Diabetes and Diabetes Therapies Flashcards
What is osmotic diuresis?
increased urination due to the presence of certain substances in the urine.
caused by high blood sugar and certain medications
Why does diabetes cause weight loss?
insulin promotes the uptake of glucose. insulin deficiency causes the body to become catabolic as it thinks its lacking sugar so it breaks down muscle and fat
What type of hormone is insulin?
anabolic - synthesises complex structures from products of catabolism
Diabetic ketoacidosis
High blood sugar and low insulin results in the liver breaking down fats to form ketones.
DKA is precipitated by__________
- infection, omitting insulin, steroids, MI, CVA , trauma, hyperthyroidism
- stress response from MI and CVA
What happens during DKA to muscle cells?
muscle cells → amino acids → glucose
Gluconeogenesis
glucose from macronutrients - protein
Glycogenolysis
glycogen → glucose
ketogenesis
fatty acids and ketogenic amino acids → ketones
What happens during DKA to fat cells?
fat → glycerol and fatty acids
glycerol → glucose
fatty acids → ketones
Symptoms of DKA?
PROLONGED HYPERGLYCAEMIA
increased thirst (polydipsia)
increased urination (polyuria)
dehydration
nausea, general malaise, abdominal pain, fruity breath
Why does increased glucose cause polyuria?
glucose is an osmotic diuretic
Treatment for DKA
- insulin IV
- Na water and K loss replaced with IV fluid
- once ketone <0.6mmol/L and patient eating/drinking convert to subcutaneous insulin
Why is potassium high on first presentation of DKA?
due to compensation, acidosis causes potassium to leak from cells into the blood
Steps of Treatment of DKA
- correct fluid loss
- correct hyperglycaemia
- correct electrolyte disturbance (specifically potassium)
- correct acid-base balance
- treat underlying trigger for DKA
Type 1 diabetes
inability to produce insulin due to an autoimmune process against pancreatic beta islet cells
Type 3c diabetes
insulin deficiency from exocrine pancreatic damage (pancreatitis, pancreatic cancer)
Type 2 diabetes
insensitivity to insulin (insulin resistance)
- associated with obesity
- associated beta cell dysfunction may be present
- may develop DKA in acute illness
- BAME subjects may be ketone prone
Effect of insulin deficiency on cells
beta cell - produces less insulin
alpha cell - produces excess glucagon → excess sugar production from liver
muscle and fat cells don’t respond to insulin - glucose uptake is low
What does measuring faecal elastase tell us?
faecal elastase is an exocrine enzyme from the pancreas. If there is an exocrine deficiency it will be low.
Complications of Diabetes?
- diabetic retinopathy
- periodontal disease
- diabetic nephropathy
- erectile dysfunction
- diabetic neuropathy
- stroke
- depression
- heart disease
- liver disease
- peripheral vascular disease
- amputation
Why does neuropathy occur in diabetics?
damage to small blood vessels supplying the nerves
what is an atheroma?
fatty material which builds up inside the arteries.
Treatment options for type 2 diabetes
- insulin sensitisation
- insulin replacement
- insulin secretion
- lifestyle intervention
- glucose excretion
Insulin sensitisation drugs
metformin, pioglitazone
Insulin secretion drugs
DPP-4 inhibitors (alogliptin, linagliptin)
GLP-1 receptor antagonists (exenatide, liraglutide)
meglitinides (repaglinide, nataglinide)
sulphonylureas (gliclazide, glibenclamide)
side effects of metformin and pioglitazone
metformin - can accumulate causing risk of lactic acidosis
pioglitazone - increase subcutaneous fat and weight gain
Glucose excretion drugs
SGLT2 inhibitors:
canagliflozin
dapagliflozin
When should metformin not be used?
in patients with a GFR < 30ml/min
When should SGLT2 inhibitors not be used?
in patients with an eGFR<45ml/min
How do sulphonylureas work?
sugar enters the beta cell to be metabolised into ATP
ATP sensitive potassium channel closes
cell depolarises
depolarisation causes potassium to influx
insulin released
Risks of sulphonylureas
hypoglycaemia - not glucose sensitive
weight gain
How do GLP-1 receptor antagonists work?
food ingested
glp-1 released
glp-1 prepares beta cells
promotes insulin secretion
suppresses excess glucagon production
GLUCOSE DEPENDENT
How do DPP-4 inhibitors work?
DPP-4 breaks down GLP-1
inhibiting this means more GLP-1 is active
can use in renal failure
Benefits of GLP-1 receptor antagonists
enhanced efficacy
weight loss due to suppressed appetite
cardioprotective
prevents strokes
reduces inflammation in blood vessels
reduce risk of atherosclerosis
How do SGLT2 inhibitors work?
blood enters the proximal tubule through the glomerulus
sugar absorbed in proximal tubule by SGLT2
in a diabetic, sugar present in urine since sglt2 saturated
an SGTL2 inhibitor reduces the renal threshold so more glucose excreted in urine
How do SGLT2 inhibitors reduce BP?
increased sodium excretion means reduced BP
Why are SGLT2 inhibitors used in heart failure?
slight increase in ketone level
ketones are a more efficient fuel for failing heart muscle
Risks of SGLT2
DKA - therefore contraindicated in type 1 and type 3c patients
increased risk of thrush
Why are SGLT2 inhibitors used in kidney disease?
kidneys hyperfiltrate sodium and glucose
reduced sodium delivered to macula densa
macula densa dilates afferent arteriole
glomerulus becomes overpressured
the abnormal glucose uptake is caused by SGLT2
inhibition of this causes normal lower reabsorption
Modern type 2 diabetes treatment
- metformin
- sglt2 inhibitor (dapagliflozin)
- GLP-1 receptor agonist (semaglitude, liraglutide)
SU effective as short term rescue therapy
Characteristics of Type 1 Diabetes
- ketone prone due to absolute insulin deficiency
- more common in childhood
- associated with other autoimmune disease e.g., underactive thyroid, celiac disease
Characteristics of Type 3c diabetes
- ketone prone due to absolute insulin deficiency
- associated exocrine pancreatic dysfunction e.g, steatorrhea due to deficiency of pancreatic enzymes
