type 2 diabetes mellitus Flashcards
what is type 2 diabetes mellitus?
condition in which the combination of insulin resistance and beta cell failure result in hyperglycaemia
associated with obesity
the resultant hyperglycaemia may be initially managed with diet and weight loss
with time, glucose lowering therapy and insulin will be needed
when dies T2DM develop?
traditionally thought to be a disease of late adulthood
but there is evidence to show it can present through every decade of life
and prevalence is increasing in all age groups, especially early adulthood
what is the epidemiology of T2DM?
prevalence varies enormously
overall increasing prevalence
occurring and being diagnosed younger
prevalence is greatest in ethnic groups that move from rural to urban areas (eg. india)
what are the stages of development of T2DM?
normal:
insulin resistance low
insulin production normal
intermediate state:
insulin resistance rising (almost at peak)
insulin production is really high
T2DM:
insulin resistance at max
insulin production really low
what are the measures of glucose like at different stages during the progression of T2DM?
FASTING GLUCOSE
normal: <6 mmol/L
middle: impaired fasting glycaemia
T2DM: >7 mmol/L
2 HR GLUCOSE (OGTT)
normal: <7.7 mmol/L
middle: impaired glucose tolerance
T2DM: >11 mmol/L
HbA1c
normal: <42 mmol/mol
middle: pre-diabetes
T2DM: >48 mmol/mol
(high random glucose with symptoms of diabetes - diagnosis)
what happens to beta cell function in T2DM?
beta cell function decreases over course of disease
at time of diagnosis it is around 50%
it continues to decrease after diagnosis and treatment (depending on efficacy)
what does relative insulin deficiency mean in terms of T2DM?
insulin is still being produced by the beta cells of the pancreas, but not enough to overcome insulin resistance
this is relative insulin deficiency
this is important as it explains why T2DM isnt associated with ketoacidosis
ketones usually form when there is no insulin present
(if type 2 people have ketones, it is usually for some other reason, such as infection)
what is long duration T2DM?
when beta cell failure may progress all the way to complete insulin deficiency
they are usually on insulin at this point anyways
but it is important not to stop as this could cause ketoacidosis
what is the pathophysiology of T2DM?
down to:
genes
intrauterine environment
adult environment
results in insulin resistance and insulin secretion defects
fatty acids are important in pathogenesis and complications
HETEROGENOUS
people develop it at variable BMIs, ages and progress differently
what happens to first phase insulin release in T2DM?
it is lost
normally there is a sharp raise in insulin as stored insulin is released
in T2DM, this doesnt happen, there is just a very slow and slight increase.
people with T2DM do not have this stored insulin
what is the result of reduced insulin production in T2DM?
there is reduced uptake of glucose into skeletal muscle
also hepatic glucose production is also increased due to both a reduction in insulin and an increase in glucagon action
so glucose is not just coming from the diet
what is the normal relationship between insulin secretion and sensitivity compared to that in T2DM?
normally at high insulin secretion, sensitivity is low
and at low secretion, sensitivity is high
in T2DM:
people fall off the curve
for any degree of insulin sensitivity they secrete less insulin
what drives insulin resistance?
very complicated
effectively:
a toxic, pro-inflammatory state is created
what is the genetics of T2DM?
monogenic:
single gene mutation –> diabetes (MODY)
“born with is, is always gonna develop it”
polygenic:
single nucleotide polymorphisms increase risk of diabetes
“not born with it but high risk and may develop later depending on other factors”
the SNP’s responsible can be investigated using GWAS
each individual SNP only has a mild effect on risk, there are just many
what is the role of obesity in T2DM?
major risk factor
fatty acids and adipocytokines are important
also central vs visceral obesity (visceral is worse)
80% of people with T2DM are obese
weight reduction is a useful treatment
apart from genes and obesity, what other factors are associated with T2DM?
perturbation is microbiota:
may cause: obesity, insulin resistance
bacterial lipopolysaccharides fermentation to short chain FA, bacterial modulation bile acids
inflammation signalling metabolic pathways
most studies are correlative
intrauterine growth retardation:
Weight at age 1 year <8.16kg, 22% had type 2 diabetes of IGT
Weight age 1 year >12.25 kg, 6% had type 2 diabetes or IGT
so lower birth weight means higher chance of T2DM
how does T2DM present?
hyperglycaemia obesity dyslipidaemia fewer osmotic symptoms than type 1 complications (micro and macrovascular) (as it comes along more gradually than type 1) insulin resistance later insulin deficiency
what are risk factors for T2DM?
age increased BMI ethnicity PCOS family history inactivity
how is T2DM diagnosed?
first line test is HbA1c: (not used for type 1 as it is sudden onset) 1x HbA1c >48mmol/L with symptoms OR 2x HbA1c >48 if asymptomatic
what is hyperosmolar hyperglycaemic state?
presents commonly with renal failure
insufficient insulin for prevention of hyperglycaemia but sufficient insulin for suppression of lipolysis and ketogenesis
absence of significant ketoacidosis
often has an identifiable precipitating event (infection, MI)
hyperosmolar must mean you are peeing loads
it is a life threatening state
how is T2DM managed?
diet oral medication (metformin) structured education may need insulin later remission/reversal
(in type 1 you give insulin to treat)
you also have to prevent complications such as retinopathy, neuropathy, nephropathy, CVD
what are the principles of what will happen during a T2DM consultation?
glycaemia:
HbA1C
glucose monitoring if on insulin, medication review
weight measurement
blood pressure
dyslipidaemia: cholesterol profile
screening for complications:
foot check
retinal screening
eGFR
what are the dietary recommendations for people with T2DM?
total calories control reduced calories as fat reduced calories as refined carbohydrate increase calories as complex carbohydrate increase soluble fibre decrease sodium
(completely different from Type 1 as you dont get them to lose weight)
what are the main facets of pathophysiology in T2DM and how do we treat them?
excess hepatic glucose production:
reduce it ->
metformin
resistance to action of circulating insulin:
increase sensitivity ->
metformin
thiozolidinediones
inadequate insulin production for extent of resistance: boost secretion -> sulphonureas DPP4-inhibitors GLP-1 agonists
excess glucose in circulation:
inhibit carbohydrate gut absorption, inhibit renal glucose reabsorption ->
alpha glucosidase inhibitor
SGLT-2 inhibitor
(all of these are addressed by weight loss)
(gastric bypass has the potential to induce remission)
