07/22/2021 Leonard A. Levy, DPM, MPH
Diabetic Neuropathy Presents Unique Research Challenges
The 81st Scientific Sessions of the American
Diabetes Association (June 26, 2021) symposium
Resolving Key Controversies in Diabetic
Neuropathy featured a panel of researchers who
discussed some of the most challenging issues
they face while investigating methods to prevent
and treat diabetic neuropathies. Nigel A.
Calcutt, PhD, Professor of Pathology at the
University of California, San Diego, opened the
symposium indicating, " And how many FDA-approved
treatments are there for diabetic neuropathy?
Zero.”
"The stressors that contribute to neuropathy in
humans are not just hyperglycemia, he said, but
also dyslipidemia as well as a strong association
with hypertension” Dr. Calcutt said. He further
indicated, "So, there’s clearly been a challenge
in translating ideas into drugs. In part, at
least to start with, this comes from the
differences between the models and humans.
Neuropathy in humans is not just hyperglycemia,
he said, but also dyslipidemia as well as a
strong association with hypertension. “Exposure
to those stressors can go on for years to decades
or more, and the presentation of neuropathy is
therefore a relatively slow onset over a number
of years and a slow progression of many years,”
Dr. Calcutt said.
In a mouse or rat model, animals that live for
only weeks or months with extreme hyperglycemia,
there is a much shorter duration of exposure and
neuropathy presents with rapid onset and
progression and, he said, and diabetic rodents
are not diabetic humans. “We have to accept that
—they are a model and there is a big ‘if’ in that
model—so one has to be very cautious.” Dr.
Calcutt said. “You can bolster things by doing as
many studies as possible to give you confidence,
but making that leap for human trials is at best
a semi-educated guess based upon cumulative data
in animal models.”
Fabiana Picconi, MD, Unit of Endocrinology,
Diabetes, and Metabolism, University of Rome Tor
Vergata, Italy, discussed the impact of lipid-
lowering statin treatment on the risk for
diabetic neuropathies. She stated that a
definitive association between statins and
peripheral neuropathy remains to be established,
and additional longitudinal studies on the role
of cholesterol metabolism in diabetic peripheral
neuropathy are required to determine whether
there is a critical threshold of serum
cholesterol for an impairment of nerve
regeneration.”
Although observational associations persist, Dr.
Picconi said a scientific statement from the
American Heart Association states there is no
conclusive evidence for a causal relationship
between statin treatment and peripheral
neuropathy. “Most importantly, the potential
risks of statins on diabetic peripheral
neuropathy is largely outweighed by the
substantial clinical effect of statins in
cardiovascular disease prevention in diabetes,”
she said.
Karolina S. Khan, MD, PhD, Department of
Neurosurgery and Neurology, Aarhus University
Hospital, Denmark, stated that, “Fall accidents
are the second-leading cause of unintentional
injury deaths in the world, and recently it has
been suggested that individuals with diabetic
neuropathy suffer from an even higher risk of
falling and more severe injuries such as
fractures.” She also noted that people with
diabetic neuropathy report a higher fear of
falling and may suffer from impaired gait and
increased postural instability and studies are
needed to describe the underlying mechanisms
regarding the direct effects of diabetic
neuropathy on skeletal fragility and fractures.”
Kara R. Mizokami-Stout, MD, Assistant Professor
of Internal Medicine, Division of Metabolism,
Endocrinology and Diabetes, University of
Michigan, concluded by analyzing the impact of
social and psychological determinants of health
on diabetic peripheral and autonomic neuropathy.
While the number of studies exploring the
association between social and psychological
determinants of health on diabetes self-
management, glycemic control, and microvascular
outcomes continues to grow, Dr. Mizokami-Stout
said, studies related specifically to an
association with diabetic neuropathy are sparse.
Leonard A. Levy, DPM, MPH, Ft. Lauderdale, FL
