Diabetic Neuropathy

Diabetic neuropathy
NICE updated it's guidance on the management of neuropathic pain in 2013.

Diabetic neuropathy is now managed in the same way as other forms of neuropathic
pain:
 first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin

 if the first-line drug treatment does not work try one of the other 3 drugs
 tramadol may be used as 'rescue therapy' for exacerbations of neuropathic
pain
 topical capsaicin may be used for localised neuropathic pain (e.g. post-
herpetic neuralgia)
 pain management clinics may be useful in patients with resistant problems
Gastroparesis
 symptoms include erratic blood glucose control, bloating and vomiting

 management options include metoclopramide, domperidone or
erythromycin (prokinetic agents)
MODY
Maturity-onset diabetes of the young (MODY) is characterised by the development

of type 2 diabetes mellitus in patients < 25 years old. It is typically inherited as an
autosomal dominant condition. Over six different genetic mutations have so far
been identified as leading to MODY.
It is thought that around 1-2% of patients with diabetes mellitus have MODY, and
around 90% are misclassified as having either type 1 or type 2 diabetes mellitus.
MODY 3
 60% of cases
 due to a defect in the HNF-1 alpha gene
 is associated with an increased risk of HCC
MODY 2
 20% of cases
 due to a defect in the glucokinase gene
Features of MODY
 typically develops in patients < 25 years

 a family history of early onset diabetes is often present
 ketosis is not a feature at presentation
 patients with the most common form are very sensitive to sulfonylureas,
insulin is not usually necessary
mnemonic DISCO helps me remember (Digoxin, isoniazid, spironolactone,

cimetidine and other (estrogens)
MTP
M: Methyl-dopa
T: TCA
V: Verapamil
Gynaecomastia
Gynaecomastia describes an abnormal amount of breast tissue in males and is

usually caused by an increased oestrogen:androgen ratio. It is important to
differentiate the causes of galactorrhoea (due to the actions of prolactin on breast
tissue) from those of gynaecomastia
Causes of gynaecomastia
 physiological: normal in puberty

 syndromes with androgen deficiency: Kallman's, Klinefelter's
 testicular failure: e.g. mumps
 liver disease
 testicular cancer e.g. seminoma secreting hCG
 ectopic tumour secretion
 hyperthyroidism
 haemodialysis
 drugs: see below
Drug causes of gynaecomastia

 spironolactone (most common drug cause)
 cimetidine
 digoxin
 cannabis
 finasteride
 gonadorelin analogues e.g. Goserelin, buserelin
 oestrogens, anabolic steroids
Very rare drug causes of gynaecomastia
 tricyclics
 isoniazid
 calcium channel blockers
 heroin
 busulfan
 methyldopa

Multiple endocrine neoplasia

The table below summarises the three main types of multiple endocrine
neoplasia (MEN). MEN is inherited as an autosomal dominant disorder.
MEN type I MEN type IIa MEN type IIb

3 P's Medullary thyroid Medullary thyroid
Parathyroid (95%): cancer (70%) cancer
hyperparathyroidism due to
parathyroid hyperplasia 2 P's 1P
Pituitary (70%) Parathyroid (60%) Phaeochromocytoma
Pancreas (50%): e.g. insulinoma, Phaeochromocytoma
gastrinoma (leading to recurrent Marfanoid body
peptic ulceration) habitus
Neuromas
Also: adrenal and thyroid
MEN1 gene RET oncogene RET oncogene
Most common presentation =

hypercalcaemia
Diabetic foot disease
Diabetic foot disease is an important complication of diabetes mellitus which should

be screen for on a regular basis. NICE produced guidelines relating to diabetic foot
disease in 2015.
It occurs secondary to two main factors:
 neuropathy: resulting in loss of protective sensation (e.g. not noticing a

stone in the shoe), Charcot's arthropathy, dry skin
 peripheral arterial disease: diabetes is a risk factor for both macro and
microvascular ischaemia
Presentations
 neuropathy: loss of sensation

 ischaemia: absent foot pulses, reduced ankle-brachial pressure index (ABPI),
intermittent claudication
 complications: calluses, ulceration, Charcot's arthropathy, cellulitis,
osteomyelitis, gangrene
All patients with diabetes should be screened for diabetic foot disease on at least an
annual basis
 screening for ischaemia: done by palpating for both the dorsalis pedis pulse
and posterial tibial artery pulse
 screening for neuropathy: a 10 g monofilament is used on various parts of
the sole of the foot
NICE recommend that we risk stratify patients:
Low risk Moderate risk High risk

