Diabetes Flashcards
Type 1 Diabetes
Characterized by Insulin deficiency.
Manifest as sudden onset of severe hyperglycemia, progression to diabetic ketoacidosis, and death if not treated with insulin.
Autoimmune disease
CAUSED BY BETA CELL DESTRUCTION
Lack of self-tolerance - so T cells that destroy self cells are not destroyed - destroy beta cells of islets of Langerhans in the pancreas
The genetic abnormality in HLA (Huma leukocyte antigen system- a group of genes that encode for major histocompatibility complex - responsible for maintain self tolerance and recognise foreign molecules.)
Symptoms - abrupt onset
0 Polyphagia - (phagia -eating , poly - a lot )
* weight loss + hunger -
Hyperglycemia but can
get into cells (insulin
deficient ) --------- > ATP
can be made ------>
alternative energy
source found ------->
lipolysis -fat in adipose
tissue broken down ,
protein in muscle
(proteolysis ) ------>
weight loss
0 glycosuria - glucose in urine (water will follow —–> increased urination —–> polyuria) ——> dehydrated
0 polyuria
0 polydipsia (poly - a lot , dipsia - thirst)
Diabetic ketoacidosis - complication.
- (weight loss - breakdown of fat , protein as alternative energy source)
- blurred vision
- fatigue
Treatment of type 1 diabetes ?
Life long insulin therapy .
What is Type 2 diabetes ?
Insulin resistance - no longer respond to insulin.
Characterised by hyperinsulinemia leading to glucose intolerance, hyperglycemia.
Caused by BETA CELL DYSFUNCTION
Body produces more insulin in order to produce the same effect - Beta cell hyperplasia (increase in number ) , beta cell hypertrophy (grow in size)
* temporary - body cannot sustain this beta cell with eventually undergo hypoplasia (cell number reduction - cell death ) and hypotrophy (decrease in size). -------> hyperglycaemia
Symptoms
polyphagia
glycosuria
Polyuria
polydipsia
HHS - hyperosmolarity hyperglycaemic state - complication.
- not exclusive to adults
- type 2 coexistence with obesity - insulin aid adipocytes to take up fat. More insulin increased in fat.
- not seen with type 1
What is gestational diabetes?
-High glucose that develops during pregnancy usually disappears after giving birth
Body does not produce enough insulin -to meet needs of pregnancy
Most common in 2nd and 3rd trimester.
*Does not include patients who have already been diagnosed with diabetes before pregnancy - pregnancy in diabetes.
Caused by peaking of Antagonistic insulin hormones e.g those released from placenta e.g
0 human placenta lactogen - produced by placenta - breaks down maternal fat to provide for growing fetus - CAN LEAD TO INSULIN RESISTANCE.
0 Human placental growth hormone. - leads to insulin resistance
Complications
- Macrosomia - excessive birth weight - above 4.5kg / 10 pounds
0 normal - 2.5kg - 4.5 kg / 5.5 to 9.9 kg. - pre - term birth
- long term maternal diabetes
Diagnosis of diabetes Mellitus ?
Fasting Glucose - no food or drink for 8 hours - blood glucose levels tested:
Blood samples taken at 30, 60 , 90 ,120 mins
0 pre-diabetes - 100 -125mg/dl (5.6 - 6.9 mmol/L)
0 diabetes - >126 mg/dl (above 7 mmol/L)
(PG Lecture - after 120mins (2 hours ) if glucose level 140 -200mg / dl - pre- diabtetes
> 200 mg /dl - diabetes.
Non - Fasting / random glucose test -
0 Diabetes - > 200mg/dl( 11.1 mmol /L)
Oral glucose Tolerance test - Patient given glucose and blood glucose level measured at intervals to see how well it is being cleared from the blood (e.g 2 hours later)
0 Pre - diabetes - 140 - 199mg/dl (7.8 -110) mmol/dl
0 Diabtes - .> 200mg/dl
HbA1c test - proportion of GLYCATED HEMOGLOBIN -cells that have haemoglobin that has GLUCOSE stuck to it - hb unable to carry out function as unable to changed shape
0pre -diabtes - 5.7 % to 6.4 % 42-47 mmol/mol
0 Diabetes - >6.5 % - 48mmol / mol
(HbA1c - doesnt change day to day so level indicate the level it has been for 2-3 months)
CANNOT BE USED IN CHILDREN OR SUSPECTED TYPE 1 ,
- SYMPTOMS LESS THAN 120 DAYS (2 MONTHS) ,
- PATIENTS WITH PANCREATIC DAMAGE
- HIGH RISK AND ACUTELY ILL PATIENTS.
C-peptide test - C -peptide - by product of insulin.
If low/absent - pancreas not making insulin
- 1 mmol/ L = 18 mg /dl
- these reference values change with source . Also if patient is very close to borderline still a cause for concern - type 2 diabetes is a slow developing disease. may become diabetic in the future - time to intervene
urine dipstick - not good diagnostically but glucose above renal threshold - 10mmol/L will be detected.
