By Dr Sajad Ahmad MRCGP FHEA
Diabetic neuropathy is one of the commonest complications of diabetes1 and is frequently managed by family physicians in the primary care setting. 90% of diabetic patients suffer from diabetic neuropathy2. While the risk of amputations due to peripheral neuropathy is 25 times more than in non-diabetic population3, it can present with or without pain, greatly affecting the quality of life for the patients as well as leading to morbidity and mortality in many individuals. Its diagnosis and appropriate management is important for the overall health of our patients. Many studies have looked at the various types of neuropathies in both diabetic and non-diabetic population and its presentation, and management has been discussed in detail. In this paper, I have attempted to summarise various types of neuropathies observed in diabetic patients in a simplistic manner. I carried out a review of literature search online and summarised different aspects of the available articles to present a broader and clearer and an up-to-date understanding to the readers.
Why is treating neuropathies important?
The importance of early diagnosis is paramount in diabetic patients for a number of reasons; firstly, non-diabetic neuropathies can occur in diabetic patients. Secondly, in diabetic patients neuropathies can be asymptomatic, which can lead to injuries that the patient may not be aware. There have been suggestions of lifetime risk of 15% – 25% in patients with distal neuropathy to develop an ulcer or gangrene14. Some pre-diabetics may also display these features, and often patients are asymptomatic, this does not rule out the absence of neuropathy, hence diagnostic procedures like quantitative electrophysiology, sensory and autonomic nerve testing / Nerve conduction studies may be required to establish the diagnosis (5). Thirdly, systemic neuropathies in diabetic patients can lead to multiple co-morbidities and mortality amongst patients.
Classification of neuropathies
The most agreed upon, the common definition of Diabetic Neuropathy is; “The presence of symptoms and/or signs of nerve dysfunction in people with diabetes after exclusion of other causes” (4). The presentation of neuropathies is heterogeneous among the population; symptoms can vary according to the involvement of organs, anatomical area and distribution, risk variables, or pathological effects. (5). Many authors have presented different classifications which aim to clarify the types of neuropathies that present in diabetic patients, some authors have attempted to divide them into general and focal distribution for ease of classification (6), while others have also differentiated on the basis of onset as well as hyperglycaemia as a causative factor (7). For the purposes of simplifying the classification, I have attempted to discuss some these versions of classification which have been presented by some authors before. In broader classification neuropathies can be divided into Sensory (acute and chronic), Focal and Multifocal and Autonomic neuropathies (6). The sensory neuropathies, which can be focal, or multifocal can also be termed as distal symmetrical polyneuropathy, these are called so, because of their presentation affecting the feet first in a stocking distribution.
(Diabetic Sensory and Motor Neuropathy)
A classical presentation of sensory neuropathy can be as noted in the example above. Patients often present with the symptoms and at times these symptoms can be quite distressing. The symptoms of sensory neuropathy can be in many forms, some can be focal, or involve multiple nerves as mentioned earlier. The commonest form usually start distally, the feet are affected first and would gradually extending to the lower legs, they are symmetrical in nature.
This is perhaps the commonest type encountered in general practice. While the description of the pain is dependent on the patients. Many have given various definitions for this, some calling it painful distal polyneuropathy5. The majority of the patients describe the pain as a pricking, burning type, sharp pain that is usually worse in the night. Although symptoms usually involve the lower limbs, arms can also be affected. Occurring distally in a symmetric distribution a decrease in sensations can be observed. Treatments usually are with tricyclics and anticonvulsants as well as serotonin reuptake inhibitors to control the symptoms. Tramadol and opiates can also be used in some cases (13)
Diabetic Symmetrical Polyneuropathy (DSPN)
Both, Thomas and Boulton (4,6,7) have opted to divide the classification in a slightly different manner.
