Diabetes Flashcards
compare diabetes mellitus vs diabetes insipidus?
similar symptons (eg large volumes of urine, excessive thirst)
DM- problem with glucose regulation
DI- problem with water regulation
what is diabetes mellitus?
a group of metabolic disease characterised by hyperglycemia resulting from defects in insulin secretion, insulin action or both
for the diagnosis of diabetes, what must the HbA1c be?
48 m/m +
what is the normal range of HbA1c?
41 m/m and below
for the diagnosis of diabetes, what must the fasting glucose be?
7.0 mmol/L +
what is the normal range of fasting glucose?
6.0 mmol/L and below
for the diagnosis of diabetes, what is the 2-hr glucose in OGTT?
11.1 mmol/L +
what is the normal range of 2-hr glucose in OGTT?
7.7 mmol and below
for the diagnosis of diabetes, what is the random glucose?
11.1 mmol/L +
what defines type 1 diabetes?
pancreatic beta cell destruction
-anti-GAD/anti-islet cell antibodies usually
insulin is required for survival
what is the initial management of type 2 diabetes?
diet control
compare type 1 and type 2 diabetes in terms of the presence of ketonuria at diagnosis?
type 1: present
type 2: minimal or absent
compare type 1 and type 2 diabetes in terms of the presence of microvascular disease at diagnosis?
type 1: no evidence
type 2: evidence in 20% of cases
compare type 1 and type 2 diabetes in terms of age at onset?
type 1: pre-school, peri-puberty
type 2: middle aged/elderly
what are the 3 most useful tests to discriminate between type 1 and type 2 diabetes?
- GAD/anti-islet cell antibodies
- ketones
- C-peptide
what is type 3 diabetes?
diabetes secondary to a disease/syndrome/drug/monogenic cause
what are the 3 main pancreatic causes of type 3 diabetes?
chronic/recurrent pancreatitis
haemochromatosis
cystic fibrosis
what are the 4 main endocrine causes of type 3 diabetes?
cushings syndrome
acromegaly
phaechromocytoma
glucagonoma
what are the 3 main drug-induced causes of type 3 diabetes?
glucocorticoids
diuretics
b-blockers
what are the 3 main genetic causes of type 3 diabetes?
CF
myotonic dystrophy
turner’s syndrome
will C-peptide be positive or negative in monogenic diabetes?
positive
what is type 4 diabetes?
gestational diabetes:
any degree of glucose intolerance arising or diagnosed during pregnancy
HbA1c provides a measure of glucose control over the past how many months?
2-3 months
what is the classic triad of type 1 diabetes symptoms?
- polyuria (enuresis in children)
- polydipsia
- weight loss
what is the ideal HbA1c range for a type 1 diabetic patient?
48-58 mmol/l
are children more likely to get type 1 diabetes if their mother or father has diabetes?
father
the normal release of insulin after a meal is biphasic how long does each phase last?
rapid phase of pre-formed insulin: 5-10 minutes
slow phase: 1-2 hours
which blood vessel is insulin secreted into?
hepatic portal vein
compare type 1, type 2 and MODY diabetes in terms of length of symptoms and severity?
type 1: short length with severe symptoms
type 2 and MODY: gradual progression
are children under 6 months presenting with diabetes more likely to have type 1 or monogenic diabetes?
monogenic diabetes
what is LADA?
latent onset diabetes of adulthood-
elevated levels of pancreatic auto-antibodies in patients with recently diagnosed diabetes who do not initially require insulin
what age does LADA tend to occur?
(males usually) 25-40
what is wolfram syndrome?
a rare genetic syndrome causing diabetes insipidus ,diabetes mellitus, optic atrophy, deafness and neurological anomalies
what is bardet-biedl syndrome caused by?
a genetic disorder
can be caused by consanguineous parents
what are the 6 main symptoms of bardet-biedl syndrome?
- polydactyly
- hypogonadal
- visual impairment
- hearing impairement
- mental retardation
- diabetes
what is the primary and secondary dysfunctions in type 2 diabetes?
primary: insulin resistance
secondary: beta cell dysfunction
what are the main 2 causes of insulin resistance?
