Patient: diabetes, ischaemic heart disease, renal involvement, ESRD, wants conservative care. New diabetic drugs.

Question 1

What are some acute complications of diabetes mellitus?

Answer 1

Hypoglycaemia
Hyperglycaemia
Diabetic coma
Non-ketotic hyperosmolar coma
Diabetic ketoacidosis

Question 2

What are some chronic complications of diabetes mellitus?

Answer 2

Microangiopathy: diabetic nephropathy, neuropathy, amyotrophy, retinopathy, encephalopathy, cardiomyopathy, erectile dysfunction, periodontal disease.
Macrovascular disease: coronary artery disease (leading to angina, MI), diabetic myonecrosis, peripheral vascular disease (contributes to intermittent claudication), stroke, carotid artery stenosis, diabetic foot, female infertility.
Abnormal immune responses: respiratory infections such as pneumonia and influenza, restrictive lung disease, lipohypertrophy, depression.

Question 3

What are some complications of diabetes mellitus?

Answer 3

Diabetic kidney disease
Blindness
Amputation
Cardiovascular disease
Congestive heart failure
Stroke
Infection
Periodontal disease
Treatment-related hypoglycaemia
Depression
Obstructive sleep apnoea
Diabetic ketoacidosis
Non-ketotic hyperosmolar state
Autonomic or peripheral neuropathy

Question 4

True or false? Half of the patients with type 2 diabetes in the UK do not know they have it.

Answer 4

True

Question 5

Type 2 diabetes has an insidious onset: true or false? How does this differ from type 1?

Answer 5

True.
Compared to type 1 diabetes that always presents acutely with ketosis, type 2 diabetes patients spend months to years not knowing they have diabetes at all: insidious. They have enough insulin to suppress ketone production. Chronic hyperglycaemia.

Question 6

What are the symptoms of slowly rising glucose?

Answer 6

Tiredness, lethargy.
Polyuria and polydipsia.
Often drink Lucozade or Coke because of thirst.
Glucose SLOWLY rises further.
With other co-morbidities it becomes difficult to drink enough.
Osmotic diuresis causes loss of water and a rise in sodium.
Eventually, the glucose is very high, as is the sodium. HHS.

Question 7

What can you see on fundoscopy of patient with background diabetic retinopathy?

Answer 7

Hard exudates (cholesterol).
Microaneurysms (dots).
Blot haemorrhages.

Question 8

What treatment should we use for background diabetic retinopathy?

a) glasses or contact lenses
b) laser treatment
c) nothing
d) improve blood pressure control
e) improve blood glucose control

Answer 8

Improve blood glucose control.

Question 9

What is likely to be seen on fundoscopy of pre-proliferative diabetic retinopathy?

Answer 9

Cotton wool spots: previously called soft exudates, indicate ischaemia.

Question 10

Cotton wool spots suggest which of the following?

a) retinal cholesterol deposits
b) retinal ischaemia
c) retinal hypertension

Answer 10

Retinal ischaemia.

Question 11

What is the management plan for patients with background diabetic retinopathy?

Answer 11

Improve control of blood glucose.

Warn patient that warning signs are present.

Question 12

What is the management plan for patients with pre-proliferative diabetic retinopathy?

Answer 12

Cotton wool spots, suggest general ischaemia. Without treatment, new vessels will grow.
Pan-retinal photocoagulation.

Question 13

What is the management plan for patients with proliferative diabetic retinopathy?

Answer 13

Proliferative = visible new vessels.

Pan-retinal photocoagulation.

Question 14

Does good glucose control prevent complications? Is there real evidence of this?

Answer 14

Yes.

Question 15

How long does it take to see benefit from good glucose control in diabetes?

Answer 15

15 years.

Question 16

What is the UKPDS?

Answer 16

UK prospective diabetes study.
20-year interventional trial 1977-1997.
4209 patients with newly diagnosed type 2 diabetes.
Received conventional (diet) or intensive glucose control (SU, insulin, or metformin in overweight patients at specific centres).
Intensive > conventional.
No difference after 9 years, difference significant at 15 years.
Tight control takes a long time to prevent heart attacks.
Heart attacks occur after many years or poor control.
Legacy effect of benefit even after the study is over.
Good control now prevents heart disease in future.

