Type 2 diabetes

Question 1

two mechanisms for T2 diabetes

Answer 1

Relative insulin deficiency

Insulin resistance

Question 2

pre diabetes for >10 years without diagnosis

Answer 2

may lead to 50% reduction in pancreatic beta-cell function and this may continue to decline even after treatment initiation which often leads the need for insulin therapy

Question 3

over weight patients

Answer 3

free fatty acids leading to insulin resistance in the muscles and the liver

Question 4

what is insulin resistance also associated with

Answer 4

atherosclerosis

Question 5

MODY

Answer 5

maturity onset diabetes of the young

several subsets with different genetic defects

Question 6

HbA1C is not suitable in some T2DM patients including..

Answer 6

• all children and young people
• patients with symptoms for < 2 months
• patients who are acutely unwell
• patients who are on medicines which are known to raise glucose for example antipyscotics and steroids
• patients with pancreatic damage

Question 7

Patients treated with one agent which is not known to cause hypoglycaemia should aim for HbA1c to be….

Answer 7

<48mmol

Question 8

Patients taking two or more agents or one agent that is known to cause hypoglycaemia should aim for HbA1c to be

Answer 8

<53mmol

Question 9

Patients who are symptomatically hyperglycaemic should be offered

Answer 9

sulphonylurea

insulin until blood glucose control is achieved.

Question 10

Treatments for T2DM if metformin is tolerated

Answer 10

1) Lifestyle factors
2) Metformin
3) Metformin MR

If HbA1c >58mmol

4) - DPP-4 inhibitor (gliptin)
- sulphonylurea
- pioglitazone
- SGLT-2 inhibitor (flozins)

HbA1C >58 mmol

Consider triple therapy of metformin with one of the following:
sulphonylurea + DPP-4 inhibitor
sulphonylurea + pioglitazone
sulphonylurea + SGLT-2 inhibitor (flozin)
pioglitazole + SGLT-2 inhibitor

Question 11

Treatment for T2DM is metformin is not tolerated….

Answer 11

1) - DPP-4 inhibitor (gliptin)
- sulphonylurea
- pioglitazone
- SGLT-2 inhibitor (florins)

if HbA1c >58mmol then….

• DPP-4 inhibitor (gliptin) + pioglitazole
• DPP-4 inhibitor + sulphonylurea
• pioglitazole + sulphonylura

if HbA1c > 58mmol then consider insulin therapy

Question 12

How does metformin work?

Answer 12

• inhibits gluconeogenesis and glyconolysis
• improve peripheral glucose uptake and utilisation in muscle
• delay gastro intestinal uptake of glucose

Question 13

metformin

Answer 13

• dose not cause hypo’s
• does not cause weight gain (actually weight loss)
• reduction on cardiovascular risk

Question 14

Metformin is C/I in….

Answer 14

• eGFR <30ml/min
• acidotic states such as ketoacidosis
• sudden drop of renal function e.g. sepsis
• conditions associated with tissue hypoxia - decompensated HF, respiratory daily, recent MI, hepatic insufficiency, acute alcohol intoxication, alcoholism.

Caution in eGFR <45ml;min (max dose 1g)

Max dose 2g eGFR 45-59ml/min

Question 15

Metformin is associated with

Answer 15

GI disturbances
B12 deficiency

Titrate up slowlyMax dose 3gram daily, no benefits beyond this.

Question 16

Sulfonyureas (gliclazide, glipizide, glibenclamide, tolbutamide)

Answer 16

Act on the pancreatic beta cells by stimulating the release of insulin and also decrease the hepatic output of glucose.

Question 17

sulphonyureas are associated with

Answer 17

• weight gain
• hypos (may not be suitable for a lorry driver)

Should always be given with meals. Gliclazide is favoured as short half life and part renal, part hepatic clearance. Longer acting ones can accumulate and cause more problematic hypos.

Question 18

DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, vildagliptin, alogliptin)

Answer 18

Hormones such as GLP1 and GIP are released by the intestinal cells throughout the day with the levels becoming elevated after a meal.

They act by stimulating insulin synthesis and release from the pancreatic beta cells and in the cause of GLP-1 decrease glucagon secretion.

Depended on glucose levels so do not cause hypos in the same way sulphonylureas do.

