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Endocrinology 2 > Type 1 Diabetes Mellitus > Flashcards

Type 1 Diabetes Mellitus Flashcards

1
Q

Define T1 DM

A

Autoimmune condition in which insulin-producing beta cells attacked and destroyed by immune system resulting in partial/complete deficiency of insulin causing hyperglycaemia. This requires life-long insulin treatment.

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2
Q

What is the overlap in diabetes classification?

A
  1. Autoimmune diabetes leading to insulin deficiency can present later in life = latent autoimmune diabetes in adults (LADA)
  2. T2DM may present in childhood
  3. Diabetic ketoacidosis can be a feature of T2DM
  4. Monogenic diabetes can present phenotypically as Type 1 or Type 2 diabetes (eg. MODY, mitochondrial diabetes)
  5. Diabetes may present following pancreatic damage or other endocrine disease
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3
Q

What are the stages of development of T1 DM?

A

Patient may have a genetic predisposition. A potential precipitating event occurs. Followed by overt immunological abnormalities but normal insulin release. Progressive loss of insulin release occurs but glucose is normal. Overt diabetes occurs but C-peptide present (usually stage at which detected). Finally no C-peptide present as endogenous insulin no longer produced.

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4
Q

Quantify stages of T1 DM development

A
  1. Genetic risk - 15x higher in those with relatives who have disease
  2. Immune activation - beta cells attacked
  3. Immune response - development of single autoantibody
  4. Stage 1 - normal blood sugar >2 autoantibodies
  5. Stage 2 - abnormal blood sugar >”
  6. Stage 3 - Clinical diagnosis
  7. Long standing T1D
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5
Q

Why is the immune basis of T1D important?

A
  • Indicates increased prevalence of other autoimmune conditions
  • Risk of autoimmunity in relatives
  • More complete destruction of B-cells
  • Autoantibodies can be clinically useful
  • Immune modulation offers possibility of novel treatment
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6
Q

Describe immune response in T1DM

A
  1. Auto-antigen presented to autoreactive CD4+ T lymphocytes
  2. CD4+ activates CD8+
  3. CD8+ travels to islets and lyse beta cells expressing auto-antigen
  4. Exacerbated by release of pro-inflammatory cytokines
  5. Defects in regulatory immune system fail to suppress autoimmunity
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7
Q

What alleles indicate genetic susceptibility?

A

Certain HLA-DR alleles increase risk - DR2,6 and 8 have protective effects while DR3+4 have significant risk. 7 and 9 hold risk to those of african descent and asian respectively.

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8
Q

What environmental factors can precipitate T1 DM?

A

Causality has not yet been established. Enteroviral infections, cow’s milk protein exposure, seasonal variation and changes in microbiota can play a role.

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9
Q

What auto-antibodies can be detected in the pancrease indicating T1 DM?

A

Detectable in the sera of people with T1 diabetes but not generally needed for diagnosis:

  1. Insulin antibodies (IAA)
  2. Anti-glutamic acid decarboxylase (GAD) - enzyme that converts glutamic acid to GABA
  3. Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc-transporter 8 (ZnT8)
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10
Q

What are symptoms of T1DM?

A

Polyuria, nocturia, polydipsia, blurring of vision, recurrent infections (thrush), weight loss, fatigue

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11
Q

What are signs of T1 DM?

A

Dehydration, Cachexia, Hyperventilation, Smell of ketones, glycosuria, ketonuria

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12
Q

What is T1 DM diagnosis based on?

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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13
Q

What are the effects of insulin deficiency?

A
  1. Proteinolysis - amino acids released
  2. Increased hepatic glucose output
  3. Lipolysis - Glycerol and NEFAs produced
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14
Q

How are ketone bodies produced?

A

No negative feedback from insulin. Lack of glucose means acetyl CoA formed from fatty acids cannot enter Krebs Cycle so end up forming ketone bodies.

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15
Q

What are the 4 aims of treatment in T1 DM?

A
  1. Maintain glucose levels without excessive hypoglycaemia
  2. Restore a close to physiological insulin profile
  3. Prevent acute metabolic decompensation
  4. Prevent microvascular and macrovascular complications
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16
Q

How is T1 DM managed?

A

Insulin Treatment
Dietary support / structured educations
Technology
Transplantation

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17
Q

Draw physiological insulin profile

A

Prandial peak has 2 phases and insulin never fully suppressed - a flat baseline level of insulin exists

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18
Q

What are the types of available insulin?

A 
1. Short acting insulin (post meals) - Human insulin: exact molecular replicate of human insulin (actrapid) or
Insulin analogue (Lispro, Aspart, Glulisine) 
2. Long-acting/Basal (baseline) - Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH) or
Insulin analogue (Glargine, Determir, Degludec)
19
Q

What is a typical basal bolus regime?

A

Once daily long-acting insulin given and 3 times a day short acting post meals. However, single peak achieved rather than post-prandial peak which is not present. Long-acting also doesn’t remain flat but is a curve.

20
Q

How does insulin pump therapy work?

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

21
Q

What can be derived from a insulin pump profile?

A

Variable basal rates
Extended boluses
Greater flexibility

22
Q

What 3 principles guide dietary advice for those with T1 DM?