Question 17

Studies of control in diabetes and their outcomes

Answer 17

DCCT: T1DM, good control improves outcome.
UKPDS: new T2DM put onto good control = low mortality in both groups for 15 years, but then good control improved outcome, legacy effect.
ACCORD: take older people who had poor control for a long time, and suddenly massively tighten control (A1c=6%)- they already had coronary artery disease, so increased unexpected death.
ADVANCE: (A1c=6.5%), reduced death.

Question 18

How is hyperglycaemia managed?

Answer 18

Diet and exercise.
Biguanide (metformin).
Sulphonylureas (e.g. gliclazide).
Insulin sensitiisers: thiozolidinediones such as pioglitazone.
Insulin analogues.
Incretins (GLP-1 analogues).
Gliptins (DPP-4 inhibitors).

Question 19

Insulin as a treatment in T2DM.

Answer 19

Insulin is an excellent treatment, even for patients who are not dependent on it.
Patients need a long acting (depot) insulin such as insulin zinc suspension.
Together with a short-acting insulin such as normal soluble insulin with each meal.
Traditionally insulatard and actrapid.

Question 20

What is the problem with insulin use in T2DM?

Answer 20

When soluble natural insulin is given subcutaneously, it forms a hexameter under the skin, which delays release.
Inject 30mins before meals.

Question 21

Why are short acting insulin analogues better than insulin in the treatment of T2DM?

Answer 21

Very rapid acting and mean that patients can inject and eat- no waiting, no risk of hypos if forget to eat.
Gives patients a licence to inject immediately before meals.
Many were doing this anyway with the old insulins.
Profile more closely mimics insulin profile of insulin following a meal.
X Twice the cost of soluble insulin X

Question 22

What is insulin glargine?

Answer 22

A long acting insulin that seems to give the least variation in plasma insulin levels for 24hr after injection.
Previous long acting insulins were Zn suspensions of insulin, efficacy waned slowly over 24hr.
Different alterations in the molecule to try and attain a plateau like concentration over time.
Once daily insulin injection improves quality of life, lower risk of hypoglycaemia.
Gives background concentration of insulin.
Normal pancreas makes continuous secretion of insulin.

Question 23

What is insulin detemir?

Answer 23

14C fatty acid chain attached to B29.
Delayed onset 7hr.
Can be used as part of basal bolus.

Question 24

What are the advantages of insulin?

Answer 24

Can give best control of HbA1c when combined with diet and exercise.
No side effects compared to metformin (diarrhoea), SU (occasional reactions), thiazolidinediones (rare hepatic, ?osteoporosis).

Question 25

What are the disadvantages of insulin?

Answer 25

If you drive HGV, cannot work (exenatide exempt).
Hypoglycaemia common with good control.
Weight gain.
Increased insulin as a consequence.
Huge doses required.

Question 26

What are the effects of GLP-1?

Answer 26

GLP-1 is secreted from the gut and signals to the pancreas to make even more insulin.
Direct effect on appetite and reduces gastric emptying.
Increases hypothalamic satiety.

Question 27

List GLP-1 analogues.

Answer 27

Exanatide
Liraglutide (Victoza or Saxenda)
Semaglutide

Question 28

How do SGLT2 inhibitors work?

Answer 28

Blocks sodium-glucose cotransporters in renal tubules.
Impairs glucose reabsorption.
Decreasing blood glucose levels.

Question 29

How do GLP-1 agonists work?

Answer 29

Increase insulin secretion.
Decrease glucagon.
Decreasing blood glucose levels.

Question 30

How do DPP-4 inhibitors work?

Answer 30

Increase incretin levels (GLP-1 and GIP).
Increase insulin and decrease glucagon.
Decreasing blood glucose levels.

Question 31

Why do patients gain weight on insulin treatment?

Answer 31

If glycosuria stops, many calories saved.
Increased appetite.
Improved wellbeing.
Set point of body weight (hypothalamic).
Poor glucose control enables weight loss.

Question 32

How do you calculate osmolality?

Answer 32

2(Na + K) + glucose

+ urea = osmolality.