Diabetes Flashcards
What effect does insulin have on blood biochemistry?
- Decreased glucose and potassium and it is taken up by cells
What is the WHO criteria for a diagnosis of diabetes?
- Fasting glucose of >7mmol/l
- Random glucose of > 11mmol/l
One if symptomatic, 2 if aysmptomatic
- HbA1c 48mmol/l or 6.5%. (type 2)
What are the symptoms of undiagnosed T1DM?
- Weight loss
- Polyuria
- Polydipsia
- Fatigue
What is the criteria of DKA?
- Hyperglycaemia (>11mmol/l)
- Hyperketonaemia or ketononuria
- Metabolic acidosis
What are the common biochemical markers of T1DM?
- Low C-Peptide
- High Diabetes associated antibodies
What is the pathogenesis of T1DM?
Genetic predisposition to autoimmunity. Often precipitated by viral illness. Association with environmental factors (cows milk)>
What are the common biochemical markers of T2DM?
- High C-Peptide
- Negative antibodies
What is the pathophysiology of MODY?
Dominant mutation in a single gene - usually HNF-1a.
What is the most common management of MODY?
Sulphonylurea and glicazide
What is the most common insulin regimen for T1Dm?
- Once a day basal, e.g. Levemir
- Bolus before meals, e.g. Novorapid
What molecule is expressed by pancreatic beta cells in order to detect glucose levels and regulate insulin secretion?
Glucokinase
Describe the epidemiology of T2DM
- Age (>50)
- Overweight
- Family history
- Ethnicity (SE asian)
What is the pathophysiology of T2DM?
Insulin resistance due to genetic pre disposition and obesity leads to hyperinsulinaemia. Aging/continued obesity results in beta cells being unable to compensate, leading to hyperglycaemia.
What is the usual pharmacological treatment of T2DM?
1st line - Metformin. If poorly tolerated, Sulphonyurea.
2nd line - Add one of: Sulphonyurea, SGLT-2 inhibitor, DPP-4 inhibitor, pioglitazone
3rd line - Add another or start injectable insulin or GLP-1 agonist
Describe the pharmacology of metformin (mechanism, CV benefit, hypo risk, side effects, contraindications)
Inhibits hepatic gluconeogenesis and increases peripheral insulin sensitivity and therefore glucose uptake and utilisation.
- High CV benefit
- Low hypoglycaemia risk
- Weight loss
- Possible gastrointestinal side effects
- Contraindicated in chronic heart failure and CKD
Describe the pharmacology of sulphonyureas (mechanism, CV benefit, hypo risk, side effects, contraindications)
Close potassium channels on beta cells, causing depolarisation and increased insulin secretion.
- No CV benefit
- High hypoglycaemia risk
- Weight gain
Describe the pharmacology of SGLT-2 inhibitors (mechanism, CV benefit, hypo risk, side effects, contraindications)
-flozins
Inhibits the SGLT-2 in the proximal convoluted tubule in the kidney, decreasing renal reabsorption of glucose
- CV benefit
- Low hypoglycaemia risk
- Weight loss
- Genitourinary side effects
Describe the pharmacology of DPP-4 inhibitors (mechanism, CV benefit, hypo risk, side effects, contraindications)
- gliptins
Inhibits DPP-4 which reduces the destruction of incretins. Incretins increase insulin secretion and decrease glucagon secretion.
- No CV benefit
- Not hypo risk
- Weight neutral
- Well tolerated
Describe the pharmacology of Pioglitazones (mechanism, CV benefit, hypo risk, side effects, contraindications).
Increases sensitivity to fat, liver and muscle cells to insulin
- Weight gain
- Low hypo risk
- Side effects of oedema and fracture risk
- Contraindicated in heart failure
Describe the pharmacology of GLP-1 agonists (mechanism, CV benefit, hypo risk, side effects, contraindications)
Injectable, mimics incretins to increase insulin secretion, decrease glucagon secretion and decrease appetite.
- CV benefit
- Weight loss
- Low hypo risk
- Gastrointestinal side effects
Describe the pharmacology of insulin (mechanism, CV benefit, hypo risk, side effects, contraindications)
Increased glucose uptake by skeletal muscle. Decreased lipolysis. Increased hepatic glycogenesis and reduced gluconeogenesis.
- No CV benefit
- Hypo risk
- ## Weight gain
What should be considered when prescribing for a diabetic with renal failure?
- Metformin should be stopped with eGFR <30
- SGLT-2 inhibitors less effective in CKD
What is hypoglycaemia in diabetic patients?
<4mmol/l
What is hypoglycaemia in a non-diabetic patient?
<2.5mmol/l with symptoms
What are the signs and symptoms of hypoglycaemia?
Sweating, tremor, hunger, palpitations.
Confusion, drowsiness, vision impairment, coma.
What is Whipples triad?
- Symptoms of hyperglycaemia
- Definite low plasma glucose
- Relief of symptoms after administering glucose
What is Whipples triad?
- Symptoms of hyperglycaemia
- Definite low plasma glucose
- Relief of symptoms after administering glucose
What investigations would be carried out on a non-diabetic patient with suspected post-prandial (eating) hypoglycaemia.
Oral glucose tolerance test can be misleading. Give mixed meal after overnight fast and measure venous plasma glucose over 5 hours.
What investigations would be carried out on a non-diabetic patient with suspected fasting hypoglycaemia.
72 hour fast to invoke the homeostatic response which stops the blood glucose from falling (glucagon, adrenaline, cortisol).
What biochemical markers would be investigated in a non-diabetic patient with hyperglycaemia?
Glucose, insulin, C-peptide, ketone bodies, insulin antibodies
What biochemical markers would suggest endogenous hyperinsulinaemic hypoglycaemia?
- Low blood glucose
- High insulin
- High C-peptide
What investigations would be carried out to determine the cause of endogenous hyperinsulinaemic hypoglycaemia?
- Imaging of pancreas
2. Arterial calcium stimulation
What hormone increases appetite in obese people?
Grhelin
What hormone decreases appetite in obese people?
Leptin
