Type 2 Diabetes Mellitus Flashcards
What is type 2 diabetes?
- condition with the combination of insulin resistance and beta cell failure in hyperglycaemia
How does the WHO classify T2DM?
- genetic risk + obesity
- insulin resistance
- relative insulin deficiency
- hyperglycaemia
What is latent autoimmune diabetes in adults(LADA)?
- autoimmune diabetes leading to insulin deficiency present later in life
How can monogenic diabetes present phenotypically?
- T1DM
- T2DM
When can T2DM present?
Can present in all decade of life
When is the prevalence of T2DM greatest?
ethnic groups that move from rural > urban lifestyle
What fasting glucose levels indicate T2DM?
> =7mmol/L
What 2hr glucose tolerance test results indicate T2DM?
> =11mmol/L
What random glucose levels indicate T2DM?
> =11.1mmol/L
What can be used to diagnose T2DM?
- random glucose (high)
- symptoms of diabetes
Why does T2DM not cause ketosis under normal circumstances?
due to T2DM being a relative insulin deficiency
What happens in long-duration T2 diabetes?
- beta-cell failure may progress to complete insulin deficiency
- usually on insulin, DO NOT STOP (ketoacidosis)
What is the biggest contributory factor to the development of type 2 diabetes?
both
- beta cell failure
- insulin resistance
What is a normal fasting glucose levels?
<=6mmol/L
What does it mean if fasting glucose levels are between 6-7mmol/L?
Impaired fasting glycaemia
What 2hr glucose tolerance test results are normal?
<7.7mmol/L
What HbA1c levels indicate type 2 diabetes?
> =48mmol/mol
What HbA1c levels are normal?
<42mmol/mol
What does 2hr glucose tolerance test result between 7.7-11 mmol/L are normal?
Impaired glucose tolerance
What does HbA1c levels between 42-48mmol/mol mean?
pre-diabetes or non-diabetic hypergylcaemia
What happens to insulin during T2 diabetes?
- max insulin resistance
- reduced insulin production
What happens to insulin during the intermediate stage of developing T2 diabetes
- increasing resistance
- maximum insulin production
What is a rapid way to diagnose T2 diabetes?
random glucose (>11.1), and symptoms
What happens to beta cell mass when developing T2DM?
already reduced at time of diagnosis
What does a relative insulin deficiency mean?
insulin is produced by pancreatic beta-cells but not enough to overcome insulin resistance
When does ketosis typically form?
when there is no insulin
What makes the tissues resistance to the action of insulin?
a mix of:
- adipose cytokines (adipokines)
- internal adiposity (fatty acids)
- pro-inflammatory state
Why is diabetes heterogenouses?
variable:
- BMI
- ages
- progression
What is one of the first signs of developing T2DM?
the loss of the first phase insulin release
What is the impact of the loss of first phase insulin release?
- less uptake of glucose into skeletal muscle
- hepatic glucose production is increased due to a reduction in insulin action and an increase in glucagon action.
What is the impact of high glucose?
- impaired insulin-mediated glucose disposal
- excessive glucagon-mediated glucose disposal
What is the relationship between insulin secretion and insulin sensitivity in T2DM?
Low insulin sensitivity, low insulin secretion
What are the consequences of insulin resistance?
- increased hepatic glucose production
- adipocytes, increased fatty acid uptake, and triglycerides form unhealthy lipids (usually inhibited insulin)
- less glucose muscle uptake
What does monogenic mean?
single gene mutation (eg; MODY)
inevitable development
What does polygenic mean?
polymorphisms increasing the risk of diabetes
factor dependent
What types of mutations cause T2DM?
polygenic
What causes T2DM?
- genetic risk
- strong environmental factor(precipitant)
What is the role of obesity in T2DM?
- major risk factor
- 80% of T2DM are obese
What is central obesity?
excess fat in the abdominal area
What are other factors implicating developing T2DM?
