5. Diabetes Mellitus Flashcards
define diabetes mellitus
a group of metabolic diseases characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action or both
where is insulin secreted
from beta cels of the islets of langerhans
what are incretins
a group of metabolic hormones that stimulate a decrease in blood glucose levels.
they are released after eating and augment the secretion of insulin
what is the incretin effect
the phenomenon where glucose consumed orally elicits higher insulin secretory responses than intravenous glucose.
how is glucose reabsorbed
using SGLT receptors
what is the renal glucose threshold, what does this mean?
10 mmol
- anything over 10 mmol ends up in the urine
name 3 other factors that contribute to hyperglycaemia (increased blood glucose)
increased glucose reabsorption
decreased glucose uptake into cells
increased glucagon secretion
where is glucagon secreted from
alpha cells
describe the structure of insulin
52 amino acids with A and B chains linked by disulphide bonds
how is insulin synthesised, and what is it cleaved into
synthesised as pre-proinsulin and cleaved into proinsulin
diabetes has an increasing global burden, what has happened to cases in the last 25 years
almost doubled!!
what 2 things does insulin inhibit
inhibits gluconeogenesis and lipolysis
what is the role of insulin
facilitates glucose transport into muscle and fat cells
name 6 clinical symptoms of DM
fatigue
wounds that won’t heal
sudden weight loss
frequent urination
sexual problems
why do people with DM experience sudden weight loss
muscle and fat is broken down for energy
why do people with DM frequently urinate, what does this lead to?
an excess of blood glucose (hyperglycaemia) results in glucose expulsion in the urine (takes the urine with it)
this then causes dehydration - the patient drinks more to replace the lost water
why do people with DM experience wounds that won’t heal
high sugar increases inflammation and decreases immunity
what does glucagon inhibit
insulin and gastric inhibitory polypeptide (GIP)
what triggers the release of insulin
glucose
GIP
parasympathetic stimulation
what triggers the release of glucagon
low glucose
sympathetic stimulation
adrenaline
which branch of the nervous system coordinates the fight or flight response
sympathetic
what is an A1C measure used for diagnosing diabetes
a good indication of how glucose has been in the past 3 months, Hb binds to glucose and it can remain in the blood stream for up to 3 months
what is the A1C threshold for diabetes
> 6.5%
what is the prevalence of type 1 diabetes
1 per 430-530 people aged 19+
what is the average age for diagnosis of DM
10-14 years
name the 5 types of diabetes
type 1
type 2
gestational diabetes
mody diabetes
lada diabetes
which type of diabetes is an autoimmune disease
type 1
which type of diabetes develops the quickest
type 1
when is type 1 diabetes typically diagnosed
in young children
when is type 2 diabetes typically diagnosed
in adults
describe what happens in gestational diabetes
pregnancy hormones redirect glucose to the growing foetus rather than the mother
is gestational diabetes pathological
normally no - in most cases it reverses following birth
what type of diabetes does gestational diabetes increase the risk for later in life
type 2 DM
how can gestational diabetes be treated
through diet and exercise and in some cases insulin
what is mody diabetes
presents similar to type 2 diabetes but in a young person
what is lada diabetes
presents similar to type 1 diabetes but in an older person
which has a strong genetic risk factor: mody or lada diabetes
mody diabetes
which one is an autoimmune disease: mody or lada diabetes
lada diabetes - a latent autoimmune diabetes of adulthood
what is the concordance rate for type 1
50%
by how many times higher is the risk of developing T1DM if you have a first degree relative with the condition
15 x higher
list 2 viruses that can cause type 1 DM
cosackie B
mumps (causes pancreatitis)
name 2 dietary factors that can cause type 1 DM
cows milk, caffeine, nitrates
name 2 lifestyle factors that can cause type 1 DM
exposure toxins
stress
what geographical factor also increases risk of DM
increasing latitude (distance away from the equator)
what happens to islet cells targeted by antibodies in T1DM
these become fibrotic
name 3 autoantibodies implicated in DM type 1 pathology
antibodies to:
insulin
glutamic acid decarboxylase (GAD)
zinc transporter 8
what are the most frequent risk factors for type 2
obesity
hypertension
strong family history
what happens to insulin in type 2
cells become insulin resistant
what is the concordance rate of T2DM
90%
if you gain how much weight over 18 years, your risk of T2DM will double
7-11 kg
why has the global burden of diabetes increased
increased westernisation and urbanisation - the western diet ubiquitous in dietary emulsifiers
how does obesity cause type 2 dm
inflammation
name 2 cytokines that increase inflammation in type 2 DM
adiponectin
TNF-alpha
what is adiponectin
an adipocyte derived cytokine
what happens if infliximab is administered to obese rodents
blocking TNF-alpha antibodies improves glucose utilisation
what happens to rheumatoid arthritis patients treated with infliximab
lower incidence of diabetes
name a chemokine molecule that increases inflammation in obesity
CXCL5
what is the action of CXCL5
it binds to CXCR2 to reduce insulin-stimulated glucose uptake in the muscle
what is evidence for the role of CXCL5 in obesity
serum levels of CXCL5 is higher in obese individuals and T2DM obese patients compared to healthy individuals of a normal weight
how can you differentiate between type 1 and type 2 DM - provide 2 methods
islet autoantibody testing - positive result in T1 and lada
serum c-peptide - if it is low it shows there is insufficient insulin (<0.2 mol/l)
what is monogenic diabetes
diabetes that arises from specific genetic mutations
name a mutation found in monogenic diabetes
mutations in glucokinase
how many diabetes cases does monogenic diabetes account for
2%
name 2 acute complications of DM
hypoglycaemia
diabetic ketoacidosis
name the 2 types of chronic complications of DM
microvascular and microvascular
what condition is diabetic ketoacidosis common in
type 1 DM
describe the process of ketoacidosis
when there is lowered insulin there is increased lipolysis which increases the concentrations of FFAs
ketosis is where these FFAs are broken down to produce energy as well as ketones - the accumulation of ketones leads to acidosis as the pH decreases
name 2 ketones
acetone and butyric acid
what are the 3 types of microvascular chronic complications
diabetic nephropathy
neuropathy
retinopathy
what is diabetic nephropathy
where concentrations of microalbuminuria rise and proteinuria happens.