They suggest that the classification should be done as generalised and focal or multifocal manner. It is the generalised type that Boulton (6) suggested dividing further into two major subgroups (9), 1– A chronic symmetrical length-dependent sensorimotor polyneuropathy (DSPN) and 2– atypical diabetic polyneuropathy (DPN) which is less common than DSPN. The key differences between the two sub-groups are the onset, length of time of the condition and its relationship to hyperglycaemias as well as symptoms of pain. DSPN is the commonest type and more long standing. It is known to occur with prolonged episodes of hyperglycaemia as well as has been associated with metabolic changes and is associated with cardiovascular risk factors (10). Although neuropathic symptoms of pain and autonomous symptoms may develop over time, as with its worsening due to prolonged hyperglycaemias, tighter control of blood sugar has shown improvements in this neuropathy (11). Boulton et al suggested the use of nerve conduction study as early as possible the recognition of the neuropathies although the in DSPN this can often be subclinical (5).
As with its occurrence, we need to understand what the diagnosis and the severity actually mean for the patients, and the impact the condition has on their day-to-day life. Dyke suggested grading criteria for the different stages according to the severity. These are five grades ranging from zero being normal with no abnormality on Nerve conduction study to grade 2b [abnormality of nerve conduction with a moderate degree of weakness at 50% of ankle dorsiflexion with or without any neuropathy. In summary, grading is closely associated with the severity of signs and symptoms and the findings of nerve conduction study (12). The definitions and diagnosis of typical DSPN can be further divided, It has been suggested that the signs and symptoms of decreased sensation with neuropathic symptoms such as pain, burning sensation particularly in the lower legs, with a decrease in absent reflexes can be termed as a Possible DSPN. Symptoms and symptoms progressing to two or more of the above is Probably DSPN. While DSPN can be confirmed with the above and an abnormality of Nerve conduction. This does tell us that there are instances when nerve conduction may be normal; in these cases, a small fibre neuropathy measure can be used as long as it is validated.
Atypical Diabetic Polyneuropathies
These are less common, its occurrence may be acute, or chronic. These may be monophasic or may fluctuate with time, as the occurrence may be acute or chronic they can occur at any time in the course of the illness (7). In addition to these major differentiating features, pain and autonomic features are more pronounced in these (7). These can be classified as polyneuropathies, we will try to discuss some of these below.
Painful diabetic polyneuropathy
It is associated with pain directly due to the consequence of an abnormality in peripheral somatosensory system in people with diabetes and round 25% people may experience this type of pain15,16. For clinical presentation the symptoms of painful neuropathy may not be any different than what is described in the clinical scenarios above, pain is usually prickling and deep aching, and can be described as debilitating and electric shock-like or burning in nature. For its management, it’s important to assess the severity of the pain and the effect it has on the patients quality of life. There are a number of pain questionnaires that can be used to do these assessments in general practice or while seeing the patients in sub-speciality17.
Management of neuropathic pain can be slightly tricky as the conventional medication would usually be of no help. The national institute of clinical excellence (NICE) recommends18 discussing the expectations of the patient as well as possible outcomes and side-effects of the medication. The effect on their lifestyle, sleep disturbances, the severity of the pain should all be discussed. Management can also include non-pharmacological therapies and lifestyle changes. Pharmacological management includes tricyclics, amitriptyline, duloxetine, gabapentin, pregabalin as the first trial medication. In general, Morphine containing medication or cannabis, etc should be avoided20.
Diabetic Autonomic Neuropathy
Autonomic neuropathies can have systemic involvement, with cardiac, gastrointestinal, genitourinary systems commonly affected and can lead to arrhythmias and sudden death in patients (8). This makes managing of these ever so important.
Its prevalence may vary amongst patients and depends upon glycemic control, blood pressure, obesity, smoking and lipids. It can be associated with a significant amount of mortality and can cause coronary artery disease including ischemia and stroke. Patients with diabetes suffering from unexplained tachycardia, unexplained tiredness and hypotension should be reviewed for cardiovascular neuropathy.
