Endocrine e-book

Question 1

Type 1 diabetes is caused

Answer 1

● when the pancreas does not produce any insulin.
o This is commonly diagnosed in people under the age of 30 and especially in childhood.
o Symptoms are usually experienced at a more severe level and the onset is usually faster.
o Treatment includes insulin therapy

Question 2

Type 2 diabetes is caused by

Answer 2

● a relative insulin deficiency and/or insulin resistance.
o This usually develops in people over the age of 40 but may also develop in younger patients who are obese.
o Symptoms are usually vague in their presentation and may develop over a longer period of time.
o Treatment includes lifestyle management such as physical activity and diet.
Oral anti-diabetics may be commenced if lifestyle advice measures fail. Insulin may be started if blood glucose concentrations are still not controlled

Question 3

Symptoms of both types of diabetes include

Answer 3

● Polyuria – frequent urination
● Nocturia – waking up more than one time at night due to frequent urination
● Polydipsia – excessive or abnormal thirst
● Lethargy
● Unexplained weight loss

Question 4

Microvascular complications

Answer 4

neuropathy, nephropathy and retinopathy

Question 5

Macrovascular complications:

Answer 5

including cardiovascular disease and stroke

Question 6

Neuropathy

Answer 6

Diabetic neuropathy is nerve damage from hyperglycaemia in people with diabetes. It affects the sensory, autonomic and motor neurons of the peripheral nervous system

Question 7

There are four main types of peripheral neuropathy

Answer 7

sensory neuropathy, autonomic neuropathy, motor neuropathy and mononeuropathy

Question 8

Sensory neuropathy

Answer 8

Sensory neuropathy occurs if the body’s sensory nerves become damaged. Sensory neuropathy starts from the extremities of the body such as the feet or hands and can
develop to affect the legs and arms

Question 9

Symptoms of sensory neuropathy

Answer 9

● Damage to large sensory fibres affects the ability to feel vibrations and touch, especially in the hands and feet. It may feel like you are wearing gloves and stockings even when you are not. This damage may contribute to the loss of reflexes (as can motor nerve damage).
● Tingling and numbness
● Burning or shooting pains – may be worse at night time
● Loss of ability to feel pain. It can be caused by pain receptors firing spontaneously without any known trigger, or by difficulties with signal processing in the spinal cord
that may cause you to feel severe pain (allodynia) from a light touch that is normally painless. For example, you might experience pain from the touch of your bedsheets,
even when draped lightly. Neuropathic pain may worsen at night, disrupting sleep.
● Loss of ability to detect changes in temperature. Small-fibre polyneuropathy can interfere with the ability to feel pain or changes in temperature.
● Loss of joint position sense often makes people unable to coordinate complex movements like walking, fastening buttons or maintaining balance with eyes shut.

Question 10

Autonomic neuropathy

Answer 10

damages the nerves that control involuntary body functions and internal organs.

Question 11

Damage to the nerves of your digestive system can cause symptoms such as the following:

Answer 11

● Bloating, fullness, and nausea
● Constipation
● Diarrhoea, especially at night
● Diarrhoea alternating with constipation
● Faecal incontinence
● Problems swallowing
● Vomiting

Question 12

Autonomic neuropathy may also cause

Answer 12

Gastroparesis is a disorder that slows or stops the movement of food from the stomach to the small intestine. Gastroparesis can keep the body from absorbing glucose and using insulin properly. These problems can make it hard to manage blood glucose.

Question 13

Motor neuropathy

Answer 13

Damages the nerves that control movement.

Question 14

Motor neuropathy symptoms

Answer 14

● Twitching and muscle cramps (fasciculations)
● Muscle weakness or paralysis affecting one or more muscles
● Thinning or wasting of muscles
● Foot drop – difficulty lifting up the front part of your foot and toes

Question 15

Mononeuropathy

Answer 15

Mononeuropathy damages a single peripheral nerve outside the central nervous system.
The most common type of mononeuropathy is carpal tunnel syndrome (CTS). The carpal tunnel is a small tunnel in your wrist. In CTS, the median nerve becomes compressed where it passes through this tunnel, which may cause tingling, pain or numbness in the fingers

Question 16

Mononeuropathy symptoms

Answer 16

● Altered sensation or weakness in the fingers
● Double vision or other problems with focusing your eyes, sometimes with eye pain
● Weakness of one side of your face (Bell’s palsy)
● Foot or shin pain, weakness or altered sensation

Question 17

Diagnosis of peripheral neuropathy

Answer 17

● Sensation, strength and reflex tests.
● Further tests by neurologists in hospitals:
o A nerve conduction test (NCS) –electrodes are placed on the skin releasing tiny electric shocks that stimulate your nerves; the speed and strength of the nerve signal is then measured.
o Electromyography (EMG) – a small needle is inserted into the muscle and the electrical activity of the muscles are measured.
o these tests are usually carried out at the same time.
● Nerve biopsy – removing a small sample of a peripheral nerve and examining it (this test is rare).
● X-ray, CT scan or MRI scan – diagnose underlying case of neuropathy.

