Diabetes Flashcards
what is type 1 DM
autoimmune disorder resulting in absolute insulin deficiency due to beta cell failure
when/how do symptoms occur in type 1 DM
acute onset pre-school and during puberty
what are the symptoms of type 1 DM
severe weight loss ketonuria +/- metabolic acidosis thirst polyuria thrush weakness/fatigue diabetic ketoacidosis
what are the investigations of type 1 DM
autoimmune markers
raised ketones in urine
low c-peptide levels
what are the autoimmune markers of type 1 DM
GAD tyrosine phosphates: - IA-2 - IA-2 beta - ZnT8 HLA association - DQ8 - DQ4
what is the treatment of type 1 DM
insulin dependent
what is Autoimmune Diabetes of Adults (LADA)
this is late onset of type 1 DM
what are the typical symptoms of Autoimmune Diabetes of Adults (LADA)
same as type 2 DM symptoms
non-obese
associated autoimmune conditions
what is the common age affected by Autoimmune Diabetes of Adults (LADA)
25-40
what are the investigations of Autoimmune Diabetes of Adults (LADA)
autoantibody positive
what HbA1c suggest diabetes, what is normal
diabetes = 48 and above normal = 41 and lower
what fasting glucose suggests diabetes, what is normal
diabetes = 7 and above normal = 6 and below
what results in a OGTT suggests diabetes, what is normal
diabetes = 11.1 and above normal = 7.7 and below
what random glucose suggests diabetes
11.1
what does HbA1c provide a measure of
average glucose control over the past 2-3 months
who should be tested for diabetes, how often
women with GDM = tested every 3 years
pre-diabetes = tested yearly
when should repeat testing be carried out for diabetes diagnosis
In the absence of unequivocal hyperglycaemia results
what is type 2 DM
relative insulin deficiency involving hyperinsulinemia and insulin resistance
when/how do the symptoms of type 2 DM start
middle aged/elderly over a few months - years
what are the symptoms of type 2 DM
thirst polyuria thrush weakness/fatigue blurred vision weight loss
what type of diabetes presents with microvascular disease
type 2 DM
what tests are done to diagnose diabetes
Fasting plasma glucose 2hr plasma glucose during oral glucose tolerance test (OGTT) HbA1C C-peptide (plasma) Random plasma glucose
what are the macrovascular complications of type 2 DM
heart disease/atheroma
stroke
what are the microvascular symptoms of type 2 DM
neuropathy
retinopathy
nephropathy
how is type 2 DM treated
in order:
lifestyle changes (lower BMI)
treat other CVD risk factors
lower blood glucose via drugs
what blood glucose should be aimed for in type 2 DM if >70
53
what blood glucose should be aimed for in type 2 DM if <70
48
what is the first line drug in type 2 DM if treatment
metformin
what is the 2nd line drug treatment of type 2 DM
add a second drug to metformin. usually a sulphonylurea
what is the 3rd line drug in treatment of type 2 DM
add a glitazone
what is
Maturity-onset diabetes of the young (MODY)
this is a type of monogenic diabetes with a genetic defect in beta function. familia former early-onset type 2 DM
what are the causes of
Maturity-onset diabetes of the young (MODY), which is more common
autosomal dominant mutation in:
- glucokinases
- transcription factors (MODY) = 75%
what would make you suspect Maturity-onset diabetes of the young (MODY)
onset before 25
strong family history
GAD negative
c-peptide positive
what is the symptoms of Maturity-onset diabetes of the young (MODY) caused by impaired glucokinase activity
onset at birth
stable hyperglycaemia
what is the treatment of MODY caused by impaired glucokinase activity
diet
what is the link between glucokinase and insulin production
Glucokinase acts as the pancreatic glucose sensor
If glucokinase activity is impaired the blood glucose threshold for insulin secretion is increased
what is the symptoms of MODY caused by mutation in transcription factors
onset = adolescence/young adult
progressive hyperglycaemia
frequent complications
what is the treatment of MODY caused by mutation in transcription factors
diet, medication, insulin
when can sulphonylureas be used to treat MODY
if mutation is in HNFA1
what are the two types of neonatal diabetes
transient
permanent
when is transient neonatal diabetes diagnosed, when does it resolve
diagnosed <1wk
resolved at 12 wks
how is transient neonatal diabetes treated
insulin until it resolves
when is permanent neonatal diabetes diagnosed
0-6wks
what is the treatment of permanent neonatal diabetes
lifelong insulin or sulphonylureas
what is the cause of permanent neonatal diabetes
potassium channel gene mutations
what symptom must be asked about in a child with suspected diabetes
new bed wetting
what symptoms must be asked about in a child with suspected DKA
abdominal pain
vomiting
heavy breathing
what is type 3 diabetes
gestational diabetes
what is gestational diabetes
any degree of glucose intolerance arising or diagnosed during pregnancy
when does gestational diabetes usually occur
2nd or 3rd trimester
what is the treatment of gestational diabetes during labour
maintain blood glucose via IV insulin and dextrose
what is the treatment of gestational diabetes
lifestyle
metformin
insulin
what investigation should be done after giving birth? when?
