T1DM

Question 1

main characteristic of T1DM?

difference to T2DM?

Answer 1

complete lack of insulin

whilst T2DM is the relative lack of insulin and insensitivity

Question 2

how can T1DM unusually end up presenting in later life?

Answer 2

as Latent Autoimmune Diabetes in Adults (LADA)

Question 3

is DKA a feature of T1DM?

Answer 3

yes

it is not a significant feature of T2DM as there is enough insulin present to suppress ketoacidosis

Question 4

How can monogenic diabetes present itself?

Answer 4

Type 1 or Type 2

e.g. MODY

Question 5

what can also cause a diabetes presentation?

Answer 5

pancreatic damage e.g. due to alcohol

Question 6

which type has more of a genetic role in its development?

Answer 6

T2DM

T1 is usually autoimmune

Question 7

why is beta cell failure in T2 relative?

Answer 7

insulin is produced by not enough to stimulate the insulin receptors

Question 8

what mediates autoimmune destruction of beta cells?

Answer 8

multiple relapse-remitting processes include different antibodies destroying the cells in phases

Question 9

what is the honeymoon phase in autoimmune destruction of beta cells

Answer 9

last phase where beta cells are in non-hyperglycaemia response with just enough insulin

Question 10

what happens to cause a breach in autoimmunity control?

Answer 10

Tregs normally keep check on effector T cells that are destructive
the Tregs are eventually overcome and complete destruction of beta cells takes place

Question 11

what increases the risk of autoimmune diabetes

Answer 11

a background of autoimmune disorders increases the prevalence of other autoimmune disorders
a risk in relatives

test for auto-antibodies

Question 12

which alleles pose a significantly increased risk of T1?

Answer 12

HLA-DR alleles specifically DR3 and DR4 have significant risk

Question 13

possible environmental triggers of T1?

Answer 13

autumn/winter months see more T1DM diagnoses due to possible infection cause

Question 14

what are the markers of T1DM?

Answer 14

o Islet cell antibodies.
o Insulin antibodies.
o Glutamic acid decarboxylase (GADA- created GABA neurotransmitter)
o Insulinoma-associated-2 autoantibodies receptor like family.

Question 15

what are the symptoms of T1DM?

Answer 15

 Polyuria
 nocturia.
 Polydipsia.

 Blurring of vision.
 Thrush- yeast infection
 Weight loss.
 Fatigue.

Question 16

what are the signs of T1DM?

Answer 16

	Dehydration.
	Cachexia – muscle wasting/weakness.
	Hyperventilation – Kussmahl breathing 
	Ketone smell.
	Glycosuria and Ketonuria.

Question 17

what is the function of insulin

Answer 17

release post-prandial to increase the absorption of glucose

- inhibits glycerol leaving adipocytes (therefore no gluconeogenesis)

Question 18

what is the result of a lack of insulin on adipocytes?

Answer 18

FFAs are released and turned into ketone bodies inside the liver

these KBs are taken up by muscles and the brain

causes ketonuria

Question 19

what are the aims of treatment for T1?

Answer 19

• reduce early mortality
• avoid acute metabolic decompensation
• prevent long term complications (retinopathy, nephropathy, vasc disease)

Question 20

how is life preserved in T1?

Answer 20

using exogenous insulin

Question 21

what dietary changes need to be made?

Answer 21

• reduce calories of fat and refined carbs
• increase calories of complex carbs and increase soluble fibre
• distribute food evenly throughout the day, regular meals and snacks

Question 22

what must be taken into consideration when giving insulin?

Answer 22

people have a basal level of insulin so treatment must retain this

Question 23

when must insulin be given?

Answer 23

• meals: short acting insulin, human or analogue (lispro, Aspart, Glulisine)
• background: long-acting, non-c bound to zinc/protamine or analogue (Glargine, Determir , Degludec)

Question 24

alternative treatment option

Answer 24

• insulin pumps: gives continuous delivery, pre-programmed basal and bolus rates but does not measure glucose feedback
• islet cells transplants: donor donates pancreas islet cells inserted into diabetic’s liver portal vessels to release insulin ; patient on immunosuppressants; treatment reserved for those with erratic control of diabetes

Question 25

how can treatment be monitored?

Answer 25

- capillary monitoring: either via a continuous monitor attached to the belly or through finger pricks. Allows adjustment of insulin dose. - HbA1c red cells monitoring: glucose binds to RBCs irreversibly so can give a long-term view of glucose control. Can allow you to monitor blood glucose over a 3-month long period (life of a RBC).