Question 18

Treatment for diabetic neuropathy - Sensory neuropathy

Answer 18

Treatments are mainly related to pain management.
Acute neuropathic pain due to rapid improvement of blood glucose – NICE NG17and NG28:
● Reassure patients that acute painful neuropathy resulting from rapid improvement of blood glucose control is self-limiting and will improve symptomatically over time.
● Simple analgesics (paracetamol, aspirin) and local measures (bed cradles) are recommended as a first step.
● If simple analgesics are ineffective, offer treatments as for chronic painful diabetic neuropathy.
● Simple analgesia may be continued until the effects of additional treatments have been established.
● Do not relax diabetes control to address acute painful neuropathy resulting from rapid improvement of blood glucose control in adults with type 1 diabetes.

Chronic painful diabetic neuropathy – NICE CG173:
● First-line: Offer a choice of amitriptyline, duloxetine, gabapentin or pregabalin.
● Second-line (if the initial treatment is not effective or is not tolerated): Offer one of the remaining three drugs; consider switching again if the second and third drugs
tried are also not effective or not tolerated.
● Consider tramadol only if acute rescue therapy is needed.
● Consider capsaicin cream for people with localised neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments.
● Patients should be reviewed early when starting treatment for dosage titration, or when changing dose to monitor for adverse effects and tolerability.
● Carry out regular reviews (NICE does not specify a time interval) to assess pain control, adverse effects, continued need for treatment, impact on lifestyle and physical and psychological well being.
● Refer to a specialist pain service and/or a condition-specific service at any stage if:
o Pain is severe
o Pain significantly limits activity
o The underlying condition (diabetes) has deteriorated

Question 19

Autonomic neuropathy treatment

Answer 19

Heart rate and blood pressure
● Increased physical activity
● Increasing salt in diet, if blood pressure drops too low when standing up
● Increasing water intake
● Elevating head when sleeping or wearing elastic stockings to improve blood flow
● Sitting or standing slowly to prevent light-headedness or fainting
● Avoiding hypoglycaemia
● A vasopressor (anti-hypotensive) may be used to increase blood pressure e.g. fludrocortisone 100-400 mg daily

Question 20

Digestive system treatment

Answer 20

● For the treatment of constipation, lifestyle advice is the first line treatment. Oral laxatives using a stepped approach can be offered if lifestyle measures are
ineffective.

● For adults with vomiting caused by gastroparesis:
○ Advise a small-size diet (mashed or pureed food) for symptomatic relief.
○ Refer to a gastroenterologist or the diabetes specialist team for consideration of treatment with a prokinetic drug, such as erythromycin (off-label use), metoclopramide, or domperidone.
○ Continuous subcutaneous insulin infusion (CSII or insulin pump) therapy may be considered in secondary care of type 1 diabetes if symptoms are ongoing

Question 21

Nephropathy

Answer 21

Diabetic nephropathy is known as kidney disease due to diabetes. This can develop slowly, over many years and patients may not experience symptoms until later. The condition is characterised by persistent albuminuria (>300 mg/24 hours), decline in GFR and raised BP

Question 22

Diagnosis - Nephropathy

Answer 22

● All diabetic patients should be screened for nephropathy once a year
● The first step in the screening and diagnosis of diabetic nephropathy is to measure albumin in a spot urine sample, collected either as the first urine in the morning or at random, for example, at the check-up.
● Blood is then taken at the same time to measure serum creatinine levels and calculate estimated glomerular filtration rate (eGFR).
● These tests then give an estimation of the albumin:creatinine ratio (ACR).
● Chronic kidney disease (CKD) is diagnosed when tests have persistently (for at least three months or more) shown a reduction in kidney function (i.e. eGFR persistently <60 mL/min/1.73m2 and/or ACR persistently >3 mg/mmol) or the presence of proteinuria

Question 23

Management of nephropathy

Answer 23

Glycaemic control
Good glycaemic control is effective in reducing diabetic microvascular complications, including diabetic nephropathy

Antihypertensives (NICE CKS (Type 1 and Type 2 Diabetes), NG17 and NG28):
● Start ACE inhibitors in all adults with diabetes and confirmed nephropathy (including those with moderately increased albuminuria alone).
○ Start with a low dose and titrate up to the maximum tolerated therapeutic dose, by doubling the dose every 1–2 weeks.
○ After each upward titration, monitor the person’s renal function, serum potassium level, and blood pressure.
● If not tolerated, offer an angiotensin II receptor antagonist.
● Combination therapy is not recommended.
● Maintain blood pressure below 130/80 mmHg
● Adding another anti-hypertensive drugs may be necessary for BP control.
● Dialysis and/or kidney transplant may be necessary for advanced CKD.
● Diuretics may be prescribed to treat oedema.

