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Phase 1b - Endocrinology > Type 1 Diabetes Mellitus > Flashcards

Type 1 Diabetes Mellitus Flashcards

-> Endocrine disorders: the pathology and pathophysiology of endocrine disorders. -> Endocrine disorders: Describe the clinical features and treatment options of endocrine disorders.

1
Q

What is T1DM?

A
  • An autoimmune condition in which pancreatic beta-cells of the Islets of Langerhans are dysfunctional
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2
Q

What is LADA?

A
  • Latent autoimmune diabetes in adults: Autoimmune diabetes leading to insulin deficiency that presents later in life
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3
Q

What are the environmental risk factors implicated in T1DM (4)?

A
  • Enteroviral infections
  • Cow’s milk protein exposure
  • Seasonal variation
  • Changes in microbiota
  • Environmental (possibly viral) variation
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4
Q

Which allele identified in Genome wide association (GWAS) is implicated in T1DM?

A
  • HLA-DR allele

Human leukocyte antigen (HLA)

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5
Q

What are the stages of development of T1DM (4)?

A
  1. Genetic Risk
  2. Immune activation
  3. Immune response
  4. Type 1 Diabetes Mellitus
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6
Q

What is the relationship between pancreatic B-cell function and age in those with a genetic predisposition to T1DM?

A
  • The number of pancreatic beta-cells progressively decrease with age, resulting in a decline in insulin output and glucose control
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7
Q

What is C-peptide used for?

A
  • Used as a marker of insulin concentrations and beta-cell function
    • ​C-peptide is the cleavage product of pro-insulin
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8
Q

What is the cleavage product of pro-insulin?

A
  • C-peptide
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9
Q

What is the pathoimmunology underlying T1DM (4 steps)?

A
  1. Presentation of auto-antigens to autoreactive CD4+ T-lymphocyte by antigen-presenting cells
  2. CD4+ cells activate CD8+ T lymphocytes
  3. CD8+ cells travel to islets and lyse beta cells expressing autoantigen (travel via lymph nodes)
  4. Release of pro-inflammatory species and reactive oxygen species
    • Granzyme and perforin are released from cytotoxic granules
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10
Q

Defects in which type of tolerance is evident in T1DM pathoimmunology?

A
  • Peripheral tolerance (Impaired regulatory T-cells)
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11
Q

What are the common pancreatic auto-antibodies involved in T1DM (4)?

A
  • Glutamic acid decarboxylase (GADA) – widespread neurotransmitter
  • Insulin antibodies (IAA)
  • Insulinoma-associated-2 autoantibodies (IA-2A)
  • Zinc transporter 8 (ZnT8)
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12
Q

What is the clinical presentation of T1DM (6)?

A
  • 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
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13
Q

What are the clinical signs of T1DM (6)?

A
  • 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
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14
Q

Which metabolic feature is characteristic of T1DM?

A
  • Diabetic ketoacidosis
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15
Q

Why does hyperventilation occur in T1DM?

A
  • Diabetic ketoacidosis (Respiratory compensation to remove carbon dioxide)
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16
Q

Why does cachexia occur in T1DM?

A
  • Catabolic catabolism increases to provide alternative substrate including amino acids gluconeogenesis & ketone body formation
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17
Q

How is T1DM diagnosed?

A

Diagnosis is based on clinical features and presence of ketones (in some cases pancreatic autoantibodies / C-peptide may be measured)

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18
Q

What are the effects of insulin deficiency (4)?

A
  • Increased production of amino acids
  • Increased release of glucose
  • Increased glycerol
  • Increased non-esterified fatty acid -> Increased ketones
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19
Q

What is the fate of non-esterified fatty acids in a hyperglycaemic state?

A
  • 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
20
Q

What are the treatment aims for a patient with T1DM (4)?

A
  • Maintain glucose levels without excessive hypoglycaemia
  • Restore a close to physiological insulin profile
  • Prevent acute metabolic decompensation
  • Prevent microvascular & macrovascular complications
21
Q

What is the long-term treatment for partial or complete insulin production in T1DM?

A
  • Chronic insulin treatment
22
Q

How many phases are associated with prandial insulin release?

A
  • 2
23
Q

What is first phase insulin release?

A
  • Prandial (around food intake time) peak of significant exocrine release of preformed insulin into circulation
24
Q

What is the second phase insulin release?

A
  • Second phase is dependent on pancreatic B-cell function and amount of food consumed
25
Q

What are the 2 forms of insulin?

