During the Virtual 80th Scientific Sessions symposium Clinical Management of Diabetic Neuropathies in 2020, three experts provided updates on the latest research and current recommendations for treating diabetic neuropathies, including the clinical management of gastrointestinal (GI) autonomic neuropathies, the impact of diet and lifestyle interventions on diabetic neuropathies, and the pharmacological management of painful neuropathy.
The symposium can be viewed by registered meeting attendees at ADA2020.org through September 10, 2020. If you haven’t registered for the Virtual 80th Scientific Sessions, register today to access all of the valuable meeting content.
Karen L. Jones, PhD, DipAppSc, reviewed gastrointestinal autonomic neuropathies, including disordered gastric emptying and the impact of gastric emptying on glycemic control.
“There has been a redefinition of gastrointestinal autonomic neuropathy over the last few decades. For example, the stomach is now recognized to be central to blood glucose homeostasis and to play a major role in blood pressure regulation,” said Dr. Jones, the William T. Southcott Research Fellow at the University of Adelaide, Principal Medical Scientist at Royal Adelaide Hospital, and Adjunct Professor at the University of South Australia. “However, the relationship between upper GI symptoms and gastric emptying in longstanding type 1 and type 2 diabetes is relatively weak.”
Dr. Jones noted that symptoms aren’t always a marker of delayed gastric emptying because some patients who have a delay in gastric emptying have few symptoms, while others who have normal emptying have a large swath of symptoms.
Studies have suggested that gastric emptying is delayed in 30% to 50% of patients with longstanding, poorly controlled type 1 or type 2 diabetes, she added.
“Gastric emptying is both determined by, as well as being a major determinant of, postprandial glycemia,” Dr. Jones said. “Slowing gastric emptying by GLP-1 (glucagon-like peptide-1 receptor) agonists reduces postprandial glycemic excursions in type 2 diabetes but may also prove useful in the management of postprandial hypotension.”
Douglas Wright, PhD, Professor of Anatomy and Cell Biology at the University of Kansas Medical Center, examined the role that lifestyle and dietary modifications play in the management of diabetic neuropathy.
“Among the risk factors that increase susceptibility to neuropathy that we think can be modified by lifestyle interventions, physical activity, and dietary changes are glycation status, insulin resistance, hypertension, obesity, triglyceride levels, and HDL (high-density lipoprotein) levels,” Dr. Wright said. “All of these are known to be responsive to physical activity and dietary interventions.”
Preclinical and translational work by Dr. Wright’s group and others have contributed to a growing body of evidence that physical activity leads to improvements in diabetic neuropathy, particularly in pain management. There is also new evidence suggesting that the ketogenic diet leads to improvements in diabetic neuropathy in prediabetes and type 1 diabetes mouse models, including pain reduction and improved epidermal innervation.
“We know that there are many different aspects that are involved in these benefits—intrinsic DRG (dorsal root ganglia) gene changes, insulin resistance, reduced inflammation, improved mitochondrial function, reduced AGE (advanced glycation end products) levels, and increased neurotrophic production all likely contribute,” Dr. Wright said. “Importantly, the translation of these approaches is very feasible. We certainly have been able to translate the physical activity interventions, and I think the ketogenic diet is also very testable as we move into human studies.”
In the symposium’s final presentation, Solomon Tesfaye, MB, ChB, MD, FRCP, discussed the management of diabetic peripheral neuropathic pain (DPNP), which he said is underdiagnosed and that current symptomatic treatments for the condition are not optimal for all patients.
“Unfortunately, many of our patients have lots of problems, including side effects from the medications that we give them—including difficulty walking and mobilizing, and they have a lot of comorbidities,” said Dr. Tesfaye, Consultant Endocrinologist at the Royal Hallamshire Hospital and Honorary Professor of Diabetic Medicine at the University of Sheffield, United Kingdom.
“Unlike other chronic pain conditions, the burden of the pain is much bigger in patients with DPNP because they have postural hypotension, ischemic heart disease, foot ulcers, problems with vision, and a number of other problems such as problems with sexual function,” Dr. Tesfaye continued. “This all leads to an impairment of function and the curtailment of quality of life in these patients, and so it is a very important clinical problem.”
Dr. Tesfaye said pharmacological treatment options for DPNP include four drugs—pregabalin, gabapentin, duloxetine, amitriptyline—and noted that treatment should be tailored to the individual patient.
“You need to take things like age and the kind of job they have into account, and then start low, titrate slowly,” he said. “We also need to look at concomitant conditions, such as disturbances of sleep and mood, CKD (chronic kidney disease), and orthostatic hypotension. Adverse events are a major criterion for nonadherence to medications.”