Endo top tier Flashcards
diabetes type 1 vs type 2
T1DM - insulin deficiency
T2DM - ineffective insulin + deficiency
diabetes diagnosis
fasting glucose: 7.0mmol/L
random glucose: 11.1mmol/L
OGGT: 11.1mmol/L
Hb1AC : 48mmol/mol , 6.5%normal
C peptide (down in type 1, normal in type 2) autoantibodies (present in type 1, not in type 2)
pre diabetes diagnosis
fasting glucose: 5.6-7.0
random glucose: 7.8-11.1
OGGT
Hb1AC: 42-47mmol/mol, 6-6.5%normal
fasting glucose test =
only water for 8 h
OGTT=
2 hours oral glucose tolerance test. 75g sugar drink given. blood taken 1 and 2h later
hb1ac =
proportion of haemoglobin with glucose stuck to it– measure of glucose levels over the last 2-3 months
type 1 vs type 2 diabetes symptoms
Type 1 symptom onset is acute
Type 2 symptom onset is gradual
diabetes symptoms
- Polydipsia, thirst
- Polyuria- nocturia, glycosuria, ketonuria
- Fatigue
- Dry skin
- Weight loss - lipid and muscle loss due to unrestricted gluconeogenesis
- Hunger - lack of usable energy source
- Infections
- – Recurrent thrush
- – Poor healing of wounds
- Blurred vision, esp at night (due to glucose/water in lens)
- Breath can smell of acetone smell (nail polish remover)/ pear drops (ketones- esp type 1
- Acanthosis nigricans = blackish pigmentation at the name of the neck and in the axillae – severe insulin resistance in DMT2
type 1 diabetes pathophysiology
Insulin deficiency due to autoimmune destruction of beta cells
— autoantibodies against insulin and islet cells
(high glucagon, more lipolysis, glycolysis, gluconeogensis, decreased peripheral glucose uptake, increased muscle breakdown)
so increased glucose conc, increased glucose lost in urine
Healthy at birth but damage to beta cells over time, eventually diabetes
type 1 diabetes untreated
high glucagon, high glucose
weak - muscle broken down
fat broken down (oxidised to ketone bodies)
prone to ketoacidosis
diabetes type 1 signs from investigations
dehydration
low BP
high levels of islet autoantibodies
no C peptide present (from pancreas)
diabetes type 1 risk factors
Northern european - especially finnish
Family history (HLA-DR3 , maybe other DRs?)
Associated with other autoimmune diseases (eg coeliac, graves, addison’s etc)
Vitamin D deficiency
ketoacidosis
free fatty acids and glucose levels high
these form acetyl coA
so increased ketones
ketones are strong acids so low blood pH. this impairs the ability of haemoglobin to bind to oxygen (dissoc curve shifted to the right)
+ pH dependant enzymes less effective
+ metabolic acidosis (high h+, low HCO3-)
+ breath smells of pear drops (=ketones)
causes of ketoacidosis
- Unknown, idiopathic
- Infection
- MI
- Treatment errors
- Undiagnosed diabetes (esp type 1)
Not really type 2, as even a small amount of insulin can halt breakdown of fat and muscle into ketones. So therefore, can occur in the very late stages where there is absolute insulin deficiency - Stopping insulin therapy
- Surgery
- Pancreatitis
ketoacidosis symptoms
Acute Polyuria Polydipsia , thirst May be unable to pass urine if not high water intake nausea , vomiting Weight loss Abdominal pain drowsiness/ confusion Weakness
ketoacidosis SIGNS
- Hyperventilation : Kussmaul’s respiration (deep rapid breathing)
- Dehydration: Urea and creatinine raised
- Hypotension
- Tachycardia
- Conscious disturbance, coma
- Breath smells of pear drops (ketones)
- Low body temperature
- Glycosuria, ketonuria
- Raised wbc maybe
ketoacidosis management
1 ABC (airways, breathing, circulation) 2 rehydration . no delay. In order to dilute acid and glucose 3 Insulin -- Stop new ketone production -- Stop glucose production in liver -- Lower glucose - convert to glycogen -- Monitor glucose 4 replace k+ -- Electrolytes -- K+ seems high (serum levels), but acc is in deficit because it moves out of cells to serum due to acidosis. It falls further with the rehydration (step 1) 5 Treat underlying cause
type 2 diabetes pathophysiology
- Impaired insulin secretion and insulin resistance in muscle and fat
- Beta cell mass reduces
- May have high levels of circulating insulin at the beginning, due to high levels of glucose from liver and reduced uptake– but this insulin is ineffective and inadequate at restoring hyperglycaemic state.