A
  • Short / quick-acting insulin (with meals)
  • Long-acting / basal (background)
26
Q

What is the typical basal bolus regime?

A
  • TDS (three times/day) short-acting
  • Once daily long-acting
27
Q

What are the 2 forms of quick acting insulin?

A
  • Human insulin (Actrapid)
  • Insulin analogue (Lispro / Aspart / Glulisine)
28
Q

What are the 2 forms of long-acting basal insulin?

A
  • Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH)
  • Insulin analogue (Glargine / Determir / Deyludec)
29
Q

What is insulin pump therapy?

A
  • 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
30
Q

What is an artificial pancreas?

A

Many advances in this field – some closed loop systems developed. Hybrid closed loop systems available on the NHS

31
Q

What are the two forms of transplantation used to treat T1DM?

A
  • Islet cell transplants
    • Isolate human islets from pancreas of deceased donor
    • Transplant into hepatic portal vein
    • Requires life-long immunosuppression
  • Simultaneous pancreas and kidney transplants
    • Better survival of pancreas graft when transplanted with kidneys
    • Requires life-long immunosuppression
32
Q

What is the aim of transplantation for treatment of T1DM?

A
  • Restore physiological insulin production to the extent that administered insulin can stop
    • Incomplete → Results in better control
33
Q

What are the limitations with transplantation for treatment of T1DM (2)?

A
  • Availability of donors
  • Complications of life-long immunosuppression
34
Q

What is the available dietary advice for diabetes?

A
  • 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)
35
Q

Why are starch and complex carbohydrates a better substitute than refined carbohydrates?

A
  • Complex carbohydrates have a low glycemic index
36
Q

How can a T1DM patient monitor glucose levels?

A
  • Capillary (finger prick) blood glucose monitoring
  • Continuous glucose monitoring (restricted availability, NICE guidelines)
37
Q

What is glycated haemoglobin (HbA1c)?

A
  • HbA1c represents 3 months of glycaemia (red blood lifespan)
    • Biased to the 30 days preceding measurement
38
Q

Which amino acid terminal is glucose associated with in HbA1C?

A
  • Associated with the N-terminal valine residue of the B-chain
    • Linear relationship
    • Irreversible reaction
39
Q

What are the 4 limitations to using HbA1c as a marker?

A
  • Erythropoiesis
    • Increased HbA1c:
      • Iron
      • Vitamin B12 deficiency
      • Decreased erythropoiesis
    • Decreased HbA1c:
      • Administration of erythropoietin / iron / vitamin B12
      • Reticulocytosis
      • Chronic liver disease
  • Altered Haemoglobin
    • Variable HbA1c:
      • Genetic or chemical alterations in haemoglobin:
        • Haemoglobinopathies
        • HbF
        • Methaemoglobin
  • 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
      • Drugs such as antiretrovirals, ribavirin and dapsone
40
Q

What are the acute complications of T1DM?

A
  • Diabetic ketoacidosis
  • Uncontrolled hyperglycaemia
  • Hypoglycaemia
41
Q

How is diabetic ketoacidosis diagnosed (4)?

A
  • pH < 7.3
  • Ketones increased (urine or capillary blood)
  • HCO3- < 15 mmol/L
  • Glucose > 11 mmol/L
42
Q

How is hypoglycaemia diagnosed?

A

Blood glucose < 3.6 mmol

43
Q

What are the risk of hypoglycaemia (5)?

A
  • Seizure / coma / death (dead in bed)
  • Impacts on emotional well-being
  • Impacts on driving
  • Impacts on day-to-day function
  • Impacts on cognition
44
Q

What are the risk factors of hypoglycaemia (5)?

A
  • Exercise
  • Missed meals
  • Inappropriate insulin regime
  • Alcohol intake
  • Lower HbA1c
45
Q

What is problematic hypoglycaemia (4)?

A
  • Excessive frequency
  • Impaired awareness (unable to detect low blood glucose)
  • Nocturnal hypoglycaemia
  • Recurrent severe hypoglycaemia
46
Q

What are the strategies to support problematic hypoglycaemia (5)?

A
  • Indication for insulin-pump therapy (CSII)
  • May try different insulin analogues
  • Revisit carbohydrate counting / structured education
  • Behavioral psychology support
  • Transplantation
47
Q

What is the acute management of hypoglycaemia?

Different at:
* Alert & Orientated
* Drowsy / confused but swallow intact
* Unconscious or concerned about swallow

A

Phase 1b - Endocrinology (19 decks)

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