Endo - T1DM Flashcards
What is Type 1 DM?
→ autoimmune condition in which insulin-producing beta-cells in the pancreas are attacked and destroyed by immune system
→ causes partial or complete deficiency of insulin production, which results in hyperglycaemia
→ requires life-long insulin treatment
What does T1DM management depend on?
individual clinical presentation
What are the 2 biggest triggers for T1DM?
→ environmental factor
→ underlying genetic risk
What is LADA?
latent autoimmune diabetes in adults
What are the 5 stages of T1DM development?
→ genetic predisposition to T1DM
→ potential precipitating event
→ overt immunological abnormalities + normal insulin release
→ progressive loss of insulin release but glucose normal
→ over diabetes with C-peptide present
→ no c-peptide present?
What are the various stages of T1DM development in the immune system?
→ genetic risk
→ immune activation (beta cells are attacked)
→ immune response (development of single autoantibody)
→ stage 1 = normal blood sugar
→ stage 2 = abnormal blood sugar
→ stage 3 = clinical diagnosis
→ long-standing T1DM
Why is the immune basis of T1DM important?
→ Increased prevalence of other autoimmune disease
→ Risk of autoimmunity in relatives
→ More complete destruction of B-cells
→ Auto antibodies can be useful clinically
→ Immune modulation offers the possibility of novel treatments
How do the autoantibodies start attacking the beta cells?
→ presentation of auto-antigen to autoreactive CD4+ T lymphocytes
→ CD4+ cells activate CD8+ T lymphocytes
→ CD8+ cells travel to islets and lyse beta-cells expressing auto-antigen
→ Exacerbated by release of pro-inflammatory cytokines
→ Underpinned also, by defects in regulatory T-cells that fail to suppress autoimmunity
Do all T1DM patients eventually not produce insulin at all?
→ no, some continue to produce small amounts of insulin
→ not enough to negate the need for insulin therapy
What are the positives of the people with T1DM who can still produce small amounts of insulin?
less complications compared to those who can’t produce some insulin
What are the environmental factors that can also influence T1DM?
→ Enteroviral infections
→ Cow’s milk protein exposure
→ Seasonal variation
→ Changes in microbiota
How does T1DM present?
→ Excessive urination (polyuria) → Nocturia → Excessive thirst (polydipsia) → Blurring of vision → Recurrent infections eg thrush → Weight loss → Fatigue → dehydration → cachexia (weight + muscle loss) → hyperventilation → smell of ketones → glycosuria → ketonuria
What are the auto-antibodies detectable in T1DM?
→ pancreatic auto-antibodies
→ not generally needed for diagnosis
• Insulin antibodies (IAA)
• Glutamic acid decarboxylase (GADA) – widespread
neurotransmitter
• Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc-
transporter 8 (ZnT8)
What are the proteins in beta cells that act as receptors to the pancreatic AAs?
What are the metabolic results of insulin deficiency?
→ proteinolysis in muscles = AAs
→ hepatic glucose output increases from liver = glucose in blood
→ lipolysis of adiposes = glycogen + NEFAs
What causes the production of ketone bodies? What does that progress to?
→ lack of insulin = no inhibition of fatty acyl-CoA
→ ketone bodies produced in liver
→ progresses to diabetic ketoacidosis
Why does T1DM cause blurred vision?
antibodies bind to eyeballs, osmosis causes water to move into eyeball, swelling eyeballs and impinging on the lenses
What is a closed-loop pump / artificial pancreas?
→ Real-time continuous glucose sensor
→ Change in glucose calculated
→ Algorithm to use glucose value to calculate insulin requirement
→ Insulin pump delivers calculated insulin
What are the 2 types of transplantation?
What is an islet cell transplant?
What is simulatneous pancreas + kidney transplants?i
What are the disadvantages of transplantations?
What are the signs and symptoms of hypoglycaemic episodes?
How can hypoglycaemia be acutely managed?
