13 - Diabetes Mellitus

Question 1

Prevalence of T1D

Answer 1

10%

Question 2

What is t1d

Answer 2

chronic autoimmune disease,

T-cell mediated disruption of pancreatic B cells within islets of Langerhans –> causes insulin deficiency

Question 3

Evidence of immune mediated disease in T2D

Answer 3

 Infiltration of pancreas islets by mononuclear cells (insulitis)
• T lymphocytes, monocytes etc.
 90 percent with autoantibodies against islets
 Immunosuppression –> delayed B cell disruption

Question 4

t2d prevalence

Answer 4

85-90%

Question 5

T2D genetics

Answer 5

gkrp

pparg

Question 6

Risk factors t2d

Answer 6

Obesity
family history
ethnicity
age

Question 7

Causes of abnormal insulin action (resistance)

Answer 7

Obesity
Hyperinsulinaemia
Adipokines
Lipoglucotoxicity

Question 8

How can obesity cause t2d

Answer 8

Lipids, metabolites + FFA

= Chronic inflammation affecting adipocytes –> altered adipokine levels –> resistance –> hyperinsulinaemia

Question 9

How does hyperinsulinaemia cause t2d

Answer 9

Obesity - cells dont respond to insulin

pancreas increases insulin levels –> increases lipid synthesis –> exacerbates

Question 10

How does Adipokine alter pathway of insulin

Answer 10

Normally, insulin causes the phosphorylation of tyrosine via IRS which activates PI3K and Akt. In resistance, Threonine and serine phosphorylated instead. No activation of Akt so no downstream activation.

Question 11

Why do fat pregnant ppls not have t2diabetes

Answer 11

Compensation of b cells

• increase in size and no
• increase in function

Question 12

Why do beta cells decrease in t2d

Answer 12

Genetic factors make some b cells more susceptible to dysfunction

Question 13

What is lipoglucotoxicity

Answer 13

Excess lipids/glucose in blood –> damage Beta cells –> even less insulin

Question 14

Treatment for T2D

Answer 14

Biguanides - Metformin
Sulfonylureas
TZD
DDP-4 inhibitors
SGLT2 inhibitors

Question 15

MoA of metformin

Answer 15

• Increases AMPK activation

1) improve insulin receptor function
2) improved glucose transport (GLUT 4)
3) reduce F.A synthesis
4) reduce hepatic gluconeogenesis via inhibiting cAMP activation
5) Increases GLP-1

Question 16

MoA of sulfonylureas

Answer 16

Closes the K+ channel –> depolarisation –>increased Ca2+ –> insulin secretion.

Question 17

MoA of thiazolidinediones

Answer 17

• Affects PPARG which is a transcription factor, so it activates genes that increase glucose uptake, decrease gluconeogenesis

Question 18

DDP-4 inhibitors

Answer 18

sitagliptin- DDP4 breaks down GLP-1 normally and GLP-1 reduces glucagon secretion

Question 19

SGLT2 inhibitors

Answer 19

target kidney reabsorption of glucose

Question 20

What is MODY

Answer 20

maturity onset diabetes of the young

Question 21

What is LADA

Answer 21

latent autoimmune diabetes in adults)
 In between the two different types of diabetes m.
 Autoantibodies present

Question 22

Type 3c diabetes

Answer 22

Malfunction in pancreas due to other disease

Question 23

Diagnostic plasma glucose

Answer 23

Random >11.1
Fasting >7
- Two fasting venous plasma glucose samples needed in asymptomatic

Question 24

Symptoms of diabetes t2

Answer 24

1) thirst, 2) increased urination 3) weight loss 4) drowsiness 5) coma 6) recurrent infections

Question 25

What is oral glucose test

Answer 25

patients drinks sugary drink then after two hours, their BGL (blood glucose level) measured o >11 = diabetes

Question 26

What does HbA1c measure

Answer 26

glycation of haemoglobin | =48 mmol/mol or 6.5 percent cut off point

Question 27

What causes ketoacidosis

Answer 27

o Lack of insulin --> prolonged fasting state--> B-oxidation increases --> accumulation of ketone bodies --> dissociate into anions and H+ --> ketoacidosis (acetoacetate + B hydroxybutarate) o Bicarbonate tries to buffer, blood and urine acidity rises --> death

Question 28

What is hypoglycaemia

Answer 28

<3.9 mmol/L/ <70mg/dl

Question 29

Causes of hypoglycaemia

Answer 29

1) excess alcohol (gluconeogenesis inhibited at low levels of lactate dehydrogenase/depletion of NAD+ 2) Insulinoma 3) Excessive exercise 4) Reactive hypoglycaemia 5) T1D- insulin injection but missed meal

Question 30

Symptoms of hypoglycaemia

Answer 30

Palpitations, trembling, anxiety, confusion, drowsiness, coma

Question 31

Prolonged effect of hypoglycaemia

Answer 31

• Growth hormone and cortisol decrease glucose utilisation in favour of fat --> shortage of glucose for brain --> coma, seizures, loss of cognitive function.

Question 32

Macrovascular complication of hyperglycaemia

Answer 32

Dyslipidaemia | Atherosclerosis

Question 33

Microvascular complications of hyperglycaemia

Answer 33

Nephropathy (kidney) Neuropathy Retinopathy

Question 34

What is nephropathy

Answer 34

o Damage to glomerular vessels critical for blood filtration  Glomerular hypertrophy, proteinuria, renal fibrosis  1/3 of diabetics get it, leading cause of renal failure

Question 35

Cause of neurophathy

Answer 35

o Damage to blood vessels supplying the nerves --> pain, weakness or autonomic control changes.

Question 36

Difference between proliferative and non proliferative retinopathy

Answer 36

 Non-proliferative- dilation of retina veins, microaneurysms which cause internal haemorrhages and oedema in central retina  Proliferative- Fragile, new blood vessels form near the optic disk and grow on the vitreous chamber and elsewhere in the retina --> can bleed

Question 37

How are bv damaged in diabetes

Answer 37

 Excess glucose diverted to other pathways e.g. PKC--> DAG pathway which damage blood vessels by increased permeability, increased occlusion, increased ROS, Increased inflammation, mitochondrial dysfunction