Pancreatic Disease Flashcards
What are the different types of diabetes
T1DM
T2DM
MODY
LADA - Latent autoimmune diabetes of adults
What is MODY?
MATURE ONSET DIABETES of the Young
non-insulin dependent diabetes which showed autosomal dominant inheritance
β cell dysfunction characterised by non-kenotic diabetes and absence of pancreatic auto-antibodies
MODY ~ HNF1-alpha gene = causes diabetes by reducing insulin synthesis
What is LADA
Latent Autoimmune Diabetes in Adults
Polydipsia
Polyuria + Nocturia
Ketosis
Rapid weight-loss
Young
BMI <25
FHX autoimmune disease
These are a presentation T1DM
Which genes are associated with T1DM
HLA DR3/HLA DR4
What is the pathogenesis of T1DM?
Autoimmune disease - ICA
TYPE 4 HYPERSENSITIVITY
Islet cells antibodies attack islet b cells resulting in absolute INSULIN deficiency
=
Low cellular glucose
Hyperglycemia
Hyperkalemia
What does insulin do?
Stimulates:
Increase GLUT4 reeceptor on cell surface thus increasing glucose uptake into cells
Glycogenesis (glycogen storage in hepatocytes)
Lipogenesis glucose > fatty acids (storage in adipocytes)
Inhibits
Glycogenolysis
Gluconeogenesis
Lipolysis
Ketogenesis - Too much can cause DKA
How may a patient with T1DM look like?
YOUNG, LEAN AND WHITE
DX T1DM
HbA1C >48 or 6.5%
Fasting >7
Random >11
Tx T1DM
BASAL-BOLUS REGIMEN
Basal - Slow acting
glargine/detmire
Bolus - Fast Acting
Novorapid (Aspart)
What do you do if patient medication isnt working and has lead to persistent and disabling hypoglycaemia
MIX INSULIN REGIMEN
and if hba1c cant be controlled at all and is above >69
consider continuous infusion pump
What are the macrovascular complication of Diabetes?
Cardiovascular - IHD, HF, PVD
Cerebrovascular disease- Stroke
what are the microvascular complications of diabetes?
Neuropathy:
Mononeuropathy/polyneuropathy - (Stocking glove neuropathy)
Autonomic neuropathy
Retinopathy
Diabetic Nephropathy
Cataracts
What is the main acute complication of T1DM?
DKA - Diabetic ketoacidosis
How Does T1DM lead to DKA?
through two mechanism:
Due to absolute def of insulin there is unrestrained GLUCONEOGENESIS - which causes hyperglycaemia and subsequently osmotic diuresis (increased URINATION)
ALSO due to unrestrained lipolysis and subsequently fatty acid oxidation (ketogenesis) - excess ketone bodies which cause ketoacidosis
How would someone with DKA present
MEDICAL EMERGENCY
Patient will have Reduced GCS
Reduced tissue turgor
Haematologically unstable - High HR, Low BP
N/V
+ Signs:
Kussmaul’s Breating - Deep laboured breathing
Pear drop breath - Acetone / nail varnishy smell
What is the diagnostic criteria for DKA involve?
Diagnostic criteria includes:
Plasma ketone >3mmol/l
RPG>11mmol/l
Blood pH <7.35 - Acidosis
Blood Bicarbonate > 15 mmol
Other observation include:
Urine dipstick: ketonuria/glucosuria
Serum U/E - Up urea / creatinine
hyperkalaemia
How is DKA mananged?
ABC management
IV fluids
IV insulin
restore electrolytes (e.g. K+)
in Hypoglycemia what do you give to patients?
