WEEK 4 Flashcards
What is the glucose profile of a non-diabetic person?
around 6mmol/L, with peaks due to dawn phenomenon (increased cortisol levels) and evening meal (range 4-10mmol/L)
What is the glucose profile of a (type 1) diabetic person?
Much larger range with higher average levels (6-15mmol/L)
What is hyperglycaemia?
High blood glucose levels
What is hypoglycaemia?
Low blood glucose levels
What is the BG threshold for hypoglycaemia?
<4mmol/L (four is the floor)
What is the BG threshold to drive?
> 5mmol/L (five to drive)
What are the NICE targets for BG?
4-7 pre-meal
5-7 on waking
5-9 90 mins after meal
What is the BG threshold for ketone testing?
at or >15mmol/L
Define diabetes
A lifelong condition that causes a person’s blood sugar levels to become too high
What are the symptoms of diabetes?
none weight loss tiredness candidiasis (thrush) abscess polyuria (excessive urination) blurred vision coma
What is the HbA1c test?
Test for glycosylated haemoglobin that reflects previous 10 weeks of ambient circulating glucose (doesn’t require fasting)
What does low HbA1c mean?
Low BG levels
What does high HbA1c mean?
High BG levels
What is the threshold HbA1c level for diagnosing Diabetes Mellitus?
6.5% or 48mmol/L
What are two standard ways of measuring blood glucose levels and what are their thresholds for diagnosing DM?
Random glucose -> ≥11.1 mmol/L
Fasting glucose -> ≥7.0 mmol/L
(repeat if they exceed threshold with no diabetic symptoms)
What is the oral glucose tolerance test?
Gold standard test for DM
done in fasting state, measure glucose t=0, 75g glucose drink over 5 min period, wait 2 hours, measure glucose t=2 hrs
What are the threshold levels of the oral glucose tolerance test?
Impaired fasting glycaemia (t=0)=6.1-6.9mmol/L
Impaired glucose tolerance (t=2h)=7.8-11.1mmol/L
Diabetic fasting value (t=0)= ≥7.0mmol/L
Diabetic 2 hour value (t=2h)= ≥11.1mmol/L
What are three ways to remove glucose from the bloodstream?
Liver
Muscle
Fat
What is the process of glucose absorption from the bloodstream?
Insulin binds to insulin receptors on cell-surface, glucose channels open (GLUT), glucose enters cells
What is the role of insulin?
To move glucose out of the bloodstream into liver/muscle/fat for storage/building (decreases BG)
What are the major metabolic functions of insulin?
Maintains supply of glucose to tissues
Regulates metabolism in muscle
Promotes protein synthesis
Inhibits fat breakdown
Where is insulin produced and secreted?
Beta cells in the pancreas
What is Type 1 diabetes?
Where the body’s immune system attacks and destroys the cells producing insulin (Insulin deficiency)
What is Type 2 diabetes?
Where the body doesn’t produce enough insulin, or the body’s cells don’t react to it (Insulin resistance and partial deficiency)
What is gestational diabetes?
Occurs during pregnancy, where women cannot produce enough insulin to absorb such high levels of BG
Characteristics of Type 1 diabetes
absolute insulin deficiency onset typically <40 yrs but can be any age onset usually dramatic family history less common presence of ketones requires insulin therapy
What is the cause of Type 1 diabetes?
Insulitis-autoimmune condition where lymphocytes think insulin-producing beta cells are foreign, so destroy them
What is the triglyceride process caused by a lack of insulin?
triglycerides->fatty acids(->TCA cycle)->acetoacetate(urine ketones)->beta-hydroxybutyrate(blood ketones)/acetone(smell of pear drops on breath)
Characteristics of Type 2 diabetes
Insulin resistance and relative insulin deficiency
onset typically >40 yrs (now getting younger)
genetic predisposition
associated with obesity
insidious onset of symptoms
no ketones
doesn’t require insulin therapy but is used by 1/3rd of Pts
What are the ‘3 steed of a diabetics chariot’?
Diet
Exercise
Insulin (medication)
=glucose control
What are the two forms of giving insulin throughout the day?
Slow-acting 1/2 injections/day
Fast-acting injections for every meal
How many capillary glucose testing (finger-prick) throughout the day?
4/6 times a day (before each meal, bed and driving)
What other medications are used to lower glucose?
