T1DM

Question 1

T1DM

Answer 1

DM is the pathological and metabolic state caused by inadequate insulin action

to be thought of as a vascular disease

selective autoimmune destruction of insulin secreting B cells in the pancreas

Question 2

risk of developing T1DM if family have it

Answer 2

genetics counts for 1/3 of the risk in T1DM

larger risk in mono and di zygotic twins, HLA identical siblings and if both parents have it

concordance is only 30% in identical twins, indicating environmental influence

(genetics plays a much larger part in T2DM)

Question 3

is the genetic risk larger in T1 or T2 DM

Answer 3

T2DM

Question 4

HLA genes

Answer 4

represent around half of familial risk

the highest risk genotype is DR3-DQ2/DR4-DQ8

95% of those diangosed with T1DM under the age of 30 have one or both of the genotypes

there is no HLA association in T2DM

Question 5

describe the development of T1DM

Answer 5

• there is a genetic predisposition, influenced by foetal risk factors
• immune dysregulation leads to insulitis and beta cell injury
• this can lead to pre diabetes, which eventually leads to overt diabetes
• environmental triggers and factors can accelerate/cause this progression

Question 6

risk factors in foetal life

Answer 6

infection

age

ABO mismatch

birth order

Question 7

auto-immune trigger factors

Answer 7

viral infection

vitamin D deficiency

dietary factors

environmental toxins

= pre-diabetes (can last for months to years)

Question 8

accelerating factors for development of T1DM

Answer 8

infection

insulin resistance

puberty

diet/weight

stress

Question 9

diagnosis of DM

Answer 9

fasting glucose ≥ 7

random glucose ≥ 11.1

and symptoms of hyperglycaemia OR repeat test

Question 10

what are the clinical features of hyperglycaemia

Answer 10

hyperglycaemia causes an osmotic diuresis, which causes dehydration: polyuria and polydipsia (excessive thirst)

unexplained weight loss

visual blurring

genital thrush

lethargy and somnolence

increase in appetite

Question 11

ensuresis

Answer 11

symptom of polyuria due to hyperglycaemia

• inability to control urination (bed-wetting)

could be a sign of diabetes in children

Question 12

why is there unexplained weight loss

Answer 12

insufficient insulin also stops glucose from entering the tissues, meaning they have to break down fats for energy

increased lipolysis (FA release from adipose tissue).

Question 13

what is a possible presentation of DM

Answer 13

acute short sightedness

later in life develop cataracts, glaucoma etc and diabetic retinopathy

Question 14

why is there visual blurring

Answer 14

high levels of glucose in the blood can be absorbed by the lens of the eye, which changes its shape

the lens will return to its normal shape once normal glycaemic control has been established

Question 15

what is lethargy and somnolence associated with

Answer 15

poor glycaemic control - go away once this is established

Question 16

investigation: urine glucose

Answer 16

normally there is no glucose in the urine, if there is too much in the blood it will be excreted via the urine

tested for using urinalysis

Question 17

random glucose

Answer 17

not diagnostic of diabetes, ≥11.1 mmol/L

diagnostic with symptoms, resting and fasting raised

OR

fasting and resting raised on 2 separate occasions

Question 18

elevated HbA1c

Answer 18

≥48mmol/L

Question 19

HbA1c

Answer 19

glycated haemoglobin

during its life a Hb molecules will slowly react and attach (non-enzymatically) to glucose present in the cell - forming glycated Hb

if patient has chronically high blood glucose they will have more HbA1c

used to measure long term blood glucose control in known diabetics as a way of evaluating the effectiveness of their management

Question 20

what is high HbA1c often a sign of

Answer 20

non compliance

Question 21

in what situations can HbA1c vary and be unreliable

Answer 21

haemolytic anaemia, acute or chronic blood loss, pregnancy

Question 22

describe the limitations of HbA1c

Answer 22

Question 23

descibe the target levels for HbA1c

Answer 23

normal = 42 mmol/L

pre- diabetes = 42-47 mmol/L

target in diabetic patients = 48 mmol/L in younger patients, 53 mmol/L in others

dangerous = >75 mmol/L

Question 24

islet autoantibodies

Answer 24

suggest T1 rather than T2

GAD 65, IA2 and IAA

Question 25

proteinuria

Answer 25

sign of kidney damage in diabetes, and could be a sign of hypertension (diabetics are more prone) or diabetic nephropathy

Question 26

what happens to patient’s kidneys when they have poor glycaemic control

Answer 26

glycation of the BM of small blood vessels thockens them , in particular the efferent arteriole which stiffens and hardens making it harder for blood to leave the glomerulus

the afferent arteriole dilates allowing more blood into the glomerulus - inc pressure

hyperfiltration

the glomerulus expands and there is thickening of the BM making it more permeable - proteins, eg albumin, are allowed through

= glomerular filtration rate decreases

Question 27

what happens to the cells in the pancreas

Answer 27

B cells are destroyed

A (glucagon), D (somatostatin) and PP (pancreatic polypeptide) cells are preserved

Question 28

pathology of pancreas in T1DM

Answer 28

active B cell destruction and islets become inflamed - insulitis

infiltrate contains many lymphocytes with a few macrophages

Question 29

pathology of pancreas in T2DM

Answer 29

not as much B cell los

amyloid present in islets

Question 30

what are some disease markers of the auto-immune process

Answer 30

autoantibodies: GAD65, IA2, IAA

candidate antigens

insulitis

Question 31

what are some disease markers of clinical diabetes

Answer 31

lowered insulin, B cell mass and C-peptide

raised glucose

ketones

Question 32

what is expected to happen to insulin secretion

Answer 32

after 5 years no endogenous insulin secretion

Question 33

why are is DM seen in CF patients

Answer 33

reduced insulin secretion secondary to pancreatic insufficiency