type 2 diabetes Flashcards
pathophysiology of type 2 diabetes
COMBINATION of insulin resistance (the unique characteristic) and beta cell failure that result in hyperglycaemia
how is the resultant chronic hyperglycaemia initially managed? can it be reversable?
diet/ weigh loss yes it can
is diet sufficient management long term?
no, glu lowering needed, including insulin
what diseases may trigger diabetes presentation?
pancreatic damage or other endocrine disease
observations on the prevalence of t2d
varies enormously across ehtnic gorups
greatest in ethnic groups that move form rural to urban lifestyle
what are the changes observed in the epidimeology of t2 diabetes?
prevalence incr in general from past
diab occuring and being diagnosed younger
how many stages are there in the t2d spectrum and what are the 3 factors that are different in each ?
3 stages: 1) normal, 2) intermediate 3) type 2 diabetes
and the three factors are: 1) fasting glucose levels 2) imparied glu tolerance 3) hba1c
range values for fasting glu, imparied glu tolerance and hba1c for the 3 stages of disease
fasting glu: 6 <intermid stage <7 mmol/L
(when equal to 6 and 7 included in the other respective categories)
impaired glu tol: 7.7</=mid<11 mmol/L
hbaic: 42</= mid< 48
at which disease stage is insulin prod the highest/ peaks? What is the overall pattern
intermediate: peak (low before and drops even lower than before- can even reach 0 during t2d)
what is the pattern of insulin resistance level?
zero at normal , slowly increases in intermediate, plateaus at t2d
what is the clinical term for the intermediate stage
pre-diabetic hyperglycaemia or pre-diabetes
what is the term for fasting glucose levels at the intermediate stage?
Impaired fasting glycaemia
what is the term for impaired glu tolerance at intermediate stage?
impaired glu tolerance
when can you diagnose diabetes?
diabetic random glu and symptoms of diabetes
(see slide 12) why do t2d patients present at earlier stages of b cell function loss compared to t1d patients?
Because even at 50% loss (in contrast to 80% loss for average presentation in type 1) you are resistant so the 50% that are working are not enough bc theres resistance while theres no resist for type 1
what is a clinical scenario of diabetes where this point of the resistance acting as a catalyst for your presentation even with not that huge losses of b cells?
pregnancy
what is this phenomenon of not enough insulin production to overcome insulin resistance called?
RELATIVE insulin deficiency
why does the hyperglycemia encountered in t2d usually does not cause ketosis?
bc of RELATIVE insulin def. bc there IS insulin to inhibit ketone body production in liver, its just that the target cells in body are resistant to it but it EXISTS in circulation so can still inhibit ketone bodies.
when can type 2 diab get ketosis?
after theyve had infection in pancreas, diabetes for very long and pancr is shutting down- no glu prod cytotoxic or lipotoxic (from too much lip not being conv to ketone bod bc too much insulin perhaps?) pancr (10-20 yrs),
is it better to stop insulin in someone with long term type 2 (maybe u see theyre on low dose and want to spare them the lifestyle burdain) or better to keep?
ITS CRUCIAL CRUCIAL to keep the isnulin treatment bc the longer into the disease the higher risk
4 categories of pathophysiology of type 2
1) genes
2) intrauterine environment/ adult environment
3) insulin resistance and insulin secretion defects
4) fatty acids (role in pathogenesis AND complications)
in what ways is type 2 diabetes variable?
1) heterogenous (means theres different causes for it:)
2) people develop it at variable BMI, ages and progress differently
what risks does gestational diabetes have?
incr. risk of mother and child having normal diabetes
mother: pancreas already has some resistance so …
child: either epigenetic changes or bc of following a certain lifestyle of mother/ family
what is a hyperglycemic clamp?
when they give you a specific amount of glucose IV for a continuous time frame to measure your body’s responding insulin production. (basically used to measure b cell function)
difference between standard glu tolerance test and hyperglycemic clamp?
GTT measures GLUCOSE after EATING usualllly a sugary drink after having FASTED, aim is to see if body can lower glu levels, used to DIAGNOSE diabetes, more natural repsonce observation. clamp is more artificial way, not used for diagnosis.
what is observed in insulin production after givinf the iv glu challeneg to t2d vs normal?
spike in insulin prod immediately after glu challenge given in normal vs minimal insul prod in t2d
2 basic mechanisms of low insulin causing increased FPG (fasting plasma glucose levels)? (and the official terms)
1) glucose cant enter target cells eg peripheral muscles (impaired-insulin mediated glucose disposal)
2) gluconeogenesis not inhibited by insulin anymore, glucagon is allowed to act on liver : hepatic glucose production is increased (excessive glucagon-mediated glucose output)
what are two ways/ terms to describe glucose not being able to enter tafrget cells due to low/ resistance to insulin?
impaired insulin- mediated glucose disposal
reduced metabolic clearance rate of glucose
what event does Cori cycling refer to?
the excessive amounts of glucose in blood converted to lactate which then returns to the liver to be metabolized back to glucose
what event could explain early morning increase in FPG in the progression to T2DM
cori cycling from previous nights meal
2 more mechanisms of Further increasing FGP in diabetes.
Inadequate insulin action also causes an increased flux of substrates – glycerol and free fatty acids – to the liver, resulting in increased gluconeogenesis.
Inappropriate glucagon secretion induces continued glucose production by stimulating glycogenolysis (release of glucose from glycogen, its stored form) (in addition to already mentioned gluconeogenesis)