Tablets:
Insulin sensitisers=causes body to be less resistant
Insulin secretogogues=makes more insulin
Gut absorption=glucose moves out of blood into gut
Glucose excretion=causes glucose to be removed
Incretin breakdown inhibitors=incretin which is released after eating and augments insulin secretion via pancreatic beta cells, has inhibitors to it’s breakdown
Injection:
Incretin mimetic=substitute for incretin
What are the three amigos of monitoring in diabetes?
High BG, BP and lipids
Medication for BP
ACE inhibitors
Beta blockers
Calcium channel blockers
Diuretics
Medication for lipids
Statins
Fibrates
What are the two types of complications of diabetes?
Microvascular (retinopathy, nephropathy, neuropathy)
Macrovascular (heart disease, renal artery disease, peripheral vascular disease, stroke)
gangrene=both micro- and macrovascular
How do you reduce complications?
control of glucose for prevention of small vessel disease, control of lifestyle/smoking/BP/cholesterol for prevention of large vessel disease
Is insulin a hyper- or hypoglycaemic agent and what is its release process?
Hypoglycaemic
Glucose enters beta cells, metabolism causes increased intracellular ATP, decreased ATP-sensitive K+ channel activity, decreased K+ efflux (depolarisation), opens V-gated Ca2+ channels which causes secretion of vesicles containing insulin/insulin release can also be from enzyme regulation or incretins
What is the profile of insulin release in normal people?
Biphasic
What are the two phases of insulin release?
1st phase (largest release) due to Ca2+ mechanism 2nd phase (smaller release) due to enzymatic release
What phase of insulin release do people with Type 2 diabetes not have?
1st phase
What phases of insulin release do people with Type 1 diabetes not have?
Both phases
Where are insulin receptors found?
Liver, Muscle and Fat
What is the process of insulin binding to the insulin receptor?
Phosphorylation of IRS (insulin receptor substrate) as a response of insulin binding
Enzyme activation and gene transcription causes increased glucose uptake (expression of GLUT-4) and glycogen synthesis
What are the routes of administration of insulin and why?
has to be given parenterally: s.c.; i.m.; i.v. due to insulin half life being short (t1/2=5 mins)
What are the complications of insulin therapy?
Hypoglycaemia
Allergy
Lipodystrophy
What are the oral hypoglycaemic agents?
Biguanides (Metformin) Sulphonylureas Thiazolidinediones Drugs based on incretin actions Acarbose SGLT2 inhibitors
What is an example of Biguanides and what is it’s mechanism?
Metformin
Decreased gluconeogenesis in the liver via activation of AMP-activated protein kinase, increased glucose uptake in muscles
What are the side effects of Biguanides?
No hypoglycaemic propensity, no increased appetite, lactic acidosis (not as bad with Metformin)
When is Metformin often used?
Obese diabetics->combination therapy
What are examples of Sulponylureas (SU) and what is it’s mechanism?
Tolbutamide (short-acting)/Glibenclamide (long-acting)/Gliclazide
SU binds to SURs in beta cells (part of Katp channel), causes channel to close (similar effect to increased intracellular ATP), depolarisation, V-gated Ca2+ channels open, causes increased insulin secretion
2ndary effect of increased tissue sensitivity to insulin
What are the side effects of SU drugs?
Hypoglycaemia, appetite stimulation (don’t use for obese), contraindicated in pregnancy/breastfeeding
What is an example of Thiazolidinediones and what is it’s mechanism?
Pioglitazone
Binds to TF, affecting gene expression:
Primary action at adipose tissue=increased fatty acid uptake and lipogenesis (weight gain)
Secondary action of decrease plasma fatty acids=increased glucose uptake and decreased gluconeogenesis
What are the side effects of Thiazolidinediones?
Liver toxicity and heart failure (due to fluid retention due to Na+ retention in the Kidney)
What are incretins?
GI hormones (eg. GLP-1) which act on the pancreas to increase insulin and decrease glucagon
What are two types of drugs based on incretin actions and what are their mechanisms?
1) Inhibitors of dipeptidyl peptidase-4 (DDP-4) which metabolises incretins
2) Glucagon-like peptide-1 (GLP-1) agonists
What is the mechanism of Acarbose?
alpha-glucosidase inhibitor which decreases carbohydrate absorption due to decreased carbohydrate metabolism (used for obese diabetics)
What are SGLT2 inhibitors, what is their mechanism (and give an example)?
Sodium-glucose transporter-2 inhibitors which act on the PCT of the kidney to increase glucose and Na+ loss (Canagliflozin)
What are the side effects of SGLT2 inhibitors?
Peripheral vascular disease, ketoacidosis (increased acidity of the blood)