- ectopic fat accumulation and increased circulating free fatty acids
- increased inflammatory mediators
what is insulin resistance a precursor for?
type 2 diabetes
what happens to the insulin levels over a period of time in a patient with impaired glucose tolerance?
insulin initially rises but then falls due to pancreatic burnout (beta cell dysfunction)
what 2 toxicities caused by insulin resistance causes declining beta-cell function?
glucotoxicity (hyperglycaemia)
lipotoxicity (elevated free fatty acids and triglycerides)
is beta-cell dysfunction reversible in type 2 diabetes?
yes
reversed by controlling diet in patients diagnosed less than 10 years ago
who is more likely to get diabetes- someone with a pear or apple shape?
apple shape- greater fat distribution around abdominal organs
[central adiposity]
are micro or macrovascular complications more likely in type 2 diabetic patients?
microvascular
what are the 3 main red flags which will help you distinguish LADA from type 2 diabetes?
- thin patient
- patient losing weight
- PMHx of pancreatic disease
why do we treat hyperglycaemia in type 2 diabetes?
to reduce the risk of complications
what is the only biguanide used in the treatment of type 2 diabetes?
metformin
how do biguanides work in the treatment of type 2 diabetes?
improves sensitivity to insulin
reduced insulin resistance
is there a hypogylcaemia risk with metformin?
no
what is the effect of metformin on weight?
weight neutral usually
can reduce weight
does metformin prevent from microvascular complications?
yes
does metformin prevent from macrovascular complications?
yes
is metformin safe to use in pregnancy?
yes
-so can be used in gestational diabetes of pre-existing type 2 diabetes
lactic acidosis is a rare side effect of metformin, what patients are more likely to get this?
patients with severe renal, cardiac or liver failure
what happens to the tissues in lactic acidosis?
become hypoxic
how do you reduce the potential GI side effects of metformin? (nausea, diarrhoea, anorexia, abdo pain, diarrhoea)
‘start low and go slow’
start at a very low dose and slowly work your way up
how do you reduce the potential lactic acidosis side effect of metformin?
use with caution in patients with liver, cardiac or renal failure
what must the eGFR be to avoid or stop the treatment of type 2 diabetes with metformin?
below 30 eGFR stop metformin
what must the eGFR be to half the treatment dose of metformin in a diabetic patient/
30-45 eGFR
what is the first line agent for type 2 diabetes?
metformin
how do sulphonylureas work?
close the ATP-dependent potassium channes causing depolarisation of the pancreatic beta cell
this depolarisation causes the opening of voltage gated calcium channels and an influc of calcium which stimulates the release of insulin
which has a faster action period- sulphonylureas or insulin sensitisers?
sulphonylureas
is there a risk of hypoglycaemia with sulphonylureas?
yes
do sulphonylureas prevent microvascular complications?
yes
do sulphonylureas prevent macrovascular complications?
no
how do sulphonylureas accelerate the progression of type 2 diabetes?
by causing the accelerated demise of pancreatic beta cells
what is the effect of sulphylureas on weight?
weight gain
when must use avoid using sulphonylureas?
in severe renal or heatic failure
what is the only thiazolidinediones (TZD) available in the treatment of type 2 diabetes?
pioglitazone
how do thiazolidinediones (TZDs) work?
work on nuclear receptors (PPAR-gamma) to increase gene transcription
this increases glucose and fatty acid uptake
(insulin sensitiser)
is there a risk of hypoglycaemia with thiazolidinediones? (TZD)
no
do TZDs prevent microvascular complications?
no
but improve microalbuminuria
do TZDs prevent macrovascular complications?
yes
what are the effects of TZD on heart attack risk and heart failure?
reduces risk of heart attacks
but makes heart failure worse
which diabetes drug increases the risk of hip fractures?
pioglitazone (TZD)
why does the oral response to glucose result in a higher insulin release than glucose entering blood vessels directly? (ie IV)
incretin effect
what are incretins stimulated by?
glucose in the gut
what enzyme breaks down incretins quickly?
DPP-IV
what are the 5 main effects of incretins?
- stimulate insulin secretion
- reduce liver gluconeogenesi
- delay gastric emptying (feeling of satiety)
- direct effect on appetite center (feeling of satiety)
- decrease glucagon secretion
how do incretins (and incretin agonists) cause an increased insulin release?
make the beta cells more sensitive to glucose
are patients on incretin agonists (eg GLP-1) at risk of hypoglycaemia?
no
how do DPP-IV inhibitors work in the treatment of type 2 diabetes?
prevent the action of DPP-IV enzymes therefore prolong the actions of incretins
which is more potent, GLP-1 mimetics or DPP-IV inhibitors?