Gastrointestinal autonomic neuropathy
is usually the diagnosis of exclusion; this is so because it is one of the difficult conditions to diagnose in patients. It may be associated with impaired oral medication absorption as well as poor glycemic control, and postprandial signs including abnormal blood pressure.
due to smooth muscle alteration and neuronal dysfunction can be a common complication of neuropathy. Common symptoms can often be confused with a urinary tract infection and include, nocturia, dysuria, frequency, urgency and incomplete bladder emptying.
is one of the commonest presentations of the urogenital system (5).
The above is no way a comprehensive list of classifications or of definitions, but rather the commonest forms of neuropathies related to diabetes in. The majority of these can be seen in our day to day general practice. The idea here is to revise these topics further for a better understanding of the topic.
- Van Acker K, Bouhassira D, De Bacquer D, Weiss S, Matthys K, Raemen H, Mathieu C, Colin IM. Prevalence and impact on quality of life of peripheral neuropathy with or without neuropathic pain in type 1 and type 2 diabetic patients attending hospital outpatients clinics. Diabetes & metabolism. 2009 Jun 30;35(3):206-13.
- Schreiber AK, Nones CF, Reis RC, Chichorro JG, Cunha JM. Diabetic neuropathic pain: Physiopathology and treatment. World journal of diabetes. 2015 Apr 15;6(3):432.
- Nerve disease (Diabetes Complications) International Diabetes Federation 2015, available online http://www.idf.org/complications-diabetes accessed on 1st March 2017
- Boulton AJ, Gries FA, Jervell JA. Guidelines for the diagnosis and outpatient management of diabetic peripheral neuropathy. Diabetic Medicine. 1998 Jun 1;15(6):508-14.
- Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes care. 2010 Oct 1;33(10):2285-93.
- Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D. Diabetic neuropathies. Diabetes care. 2005 Apr 1;28(4):956-62.
- Thomas PK. Classification, differential diagnosis, and staging of diabetic peripheral neuropathy. Diabetes. 1997 Sep 1;46(Supplement 2):S54-7.
- Deli G, Bosnyak E, Pusch G, Komoly S, Feher G. Diabetic neuropathies: diagnosis and management. Neuroendocrinology. 2014 Jan 22;98(4):267-80.
- Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, Wilson DM, O’brien PC, Melton L. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population‐based cohort The Rochester Diabetic Neuropathy Study. Neurology. 1993 Apr 1;43(4):817-.
- Giannini C, Dyck PJ. Ultrastructural morphometric abnormalities of sural nerve endoneurial microvessels in diabetes mellitus. Annals of neurology. 1994 Sep 1;36(3):408-15.
- Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH. Vascular risk factors and diabetic neuropathy. New England Journal of Medicine. 2005 Jan 27;352(4):341-50.
- Dyck PJ. Detection, characterization, and staging of polyneuropathy: assessed in diabetics. Muscle & nerve. 1988 Jan 1;11(1):21-32.
- Tesfaye S. Advances in the management of diabetic peripheral neuropathy. Current opinion in supportive and palliative care. 2009 Jun 1;3(2):136-43.
- Vinik AI. Diabetic sensory and motor neuropathy. New England Journal of Medicine. 2016 Apr 14;374(15):1455-64.
- Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J. Neuropathic pain redefinition and a grading system for clinical and research purposes. Neurology. 2008 Apr 29;70(18):1630-5.
- Boulton AJ, Malik RA, Arezzo JC, Sosenko JM. Diabetic somatic neuropathies. Diabetes care. 2004 Jun 1;27(6):1458-86.
- Cruccu G, Sommer C, Anand P, Attal N, Baron R, Garcia‐Larrea L, Haanpaa M, Jensen TS, Serra J, Treede RD. EFNS guidelines on neuropathic pain assessment: revised 2009. European Journal of Neurology. 2010 Aug 1;17(8):1010-8.
- NICE Clinical Guidance CG173, Neuropathic pain in adults : Pharmacological management in non-specialist setting. Nov 2013 updated Feb 2017.
- Selvarajah D, Gandhi R, Emery CJ, Tesfaye S. Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy. Diabetes care. 2010 Jan 1;33(1):128-30.