Diabetes Flashcards
whats diabetes mellitus
group of metabolic disorderes characterised by chronic hyperglycaemia
due to insulin deficeny, insulin resistance or both
types of diabetes
their epidemiology
probable causation
treatment
TYPE 1
- young people
- characterised by progressive loss of all / almost all B cells
- rapidly fatal if not treated
- must be treated with insulin
TYPE 2
- usually older individuals
- characterised by the slow progressive loss of B cells along with disorders of insulin secretion ad tissue resistance to B cells
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can be present for long time before diagnosis
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lifestyle changes, drugs
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lifestyle changes, drugs
complications of diabetes
-CVD - Kidney disease - amputations
why does bgl ^
- inability to produce d to beta cell failure - insulin adequate B resistance / not working very well
type 1 how many people diagnosed annually?
what age group ^ common?
what causes it?
is there a genetic predispositon
15/100,000
younger people
autoimmune condiion where the body cant recognise self antigens from foreign antigens wc leads to the destrution of beta cells
there is, it is associated with genetic markers HLA DR3 and HLA DR4
there’s seasonal variationthough wc suggests a link viral infection acting asa trigger to rapid deterioration
how does a person with type 1 diabetes present
usually young with a triad of symtpoms:
polyuria - excess urine production. in the nephron of healthy individual all glucose filtered from the blood reabsorded, at the end of proximal convuluted tubule, resaborption is isosmotic. in diabetes mellitus large quantities of glucose is filtered by the kidney because bgl levels are high, so not all glucose reabsordbed. this extra glucose in the nephron tubule puts extra somotic pressure on the nephron so less water is resabsorbed to maintain the isoosmotic character of this section of the nephron. this extra water then reians with the glucose in the nephron tubule and is excreted in copius urine
weightloss - because fat an protein tissue is being metabolised because insulin is absent
thirst - due to water loss polydipsia
type 2
- not enough insulin - B deficiency relative , problem isn’t the beta cella but the target tissues wc have v sensitivity for insulin and so cant c glucose movement into liver,adopise, skeletal via GLUT4 -‘insulin resistance’
how does diabetes present?
- renal threshold related c excretion of urine and since glucose is osmoticallyaactive water s lost too; - polyuria, polydipsia , dehydration, blurred vision, urogenital infections (since bacteria like glucose, so ^ susceptible to thrush) -tiredness, fatugw, lethargy,weightloss -severitydeodning on the rate of bgl
how diagnosed type 1
- measuring plasma glucose levels wc is elevated d less insulin
- glucose in the urine ; glucosuria/glycosuria
- high ketones in the blood
how to diagnose type 2 diabetes
presence of symptom (polyuria/polydipsia/unexplained weightloss)
- random venous plasma glucose conc >11.1mmol/L or
- fasting plasma conc >7mmol/L or
- plasma glucose conc >11.1mmol/L 2 hours after andhydroud glucose adminstrered in oral glucose tolerance test OGTT
why do patients with type 1 present with diabetic ketoacidosis
due to less insulin you have a higher glucagon to insulin ration and so lyase HMG is activated + this paired with the high rate of beta oxidation favours the metabolism (of acetylCoA) and synthesis of ketone bodies e.g acetoacetate,acetone, and beta-hydroxybutyrate
acetone is breathed out and can be smelt on the breathe
due to these ketones bodies being produced they make the blood more acidic , metabolic acidosis occurs
patients prestn with hyperventilation, nausae, dehydration, stomach pain adn vomitting
test ketones in the pee
treatment
- replace hormone that’s lacking, insulin TYPE 1 always no tablet , just subcutaneous
what causes insulin resistance to develop
- physical inactivity -genetic influence -muscle na liver fat deposition -physical inactivity -central obesity
treatment for t2
- diet
- excersise
- pramalintide ( contains amylin wc c glucagon suppression form beta cells and slows down stomach emptying)
- biguanides METFORMIN wc v livers resistance to insulin so can take it up,
weightloss surgery (bariatric surgery)
acute complications
-diabetic ketoacidosis in t1 -hyperosmolar non-ketotic syndrome in type 2 (D waterloss you get ionic imbalance) -acure complication of hypoglycaemia IF TAKE TOO MUCH INSULIN WC IS HIGHEST CAUSE OF HYPOGLYCAEMIA ; coma since brain needs it
chronic complcations
- MACROVASCULAR; cerebrovascular/cardiovascular/peripheral ; stroke, heart attack, intermittent claudication, gangrene -MICROVASCULAR ;
- retinopathy ; (damage of te b vessles in the retina wc can lead to blindness as they leak and form protein exudates on the retina or they can rupture and bleed into the eye)
- proliferative retinopathy (new bllod vessels form in the retina due to occlusions, these new b vessels are very weak and can rupture and bleed easily)
