diabetes Flashcards
what is involved in type 1 diabetes
absolute insulin deficiency - autoimmune beta cell destruction
what is the inflammation seen in beta cells in diabetes called
insulitis
T1DM has a strong link to what HLA genes
HLA DQA
HLA DQB
HLA DR3 +/- DR4
what antibodies are seen in T1DM
anti-GAD (GAD65)
anti-islet cell
tyrosine phosphatases (IA-2, IA2B, ZnT8)
what age does T1DM usually present
pre-school and puberty
small peak in late 30s
is the onset of T1DM acute or gradual
acute
what are the s/s of T1DM
polyuria polydipsia fatigue weight loss ketonuria blurred vision genital thrush
is there normally evidence of microvascular disease at diagnosis in T1DM
no
what infections are people with diabetes more prone to
candida infections
what is the treatment for T1DM
insulin
what is target blood glucose pre meal
4-7 mmol/L
what is the target glucose 1-2 hours after a meal
5-9 mmol/L
what is LADA
late onset diabetes of adulthood - elevated levels of pancreatic autoantibodies in a patient with previously diagnosed diabetes who did not initially require insulin
who tends to get LADA
non-obese males, 25-40
how is LADA differentiated from T2DM
patient is thin/losing weight or has a history of pancreatic disease
is LADA autoantibody positive or negative
positive
what is idiopathic T1DM
patients have permanent insulinopenia and prone to DKA but no evidence of Beta cell autoimmunity
what race are people with idiopathic T1DM
african/asian
is idiopathic T1DM familial/HLA assocaited
strongly inherited
not HLA associated
what is T2DM
non insulin dependent diabetes mellitus
relative insulin deficiency
what is the first line management in T2DM
diet control
who tends to get T2DM
elderly/middle aged
usually obese
are there usually complications at the point of diagnosis of T2DM
yes (prediagnosis time of 6-10 years) e.g. blurred vision
what are 2 causes of insulin resistance
ectopic fat accumulation and increased circulating fatty acids
increased inflammatory mediators
is there usually ketonuria at diagnosis of T2DM
no
what is the WHO criteria for T1DM
raised venous glucose on 2 occasions or OGTT 2 hr value > 11.1 or HbA1c > or = 48 mmol/L
according to WHO, what must a person have in addition to symptoms of hyperglycaemia to have T1DM
raised venous glucose detected once (fasting > 7 or random > 11.1)
according to WHO what must a persons venous glucose be on 2 occasions to have T1DM
raised venous glucose on 2 occasions (fasting > 7 or random > 11.1)
according to WHO what must a persons results be from a OGTT to have T1DM
OGTT 2hr value > 11.1
according to WHO what must a persons HbA1c be to have T1DM
> or = 48mmol/L
what is more accurate to measure glucose levels - urine or blood
blood
what ethnicity is more prone to diabetes
asian/african/afro-carribean
what is the pathophysiology of T2DM
hyperglycaemia –> hyperinsulinaemia –> insulin resistance
compensatory Beta cell hyperplasia causing normoglycaemia
beta cell early failure causing impaired glucose tolerance
beta cell late failure causing diabetes
increased what causes the hyperglycaemia in diabetes
lipolysis
glucose reabsorption
glucagon secretion
hepatic glucose production
decreased what causes the hyperglycaemia in diabetes
insulin secretion
incretin effect
glucose uptake
neurotransmitter dysfunction
what does HbA1c measure
glucose control over past 2-3 months
what is a normal HbA1c
< or = 41
what is a diabetic HbA1c
> or = 48
what is a normal fasting glucose
< or = 6
what is a diabetic fasting glucose
> or = 7
what is a normal 2 hr glucose in OGTT
< or = 7.7
what is a diabetic 2 hr glucose in OGTT
> or = 11.1
what would a diabetic random glucose test be
> 11.1 mmol/L
what are the levels of C peptide like in T1 and T2 diabetes
T1 diabetes - no C peptide
T2 diabetes - some C peptide
what type of diabetes is gestational diabetes
type 3
what is gestational diabetes
any degree of glucose intolerance arising or diagnosed during pregnancy