Question 26

what is a low Hb1AC associated with?

Answer 26

Lowering HbA1C is associated with a lower risk of microvascular complications.

Question 27

acute complications of T1?

Answer 27

- metabolic acidosis (ketoacidosis) | - hyperglycaemia

Question 28

what causes the acute complication: metabolic acidosis?

Answer 28

due to circulating acetoacetate/hydroxybutyrate (ketone bodies) and osmotic dehydration and poor tissue perfusion. [Diabetic ketoacidosis CAN occur in T2DM and new onset diabetes BUT it is most common in T1DM]

Question 29

what essentially causes hyperglycaemia (high glucose in the blood)? pathophysiology

Answer 29

- reduced uptake of glucose - reduced tissue glucose utilisation - increased HGO. - In treating hyperglycaemia, patients MAY become hypoglycaemic.

Question 30

what may be a consequence of treating diabetes?

Answer 30

hypoglycaemia (<3.6mmol/L) - most mental processes inhibited at <3 - coma at <2 with long term effects on brain - severe hypoglycaemia contribute to arrhythmia and sudden death - recurrent hypos--> loss of warning to body

Question 31

who are affected by hypos?

Answer 31

o Low quality glycaemic control patients. | o More common in patients with low HbA1C.

Question 32

when can hypos strike?

Answer 32

o Anytime but often a clear pattern (i.e. pre-lunch hypos). | o Nocturnal which are common but not often recognised by the patient.

Question 33

what are the triggers of hypos?

Answer 33

o New exercise. o Missed meals. o Inadequate snacks and alcohol. o Bad insulin regime.

Question 34

symptoms and signs of hypoglycaemia

Answer 34

<3.6 mmol/L - increased autonomic activation (palpitations, sweating, tremor) - impaired CNS functions

Question 35

increased autonomic activation due to hypoglycaemia

Answer 35

``` o Palpitations. o Tremor. o Sweating. o Pallor/cold extremities. o Anxiety. ``` hypoglycaemia increases the release of catecholamines in order to increase glucose production and decrease glucose utilisation in order for the brain to have sufficient glucose. There is increased adrenergic activity.

Question 36

what are the impaired CNS function symptoms due to hypoglycaemia?

Answer 36

o Drowsiness, confusion and altered behaviour. | o Coma.

Question 37

treatment of hypoglycaemia due to diabetes treatment

Answer 37

- oral feed glucose (tablets or solution) and complex carbs - parenteral if unconscious (IV dextrose, 1mg glucagon IM)

Question 38

how is DKA precipitated?

Answer 38

o New diagnosis of T1DM. o Not taking insulin. o Intercurrent stress (e.g. pneumonia). o Fasting and not taking enough insulin.

Question 39

what are the main 4 causes of DKA?

Answer 39

- fasting - insulin def - stress hormones - dehydration

Question 40

how is metabolic acidosis caused?

Answer 40

due to ketones (these are slightly acidic) - produced as a result of fatty acid breakdown (lipolysis) - reduction in bicarbonate production decreases blood pH leads to - Kussmahls respiration to blow off CO2 - hyperventilation - vomiting - abdominal pain - fruity smell in breath - ketonuria

Question 41

urinary losses in DKA

Answer 41

water lost in urine so Na+ is lost | K+ is also lost but even though acidosis shows high K+to compensate for the acidosis, total body K+ is low

Question 42

clinical features of DKA

Answer 42

o Polyuria & polydipsia due to diuresis. o Dehydration. ``` due to drop in blood pH: o Hyperventilation. o Abdominal pain and vomiting. o Coma. o Glycosuria and Ketonuria. ```

Question 43

investigations for DKA

Answer 43

``` o Capillary and plasma glucose. o Creatinine, K+, Na+. o FBC. o Arterial blood gas. o Amylase. o ECG, CXR, septic screen. ```

Question 44

what are the treatments for DKA? | [FIPBO]

Answer 44

``` 1) Fluids: H2O as normal saline 2) Insulin: dependent on blood glucose levels In second phase DKA, give 5% dextrose. 3) Potassium: usually found intracellular 4) Bicarbonate (increase pH) 5) Other: Cardiac monitor, catheterise, antibiotics, NG tube, heparin, arterial line or central line ```

Question 45

why does blood pH drop?

Answer 45

ketone bodies are slightly acidic causes hyperventilation/Kussmahls in order to remove CO2