1b T2DM Flashcards
What is type 2 diabetes?
A condition in which the combination of insulin
resistance and beta-cell failure result in
hyperglycaemia
What is T2DM associated with?
Obesity
How is the resultant hyperglycaemia due to T2DM initially managed?
changes to diet / weight loss
Can you get diabetic ketoacidosis in T2DM?
Yes
What is LADA?
Autoimmune diabetes leading to insulin
deficiency can present later in life = latent
autoimmune diabetes in adults
Describe the age distribution of type 2 diabetes?
Traditionally thought to be only late adult hood condition
Now increasing evidence that is can occur earlier in life as well
In which ethnic groups is T2DM prevalence the highest?
*Greatest in ethnic groups
that move from rural to
urban lifestyle
Above what level of HbA1c levels indicative of Diabetes?
greater than or equal to 48 mmol/mol
Between what range of HbA1c levels indicates prediabetes?
42-48 mmol/mol
What are some features of prediabetes?
Impaired glucose tolerance
Impaired fasting glycaemia
What is needed to make a diagnosis of T2DM?
High random glucose with symptoms
Between what levels of fasting glucose would indicate impaired fasting glycaemia?
6-7
Between what levels of 2hour oral glucose would indicate impaired glucose tolerance?
7.8-11.1
What is meant by an insulin deficiency in T2DM?
Insulin is produced by pancreatic beta-cells but not enough to overcome insulin resistance, therefore RELATIVE INSULIN DEFICIENCY
What happens in long-duration diabetes?
beta cell failure may progress to complete insulin deficiency - therefore highly important to continue on insulin due to the risk of ketoacidosis
What is lost in patients with type 2 diabetes?
The first phase insulin release
Describe the graphs showing plasma insulin levels over time for patients with a normal glucose tolerance and patients with diabetes?
After the IV glucose challenge, for the patients with normal glucose tolerance, their plasma insulin levels rapidly shoot up - this represents the first phase insulin release
For patients with type 2 diabetes - there is only a curved, small increase in plasma insulin
What are the effects of T2DM on the skeletal muscle?
reduced insulin action causes less uptake of glucose into the skeletal muscle
What are the effects of T2DM on the hepatic glucose production?
hepatic glucose production increases due to a reduction in insulin action and increase in glucagon action
What happens to glucagon levels in T2DM and what is the effect?
Excessive glucagon mediated glucose output - causes an increase in the hepatic glucose production
What is the relationship between insulin resistance and insulin secretion?
Sigmoidal curve - high insulin sensitivity = low insulin secretion
What is the effect of T2DM on the insulin secretion/insulin sensitivity curve
They have “Fallen off the curve” - for a given degree of insulin sensativity, they secrete less insulin
Whole curve shifts inwards to the left
In a hyperglycaemic clamp, what is infused continuously to induce an insulin response?
Glucose - Hyperglycaemic clamp allows for quantification of beta cell sensitivity to glucose
Explain beta-cell function at diagnosis of T2DM.
At the time of diagnosis (t=0), the beta-cell function (%) has a diminished capacity to that prior to diagnosis.
- Insulin production is compromised.
- Homeostasis model can be used to calculate beta-cell function (Index).
Under usual circumstances, does hyperglycaemia associate with ketosis?
NO
What two factors contribute to increased fasting glucose in patients with T2DM?
Decreased glucose disposal and increased hepatic glucose output contributes to increased fasting plasma glucose (FPG) in diabetes mellitus.
In T2DM, what is the excessive amounts of glucose converted into?
Lactate
Insulin insufficiency reduces the rate of what?
Insulin insufficiency reduces the rate at which glucose-6-phosphate is converted into glycogen
What happens to glucose uptake by the adipocytes and monocytes in T2DM?
Reduced uptake by adipocytes and myocytes
What happens to serum triglycerides in Insulin resistance?
Elevation in serum triglycerides
What is monogenic?
When a single gene mutation causes Diabetes - MODY
What is polygenic diabetes?
Polymorphisms increasing the risk of developing diabetes - may develop it if high risk and other risk factors
Describe the role of GWAS in T2DM?
Take people with diabetes and people without
Note the nucleotide changes present in type 2 diabetes group but not the control group
assess the size of the effect seen
What is the effect of SNP’s on the risk of developing diabetes?
each SNP has a relatively small effect, but cumulatively they have a larger effect
what is the role of obesity in T2DM?
Large risk factor for diabetes, 80% of people with T2DM are obese - therefore weight reduction treatment is useful
What are important in T2DM that relate to Obesity?
fatty Acids And adipocytokines
What is the difference between central and visceral obesity?
Abnormally high deposition of visceral adipose tissueis known as visceral obesity whereas central obesity isan excess accumulation of fat in the abdominal area.
What is the presentation of a patient with T2DM?
