Glycaemic control in long-established diabetes

Question 1

What are the major modifiable risk factors for macrovascular disease?

Answer 1

Diabetes
Hypertension
Smoking
Dyslipidaemia
Lack of exercise

Question 2

What is the mechanism of action of the Sulfonylureas?

Answer 2

Increase pancreatic insulin secretion.

Question 3

In which patients would the Sulfonylureas be used as a first-line treatment?

Answer 3

Patients with type 2 diabetes in whom hypoinsulinaemia (rather than insulin resistance) is the predominant cause of hyperglycaemia

Question 4

What are four examples of sulfonylureas?

Answer 4

Glibenclamide
Gliclazide
Glipizide
Glimepiride

Question 5

How are sulfonylureas used in most T2DM patients?

Answer 5

as second-line treatment, after metformin

Question 6

What is the mechanism of action of Thiazolidinediones?

Answer 6

Increase peripheral insulin sensitivity.

Decreases hepatic glucose output.

( Agonist of peroxisome proliferator-activated receptor gamma, which regulates genes involved in lipid and glucose metabolism)

Question 7

How are Thiazolidinediones used in glycaemic control?

Answer 7

Reserve for patients unable to take other antidiabetics

Question 8

Name 2 Thiazolidinediones

Answer 8

Rosiglitazone

Pioglitazone

Question 9

What is the mechanism of action of acarbose?

Answer 9

Reduces carbohydrate absorption in gut. Prevents the breakdown of polysaccharides to monosaccharides. (e.g. sucrose to glucose)

Question 10

To which group of drugs does metformin belong?

Answer 10

Biguanides

Question 11

What is the mechanism of action of metformin?

Answer 11

The glucose-lowering, insulin-sensitizing agent metformin works mainly by reducing gluconeogenesis and opposing glucagon-mediated signalling in the liver and, to a lesser extent, by increasing glucose uptake in skeletal muscle

The primary site of metformin action is the mitochondrion

The antihyperglycaemic effect of metformin is probably owing to defective protein kinase A signalling

Metformin affects lipid metabolism primarily via 5′-AMP-activated protein kinase (AMPK) activation

Question 12

What tests are performed to monitor the microvascular complications of diabetes?

Answer 12

neuropathy: clinical examination
nephropathy: urine albumin creatinine ratio
retinopathy: ophthalmological retinal screening

Question 13

What are the microvascular complications of diabetes?

Answer 13

Neuropathy
Nephropathy
Retinopathy

Question 14

What is a possible complication of using sulfonylureas?

Answer 14

Hypoglycaemia

Question 15

What is the first line treatment for T2DM?

Answer 15

Metformin

Question 16

What is the major side effect of Metformin?

Answer 16

Gastrointestinal upset (1/3 of patients)

Question 17

What is the daily dose of Metformin?

Answer 17

250-1000mg daily

Question 18

How is metformin cleared from the body?

Answer 18

Renally (100%)

Question 19

What is the mechanism of action of GLP-1 Analogues?

Answer 19

Analogues of glucagon-like peptide‑1 (an incretin);

• increase glucose-dependent insulin secretion
• suppress inappropriate glucagon secretion.
• delay gastric emptying, which slows glucose absorption,
• decrease appetite.

Question 20

What is an example of a GLP-1 Analogue?

Answer 20

Semaglutide
Exenatide
Dulaglutide
Liraglutide

Question 21

What is the mode of administration of exenatide?

Answer 21

Subcutaneous

Question 22

What is the dosing regimen for exenatide?

Answer 22

Initially 5mg SC BD

If tolerated, 10mg SC BD

Question 23

What is the mechanism of action of DPP-IV inhibitors?

Answer 23

Stimulate insulin secretion and suppress glucagon release by increasing concentrations of GLP-I and related peptides by blocking their metabolism.

Question 24

How are DPP-IV inhibitors used to treat T2DM?

Answer 24

In combination with metformin or a sulfonylurea

Question 25

What is the name of a DPP-IV inhibitor?

Answer 25

``` Sitagliptin Linagliptin Saxagliptin Alogliptin Vildagliptin ```

Question 26

How is sitagliptin cleared from the body?

Answer 26

Renally (100%)

Question 27

In which patients are Thiazolidinediones contraindicated?

Answer 27

In patients with heart failure.

Question 28

How often should one monitor HBA1c levels?

Answer 28

HbA1c most accurately reflects the patient's glycaemic control for the previous eight to 12 weeks. Testing every 3 months is sufficient.

Question 29

How can patients mitigate the gastrointestinal side-effects of metformin?

Answer 29

Taking with meals, gradual dose titration or using the extended release preparation.

Question 30

What is one rare but significant risk of metformin usage? And what feature of a patient would make this outcome more likely?

Answer 30

Lactic acidosis. Renal impairment.

Question 31

What proportion of patients will not respond to thiazolidinediones?

Answer 31

up to 1/3

Question 32

What are the common adverse effects of sulfonylureas?

Answer 32

Weight gain and hypoglycaemia

Question 33

What are the benefits of initiating insulin therapy early?

Answer 33

Potentially improves or preserves beta-cell function Prevents loss of glycaemic control Reduces the risk of microvascular complications.