Diabetes Flashcards
What is glycogen?
Storage of glucose. Stored in the liver & skeletal muscle
What is glucagon?
Antagonist of insulin, secreted from alpha cells in the islets of Langerhans. Which convertes glycogen back into glucose.
What is somatostatin?
A hormone that inhibits digestion & absorption. Inhibits secretion of pancreatic hormones.
How is insulin secreted?
Glucose enters via GLUT2 transports. Increase in glucose stimulates metabolism -> an increase in ATP. Increase in ATP inhibits an ATP sensitive K+ channel. causes depolarisation which causes the activation of Ca2+, which causes exocytosis of Ca2+ causes the release of insulin too.
Symptoms of DM?
Polyuria, polydipsia, weight loss, fatigue, blurred vision.
What are the symptoms of DKA?
Hyperventilation, nausea & vomiting, dehydration, weakness, ketone breath, reduces alertness.
Symptoms of HONK?
Same as DKA but doesnt have ketosis or acidsis.
WHO criteria for blood glucose test.
Random venous plasma >=11.1mmol/L
Fasting venous plasma >= 7mmol/L
HBA1c >48mmol/mL (6.5%)
What is classed as hypoglycemia?
blood glucose of less than 4mmol/L.
Treatment of the different severties of Hypoglycemia?
Mild :
15-20g rapidly absorbed sugar, then after this you would have a snack or your next meal to have sustained carbohydrates.
Moderate :
1.5 - 2 tubes of glucogel or inter muscular injection of glucagon (1mg)
Severe :
IM glucagon (1mg) or IV glucose (150mL of 10% over 10 - 15 mins)
What are the microvascular complications of type 2 DM?
Retinopathy, nephropathy, neuropathy.
Why does microvascular complications occur?
Endothelial cells of the retina, kidney, peripheral nervous system allows glucose to enter the cells even in the absense of inslulin.
What should be the first line treatment of Diabetic with hypertension?
ACE-i because it has renoprotective effects. Bc studies showed prevented / delayed progression of renal disease.
What is retinopathy?
Small haemorages, new blood vesseles form which are fragile which tend to bleed which destroy the retina.
What is nephropathy?
Failure of the kidney, and can be cause there to be small amounts of albumin to be found in the urine.
What is neuropathy?
Numbess that occurs in both legs, may or may not cause pain, impaired sense of position.
What causes diabetic foot?
Peripheral vascular disease, causes poor circulation & ischaemia of lower limbs. Can effect getting antibiotics to the site of infection.
What are the macrovascular complications of DM?
Cardio vascular disease.
Hypertension.
Name rapid-acting Insulins.
Novorapid, Humalog, Apidra.
Name short acting Insulins.
Actrapid, Humulin S, Hypurin porcine neutral.
Name Medium acting Insulins.
Insulaterd, Humulin I, Hypurin Porcine Isophane.
Name long acting Insulin.
Levemir & Lantus.
Analogue mixture of insulin.
Novomix 30, Humalog 50/25.
Mixtures of insulin.
Humulin M3, Insuman combi 15,25,50 , Hypurin Porcine 30/70.
Administration sites of insulin.
Abdomen (fast absorption)
Thighs (Slower absorption)
Upper arm (Medium absorption)
Buttocks (Slowest absorption)
Name an example of an Sulphonylureas?
Glyclazide
MOA of Sulphonylureas?
Block the KATP channel causing depolarisation of the membrane potential -> downstream actions and increases the secretion of insulin.
What is a side effect of Sulphonylureas, and why is it caused?
Can cause hypoglycemia bc insulin secretion is increased even in the absence of glucose.
Name an example of a GLP-1 Agonist?
Exenatide
MOA of GLP-1 Agnosits?
Peptide hormone released from the ilium that acts on the GLP-1 Gas coupled receptors in the pancreatic B - cells. Which cause a decrease in gastric emptying, decrease in glucagon secretion and increases in satiety.
Name a DPP-4 Inhibitor?
Alogliptin.
MOA of DDP-4 Inhibitors?
