Diabetes Flashcards
what is diabetes
an elevation of blood glucose above a diagnostic threshold
what is type 1 diabetes
autoimmune destruction of the pancreatic beta-cells resulting in absolute insulin deficiency
what are the 2 main subdivisions of type 1 diabetes
1A: immune mediated
1B: non-immune mediated
what is the most common subtype of type 1 diabetes
type 1A
type 1A T1DM
involves an environmental trigger in a genetically susceptible individual mediated by an auto-immune process within the pancreatic β-cell
what does LADA stand for
latent autoimmune disease in adults
what is LADA
a ‘slow-burning’ variant of type 1A with slower progression to insulin deficiency occurs in later life
type 1B T1DM
involves patients with permanent insulinopenia and who are prone to DKA but have no evidence of β-cell dysfunction or autoantibodies
ethnicity associated with type 1B T1DM
African or Asian ancestry
peak incidence of diagnosis of T1DM
10-14 yrs
name the 2 high risk genotypes associated with T1DM
HLA
DR3-DQ2 and DR4-DQ8
what is the cause of symptoms of T1DM in patients under 1
MODY
why cant children under 1 be diagnosed with type 1 diabetes
you need an immune system to develop T1DM
pathophysiology of T1DM (4)
- genetic susceptibility
- environmental trigger
- T-cell mediated autoimmune response with production of autoantibodies that destroy b-cells
- absolute insulin deficiency
clinical presentation of T1DM
acute onset
severe weight loss
polydipsia, polyuria
weakness, fatigue
diagnostic criteria for T1DM
fasting glucose >7 with symptoms
random glucose >11 with symptoms
if asymptomatic repeat test
use of HbA1C in type 1 diabetes
used to monitor disease NOT as a diagnostic tool
management of T1DM
basal bolus insulin regimen
name the 4 main antigens linked to T1DM
glutamic acid decarboxylase
islet antigen 2
insulin
ZnT8 transporter
complication of injecting insulin into the same place
lipohypertrophy
name the 2 surgical management options for type 1 diabetes
pancreatic islet transplantation
whole pancreas transplantation
who usually gets a pancreatic islet transplantation
people with really badly controlled diabetes + complications despite maximal treatment
when do people with T1DM usually get a whole pancreas transplant
end-stage kidney disease at the same time as a kidney transplant
what is insulin resistance
reduced ability of organs to respond to ‘physiological’ insulin levels due to reduced insulin sensing and/or signalling
what is the most common association with insulin sensitivity
obesity
name some risk factors for insulin sensitivity
inactivity, FHx of diabetes, PCOS, hypertension, heart disease, smoking
cause of insulin resistance in skeletal muscle
impairment of insulin signalling
cause of insulin resistance in adipose tissue
obesity-induced inflammation as adipose tissue secretes pro-inflammatory cytokines e.g. TNF-⍺
pathway-selective hepatic insulin resistance
hepatic lipogenesis remains elevated as insulin signalling to lipid metabolism is intact
what is leprechaunism
rare autosomal genetic trait involving mutations in the insulin receptor
what is another name for leprechaunism
Donohue syndrome
clinical presentation of leprechaunism
severe insulin resistance
developmental abnormalities: elfin facial appearance, growth retardation, absence of SC fat, decreased muscle mass
what is rabson medenhall syndrome
rare autosomal recessive trait which presents with severe insulin resistance, hyperglycaemia and compensatory hyperinsulinemia
name a skin change seen in rabson medenhall syndrome
acanthosis nigricans (hyperpigmentation)
how do we measure insulin sensitivity
hyperinsulinemic-euglycemic clamp
management of insulin resistance
eat less, move more
meds: metformin, TZDs
name some complications of insulin resistance
diabetes, Alzheimer’s, chronic kidney disease, gout, acne, PCOS, cancer
what causes type 2 diabetes
insulin resistance with relative insulin deficiency
name some non-modifiable risk factors of T2DM
increasing age - β-cell function declines with age
genetics
ethnicity - south asian, african and afro-caribbean descent
modifiable risk factors for T2DM
obestiy
diet - high dietary fat, red and processed meat
physical inactivity
symptoms of T2DM
gradual onset
symptoms of complications may be the first clinical encounter
thirst, polyuria, blurred vision, weight loss, recurrent infections and tiredness
clinical sign of T2DM
acanthosis nigricans