Refer to a nephrologist if (NICE CKS - Type 1 Diabetes):
● Stage 4 or 5 CKD i.e. eGFR <30 mL/min/1.73m2
● There is a sustained decrease in eGFR by of 25% or more within 12 months and a change in eGFR category OR a sustained decrease in eGFR of 15 mL/min/1.73 m2 or
more within 12 months.
● Urinary albumin:creatinine ratio (ACR) of 70 mg/mmol or more.
● Urinary ACR of 30 mg/mmol or more, together with persistent non-visible haematuria (two out of three dipstick tests show 1+ or more of blood).
● Hypertension that remains poorly controlled despite the use of at least 4 antihypertensive drugs at therapeutic doses.
● Complications of CKD, such as renal anaemia and renal bone disease

Question 24

Retinopathy

Answer 24

Diabetic retinopathy is an eye complication developed by people with diabetes. If left untreated, this can lead to long-term complications and even sight loss. The condition can most likely be treated if it is in its early stages.

Question 25

There are four main types of retinopathy

Answer 25

● Background retinopathy (stage 1) – eye sight isn’t affected but there is a need to prevent the problem getting worse.
● Non-proliferative retinopathy (stage 2) - the damage is more serious and there is a need to get the eyes screened more often to check for any changes.
● Proliferative retinopathy (stage 3) – very high risk of losing sight and there is a need for treatment

Question 26

Management of retinopathy

Answer 26

Reduce the risk of developing diabetic retinopathy or prevent it from getting worse by:
● Strict control of blood sugar, blood pressure and cholesterol levels
● Taking anti-diabetic medication as prescribed
● Attending regular eye screening appointments
● Getting medical advice quickly if patient notices any changes to your vision
● Maintaining a healthy weight, eating a healthy, balanced diet, exercising regularly and stopping smoking
In Stage 1 and 2 retinopathies, there is usually no need for treatment. The prevention steps can be used to delay and prevent progression of retinopathy. For all diabetics:
● Ensure that emergency review by an ophthalmologist occurs for:
o Sudden loss of vision
o Rubeosis iridis (new abnormal blood vessels found on the surface of the iris)
o Pre-retinal or vitreous haemorrhage
o Retinal detachment
● Ensure that rapid review by an ophthalmologist occurs for new vessel formation.
● Refer to an ophthalmologist for:
o Referable maculopathy
o Referable pre-proliferative retinopathy
o Any large sudden unexplained drop in visual acuity

Treatment of advanced retinopathy (proliferative and maculopathy) may include:
● Laser treatment
○ The most common type of treatment for advanced retinopathy
○ It can prevent the eye damage getting worse, but won’t improve eyesight
○ Pan-retinal photocoagulation; Pan-retinal photocoagulation applies hundreds of laser burns to the peripheral retina, reducing the amount of ischemic retina that drives angiogenesis (formation of new blood vessels).
○ Focal laser photocoagulation; indicated for patients with clinically significant macular edema; it targets microaneurysms near the macula, reducing the plasma leakage responsible for intraretinal swelling.
● Intraocular administration of pharmacological agents such as steroids and antiVEGF agents
● Corticosteroids
○ Corticosteroids, either injected or implanted into the eye, may be used alone or in combination with other drugs or laser surgery to treat diabetic macular edema (DME).
○ Dexamethasone implant is for short-term use,
○ Fluocinolone acetonide implant is longer lasting. Both are biodegradable and release a sustained dose of corticosteroids to suppress DME.
○ Corticosteroid use in the eye increases the risk of cataract and glaucoma. DME patients who use corticosteroids should be monitored for increased pressure in the eye and glaucoma.
● Anti-VEGF Injection Therapy
○ Levels of vascular endothelial growth factor (VEGF) are elevated in the vitreous and retina in patients with diabetic retinopathy and diabetic macular oedema
○ VEGF can stimulate abnormal blood vessels to grow and leak fluid
○ Blocking VEGF can reverse abnormal blood vessel growth and decrease fluid in the retina.
○ Available anti-VEGF drugs include bevacizumab, ranibizumab, and aflibercept
● Vitrectomy
○ A vitrectomy is the surgical removal of the vitreous gel in the center of the eye, blood, and fibrovascular retinal tissue
○ The procedure is used to treat severe bleeding into the vitreous
○ It is recommended for severe proliferative diabetic retinopathy when it is unresponsive to pan-retinal photocoagulation, associated with severe vitreous haemorrhage, or associated with traction on the macula.

