Intro to Diabetes Flashcards
LADA
happens later in life, destruction of beta cells but a a slower rate
Risk factors for diabetes
male, age, ethnicity, aboriginal, overweight, low income,
undiagnosed diabetes
27.4% living with it or many years - uncontrolled blood glucose levels which can have detrimental effects
Type 1 causes
body produces islet cell auto-antibodies
- still not sure why this starts; some gene involved but not sure which one; is it environmentally triggered?- virus, toxins and stress.
steps: genetic predisposition leads to islet cell auto-antibodies if exposed to environmental factors ( virus, toxins, stress), net other causes will cause B cell injury and there will be no insulin
symptoms of diabetes
polydipsia, polyuria, polyphasic, weight loss ( T1) or weight gain ( T2)
where are symptoms more severe?
T1
clinical lab test results indicating diabetes
glycosuria
hyperglycaemia
abnormal glucose tolerence (GTT)
diagnosis criteria:
-A1C
-FPG
for T1 need to measure antibodies
what does insulin do?
promote glucose uptake
stimulate glycogenesis (making glycogen) making protein and making TG (lipogenesis)
decrease gluconeogenesis, glycogenolysis, lipolysis and proteolysis
total def in insulin (type 1) leads to what in terms of glucose metabolism? (talk through table)
1) in terms of glucose metabolism = less uptake in HAM (GLUT 4)- leads to intracellular glucose def= polyphasic. In contrast there is greater hepatic glucose output ( highest rate of gluconeogenesis from lipids and aa’s)
- these both lead to hyperglycaemia in which some spills into the urine. bc glucose is osmotic ( attracts water) –> polyuria which can lead to dehydration–> polydipsia ( always thirsty). with dehydration we can have cell shrinking and therefore NS malfunction ==> death
there may also be a decrease in blood volume-> increase HR, peripheral circulatory flare and low blood flow and renal failure==> death
describe how polyuria happens in type 1
hyperglycaemia leads to glycosuria which attracts water and leads to polyuria
How does total deficiency in insulin (type 1) fat metabolism? (talk through table)
Cells fell starved–> increase in gluconeogenesis–> lipolysis and decreases in TG synt, which ultimately leads to increase in blood FFA ( used as an alternate fuel source = ketosis => which may lead to metabolic acidosis –> increased ventilation and diabetic coma and death
why is there increase in ventilation in T1 DM?
increase in blood FA leads to ketosis and metabolic acidosis; therefore, to excrete more H+ ( more CO2 and H2O in breath) fall in plasma H2CO3
is ketosis state a big deal in T1?
not a big deal, but the issue is when ketosis is prolonged and develops into metabolic acidosis
what is metabolic acidosis
ketone bodies 10x higher than in ketosis
why is metabolic acidosis so bad?
affects the respiratory system –> increased ventilation to excrete CO2 and decrease in pH and metabolic imbalances that accompany could lead to diabetic coma
when do most ppl find out they have T1
administered to hospital with symptoms of diabetic coma ( increased ventilation, decrease in pH )
how does Type 1 affect protein metabolism?
less aa uptake in cells and increase protein catabolism –> muscle wasting and weight loss
- more aa in circulation causes more gluconeogenesis, aggravating hyperglycaemia
diabetes fasted state
exacerbated fasted state due to lack of insulin
- lots of gluconeogenesis, proteolysis and lipolysis
- cause negative nitrogen balance due to non-gluconeogenic AA’s getting catabolized and broken down
what happens when type 1 fed?
worsens the situation
- increases the substrates to the liver- more hyperglycaemia as cells can still not uptake glucose(none getting converted to glycogen ) more glucosuria
ER type 1 blood sugar is normally at?
above 25mmol/L and mediate insulin infusion, electrolytes and potassium
cause of T2DM?
major cause is obesity and inflammation ( which goes hand in hand with obesity)
- obestity caused by genetics, lack of exercise and excess calories
- this leads to IR= hyperglycaemia and the pancreas trying to overcompensate and secreting more insulin.
-
is sugar a cause of diabetes?
no
when IR develops is this diabetes?
NO, bc the hyperinsulinemia will work to control blood glucose
- officially have diabetes when there is B-cell destruction and the pancreas can no longer compensate with enough insulin
what causes the transition from IR to B-cell destruction leading to diabetes?
may be genetic component or lipotoxicity
high levels of lipids in the blood that impact cell function and causes inflammation
what is IR? why does it happen?
less sensitivity to insulin’s actions of stoping gluconeogeneis and up taking glucose
- mostly due to defect in cell signalling, NOT THE RECEPTOR
what organs don’t get effected by insulin resistance ( in terms of glucose def)
brain, RBC, liver
is T1DM genetic?