how is gestational diabetes caused
placental hormones that cause insulin resistance in mother - human placental lactogen and placental progesterone
when is gestational diabetes most likely to occur and why
3rd trimester
- placenta grows most so levels of placental hormones increase
what are the 3 main complications of gestational diabetes in utero
macrosomia
polyhydramnios
intrauterine death
what are the 3 main complications of gestational diabetes in the baby after delivery
respiratory death due to immature lungs
hypoglycaemia
hypocalcaemia
why would you get macrosomia in a baby whose mother has gestational diabetes
hyperglycaemia causes excess insulin production which is a growth factor
why would a neonate whose mother has gestational diabetes become hypoglycaemic
high sugar load from mother near birth causes excess insulin production - once the baby is born no longer getting the high blood sugars yet still has high insulin producing hypoglycaemia
what should be done 6 weeks after delivery to decide if the gestational diabetes is now actually T2DM
glucose tolerance test
what is gestational diabetes screened for with
OGTT
Monogenic diabetes is…
young/old onset
GAD positive/negative
C peptide negative/positive
young onset
GAD negative
C peptide positive
monogenic diabetes has a strong family history
true/false
true
what are some assocaited features of monogenic diabetes
renal cysts
what is MODY
mature onset diabetes of young
monogenic diabetes with genetic defect in beta cell function - primary defect in insulin secretion
what is the inheritance of MODY
autosomal dominant
how is MODY differentiated from T1DM
genetic screening
what is the treatment of MODY
diet treatment and sulfonylurea
do MODY patients usually have no Beta function or some
some beta function
where can mutations occur to cause MODY
glucokinase (GCK/MODY2)
several transcription factors
how does a defect in glucokinase cause MODY
alters the point where glucokinase can sense present of glucose, meaning body can only sense glucose above 7 leading to stable hyperglycaemia
when is the onset of MODY2
birth
what is the treatment of MODY2 with a genetic defect in glucokinase
diet treatment
what is the onset of MODY if the defect is in one of the transcription factors
young adult onset
what is the most common form of MODY
genetic defect in transcription factors
what is MODY1
defect in HNF-4alpha
what is MODY3
defect in HNF-1alpha
what is MODY4
defect in IPF1
what is MODY6
NDF1/neuroD1/B2
what do HNF-transcription factors play a key role in
pancreas foetal development and neogenesis
also regulate B cell differentiation and function
what is the hyperglycaemia like that is seen in MODY with defects in transcription factors
progressive
what is the treatment for MODY with defects in transcription factors
diet treatent
sulfonylureas
insulin
are complications frequent with MODY with defects in transcription factors
yes
what are the 4 categories of type 4 diabetes
pancreatic disease
endocrine disease
drug induced
problems with insulin and its receptor
what pancreatic diseases cause type 4 diabetes
chronic or recurrent pancreatitis
haemochromatosis
cystic fibrosis
what endocrine diseases can cause type 4 diabetes
cushings
acromegaly
phaeochromocytoma
glucagonoma
what drugs can cause diabetes
glucocorticoids
diuretics
BBs
give 3 genetic diseases that can cause diabetes
cystic fibrosis
myotonic dystrophy
turners syndrome
what is the incretin effect
insulin response to oral glucose is greater than the response to IV glucose
what happens to the incretin effect in T2DM
it is reduced
ingestion of food stimulates the release of what (2)
GLP-1
GIP
where is GLP-1 released from
L cells of the ileum
where is GIP released from
K cells in the duodenum
where do GLP-1 and GIP go when they are released
into the hepatic portal vein
what do GLP-1 and GIP do
enhance insulin release from pancreatic B cells and delay gastric emptying causing enhanced glucose uptake and utilisation