Question 27

CVD Risk factors

Answer 27

● Age over 50 years
● Hypertension
● Hyperlipidaemia
● Diabetes
● Smoking, excessive alcohol consumption, poor diet and physical inactivity
● Overweight or obese
● Family history of CVD
● Ethnic – more common in people of south Asian and African-Caribbean

Question 28

CVD Diagnosis

Answer 28

● People with diabetes should have their cardiovascular risk factors assessed annually
● Assess:
o Smoking status
o Family history of CVD
o Albuminuria
o Blood glucose control and blood pressure control
o Full lipid profile, including HDL cholesterol, LDL cholesterol and triglycerides
o Abdominal adiposity
● Use the QRISK2 risk assessment tool to assess CVD risk for the primary prevention of CVD in people up to and including age 84 years.
o Only for type 2 diabetic patients, not for type 1.
o Do not use for patients with eGFR < 60 mL/min/1.73m2 and/or albuminuria since they are already at increased risk of CVD.
o Do not use for people at high risk of developing CVD because of familial hypercholesterolaemia or other inherited disorders of lipid metabolism.

Question 29

first choice for primary and secondary prevention of CVD

Answer 29

Statins

Question 30

Before initiating statins, assess

Answer 30

● smoking status
● alcohol consumption
● blood pressure
● BMI or other measure of obesity
● total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides
● HbA1c
● renal function and eGFR
● transaminase level (alanine aminotransferase or aspartate aminotransferase)
● thyroid‑stimulating hormone

Question 31

Primary prevention of CVD

Answer 31

The aim of primary prevention is to prevent the development of CVD at both the individual and the population level. For this reason, identifying and assessing at-risk individuals are important so that lifestyle changes and lipid modification can be offered.

● DO NOT offer antiplatelet therapy such as aspirin for the primary prevention of CVD to adults with diabetes.
● Consider statin treatment for all adults with type 1 diabetes but offer atorvastatin 20mg to those who:
o Are older than 40 years or
o Have had diabetes for more than 10 years or
o Have established nephropathy or
o Have other CVD risk factors
● Offer atorvastatin 20 mg for all adults with type 2 diabetes who have a 10% or greater 10-year risk of developing CVD.

Question 32

Secondary prevention of CVD

Answer 32

Secondary prevention is the prevention of further cardiovascular events occurring in an individual who is already known to have cardiovascular disease or who has experienced a cardiovascular event, for example, myocardial infarction.
Secondary prevention includes lifestyle changes, drug treatments and rehabilitation appropriate to the cardiovascular event experienced
● Start atorvastatin 80 mg
● Lower dose of atorvastatin if there are possible drug interactions or high risks of adverse effects are due to patient preference.
● If a person has acute coronary syndrome, do not delay statin treatment.

Statins have a number of adverse effects including an association with muscle toxicity (myositis, myopathy and rhabdomyolysis). Patients should be counselled to report any adverse effects including muscle aches and pains. Statins can raise liver enzymes and NICE recommends baseline liver function tests before, at 3 months and at 12 months of statin therapy. Statins interact with a number of drugs and checking for potential interactions prior to initiating treatment is essential.

Question 33

DO NOT routinely offer.. for the primary and secondary prevention of CVD for people with type 1 and type 2 diabetes

Answer 33

DO NOT routinely offer fibrates and DO NOT offer nicotinic acid, bile acid sequestrants, omega-3 fatty acid compounds or the combination of them for the primary and secondary prevention of CVD for people with type 1 and type 2 diabetes

Question 34

BP of adults with type 1 diabetes should be

Answer 34

below 135/85 mmHg

o If the adult with type 1 diabetes has albuminuria or 2 or more features of metabolic syndrome, it should be below 130/80 mmHg,
o For adults with confirmed nephropathy and type 1 diabetes, blood pressure should be below 130/80 mmHg.
o In people with renal impairment, type 1 diabetes, and an ACR of 70 mg/mmol or more, aim to keep the systolic blood pressure below 130/80 mmHg

Question 35

BP of adults with type 2 diabetes should be

Answer 35

below 140/80 mmHg

o Monitor blood pressure every 1-2 months and intensify therapy, until the blood pressure is consistently below target (below 130/80 mmHg if there is kidney, eye or cerebrovascular damage).

