State-of-the-art pharmacotherapy for diabetic neuropathy

Azmi, Shazli; Alam, Uazman; Burgess, Jamie; Malik, Rayaz A.

doi:10.1080/14656566.2020.1812578

Cited by 22 publications

(31 citation statements)

References 192 publications

(188 reference statements)

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“…Until now there is no FDA approved therapy for DPN, other than the recommendation to improve glycaemic control and therapy to relieve symptoms (25). Thus, development of effective therapies for this common disease is urgently needed and blocking hIAPP (aggregation) is a novel candidate approach to treat and/or prevent DPN.…”

Section: Resultsmentioning

confidence: 99%

Human IAPP is a contributor to painful diabetic peripheral neuropathy

Asiri¹,

Versteeg²,

Brakkee

et al. 2021

Preprint

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Peripheral neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM), of which the pathogenesis is not fully understood. We investigated whether human islet amyloid polypeptide (hIAPP), which forms pathogenic aggregates that damage islet β-cells in T2DM, is involved in T2DM-associated peripheral neuropathy. In vitro, hIAPP incubation with sensory neurons reduced neurite outgrowth. Transgenic hIAPP Ob/Ob mice, an established animal model for T2DM, as well as hIAPP mice, which have elevated plasma hIAPP levels but no hyperglycaemia. Both transgenic mice developed peripheral neuropathy as evidenced by pain-associated behavior and reduced intra-epidermal nerve fibers (IENF), suggesting hIAPP is a mediator of diabetic neuropathy. Intraplantar and intravenous hIAPP injection in WT mice induced long-lasting mechanical hypersensitivity and reduced IENF, whereas non-aggregating murine IAPP or mutated hIAPP (Pramlintide) did not have these effects, and were not toxic for cultured sensory neurons. In T2DM patients, significantly more hIAPP oligomers were found in the skin compared to non-T2DM controls. Thus, we provide evidence that hIAPP is toxic to sensory neurons, and mediates peripheral neuropathy in mice. The presence of hIAPP aggregates in skin of humans with T2DM supports the notion that human IAPP is a potential driver of T2DM neuropathy in man.

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Section: Resultsmentioning

confidence: 99%

Human IAPP is a contributor to painful diabetic peripheral neuropathy

Asiri¹,

Versteeg²,

Brakkee

et al. 2021

Preprint

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“… 8 The association between DM and pathological changes in the central nervous system causes memory loss and affective retardation, which later increase the risk of vascular depletion of the brain. 9 However, the currently available drugs for the treatment of these conditions merely alleviate the symptoms. 10 …”

Section: Introductionmentioning

confidence: 99%

Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment

Onikanni¹,

Lawal²,

Olusola³

et al. 2021

JIR

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Background Sterculia tragacantha is a medicinal plant commonly used in the western part of Nigeria, for managing diabetes mellitus. However, there is a dearth of scientific information on the antidiabetic and neuroprotective properties of the plant. Methods The in silico, in vitro and in vivo models were used to evaluate the antioxidants, antidiabetic, anti-inflammatory and neuroprotective potential of aqueous extract of Sterculia tragacantha leaf (AESTL) in streptozotocin (STZ)-induced diabetic rats. Thirty (30) male albino rats (155.34±6.33 g) were intraperitoneal injected with 40 mg/kg of freshly prepared streptozotocin and were divided into 5 groups (A-E) of 6 animals each. Groups A–D were treated with 0, 150 and 300 mg/kg of AESTL, and 200 mg/kg body weight of metformin respectively, while group E serve as the normal control. Results The results of in vitro analysis revealed dose-dependent antioxidant activities; ABTS (IC 50 = 63.03±2.57 μg/mL), DPPH (117.49±2.35 μg/mL), FRAP (15.19±0.98 mmol/100g), TAC (43.38±0.96 mg/100g), hypoglycaemic effect; α-amylase (IC 50 = 77.21±4.35 μg/mL) and α-glucosidase (IC 50 = 443.25±12.35), and anti-cholinesterase; AChE (IC 50 = 113.07±3.42 μg/mL) and BChE (IC 50 = 87.50±4.32 μg/mL) activities of AESTL. In vivo study revealed dose-dependent hypoglycemic effect and body weight improvement in rats treated with the AESTL. In addition, AESTL improved the antioxidant status and attenuated STZ-induced dysregulations of Na + -K + -ATPase, cholinesterases and neurotransmitters in the brain tissue of experimental rats. The results also demonstrated that AESTL could regulate anti-inflammatory response via inhibition of COX-2/NO signaling axis in the brain of diabetic rats. Molecular docking analysis revealed that epicatechin and procyanidin B2, the bioactive compounds from AESTL, docked well to the binding cavities of acetylcholinesterase, butyrylcholinesterase, α-amylase and α-glucosidase with binding affinities ranges between –8.0 and –11.4 kcal/mol, suggesting that these compounds are the bioactive component that could be responsible for the antidiabetic and neuroprotective activities of AESTL. Conclusion The results of the present study strongly suggested that the AESTL extract could be very useful for halting diabetes progression and its associated neuroinflammation complications.

