Type II Diabetes Mellitus Flashcards
Definition
A STATE OF CHRONIC HYPERGLYCAEMIA SUFFICIENT TO CAUSE LONG-TERM DAMAGE TO SPECIFIC TISSUES, NOTABLY THE RETINA, KIDNEYS, NERVES AND ARTERIES
Is T2DM ketosis prone? Why
No, we still have insulin and that will stop ketone production
Fasting sugar should be X or below, but Y or above means diabetes
6
7
2-hour sugar should be X or below, but above Y means diabetes
7.8
11
What is someone described as being if their fasting/2 hour sugar is in-between normal and diabetic
Impaired glucose tolerance
Using random glucose is unreliable as ….
you don’t know where the reference range should be.
Diabetes is most prevalent in which race
The White™
Biggest environmental factor for T2DM?
Greatest in ethnic groups that move from rural to urban lifestyle
What factors influence TIIDM? (5)
Genes
Obesity
Genes and Intrauterine Environment
Adult environment
What needs to happen for T2DM? (4)
Beta cell failure
Inflammation
Metabolic dyslipidaemia
Hyperglycaemia
What is MODY?
- Autosomal dominant – single gene defect
- Leads to Ineffective pancreatic Beta cell insulin production
What gene is commonly affected in MODY
Glucokinase
TIIDM is largely influenced by what?
Genetic
What is T2DM fundamentally
There is insulin resistance
What modulates insulin resistance
modulated by adipocytokines
How does birth weight come in with T2DM
Being born light IUGR is associated with genetic mechanisms of T2DM
Insulin resistance and high glucose can also contributes to failure of what cells?
Beta islet cells
ONLY diabetes can cause microvascular ….
complications
The β-cell failure will eventually lead to …
insulin requirement as the pancreas fails.
with age, insulin resistance [increases/decreases]
Increases
with age, potential insulin secretion [increases/decreases]
decreases
What does the potential Isec/insulin resistance graph suggest
That everyone will get diabetes at some point
Presentation of T2DM
- Heterogeneous – TIIDM is a range of conditions with a final common pathway of high sugar.
- Obesity
- Insulin resistance and insulin secretion deficit
- Hyperglycaemia and dyslipidaemia
- Acute and chronic complications
Insulin effects?
Encourages glucose uptake into muscle
Decreases hepatic glucose output
Decreases adipocyte FA output
Decreases adipocyte glycerol output
Adipocytokines are produced by…..
Adipocytes
Adipocytokines role is to …
tell the brain of the level of fat in your body
Most simple way to test risk of ischaemic heart disease?
Measure waist circumference
gut microbiota and T2DM / obesity?
There is an association but no causation thus far
Common side effect of diabetes treatments?
Weight gain
Which diabetes drug doesn’t cause weight gain?
Metformin
What factors affect Isec potential?
Genes
What factors affect IR? (6)
Intrauterine environment Microbiota Adipocytokines Exercise Diet Medication
Early Presentation of T2DM:
- Osmotic symptoms- glycosuria which leads to polyuria, polydipsia
- Infections
- Late presentation is in the form of complications
Microvascular complications of T2DM? (3)
Retinopathy
Nephropathy
Neuropathy
Metabolic complications of T2DM? (2)
Lactic acidosis
Hyperosmolar
Macrovascular complications of T2DM? (4)
Ischaemic heart disease
Cerebrovascular problems
Renal artery stenosis
PVD
Treatment complications of T2DM?
Hypoglycaemia
Basics of managing T2DM (4)
- Education
- Diet
- Pharmacological treatment
- Complication screening
how to manage diet in diabetes:
- Control total calories/increase exercise (weight)
- Reduce refined carbohydrate (less sugar)
- Increase complex carbohydrate (more rice etc.)
- Reduce fat as a proportion of calories (lowers IR)
- Increase unsaturated fat as a proportion of fat (IHD)
- Increase soluble fibre (longer to absorb carbs)
- Address salt (BP risk)
4 targets for treating T2DM?
- Weight
- Glycaemia
- BP
- Dyslipidaemia
What is used to treat weight in T2DM? (2)
Orlistat- a GI lipase inhibitor, surgery (gastric bypass)
What is used to treat glycaemia in T2DM? (2)
METFORMIN insulin sulphonylureas metaglinides alpha glucosidase inhibitors thiazolidinediones GLP DPP4 inhibitors SGLT2 inhibitor
What does metformin do
Reduces HGO
Increases peripheral glucose disposal
When is metformin contraindicated
if severe liver, severe cardiac, or mild renal failure
Huge pro of metformin?
Doesn’t cause weight gain
MoA of metformin?
- Bypasses the need for entry of glucose in order to block the ATP sensitive K+ channel
- Causes blockage of this channel when it binds to receptors, irrespective of glucose entry
- Calcium ions rush in, causing insulin secretion
What is acarbose
- Alpha glucosidase inhibitor - enzyme that digests carbohydrates
What does acarbose do
- Prolongs absorption of oligosaccharides
- Allows insulin secretion to cope, following defective first phase insulin
Side effect of acarbose?
Flatus
What is thiazolidinedione
- Peroxisome proliferator-activated receptor agonists- PPAR-GAMMA
effect of thiazolidinedione
- Insulin sensitizer, mainly peripherally effective
What is GLUCAGON LIKE PEPTIDE-1 (GLP-1):
- Secreted in response to nutrients in the gut by L cells
Effect of GLUCAGON LIKE PEPTIDE-1 (GLP-1): (2)
- Stimulates insulin, suppresses glucagon
WHY DO WE COADMINISTOR DPPG4 INHIBITORS INSTEAD OF JUST GLP1?
- Short half-life, rapid degradation
EMPAGLIFOZIN IS A …
SGLT2 inhibitor
WHAT DOES AN SGLT2 INHIBITOR SUCH AS EMPALIFOZEN DO
- Inhibits Na-Glu transporter, increases glycosuria (and so polyuria unfortunately)
Best way to precent diabetes/
Diet and exercise
