Type 1 Diabetes Mellitus

Question 1

Define diabetes mellitus [1]

Answer 1

A metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, protein and fat metabolism resulting from defects in insulin secretion, insulin action, or both

Question 2

The glucose tolerance test (GTT) is an important diagnostic test for diabetes. What are fasting glucose and post-2hrs values correspond to:

1. normal [2]
2. impaired glucose tolerance (IGT) [2]
3. diabetes [2]

Answer 2

1. normal:
   
   • fasting glucose < 7.0
   • post-2hrs < 7.8
2. impaired glucose tolerance (IGT):
   
   • fasting glucose < 7
   • post-2hrs 7.8-11.0
3. diabetes:
   
   • fasting glucose ≥7
   • post-2hrs ≥ 11.1

Question 3

Describe the WHO criteria for diagnosing diabetes [7]

Answer 3

1. Fasting plasma glucose of ≥7.0mmol/L
2. Random plasma glucose of ≥11.1mmol/L
3. 1 abnormal value diagnostic if symptomatic
4. 2 abnormal values diagnostic if asymptomatic
5. HbA1c 6.5% or 48mmol/mol (pitfalls)
6. Diabetes should not be diagnosed on the basis of glycosuria or a BM stick
7. OGTT (oral glucose tolerance test) only required for diagnosis if IFG (impaired fasting glycemia) or GDM (gestational diabetes mellitus)

Question 4

Name the 3 other diagnostic aids for diabetes (other than GTT) [3]

Answer 4

1. Ketone testing +/- bicarbonate
2. Pancreatic auto-antibodies
3. C-peptide testing

Question 5

What are the figures in ketone testing that indicate:

1. normal levels?
2. caution?
3. high risk of ketoacidosis?

Answer 5

1. Normal: <0.6mmol/l
2. Caution: 0.6-1.5mmol/l
3. High risk of ketoacidosis: >1.5mmol/l

Question 6

What are islet autoantibodies and what is the most common type that is checked? [2]

Answer 6

1. Markers of autoimmune process associated with T1DM
2. anti-GAD is most common checked

Question 7

What is C-peptide and how can it be used to diagnose diabetes? [3]

Answer 7

1. Secreted in equimolar concentrations to insulin
2. Useful marker of endogenous insulin secretion
3. Can be measured in blood or urine
   
   • (urine C-peptide/creatinine ratio)

Question 8

Describe the pathogenesis of Type 1 diabetes [3]

• hints:
  
  • definition? [1]
  • pathological cause? [1]
  • who gets it? [1]

Answer 8

1. Chronic, progressive metabolic disorder characterised by hyperglycaemia and the absence of insulin secretion
2. Type 1 diabetes results from autoimmune destruction of the insulin-producing beta cells in the islets of Langerhans
3. Occurs in genetically susceptible subjects and is probably triggered by one or more environmental agents

Question 9

Describe the progression of T1DM [7]

Answer 9

1. Genetic risk
2. Immune activation
   
   • Beta cells are attacked
3. Immune response
   
   • Development of 1 autoantibody
4. Stage 1:
   
   • Normal blood sugar with ≥ 2 autoantibodies
5. Stage 2:
   
   • Abnormal blood sugar with ≥ 2 autoantibodies
6. Stage 3
   
   • Clinical diagnosis with ≥ 2 autoantibodies
7. Stage 4
   
   • Long-standing T1DM

Question 10

What are the factors that could potentially increase your risk of developing T1DM? [7]

Answer 10

1. Viral infections, particularly enterovirus infections
2. Immunisations
3. Diet, especially exposure to cow’s milk at an early age
4. Higher socioeconomic status
5. Obesity
6. Vitamin D deficiency
7. Perinatal factors such as:
   
   • maternal age,
   • history of preeclampsia,
   • neonatal jaundice
   • low birth weight (reduced risk)

Question 11

Describe the pathogenesis of Type 2 diabetes? [3]

• hints:
  
  • definition? [1]
  • who more commonly gets it? [1]
  • potential cause? [1]

