Diabetes

Question 1

Immune cell responsible for T1DM

Answer 1

T cell

Question 2

Metabolic memory refers to

Answer 2

The effect of prior glucose control on risk of diabetes complications

Question 3

Subtypes of T1DM

Answer 3

• Type 1A
  – Immune mediated
  – > 90% of caucasians
• Type 1B
  – Idiopathic
  – Islet autoantibodies negative
  – Rare in Caucasians

~ Monogenic Diabetes
~ LADA

Question 4

What do MODY and LADA stand for?

Answer 4

Maturity-onset diabetes of (in) the young

Latent autoimmune diabetes in adulthood

Question 5

When to suspect MODY?

Answer 5

– 20% if islet antibodies are negative and C-peptide secretion maintained

Not as bad as T1DM

Question 6

monogenic forms of T1aDM

Answer 6

APS (Autoimmune Polyglandular Syndrome) Type 1: AIRE gene mutation
* 20% develop Type 1 diabetes
* Usually also develop Addison’s Disease and Hypoparathyroidism

X-linked polyendocrinopathy, immune dysfunction, and diarrhoea (Scurfy gene) XPID
–Mutation of FoxP3 - important for regulatory T cell function

Question 7

Adult vs child T1DM presentation

Answer 7

Adults:
– Slower onset of disease
– Less likely to present with DKA
– GAD65 antibodies more frequent,
- Not as high levels of insulin autoantibodies

Question 8

LADA vs classic T1aDM

Answer 8

• Have the same HLA alleles as that of Type 1A
• Much slower rate of beta cell decline
• less likely to have DKA at presentation

Question 9

Risk of T1DM in monozygotic twin

Answer 9

50% concordance (greater the younger age that 1 st twin affected)

Question 10

Main genetic risk for polygenic T1DM?

Answer 10

• Mainly HLA class II molecules HLA DR and DQ regions
  – Highest risk haplotype (DR3/DR4):
• 1st Chromosome (DR3)
  – DRB103:01-DQA105:01-DQB1*02
• 2 nd Chromosome (DR4 – DQ8)
  – DRB104:01/02/04/05/08-DQA103:01-DQB1*03:02/04

Question 11

T1DM Autoantibodies

Answer 11

– Insulin autoantibodies (IAA)

– Glutamic Acid Decarboxylase antibodies (GAD)

– Islet cell tyrosine phosphatase-2 (IA-2)

– Tetraspanin-7

– Zinc Transporter-8 (ZnT8)

Question 12

Test for T1DM if patient already had several years of DM/ therapy?

Answer 12

Beyond 3 years of diagnosis use plasma C-peptide

– >600pmol/L suggest Type 2 diabetes

– Low or absent C-peptide suggests Type 1 diabetes

Question 13

When to suspect Monogenic DM

Answer 13

One or More of:

• Age <35 years
• HBA1c at diagnosis of <58mmol/mol
• One parent with diabetes
• Features of specific monogenic cause:
  – Renal cysts
  – Maternally inherited deafness
  – Severe insulin resistance in the context of normal BMI
• Autoantibody negative
• Non-fasting C-Peptide >200pmol/L

Question 14

Method for Glargine long duration?

Answer 14

• Microprecipitates form at physiologic pH
• Dispersion required for absorption

(Lasts 24 hours but begins to wane at 15 hours)

Question 15

Method for Detemir long duration?

Answer 15

• Binds to albumin in the plasma after absorption

(Action duration: 20 hours)

Question 16

Method for Degludec long duration?

Answer 16

• Forms multihexamers
• Binds to Albumin

(Half life: 25 hours, Duration of action: > 40 hours)

Question 17

What is insulin meal ratio?

Answer 17

ratio of how much CHO one unit of rapidly acting insulin ‘covers’ to keep blood glucose in the optimal range

500/TDD = CHO ratio

Example:
* Patient had TDD of 33 U of insulin. CHO ratio is 500/33 = 15
* 1 unit of insulin covers approximately 15g CHO
* If the patient’s meal contains 60g CHO should give 4 units of insulin

Question 18

What is insulin meal ratio?

Answer 18

What is insulin meal ratio?ratio of how much CHO one unit of rapidly acting insulin ‘covers’ to keep blood glucose in the optimal range

500/TDD = CHO ratio

Example:
* Patient had TDD of 33 U of insulin. CHO ratio is 500/33 = 15
* 1 unit of insulin covers approximately 15g CHO
* If the patient’s meal contains 60g CHO should give 4 units of insulin

Question 19

What is Insulin Sensitivity Factor?

Answer 19

Tells how many mmol/L the BGL will drop with 1unit of insulin

ISF = 100/TDD

Example:
* The patients TDD is 33 units making the ISF 3.0
* If patients BSL is 14mmol/L and we are aiming for 8 mmol/L the the ‘gap’ is 6 mmol/L.
* The patient should correct this gap by giving 6/3 = 2 units of insulin

Question 20

Classes of hypoglycaemia Sx (and BSL levels)

Answer 20

Autonomic (Neurogenic) - Plasma glucose 2.8-3.1
* Adrenergic [NA + A]
– Palpitations
– Tremor
– Anxiety

• Cholinergic [Ach]
  – Sweating
  – Hunger
  – Parasthesiae

Neuroglycopenic - Plasma glucose <2.8
* Brain glucose deprivation
– Confusion
– Fatigue
– Weakness
– Visual changes
– Seizure
– Loss of consciousness