- diabetic eye (visuial changes due to osmotic pressure changes in the eye lens glaucoma, possibly cataracts
- nephropathy ; (damage to the kidney golemruli, poor blood supply because changes to kidney b vessels, or damage from infections or the urinary tract wc are more common in diabetetics. an early sign is micoalbuminuria - proteins in pee)
- neuropathy ; (loss of sensation, due to damages to peripheral nerves- metabolic changes due to increased glucose conc)
- diabetic foot; (poor blood supply, or due to damaged nerves, c increased risk of infections since you dont feel the damage, patients often suffer wuth gangrene)
- (erectile dysfunction, blindness, painful peripheral neuropathy, constipation, renal replacement therapy)
whats the staging of T1 and T2 diabetes
type 1
- people can be found with the relevant human leucocyte antgen HLA markers and auto-antibodies but without insulin or glucos abnormalities
- but some with HLA may develop impaired glucose tolerance then diabetes wc can be controlled wwithout drugs, then finally bceome insulin dependent
type 2
- people found with insulin resistance
- then as insulin production fails they develop impaired glucose tolerance
- develop diabetes
- diet adn tablets to help manage then insulin
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- diet adn tablets to help manage then insulin
how many people have diabetes in the uk
3.9 million UK, 0.59 million are thought to be undiagnosed
metabolic consequences of persistent hyperglycaemia
abnormal metabolism of glucose wc create products that cause harm to the cells
this is due to the brain, peripheral nerves, kidneys and eyes not regulating glucose take up using glut 4 channels that are insulin dependent, since they dont rely on insulin and only tae up g depending on bgconc
due to their being a higher extracellular glucose conc they take up more glucose and more glucose is metabolised via aldose reductase wc cata;yses this reaction
G + NADPH + H+ = NADP+ + sorbitol
you’ve used upNADPH so inappropiate disulfide bridges sf sorbitol accumulation results in osmotic changes to the cell
why does the diabetic person present wht polyuria
their bgl are so high and so when in the nephron glucose isnt reabsorbed into the blood, adn remains in the nephron. since glucose is osomotically active, water also occupies the nephron adn increases the osomotic in the nephron, this extra water reamins with the glucose and is excreted
why is the diabetic person more thristy
because they lose water when they excrete since lots of water being lost due to the increased osmotic presure as aresult of high bgl theresgreater water loss wc stimualtes the osmotregaultory centres in the hypothalamus to tell the indiviual to trink more wter
polydipsia
what is persistent hyperglycaemia associated with
glycation (non-enxymatic glcosylation) of plasma protiens (lipoproteins) that causes a distrubance in their functions. in involves glocse reacting with free aminoacids in proteins to form strong covalent linkages
the extend of glycation depends on the half life of the protein and the glucoseconcetration and since the conc of glucose has increased you increasedthe % of glycation
glycation changes the net charge of the protein and therefore its function
so you end up with glycated Hb
how do you get glycated hb
due to the high bgl levels glycation occurs (when add free amino acids from a protein onto glucose) so it forms strong covalent linkages and changes its net charge
in glycated hb,glucose reacts with the terminal valine of the hb molecule to produce glycatedhb HbA1c
this si a good measure for bgl becuase RBc usually tend to take 3 months to make so it gives you the bgl of teh 3 months
whats the HbA1c test
its a blood test where you measure the bgl% of the three preceeding months
it involves measure the % of hb thats glycasted wc in normal = 4-6%
diabeteics poorly ocntrolle = >10%
whats metabolic syndrome whatare 2 main aetiological causes
thirfty phenotype - where indiviuals are gentically predisposed to store energy more efficently during times of plenty to increase the odds of survival during subsequent famine
defintion = group of symptoms including insulin resistance, dyslipidaemia, glucose intolerance, hypertension associated with central adiposity
central obseity an dinsulin ressitane
whats the major factor that predispose to insulin resistance
obesit and seentary lifes tyle
whats dyslipidaemia and what promotes it
insulin resistance promotes it, andits ^ VLDL ^ LDL and v HDL that is very atherogenic
wc in turn ^ risk of hypertension
genteticall what culture is more liekly to suffer from central adiposity
south asians than europeans
but more europeans than african-caribbeans
whats central adiposity associated with
insulin resistance
17) Epidemiological studies have shown that the children of women who were exposed to famine during early pregnancy are more susceptible to diabetes, obesity and cardiovascular disease in adult life.
Which change DNA is the most likely cause of this increased suceptibility to dssease?
DNA methylation
Correct. Epigenetic changes such as DNA methylation and histone modifications are thought to underlie this type of suceptibility to disease