GLP-1 mimetics
what is the main disadvanatage of GLP-1 over DPP-IV?
injection to administrate
DDP-IV is oral
what is the effect of GLP-1 receptor agonists on weight?
weight loss
what is the effect of DPP-IV inhibitors on weight?
weight neutral
How do SGLT-2 inhibitors work?
prevent the reabsorption of glucose within the kidney tubules by SGLT-2 transporters
is there a risk of hypoglycaemia with DPP-IV inhibitors?
no
is there a risk of hypoglyaemia with SGLT-2 inhibitors?
no
what is the effect of SGLT-2 inhibitors on weight?
weight loss
what are the main disadvantages of SGLT-2 inhibitors? and explain why?
thrush
UTIs
due to increased sugar in urine
what are the 2 broad classes of drugs for type 2 diabetes mellitus? (ignoring insulin)
- insulin dependent
- insulin independent
within the insulin dependent drug group for type 2 diabetes mellitus, what are the 2 sub-groups of drug action?
- drugs which increase insulin secretion
- drugs which increase insulin sensitivity
within the insulin independent drug group for type 2 diabetes mellitus, what are the 2 sub-groups of drug action?
- drugs which slow glucose (or lipid) absorption from the GI tract
- drugs which increase kidney excretion of glucose
what is the action of orlistat for type 2 diabetes?
orlistat decreases the absorption of fats
(insulin-independent)
this indirectly is a benefit to diabetes because it leads to weight loss
compare the polarisation state of a pancreatic beta cell when there is high blood glucose and when there is low blood glucose?
high blood glucose- depolarised
low blood glucose- resting potential is maintained
what is the structure of a ATP-sensitive K channel?
4 inner Kir6.2 subunits
4 outer SUR1 subunits
what are the functions of the Kir6.2 and SUR1 subunits within the ATP-sensitive K channel?
4 Kir6.2 subunits form the potassium selective ion channel
SUR1 subunits regulare the activity of the potassium ion channel
when extracellular glucose is high, ATP binds to what part of the ATP-sensitive K channel and what does this cause?
ATP binds to Kir6.2 subunits
causes closing of channels and depolarisation
when extracellular glucose is low, ADP-Mg++ binds to what part of the ATP-sensitive K channel and what does this cause?
ADP-Mg++ binds to SUR1 subunits
causes opening of channels and maintains the resting potential
sulfonylureas bind to what part of the ATP-sensitive K channel and what does this cause?
bind to SUR1 subunits and so displace the binding of ADP-Mg++
causes closing of channels and depolarisation
compare 1st generation sulfonylureas to 2nd generation sulfonylureas in terms of potency and acting-time?
2nd generation are more potent and longer acting than 1st
why can sulfonylureas cause hypoglycaemic episode?
excessive insulin secretion
which generation of sulfonylureas have a higher hypoglycaemia risk?
2nd generation
why might you give an elderly patient or a patient with reduced hepatic/renal function a 1st generation SU instead of 2nd generation?
to reduce risk of hypos
this patient group is at higher risk
what is the action of glinides for type 2 diabetes?
glinides act similarly to sulfonylureas
bind to SUR1 subunits on ATP-sensitive K channel to close channel and cause depolarisation and hence insulin secretion
(insulin dependent, cause increased insulin secretion)
which drug is more likely to cause hypoglycaemia- sulfonylureas or glinides?
and why?
sulfonylureas
longer-acting than glinides which have rapid onset/offset kinetics
when are glinides taken and why?
before/with meals to reduce postprandial rise in blood glucose
what is GLP-1?
glucagon like peptide-1
what is the function of GLP-1?
enhances glucose uptake by pancreatic beta cells
decreases glucagon release from pancreatic alpha cells
decreases gluconeogenesis by the liver
all to reduce blood glucose
what is GIP?
glucose-dependent insulinotrophic peptide/
gastric inhibitory peptide
what is the function of GIP?
enhances glucose uptake by pancreatic beta cells
slows gastric emptying
both to decrease blood sugar
what cells produce GLP-1?
L cells from ilium and colon
what cells produce GIP?
K cells from jejunum/duodenum
what blood vessel do GLP-1 and GIP first enter?
hepatic portal vein
what hormone do incretin analogues mimic?
