diabeties Flashcards
Where is insulin and glucagon released from
islet of langerhans
where does all glucose come from
LIVER
what does insulin do
Supresses hepatic glucose output
Glycogenolysis
Gluconeogenesis
Increases glucose uptake into insulin sensitive tissues (muscle, fat)
Suppresses Lipolysis
what does glucagon do
Increases hepatic glucose output
Glycogenolysis
Gluconeogenesis
Reduce peripheral glucose uptake
Stimulate peripheral release of gluconeogenic precursors (glycerol, AAs)
Lipolysis
Muscle glycogenolysis and breakdown
what is diabeties mellitus
A disorder of carbohydrate metabolism characterised by hyperglycaemia
high sugar levels
how does diabeties mellitus cause morbidity
acute metabolic emergencies diabetic ketoacidosis (DKA) and hyperosmolar coma (Hyperosmolar Hyperglycaemic State )
Chronic hyperglycaemia leading to tissue complications
Complications of diabeties mellitus
stroke
blindness
diabaetic neuropathy
heart disease
types of diabetes
type 1
type 2 to include gestational and medication induced
MODY
pancreatic
endocrine diabeties
malnutrition related
symptoms of diabetes
polyuria
fatigue
fasting plasma glucose more than 7
Hba1c > 48mmol/ mol
treatment of type 1 diabetes
insulin treatment - basal bolus
once or twice daily of slow acting
ability to judge carbohydrate intake
awareness of blood glucose lowering effect of exercise
pathogenesis of type 1 diabates
Destruction of beta cells in the islet of langherhans caused by an autoimmune response
what would happen if you take too much insulin
cerebral dysfunction
hypoglycaemia
- release of glucagon
-sweating
-hunger
-loss of consciousness
failure of insulin secretion leads to
-Continued breakdown of liver glycogen
-Unrestrained lipolysis and skeletal muscle breakdown providing gluconeogenic precursors
-Inappropriate increase in hepatic glucose output and suppression of peripheral glucose uptake
failure to treat insulin resistance leads to :
- increase in circulating glucagon, increases glucose
-perceived ‘stress’ leads to increased cortisol and adrenaline - progressive catabolic state and increasing levels of ketones
aetiology of type 2 diabetes
genes and environment
impaired insulin secretion/ insulin resistance
impaired glucose tolerance
type 2 diabetes
progressive hyperglycaemia
impaired insulin action leads to
Reduced muscle and fat uptake after eating
Failure to suppress lipolysis and high circulating FFAs
Abnormally high glucose output after a meal
summary of type 1 diabetes
Severe insulin deficiency due to autoimmune destruction of the beta cell
signs and symptoms of type 1 dibaetes
polydipsia, polyuria, weight loss
- short history of severe symptoms
typical patient presenting with new T1DM
polydipsia, polyruia, rapid weight-loss, young, BMI >25
genetic history of disease
summary of type 2 diabetes
Insulin resistance and impaired insulin secretion due to a combination of genetic predisposition and environmental factors (obesity and lack of physical activity)
principles of treatment for diabetes
- control of symptoms
-prevention of acute emergencies, ketoacidosis - correct diagnosis
risk factors for T2DM
Lifestyle- obesity, lack of exercise, calorie and alcohol excess
- asian men
- HT
- ABOVE 40
SIGNS and symptoms of type2 diabetes
polydipsia
polyuria
glycosuria
central obesity
slower onset
blurred vision
3 step management process for diabetes
1- metformin - to inc insulin sensitivity
2- if HBA1C still high then dual therapy with dpp4, sulphonyl
3- if still high - triple therapy
then insulin
define DKA
Diabetic ketoacidosis
- complete lack of insulin results in high ketone production and hyperglycaemia
medical emergency
glucose and ketones escape in urine but lead to osmotic diresis
Absence of insulin would cause
absence of insulin- uncontrolled catabolism,- unrestrained gluconeogenesis and decreased peripheral glucose uptake
signs of DKA
Pear drop breath due to ketones
hypotension
tachycardia
symptoms of DKA
Nausea+ vomitting
weight loss
very thirsty
confusion
lethargy
abdo pain
dka complications
cerebral oedema
adult resp distress syndrome
thromboembolism
aspiration pneumonia
death
treatment for DKA
replace fluid - 0.9 saline 3l for 3hrs
IV insulin- to stop ketones being made
restore electrolytes
how do sulphonylureas work
- stimulate insulin release by binding to b-cell receptors
- improve glycaemic control
-can cause hypoglycaemia
what medication can cause osteoporosis, heart failure and weight gain
thiazolidinediones
ideal drug for type 2 diabetes would;
Reduce appetite and induce weight loss
Preserve -cells and insulin secretion
Increase insulin secretion at meal time
Inhibit counterregulatory hormones which increase blood glucose such as glucagon
Not increase the risk of hypoglycaemia during treatment
what do SGLT2 inhibitors do
-block the reabsorption of glucose in kidney in the Pct, increase glucose excretion and lowers blood glucose
define HHS
hyperosmolar hyperglycaemic state
marked hyperglycaemia
mild/ no ketosis
signs and symptoms of hhs
confusion and reduced mental state
lethargy
severe dehydration
investigations for HHS
- random plasma glucose >11 mmol
-urine dipstick- glucosuria - plasma osmolality -high
U + E
pathophysiology of hhs
low insulin> increased gluconeogenesis
first line treatment for diabetes type 2
metformin
How do ddp4 inhibitors work
Inhibit the release of glucagon
Can cause weight gain
side effects of sglt2 inhibitors
-genital thrush
- inc risk of euglycaemic ketoacidosis
what is shown with euglycaemic ketoacidosis
breakdown of fats with fasting
ketone levels rise
acidotic and nauesous
glucose levels are normal
hypoglycaemia?
