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
What does fasting glucose show?
≤ 6 mmol/L
Impaired fasting glycaemia
≥7 mmol/L
What does 2-hr glucose (OGTT)
< 7.7 mmol/L
Impaired glucose tolerance
≥11 mmol/L
What does HbA1c show
< 42 mmol/mol
Pre-diabetes or non-diabetic hyperglycaemia
≥ 48 mmol/mol
What does random glucose show?
> 11.1 with symptoms is diabetic
How is the beta cell function diagnosis of T2DM different from T1
The start of treatment is at a higher level of beta cell function
Why type of insulin deficiency is present in type 2 diabetes and why is this important
Insulin is produced by pancreatic beta-cells but not enough to overcome insulin resistance
There is therefore a relative deficiency of insulin
This is important to understand as it explains why the hyperglycaemia encountered does not cause ketosis under ‘usual’ circumstances
What are factors that affect insulin secretion and action
Body weight
Physical activity
Smoking
Heavy alcohol consumption
Genetic predisposition
Gene-environment interaction
Epigenetics
What does insulin resistance and beta cell dysfunction lead to
Increase in hepatic glucose production (also due to increase in glucagon action)
Decrease in glucose uptake in adipose tissue and skeletal muscle
What happens to the first phase inulin release in type 2 diabetes?
There is no sharp first phase insulin release
Describe the relationship between insulin resistance and insulin secretion
The more sensitive, the less is needed to be secreted
People developing type 2 diabetes have ‘fallen off the curve’
And for a given degree of insulin sensitivity secrete less insulin
Where are the consequences of insulin resistance seen
Liver
Adipocytes
Muscle
What happens in terms of inflammatory adipokines?
There is an excess
What is monogenic
Single gene mutation ==> Diabetes (MODY)
‘Born with it, always going to develop diabetes’
What is polygenic
Polymorphisms increasing risk of diabetes
‘Not born with it but high risk and may develop later depending on other factors
What is the role of obesity in type 2 diabetes
Major risk factor for T2DM
Fatty acids and adipocytokines important
Central vs visceral obesity
80% T2DM are obese
Weight reduction useful treatment
What else plays a role in type 2 diabetes
Perturbations in gut microbiota
Intra-uterine growth retardation
What are the presentations of T2DM
Hyperglycaemia
Overweight
Dyslipidaemia
Fewer osmotic symptoms
With complications
Insulin resistance
Later insulin deficiency
What are the risk factors for T2DM
Age
PCOS
Inc BMI
Family Hx
Ethnicity
Inactivity
How to diagnose type 2 diabetes
First line test for diagnosis is HbA1c. – more practical
1x HbA1c >=48mmol/L with symptoms
Or
2x HbA1c >=48 mmol/mol if aysymptomatic
Osmotic symptoms
Infections
Screening test: incidental finding
at presentation of complication
Acute; hyperosmolar hyperglycaemic state,
Chronic; ischaemic heart disease, retinopathy
What is 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).
Dehydration -
What is the management difference between type 1 and type 2 diabetes
Exogenous insulin (basal-bolus regime)
Self-monitoring of glucose
Structured education
Technology
Diet
Oral medication
Structured education
May need insulin later
Remission / reversal
What diabetes-related complications and their risk factors are we trying to prevent
Retinopathy
Neuropathy
Nephropathy
Cardiovascular
What are the principles of a diabetes 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 to do when there is excess hepatic glucose production
Reduce hepatic glucose production
Meformin
What to do when there is resistance to action of circulating insulin
Improve insulin sensitivity
Metformin
Thiozolidinediones
What to do when there is an inadequate insulin production for extent of insulin resistance
Boost insulin secretion
Sulphonylureas
DPP4-inhibitors
GLP-1 Agonists
What to do when there is excess glucose in circulation
Inhibit carbohydrate gut absorption
Inhibit renal glucose resorption
Alpha glucosidase inhibitor
SGLT-2 inhibitor
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
Sulphonylureas
Normal insulin release requires closer of the
ATP-sensitive potassium channel
Sulphonylureas eg gliclazide, bind to the ATP-sensitive potassium channel and close it, independent of glucose / ATP
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
Glucagon like (GLP-1) peptide-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
Incretin effect?
Orally ingested glucose elicits a much greater insulin response than that obtained when glucose is infused intravenously to give identical blood glucose levels
GLP-1 agonist
Liraglutide, Semaglutide
Injectable –daily, weekly
Decrease [glucagon]
Decrease [glucose]
Weight loss
Gliptins (DPPG-4 inhibitor)
Increase half life of exogenous GLP-1
Increase [GLP-1]
Decrease [glucagon]
Decrease [glucose]
Neutral on weight
SGLT-2 inhibitors
Inhibits Na-Glu transporter, increases glycosuria
Empagliflozin, dapagliflozin, canagliflozin
HbA1c lower
32% lower all cause mortality
35% lower risk heart failure
Improve CKD
Remission of T2DM?
Gastric bypass surgery has the potential to induce remission of type 2 diabetes
Very low-calorie diet (800 kcal/day) for 3-6 months has the potential to induce remission, which appears to be sustained at 2 years
What are the other aspects of management for T2DM?
Blood Pressure management
Hypertension very common in T2DM
Clear benefits for reduction esp with use of ACE-inhibitors
Lipid management
Total cholesterol raised
Triglycerides raised
HDL cholesterol reduced
Clear benefit to lipid-lowering therapy