what effect do GLP-1 and GIP have on the diet
cause feeling of satiety
what does GLP-1 do to liver gluconeogenesis
reduces
what effect does GLP-1 have on glucagon release from pancreatic alpha cells
decreases glucagon production –> decreased glucose production
how are the actions of GLP-1 and GIP terminated and by what
DPP4 within minutes
dipeptidyl peptidase 4
where is insulin released into
hepatic portal vein
what does insulin do to gluconeogenesis
inhibits
what does insulin do to glycogenolysis
inhibits
what does insulin do to glucogenesis
stimulates
how does insulin inhibit lipolysis
encourages entry of fatty acids into adipose tissues of body
how does insulin promote protein synthesis
promotes uptake of amino acids into muscles and other tissues
how would you describe the normal release of insulin
biphasic - rapid phase of preformed insulin (5-10 mins) and slow phase (1-2 hours)
what are 2 macrovascular complications of diabetes
heart disease
stroke
what does AGE-RAGE stand for
Advanced Glycation End products
Receptor for AGE
what is glycation
non-enzymatic covalent bonding of a protein or lipid molecule with carbohydrates such as glucose
what are the 3 main microvascular complications of diabetes
retinopathy
nephropathy
neuropathy
how do these microvascular complications happen
Hyperglycaemia + hyperlipidaemia –> AGE-RAGE, hypoxia, oxidative stress, inflammation, mitochondrial dysfunction
how does neuropathy occur
small blood vessels to vessels become damaged due to high glucose levels - reduced oxygen supply causes nerves to become damaged
how do you describe the distribution of peripheral neuropathy in diabetes
glove and stocking distribution
distal symmetric or sensorimotor neuropathy
what are some s/s that indicate peripheral neuropathy
numbness//insensitivity tingling/bussing sharp pains/cramps sensitivity to touch allodynia loss of balance coordination
what are some treatments for painful neuropathy
amitriptyline duloxetine gabapentin pregabalin (Combinations not recommended)
what is diabetic focal neuropathy
appears suddenly and affects specific nerve/group of nerves
what nerves/groups of nerves are most commonly affected in focal neuropathy
head
torso
leg
what are some s/s of focal neuropathy
unable to focus eye/double vision/aching behind eyes
bell’s palsy
pain in thigh/chest/lower back/pelvis
pain on outside of foot
proximal neuropathy is more common in who
elderly T2DM
what is proximal neuropathy assoc. with
proximal muscle weakness and marked weight loss
what are some other names for proximal neuropathy
lumbosacral plexus neuropathy, femoral neuropathy or diabetic amyotrophy
what does proximal neuropathy start with
pain in the thighs, hips, buttocks or legs
does proximal neuropathy usually start on one or both sides of the body
one
what is the name for the neuropathy that affects nerves regulating heart rate and blood pressure as well as control of internal organs e.g. those involved in gastric motility, respiratory function, urination, sexual function and vision
autonomic neuropathy
why might someone with autonomic neuropathy not be able to see well in the dark
autonomic system not working so not able to dilate pupil properly
what are 4 manifestations of autonomic neuropathy affecting the digestive system
constipation (gastric slowing)
diarrhoea (gastric frequency)
gastroparesis
oesophagus nerve damage
what is gastroparesis
slow stomach emptying
what are some s/s of gastroparesis
persistent nausea and vomiting, bloating and loss of appetite
how can gastroparesis make someone at risk of hypo
can make blood glucose fluctuate widely and insulin may be in system before food is digested due to abnormal digestion
what is some dietary advice you could give to someone with gastroparesis
smaller, more frequent food portions
low fat, low fibre
may need liquid meals
what drugs can help with gastroparesis
promotility drugs
anti-nausea medications
serotonin antagonists