Answer 11

1. Chronic, progressive metabolic disorder characterised by hyperglycaemia, insulin resistance and relative impairment of insulin deficiency
2. Common with a prevalence that rises markedly with increasing levels of obesity
3. Most likely arises through a complex interaction among many genes and environmental factors

Question 12

Fill in the following table on the features of Type 1 diabetes vs. Type 2 diabetes [20]

Answer 12

Question 13

How is type 1 diabetes managed? [4]

Answer 13

1. Insulin replacement
2. Glucose/Ketone monitoring
3. CHO counting/Structured education
4. Supported self management

Question 14

What are the typical glucose targets for a patient with good management of their type 1 diabetes? [5]

• hints:
  
  • HbA1c?
  • glucose levels:
    
    • before breakfast?
    • before other meals?
    • before bed?
  • glucose rise aim 2hrs post bolus?

Answer 14

1. HbA1c <53mmol/I
2. Before breakfast: 5.5 - 7mmoI/l
3. Before other meals: 4.5 - 7.5mmoI/I
4. Before bed: 6.5 - 8mmol/I
5. Aim for glucose to rise <2mmoI/l 2hrs post bolus

Question 15

What must a patient recently diagnosed with type 1 diabetes be educated on? [9]

Answer 15

1. Administration of Insulin
2. Glucose/Ketone Monitoring
3. Sick Day Rules
4. Hypoglycaemia
5. Driving Regulations
6. Exercise & Alcohol
7. Pregnancy
8. Targets
9. Complications

Question 16

Describe the genetic basis of maturity-onset diabetes of the young (MODY) [2]

Answer 16

1. Caused by change in a single gene (monogenic).
2. Autosomal dominant (50% chance of inheriting)

Question 17

What are the main features of MODY? [7]

• hints:
  
  • who gets it?
  • C-peptide low or high?
  • pancreatic antibiotics positive or negative?
  • genetics?
  • how is it managed? [3]

Answer 17

1. Often <25yrs onset
2. C peptide not low
3. Pancreatic antibodies negative
4. Runs in families from one generation to next
5. Managed by diet, OHAs, insulin (not always)

Question 18

What are the main causes of pancreatic diabetes? [5]

Answer 18

1. Pancreatectomy,
2. Pancreatitis,
3. Haemochromatosis (liver disease, cardiomyopathy, pituitary disease),
4. Carcinoma,
5. Cystic fibrosis

Question 19

Why is the risk of hypoglycaemia higher in pancreatic diabetes than in Type 1 diabetes? [1]

Answer 19

due to loss of alpha cells that produce glucagon

Question 20

Describe the main features of pancreatic diabetes [7]

• hints:
  
  • biochemistry? [2]
  • c peptide low or high?
  • pancreatic antibiotics positive or negative?
  • specific diagnostic test?
  • management? [2]

Answer 20

1. May have ketones and be acidotic
2. C peptide low but often detectable
3. Pancreatic antibodies negative
4. May require imaging
5. Managed by SU +/- insulin

Question 21

Name the 3 types of insulin dependent diabetes [3]

Answer 21

1. latent auto-immune diabetes of adulthood
2. early onset type 2 diabetes
3. maturity onset diabetes in the young

Question 22

List the other causes of diabetes under the following headings:

1. genetic defects in… [2]
2. endocrinopathies [3]
3. immunosuppressive agents [3]
4. anti-psychotics [2]
5. genetic syndromes [5]

Answer 22

1. Genetic Defects:
   
   • Genetic defects of beta-cell function
   • Genetic defects in insulin action
2. Endocrinopathies
   
   • Acromegaly
   • Cushing’s
   • Pheochromocytoma
3. Immunosuppressive agents
   
   • Glucocorticoids
   • Tacrolimus
   • Cyclosporin
4. Anti-Psychotics
   
   • Clozapine
   • Olanzapine
5. Genetic syndromes associated with DM
   
   • Down’s Syndrome
   • Friedreich’s Ataxia,
   • Turner’s
   • Myotonic Dystrophy,
   • Klinefelter’s Syndrome