Treatment of Diabetes Flashcards
At what blood glucose level would you expect it to be detected in the urine?
> 10mM
Give some examples of insulin medications given in diabetes treatment and their formulations
- rapid-acting soluble insulin: insulin (eg. insulin lispro): wutg amino acid modifications which prevents dimer/hexamer formation increasing bioavailability of active monomers
- intermediate-acting (eg. isophane insulin): forms precipitate suspensions that slowly dissolve
- longer-acting insulin (eg. insulin glargine): forms aggregates that slowly dissolve and has decreased solubility at neutral pH
- longer-acting insulin with fatty acid (eg. insulin detemir): confers albumin binding, slowly dissociates to prolong activity
Describe fixed insulin regimens
- amount of insulin taken at each meal will not vary from day to day
- helps simplify understanding of blood glucose results but not much flexibility of how much carbs patient may choose to consume at a meal
- means routine and consistency needed
Describe flexible insulin regimens
- used for patients that really understand glucose metabolism and gives patients more control of what they eat and how they balance their blood glucose levels
- patients choose how much insulin to inject at each meal and allows for doses to be varied in response to different carb quantities at meals
- means patients must check their blood glucose readings, calculate how much carbs they are going to consume and adjust their dose accordingly
Describe the 1, 2, 3 insulin therapy
- 1-3 injections a day taken in the morning and meals
- suitable for T2D with basic understanding of glucose metabolism
- rapid-acting/short-acting insulins mixed with intermediate insulins used
- meal times and content are fixed
Describe the basal-bolus insulin therapy
- > 3 injections a day (intensive) given throughout the day
- suitable for T1D and some T2D with a high understanding of glucose metabolism
- intermediate/long-acting with short-acting insulins
- meal time and content more flexible
Describe the insulin pump therapy
- semi-automated injections given when needed throughout the day
- suitable for T1D with medium/high understanding of glucose metabolism
- short-acting formulation used
- meal times and content flexible
List some lifestyle modifications to prevent prediabetes
- increasing exercise and having a healthy diet:
- decreasing intake of processed carbs
- ensure carbs come from fruits, veg, and whole grains
- eat low-fat dairy and oily fish
- limit trans/saturated fats
- eat small frequent meals to prevent glucose spikes
- increase fibre and eat complex carbs
- decrease alcohol consumption
What are oral hypoglycaemic agents?
- drugs used to alter glucose metabolism in type II diabetics
- first-line drug is metformin
Describe the physiological action of metformin
- reduces gluconeogenesis in liver
- opposes action of glucagon
- increases glucose uptake and utilisation in skeletal muscle
- delays carb absorption in gut
- increases fatty acid oxidation (reduces circulating LDL and VLDL which can help obesity and atherosclerosis development)
- suppresses appetite
Describe the cellular action of metformin
- enters the cell through transporter in membrane
- acts on mitochondria to increase ratio of AMP to ATP
- activates AMP-activated protein kinase (switches on metabolism)
- inhibits glucagon signalling and gluconeogenic pathways
- increases transcription of genes for glucose transport, fatty acid oxidation and inhibits fatty acid synthesis
What are the insulin secretagogues: sulphonylureas/meglitinides?
- older class of hypoglycaemic drugs
- eg. gliclazide and tolbutamide (sulphonylureas) repaglinide and nateglinide (metlitinides)
- used in early stages of type II diabetes because it needs functional beta cells to work
- can lead to weight gain as it can stimulate appetite
- can be combined with other insulin drugs
Describe the cellular mechanism of action of sulphonylureas
- high affinity receptor on B cell membrane
- drug enters and blocks ATP-sensitive K+ channels
- causes beta cell depolarisation leading to insulin secretion
- only works in functional beta cells
What are examples of SGLT2 inhibitors and when are they indicated?
- empagliflozin and canagliflozin
- used in type II diabetes as monotherapy
- used when exercise alone is not adequate and metformin is contraindicated or inappropriate
Describe the action of SGLT2 inhibitors
- block SGLT2 transporters in proximal tubule of kidney
- would normally reabsorb glucose from the forming urine into the blood
What are incretins and their actions on the body?
- GKP-1 secreted by L cells and GIP secreted by K cells in the gut
- stimulate insulin biosynthesis/secretion, inhibit glucagon secretion in pancreas
- delay gastric emptying
- increase CO and brain satiety signals
- indirectly increase insulin sensitivity in muscle and decrease gluconeogenesis in liver
What enzyme is responsible for the breakdown of incretins?
dipeptidyl peptidase-4 (DPP-4)
What are examples of incretin mimetics and their physiological action
- exenatide
- liraglutide (has additional fatty side chain which albumin can bind to, slows clearance)
- increases insulin secretion and suppresses glucagon secretion
Describe the mechanism of action of the gliptins and examples
- blocks DPP-4 enhancing endogenous incretin effects
- lowers blood glucose by increasing first phase of insulin response after meals
- eg. sitagliptin and vildagliptin
Describe the mechanism of action and example of glitazones
- PPAR-gamma agonists (receptors in adipose tissue, muscle and liver)
- increases insulin sensitivity, lowers blood glucose,
- promotes esterification/storage of FFAs in adipose tissue (increases transcription of genes that promote this)
- eg. pioglitazone
What are the drawbacks of glitazones?
associated with bladder cancer, heart failure, and osteoporotic fractures
Describe the mechanism of action of alpha-glucosidase inhibitors with an example
- competitive inhibitor of intestinal alpha-glucosidase
- delays carb absorption in small intestine reducing post-meal spike in glucose
- allows cells time to absorb and process glucose
- acarbose