- Hyperglycaemia
- Overweight
- Dyslipidaemia
- Fewer osmotic symptoms
- With complications
- Insulin resistance
- Later insulin deficiency
What are the risk factors for T2DM?
Age
Increased BMI
PCOS
Ethnicity
Inactivity
Family Hx
What is the first lline test for diagnosis of Diabetes?
HbA1c
What are the two sets requirements for diagnosis of T2DM?
- 1 x HbA1c >= 48 with SYMPTOMS
- 2 x HbA1c >= 48 without symptoms
What are the osmotic symptoms of diabetes?
Osmotic symptoms: Nocturia, polyuria & polydipsia.
What is a hyperosmolar hyperglycaemic state?
When there is insufficient insulin for the prevention of hyperglycaemia but sufficient insulin for the suppression of lipolysis and ketogenesis - therefore absense of significant acidosis
What do patients with hyperosmolar hyperglycaemia often present with?
Renal failure
What is the management of T2DM?
Diet
oral Medication
Education
may need insulin later
remission / reversal
What are the principles of a T2DM consultation?
Glycaemia: HbA1c, glucose monitoring if on insulin, medication review
Weight assessment
BP
Dyslipidaemia: cholesterol profile
Screening for complications: foot check, retinal screening
What are the dietary requirements / education which would be given to T2DM patients
Total calories control
Reduce calories as fat
Reduce calories as refined carbohydrate
Increase calories as complex carbohydrate
Increase soluble fibre
Decrease sodium
What is the strategy and drug used to solve the problem of excess hepatic glucose production?
Reduce hepatic glucose production - using Metformin
What is the strategy and drug used to solve the problem of resistance to action of circulating insulin ?
Improve insulin sensativity - metformin
Thioozolidinediones
What is the strategy and drug used to solve the problem of Inadequate insulin production for extent of insulin resistance?
Boost insulin secretion -
1. Sulphonylureas
DPP4-Inhibitors
GLP-1 Agonists
What is the strategy and drug used to solve the problem of excess glucose in circulation?
Inhibit Carb gut absorption
Inhibit renal glucose absorption
Alpha Glucosidase Inhibitor
SGLT-2 Inhibitor
In what instance is metformin the first line treatment for T2DM?
If dietary / lifestyle adjustments has made no difference
How does metformin reduce insulin resistance?
- Reduced Hepatic glucose output
- Increases peripheral glucose disposal
In which contexts is Metformin contraindicated>
Severe liver disease
Severe cardiac Disease
moderate Renal Failure
What does normal insulin release require?
The closure of the ATP sensitive potassium channel
How do Sulphonylureas work?
Bind to the ATP-sensitive potassium channel and close it, so more insulin can be released
What is the rate limiting step in the secretion of insulin?
When glucose enters into the cell, glucokinase converts it into glucose-6-phosphate
What is Pioglitazone?
Peroxisome proliferator-activated receptor agonists PPAR-y
Insulin sensitiser (peripheral).
How does pioglitazone help in the management of T2DM?
Adipocyte differentiation modified
Weight gain but peripheral not central
Improvement in glycaemia and lipids (evidence based on vascular outcomes)
-
What is GLP-1?
A gut hormones which is secretes in response to nutrients in the gut
What is the effect of GLP-1?
stimulates insulin and suppresses glucagon - also increases the feeling of satiety
Why does GLP-1 have a short half life?
due to rapid degeneration from enzyme DPP-4
What are the names of the two GLP-1 Agonists?
Liraglutide and Semaglutide
What do GLP-1 agonists do?
decrease glucagon and decrease glucose, causes weight loss
What is the name of the a DPP-4 inhibitor?
Gliptins
What are the effects of Gliptins?
Increase half life of exogenous GLP-1
Increase GLP-1
Decrease glucagon
Decrease glucose
Neutral on Weight
What do sulphonylureas do?
Inhibit Na+-Glu transporter which increases glycosuria
Lowers HbA1c
Improves CKD
What happens to beta-cell function despite continued insulin treatment
Continues to decline
What helps to induce remission of T2DM?
Gastric bypass surgery
very low calorie diet
How is blood pressure managed?
ACE Inhibitor
What lipids are raised during diabetes?
total cholesterol raised
triglycerides raised
HDL cholesterol reduced
When does DKA occur in T2DM patients?
When lipolysis is not suppressed enough due to illness associated with t2DM
What are some factors which affect insulin secretion and action?
Body weight
physical activity
smoking
genetic predisposition
gene environment
epignetics
What are the two probems of T2DM?
beta cell dysfunction and insulin resistance
Which fat is pro-inflammatory?
Visceral fat - generates adipocytokines
What is a hyperglycaemic clamp?
research - assess how insulin resistant someone is in a research facility, not clinical
