Diabetes mellitus Flashcards
What are Kimmelstiel-Wilson lesions?
Nodular glomerulosclerosis
What is the most common cause of amputation in Australia?
Diabetic peripheral neuropathy
What are the 3 ways of monitoring diabetes control?
BSL. Hb1Ac. Fructosamine.
If a diabetic patient has HbA1c of 7%, but high BSLs, what should you consider?
Bleeding
Which cells make up 80% of the islets of Langerhans?
Beta cells
List three reasons for why is there increased atherosclerosis in DM
1 Increased hepatic production of atherogenic lipoproteins 2 Suppression of lipid uptake in peripheral tissues 3 Abnormal endothelial function with pro-coagulant effects
Which conditions are a contraindication for alpha-glucosidase inhibitors?
Cirrhosis or IBD
What is insulin glulisine?
Short acting insulin
Which enzyme converts pro-insulin => insulin?
Prohormone convertase 1
What are the side effects of sulphonylureas?
Weight gain and hypoglycaemia
What is the molecular target of metformin?
AMP kinase
Is more insulin released after IV or oral administration of glucose?
Oral
How do sulphonamides work at an organ level when treating diabetes?
Increase insulin release from the beta cells of the pancreas
Which cells have receptors for AGEs?
Macrophages, endothelial, vascular smooth muscle, T cells
What is exenatide?
A GLP-1R agonist
Which hormone is released with a fall in BSL?
Glucagon
What is the molecular action of sulphonylureas?
Inhibit ATP-dependent K+ channels
What class of drug is metformin?
Biguanide
What class of drug are the -liptins
DPP-IV inhibitors (prevents breakdown of GLP-1 to treat diabetes)
What does ‘diabetes’ mean?
Production of abundant urine
Which conditions are a contraindication for metformin?
Renal impairment
What is the tissue level effect of alpha-glucosidase inhibitors?
Reduce digestion and absorption of CHOs from small intestine
What type of cells kill beta islet cells in T1DM
Cytotoxic T cells
What are the main side effects of alpha-glucosidase inhibitors?
Flatulence, abdominal discomfort, loose stools
What is insulin lispro?
Short acting insulin
What is HbA1c?
Glycosylated haemoglobin - a marker for diabetes control
Which three tissue are particularly vulnerable to complications in diabetes mellitus?
Kidneys, retina, nerves
Name 2 main effects of GLP-1
Delays gastric emptying Stimulates pro-insulin syntheis
How doe DPP-4 drugs treat diabetes on a tissue level?
Inhibit breakdown of incretins, thus increasing insulin:glucagon ratios
How does diabetes cause peripheral neuropathy?
Ischaemic damage AGEs damage axons and schwann cells
What are the 4 main actions of metformin at a tissue level?
GAIL Gluconeogenesis in liver is inhibited Absorption of carbohydrates is reduced Insulin-mediated glucose uptake is enhanced LDL and TAG levels are decreased
What is the cascade for insulin release from beta cells?
Glucose enters through GLUT-2 Glycolysis and TCA cycle yields ATP ATP displaces ADP from K+ ATP channel K+ influx depolarises cell Depolarisation opens voltage gated Ca2+ channel Ca2+ enters cell and causes vesicles to exocytose insulin
Which country has the highest prevalence of Type 1 diabetes?
Finland
What type of drug is exenatide?
Glucagon-like peptide-1 agonist
How long does the second phase of insulin release last for?
As long as the stimulus is present
What do fructosamine levels tell you in a diabetic patient?
How good BSL control has been over the past 6 to 8 weeks
Why is there polyuria in DM?
Hyperglycaemia => glucosurea => osmotic diuresis => polyurea
Which is the most potent incretin?
GLP-1
What are the 2 classical symptoms of Type 1 diabetes?
Polyuria and polydipsia
Name 3 effects of amylin
Delays gastric emptying Inhibits glucagon secretion Reduces food intake
What do theta cells of the pancreas secrete?
Pancreatic polypeptide
What is detemir insulin?
A long acting form of insulin
What are the two long acting forms of insulin?
Glargine and determir
What are the three short acting forms of insulin?
Glulisine, lispro, aspart
How do you treat an unconscious diabetic patient with hypoglycaemia?
IV glucose or glucagon
Which cells secrete GIP ()glucose-dependent insuinotropic polypeptide)?
K cells of duodenum
How is exenatide administered?
S.C.
What is the most common cause of blindness in Australia?
Diabetic retinopathy
What do HbA1c levels tell you in a diabetic patient?
How good BSL control has been over the past 3 months
Name 5 ways that AGEs may lead to atherosclerosis?
Stimulate macrophages to release pro-inflammatory cytokines Stimulate vascular smooth muscles to proliferate Generate ROS in endothelial cells Cause endothelial cells to become pro-coagulant AGEs can cross-link with collagen, trapping LDL
What effect does insulin have on potassium?
Lowers plasma K+ but transferring it intracellularly
Which phase of insulin release is most impaired in T2DM?
Initial spike
How long does the first phase of insulin release last for?
2-5 mins
What is the magic number for HbA1c?
7%
What are the main side effects of metformin?
GI upset and lactic acidosis
What is the eponymous name for nodular glomerulosclerosis?
Kimmelstiel-Wilson lesions
What degrades GLP-1?
DPP-IV Di-peptidyl peptidase-IV
What is the most common cause of kidney failure in Australia?
Diabetic nephropathy
What is the main macrovascular complication of DM?
Atherosclerosis
What does glucagon do?
Causes liver to release glucose via GNG or glycogenolysis
Why does orally administered glucose cause a greater increase in insulin levels?
It activates incretins (Glucagon-like peptide 1 and glucose-induced insulinotropic polypeptide)
What is insulin aspart?
Short acting insulin
What are 3 candidates for diabetes-mediated pathology?
Advanced glycation end products Activation of Protein Kinase C Polyol pathways
What is the glycosylated form of haemoglobin?
HbA1c
What are three typical pathological effects of diabetes in the kidneys?
Kimmelsteil-Wilson nodules Thickening of glomerular basement membrane Hyaline arteriolosclerosis
Which cells secrete GLP-1?
L cells of small intestine
What does dipeptidyl-peptidase do?
Breaks down incretins
What is glargine insulin?
A long acting form of insulin
What BSL levels indicate hypoglycaemia?
< 4 mmol/L
What is the advantage of detemir insulin?
It has a FA added, meaning it has a longer half life and can cross BBB
What effect does insulin have on fat metabolism?
Decreases lipolysis
What is the most common precipitating event for diabetic ketoacidosis?
Infection
What is released with insulin?
C-peptide and amylin
How do sulphonylureas work at an organ level when treating diabetes?
Increase insulin release from the beta cells of the pancreas
