Long Term Complications of Diabetes

Question 1

how does the risk of complications from diabetes change with worsening glycaemic state?

Answer 1

Question 2

what are examples of macrovascular complications?

Answer 2

Coronary vascular disease
Cerebrovascular disease
Peripheral vascular disease

Question 3

what are examples of microvascular disease?

Answer 3

Retinopathy
Nephropathy
Neuropathy

Question 4

how does diabetes affect the risk of cardiovascular disease?

Answer 4

Question 5

what are the stages of atherosclerosis?

Answer 5

Macrophages and foam cells

Intracellular lipids

Extracellular lipid accumulation

Fibrotic and calcific layers

Damage to surface, exposure to platelets and clotting

Question 6

what is dyslipidaemia?

Answer 6

the imbalance of lipids such as cholesterol, low-density lipoprotein cholesterol, (LDL-C), triglycerides, and high-density lipoprotein (HDL)

Question 7

what is the HDL cholesterol, triglycerides, LDL cholesterol like in atherosclerosis?

Answer 7

HDL Cholesterol is lower

Triglycerides are higher

LDL cholesterol is in the form of small dense particles which are worse

Question 8

what does oxidation of HDL, triglycerides, LDL cholesterols result in?

Answer 8

Oxidisation of these particles promotes the features that lead to plaque formation (and glycation of the particles worsens the effect)

Question 9

what other than dyslipidaemia is caused by atherosclerosis?

Answer 9

Endothelial dysfunction
Hypercoagulability

Question 10

what effects can atherosclerosis have on diabetes?

Answer 10

Ischaemic cerebrovascular disease - strokes

Ischaemic Heart Disease - angina, myocardial infarctions

Heart Failure - related to coronary disease and abnormal cardiac myocyte glucose handling
Peripheral vascular disease

Causes lower limb ischaemia, leading to ulcers and poor healing of these ulcers. Amputations are a potential outcome.

Question 11

how can macrovascular disease be prevented?

Answer 11

Good diabetes control
Blood pressure control
Lipid control
Smoking cessation, weight, exercise

Question 12

57M
Admitted with a non-healing foot ulcer needing investigations and IV antibiotics.
Type 2 diabetes diagnosed 8 years ago

On gliclazide 160mg BD and metformin 1gm BD.
HbA1c 87 mmol/mol (ideally <58)

Hypertension
Previous NSTEMI
On clopidogrel, ramipril, amlodipine, atorvastatin (irregularly taken)

Current smoker
BMI = 42.5 kg/m2
BP 150/95 mmHg

Total cholesterol 6.8 mmol/L (ideally <4), HDL 0.8 mmol/L (ideally >1.0), LDL cholesterol 4.0, Triglycerides 7.6 mmol/L.

how would you manage this patient?

Answer 12

Improve glycaemic status

Optimise lipid levels – was not taking atorvastatin regularly
Review cardiac status

Smoking cessation

Education, support

Question 13

what is non proliferative diabetic retinopathy?

Answer 13

retinal capillary dysfunction, platelet dysfunction, blood viscosity abnormality.

Question 14

what is proliferative diabetic retinopathy?

Answer 14

Retinal ischaemia, new blood vessel formation, vitreous haemorrhage, retinal tears/detachment.

Treatment with laser photocoagulation.

Question 15

how is proliferative diabetic retinopathy managed?

Answer 15

Treatment with laser photocoagulation.

Question 16

what is retinopathy?

Answer 16

disease of the retina.

There are several types of retinopathy but all involve disease of the small retinal blood vessels.

Question 17

how do clinicians diagnose proliferative and non proliferative retinopathy?

Answer 17

Your eye doctor can identify diabetes by looking at the retina’s blood vessels. These tiny vessels can leak fluid or blood when you have diabetic retinopathy, which only develops when you have diabetes. Some patients may develop this condition before they’re officially diagnosed with diabetes.

Question 18

what is the impact of diabetic retinopathy currently?

Answer 18

Over a period of 20 years after diagnosis, 100% of people with Type 1 diabetes and 60% of those with Type 2 diabetes will have some form of retinopathy (mild-to-severe)

7% of people who are registered blind have advanced diabetic retinopathy (EnglandWales figure)

[Other eye effects of diabetes include a 50% increase in glaucoma, and a 3-fold increase in cataracts}

Question 19

what is treatment of diabetic retinopathy?

Answer 19

improve glycaemic control

Laser photocoagulation

Question 20

what is nephropathy a type of?