A
  1. Dose adjustment for carbohydrate content of food.
  2. All people with type 1 diabetes should receive training for carbohydrate counting
  3. Where possible, substitute refined carbohydrate containing foods (sugary / high glycaemic index) with complex carbohydrates (starchy / low glycaemic index)
23
Q

What are NICE guidelines for T1 DM?

A

All people with type 1 diabetes should be offered a Structured Education Programme e.g. DAFNE but many others. 5 day course on skills and training in self-management.

24
Q

How do closed loop systems work?

A

A real-time continuous sensor monitors glucose levels and if there is a change, algorithm used to calculate insulin requirement and pump delivers this amount of insulin.

25
Q

What are the types of transplantation available?

A
  1. Islet cell transplant - Isolate human islets from pancreas of deceased donor. Transplant into hepatic portal vein. Requires life-long immunosuppression.
  2. Simultaneous pancreas and kidney transplants - Better survival of pancreas graft when transplanted with kidneys. Requires life-long immunosuppression.
26
Q

What are the aims of transplantation as well as limitations

A

Aim: try to restore physiological insulin production to the extent that insulin can be stopped. Even if incomplete, often results in better control.
Limitations: availability of donors, complications of life-long immunosuppression

27
Q

What are 2 methods of glucose level monitoring?

A
  1. Capillary blood glucose - finger prick

2. Continuous glucose monitoring (restricted availability, NICE guidelines)

28
Q

What is HbA1C?

A

When glucose is added to N-terminal valine residue on the beta chain this forms Schiff base. This reaction is reversible and fast, happening in a matter of hours. However, if glucose high, forward reaction greater and so more Schiff base made. Schiff base is converted into HbA1c also known as Amadori product in an irreversible reaction over a matter of days.

29
Q

What 4 factors can skew HbA1c making it unreliable?

A

Erthyropoeisis, altered haemoglobin, glycation and erythrocyte destruction.

30
Q

How does erythropoeisis affect HbA1c?

A

Increased HbA1c seen when there is an iron, vitamin B12 deficiency or reduced erythropoeisis. Decreased HbA1c seen when erythropoeitin, iron or vit B12 administered, in case of reticulocytosis or chronic liver disease.

31
Q

How does altered haemoglobin affect HbA1c?

A

Any genetic or chemical alterations in haemoglobin e.g. haemoglobinopathies, HbF, methaemoglobin, may increase or decrease HbA1c.

32
Q

When impacts glycation of HbA1c?

A

Increased HbA1c: alcoholism, chronic renal failure, decreased intra-erythrocyte pH
Decreased: aspirin, vitamin C and E, certain haemoglobinopathies, increased intra-erythrocyte pH
Variable HbA1c: genetic determinants

33
Q

How does erythrocyte destruction impact HbA1c?

A

Increased HbA1c: increased erythrocyte lifespan due to splenectomy
Decreased: decreased erythrocyte lifespan due to haemoglobinopathies, splenomegaly, rheumatoid arthritis, drugs (antiretrovirals, ribavirin, dapsone)

34
Q

What is used to guide insulin doses?

A

Using self-monitoring of blood glucose results at home and HbA1c results every 3-4 months. Based on results, increase or decrease insulin doses.

35
Q

What are acute complications from type 1 diabetes?

A
  1. Diabetic ketoacidosis
  2. Uncontrolled hyperglycaemia
  3. Hypoglycaemia
36
Q

How is diabetic ketoacidosis diagnosed?

A

pH <7.3, ketones increased (urine or capillary blood), HCO3- <15 mmol/L and glucose >11 mmol/L

37
Q

When can a patient present with diabetic ketoacidosis?

A

Can be a presenting feature of new-onset type 1 diabetes
Occurs in those with established type 1 diabetes due to: Acute illness, Missed insulin doses or Inadequate insulin doses
Can occur in any type of diabetes

38
Q

How is hypoglycaemia defined?

A

Numerical definition (variable) <3.6 mmol/L. Severe hypoglycaemia: any event requiring 3rd party assistance.

39
Q

What are adrenergic and neuroglycopaenic symptoms of hypoglycaemia?

A

Adrenergic symptoms: Tremors, Palpitations, Sweating, Hunger
Neuroglycopaenic: Somnolence, Confusion, Incoordination, Seizures and Coma

40
Q

When does hypoglycaemia become a problem?

A
  1. Excessive frequency
  2. Impaired awareness (unable to detect low blood glucose)
  3. Nocturnal hypoglycaemia
  4. Recurrent severe hypoglycaemia
41
Q

What are the risks of hypoglycaemia?

A
  1. Seizure / coma/ death (dead in bed)
  2. Impacts on emotional well-being
  3. Impacts on driving
  4. Impacts on day to day function
  5. Impacts on cognition
42
Q

What are risk factors for hypoglycaemia?

A 
Risk factors:
Exercise
Missed meals
Inappropriate insulin regime
Alcohol intake
Lower HbA1c
Lack of training around dose-adjustment for meals
43
Q

What are management strategies for hypoglycaemia depending on awareness of patient?

A

Awake: oral carbohydrate, rapid acting glucose (juice, sweets) or longer acting (sandwich)
Drowsy: buccal glucose, complex carbohydrate
Unconscious: IV glucose
Deteriorating / refractory /insulin induced /difficult IV access: consider IM /SC 1mg Glucagon

Endocrinology 2 (11 decks)

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