For the one in 10 Americans with diabetes, how to best manage and slow the progression of the disease is often a top concern.

Diabetes requires a lifelong commitment to having a healthy diet, exercising regularly and taking the right amount of insulin.

Poor disease management can lead to a multitude of serious and life threatening complications. But according to Rodica Pop-Busui, M.D., Ph.D., a researcher and endocrinologist at Michigan Medicine, not all diabetes is created equally and high blood sugar isn't the only culprit of significant complications.

Although intensive glucose control is important to stay as healthy as possible, Pop-Busui and her research team sought to understand why some people developed major complications while others didn't.

The answer may provide physicians better guidance on how they can differentiate patients and give effective, personalized care.

Published in the American Diabetes Association journal Diabetes, the largest study which most comprehensively phenotyped diabetic neuropathy, found that different factors, including blood sugar, body mass index, age and other complications, play different roles in the development of diabetic peripheral neuropathy and cardiac autonomic neuropathy.

In parallel, a study from Pop-Busui's endocrinology colleagues Kara Mizokami-Stout, M.D., and Lynn Ang, M.B.B.S., included thousands of patients with type 1 diabetes and reported similar findings: other factors aside from blood sugar, like gender, BMI, and socio-economic factors including annual income, access to medical insurance and level of education made a significant difference in a person's risk of developing diabetic neuropathy.

Quality of life

Diabetic peripheral neuropathy is nerve damage that affects sensations of pain, pressure and temperature. The condition also affects movement and strength, typically in the lower legs and feet, according to Pop-Busui.

This greatly affects a person's quality of life. The unsteadiness can result in injuries from falls. Driving becomes more difficult because of the loss of sensation or decreased strength in the feet, which impairs pedal control. The pain can disrupt sleep and affect mental health. And, as the condition progresses, a patient may even lose their foot.

"Diabetic peripheral neuropathy is one of the most prominent causes of foot ulceration and lower extremity amputations in the U.S.," she says. "And patients with this amputation are at a 50% higher risk for losing a second limb within the next two years."

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Symptoms of cardiovascular autonomic neuropathy are less obvious, or may not be present at all, says Pop-Busui. However, these abnormal heart rhythms increase the risk of an arrhythmia, which damages the heart and can lead to heart failure.

"We can't just tell a patient to only bring their blood sugar down," Mizokami-Stout says, who is also a member of the University of Michigan's Institute for Healthcare Policy and Innovation. "Glucose levels are important in diabetes management, but providers need to be aware of how access to quality care and socioeconomic factors affect a patient's outcome as well."

'We can't just tell a patient to only bring their blood sugar down'

Mizokami-Stout and Ang's study followed almost 6,000 adults with type 1 diabetes for more than 23 years through comprehensive questionnaires. Nearly 11% of the participants had diabetic peripheral neuropathy and the majority of that subgroup had burning foot pain.

Those with diabetic peripheral neuropathy were older (average age of 51 versus 37 for those without the condition). In fact, diabetic peripheral neuropathy prevalence increased drastically with age, from 4% for those aged 18-25 to 8% for those aged 26-29 and 21% by age 50.

This population, compared to those without this complication, also had a higher frequency of other diabetes complications like cardiovascular disease, retinopathy, which is when nerve cells are damaged in the eye and gastroparesis, which is when the nerves to the stomach are damaged or don't work anymore, prolonging digestion.

These patients were also more likely to be female and have a longer duration of diabetes and were less likely to have a college education and private insurance.

"About half of the participants had an annual income less than $75,000," Mizokami-Stout says. "Those with a lower socioeconomic status or less education may rely on public insurance options and be unable to afford insulin."

Consequently, effective diabetes self-management becomes more difficult. Despite two-thirds of participants using an insulin pump, those with diabetic peripheral neuropathy were twice as likely to have life threatening conditions like severe hypoglycemia or diabetic ketoacidosis.

The future of diabetes care

The teams' next endeavor is to develop a better understanding of the mechanism driving the increasing risk of diabetes complications towards developing chronic complications in diabetes, as well as what the phenotype is of someone that develops painful diabetic peripheral neuropathy versus someone that develops painless diabetic peripheral neuropathy.

The hope is to understand the influence of biopsychosocial factors and intervene in order to halt the progression of this complication before a patient has to resort to using pain medications.

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"Pain is a huge problem in this country and opioids may be the easiest way to deal with it, but this puts patients at increased risk for addiction," Pop-Busui says. "If we understand who's at risk of this debilitating complication, we can intervene early and close the vicious cycle of managing a patient's pain with different drugs."

Prevention is important because, according to Pop-Busui, it can take up to nine years to reverse neuropathy for someone with diabetes.

"These studies highlight the importance of ongoing diabetes research in general, and in particular of disadvantaged populations with type 1," Pop-Busui says. "It's a daily burden to live with this disease, and I hope one day, no one has to live with that burden anymore."

Papers cited: "Risk Factors for Diabetic Peripheral Neuropathy and Cardiovascular Autonomic Neuropathy in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study," Diabetes. DOI: 10.2337/db19-1046.

"The Contemporary Prevalence of Diabetic Neuropathy in Type 1 Diabetes: Findings From the T1D Exchange," Diabetes Care. DOI: 10.2337/dc19-1583.