T1 Diabetes mellitus

Question 1

Discuss the epidemiology of T1DM

Answer 1

Prevalence: 0.5%
Peak onset at adolescence
M=F
White caucasian (more prevalent in northern latitudes)
Seasonal variability

Question 2

Describe the genetic predisposition

Consider HLA and GRS2

Answer 2

0.5% background risk

1-2% if mother affected; 3-6% if father
6% if siblings –> 36% if monozygotic twin

Associated with HLA antigens (HLA DR3-DQ2 & DR4 DQ8 predispose)
- Accounts for 90% of scandinavians with T1DM (have both)

GRS2 discriminates those with T1 and T2 DM. T1> 82.7% (T2 < 87.8%)- SOME OVERLAP

Question 3

Describe the pathophysiology of T1DM

Answer 3

There might be environmental trigger: ER stree? cytokines? virus?

• Lack of understanding arise from difficulty in investigating pancreas

B cell events trigger AI response,antibodies to insulin or GAD generally appear first

• immune destruction is selective
• check or b-cell antibodies e.g. IA2, Zn2+ transfer 8

Question 4

What other diseases is T1DM associated with?

Answer 4

Coeliac disease **
Hypothyroidism
Graves
Addisons
Hypogonadism
Pernicious anaemia
Vitiligo
AI polyglandular syndromes

Question 5

State 5 common symptoms of T1DM

Answer 5

• Lethargy
• Polyuria
• Polydipsia
• Blurred vision
• Weight loss

Question 6

State 2 clinical signs of T1DM

Answer 6

• Recurrent candida infections
• Ketosis/ ketoacidosis (if you cant use glucose in lack of insulin you metabolise other products –> ketone bodies –> low pH blood)

Question 7

CLINICAL APPLICATION

How would you make a diagnosis of T1DM?

How is C peptide relevant?

Answer 7

• FHx > PMHx
• Age of onset
• Rapidity of onset
• Phenotype
• Weight loss
• Ketoacidosis
• GAD/ IA2/ Zince transporter 8 antibody positive
• C peptide

C peptide is produced in 1:1 ration with insulin (from pro-insulin). Need adequate stimulus for secretion

Question 8

Describe how and when insulin is administered

Answer 8

Peptide hormone so needs to given parenterally

• Sc, inhaled, mucous membranes
• Various types (primary structure, human/animal; duration of action, strength) Addition of protamine? Altered solubiity, FA chain?

Injection sites (sc space): lower abdomen, upper outer thighs/arms, buttocks

Administeration follows physiological secretion patterns ([plasma insulin] to spike just after breakfast, lunch and dinner)

Question 9

Which different regimens of insulin administeration are there?

Answer 9

1. Basal bolus regimen
   - rapid acting insulin pr-meal (bolus)
   - long acting background insulin (basal)
2. Balanced regimen

** Rapid activity insulin reflects CHO intake

Question 10

What factors affect [b/g]?

Answer 10

• Diet
• Injection site
• Temperature
• Exercise
• Illness
• Stress
• Alcohol
• Menstrual cycle

Question 11

What is a subcutaneous insulin pump?

Answer 11

Pumps little insulin throughout the day

Question 12

What transplant options are available as treatment for T1DM?

Answer 12

1. Pancreas
   - infrequent (not that many around)
   - requires lifetime immunosuppressants (–> cancers -skin), increases mortality
2. Islet cells
   - use restricted to those with high demand disease

Question 13

CLINICAL APPLICATION

What should be monitored in a T1 diabetic patient

• By the patient
• By the clinician

Answer 13

• Glucose (a minimum of 4x/day)
• CGMS, Hash CGMS
• Ketone monitoring: urine (acetoacetate?), blood (B-hydroxybutyrate)

HbA1c (glycated Hb)

• reflects glucose over 3 months (weighted towards last 6 weeks)
• affected by RBC lifespan