glomerular death occurs and so does renal failure
what is diabetic neuropathy
loss of sensation of injury
what can form as a result of diabetic neuropathy
foot ulcers - pain of standing on an object is not detected by nociceptors due to damaged blood vessels, pressure depends the stone into the tissue which can become infected
what is diabetic retinopathy
the thinning out of vasculature and eventual haemorrhage
what does hyperglycaemia result in the production of
advanced glycation end products
what do advanced glycation end products do
bind to receptors to induce a pro inflammatory cascade of cytokines and adhesion molecules.
they can also alter the function of proteins to result in vascular changes or endothelial permeability changes.
name three macrovascular chronic complications
stroke
heart damage
atherosclerosis
what percentage of newly presenting patients with type 2 DM already have one or more complication at diagnosis
50%
what 5 methods can be used to monitor glycaemic control
- symptoms
- urinalysis
- capillary glucose
- HbA1c
- interstitial glucose
which method for monitoring glycemic control has become redundant
urinalysis
how is capillary glucose measured
using a finger prick
what is capillary glucose critical for monitoring
type 1
what does HbA1c measure
the amount of glucose attached to RBCs - provides an indication of what someones blood glucose has been doing over the past 3 months
what two tools can be used to measure interstitial glucose
continuous glucose monitoring
flash glucose monitoring
how does continuous glucose monitoring work
sensor monitors interstitial glucose levels - the date is transmitted to a monitor which beeps when it is either too low or too high. it then is transmitted to an insulin pump which corrects glucose levels
what is the benefit of continuous glucose monitoring
it is a closed loop system - blood sugar is automatically fixed by the pump
how far behind blood glucose levels is interstitial glucose levels
interstitial levels are 15 minutes behind blood glucose
describe how flash glucose monitoring works
sensor is worn on the arm, the date is transmitted to a device when it is passed over the sensor. the monitor will show a glucose trend which can warn of hypoglycaemia
which is more expensive, continuous glucose monitoring or flash glucose monitoring
continuous glucose monitoring
how long can the sensor be worn on the arm for
up to 14 days
what are the typical treatments of type 1 diabetes
insulin
glycemic control
screening to prevent complications
where was insulin originally derived from
pigs and cows
how is insulin extracted nowadays
the gene for human insulin is expressed in bacteria or yeast
most patients are on a basal-bolus regime, what does this mean>
they are given a long acting insulin analogue
and a prandial rapid acting insulin
the prandial insulin dose is adjusted according to the carbohydrate content of meals and blood sugar levels.
to improve patient outcomes, what lifestyle changes are encouraged
physical exercise
smoking cessation and lowering alcohol intake
what are biguanides
drugs that increase glucose uptake and utilisation by target tissues and reduce insulin resistance
they also suppress hepatic glucose production
what is the only available biguanide
metformin
what is a side effect of metformin
weight loss
what is the mode of action of sulfonylureas
works on beta cells to increase insulin secretion - it does this by closing K+ channels on the membrane and depolarising them
what happens when beta pancreatic cells are depolarised
calcium channels open which leads to an increased fusion of insulin granular with the cell membrane = secretion of proinsulin
what is the side effect of sulfonylureas
weight gain - it prompts people to eat more
name 2 inhibitors used to treat type 2 DM
DPP-IV inhibitors
SGLT2 inhibitors
what must be present for DPP-IV inhibitors to work
food
how does DPP-IV inhibitors work
inhibits the DPP-IV enzyme, causing levels of incretin hormones GLP-1 and GIP to increase.
this prompts beta-cell insulin secretion and reduces postprandial hyperglycaemia
how does GLP-1 work (an incretin hormone)
lowers blood glucose by stimulating insulin secretion and reducing glucagon concentrations
what drug also works on GLP-1 and what does it do
GLP-1 agonists used in the treatment of T2DM
it delays gastric emptying, inhibits glucagon production and stimulates insulin secretion.
what plastic response can worsen hyperglycemia
when there is more glucose in the blood, the expression of SGLT2 can be up-regulated. this worsens the response as more glucose gets reabsorbed
how do SGLT2 inhibitors work
decrease glucose reabsorption leading to greater excretion
what is a side effect of SGLT2 inhibitors
can cause dehydration as glucose is osmolarity active and takes water with it as its excreted.