Initially a fast acting carb - Glucose tablets
then a long acting carb - Bread
If reduced GCS - IV glucose / IM glucagon
What is the pathology of T2DM
AND ASSOCIATED RF
Peripheral insulin resistance (Down GLUT4 expression)
+/- partial insulin insufficiency
RF:
Steroids/Cushing’s
Chronic pancreatitis
T2DM risk factors
Lifestyle: obesity, sedentary, high calorie or alcohol excess
Higher prevalence in Asian men
Above 40 years old (late onset)
Hypertension
presentation of T2DM
30+, Obese, HTN, Asian
px/ Triad
Polydipsia
polyuria + Nocturia
Wt gain / Then wt loss later on
Glucosuria
Acanthosis nigrican (dark thick velvety skin at body folds/creases)
1st line management of T2DM
Lifestyle changes for allll
Tx T2DM
1st - Metformin Biguanide
2nd - + Sulphonyl urea
+ DPP4 Inhibitors
+ Pioglitazone
If contradications (CKD/HF/CVD) - Use SGLT2 Inhibitors
Metformin MOA and SE
Decrease gluconeogenesis
and
Increases insulin sensitivity (up GLUT 4)
Thus increases glucoses reuptake into cells
SE - Decreased B12 absorption - peripheral neuropathy
GI disturbances
CI- CKD
Sulphonylurea E.g Glicazide MOA / SE
Acts on B cell to promote insulin secretion
SE - Wt Gain/ Hypoglycemia/ GI disturbance
Pioglitazone MOA / SE
Reduces peripheral insulin resistance / Increases glucose metabolism
SE - Bone fracture/ Wt Gain
CI - HF
DPP4i e.g sitagliptin MOA / SE
Inhibits dipeptidylpeptidase-4 to increase insulin secretion adn reduce glucagon secretion
SGLT2 inhibitor
Inhibits sodium-glucose 2 co-transporter to reduce glucose reabsorption and increase urinary glucose excretion
SE: DKA, Uti, Back Pain
What are the glucose range for OGTT?
OGTT - Oral glucose tolerance test
Give 75mg of fast acting glucose than after 2 hours take blood glucose level
Normal range - <7.8mmol/l
Prediabetic 7.8-11 mmol/L
DM>11mmol/l
What are the glucose range for FPG?
First measure taken at OGTT is considered FPG
Normal <6
Prediabetic -6.1-6.9
DM >7
What does it mean if someone has impaired fasting glucose IFG
Prediabetic patient w/ hepatic insulin resistance
FPG- 6.1-7mmol/l (Prediabetic range)
OGTT- <7.8 - Normal
What does it mean if someone has impaired glucose tolerance IGT
Prediabetic patient w/ muscle insulin resistance
OGTT - 7.8-11
FPG<6mmol/l - Normal
What is the main acute complication of T2DM?
Hyperosmolar Hyperglycaemic State - HHS
This in turns causes severe osmotic diuresis
What causes hyperosmolar hyperglycaemic state?
Excess gluconeogenesis and lipolysis result in hyperglycaemia.-> Osmotic diuresis
However sufficient insulin to prevent ketogenesis (DKA)
What are the diagnostic criteria for HHS?
Urine dipstick - Glucosuria
High plasma osmolality
profound hyperglycaemia (glucose ≥30 mmol/L [≥540 mg/dL]), hyperosmolality (effective serum osmolality usually ≥320 mOsm/kg
volume depletion
in the absence of significant ketoacidosis (pH ≥7.3 and bicarbonate ≥15 mmol/L [≥15 mEq/L]),
HHS TX
IV fluids
Insulin (at low rate of infusion)
Restore electrolytes
LMWH
Describe Insulin release?
Glucose in blood bind to low affinity GLUT 2 receptors on beta pancreatic cells.
So at high glucose conc->inward glucose movment -> metabolism and atp production results in K+ chanels closing - > depolarisation-> calcium influx -> insulin vescile exocytosed
What does HbA1c represent?
Measure of glycated haemoglobin over the previous 3 months
Measures: >48mmol/L or >6.5% or greater is diagnostic but less is not definitive
When cant we use HbA1C
Anything that affects
Anyone younger than 18
pregnant or 2 month post partum (gestational diabetes)
sx of diabetes less than 2 months
Anything that affects glucose levels:
Acutely unwell - infection associate hyperglycaemia
Hyperglycaemia induce medications - corticosteroids
Anything that affects RBC
Acute pancreatitis
CKD
HIV
Anemias