Question 36

Treatment of hypertension with Type 1 diabetes mellitus

Answer 36

● Start a trial of a renin–angiotensin system (RAS) antagonist as first‑line therapy for hypertension in adults with type 1 diabetes.
o Offer an angiotensin-converting enzyme (ACE) inhibitor. If an ACE inhibitor is not tolerated, offer an angiotensin-II receptor antagonist (A2RA/ARB) instead.
o Start with a low dose and titrate up to maximum tolerated therapeutic dose (within the maximum licensed dose) by doubling the dose every 1-2 weeks.
o Monitor renal function, serum potassium level and blood pressure after each upward titration.
● For all adults with confirmed nephropathy (including those with moderately increased albuminuria alone) and type 1 diabetes, start an ACE inhibitor and titrate to full dose.
o If an ACE inhibitor are not tolerated, substitute with an A2RA instead.
Combination therapy is not recommended.
● It may be necessary to prescribe other antihypertensive drugs to improve blood pressure control.
o Do not offer cardio-selective beta-blockers (such as atenolol and metoprolol) where indicated in adults on insulin.
o Low-dose thiazides may be combined with beta-blockers.
o When calcium-channel blockers (CCBs) are prescribed, use only long-acting preparations.

Question 37

Guidance on blood pressure management in adults with type 1 diabetes and evidence of renal involvement

Answer 37

● Offer a low-cost RAS antagonist to people with CKD and:
o diabetes and an ACR of 3 mg/mmol or more (ACR category A2 or A3)
o hypertension and an ACR of 30 mg/mmol or more (ACR category A3)
o an ACR of 70 mg/mmol or more (irrespective of hypertension or cardiovascular disease).
● Do not offer a combination of RAS antagonists to people with CKD.

Question 38

Treatment of hypertension with Type 2 diabetes mellitus

Answer 38

● First-line treatment should be a generic ACE inhibitor, taken once-daily.
o For African-Caribbean origin – an ACE inhibitor plus either a diuretic or a CCB.
o For a woman with the possibility of becoming pregnant – a CCB
o Substitute to an A2RA if intolerant to an ACE inhibitor.
● If the target is not achieved after first-line therapy, add a CCB or a diuretic (usually a thiazide or a thiazide-like diuretic) to the first-line treatment.
● If the target is not achieved with dual therapy, add the other drug (i.e. the CCB or the diuretic) for triple therapy.
● If target is not achieved with triple therapy, add an alpha-blocker, a beta-blocker or a potassium-sparing diuretic.
● DO NOT combine an ACE inhibitor with an A2RA to treat hypertension.
● Monitor the blood pressure of patients who have attained their target every 4-6 months and check for possible adverse effects from the treatment including the risk of hypotension

Question 39

Preferred ACE inhibitors

Answer 39

● Enalapril, Lisinopril, Perindopril, Ramipril, Trandolapril

Question 40

Preferred A2RAs

Answer 40

● Candesartan, Irbesartan, Losartan, Valsartan

Question 41

Preferred CCBs

Answer 41

● Amlodipine, Felodipine, once-daily modified-release nifedipine

Question 42

Beta-blockers

Answer 42

● Beta-blockers should be used in caution in people with diabetes. This is because beta-blockers may mask warning signs of hypoglycemia, such as tremor.

Question 43

Thiazide-type diuretics

Answer 43

● Thiazide-type diuretics should be used in caution in people with diabetes. This is because of the risk of exacerbation of diabetes

Question 44

How to manage the switching of antiplatelet treatments:

Answer 44

● If switching from clopidogrel to:
o Ticagrelor — start 90 mg twice daily, 24 hours after the last clopidogrel dose.
o Prasugrel — start 10 mg daily, 24 hours after last clopidogrel dose.

● If switching from prasugrel to:
o Clopidogrel — start 75 mg daily, 24 hours after the last prasugrel dose.
o Ticagrelor — start 90 mg twice daily, 24 hours after the last prasugrel dose.

● If switching from ticagrelor to:
o Clopidogrel — give a loading dose of 600 mg, 24 hours after the last ticagrelor dose. Then continue with 75 mg daily.
o Prasugrel — give a 60 mg loading dose, 24 hours after the last ticagrelor dose. Then continue with 10 mg daily

Question 45

People are at high risk of GI adverse effects with antiplatelet treatment if the following risk factors are present

Answer 45

● High dose of aspirin.
● Older age especially aged over 70 years.
● History of gastroduodenal ulcer, GI bleeding, or gastroduodenal perforation.
● Helicobacter pylori infection.
● Concomitant use of medicines that are known to increase the risk of GI bleeds.