This is not a cure. We are not talking about unbinding excess sugar from nerves or increasing blood flow, but about managing pain by stimulating the spinal cord. Abbott Labs has obtained FDA approval for its SCS implant for relieving the pain of diabetic peripheral neuropathy.
Connecting the Dots to Diabetes Pain Relief
Proclaim XR is now being used for painful diabetic peripheral neuropathy. The future may hold even more promises.
Through our glucose monitoring products [Abbott’s FreeStyle Libre CGMs] and chronic pain management innovations, we know some things about these challenges and how to work across disciplines to find solutions.
Which is why we are excited to announce FDA approval for our Proclaim™ XR spinal cord stimulation (SCS) system to treat painful diabetic peripheral neuropathy (DPN), a serious complication of diabetes.
If you are not familiar with painful DPN, that's good. It means you haven't experienced it.
My father and my mentor went through increasing DPN for many years, getting worse and worse, spreading from their feet to their whole bodies. My father also had non-healing sores on his feet.
Note: The ProclaimTM XR web site is misconfigured. Firefox warned me to be careful about accessing it.
When I was first diagnosed with diabetes, the most important thing I learned was the news that neuropathy could be prevented for at least 20 years with diet, medications, and glucose monitoring. I have mentioned that I use a low-carb, high fat ketogenic diet, Ozempic once a week, insulin injections only when my glucose spikes, and a FreeStyle Libre 3 CGM to keep my GMI around 6.5. I’m at 26 years without numbness from neuropathy, just some tingling (NOT pins and needles) in the toes for which I exercise to increase blood flow.
HealthDirect: Diabetic neuropathy
The most common symptoms of diabetic neuropathy are numbness, tingling, a burning feeling, aching, cramps and weakness.
Pain relievers, such as paracetamol and ibuprofen, might not work with the pain of diabetic neuropathy. If so, talk to your doctor about other forms of pain relief.
When you have diabetes it is important to take care of your feet. Appropriate footwear is important. You can also visit a podiatrist (up to 5 visits a year are subsidised for people living with diabetes). They will give you advice on the best shoes and socks to help your feet.
Abbott:
The Proclaim system takes a non-opioid approach to pain management, providing DPN relief by delivering electrical stimulation through a device placed as an outpatient along the spinal cord.
Causes
Wikipedia:
Peripheral neuropathy
Common causes include systemic diseases (such as diabetes or leprosy), hyperglycemia-induced glycation,[2][3][4] vitamin deficiency, medication (e.g., chemotherapy, or commonly prescribed antibiotics including metronidazole and the fluoroquinolone class of antibiotics (such as ciprofloxacin, levofloxacin, moxifloxacin)), traumatic injury, ischemia, radiation therapy, excessive alcohol consumption, immune system disease, celiac disease, non-celiac gluten sensitivity, or viral infection. It can also be genetic (present from birth) or idiopathic (no known cause).[5][6][7][8] In conventional medical usage, the word neuropathy (neuro-, "nervous system" and -pathy, "disease of")[9] without modifier usually means peripheral neuropathy.
Diabetic neuropathy
Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic changes such as urinary symptoms. These changes are thought to result from a microvascular injury involving small blood vessels that supply nerves (vasa nervorum).
Elevated levels of glucose within cells cause a non-enzymatic covalent bonding with proteins, which alters their structure and inhibits their function. Some of these glycated proteins have been implicated in the pathology of diabetic neuropathy and other long-term complications of diabetes.
Glycation
Glycation (non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein, lipid or nucleic acid molecule.[1] Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic process responsible for many (e.g. micro and macrovascular) complications in diabetes mellitus and is implicated in some diseases and in aging.[2][3][4] Glycation end products are believed to play a causative role in the vascular complications of diabetes mellitus.[5]
Advanced glycation end-product
Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars.[1] They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease.[2]
AGEs arise under certain pathologic conditions, such as oxidative stress due to hyperglycemia in patients with diabetes.