fasting glucose or OGTT 6wks postnatal to ensure resolution
what is type 4 DM
diabetes secondary to another conditions
what conditions can cause type 4 DM
CF haemochromatosis cushing's acromegaly Pheochromocytoma
what drugs can cause type 4 DM
Glucocorticoids
Diuretics
B-blockers
what is diabetic ketoacidosis (DKA)
a disordered metabolic state that usually occurs in the context of an absolute or relative insulin deficiency accompanied by an increased in counter-regulatory hormones
what conditions can cause DKA, which is more common
Type 1 DM = more common
type 2 DM
what are the symptoms of DKA
flushed vomting abdominal pain/tenderness breathless coma
what are the biochemical markers that should be checked in a diagnosis of DKA
ketoaemia significant ketonuria (++) blood glucose Bicarb Venous pH CK Sodium K Blood ketones
what Bicarb would you suspect in DKA
<15
severe <10
what venous pH would you suspect in DKA
<7.3
what ketoaemia would you suspect in DKA, what else could you measure
> 3
OR significant ketonuria (++)
what Blood Glucose would you suspect in DKA, when would you not need this
> 11
BG is not needed if the patent is already known diabetic
what CK would you suspect in DKA
raised
what Na and K would you suspect in DKA
Na = low
K >5.5
what blood ketones would you suspect in DKA
> 5
what amylase and lactate levels would you suspect in DKA
raised
what is the treatment of DKA
replace losses: - fluid (0.9% NaCl, switch to dextrose once glucose <15) -insulin -K prophylactic LMWH monitor ketones
how are ketones monitored in DKA
measure beta-hydroxybutyrate (optimum meter) in blood
measure acetoactate in urine
what is hyperglycaemic hyperosmolar syndrome
a complication of diabetes in which high blood sugar results in high osmolarity without significant ketoacidosis
what are the risk factors to getting hyperglycaemic hyperosmolar syndrome
elderly
type 2 DM
steroids
what are the biochemical markers of hyperglycaemic hyperosmolar syndrome
Hypovolaemia (usually marked) Hyperglycaemia >30 No/mild ketonaemia Bicarb >15 Venous pH >7.3
what causes alcoholic ketoacidosis
excessive consumption of alcohol
what biochemical markers would you expect to find in alcoholic ketoacidosis
dehydrated ketonaemia >3 significant ketonuria (++) Bicarb <15 venous pH <7.3 glucose normal but may be low
what causes lactic acidosis
build up of lactate resulting in a low pH
treatment of alcoholic ketoacidosis
IV pabrinex = high dose vitamins IV fluids = particularly dextrose IV anti-emetics Insulin may be required on occasion Address alcohol dependency
what are the symptoms of alcoholic ketoacidosis
Abdominal pain
Vomiting
Hypotensive
tachypnoeic
what are the types of lactic acidosis
A and B
what is type A lactic acidosis associated with
tissue hypoxaemia (infarct, sepsis, haemorrhage)
when might type B lactic acidosis occur
liver disease
diabetes/ DKA
leukaemic states
what is the treatment of lactic acidosis
Treat underlying condition
Fluids
Antibiotics
Withdraw offending medication
what are the symptoms of lactic acidosis
Hyperventilation
Confused
Coma if severe
what biochemical markers would you expect in lactic acidosis
Reduced bicarb
Glucose variable (often raised)
Absence of ketonaemia
Raised phosphate
when should diabetes tested for in asymptomatic patients
if they are >45 with a BMI >25 (or >23 if asian) and have 1 risk factor
what risk factors would make you consider screening for diabetes
First degree relative with diabetes High-risk ethnicity (non-white) History of CVD Hypertension high HDL cholesterol Polycystic ovary syndrome
how often should diabetes testing be carried out in those with risk factors
minimum of every 3 years
how often should a woman who had gestational diabetes be tested
minimum of every 3 years
what class of drugs metformin
biguanides
what is the mechanism of action of metformin
stimulates AMP-activated protein kinase (AMPK) to reduce hepatic gluconeogenesis.
this decreases insulin resistance and reduces hepatic glucose output
what are the contraindications to metformin
Significant hepatic disease
Significant renal disease (CKD)
Excessive alcohol consumption = risk of lactic acidosis
give examples of Sulfonylureas
gliclazide, glipizide
what is the mechanism of action of Sulfonylureas
cause pancreatic beta cells to secrete insulin by displacing the binding of ADP from the SUR1 subunit which blocks the KATP channel
increases secretion of insulin
what are the side effects of Sulfonylureas
weight gain
hypoglycaemia
abnormal LFTs
what are the contraindications of Sulfonylureas
pregnancy
CDK
give examples of glinides
repaglinide
what are the contraindications to glinides
hepatic impairment
pregnancy
breast feeding
when would glinides be used
if the patient has CKD
give examples of SGLT2 inhibitors
dapagliflozin, canagliflozin, empagliflozin
what is the mechanism of SGLT2 inhibitors
selectively blocks the reabsorption of glucose by SGLT2 un the proximal tubule of the kidneys
what is the side effect of SGLT2 inhibitors
aids weight loss
UTI
thrush
give an example of a glitazone
pioglitazone
when is gliazones used the treatment of type 2 DM
3rd line
what are the side effects of gliazones
weight gain
fluid retention
increased incidence of bone fracture
what is the mechanism of action of gliazones
enhance the action of insulin at target tissues but do not directly affect insulin secretion i.e. they reduce insulin resistance
give examples of incretin analogues
extenatide, liraglutide
what is the mechanism of action of incretin analogues
mimic the action of GLP-1, bind to receptors to increase intracellular cAMP concentrations which stimulates insulin expression and release.
how is incretin analogues administered
SC
what are the side effects of incretin analogues
nausea
pancreatitis
NO hypoglycaemia
what is the mechanism of action of gliptins
competitively inhibits GLP-1 and GIP by the enzyme DPP-4 causing the plasma tireless insulin
give examples of gliptins
sitagliptin (most common), saxagliptin, vildagliptin, linagliptin, alogliptin
what are the side effects of gliptins
nausea