low blood sugar
pathophysiological effects of hypoglycaemia
brain- cognitive dysfunction, seizures
heart- heart attack
msk- falls, fractures
circulation- inflammation, blood coagulation, endothelial dysfunction
neuroglycopenia?
shortage of glucose in the brain resulting in alteration of neuronal function.
neuroglycopenia symsptoms
-difficulty concentrating
- confusion
-weakness
-dizziness
-vision changes
-fatigue
symptoms of hypoglycaemia
- trembling
-palpations
-sweating
-anxiety
-hunger
causes of hypoglycaemia
-long duration of diabetes
-tight glycaemic control
-old age
-drugs, alcohol
-sleeping
-increased physical activity
to prevent hypoglycaemia in community
- educate patients and caregivers on how to treat and recognise
-instruct patients to report
how to treat hypoglycaemia
- recognise symptoms
-confirm the need for treatment
-treat with fast acting 15g carb to relieve symptoms
-retest in 15 mins to ensure blood glucose
-eat a long acting carb to prevent recurrence of symptoms
Adv and dis of pre mixed insulin in diabetes
- both basal and prandial components in a single prep
- can cover insulin requirements for whole day
Dis
- requires consistent diet and exercise
- increase risk for nocturnal hypoglycaemia
How would hypoglycaemia be avoided in the body
When glucose levels are low
Glucagon and adrenaline are released which allows for glycogenolysis
Consequences of low blood sugar with diabetics
Altered thresholds, patient is unable to realise that levels are low
Glucose levels can go very low and they may pass out
objectives if t2dm treatment other than glucose control
to reduce risk of cvd
chronic kidney disease
microvascualr complications
microvascular complications linked to diabetes
diabetic retinopathy
nephropathy
severe non / proliferation
neuropathy
microalbuminuria
hba1c target
7%
presenting feautures of diabetes
thirst
polyuria- excess urine
weight loss and fatigue
hunger
blurred vision
vaginal candidiasis
type 1 sugggestive features
onset in childhood/ normally sudden
lean body habitus
prone to DKA
high levels of islet autoantibodies
what would happen if you stopped producing insulin
increased and uncontrolled fat metabolism, impair glucose uptake, FFA are transported into the liver
three things you need for definitive diagnosis of DKA
- HYPERGLYCAEMIA
-RAISED PLASMA KETONES
-METABOLIC ACIDOSIS
what is the significance of ANTI- gad
the more anti gad you have the more likely you are to have type 1 diabetes
type 2 suggestive feautures
usually presents in over 30’s
onset is gradual
FH is often positive
diet exercise and oral meds can control it
3 main issue with neuropathy
pain
autonomic issues
insensitivity
signs of vascular disease
diminished or absent pedal pulses
cold feet and toes
poor skin and nails
abscence of hair and nails
most common cause of blindness in the working population
diabetic retinopathy
risk factors of DR
long duration diabetes
poor glycaemic control
hypertensive
on insulin treatment
pregnancy
hallmark of diabetic nephropathy
development of proteinuria
followed by progressive decline in renal function
risk factors for diabetic nephropathy
poor bp control
poor bg control
pathophysiology of diabetic nephropathy
glomerulus changes
increase ofr glomerular injury
filtration of proteins
diabetic nephropathy
treatment of diabetic nephropathy
blood pressure control
glycemic control
ARB/ACEI
proteinuria control
cholestrol control
leading cause of amputations
diabetic nephropathy
what can cause excess protein in urea
exercise
infection
fever
congestive heart failure
marked hypertension
pregnancy
specific values needed to diagnose diabetes
symptoms and random glucose of more than 11.1 mmol/l
fasting plasma glucose more than 7.0 mmol/l
hba1c of more than 48
what is a normal glucose level
between 4-7 mmol/l
biochemical values of DKA
glucose around 50mmol/l
high K+
hco3- less than 15mmol
urea and creatinine raised
what is MODY
maturity onset diabetes of the young
diagnosed at <25y
which genes have been found to have mutations that cause MODY
HNF1A
HNF4A
how would you treat MODY3
with sulphonylurea
often do not need insulin
what would make you think MODY instead of type 1 diabetes
if a parent is affected
absecence of islet autoantibodies
what would c peptide tell you about mody and type 1
MODY the patient would have normal levels of c peptide meaning they can produce their own insulin
T1- low levels of c peptide
what physical signs would indicate permanent neonatal diabetes
small babies
epilepsy
muscle weakness ( floppy baby )
most common cause of chronic pancreatitis
alcohol
cushings syndrome ?
Body produces excess cortisol
increased insulin resistance , reduced glucose uptake into peripheral tissues
what occurs in pheochromocytoma
excess production of adrenaline
increased gluconeogenesis
decreased glucose uptake
which group of drugs increase insulin resistance the most
steroids
macrovascular complications of DM
-coronary artery disease
-peripheral ischemia
-stroke
-ht
microvascular complications of DM
-peripheral neuropathy
- retinopathy
- kidney disease
infection related complications of DM
- UTI
- pneumonia
-skin and soft tissue infection
-fungal infection
Sglt2 inhibitors cause a side effect of ….
Glycosuria
Common examples of sglt2 Inhibitors
Dapaglifozin
Cinaglifozin
Empaglifozin
What are dpp4 inhibitors
They work to inhibit the dpp4 enzyme
Pathiphysiology of dpp4 inhibitors
Glp1 aids in
Decrease in gastric emptying
Increase insulin release, decrease glucagon
Decreases appetite
Inhibits allow this to occur
Common example of dpp4 inhibitor
Sitagliptib
What medication commonly causes hypoglycaemia
Gliclazide
What medication can cause UTI in women
Sglt2
When managing dka what electrolyte should be managed closely
Potassium