GLP-1
what type of drug is extenatide?
incretin analogue
how is extenatide administered?
twice a day subcutaneously
what type of drugs are gliptins?
DDP-IV inhibitors
what is the function of a-glucosidase?
breaks down starch/diasaccharides into absorbable glucose
what is the action of a-glucosidase inhibitors?
inhibit the action of a-glucosidase and so delay absorption of glucose and therefore reduce postprandial increase in blood glucose
what are the main side effects of glucosidase inhibitors?
GI Upset: flatulence loose stools diarrhoea abdo pain bloating
do a-glucosidase inhibitors cause hypos?
no
what are the 3 main adverse effects of TZDs?
weight gain
fluid retention
increased risk of bone fractures
what type of T2DM drus ig dapagliflozin?
SGLT2 inhibitor
what does MODY stand for?
Maturity Onset Diabetes of the Young
what type of inheritence is Maturity Onset Diabetes of the Young (MODY)?
autosomal dominant inheritance
what is the age of onset of Maturity Onset Diabetes of the Young (MODY)?
usually before the age of 25
what are the 2 mutations causing Maturity Onset Diabetes of the Young (MODY) that give 2 distinct phenotypes?
mutation in transciption factor HNF
mutation in glucokinase
compare MODY glucokinase mutations to transcription factor mutations in terms of onset?
glucokinase mutations- onset at birth
transcription factor mutations- young adult onset
compare MODY glucokinase mutations to transcription factor mutations in terms of hyperglycaemia progression?
glucokinase mutations- stable hyperglycaemia
transcription factor mutation- progressive hyperglycaemia
compare MODY glucokinase mutations to transcription factor mutations in terms of treatment?
glucokinase mutations- diet treatment
transcription factor mutations- 1/3 diet, 1/3 oral hypoglycaemic agents, 1/3 insulin
compare MODY glucokinase mutations to transcription factor mutations in terms of complications?
glucokinase mutations- complications rare
transcription factor mutations- complications frequent
what are the 2 classes of neonatal diabetes?
transient neonatal diabetes
permanent neonatal diabetes
when is permanent neonatal diabetes usually diagnosed?
0-6 weeks
when should insulin treatment for transient neonatal diabetes be stopped?
once diabetes has resolved
usually after 3 months
when should insulin treatment for permanent neonatal diabetes by stopped?
lifelong treatment
what is the target blood glucose concentration for a type 1 diabetic pre-meal?
4-7 mmol/l
what is the target blood glucose concentration for a type 1 diabetic 1-2 hours after a meal?
5-9 mmol/l
what are the 4 life-threatening complications of diabetic ketoacidosis?
- cardiac arrest due to hyperkalaemia
- cerebral oedema
- ARDS
- aspiration due to gas in stomach
what is the typical osmolarity in a normal patient?
285 - 295
what is the osmolarity of a patient in hyperglycamic hyperosmolar Syndrome typically?
around 400
how do you calculate osmolarity?
2(Na + K) + glucose + urea
how do you treat hyperosmolar hyperglycaemic state?
- treating underlying cause
- replace fluid and electrolyte losses
- normalising blood glucose
what is the normal range of lactate?
0.6 to 1.2 mmol/L
how do you calculate the ion gap?
[Na+ + K+]- [HCO3- + Cl-]
what is the normal ion gap range?
10 - 18 mmol/L
what is usually associated with type A lactic acidosis?
tissue hypoxaemia
infarcted tissue, cardiogenic shock, hypovolaemic shock
which type of lactic acidosis is associated with diabetes?
type B lactic acidosis
what are the 3 clinical features of lactic acidosis?
hyperventilation
mental confusion
stupor/coma
does a raised anion gap suggest metabolic acidosis or alkalosis?
metabolic acidosis
compare severe DKA to alcohol-induced keto-acidosis in terms of blood glucose levels?
DKA- high blood glucose levels
alcohol-induce keto-acidosis- normal blood glucose lebels
as Hb1Ac increases, what happens to the risk of microvascular complications?
increases
what is the basis of neuropathy?
- small blood vessels to nerves become damaged due to high glucose levels
- reduced oxygen supply causes the nerves to become damaged
what are the 4 main types of neuropathy caused as a complication of diabetes?