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“…In addition to early intervention and strict glycemic control, a variety of conservative/pharmacological and neuromodulatory treatment modalities have emerged for the management of painful diabetic neuropathy (PDN). The conservative treatment options include the common first-line neuropathic pain agents, such as pregabalin, gabapentin, and duloxetine ( 3 , 4 ). Notably, the use of oral opioids is discouraged due to significant morbidity, mortality concerns, and lack of efficacy for neuropathic pain ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Recommendations for Neuromodulation in Diabetic Neuropathic Pain

et al. 2021

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Over 50% of the 34 million people who suffer from diabetes mellitus (DM) are affected by diabetic neuropathy. Painful diabetic neuropathy (PDN) impacts 40–50% of that group (8.5 million patients) and is associated with a significant source of disability and economic burden. Though new neuromodulation options have been successful in recent clinical trials (NCT03228420), still there are many barriers that restrict patients from access to these therapies. We seek to examine our tertiary care center (Albany Medical Center, NY, USA) experience with PDN management by leveraging our clinical database to assess patient referral patterns and utilization of neuromodulation. We identified all patients with a diagnosis of diabetes type 1 (CODE: E10.xx) or diabetes type 2 (CODE: E11.xx) AND neuralgia/neuropathic pain (CODE: M79.2) or neuropathy (CODE: G90.09) or chronic pain (CODE: G89.4) or limb pain (CODE: M79.6) OR diabetic neuropathy (CODE: E11.4) who saw endocrinology, neurology, and/or neurosurgery from January 1, 2019, to December 31, 2019. We then determined which patients had received pain medications and/or neuromodulation to divide the cohort into three groups: no treatment, conservative treatment, and neuromodulation treatment. The cohorts were compared with chi-square or one-way ANOVA with multiple comparisons to analyze the differences. A total of 2,635 PDN patients were identified, of which 700 received no treatment for PDN, 1,906 received medication(s), and 29 received neuromodulation (intrathecal therapy, spinal cord stimulation, or dorsal root ganglion stimulation). The patients who received pain medications for PDN visited neurology more often than the pain specialists. Of the patients that received neuromodulation, 24 had seen neurology, 6 neurology pain, and 3 anesthesia pain. They averaged 2.78 pain medications prior to implant. Approximately 41% of the patients in the conservative management group were prescribed three or more medications. Of the 1,935 treated patients, only 1.5% of the patients received neuromodulation. The patients on three or more pain medications without symptomatic relief may be potential candidates for neuromodulation. An opportunity, therefore, exists to educate providers on the benefits of neuromodulation procedures.

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State-of-the-art pharmacotherapy for diabetic neuropathy

Cited by 22 publications

References 192 publications

Human IAPP is a contributor to painful diabetic peripheral neuropathy

Human IAPP is a contributor to painful diabetic peripheral neuropathy

Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment

Recommendations for Neuromodulation in Diabetic Neuropathic Pain

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