Then levels decrease due to secretory failure.
So insulin deficiency relative to increased demands causes hypersecretion by depleted beta cell mass → progresses to absolute insulin deficiency (where levels are low (not only relatively))
what is the viscous cycle of insulin resistance ? which type of diabetes
type 2
impaired glucose secretion (less insulin) and insulin resistance in muscle and fat (less effective insulin)
this causes impaired glucose tolerance, take up and clearance
this causes hyperglycaemia, this worsens glucose secretion and insulin resistance
diabetes risk factors
Modifiable:
- Obesity- high fat levels
- High cholesterol levels
- Sedentary lifestyle
- Low activity levels/ exercise
- Smoking
- High blood pressure
- medications - thiazide diuretic with beta blocker
Non–modifiable:
- Race: south asians, Chinese, middle-eastern, African-Caribbean or black African origin
- Gender (male>female)
- Genetic disposition
- Family history of diabetes
- Low birth weight
- History of gestational diabetes
gestational diabetes inc risk factors
- high blood sugar when foetus in pregnancy, usually disappears after birth
- Likely to have this if mum is overweight, south Asian, Black, African-Caribbean or Middle Eastern origin, had pregnancies with previous gestational diabetes/ large baby
- 40 yrs +
MODY=
MODY = maturity onset diabetes of youth
Dominant
type 2 risk factor
‘typical’ type 1 vs type 2 presentation
1 symptoms sudden young lean associated with other autoimmune diseases
2 symptoms sudden 30y+ overweight familial hypercholestrolemia often present hypertension alcohol family history
peptide C diabetes
from pancreas
not present in type 1
yes present in type 2
diabetes symptoms control
- control symptoms eg infections, fatigue
- control diabetes related eg gangrene feet, retinopathy
- prevent acute emergencies eg hyperglycaemia, ketoacidosis
- lifestyle changes – only for type 2
- glycaemic control medication (metformin, TZDs, sulphonylurea, incretin mimics, insulin)
if acute diabetes and you are not sure if it is type 1 or 2 what should you do?
treat with insulin – assume type 1 until you know otherwise – test for autoantibodies / peptide c
diabetes lifestyle changes
only for type 2
- smoking cessation
- sustained weight loss and exercise
- – can reverse insulin resistance! and lipotoxicity! so hyperglycaemia reduced
- – orlistat - inhibits intestinal lipase so reduces absorption of fat - weight loss and lower fat levels
- – bariatric surgery - makes stomach smaller - more satiety
- – reduce CV risk : ACEi, statins
compliance is hard
metformin
- action
- why bad/good?
1st line treatment
- decrease hepatic glucose production (gluconeogenesis)
- Decreases absorption of glucose in intestine
- Increases peripheral glucose uptake
- Improves insulin sensitivity, reduces insulin resistance
Weight gain- avoid for overweight
Less weight gain and less hypos than insulin
TZDs=
- action
- contraindications
Thiazolidinediones
Lower insulin resistance
Bad for individuals with heart failure, bone fractures, eye damage
sulphonylurea
- action
- why bad
- used when
Stimulates insulin secretion by increases B cell function
Short term is good but causes increase in stress to B cell so several years later, more B cell dysfunction Weight gain Contact DVLA (driving risk)
Used when metformin not adequate for glycemic control
incretin mimics
- what are incretins
- action of incretins
- why good
- types
Incretins are hormones produced after meals(triggered by nutrient intake), secreted by intestinal endocrine cells
- body produces more insulin,
- suppress post-prandial (post mealtime) glucagon release
- delay stomach emptying
- increase insulin sensitivity
- Promotes satiety
- Decreases gluconeogenesis?
No weight gain
- Mimic GLP1 = incretin mimics (GLP1 is an incretin)
Enhance GLP1= DDP 4 inhibitors
DDP 4 is an enzyme that inactivates incretins. Incretins have a short half life. So DDP 4 inhibitors allow the incretins to function better and extends their usage
which glycaemic medicine is injection and which isnt
injection
- insulin
- GLP1 analogues
not injection
- DDP4 inhibitor
- metformin
- sulphonylurea
- TZD
- SGLT-2 inhibitor
insulin
types - difference and when they are taken
basal insulin = long acting (mixed with retarding agents). taken during fasting . basal analogues = flatter – longer duration and lower peak
prandial/bolus insulin = rapid acting, taken pre-glucose spike of meal, adjusted according to meal’s carb content
can take separately or in mixed forms
-mixed forms = single preperation however cannot seperate doses so requires consistent meal and exercise times and amounts
type 2 diabetes - when should it be treated with insulin
there is a shift to treat it early as there is reduced complications with tighter glycaemic control
however, it can be impacted largely by lifestyle changes
and insulin causes weight increase
- this causes insulin resistance which then requires more insulin (vicious cycle)
glucose targets
- aim for what?