- peripheral neuropathy
- autonomic neuropathy
- proximal neuropathy
- focal neuropathy
what type of neuropathy leads to hypoglycaemic unawareness?
autonomic neuropathy
what is amyotrophy?
progressive wasting of muscle tissues
what distribution is peripheral neuropathy usually in?
glove + stocking distribution
is there an increased risk of neuropathy with type 1 or type 2 diabetes?
type 1 diabetes
what is allodynia?
pain from a non-painful stimulation of the skin
what is gastroparesis?
slow stomach emptying
what symptoms does gastroparesis cause?
nausea
vomitting
bloating
loss of appetite
why can gastroparesis make blood glucose levels fluctuate widely and make patient susceptible to hypoglycaemia?
abnormal food digestion
insulin may be in system before food has been absorbed
what is gustatory sweating?
sweating after eating
why might a patient with autonomic neuropathy have trouble seeing in the dark?
autonomic system not working properly so pupil might not dilate enough
what is focal neuropathy?
sudden weakness in one nerve/group of nerves causing muscle weakness
how many times a year should diabetics have a foot exam?
at least once a year
what does low risk mean in terms of diabetic foot risk stratification?
no loss of sensation or pulses
what does moderate risk mean in terms of diabetic foot risk statification?
loss of sensation OR loss of pulses
what does high risk mean in terms of diabetic foot risk stratification
loss of sensation AND loss of pulses
what is charcot foot?
progressive degeneration of weight-bearing joints leading to deformity
how does a charcot foot present?
hot, red, swollen foot
-often mistaken for cellulitis, DVT
(maybe be deformed)
what are the 3 main consequences of diabetic nephropathy?
- development of hypertension
- decline in renal function
- accelerated vascular disease
what do you use to screen for diabetic kidney disease?
urinary albumin creatinine ratio
what drug is used to improve mortality in diabetic kidney disease (ie microalbuminuria or proteinuria)?
ACE inhibitors
can pioglitazone (TZD) be used in chronic kidney disease?
yes
can gliclazide (SU) be used in chronic kidney disease?
in moderate disease yes
not in severe disease
can metformin be used in chronic kidney disease?
in moderate disease yet
not in severe disease
what is glaucoma?
increase in fluid pressure in the eye leading to optic nerve damage
compare diabetic retinopathy and acute hyperglycaemia visual blurring in terms of reversibility?
diabetic retinopathy- irreversible
acute hyperglycaemia- visual blurring- reversible
what are the 4 main stages of retinopathy?
mild non-proliferative
moderate non-proliferative
severe non-proliferative
proliferative
what are cotton wool spots on retinopathy?
ischaemic areas
what are hard exudates the break down products of?
lipids
what hormone does the fertilised egg release which is used to detect pregnancy?
HCG
what are the 3 main hormones that the placenta produces?
human placental lactogen
placental progesterone
placental oestrogens
what 2 hormones produced by the placenta cause insulin resistance in the mother?
placental progesterone
human placental lactogen
if the mother is already predisposed to insulin resistance, what happens when the placental hormones cause further insulin resistance?
raised blood glucose and gestational diabetes
in what trimester does gestational diabetes tend to come on?
third trimester
why does gestational diabetes tend to come on in the third trimester?
because this is the time when the placental grows significantly and so the levels of placental hormones increases
what are the 3 main complications of gestational diabetes? (before delivery)
macrosomia
polyhydramnios
intrauterine death
what are the 3 main complications of maternal diabetes in neonates? (after delivery)
respiratory death (due to immature lungs)
hypoglycaemia
hypocalcaemia
why can neonates born to diabetic mothers (DM or gestational) have hypoglycaemia after delivery?
high sugar load from mother near birth causes excess insulin production.
once born, the baby no longer gets the high blood sugars yet still has high insulin production causing hypoglycaemia
why can macrosomia be a complication of babies born to diabetic (DM or gestational) mothers?
hyperglycaemia causes excess insulin production
insulin is a major growth factor
why should a diabetic pregnant woman have regular eye checks?
pregnancy accelerates retinopathy
compare folic acid dose for a non-diabetic pregnant patient to a diabetic pregnant patient?
diabetic: 5mg
non-diabetic: 400 micrograms
what is the one exception to avoiding the use sulfonylureas in pregnancy?
glibenclamide in MODY
why must you do a post natal glucose tolerance test 6 weeks after delivery in a patient with getational diabetes?
to ensure diabetes has gone
if it still remains after 6 weeks- patient now has type 2 diabetes