Poor diagnostically
0 Urine glucose levels lag behind blood glucose changes
0 Urinary glucose concentration affected by fluid intake
0 Tubular threshold for glucose altered in pathology - high blood glucose a n be caused by kidney issues effecting re-absorption. of glucose
Complications of diabetes ?
Hyaline arteriolosclerosis - hyaline (protein) deposited in the arteriole causing it to harden -inflexible
Hypoxia - basement membrane of capillaries thicken — hard for 02 to diffuse to tissues
Atherosclerosis - increased risk of medium /large damage to arterial wall——> atherosclerosis occurs ——> increased risk of stroke, heart attack
0 Heart attack
0 Stroke
0 Diabetic retinopathy. - High blood sugar levels damage retina - if untreated can cause blindness
0 Nephrotic syndrome - too much protein urine -diabetes can damage afferent and efferent vessel and glomerulus of nephron
(CAN LEAD TO DIALYSIS )
0 Peripheral neuropathy- decrease in sensation -(nerves ) in toes and fingers
0 Autonomic nerve system
malfunction.
Poor blood supply + nerve damage = ulcers (on foot - do not heal well can result in amputation - worse case)
Complications of diabetes ?
osmosis
Hyaline arteriolosclerosis - hyaline (protein) deposited in the arteriole causing it to harden -inflexible
Hypoxia - basement membrane of capillaries thicken — hard for 02 to diffuse to tissues
Atherosclerosis - increased risk of medium /large damage to arterial wall——> atherosclerosis occurs ——> increased risk of stroke, heart attack
0 Heart attack
0 Stroke
0 Diabetic retinopathy.
0 Nephrotic syndrome - too much protein urine -diabetes can damage afferent and efferent vessel and glomerulus of nephron
(CAN LEAD TO DIALYSIS )
0 Peripheral neuropathy- decrease in sensation -(nerves ) in toes and fingers
0 Autonomic nerve system
malfunction.
Poor blood supply + nerve damage = ulcers (on foot - do not heal well can result in amputation - worse case)
NICE guidelines - complications of Type diabetes mellitus.
0 Hyperglycaemia — the characteristic features (thirst, polyuria, blurred vision, weight loss, recurrent infections, and tiredness) are not usually severe and may be absent.
0 Risk factor(s) for type 2 diabetes.
0 Evidence of insulin resistance (for example acanthosis nigricans - SKIN CONDITION - DARK DISCOLOURATION OF BODY FOLDS, CREASES ).
0 No additional features of type 1 diabetes (such as rapid onset, often in childhood, insulin dependence, or ketoacidosis).
0 No features of monogenic diabetes or diabetes secondary to a pathological condition or disease, drug treatment, trauma, or pancreatic surgery.
drugs used to treat Diabetes Type 2 ?
Metformin -most common
Dapagliflozin - commonly used if metformin cant
non -insulin Anti-diabetic drugs
0 Metformin
0 sulfunoylureas
- glibenclamide,
- gliclazide,
- glimepiride,
- glipizide,
- tolbutamide
0 Pioglitazone
0 Gliptins -The
dipeptidylpeptidase-
4 inhibitors :
- alogliptin,
- linagliptin,
- sitagliptin,
- saxagliptin,
- vildagliptin,
0 Sodium-glucose
cotransporter 2
inhibitors (SGLT-2i)
- Canagliflozin
- Dapagliflozin
- Empagliflozin
if lifestyle + drug management - fails ( HbA1c target level not reached /lowered - insulin given )
What is the normal blood glucose level ?
Fasting - 4 - 5.4mmol / L (72 to 99 mg/dl)
Non -fasting - up to 7.8 mmol/L ( 140mg/dl) up to 2 hours after eating.
Treatment of Hypoglycaemia ?
Low glucose - can eat and swallow - sugary drink / oral glucose
severe / bad hypo
- IM Glucagon or Glucogel gel put inside cheek
- if you cannot eat or drink easily
- should not use gel or oral if trouble staying awake cause could choke.
What is Diabetes Mellitus?
Heterogenous group of disorders which share the common characteristics of Hyperglycemia and glucose intolerance
They can have different causes.
Includes Type 1 and Type 2
Type 1 -
Type 2 - link more to environment
What is Diabetes insipidus?
ADH - Anti- diuertic horomone /vasopressin defieciency
frequent urination
excretion of a large amount of dilute urine
excessive thirst
What is Maturity-onset Diabetes of the young?
Group of mongenic (single-gene ) disorders - non insulin dependent (like type 2)
Autosomal dominant - enterly genetic cause.
CAUSED BY BETA CELL DYSFUNCTION.
Rare
Frequently misdignoised as type 1 and tyoe 2
Insulin mechanism of action
- Insulin binds to tyrosine kinase receptor
- Phosphorylation of IRS - insulin receptor substrates.
- This stimulates secondary messenger pathways - These can effect the nucleus - modify genetic expression —-> alter transcription and thus protein synthesis —–> cause changes to cell metabolism
or can effect - transport activity - transport of vesicles from inside cell to membrane e.g GLUT 4 (found inside cell - when insulin binds to tyrosine receptor and following steps occur GLUT 4 migrates to membrane) - membrane transport modified .
alter protein synthesis