- special cases
aim for lowest Hb1ac balanced with hypoglycaemic risks relax targets if hypos are more dangerous: - old - complications / chronic illness - high risk of hypos - high risk of falls - cognitive impairment with these groups try to minimise chance of hyperglycaemia
hypoglycaemia
- what is it, pathophysiology
- levels (types)
- effects
- low plasma glucose
- glucagon is first defence (not present in T1/2DM)
- second line defence is adrenaline. each episode weakens response so threshold for a response increases
- impaired brain function
Level 1. Mild- 3.0-3.9
- Self treated (Unless child- child always requires 3rd party assistance)
- Mild cognitive impairment
- Many episodes are asymptomatic
Level 2. Severe- <3.0
- Require 3rd party assistance
- (as) Cognitive function significantly impaired
- can cause anxiety- fear of future hypos
- can cause accidents (driving, tree surgeon)
- increases CV risk
hypoglycaemia more common in which type of diabetes and why
type 1 because higher proportion take insulin and are on insulin for much longer time
hypoglycaemia causes
diabetics, non diabetics
diabetics:
- missed meal
- increased activity
- overdose
non diabetics : EXPLAIN
Exogenous drugs - insulin, alcohol binge with no food
Pituitary insufficiency
Liver failure
Addisons
Islet cell tumour (= insulinoma) and immune hypoglycaemia
Non-pancreatic neoplasm (eg firbosarcomas)
risk factors for severe hypos
- type 1
- type 2
type 1
- history of episodes - adrenaline response weakened
- long duration of diabetes
- less awareness
- very young/old
type2
- history of episodes - adrenaline response weakened
- long duration of insulin treatment
- cognitive impairment (forget if eaten, take insulin)
- old
- depression
+ High exercise levels
+Low HbA1C
+High daily insulin dosage
+Renal impairment – loss of glucose (less reabsorption)
hypos symptoms
Neuroglycopenia (shortage of glucose in brain)
- confusion
- weakness
- Drowzy, fatigue
- dizzy
- Difficulty concentrating
- Difficulty speaking (appears drunk sometimes)
- Visual changes
Autonomic -caused by adrenaline
- Sweat
- anxious
- trembling
- palpitation
- hunger
- — these symptoms before the neuro ones if glucose level falls slowly
Non-specific
- Nausea, malaise
- headache
- Patient had jaw clamp, cramp
- Tingling around mouth
severe = collapse, convulsion, coma
hypoglycaemia management
confirm diagnosis - fingerprick blood
fast acting carbohydrate given
retest in 15 mins and retreat if necessary
give long acting carbohydrate
whipple’s triad
for hypoglycaemia
biochemical confirmation, symptoms, symptoms relieving with treatment
prevention of hypos
Screening:
– See risk factors
Education of patients/carers eg DAFNE
- Risk factors
- Recognition
- Treatment
Cut back on treatment if previous hypos/ exercise (unless intense- as adrenaline is released)
hyperglycaemia
risk factors
not related to patient / diabetes
- Infection
- High glucose intake
- Medication
- — Thiazide diuretics
- — Steroids
hypo/hyperglycaemia relates to hypo/hyperosmolar states how?
hypoglycaemic =
hypoosmolality
hyperglycaemic = hyperosmolality
hyperglycaemia signs/ investigations
- Dehydration (osmotic diuresis, due to high glucose → water excreted (polyuria))
- — Low K+ in body but serum is high due to no insulin
- — Polydipsia, polyuria
- —Kidney failure due to lack of blood volume
Decreased consciousness. Stupor, coma
Hyperglycemia - serum and urine
Hyperosmolality
No ketones in serum/urine. Bicarbonate not lowered
hyperglycaemia treatment
Insulin
Fluid replacement (0.9% saline)
LMW Heparin -
- as blood is thick due to hyperglycemia so increased thromboses so more emboli
- reduce risk of thromboembolism/MI/stroke due to hyperosmolality
hyperglycaemia complications
acute and chronic
Acute
- Diabetic ketoacidosis
- Hyperosmolar coma
Chronic
- Tissue complications
- – Microvascular
- – Macrovascular
complications of diabetes
macrovascular
- atherosclerosis
- – CV disease
- – stroke,
- – peripheral vascular disease (claudication, rest pain, amputation)
microvascular
- diabetic retinopathy
- diabetic nephropathy
- diabetic neuropathy
- peripheral vascular disease (kinda micro, kinda macro)
