At least half of all people with diabetes develop neuropathy, making it one of the most common diabetes complications. Rodica Pop-Busui, MD, PhD, the Larry D. Soderquist professor of diabetes and vice chair of clinical research at the University of Michigan Medical School’s Department of Internal Medicine, shares insights about caring for patients with peripheral and autonomic neuropathy.

Q: What is diabetic neuropathy, and how common is it?

A: Diabetic neuropathy is nerve damage and dysfunction caused by diabetes. In fact, diabetes is the most common cause of neuropathy overall.

Neuropathy typically develops over several years, as high levels of glucose and fats in the blood damage nerves and small blood vessels that supply oxygen and nutrients. It is more common in adults than children. People with diabetic neuropathy can have a significant decline in quality of life, with symptoms such as severe, burning pain; loss of sensation, which can lead to loss of balance, trouble walking, falls, and fractures; and foot ulcers, which, if infected, may result in foot or leg amputations.

People may also develop poor sleep, depression, and anxiety and may not be able to do normal daily activities. They are also at increased risk of cardiovascular complications such as arrhythmias and heart failure, as well as gastrointestinal and urological complications and death.

Q: What types of neuropathy occur in people with diabetes?

A: The most common type of neuropathy in people with diabetes is peripheral neuropathy, caused by nerve damage affecting the feet and legs and sometimes the hands and arms. Another common type is autonomic neuropathy, which is damage to nerves that control internal organs. Autonomic neuropathy can affect the cardiovascular system—that’s called cardiovascular autonomic neuropathy, or CAN—as well as the gastrointestinal tract, bladder, sweat glands, sex organs, and eyes. It can also affect the ability of people with diabetes to sense hypoglycemia.

Q: What are the primary risk factors for diabetic neuropathy?

A: The chance of developing neuropathy increases with inadequate glucose control, older age, and longer duration of diabetes. For example, at least 10% to 15% of patients who are newly diagnosed with diabetes may have peripheral neuropathy, with the rate increasing to 50% after 10 years of having diabetes. Other risk factors include obesity, tall height, high blood pressure, high cholesterol, advanced kidney disease, smoking, and drinking too much alcohol.

It’s worth noting the significant racial and ethnic disparities in patients with diabetic neuropathy. Although data on the risk of neuropathy in racial and ethnic minority groups is relatively scarce, a wealth of evidence shows disproportionally worse outcomes and higher rates of amputations in African American, Hispanic, and Native American patients with diabetic foot ulcers, compared with white patients with diabetic foot ulcers. (Most diabetic foot ulcers are due to peripheral neuropathy.)

Q: How can diabetic neuropathy be prevented or delayed?

A: Glycemic control is important, particularly in people with type 1 diabetes. Based on evidence from well-designed clinical trials and studies, the American Diabetes Association (ADA) 2022 Standards of Medical Care recommend that people with type 1 diabetes keep their blood glucose levels in target range to prevent or delay peripheral neuropathy and CAN. In people with type 2 diabetes, adequate glucose control may modestly slow these conditions’ progression.

Research backs this up. The Diabetes Control and Complications Trial (DCCT) showed that people with type 1 diabetes who got intensive glucose-lowering treatment reduced their risk of neuropathy by 60%. The follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study showed that early and intensive blood glucose control during the DCCT lowered the risk of neuropathy by about 30%, 14 years after the DCCT ended.

However, in type 2 diabetes, intensive glucose control alone does not effectively prevent neuropathy. For these patients, we need a more comprehensive approach that targets other risk factors such as obesity, high lipid levels, high blood pressure, and smoking.

Exercise and lifestyle changes are emerging as effective ways to prevent and possibly reverse diabetic neuropathy. Ongoing research is evaluating the best exercise and behavioral regimens for health care professionals to recommend.

Q: What symptoms of peripheral neuropathy should health care professionals look for? What screening and diagnostic tests can they perform?

A: The main symptoms of peripheral neuropathy are burning or shooting pain and loss of sensation that start in the feet and progress upward. Patients may also report tingling (“pins and needles”), pain upon light touch, swelling, weakness, or feeling very hot or very cold.

The ADA Position Statement on Neuropathy and the 2022 Standards of Medical Care in Diabetes recommend that all patients be screened for peripheral neuropathy starting at diagnosis of type 2 diabetes and 5 years after diagnosis of type 1 diabetes, and then at least annually.

Health care professionals should examine a patient’s feet at least annually and ask patients to check their feet every day and report any sores, swelling, or other problems. You’ll want to rule out other possible causes of neuropathy such as thyroid or kidney disease, vasculitis, and vitamin B12 deficiency. For example, metformin can cause low vitamin B12 levels.

To diagnose peripheral neuropathy (PDF, 5 MB) , health care professionals can perform various tests using simple instruments and screening tools such as

• the Michigan Neuropathy Screening Instrument
• 128-Hz tuning fork test to check vibration sensation
• touch with a cool object to check temperature sensation
• touch with a sharp object to check pinprick sensation
• review of gait and balance
• 10-g monofilament test to assess protective sensation

Referral to a neurologist is needed only when a patient’s symptoms are atypical or the diagnosis is unclear.

Q: What symptoms of autonomic neuropathy should health care professionals look for?

A: Patients with diabetes who have microvascular complications, such as nephropathy, diabetic kidney disease, or retinopathy, should be assessed for autonomic neuropathy after 5 years of type 1 diabetes and when they are diagnosed with type 2 diabetes.

A patient’s symptoms and the diagnostic tests used depend on which organ(s) or system(s) is affected. For example, CAN may be completely asymptomatic in the earliest stages, with only decreased heart rate variability. In later stages, people may have other symptoms, including exercise intolerance, heart palpitations, dizziness, resting tachycardia, or orthostatic hypotension. If autonomic neuropathy affects the gastrointestinal system, your patient may develop constipation, diarrhea, or gastroparesis. If it affects the urogenital system, patients may have bladder problems, erectile dysfunction, or low libido.

Autonomic neuropathy can also cause hypoglycemia unawareness. Without treatment for low blood glucose, patients may develop life-threatening hypoglycemia.

Q: What are the treatment options for diabetic neuropathy? 

A: Once it occurs, nerve damage can’t be reversed. So, the treatment goals are to prevent neuropathy from getting worse, relieve pain and other symptoms, and improve quality of life.

Health care professionals should help patients keep their blood glucose levels in target range, manage blood pressure and cholesterol levels, and make changes in diet and exercise. In type 2 diabetes, specific classes of glucose-lowering medicines that target insulin resistance and chronic inflammation may be effective. For neuropathic pain, several classes of medicines have been shown to work. Newer management strategies include topical agents, lifestyle interventions, and high-frequency spinal cord stimulation. The ADA strongly warns against using opioids to treat pain associated with diabetic neuropathy, given their lack of efficacy and high risk of complications, addiction, and death.

Treatment of autonomic neuropathy depends on which organ or system is involved and a patient’s specific symptoms.

Q: What are the key areas in current research on diabetic neuropathy?

A: First and foremost is the development of safe and effective disease-modifying therapies for peripheral and autonomic neuropathy. We also need more effective, better-tolerated therapies for pain. I would also mention research on sensitive biomarkers for diabetic neuropathy and pain phenotypes in diabetic neuropathy.

How do you treat patients with diabetic neuropathy? Share below in the comments.