1b T2DM

Question 1

What is type 2 diabetes?

Answer 1

A condition in which the combination of insulin
resistance and beta-cell failure result in
hyperglycaemia

Question 2

What is T2DM associated with?

Answer 2

Obesity

Question 3

How is the resultant hyperglycaemia due to T2DM initially managed?

Answer 3

changes to diet / weight loss

Question 4

Can you get diabetic ketoacidosis in T2DM?

Answer 4

Yes

Question 5

What is LADA?

Answer 5

Autoimmune diabetes leading to insulin
deficiency can present later in life = latent
autoimmune diabetes in adults

Question 6

Describe the age distribution of type 2 diabetes?

Answer 6

Traditionally thought to be only late adult hood condition

Now increasing evidence that is can occur earlier in life as well

Question 7

In which ethnic groups is T2DM prevalence the highest?

Answer 7

*Greatest in ethnic groups
that move from rural to
urban lifestyle

Question 8

Above what level of HbA1c levels indicative of Diabetes?

Answer 8

greater than or equal to 48 mmol/mol

Question 9

Between what range of HbA1c levels indicates prediabetes?

Answer 9

42-48 mmol/mol

Question 10

What are some features of prediabetes?

Answer 10

Impaired glucose tolerance
Impaired fasting glycaemia

Question 11

What is needed to make a diagnosis of T2DM?

Answer 11

High random glucose with symptoms

Question 12

Between what levels of fasting glucose would indicate impaired fasting glycaemia?

Answer 12

6-7

Question 13

Between what levels of 2hour oral glucose would indicate impaired glucose tolerance?

Answer 13

7.8-11.1

Question 14

What is meant by an insulin deficiency in T2DM?

Answer 14

Insulin is produced by pancreatic beta-cells but not enough to overcome insulin resistance, therefore RELATIVE INSULIN DEFICIENCY

Question 15

What happens in long-duration diabetes?

Answer 15

beta cell failure may progress to complete insulin deficiency - therefore highly important to continue on insulin due to the risk of ketoacidosis

Question 16

What is lost in patients with type 2 diabetes?

Answer 16

The first phase insulin release

Question 17

Describe the graphs showing plasma insulin levels over time for patients with a normal glucose tolerance and patients with diabetes?

Answer 17

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

Question 18

What are the effects of T2DM on the skeletal muscle?

Answer 18

reduced insulin action causes less uptake of glucose into the skeletal muscle

Question 19

What are the effects of T2DM on the hepatic glucose production?

Answer 19

hepatic glucose production increases due to a reduction in insulin action and increase in glucagon action

Question 20

What happens to glucagon levels in T2DM and what is the effect?

Answer 20

Excessive glucagon mediated glucose output - causes an increase in the hepatic glucose production

Question 21

What is the relationship between insulin resistance and insulin secretion?

Answer 21

Sigmoidal curve - high insulin sensitivity = low insulin secretion

Question 22

What is the effect of T2DM on the insulin secretion/insulin sensitivity curve

Answer 22

They have “Fallen off the curve” - for a given degree of insulin sensativity, they secrete less insulin

Whole curve shifts inwards to the left

Question 23

In a hyperglycaemic clamp, what is infused continuously to induce an insulin response?

Answer 23

Glucose - Hyperglycaemic clamp allows for quantification of beta cell sensitivity to glucose

Question 24

Explain beta-cell function at diagnosis of T2DM.

Answer 24

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).

Question 25

Under usual circumstances, does hyperglycaemia associate with ketosis?

Answer 25

NO

Question 26

What two factors contribute to increased fasting glucose in patients with T2DM?

Answer 26

Decreased glucose disposal and increased hepatic glucose output contributes to increased fasting plasma glucose (FPG) in diabetes mellitus.

Question 27

In T2DM, what is the excessive amounts of glucose converted into?

Answer 27

Lactate

Question 28

Insulin insufficiency reduces the rate of what?

Answer 28

Insulin insufficiency reduces the rate at which glucose-6-phosphate is converted into glycogen

Question 29

What happens to glucose uptake by the adipocytes and monocytes in T2DM?

Answer 29

Reduced uptake by adipocytes and myocytes

Question 30

What happens to serum triglycerides in Insulin resistance?

Answer 30

Elevation in serum triglycerides

Question 31

What is monogenic?

Answer 31

When a single gene mutation causes Diabetes - MODY

Question 32

What is polygenic diabetes?

Answer 32

Polymorphisms increasing the risk of developing diabetes - may develop it if high risk and other risk factors

Question 33

Describe the role of GWAS in T2DM?

Answer 33

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

Question 34

What is the effect of SNP's on the risk of developing diabetes?

Answer 34

each SNP has a relatively small effect, but cumulatively they have a larger effect

Question 35

what is the role of obesity in T2DM?

Answer 35

Large risk factor for diabetes, 80% of people with T2DM are obese - therefore weight reduction treatment is useful

Question 36

What are important in T2DM that relate to Obesity?

Answer 36

fatty Acids And adipocytokines

Question 37

What is the difference between central and visceral obesity?

Answer 37

Abnormally high deposition of visceral adipose tissue is known as visceral obesity whereas central obesity is an excess accumulation of fat in the abdominal area.

Question 38

What is the presentation of a patient with T2DM?

Answer 38

* Hyperglycaemia * Overweight * Dyslipidaemia * Fewer osmotic symptoms * With complications * Insulin resistance * Later insulin deficiency

Question 39

What are the risk factors for T2DM?