AGEs have been implicated in Alzheimer's Disease,[15] cardiovascular disease,[16] and stroke.[17] The mechanism by which AGEs induce damage is through a process called cross-linking that causes intracellular damage and apoptosis.[18] They form photosensitizers in the crystalline lens,[19] which has implications for cataract development.[20] Reduced muscle function is also associated with AGEs.[21]
Proteins are usually glycated through their lysine residues.[29] In humans, histones in the cell nucleus are richest in lysine, and therefore form the glycated protein N(6)-Carboxymethyllysine (CML).[29]
A receptor nicknamed RAGE, from receptor for advanced glycation end products, is found on many cells, including endothelial cells, smooth muscle, cells of the immune system[which?] from tissue such as lung, liver, and kidney.[clarification needed][which?] This receptor, when binding AGEs, contributes to age- and diabetes-related chronic inflammatory diseases such as atherosclerosis, asthma, arthritis, myocardial infarction, nephropathy, retinopathy, periodontitis and neuropathy.[30] The pathogenesis of this process hypothesized to activation of the nuclear factor kappa B (NF-κB) following AGE binding.[31] NF-κB controls several genes which are involved in inflammation.[32] AGEs can be detected and quantified using bioanalytical and immunological methods.[33]
Other Treatments
We know how to prevent blood vessel and nerve damage with diet, exercise, medications, and monitoring. In principle, glycation should be reversible, but there are no indications that this is practical for damaged nerves involved in neuropathy.
That leaves us with nothing better than treating the pain in most cases. Treating intractable pain is huge, compared with not being able to do anything.
In clearance, or the rate at which a substance is removed or cleared from the body, it has been found that the cellular proteolysis of AGEs—the breakdown of proteins—produces AGE peptides and "AGE free adducts" (AGE adducts bound to single amino acids). These latter, after being released into the plasma, can be excreted in the urine.[34]
Although the only form suitable for urinary excretion, the breakdown products of AGE—that is, peptides and free adducts—are more aggressive than the AGE proteins from which they are derived, and they can perpetuate related pathology in diabetic patients, even after hyperglycemia has been brought under control.[22]
Some AGEs have an innate catalytic oxidative capacity, while activation of NAD(P)H oxidase through activation of RAGE and damage to mitochondrial proteins leading to mitochondrial dysfunction can also induce oxidative stress. A 2007 in vitro study found that AGEs could significantly increase expression of TGF-β1, CTGF, Fn mRNA in NRK-49F cells through enhancement of oxidative stress, and suggested that inhibition of oxidative stress might underlie the effect of ginkgo biloba extract in diabetic nephropathy. The authors suggested that antioxidant therapy might help prevent the accumulation of AGEs and induced damage.[23] In the end, effective clearance is necessary, and those suffering AGE increases because of kidney dysfunction might require a kidney transplant.[22]
In diabetics who have an increased production of an AGE, kidney damage reduces the subsequent urinary removal of AGEs, forming a positive feedback loop that increases the rate of damage. In a 1997 study, diabetic and healthy subjects were given a single meal of egg white (56 g protein), cooked with or without 100 g of fructose; there was a greater than 200-fold increase in AGE immunoreactivity from the meal with fructose.[37]
Compounds that are thought to break some existing AGE crosslinks include Alagebrium (and related ALT-462, ALT-486, and ALT-946)[48] and N-phenacyl thiazolium bromide.[49] One in vitro study shows that rosmarinic acid out performs the AGE breaking potential of ALT-711.[50]
There is, however, no agent known that can break down the most common AGE, glucosepane, which appears 10 to 1,000 times more common in human tissue than any other cross-linking AGE.[51][52]
Glucosepane
Glucosepane is a lysine-arginine protein cross-linking product and advanced glycation end product (AGE) derived from D-glucose.[1] It is an irreversible, covalent cross-link product that has been found to make intermolecular and intramolecular cross-links in the collagen of the extracellular matrix (ECM) and crystallin of the eyes.[2] Covalent protein cross-links irreversibly link proteins together in the ECM of tissues. Glucosepane is present in human tissues at levels 10 to 1000 times higher than any other cross-linking AGE, and is currently considered to be the most important cross-linking AGE.[3]
Studies done on glucosepane by the Monnier group have shown that the level of glucosepane cross-links in human collagen in the ECM increases progressively with age and at a more rapid pace in people with diabetes, thus suggesting the role of glucosepane in the long-term effects associated with diabetes and aging such as arteriosclerosis, joint stiffening and skin wrinkling.[6]
Because of the important role glucosepane has been found to play in many pathologies of aging, many researchers have been investigating ways in which the levels of glucosepane could be reduced in tissues.
Well, at least we know what the question is. Unanswered questions are the greatest treasures in science, because that how it advances.
Watch this space.
Your Experiences
As usual, we would like to hear from those who have experience with neuropathy, personal or among people you know.