Type 1 diabetes - pathophysiology and clinical features

Question 1

Define T1DM

Answer 1

A state of absolute insulin deficiency (pancreas produces little or no insulin)

Question 2

How is diabetes in general diagnosed ?

Answer 2

As previously mentioned in other flashcards there are a number of tests which can be done to point towards diabetes diagnosis but following are the main ones used:

• Fasting glucose ≥ 7.0 mmol/L
• Random glucose ≥ 11.1 mmol/L
• And symptoms, OR repeat tests to diagnose

Question 3

How is T1DM specifically diagnosed after initally diagnosing diabetes in general ?

Answer 3

Often T1DM is diagnosed on history and presentation

• If in doubt check for GAD/IA2 antibodies - these would be positive

(C-peptide can sometimes still be positive so not relied on but this is usually negative

Question 4

What is HLA ?

Answer 4

It is human leukocyte antigen which is a protein or marker found on most of the cells in your body

Question 5

What are the genotypes associated with T1DM?

Answer 5

HLA-DR3 and HLA-DR4

95% of patients with T1DM have one or both of these genotypes

Question 6

What are the autoantibodies associated with T1DM ?

Answer 6

• Anti-GAD
• IA2 antibodies
• IAA
• ZnT8

Question 7

Define gluconeogenesis

Answer 7

Metabolic pathway that results in generation of glucose from non-carb substrates

Question 8

Define glycogenolysis

Answer 8

Biochemical breakdown of glycogen to glucose (glycogenesis is the opposite)

Question 9

Define ketogenesis

Answer 9

Biochemical breakdown of fatty acids and ketogenic amino acids to produce ketone bodies

Question 10

Describe the pathogenesis of T1DM

Answer 10

• Develops as a result of auto-immune destruction of pancreatic β-cells in the islets of langerhans
• β-cell destruction proceeds sub-clinically for months to years as insulitis (inflammotion of β-cells)
• When 80-90% of β-cells are destroyed hyperglycaemia develops due to insulin deficiency (unable to utilise glucose in peripheral or adipose tissues now)
• This stimulates the secretion of counter regulatory hormones such as glucagon, adrenaline, cortisol & growth hormone
• These hormones esp. glucagon promote gluconeogenesis, glycogenolysis and ketogenesis in the liver
• As a result patients present with hyperglycaemia and metabolic acidosis

Question 11

What does long-term hyperglycaemia lead to ?

Answer 11

Micro and macrovascular complications

Question 12

What are the typical presenting symptoms of T1DM ?

Answer 12

• Polyuria
• Polydipsia (thirst)
• Weight loss
• Fatigue
• Blurred vision
• Candidal infections - e.g. Puritis vulvae (itchiness of the vulva (area just outside the vagina)), Balanitis (inflammation of the head of the penis)
• DKA
• Increased appetite

Question 13

What is the standard management of T1DM ?

Answer 13

• Blood glucose and ketone monitoring
• Regular check of glycaemic control using HBA1c
• Insulin regime - usually basal bolus

Question 14

When doing an annual review of a diabetic patient what things would you check to check for any complications/risk of complications developing ?

Answer 14

• Weight
• BP
• Bloods (HBA1c, renal function & lipids)
• Retinal screening
• Foot risk assessment

Question 15

What condition is strongly associated with the development of diabetes ?

Answer 15

Cystic fibrosis

Question 16

Go over the clinical features of different types of diabetes

Answer 16

Question 17

Go over the table comparing the differences between Type 1 and Type 2 diabetes

Answer 17

Question 18

Children diagnosed under the age of 6 months are most likely to have what type of diabetes ?

Answer 18

Neonatal diabetes (Monogenic diabetes) rather than e.g. T1DM

Question 19

When should you suspect LADA ?

Answer 19

• Occurs in young adults 25-40
• More common in males
• Usually non-obese
• Auto-immune positive
• Patient has associated auto-immune conditions
• Non-insulin requiring at diagnosis (although its a type 1)
• Patient may be put on type 2 treatment but achieves sub-optimal control which could point towards LADA

Question 20

what screening test is recommened for patients with CF ?

Answer 20

OGTT

Question 21

What is the preferred managemeant of diabetes in patients with CF?

Answer 21

Insulin

Question 22

Go over and compare the features of the different types of diabetes

Answer 22

Question 23

What is DIDMOAD or wolfram syndrome ?

Answer 23

Is a rare autosomal recessive condition that causes the following features:

• Diabetes Insipidus
• Diabetes mellitus
• Optic atrophy
• Deafness
• Neurological anomalies

Question 24

What is Bardet- Biedl syndrome ?

Answer 24

A disorder which is associated with kids born from insecest:

They are often:

• Very obese
• Have polydactyly
• Hypogonadal
• Have visual and hearing impairment
• Mental retardation
• Diabetes

Question 25

What are the relatively common auto-immune conditions associated with diabetes ?

Answer 25

• Thyroid disease
• Coeliacs
• Pernicious anaemia
• Addisons disease
• IgA deficiency