Diabetic Polyneuropathy: Causes

Pathogenesis (disease development)

The pathophysiology of diabetic polyneuropathy is not yet fully understood. However, several factors that attack and damage the nerves are considered proven:

  • Microangiopathy (disease of the small blood vessels) of the vasa nervorum (small blood vessels supplying the nerves).
  • Direct metabolic-toxic damage to neurons by various substances (such as sorbitol and fructose) produced during glucose metabolism and by oxygen radicals.
  • Inflammatory processes (inflammatory processes): due to the formation of “advanced glycation end-products” (AGE) and mitochondrial dysfunction, oxidative stress occurs with the consequence that it comes to DNA damage and thus also to cell necrosis (cell death).
  • Dysfunctional Schwann cell interaction

The damage manifests as demyelination (demyelination of nerves) and degeneration of neurons. Diabetic neuropathy is divided into:

  • Peripheral sensorimotor diabetic polyneuropathy (synonym: diabetic sensorimotor polyneuropathy, DSPN): the distribution in this polyneuropathy is distal and symmetrical (hands and feet are affected) (= distal symmetric polyneuropathy); typical symptoms are: Paresthesias (sensory disturbances) and neurogenic pain. Furthermore, reduction of touch, pain and temperature sensation and weakened or absent Achilles tendon reflex (ASR, also triceps-surae reflex); in the late stages occur paralysis.
  • autonomic diabetic neuropathy (ADN; autonomic neuropathy): affected here:
    • Cardiovascular system (cardiovascular system) in terms of cardiovascular autonomic diabetic neuropathy (CADN); symptoms: tachycardia (heartbeat too fast: > 100 beats per minute), orthostatic hypotension (low blood pressure), lack of respiratory variability of heart rate → cardiovascular autonomic neuropathy (CADN).
    • Gastrointestinal tract/gastrointestinal tract; symptoms: slowed gastric emptying with gastroparesis (gastric paralysis) or diabetic diarrhea (diarrhea) → gastrointestinal tract autonomic neuropathy.
    • Genitourinary tract: diabetic cystopathy (diabetic bladder disease; bladder emptying disorder); symptoms: Bladder atony (flaccidity of the bladder muscles), micturition disorders (bladder dysfunction) erectile dysfunction (ED; erectile dysfunction) → autonomic neuropathy at the urogenital tract.
    • Neuroendocrine system: lack of catecholamine release (norepinephrine and dopamine, as well as epinephrine and its derivatives) during orthostasis (ability to adjust blood pressure in the upright position) and stress; lack of counterregulation during hypoglycemia (low blood sugar) → autonomic neuropathy of the neuroendocrine system.
    • Impaired pupillary reflexes (slowed mydriasis = unilateral or bilateral dilatation of the pupil).
    • Decrease in sweat secretion; symptoms: dry feet.
  • Focal neuropathy; here, failures of individual peripheral and radicular nerves due to infarction of the vasa nervorum. This leads, among other things, to cranial nerve palsies (III, IV, VII), diabetic amyotrophy (usually unilateral (one-sided) upper lumbosacral plexopathy, LSP; pain syndrome) and mononeuritis multiplex (inflammation of individual nerves at different sites in the body). The most common diabetic focal neuropathy is lumbosacral plexus neuropathy (diabetic amyotrophy), which is usually unilateral and results in weakness in the leg with muscle wasting. Symptoms include severe pain in the thigh, buttock or leg.

It has now also been demonstrated that the changes do not only occur in the peripheral nerves, but that structural changes also occur in the CNS (central nervous system). Imaging techniques, for example, show circumscribed atrophy in the spinal cord, and MR spectroscopy can also detect neuronal dysfunction (malfunction) in the thalamus (diencephalon).

Etiology (causes)

Biographic causes

  • Age of life – with increasing age.

Behavioral causes

  • Nutrition
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • Consumption of stimulants
    • Alcohol
    • Tobacco (smoking); moderate association between smoking and diabetic peripheral neuropathy (DPN).
  • Physical activity
    • Lack of physical activity
  • Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type)-there is a high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)); increased abdominal fat has a strong atherogenic effect and promotes inflammatory processes (“inflammatory processes”)When measuring waist circumference according to the International Diabetes Federation guideline (IDF, 2005), the following standard values apply:
    • Men < 94 cm
    • Women < 80 cm

    The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.

Disease-related causes, including risk factors and comorbidities (concomitant diseases) for the development of diabetic polyneuropathy.

  • Diabetes mellitus (long duration, poor adjustment (hyperglycemia/ hypoglycemia); presence of retino- and nephropathy already, if applicable).
  • Arterial hypertension (high blood pressure).
  • Depression
  • Dyslipidemia/hyperlipidemia (lipid metabolism disorder)
  • Mediasclerosis (von Mönckeberg) or medial calcinosis (calcification of the middle wall layer (tunica media) of the extremity arteries).
  • Peripheral arterial occlusive disease (pAVK; progressive stenosis (narrowing) or occlusion (closure) of the arteries supplying the arms / (more often) legs, usually due to atherosclerosis (arteriosclerosis, arteriosclerosis)).

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.