no not atall
T2Dm risk factors
GDM, low or high BW, PCOS, aboriginal, African, south asian, hispanic, obesity, sedentary, male, age, prediabetes
describe the stages and development of type 2 diabetes
obesity—> IR –> hyperinsulemia and hyperglycaemia –> impaired glucose tolerance and overnight fasting glucose ( always high) –> beta-cell defect leads to early diabetes ( we can intervene here with diet, medication and lifestyle and reverse the disease BUT if beta- cell failure ( genetic and lipotoxicity) then leads to late diabetes
short term complications of DM
- hypoglycaemic episodes
- diabetic keto acidosis ( more in T1)
- HHS ( more in type 2) (when BG >33 mol/L)
how does hypoglycaemia happen in DM
BG < 3.9 mol/L but individual symptoms
- neurogenic –> sweating, tachycardia, anxiety, sensation of hunger
- neuroglycopenia ( weakness and dizziness, confusion and poor coordination blurred vision
- this happens when skip meal, delay meal, reduce CHO intake without med compensation or unplanned exercise
long term complications
microvascular and microvascular (CVD, CHD, stroke)
pathophysiology of the long term consequences of DM
ultimately from endothelial damage caused by chronic amounts of glucose in circulation (glucotoxity) and which glycosyalte certain proteins ( glycated hemoglobin- A1C) there will also be lipotoxicity which further increases endothelial damage–> leading to increased acceleration of atherosclerotic plaque –> HPT, thrombosis, ischemic and organ failure
what is A1C
glycated hemoglobin - one molecule of glucose is bound to hemoglobin
- measured as % of total Hb in circulation - normal is 4.3-6 but when higher indicative of chronic glycemia
why is there hyperTG in T1
defective removal of CM and VLDL bc LPL is insulin dependent and if no insulin than no LPL activity
can hyper TG be cured ?
with insulin injections and controlled T1 yes
what happen to HDL and LDL in hyperTG in T! vs T@
in T! hdl and ldl may be normal but in T@ HDl is usually low bc obesity and Ldl is usually high bc obesity
why can hyperTG arise in T2
due to elevated de nova synthèses from glucose and from FFA (similar to obesity) - excess substrates
diabetes and heart disease, why is there’s such a great risk?
2-4x greater risk of CVD - greater risk than smoking, HPT, HyperCH, obesity
- risk due to elevated glucose which has a huge impact on endothelial damage
heart disease is the cause of ____ of deaths related to DM
65%
diabetes screening- who to screen?
everyone over 40 every 3 years OR ppl at high risk then screen more regularly with ppl who have additional risk factors for diabetes
who doesn’t need to be screened?
under 40 and no risks
what does screening mean? what is the main screening tool
blood test
- fasting plasma glucose (FPG)
diagnostic criteria * very important
1) FPG - 6.1-6.9 indicates impaired fasting and above 7 indicates diabetes
2) plasma glucose after 2 hours after oral glucose tolerance test ( not often for screening - long test) but 7.8 to 11 indicate impaired fasting glucose and >11 indicate diabetes
3) A1-C % –> 6-6.4% indicate prediabetes and >6.5 indicates diabetes
what happens if patients blood work indicates diabetic BUT asymptomatic?
redo confirmatory test (FPG, A1C or 2hrPG)
if half the tests are in diabetes range than what?
tests repeated
when is the only case when diabetes can be diagnosed with only one test?
random glucose test and symptoms
derive the difference between impaired glucose tolerance and T2DM in relation tot he OGTT blood glucose curve
T2DM has a higher base line (set point) before administration whereas IGT will have a normal level before oral glucose administered
diabetes prevention program effective?
YES, prediabetes diagnosis is crucial - DPP study found that diet, exercise or metformin conducted over 4 years with 3234.
metformin = 31% decreases diabetes
lifestyle intervention - decrease by 58%
what are ABCDEs of diabetes
recommendations fro vascular protection with diabetes:
A1C, BP, CH, Drugs to protect the heart, exercise, smoking
what A1C target should aim for?
not nessasarily the non-diabetic target, but a healthy safe range–> have to keep in mind intensity of medications and the side effects along with them ( main risk of treating hyperglycaemia is hypoglycaemia)
- target is >7% for MOST patients with T1 tr T2
limited life expectancy A1C target
7.1-8.5%
can 6.5% be a realistic target?
for SOME T2 patients but must be carefully balanced with hypoglycemia
optimal ranges for DM patients (A1C, FG, 2hrPG)
<7%, 4-7, 5-11
what is the CANRISK
the Canadian diabetes risk questionnaire –> tells you (for adults aged 40-75) if you are at risk
- age
- waist circumference
- sex
- PA
- vegtable intake
- BP, BG and pregnency
- family history
- ethnicicty
low risk, moderate risk and high risk
if patient has CVD which medications ?
statins + ACEi?ARB + ASA
if patients is above 40 and has diabetes, should they be on statins?
yes, or if have had diabetes for more than 15 years