what are 3 examples of promotility drugs
metoclopramide
domperidone
erythromycin
what is an example of an anti-nausea drug
prochlorperazine
what is an example of a serotonin antagonist
ondansetron
how could you treat the abdominal pain in gastroparesis
NSAIDs low dose tricyclic antidepressents gabapentin tramadol fentanyl
what are 2 other treatments for gatroparesis
botulinum toxin
gastric pacemaker
what would be a symptom of oesophageal nerve damage
difficulty swallowing
how can diabetic autonomic neuropathy affect the sweat glands
stops them working so cant regulate temperature or causes perfuse sweating at night or while eating (gustatory)
what are some treatments for diabetic autonomic neuropathy affecting the sweat glands
topical glycopymolate
clonidine
botulinum toxin
how does diabetic autonomic neuropathy affect the heart and blood vessels
interferes with ability to adjust BP and HR
in diabetic foot screening for diabetic neuropathy what is considered low risk
no loss of sensation or pulses
in diabetic foot screening for diabetic neuropathy what is considered moderate risk
loss of sensation or pulses
in diabetic foot screening for diabetic neuropathy what is considered high risk
loss of sensation and pulses
what are 4 other diagnostic tools for diabetic neuropathy
nerve conduction studies/electromyography
HR variability
US of bladder/urinary tract
gastric emptying study
what is diabetic nephropathy
progressive kidney disease caused by damage to capillaries in kidney glomeruli
what is diabetic nephropathy characterised by
nephrotic syndrome and diffuse scarring of glomeruli
what are 2 other names for diabetic nephropathy
kimmelsteil wilson syndrome
nodular glomerulosclerosis
what are the consequences of diabetic nephropathy
hypertension
decline in renal function
accelerated vascular disease
who is screened for diabetic nephropathy
all patients 12 or older at diagnosis and annually
what is used to screen for diabetic nephropathy
urinary ACR
dipstick test
U+Es (eGFR)
may use random rather than first pass sample as initial check
what are some risk factors for nephropathy progression
hypertension cholesterol smoking poor glycaemic control albuminuria
what is the target BP in all diabetic patients
< 130/80
what is the target HbA1c in diabetic patients
around 53 (48-58)
what should diabetic patients with microalbuminuria or proteinuria be started on
ACEI/ARB
what eye changes occur in acute hyperglycaemia
visual blurring (reversible)
what 4 other diabetic eye diseases are there
diabetic retinopathy
cataracts
glaucoma
retinal detachment
what are the 4 stages of diabetic retinopathy
mild non-proliferative (background)
moderate non-proliferative
severe non-proliferative
proliferative
how is retinopathy graded
R0-R4
M1 and M2
how often should diabetic patients be screened for retinopathy
annually
what are cotton wool spots
ischaemic areas
what are hard exudates
lipid breakdown products
what is IRMA
intra-retinal microvascular abnormalities - abnormalities of blood vessels/precursor to neovascularisation but blood vessels aren’t leaking
what are some treatments for diabetic retinopathy
laser
vitrectomy
anti-VEGF injections
what % of diabetic men have erectile dysfunction
50%
what are the 2 causes of erectile dysfunction in diabetes
vascular
neuropathy
what causes diabetic ketoacidosis
uncontrolled lipolysis
what are some precipitants of DKA
insulin omission
infection
MI
who is more prone to DKA type 1 or 2
type 1
in DKA what would ketonaemia be
> 3 mmol
in DKA what would ketonuria be
> ++
in DKA what would blood glucose be
> 11
in DKA what would bicarbonate be
< 15
< 10 in severe
in DKA what would venous pH be
< 7.3
in DKA what would K be
> 5.5
in DKA what would creatinine be
raised
in DKA what would Na be
low
in DKA what would lactate be
raised
in DKA what would amylase be
raised
in DKA would the anion gap be raised or decreased
raised
what are some s/s of DKA
