Type 2 diabetes Flashcards
What is type 2 diabetes?
A condition in which the combination of insulin resistance and beta-cell failure result in hyperglycaemia
Associated with obesity but not always
The resultant chronic hyperglycaemia may initially be managed by changes to diet / weight loss and may even be reversible
With time glucose lowering therapy including insulin, is needed
At what age can you get type 2 diabetes?
Traditionally thought to be a condition of late adulthood
Now good evidence that it can present throughout every decade of life
Increasing in all age groups but rapidly in early-adulthood
What are the fasting glucose levels at different stages of diabetes?
Normal - ≤ 6 mmol/L
Intermediate - impaired fasting glyaemia
Type 2 Diabetes - ≥7 mmol/L
What are the 2 hour glucose results at different stages of type 2 diabetes?
Normal - <7.7 mmol/L
Intermediate - Impaired glucose tolerance
Type 2 Diabetes -≥ 11 mmol/L
What are the HbA1c results at different stages of type 2 diabetes?
Normal - < 42 mmol/L
Intermediate - pre-diabetes or non diabetic hyperglycaemia
Type 2 Diabetes -≥ 48 mmol/L
At what stage is insulin production the highest?
Intermediate stage of diabetes
Why does hyperglycaemia in type 2 diabetes not normally cause ketosis?
Ketones are produced when there is no insulin, Insulin is produced by pancreatic beta-cells in T2D but not enough to overcome insulin resistance
There is therefore a relative deficiency of insulin
Why do people with T2D end up needing insulin in the long term?
In long-duration type 2 diabetes, beta-cell failure may progress to complete insulin deficiency
, but important not to stop as at risk of ketoacidosis
What causes insulin resistance in T2D?
perfect storm of internal adiposity, pro-inflammatory state and production of adipose cytokines. This cocktail makes the tissues resistant to the action of insulin.
What is lost in T2D in terms of insulin response?
First phase insulin release is lost
What are the problems with reduced insulin action?
In type 2 diabetes, reduced insulin action causes less uptake of glucose into skeletal muscle
Hepatic glucose production is also increased due to both a reduction in insulin action and increase in glucagon action. More glucose coming from the liver.
Is type T2D monogenic or polygenic?
Polygenic
What have GWAS shown in regards to T2D?
Individual SNP’s only have a mild effect on chance of developing T2D, but cumulative effects of all SNP’s have a bigger effect.
What is the role of obesity in T2D?
Major risk factor for T2DM Fatty acids and adipocytokines important Central vs visceral obesity 80% T2DM are obese Weight reduction useful treatment
What are other associations with T2D?
Perturbations in gut microbiota
Obesity, insulin resistance T2DM
Bacterial lipopolysaccharides fermentation to short chain FA, bacterial modulation bile acids
Inflammation, signaling metabolic pathways
Most studies correlative
Intra-uterine growth retardation
Hales et al 1991
Weight at age 1 year <8.16kg, 22% had type 2 diabetes of IGT
Weight age 1 year >12.25 kg, 6% had type 2 diabetes or IGT
What is the presentation of type 2 diabetes?
Hyperglycaemia Overweight Dyslipidaemia Fewer osmotic symptoms With complications Insulin resistance Later insulin deficienc
What are the main risk factors for T2D?
Age PCOS BMI Family Hx Ethnicity Inactivity
What is the first line test for diagnosis?
HbA1c
1 x HbA1c> 48 mmol/L & symptoms
OR
2x HbA1c> 48 mmol/L & no symptoms
What happens in a Hyperosmolar hyperglycaemic state?
Presents commonly with renal failure.
Insufficient insulin (NOT ABSENT) for prevention of hyperglycemia but sufficient insulin for suppression of lipolysis and ketogenesis.
Absence of significant acidosis.
Often identifiable precipitating event (infection, MI).
What are acute and chronic T2D presentation?
Acute; hyperosmolar hyperglycaemic state,
Chronic; ischaemic heart disease, retinopathy
What is the management for T2D?
Diet Oral medication Structured education May need insulin later Remission / reversal
What are the principles for a T2D consultation?
Glycaemia: HbA1c, glucose monitoring if on insulin, medication review
Weight assessment
Blood pressure
Dyslipidaemia: cholesterol profile
Screening for complications: foot check, retinal screening
What are the dietary recommendations for T2D?
Total calories control Reduce calories as fat Reduce calories as refined carbohydrate Increase calories as complex carbohydrate Increase soluble fibre Decrease sodium
Which drug reduces excess hepatic glucose production?
Metformin
weight loss
Which drugs improve insulin sensitivity?
Metformin
Thiozolidinediones
weight loss
Which drugs Boost insulin secretion?
Sulphonylureas
DPP4-inhibitors
GLP-1 Agonists
weight loss
Which drugs inhibit carbohydrate gut absorption & renal glucose resorption?
Alpha glucosidase inhibitor
SGLT-2 inhibitor
weight loss
Describe the use of Metformin:
Biguanide, insulin sensitiser
First line if dietary / lifestyle adjustment has made no difference
Reduces insulin resistance
Reduced hepatic glucose output
Increases peripheral glucose disposal
GI side effects
Contraindicated in severe liver, severe cardiac or moderate renal failure
Describe the mechanism of action of Sulphonylureas?
boost insulin production, When ATP-sensitive potassium channel closes you get insulin production. Sulphonylureas bind to this channel independent of glucose and close it.
Describe the use of Pioglitazone:
Peroxisome proliferator-actived receptor agonists PPAR-γ
Pioglitazone
Insulin sensitizer, mainly peripheral
Adipocyte differentiation modified, weight gain but peripheral not central
Improvement in glycaemia and lipids
Evidence base on vascular outcomes
Side effects of older types hepatitis, heart failure
What is the major side effect seen with some of the older T2D drugs?
Cause a slight increase in weight
Describe the use of GLP-1:
Gut hormone
Secreted in response to nutrients in gut
Transcription product of pro-glucagon gene, mostly from L-cell
Stimulates insulin, suppresses glucagon
↑ satiety (feeling of ‘fullness’)
Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPP4 inhibitor)
Used in treatment of diabetes mellitus
How are GLP-1 drugs prescribed in T2D?
Liraglutide, Semaglutide Injectable –daily, weekly Decrease [glucagon] Decrease [glucose] Weight loss
How are DPP4-inhibitors used in T2D?
Gliptins Increase half life of exogenous GLP-1 Increase [GLP-1] Decrease [glucagon] Decrease [glucose] Neutral on weight
How are SGLT-2 inhibitors used?
Inhibits Na-Glu transporter, increases glycosuria
Empagliflozin, dapagliflozin, canagliflozin
HbA1c lower
32% lower all cause mortality
35% lower risk heart failure
Improve CKD
What has the potential to induce remission of T2D
weight loss
Gastric bypass surgery
