Diabetes Type 2 Flashcards
What factors cause insulin resistance?
Genetic risk
Obesity
What is LADA?
Latent autoimmune diabetes in adults
- need be aware aware that there are cases where diabetic ketoacidosis is a feature of T2DM, and it may be present in the youth
What is monogenic diabetes?
Can present phenotypically as type 1 or type 2 e.g. MODY mitochondrial disease
Which country as the highest projected prevence?
India
Whats a normal fasting glucose vs a T2 fasting glucose?
<6mmol/L
vs
> 7mmol/L
What is a normal 2 -hr glucose vs a T2?
<7.7 mmol/L
vs
> 11mmol/L
What happens to Beta cell function after T2DM?
If treatment is started, function % may increase by a very small %. then it will decrease a few years after being on treatment steadily
What does it mean to have relative deficiency of insulin?
Insulin is being produced but not enough to overcome insulin resistance
In which cases may T2DM have complete insulin deficiency?
Long duration T2, beta cell failure may progress to complete deficiency
Usually they are started on Insulin at this point and do not stop as they are at risk of ketoacidosis
How can genetics cause B cell failure *as a factor of T2?
IUGR or involving obesity/fatty acids which are both affected by genetics
Can cause insulin resistance adipocytokines
And these cause B cell failure
What happens to first phase insulin in T2?
is lost : plasma levels do not shoot up although they start slightly higher
How does T2 diabetes affect skeletal muscle uptake?
Less glucose uptake due to reduced insulin
How to T2DM affect hepatic glucose production?
Increased due to a reduction in insulin action and increase in glucagon action
What physiological processes contribute to a high fasting plasma glucose in T2DM?
- impaired glucose removal
- Increased hepatic production
- inability to oxidise and store in muscles due to bad insulin
= reduction in metabolic clearance rate of glucose
–> excess glucose turned into lactate which enters Cori cycle and turns back into glucose * this results in the increased fasting glucose e.g. from last nights meal
How can glucagon result in hepatic glucose production in T2DM?
excessive glucagon mediated glucose output cause gluconeogenesis
and this is supported by inadequate insulin which causes an influx of substances like glycerol and free fatty acids to live also increasing gluconeogensis
What does the graph of insulin sensitivity by insulin secretion look like and how does this differ for T2DM
Reciprocal graph
Those people have ‘fallen off the curve’ and for a given degree of insulin sensitivity they secrete less insulin
Which inflammatory adipokines are in excess?
TNF-a IL-6
Glucocorticoids
Visfatin
Adiponectin
Endocannabinoids
Leptin
Resistin
Apelin
Fatty acids
What does TNF-a IL-6 do in T2DM?
- -> lipolysis
- -> VLDL secretion
- -> insulin R
decreases adiponectin expression
What does adiponectin do in T2DM?
Decrease insulin resistance and is predictive of diabetes
What does Visfatin do in T2DM?
Visceral fat
Decreased insulin R in whole body
What does Glucocorticoids do in T2DM?
- -> 11B HSD-1 in fat
- -> fat cell size and IR
–> glucose BP lipids
What does ENdocannabinoids do in T2DM?
Insulin inhibits expression in fat
fat resistance > circulating EC ?
What does Leptin do in T2DM?
Elevated in obesity
resistance increases in body, muscle, liver
appetitie decreaser
metabolic rate increaser
What does resistin do in T2DM?
Elevated in obesity and T2DM
Insulin resistance in whole body and liver
Liver TG secretion increaser
What do fatty acids do in T2DM?
Elevated in obesity and T2DM --> IR Whole body muscle and liver decreases B cell function --> Liver TG secretion --> Organ fat, oxidative stress
What does Apelin do in T2DM?
Insulin stimulates expression in fat
elevated in hyperInsulin
Cardiovascular effects
What is SNPs?
single nucleotide polymorphisms
- each individual SNP has only a mild effect on risk
- cumulative effect of all SNPs have a bigger effect
What are the presentations of T2DM?
- Hyperglycaemia
- Overweight
- Dyslipidaemia
- Fewer osmotic symptoms
- With complications
- Insulin resistance
- later insulin deficieny
What is considered during the diagnosis of Type 2?
Osmotic symptoms
Infections
Screening test
At presentation of complication
All above can be reasons to look into diagnostic testing:
- 1 HbA1c with symptoms
- 2 HbA1c is asymptomatic
What type of complications may a potential diabetic present with?
Acute: Hyperosmolar hyperglycaemic state
Chronic : ischaemic heart disease, retinopathy
Which type of px present with hyperosmolar hyperglycaemia state?
Renal failure
insulin is insufficient to stop hyperglycaemia but enough to suppress lipolysis + ketoacidosis
often identifiable precipitating event e.g. infection, MI
What is checked during a T2DM consultation?
Glycaemia HbA1c, medication review
Weight assessment
Blood pressure
Dyslipidaemia- cholesterol profile
Screening for complications
Why is Metformin given?
- Reduces the excess hepatic glucose production
- lowers the glucose resistance of insulin so increases sensitivity
- GI side effects
What does Thiozolidinediones do?
- lowers the glucose resistance of insulin so increases sensitivity
What do Sulphonylureas,
DPP4-inhibitors.
GLP-1 Agonists do?
Boost insulin secretion
What does Alpha glucosidase inhibitor and SGLT-2 inhibitor do?
inhibit carb gut absorption and inhibit renal glucose resorption to reduce excess glucose in circulation
What is metformin contraindicated?
Severe liver, severe cardiac, moderate liver failure
What is the mechanism of action of sulphonylureas?
Bind to ATP sensitive potassium channel and close it, independent of glucose releasing insulin
What is Pioglitazone?
Peroxisome proliferator-activated receptor agonists
peripheral adipocyte differentiation modified = insulin sensitizer
glycaemia and lipid improvements
vascular outcomes
side effects of older types hep, heart failure
Which glucose lowering therapy causes most weight gain?
Thiozolidinediones
What is GLP-1?
glucagon like peptide
gut hormone secreted in response to nutrients
transcription product of pro glucagon gene, from L cell
increases satiety
short half life due to rapid degradation from enzyme dipeptidyl peptidase-4
used in DM treatmentq
What effects do GLP-1 agonists have?
decrease glucagon
decrease glucose
weight loss
- injectable
- e.g:
liraglutide, semaglutide
What is Gliptins?
DPPG-4 inhibitor (inhibits enzyme)
increases half life of exogenous GLP-1
Increases GLP-1
Decrease glucagon
decrease glucose
neutral on weight
What do SGLT-2 inhibitors do?
inhibits Na-Glu transporter, increases glycosuria
e.g.
Empagliflozin, Canagliflozin, Deapagliflozin
HbA1c lower
lowers all cause mortality and heart failure
improve CKD
What may allow remission of T2DM?
Gastric bypass surgery
very low cals - 800 daily for 3-6 months can induce remission
Why is lipid management important?
Total cholesterol raised
Triglycerides raised
HDL cholesterol reduced
Clear benefit to lipid-lowering therapy
