Minocycline improves peripheral and autonomic neuropathy in type 2 diabetes: MIND study

Abstract

Diabetic peripheral neuropathy and diabetic autonomic neuropathy are serious and common complications of diabetes associated with increased risk of mortality and cardiovascular disease. We sought to evaluate the safety and efficacy of minocycline in type 2 diabetic patients with diabetic peripheral and autonomic neuropathy. In a randomized placebo controlled study, 50 outpatients were randomly assigned to receive 100 mg minocycline or placebo. Outcome measures included the vibration perception threshold (VPT), Leeds assessment of neuropathic symptoms and signs (LANSS), Pain Disability Index (PDI), Visual Analog Scale (VAS), beck depression inventory (BDI), health assessment questionnaire (HAQ) and autonomic neuropathy, assessed by cardiovascular reflex tests according to Ewing and peripheral sympathetic autonomic function was assessed by FDA approved Sudoscan. At baseline there were no significant differences between demographic variables and the neuropathy variables in the minocycline and placebo groups. After treatment, VPT significantly improved in the minocycline group as compared to the placebo group. Mean posttreatment scores on the LANSS, PDI and HAQ were significantly lower in the minocycline group compared with the placebo group. However, BDI and VAS significantly (p = 0.01) improved in both minocycline and placebo groups (Table 2). After treatment with minocycline, heart rate (HR) response to standing significantly improved, while there was a borderline significance toward a reduction in HR response to deep breath. These finding indicate that 6-week oral treatment with minocycline is safe, well tolerated and significantly improves peripheral and autonomic neuropathy in type 2 diabetic patients.

Effect of Minocycline on Lumbar Radicular Neuropathic Pain

“…9 With this result, we not only support the conclusion made by Syngle et al 17 that minocycline reduces neuropathy but also extend it to lumbar radicular pain. After 2 weeks of treatment, minocycline and amitriptyline reduced pain intensity by 1.47 and 1.41 points on the NRS, respectively.…”

Stabilization of endogenous Nrf2 by minocycline protects against Nlrp3-inflammasome induced diabetic nephropathy

“…Mechanistically minocycline maintains renal protein levels of Nrf2, possibly by reducing its ubiquitination and degradation. The inhibition of inflammasome activation via Nrf2 identifies a new minocycline-dependent cytoprotective mechanism that is of potential translational relevance in dNP, but may also have implications beyond dNP 28 29 . Furthermore, the protection from dNP through inflammasome inhibition and the failure of the poly-caspase inhibitor CIX (targeting caspases-3,-6,-7,-8,-10, but not caspase-1) strengthens the recently described pathogenetic role of inflammasome activation and sterile inflammation in dNP while supporting the notion that caspase-3-dependent apoptosis is negligible 21 22 .…”

Upper extremity impairments in type 1 diabetes with long duration; common problems with great impact on daily life

“…In the second part of the questionnaire, difficulties to perform daily activities were reported by a previously validated tool, Health Assessment Questionnaire (HAQ) [17]. HAQ is often used for patients with rheumatoid arthritis (RA), but it has also been used in several other rheumatic as well as non-rheumatic settings, including diabetes [11,18,19]. HAQ is composed of 20 questions in eight categories, describing the subjects' subjective degree of activity limitation based on their experiences in the most recent 7 days.…”