• no risk factors • deformity or • previous ulceration or
except callus alone • neuropathy or • previous amputation or
• non-critical limb • on renal replacement therapy or
ischaemia. • neuropathy and non-critical limb
ischaemia together or
• neuropathy in combination with callus
and/or deformity or
• non-critical limb ischaemia in
combination with callus and/or
deformity.
All patients who are moderate or high risk (I.e. any problems other than simple
calluses) should be followed up regularly by the local diabetic foot centre.
Corticosteroids
Corticosteroids are amongst the most commonly prescribed therapies in clinical

practice. They are used both systemically (oral or intravenous) or locally (skin
creams, inhalers, eye drops, intra-articular). They augment and in some cases
replace the natural glucocorticoid and mineralocorticoid activity of endogenous
steroids.
The relative glucocorticoid and mineralocorticoid activity of commonly used

steroids is shown below:
Minimal Predominant Very high

glucocorticoid Glucocorticoid glucocorticoid glucocorticoid
activity, very high activity, high activity, low activity, minimal
mineralocorticoid mineralocorticoid mineralocorticoid mineralocorticoid
activity, activity, activity activity
Fludrocortisone Hydrocortisone Prednisolone Dexamethasone
Betmethasone
Side-effects
The side-effects of corticosteroids are numerous and represent the single greatest
limitation on their usage. Side-effects are more common with systemic and
prolonged therapy.
Glucocorticoid side-effects
 endocrine: impaired glucose regulation, increased appetite/weight gain,

hirsutism, hyperlipidaemia
 Cushing's syndrome: moon face, buffalo hump, striae
 musculoskeletal: osteoporosis, proximal myopathy, avascular necrosis of the
femoral head
 immunosuppression: increased susceptibility to severe infection,
reactivation of tuberculosis
 psychiatric: insomnia, mania, depression, psychosis
 gastrointestinal: peptic ulceration, acute pancreatitis
 ophthalmic: glaucoma, cataracts
 suppression of growth in children
 intracranial hypertension
Mineralocorticoid side-effects
 fluid retention
 hypertension
Selected points on the use of corticosteroids:
 patients on long-term steroids should have their doses doubled during

intercurrent illness
 the BNF suggests gradual withdrawal of systemic corticosteroids if patients
have: received more than 40mg prednisolone daily for more than one week,
received more than 3 weeks treatment or recently received repeated courses
Thyroid eye disease
Thyroid eye disease affects between 25-50% of patients with Graves' disease.
Pathophysiology
 it is thought to be caused by an autoimmune response against an

autoantigen, possibly the TSH receptor → retro-orbital inflammation
 the inflammation results in glycosaminoglycan and collagen deposition in
the muscles
Prevention
 smoking is the most important modifiable risk factor for the development of
thyroid eye disease
 radioiodine treatment may increase the inflammatory symptoms seen in
thyroid eye disease. In a recent study of patients with Graves' disease around
15% developed, or had worsening of, eye disease. Prednisolone may help
reduce the risk
Features
 the patient may be eu-, hypo- or hyperthyroid at the time of presentation

 exophthalmos
 conjunctival oedema
 optic disc swelling
 ophthalmoplegia
 inability to close the eye lids may lead to sore, dry eyes. If severe and
untreated patients can be at risk of exposure keratopathy
Management
 topical lubricants may be needed to help prevent corneal inflammation

caused by exposure
 steroids
 radiotherapy
 surgery
Monitoring patients with established thyroid eye disease
For patients with established thyroid eye disease the following symptoms/signs
should indicate the need for urgent review by an ophthalmologist (see EUGOGO
guidelines):
 unexplained deterioration in vision

 awareness of change in intensity or quality of colour vision in one or both
eyes
 history of eye suddenly 'popping out' (globe subluxation)
 obvious corneal opacity
 cornea still visible when the eyelids are closed
 disc swelling

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Diabetic neuropathy

NICE updated it's guidance on the management of neuropathic pain in 2013.

 first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin

 symptoms include erratic blood glucose control, bloating and vomiting

Maturity-onset diabetes of the young (MODY) is characterised by the development

 typically develops in patients < 25 years

mnemonic DISCO helps me remember (Digoxin, isoniazid, spironolactone,

Gynaecomastia describes an abnormal amount of breast tissue in males and is

 physiological: normal in puberty

Drug causes of gynaecomastia

Very rare drug causes of gynaecomastia

MEN type I MEN type IIa MEN type IIb

Most common presentation =

Diabetic foot disease

Diabetic foot disease is an important complication of diabetes mellitus which should

It occurs secondary to two main factors:

 neuropathy: resulting in loss of protective sensation (e.g. not noticing a

 neuropathy: loss of sensation

NICE recommend that we risk stratify patients:

Low risk Moderate risk High risk

Corticosteroids are amongst the most commonly prescribed therapies in clinical

The relative glucocorticoid and mineralocorticoid activity of commonly used

Minimal Predominant Very high

 endocrine: impaired glucose regulation, increased appetite/weight gain,

Selected points on the use of corticosteroids:

 patients on long-term steroids should have their doses doubled during

Thyroid eye disease

 it is thought to be caused by an autoimmune response against an

 the patient may be eu-, hypo- or hyperthyroid at the time of presentation

 topical lubricants may be needed to help prevent corneal inflammation

Monitoring patients with established thyroid eye disease

 unexplained deterioration in vision

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