Diabetic sensorimotor polyneuropathy

Diabetic sensorimotor Polyneuropathy (DSPN) is the most common and clinically most significant manifestation of diabetic neuropathies. Around one in three people with diabetes is affected by DSPN. It may be symptomatic or asymptomatic.

Typical symptoms

The symptomatic form is characterised by discomfort in the feet or hands, which usually worsens at night or at rest.

The following symptoms may occur:

  • Burning/pain
  • Tingling paraesthesia
  • Numbness.
  • Feeling of weakness.
  • Cramps.

 

Dangerous: “silent” progression.

The asymptomatic form of DSPN affects up to 50% of patients.1 It is also clinically significant, as neuropathic deficits are involved in the development of diabetic foot syndrome in 85 - 90% of cases.2 For instance, patients with diabetic neuropathy often only notice injuries to their feet at a late stage due to reduced or absent sensitivity.

Typical deficits are:

  • Reduced sensitivity to vibration and/or touch.
  • Reduced perception of pain and/or temperature.
  • Reduced muscle reflexes.

 

Earlier diagnosis required!

Diabetic neuropathy was long regarded as a late complication of diabetes. We now know that the degeneration of the nerves begins in the pre-diabetic stage and continues as the disease progresses3. In many type 2 diabetics, DSPN can be detected at the time of diabetes diagnosis or less than a year later4.

However, many people with DSPN do not realise that they have a nerve dysfunction - especially if they are asymptomatic or have subtle symptoms5,6,7. Regular screening and earlier diagnosis and therapy are therefore urgently required!

Autonomic neuropathy

In principle, autonomic diabetic neuropathy (ADN) can affect any autonomously innervated organ system, e.g. the cardiovascular system, the gastrointestinal or urogenital tract. Since DSPN and ADN often occur simultaneously, possible ADN manifestations should always be considered when a sensorimotor neuropathy is detected. Up to 50% of diabetics with DSPN also have cardiovascular autonomic diabetic neuropathy2.

The following symptoms can be indicative in the diagnosis of ADN, albeit with low specificity and sensitivity8:

  • Resting tachycardia
  • Gastrointestinal disorders (dyspeptic symptoms, constipation, diarrhoea, faecal incontinence)
  • Bladder dysfunction, sexual dysfunction
  • impaired hypoglycaemia perception
  • Sweat secretion disorders
  • Blood glucose fluctuations that are not otherwise justified.

These symptoms of ADN should also be asked about when establishing the anamnesis of diabetics.

Causes

One disease - many nerve-damaging factors

Hyperglycaemia is the main cause of diabetic polyneuropathy. This results in oxidative stress and activates pathogenic processes, such as the formation of AGEs (Advanced Glycation Endproducts). This leads to circulatory disorders and morphological changes in the nerves9. Other risk factors such as obesity, high blood pressure, hyperlipidaemia, peripheral arterial occlusive disease (PAOD), alcohol and nicotine abuse, lack of physical activity and obesity can also favour the development of neuropathy2.

Vitamin B deficiency in patients with diabetes

It should be noted that a vitamin B1 deficiency can also cause or exacerbate neuropathies. A vitamin B1 deficiency leads to complex metabolic disorders that can exacerbate the toxic effects of hyperglycaemia10. As the renal excretion of vitamin B1 is often increased in diabetics, they are at increased risk of a deficiency. In a British study, vitamin B1 plasma levels in type 1 and type 2 diabetics were found to be on average 75% lower than in healthy people11.

A vitamin B12 deficiency is also associated with an increased risk of neuropathies. It occurs more frequently as a result of long-term therapy with metformin12,13.

Important risk factors at a glance

 

  • Diabetes duration and management
  • Arterial hypertension
  • PAOD
  • Hyperlipidaemia
  • Alcohol and nicotine
  • Vitamin B1 and B12 deficiency
  • Age, height and weight

 

Bibliography:

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  2. Zieger D, Keller J, Maier C, Pannek J. DDG Praxisempfehlungen (practice recommendations). Diabetic neuropathy. Diabetologie 2020; 15 (Suppl 1): p181–p195
  3. Ziegler D, Papanas N, Vinik AI, Shaw JE. Epidemiology of polyneuropathy in diabetes and prediabetes. Handb Clin Neurol. 2014;126:3-22.
  4. Ziegler D, Papanas N, Zhivov A, Allgeier S, Winter K, Ziegler I, Brüggemann J, Strom A, Peschel S, Köhler B, Stachs O, Guthoff RF, Roden M; German Diabetes Study (GDS) Group. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes. 2014;63(7):2454-63.
  5. Ziegler D, Strom A, Lobmann R, Reiners K, Rett K, Schnell O. High prevalence of diagnosed and undiagnosed polyneuropathy in subjects with and without Diabetes participating in a nationwide educational initiative (PROTECT-Study). J Diabetes Complications. 2015;29(8):998-1002.
  6. Ziegler D, Landgraf R, Lobmann R, Reiners K, Rett K, Schnell O, Strom A. Painful and painless neuropathies are distinct and largely undiagnosed entities in subjects participating in an educational initiative (PROTECT-Study). Diabetes Res Clin Pract. 2018;139:147-154.
  7. Bongaerts BW, Rathmann W, Heier M, Kowall B, Herder C, Stöckl D, Meisinger C, Ziegler D. Older subjects with diabetes and prediabetes are frequently unaware of having distal sensorimotor polyneuropathy: the KORA F4 study. Diabetes Care. 2013;36(5):1141-6.
  8. German Medical Association (BÄK), National Association of Statutory Health Insurance Physicians (KBV), Association of the Scientific Medical Societies in Germany (AWMF). National care guidelines for neuropathy in adult diabetes - long version, 1st edition. Version 5. 2011.
  9. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54(6):1615-25.
  10. Page GL, Laight D, Cummings MH. Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease. Int J Clin Pract. 2011;65(6):684-90.
  11. Thornalley PJ, Babaei-Jadidi R, Al Ali H, Rabbani N, Antonysunil A, Larkin J, Ahmed A, Rayman G, Bodmer CW. High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia. 2007;50(10):2164-70.
  12. Niafar M, Hai F, Porhomayon J, Nader ND. The role of metformin on vitamin B12 deficiency: a meta-analysis review. Intern Emerg Med. 2015 Feb;10(1):93-102.
  13. Damião CP, Rodrigues AO, Pinheiro MF, Cruz RA Filho, Cardoso GP, Taboada GF, Lima GA. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J. 2016;134(6):473-479.