Answer 20

microvascular disease

Question 21

what is the cause of nephropathy?

what is the result of this?

Answer 21

Microalbuminuria - leak of protein (albumin) starts

Glomerular basement membrane changes, mesangial tissue proliferation, “glomerular hypertension” all contribute to renal dysfunction. Progressive renal impairment - note kidneys do not shrink when the disease progresses.

Progressive renal failure progresses to end-stage renal disease if unchecked.

Question 22

what is the glomerulus?

Answer 22

the filtering unit of the kidney, is a specialized bundle of capillaries that are uniquely situated between two resistance vessels (Figure 1). These capillaries are each contained within the Bowman’s capsule and they are the only capillary beds in the body that are not surrounded by interstitial tissue.

Question 23

what is the impact of diabetic nephropathy on an individual?

Answer 23

75% of people with diabetes have some renal effects, and 20% go on to overt kidney disease that may need treatment.

Diabetes is the biggest single cause of end stage renal disease needing renal replacement therapy (dialysis).

Renal failure ultimately leads to death in 21% of people with Type 1 and 11% of people with Type 2 diabetes.

Question 24

what is the late stage impact of diabetic retinopathy?

Answer 24

Question 25

how can nephropathy be prevented?

Answer 25

Screening of urine for albumin is vital!

Question 26

how can nephropathy be treated?

Answer 26

Diabetes control

Renin-angiotensin system blockade - ACE inhibition, angiotensin receptor blockade, renin inhibition.

Very good results in slowing/preventing progression of renal disease (ACE-I, ARB).

Hypertension control

Question 27

what is neuropathy?

Answer 27

Peripheral neuropathy happens when the nerves that are located outside of the brain and spinal cord (peripheral nerves) are damaged.

Sensory, Motor, Autonomic

Question 28

what is the sensory effect of neuropathy?

Answer 28

objective loss, particularly in feet & lower legs; subjective symptoms, especially paresthesia.

Question 29

what can loss of sensory function result in?

Answer 29

Can be symptomatically troublesome. However, lack of sensation can lead to the development of neuropathic ulcers, which, alongside poor macro-vasculature, leads to severe foot infections.

Question 30

what can autonomic neuropathy cause?

Answer 30

can cause GI effects (stomach, intestines), or the cardiovascular system (tachycardia, blood pressure fluctuations).

Watch out for silent myocardial infarction!

Question 31

how should feet with ulcers be systematically treated?

Answer 31

Question 32

what is charcots foot?

Answer 32

It is a problem which can affect the foot in people with neuropathy (nerve damage with numbness). The bones of the foot become very fragile and can start to break or dislocate in response to very minor forces – even in response to the forces which occur with standing or walking.

Question 33

what other conditions can be caused by poor diabetic control?

Answer 33

Erectile dysfunction/sexual dysfunction

Depression - possibly twice as common as in the general population.

Question 34

42F
Admitted with diabetic ketoacidosis (DKA).

Also has problems with severe hypogycaemia, with lack of awareness of low blood glucose levels (among other factors, autonomic neuropathy contributes to the loss of normal autonomic responses to low glucose)

Type 1 diabetes diagnosed at age 14
On insulin: long-acting Lantus once a day (bedtime) and short-acting Novorapid with each meal.
HbA1c 78 mmol/mol (ideally <53)

Nephropathy with significant proteinuria, deteriorating renal function – under monitoring from Renal team with anticipatory planning for dialysis.

Retinopathy – laser treatment.
Peripheral neuropathy and peripheral vascular disease, non-healing ulcer on L 5th toe with osteomyelitis, leading to amputation of that toe previously.

BMI = 22 kg/m2

how would you manage this patient?

Answer 34

Acute complication of DKA treated using IV insulin as per standard protocol, with good recovery.

Deteriorating renal functions worsening – followup arranged in the pre-dialysis clinic.

Attempts to improve glycaemic control while addressing the risk of impaired hypoglycaemia awareness.

Question 35

what newer techniques can help improve glycaemic control?

Answer 35

Newer techniques for glucose monitoring to help improve glycaemic control.

Possibility of kidney-pancreas transplantation in the setting of established end-stage renal disease.

Question 36

Macrovascular disease (coronary, stroke disease and heart failure) can be prevented by controlling risk factors as well as glycaemic status.

Microvascular disease (nephropathy, retinopathy, neuropathy) must be screened for, and some preventative measures are good, e.g., for nephropathy, while some treatments are valuable in preventing severe dysfunction, e.g., retinal laser treatment. Good glycaemic control reduces risk of progression.