GLP-1 has a very short half life, Inhibition of DPP-4 decreases the breakdown of GLP-1 which therefore allows GLP-1 to perform its biological actions for longer.
What does metformin do?
Decreases gluconeogenesis in liver, increases peripheral glucose uptake & utilisation, improves insulin sensitivity, decreases carbohydrate absorption from the GIT, Decreases lipid synthesis.
MOA of Metformin?
Inhibits complex 1 -> decreases ATP production, increase in AMP : ATP ratio, inhibition of gluconeogenesis, decrease in ATP -> decrease in CAMP lvls, Activation of AMPK, increase of CAMP, decreases fat synthesis, and an increase in fat oxidation.
Name a PPAR gamma Agonist.
Pioglitazone
MOA of PPAR gamma Agonist?
Increase sensitivity of insulin by increasing transcription of genes involved in insulin signalling -> enhancing the effectiveness of insulin.
Name an SGLT-2 Inhibitor.
Dapagliflozin, empagliflozin
MOA of SGLT-2 Inhibitors?
These will reduce & therefore increase excretion of glucose in the urine which then decrease the plasma [ ] of glucose.
Name a alpha-glucoside inhibitor.
Maltase.
What is a multiple dose regime?
Intermediate/long acting basla once daily at night + multiple short acting at meals times.
What are the advantages of Multiple?
Flexible if need to delay meal/adjust for exercise.
Suitable for shift workers.
Disadvantages of Multiple?
More injections.
What is a twice daily regime?
Short + intermediate acting premixed.
What are the advantages of Twice daily?
Simple, good control.
Less injections.
What are the disadvantages of twice daily?
Inflexible, fixed time.
Timed and constant food intake and lifestyle.
What is a Once Regime?
Intermediate / long acting basal once daily at night. Often used with type 2 diabetics.
Starting insluin regime?
Start with low doses and increase slowly
Twice daily : 6-10 units BD
Multiple : short 60% & long 40% (4 units TDS & 8 units NOCTE)
Adjusting Insulin doses.
Adjust doses by 10% alloquots.
Do not omit doses if too low.
Storage?
Long term storage in fridge loss of 5-10 % poteny at room temp.
Current use keep out of fridge.
1 month out of fridge.
Why should longer acting sulphanolureas be avoided in the elderly?
Longer acting such as glimperide should be avoided beause it can cause hypoglycaemia.
What is the SAR for sulphonylureas?
p- subunit on aromatic ring, not amine to avoid antibacterial activity.
Alkyl substituient on urea.
What are the main things that cause oxidative stress?
Hydrogen peroxide
Superoxide
Hydroxyl radicals
What causes polyuria?
Osmotic diuresis when blood glucose exceeds renal threshold.
What causes polydipsia?
Due to resulting fluid & electrolyte loss.
Why does weight loss occur in DM?
Due to fluid delpletion & increased breakdown of fat & muscle.
Why does fatigue occur in DM?
Body’s inability to get glucose from blood into cells to meet energy needs.
Why does blurred vision occur in DM?
Due to blood glucose induced changes in refraction.
What is the ETC?
Series of biochem reactions in which electrons and hydrogen atoms from NADH and FADH are passed to intermediate carriers and then ultimately react with molecular oxygen to prod water.
How is AcetylCoA converted to Ketone bodies?
Converted to AcetoacetylCoA
Then converted to 3-hydroxy-3methylglutarylCoA
Which is then converted into acetoacetate -> Acetone.
What is the PKC pathway?
Excess DHAP converted to Diacyl glycerol (DAG)
DAG activates PKC.
Activated PKC leads to blood-flow abnormalities, capillary and vascular occlusion, pro-inflammatory gene expression, Increased NADPH which is a ROS which causes oxidative stress.
What does glutathione do to methylgyoxal
Reduces it (DHAP) via the glyoxalase pathway into lactic acid.
same occurs with the polyol pathway but this decreases NADPH which is used to regenereate glutathione.
What cells in the islets of langerhands secrete glucagon?
Alpha cells.
What cells in the islets of langherans secrete insulin
Beta cells.
What receptotr does insulin act at?
RTK.
What receptor does glucagon act at?
GPCR Gas