- pertubations in microbiota
- intra-uterine growth retardation (little when born)
How does T2DM present?
- hyperglycaemia
- overweight
- dyslipidaemia
- fewer osmotic symptoms (blurred vision, polyuria…)
- complications (eg retinopathy)
- insulin resistance
- later insulin deficiency
What are the risk factors of T2DM?
- age
- high BMI
- ethnicity
- PCOS
- family history
- sedentary
What is the first line test for diagnosis?
HbA1c
1 x HbA1c >=48mmol with symptoms
or
2 x HbA1c >=48mmol asymptomatic
What is an acute metabolic decompensation?
life threatening state due to hyperglycaemia
in T2DM hyperosmolar hyperglycaemic state
What is an acute metabolic decompensation?
life threatening state due to hyperglycaemia
in T2DM hyperosmolar hyperglycaemic state
What is hyperosmolar hyperglycaemic state?
unchecked gluconeogenesism and osmotic diuresis
How does hyperosmolar hyperglycaemic state present?
common with renal failure
unlikely to present with acidosis
Why does a hyperosmolar hyperglycaemic state occur?
insufficient insulin for prevention of hyperglycaemia but sufficient insulin for suppression of lipolysis and ketogenesis
How do you manage T2DM?
- diet + physical activity
- oral medication
- education
- insulin later
- remission/reversal
What are the complications associated with T2DM?
- retinopathy
- neuropathy
- nephropathy
- cardiovascular problems
How do you prevent the complications associated with T2DM?
- good cholesterol
- good HbA1c
- good blood pressure
What is involved in a T2DM consultation?
- glucose levels
- weight assessment
- blood pressure
- cholesterol profile
- complications screening
How do you check on glucose levels for a consultation?
- HbA1c
- if on insulin, glucose monitor
How do you screen for the complications associated with T2DM?
- foot check
- retinal screening
- urine test
What are the dietry recommendations for T2DM?
- calorie control reduce: - fat - refined carbohydrates - sodium increase - complex carbohydrates - soluble fibre
What treats all 4 aspects for T2DM pathophysiology?
weight loss
What can be used to treat the excess hepatic glucose production in T2DM?
metformin
What can be used to increase insulin sensitivity in T2DM?
- metformin
- thiozolidinediones
What can be used to boost insulin secretion?
- sulphonylureas
- DPP4 inhibitors
- GLP-1 agonists
What can be used to inhibit carbohydrate gut abosrption and renal glucose absorption to reduce the excess glucose in circulation?
- alpha glucosidase inhibitor
- SGLT-2 inhibitor
What is Metformin?
Biguanide
insulin sensitiser
When is metformin used?
first line (if dietry/lifestyles changes have made no difference)
What does metformin do?
- reduced hepatic glucose output
- increases peripheral glucose disposal
What are the side effects of metformin?
GI side effects
When is metformin contraindicated?
- severe liver failure
- servere cardiac failure
- moderate renal failure
How do sulphonylureas increase insulin release?
bind to the ATP sensitive potassium channel causing it to close and causing it to produce insulin (independent of glucose/ATP)
What is Pioglitazone?
insulin sensitiser (through peripheral tissues) Peroxisome proliferator-activated receptor agonists.
How does Pioglitazone work?
modifies adipocyte differentiation, causing production of peripheral fat not central when weight is gained.
What are the side effects of Piogiltazone>
- hepatitis
- heart failure
What is GLP-1?
a hut hormone that is secreted in response to
nutrients
transcription production from L cells
What does GLP-1 do?
- simulates insulin, suppreses glucagon
- increased satiety
What do GLP-1 agonists do?
(Liraglutide, Semaglutide)
decrease glucagon, decrease glucose
weight loss
What do SGLT-2 inhibitors do?
inhibits the Na-Glu transporter, increases glycosuria
- lowers HbA1c
What is the effect of treatment on beta cell failure?
nothing
