(endo) type II diabetes mellitus Flashcards
what is type II diabetes mellitus?
a condition that occurs arises as a result of insulin resistance and beta cell failure causing chronic hyperglycaemia
what is type II diabetes mellitus associated with?
associated w obesity (and genetic risk)
how is the resultant hyperglycaemia of T2DM managed most commonly?
most commonly initially managed by changes to diet + weight loss
with time, may need insulin therapy
how does the age at which T2DM develops affect life expectancy?
if diagnosed later in life = not much change in life expectancy
if diagnosed earlier in life = reduces life expectancy a fair amount
what are the stages of T2DM development?
1) normal
2) intermediate state
3) T2DM
what results are expected in normal healthy patients for the following tests?
1) fasting glucose levels
2) 2-hour glucose OGTT
3) HbA1c
1) fasting glucose = <6 mmol/L
2) OGTT = <7.7 mmol/L
3) HbA1c = <42 mmol/mol
what results are expected in T2DM patients for the following tests?
1) fasting glucose levels
2) 2-hour glucose OGTT
3) HbA1c
1) fasting glucose = >7 mmol/L
2) OGTT = >11 mmol/L
3) HbA1c = >48 mmol/mol
what is it the term to describe a fasting glucose level between 6-7 mmol/L?
impaired fasting glycaemia
what is it the term to describe a OGTT between 7.7-11 mmol/L?
impaired glucose tolerance
what is it the term to describe a HbA1c between 42-48 mmol/mol?
pre-diabetes
non-diabetic hyperglycaemia
explain how insulin resistance and insulin production change as T2DM develops
insulin production is high and resistance is low in healthy patients
progressively, insulin resistance increases and to compensate, initially, insulin production increases
by the time T2DM develops, insulin resistance peaks and insulin production falls very low
(as beta cell failure occurs due to persistent insulin resistance even after increased production)
what is the biggest contributory factor to the development of T2DM?
insulin resistance
but a degree of beta cell failure is required
what random glucose level allows for a diagnosis of diabetes?
a random glucose levels of = 11.1 mmol/L
+ SYMPTOMS
= diagnosis of diabetes
explain how beta cell failure occurs in T2DM
there is compensatory insulin production by beta cells as a response to the increasing insulin resistance in developing T2DM
insulin production begins to wane + cannot keep up w/reverse the insulin resistance
= beta cell failure (due to being overworked)
patients w T1DM have absolute insulin deficiency
patients w T2DM have relative insulin deficiency
differentiate between the two
absolute insulin deficiency = no insulin production at all due to autoimmune damage to the beta cells of the pancreas
relative insulin deficiency = some insulin production occurs BUT is not sufficient enough to overcome the insulin resistance
why does T2DM no usually lead to ketogenesis?
normally w T2DM = there is RELATIVE, not absolute insulin deficiency
so there is sufficient insulin to inhibit ketogenesis in the liver
= reducing the risk of diabetic ketoacidosis
in which scenarios do patients w T2DM present with DKA?
possible due to infection, sepsis etc
what is the biggest risk with long-duration T2DM?
long duration can lead to absolute insulin deficiency as the overworked beta cells lose their function completely eventually
= no insulin production at all
= DKA risk (if not on insulin therapy, which is unlikely at this stage)
what underpins the pathophysiology of T2DM?
adipocytokines internal adiposity insulin resistance beta cell failure genetics
what is the response of the following individuals to an IV glucose challenge?
a) normal glucose tolerance
b) impaired glucose tolerance
c) T2DM
(describe the glucose levels initially and the level of insulin production)
a) normal glucose levels initially; followed by a sharp peak of insulin release (first + second phase)
b) slightly higher than normal glucose levels; followed by a medium peak in insulin levels
c) very high glucose levels; followed by no/negligible peak in insulin
first phase insulin release is lost in patients w T2DM
what does this meal?
in response to a meal, stored insulin is released as part of the first phase insulin response in the first 10 mins and then over the next 2-3 hours, in the second phase insulin response, more insulin is produced
in T2DM, no stored insulin is released (i.e. first phase insulin release) is lost
what are the main implications of a lack of insulin in T2DM?
reduced/no insulin (also increases glucagon secretion)
= less glucose uptake into myocytes and hepatocytes
= increased glycogenolysis + gluconeogenesis
= increased HGO
the metabolic clearance rate of glucose in T2DM is significantly diminished
why is this the case?
in T2DM, no insulin
= no glucose uptake into hepatocytes + no subsequent conversion into glycogen for storage
= resultant excess glucose is converted into lactate
= lactate then taken to liver and converted into glucose
= increases plasma glucose even more
why does gluconeogenesis increase in T2DM?
in T2DM, no insulin
= increased lipolysis and proteolysis
= increased released of substrates (i.e. glycerol, NEFAs, gluconeogenic AAs)
= influx of substrates in the liver that can be used for gluconeogenesis
(further stimulated by increased glucagon secretion)