Answer 39

Age Increased BMI PCOS Ethnicity Inactivity Family Hx

Question 40

What is the first lline test for diagnosis of Diabetes?

Answer 40

HbA1c

Question 41

What are the two sets requirements for diagnosis of T2DM?

Answer 41

1. 1 x HbA1c >= 48 with SYMPTOMS 2. 2 x HbA1c >= 48 without symptoms

Question 42

What are the osmotic symptoms of diabetes?

Answer 42

Osmotic symptoms: Nocturia, polyuria & polydipsia.

Question 43

What is a hyperosmolar hyperglycaemic state?

Answer 43

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

Question 44

What do patients with hyperosmolar hyperglycaemia often present with?

Answer 44

Renal failure

Question 45

What is the management of T2DM?

Answer 45

Diet oral Medication Education may need insulin later remission / reversal

Question 46

What are the principles of a T2DM consultation?

Answer 46

Glycaemia: HbA1c, glucose monitoring if on insulin, medication review Weight assessment BP Dyslipidaemia: cholesterol profile Screening for complications: foot check, retinal screening

Question 47

What are the dietary requirements / education which would be given to T2DM patients

Answer 47

Total calories control Reduce calories as **fat** Reduce calories as **refined carbohydrate** Increase calories as **complex carbohydrate** Increase **soluble fibre** **Decrease sodium**

Question 48

What is the strategy and drug used to solve the problem of excess hepatic glucose production?

Answer 48

Reduce hepatic glucose production - using Metformin

Question 49

What is the strategy and drug used to solve the problem of resistance to action of circulating insulin ?

Answer 49

Improve insulin sensativity - metformin Thioozolidinediones

Question 50

What is the strategy and drug used to solve the problem of Inadequate insulin production for extent of insulin resistance?

Answer 50

Boost insulin secretion - 1. Sulphonylureas DPP4-Inhibitors GLP-1 Agonists

Question 51

What is the strategy and drug used to solve the problem of excess glucose in circulation?

Answer 51

Inhibit Carb gut absorption Inhibit renal glucose absorption Alpha Glucosidase Inhibitor SGLT-2 Inhibitor

Question 52

In what instance is metformin the first line treatment for T2DM?

Answer 52

If dietary / lifestyle adjustments has made no difference

Question 53

How does metformin reduce insulin resistance?

Answer 53

1. Reduced Hepatic glucose output 2. Increases peripheral glucose disposal

Question 54

In which contexts is Metformin contraindicated>

Answer 54

Severe liver disease Severe cardiac Disease moderate Renal Failure

Question 55

What does normal insulin release require?

Answer 55

The closure of the ATP sensitive potassium channel

Question 56

How do Sulphonylureas work?

Answer 56

Bind to the ATP-sensitive potassium channel and close it, so more insulin can be released

Question 57

What is the rate limiting step in the secretion of insulin?

Answer 57

When glucose enters into the cell, glucokinase converts it into glucose-6-phosphate

Question 58

What is Pioglitazone?

Answer 58

Peroxisome proliferator-activated receptor agonists PPAR-y Insulin sensitiser (peripheral).

Question 59

How does pioglitazone help in the management of T2DM?

Answer 59

Adipocyte differentiation modified **Weight gain but peripheral not central** Improvement in glycaemia and lipids (evidence based on vascular outcomes) -

Question 60

What is GLP-1?

Answer 60

A gut hormones which is secretes in response to nutrients in the gut

Question 61

What is the effect of GLP-1?

Answer 61

stimulates insulin and suppresses glucagon - also increases the feeling of satiety

Question 62

Why does GLP-1 have a short half life?

Answer 62

due to rapid degeneration from enzyme DPP-4

Question 63

What are the names of the two GLP-1 Agonists?

Answer 63

Liraglutide and Semaglutide

Question 64

What do GLP-1 agonists do?

Answer 64

decrease glucagon and decrease glucose, causes weight loss

Question 65

What is the name of the a DPP-4 inhibitor?

Answer 65

Gliptins

Question 66

What are the effects of Gliptins?

Answer 66

Increase half life of exogenous GLP-1 Increase GLP-1 Decrease glucagon Decrease glucose Neutral on Weight

Question 67

What do sulphonylureas do?

Answer 67

Inhibit Na+-Glu transporter which increases glycosuria Lowers HbA1c Improves CKD

Question 68

What happens to beta-cell function despite continued insulin treatment

Answer 68

Continues to decline

Question 69

What helps to induce remission of T2DM?

Answer 69

Gastric bypass surgery very low calorie diet

Question 70

How is blood pressure managed?

Answer 70

ACE Inhibitor

Question 71

What lipids are raised during diabetes?

Answer 71

total cholesterol raised triglycerides raised HDL cholesterol reduced

Question 72

When does DKA occur in T2DM patients?

Answer 72

When lipolysis is not suppressed enough due to illness associated with t2DM

Question 73

What are some factors which affect insulin secretion and action?

Answer 73

Body weight physical activity smoking genetic predisposition gene environment epignetics

Question 74

What are the two probems of T2DM?

Answer 74

beta cell dysfunction and insulin resistance

Question 75

Which fat is pro-inflammatory?

Answer 75

Visceral fat - generates adipocytokines

Question 76

What is a hyperglycaemic clamp?

Answer 76

research - assess how insulin resistant someone is in a research facility, not clinical