaemia • Recurrent severe hypoglycaemia
- Seizure/coma/death
- Impacts on emotional well-being
- Impacts on driving
- Impacts on day-to-day function
- Impacts on cognition
What are the risk factors for hypoglycaemia?
Risk factors • Exercise • Missed meals • Inappropriate insulin regime • Alcohol intake • Lower HbA1c • Lack of training around dose-adjustment for meals
