Blood Sugar and Nerve Health: How High Glucose Damages Nerves and What Protects Them

How nerves are damaged

Peripheral nerves are long, thin cells, and in diabetes they are under constant metabolic strain. A single nerve fibre running from the spine to the toe can be a metre long, and keeping that length alive depends on a constant supply of energy and blood. High glucose attacks both.

Metabolic injury. Nerve cells take up glucose without needing insulin, so when blood glucose is high, so is glucose inside the nerve. Processing the excess through alternative pathways generates oxidative stress, depletes the cell's antioxidant reserves, produces sugar alcohols that draw in water and disturb the cell's chemistry, and creates glycated proteins that interfere with nerve structure and signalling.

Vascular injury. Each nerve is fed by a network of tiny vessels (the vasa nervorum). High glucose thickens and narrows them in the same way it damages the vessels of the retina and kidney (see how high blood sugar affects the body). The nerve becomes starved of oxygen, and repair falls behind damage.

Why the feet first. The longest fibres have the most territory to maintain and the greatest exposure. Damage accumulates from the far end backward, which is why symptoms start in the toes, spread up the feet and legs in a "stocking" pattern, and only later reach the fingers in a "glove" pattern.

The risk of neuropathy rises with the duration of diabetes and with how high glucose has been. It is also worsened by high triglycerides, obesity, smoking, high blood pressure and alcohol — which is why nerve health is not only about glucose.

The types of diabetic neuropathy

Peripheral neuropathy is the commonest, affecting sensation and later movement in the feet and hands. Symptoms: tingling, pins and needles, burning, sharp or shooting pain (often worse at night), heightened sensitivity to touch, and — as it progresses — numbness and loss of sensation. Balance suffers because the feet no longer report the ground accurately.

Autonomic neuropathy affects the nerves that regulate internal organs. Depending on which are affected: slow stomach emptying (gastroparesis) with bloating and nausea; constipation or diarrhoea; difficulty emptying the bladder; dizziness on standing as blood pressure fails to adjust; a fixed, fast heart rate; reduced sweating; and erectile dysfunction, which affects a majority of men with long-standing diabetes. Autonomic neuropathy also blunts the warning signs of low blood sugar, which is dangerous for people on insulin.

Focal neuropathies affect single nerves, causing sudden weakness or pain in one area — a drooping eyelid, double vision, carpal tunnel syndrome, or pain in the thigh. Many improve over months.

Proximal neuropathy (diabetic amyotrophy) causes pain and weakness in the hips and thighs, usually on one side, and usually in older men with type 2 diabetes. It typically improves slowly.

Why it is dangerous

Loss of sensation is more dangerous than pain. A person who cannot feel the sole of their foot does not notice a stone in a shoe, a blister, a burn from a hot bath, or a cut. The injury goes untreated, infection develops, poor circulation slows healing, and a foot ulcer forms. Foot ulcers precede most diabetes-related amputations. Almost all of this is preventable with daily foot inspection, properly fitting footwear and prompt attention to any wound.

Early signs

The earliest signs are subtle and easy to attribute to shoes, age or posture:

• tingling or "buzzing" in the toes, especially at night
• a feeling of walking on cotton wool or pebbles
• burning soles
• reduced ability to feel temperature in the feet
• unexplained blisters or sores
• unsteadiness in the dark or with eyes closed

At the diabetes annual review, the feet are examined with a monofilament (a thin nylon fibre pressed against the skin) and a tuning fork to test pressure and vibration sensation. Loss of either is an early, objective sign.

What protects nerves

Glucose control — measured over time by A1C — is the only intervention shown to prevent diabetic neuropathy. In type 1 diabetes, intensive control reduced the development of neuropathy by about 60% in the landmark DCCT trial; in type 2 diabetes the effect is smaller but real, and the UKPDS found fewer microvascular complications overall with tighter control. Avoiding large swings in glucose may matter as well as the average.

Cardiovascular risk factors. Treating high blood pressure and high triglycerides, stopping smoking and limiting alcohol all reduce neuropathy risk.

Weight loss and exercise improve nerve function measures in trials of people with prediabetes and insulin resistance and early neuropathy, probably through better glucose, better blood flow and reduced inflammation.

Vitamin B12. Metformin reduces B12 absorption; deficiency causes neuropathy of its own and can compound diabetic neuropathy. People on long-term metformin should have B12 checked periodically, and certainly if nerve symptoms appear.

Foot care. Daily inspection (using a mirror for the soles), moisturising dry skin but not between the toes, well-fitting shoes, never walking barefoot, and prompt professional attention to any break in the skin.

Treatment once neuropathy is established

Treatment has two aims: relieving symptoms and preventing injury.

Pain relief. First-line medications are certain antidepressants (duloxetine, amitriptyline) and anticonvulsants (pregabalin, gabapentin), which act on nerve signalling rather than on pain in the ordinary sense. Topical capsaicin and lidocaine help some people. Ordinary painkillers are usually ineffective, and opioids are avoided because of dependence risk and limited benefit.

Autonomic symptoms are treated individually: dietary changes and medication for gastroparesis, compression and medication for dizziness on standing, PDE5 inhibitors for erectile dysfunction.

Physical therapy and balance training reduce falls.

Supplements. Alpha-lipoic acid at 600 mg per day has reduced pain and paraesthesia in several trials of diabetic neuropathy, with a modest effect; it is prescribed in some countries. Evidence for benfotiamine (a form of vitamin B1) and acetyl-L-carnitine is weaker. These address symptoms, not the underlying damage, and should be discussed with the prescriber managing your diabetes, since alpha-lipoic acid can lower glucose; see Can supplements lower blood sugar? for the evidence.

When to see a doctor

Report new tingling, numbness, burning or pain in the feet at your next review, and sooner if it is progressing. See a doctor promptly for any sore, blister or cut on the foot that is not healing within a few days, any change in the colour or temperature of a foot, or dizziness on standing, unexplained digestive symptoms or urinary difficulty. A foot that is red, hot, swollen and painful, with or without a wound, needs same-day assessment.

Frequently asked questions

References