Diabetes Mellitus

Question 1

How does hyperglycaemia stimulate insulin secretion

Answer 1

Hyperglycaemia lead to inc glucose uptake by cells
Glucose metabolism lead to inc levels of ATP within cells
Inc ATP causes K+ channels to close
Depolarisation of cell membrane
Ca2+ channels open
Inc Ca2+ causes exocytosis of insulin containing vesicles
Insulin realised by pancreatic beta cells/cell in Islet of langerhans

Question 2

Definition of diabetes mellitus

Answer 2

Common group of metabolic disorders characterised by chronic hyperglycaemia resulting from relative insulin deficiency / resistance or both

Question 3

Epidemiology of type 1 diabetes

Answer 3

Young <30
Lean
Northern European

Question 4

Risk factors for type 1

Answer 4

Family history of auto immune diseases or a past medical history (HLA-DR3 HLA-DR4)
Environmental factors -exposure to viral illness or extreme stress

Question 5

Pathology of Type 1 diabetes

Answer 5

AUTOIMMUNE
destruction of pancreatic beta cells
associated with HLA genetics but also triggered by one or more environmental antigens
autoantibodies directed against insulin and islet cell antigens predate onset by several years
polyuria caused by: blood glucose levels exceed renal tubular reabsorption capacity = Osmotic diuresis
weight loss caused by : fluid depletion, insulin deficiency -> muscle and fat breakdown

Question 6

symptoms of diabetes

Answer 6

over 2-6 weeks
weight loss - this causes polyphagia (excessive eating)
polyuria- excessive urine/ lack quantities
polydipsia- excessive thirst
ketoacidosis if not caught soon - fruity breath
older will present with these but over a longer period but also lack of energy, eye problems and neuropathy

Question 7

aetiology of type 1 compared to type 2

Answer 7

HLA-DRA3/4 affected in 90% type 1
autoimmune
type 2 no HLA link but genetic susceptibility

Question 8

investigations for type 1

Answer 8

fasting plasma glucose
HbA1c
C peptide

Question 9

results of investigations causing diagnosis

Answer 9

fasting glucose- >7mmols/L / random glucose >11.1mmol/L
HbA1c > 6.5 % / 48mmol/mol
C peptide down in type 1 resides in type 2

Question 10

treatment of type 1

Answer 10

glycaemic control through diet - low sugar low-fat high starch
insulin twice daily with meals
- short-acting insulin: soluble (30-60 mins and last 6 hours) or analogues (faster onset shorter duration)
- long-acting insulin - mixed w protamine/zinc can be intermediate lasting 12-24hours
exercise encouraged

Question 11

epidemiology of type 2 diabetes

Answer 11

older - over 40yr
obese
African/Asian
some teenagers are now getting it

Question 12

risk factors of t2dm

Answer 12

obesity
low exercise
hypertension
hypercholesterolaemia
family history- PMH/T2DM
genetics- twins both more likely

Question 13

pathology of t2dm

Answer 13

polygenic
environmental - trigger onset in genetically susceptible
beta-cell dysfunction mass reduced to 50% of normal due to amyloid deposits in the pancreas
low insulin secretion = hyperglycemia
peripheral insulin resistance
bet cell hypertrophy and hyperplasia - more insulin

Question 14

annual review of t2dm

Answer 14

annual review :
HbA1c
Bmi
BP
plasma lipids
creatinine- renal function 
retina check 
neurology check
urine test- proteiuria/microalbinuria

Question 15

management of t2dm

Answer 15

lifestyle advice
first-line metformin -reduced gluconeogenesis in liver
2nd line is if HbA1c raises to 58 = dual therapy
3rd line is if HbA1c is still 58 = triple therapy
4th line is if triple still not tolerated

Question 16

2nd line dual therapy medications

Answer 16

metformin +
gliclazide - sulfonylurea
sitagliptin - SGLT-2i
glifazon -DPP4 Inhibitor

Question 17

3RD line triple therapy

Answer 17

Metformin+
gliclazide +
- sitagliptin
- pioglitazone

Question 18

if triple therapy not tolerated

Answer 18

insulin based therapy

Question 19

complications of diabetes

Answer 19

ketoacidosis
nephropathy 
neuropathy
retinopathy
hyperosmolar hyperglycaemic nonketoic coma (T2)

Question 20

Metformin

Answer 20

drug class:  Biguanide 
mechanism - reduce gluconeogenesis in liver 
inc glucose uptake and utilization in skeletal muscle 
side effects- abdo pain
anorexia
diarrhoea
nausea
weight loss

Question 21

Glipizide

Answer 21

sulfonylurea
stimulate B cell to secrete insulin
but can transfer across placenta in pregnancy and cause hypoglycaemia in newborn

side effects
hypoglycemia
weight gain- stimulates appetite

Question 22

sitagliptin

Answer 22

DPP4 inhibitor
inhibits DPP4 increasing the effects of incretins which stimulate insulin secretion
incretins- a group of hormones released after eating & augment secretions on insulin
doesn’t cause weight gain or loss

Question 23

pioglitazone

Answer 23

Glitazone
enhance uptake of fatty acids and glucose
fluid retention (inc na+ reabsorption)- can worsen HF
weight gain