Diabetes Mellitus Flashcards
How does hyperglycaemia stimulate insulin secretion
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
Definition of diabetes mellitus
Common group of metabolic disorders characterised by chronic hyperglycaemia resulting from relative insulin deficiency / resistance or both
Epidemiology of type 1 diabetes
Young <30
Lean
Northern European
Risk factors for type 1
Family history of auto immune diseases or a past medical history (HLA-DR3 HLA-DR4)
Environmental factors -exposure to viral illness or extreme stress
Pathology of Type 1 diabetes
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
symptoms of diabetes
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
aetiology of type 1 compared to type 2
HLA-DRA3/4 affected in 90% type 1
autoimmune
type 2 no HLA link but genetic susceptibility
investigations for type 1
fasting plasma glucose
HbA1c
C peptide
results of investigations causing diagnosis
fasting glucose- >7mmols/L / random glucose >11.1mmol/L
HbA1c > 6.5 % / 48mmol/mol
C peptide down in type 1 resides in type 2
treatment of type 1
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
epidemiology of type 2 diabetes
older - over 40yr
obese
African/Asian
some teenagers are now getting it
risk factors of t2dm
obesity low exercise hypertension hypercholesterolaemia family history- PMH/T2DM genetics- twins both more likely
pathology of t2dm
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
annual review of t2dm
annual review : HbA1c Bmi BP plasma lipids creatinine- renal function retina check neurology check urine test- proteiuria/microalbinuria
management of t2dm
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
2nd line dual therapy medications
metformin +
gliclazide - sulfonylurea
sitagliptin - SGLT-2i
glifazon -DPP4 Inhibitor
3RD line triple therapy
Metformin+
gliclazide +
- sitagliptin
- pioglitazone
if triple therapy not tolerated
insulin based therapy
complications of diabetes
ketoacidosis nephropathy neuropathy retinopathy hyperosmolar hyperglycaemic nonketoic coma (T2)
Metformin
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
Glipizide
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
sitagliptin
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
pioglitazone
Glitazone
enhance uptake of fatty acids and glucose
fluid retention (inc na+ reabsorption)- can worsen HF
weight gain