investigations of T2DM
fasting glucose > 7
random glucose >11.1
HbA1C > 48
first line pharm management of T2DM
metformin
what should a T2DM patient with atherosclerotic CVD be given
metformin + GLP1 receptor antagonist
what should a T2DM patient with heart failure or CKD be given
metformin + SGLT2i first line
or
GLP-1 receptor antagonist second line
HbA1C target for T2DM patients
53
how can we prevent T2DM
weight loss in patient with a BMI >30
what does MODY stand for
maturity onset diabetes of the young
what is MODY
early onset of non-insulin dependent diabetes
what is the most common form of monogenetic diabetes
MODY
inheritance seen in MODY
autosomal dominant
name the most common type of mutation seen in MODY
transcription factors
what are the 3 main types of mutations seen in MODY
transcription factors
glucokinase
MODY X
pathophysiology of MODY
Genetic defective glucose sensing in the pancreas and/or loss of insulin secretion
glucokinase mutation in MODY
glucose sensing defect - blood glucose threshold for insulin secretion is increased
name the main transcription factor mutations seen in MODY
HNF-1⍺, HNF-1β, HNF-4⍺
clinical presentation of glucokinase mutations in MODY
onset at birth
stable hyperglycaemia
clinical presentation of transcription factor mutations in MODY
adolescence/ YA onset
progressive hyperglycaemia
investigations used to diagnose MODY
oral glucose test
genetic testing to confirm the type of mutation
oral glucose test result for a patient with glucokinase mutation MODY
high fasting blood glucose but bring their glucose down when given oral challenge
oral glucose test result for a patient with transcription factor mutation MODY
normal fasting blood glucose but doesn’t respond well to glucose challenge
management of glucokinase mutation MODY
can be managed with diet alone
management of transcription factor mutation MODY
DIET + insulin or sulphonylureas
what kind of diabetes is neonatal diabetes
monogenetic diabtetes
name a mutation that commonly causes neonatal diabetes
Kir6.2
pathophysiology of neonatal diabetes
mutations in the glucose sensing mechanism e.g. in the ATP sensitive K channel
clinical presentation of neonatal diabetes
diabetes diagnosed < 6 months
polydipsia, polyuria
dehydration
DKA
investigation of neonatal diabetes
blood glucose
management of neonatal diabetes
sulphonylureas
what is congenital hyperinsulinism
inappropriate and unregulated insulin secretion, which results in severe, persistent hypoglycaemia in new born babies, infants, and children
management of congenital hyperinsulinism
diazoxide
name 3 conditions associated with diabetes
cystic fibrosis
wolfram syndrome
barget-biedl syndrome
what is gestational diabetes
diabetes that is diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation
what causes gestational diabetes
Placental progesterones and hPL produce insulin resistance in the mother, meaning more nutrients diverted to foetus
in patients with insulin resistance before pregnancy, this raises blood glucose too high
management of pre-existing diabetes during pregnancy
pre-pregnancy counselling
folic acid 5mg
consider change of meds
start aspirin 150mg at 12 weeks
why do we give high risk pregnancies aspirin
reduce the risk of pregnancy-induced hypertension
drug treatment of T1D during pregnancy
insulin
may require an increased dose
drug treatment of T2D during pregnancy
metformin
will probably need to add insulin
management of gestational diabetes
lifestyle, metformin
may need to add insulin
management of gestational diabetes after birth
6 week post natal fasting glucose or GTT to ensure resolution
gestational diabetes that persists post-natally
type 2 diabetes
how to prevent type 2 diabetes after gestational diabetes
healthy weight and diet
annual fasting glucose
complications associated with type 1+2 diabetes in pregnancy
congenital malformation
prematurity
intra-uterine growth retardation
name some complications of gestational diabetes
macrosomia
polyhydramnios
interuterine death
what is macrosomia
very large baby - > 90th centile
what causes macrosomia in gestational diabetes
maternal hypoglycaemia is transferred across the placenta, resulting in foetal hyperglycaemia
causes foetal hyperinsulinemia
what is polyhydramnios
too much fluid around the foetus
complications in a neonate following gestational diabetes
respiratory distress
caudal regression syndrome
ureteric duplications