thirs/dehydration polyuria flushed vomiting abdo pain kussmaul breathing smell of ketones on breath (pear drops) increased HR
what is the treatment for DKA
fluids - 0.9% saline
insulin: IV infusion, 0.1 unit/kg/hour
once glucose is below 15 start infusion of 5% dextrose
what does blood ketone testing measure
beta-hydroxybutyrate
what is normal blood ketone level
< 0.6
what does urine ketone testing measure
acetoacetate - measures levels 2-4 hours previously
what are some life threatening complications of DKA
cardiac arrest due to hyperkalaemia - arrhythmias cerebral oedema following fluid resus ARDS aspiration due to gas in stomach gastric stasis thromboembolism AKI
who is more prone to hyperglycaemic hyperosmolar syndrome
T2DM
what is the mortality rate of DKA
<2 %
what is the mortality rate of HHS
10-50%
who tends to get HHS
older patients or younger afro-carribean
what has often occurred pre presentation of HHS
high refined CHO intake
what drugs is HHS associated with
glucocorticoids/steroids
thiazide diuretics
is diabetes always known on presentation of HHS
not always
what are some precipitants of HHS
infection
is hyperglycaemia higher in DKA or HHS
HHS, usually > 50
is there any ketonuria in HHS
none/mild
what is bicarbonate level in HHS
> 15
what is the venous pH in HHS
> 7.3 - not acidotic
what is osmolality in HHS
> 320, usually around 400
what is Na like in HHS
raised
what is the treatment of HHS
fluids
insulin
sodium (o.5 mmol/L/hr)
LMWH
why should fluids be given more cautiously in HHS
higher risk of fluid overload
is insulin always required in HHS
no
also given more slowly as more sensitive (3 units/hour)
why is LMWH given in HHS
comorbidities common - screen for vascular events e.g. MI, sepsis
what is going on…
elderly female
heavy alcohol intake for years
admitted with recurrent vomiting
on 16 different medications including acamprosate
she is hypotensive, tachypnoeic and difficult to rouse
alcohol induced ketoacidosis
what is the treatment for alcohol induced keto-acidosis
IV pabrinex
IV fluids
IV antiemetics
insulin (maybe)
is there ketonuria/ketonaemia in AIKA
ketonaemia > 3
ketonuria significant
what is bicarb usually in AIKA
< 15
what is venous pH in AIKA
< 7.3
what is glucose levels in AIKA
normal/low
what is lactate
end product of anaerobic metabolism of glucose
clearance of lactate involves ____ uptake and ____ conversion into _____ then _____
hepatic uptake
aerobic conversion
pyruvate
glucose
what is normal lactate
0.6 - 1.2
when is lactate lowest
fasting state
what can increase lactate to 10
severe exercise
what happens to the ion gap in lactic acidosis
raised
what is the ion gap
[K+ + Na+] - [HCO3- + Cl-]
what is a normal ion gap range
10-18
what is lactic acidosis type A
assoc. tissue hypoxaemia
e. g. infarcted tissue (ischaemic bowel), cardiogenic shock, hypovolaemic shock, sepsis, haemorrhage
what is lactic acidosis type B associated with
liver disease
leukaemic states
diabetes
rare inherited conditions
what are the clinical features of lactic acidosis
hyperventilation
mental confusion
stupar/coma
what happens to bicarbonate in lactic acidosis
reduced
is there ketonaemia in lactic acidosis
no
what happens to phosphate in lactic acidosis
raised
what is the tx of lactic acidosis
fluids, antibiotics
what is wolfram syndrome
rare genetic condition causing DI, DM, optic atrophy, deafness and neuro abnormalities (DIMOAD)
what is the equation for osmolarity
2(Na + K) + glucose + urea
what is charcot foot
progressive degeneration of weight bearing joints leading to deformity
how does charcot foot present
hot red swollen foot
what can charcot foot often be mistaken for
DVT or cellulitis
what causes Bardet Biedl syndrome
insest parents
what are some s/s of bardet biedl syndrome
polydactyly hypogonadal visual/hearing impairment mental retardation diabetes obese
what is the folic acid dose for non-diabetic pregnant patient
400mcg
what is the folic acid dose for diabetic pregnant patient
5mg