Question 19

DPP-4 inhibitors - GLIPTINS are associated with

Answer 19

pancreatitis

Question 20

Which DDP-4 inhibitor does not require a dose reduction based on eGFR?

Answer 20

linagliptin.

Question 21

What other anti diabetic drug are DPP-4 inhibitors not licensed to be prescribed along side?

Answer 21

GLP1 agonistis (exenatide, liraglutide, dulaglutide)

Question 22

GLP-1 agonists (exentide, liraglutide, dulaglutide)

Answer 22

work by mimicking the GLP1 hormone

They also slow gastric emptying reducing the rate at which glucose is absorbed into the circulation.

Question 23

GLP-1 agonists are associated with

Answer 23

pancreatitis

additional hypoglycaemic effect with sulphonylureas however they individually do not cause hypos.

rapid weight loss (expensive so reserved with patients with high BMI)

continued if a reaction of 1% HbA1C and 3% body weight in 6 months

Question 24

pioglitazone works by

Answer 24

reducing peripheral resistance of insulin and they do not cause hypos

Question 25

piogliazole is C/I in

Answer 25

HF co-morbidities that can cause HF e.g. MI Bladder cancer fracture risk

Question 26

if patient on pioglitazole gets weight gain what should we check?

Answer 26

LFT's not recommended in patients with hepatic dysfunction

Question 27

SGLT-2 inhibitors (Dapagliflozin, canagliflozin, empagaflozin)

Answer 27

Removed glucose

Question 28

SGLT-2 inhibitors are associated with

Answer 28

diuresis so can lower BP. They should be avoided in patients who are volume depleted or taking loop diuretics. - ketoacidosis - lower limb amputations primarily big toe. - They cannot be initiated in patients with eGFR <60ml/min however canagliflozin and empagliflozin can be continued down to 45ml.min They promote weight loss

Question 29

if a patient is volume deplete what should we do?

Answer 29

Suspend the SGLT-2 inhibitor as risk of UTI and gynae infections can occur including urosepsis.

Question 30

insulin therapy in T2DM

Answer 30

OD or BD intermediate acting. - neutral porcine hagedorn or isophane insulin. - humulin I, insulated, Inhuman Basal,

Question 31

Long acting insulins should be trialled in patient who

Answer 31

- daily to achieve HbA1C target - get hypos - cannot use divide - need assistance injecting - need intermediate + oral tabs

Question 32

Should metformin be continued with insulin?

Answer 32

Yes

Question 33

What is HHS?

Answer 33

uncommon complication of T2 DM

Question 34

HHS is complicated by

Answer 34

MI, thrombosis, stroke. Seizures cerebral oedema and central pontine myelinolysis are less common but well documented complications.

Question 35

what is the basic underlying cause off HHS?

Answer 35

circulating insulin deficiency Precipitants of HHS include vascular events, infections and undiagnosed T2DM.

Question 36

Features that differentiate HHS from DKA are

Answer 36

- hypovolaemia (significant dehydration) - Marked hyperglycaemia ( a blood glucose >30mmol) but can be higher without the presence of ketones or acidosis. - serum osmolality of 320mosmol/kg or greater

Question 37

Treatment

Answer 37

1) FLUID (aim to reduce serum osmolality by maximum 3-8mosmol/kg/hr) to reduce the risk of CPM 2) potassium replacement 3) IV insuline (not all will need). If blood glucose is not dropping despite adequate fluid replacement generally after 8 hours then can start at a rate of 0.05 units/kg/hr

Question 38

Does metformin reduce the risk of CVD in T2DM

Answer 38

YEs

Question 39

metformin should be stopped at EGFR

Answer 39

30ml/min

Question 40

Medicines which can cause pancreatitis?

Answer 40

GLP-1 - Exenatide, liraglutide DPP-4 - gliptins

Question 41

Facts about pioglitazone

Answer 41

- it should be avoided in combination with insulin - it is associated with increased fracture risk - it reduced peripheral insulin resistance - in those that respond to treatment the benefits outweigh the risk of developing bladder cancer

Question 42

Which T2DM drug is associated with ketoacidosis?

Answer 42

FLOZINS Dapagliflozin.

Question 43

HHS facts

Answer 43

- fluid replacement if more important than IV insulin - Patients are at an increased risk of VTE - Higer mortality rate than ketoacidosis