Vitamin B12 supplementation in diabetic neuropathy: a 1-year, randomized, double-blind, placebo-controlled trial

Aim: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/day for one year in patients with diabetic neuropathy (DN). Patients and methods: In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score). Results: B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, p < 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p < 0.001, p = 0.002, p < 0.0001, p < 0.000, p < 0.0001, p < 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p < 0.0001, and p < 0.0001, respectively). Conclusions: The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE

Updated Perspectives on the Diagnosis and Management of Familial Adenomatous Polyposis

Filippos Kyriakidis,1,&ast; Dionysios Kogias,2,&ast; Theodora Maria Venou,1,&ast; Eleni Karlafti,3,4 Daniel Paramythiotis5 1Second Chemotherapy Department, Theagenio Cancer Hospital of Thessaloniki, Thessaloniki, Greece; 2First Department of Internal Medicine, University General Hospital of Alexandroupolis, Alexandroupolis, Greece; 3Emergency Department, AHEPA General University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4First Propaedeutic Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece; 5First Propaedeutic Surgery Department, AHEPA University General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece&ast;These authors contributed equally to this workCorrespondence: Filippos Kyriakidis, Tel +30 6984996573, Email [email protected]: Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome marked by extensive colorectal polyposis and a high risk of colorectal cancer (CRC). Having access to screening and enrollment programs can improve survival for patients with FAP by enabling them to undergo surgery before the development of colorectal cancer. Provided that there are a variety of surgical options available to treat colorectal polyps in patients with adenomatous polyposis, the appropriate surgical option for each patient should be considered. The gold-standard treatment to reduce this risk is prophylactic colectomy, typically by the age of 40. However, colectomy is linked to morbidity and constitutes an ineffective way at preventing extra-colonic disease manifestations, such as desmoid disease, thyroid malignancy, duodenal polyposis, and cancer. Moreover, extensive studies have been conducted into the use of chemopreventive agents to prevent disease progression and delay the necessity for a colectomy as well as the onset of extracolonic disease. The ideal chemoprevention agent should demonstrate a biologically plausible mechanism of action and provide safety, easy tolerance over an extended period of time and a lasting and clinically meaningful effect. Although many pharmaceutical and non-pharmaceutical products have been tested through the years, there has not yet been a chemoprevention agent that meets these criteria. Thus, it is necessary to develop new FAP agents that target novel pathways, such as the mTOR pathway. The aim of this article is to review the prior literature on FAP in order to concentrate the current and future perspectives of diagnosis and treatment. In conclusion, we will provide an update on the diagnostic and therapeutic options, surgical or pharmaceutical, while focusing on the potential treatment strategies that could further reduce the risk of CRC.Keywords: FAP, colorectal cancer, surveillance, genetic testing, surgery, chemopreventio

Efficacy and safety of the combination of superoxide dismutase, alpha lipoic acid, Vitamin B12, and carnitine for 12 months in patients with diabetic neuropathy.

Aim: To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl LCarnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN). Patients-methods: In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group, n = 43), or placebo (n = 42) for 12 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured the vibration perception threshold (BIO), and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Pain (PS) and quality of life (QL) questionnaires were administered. Results: At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group (p &lt;0.001, p&lt;0.001, p&lt;0.001, p&lt;0.001, p = 0.027, p = 0.031, and p&lt;0.001 respectively), whereas the inplacebo group MCR (mean circular resultant) and PAIN deteriorated (p&lt;0.001, p &lt;0.001). The changes in MNSIQ, QL, SNCV, BIO, and PAIN differed significantly between groups (p &lt;0.001, p &lt;0.001, p = 0.031, p &lt;0.001, and p &lt;0.001 respectively). Conclusions: The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE

Comparison of premixed human insulin 30/70 to biphasic aspart 30 in well-controlled patients with type 2 diabetes using continuous glucose monitoring.

Aim: To compare in terms of glycemic variability two premixed insulins, Premixed Human Insulin 30/70 (PHI) and Biphasic Aspart 30 (BiAsp30), using Continuous Glucose Monitoring (CGM) and to estimate the correlation of Glycated Albumin (GA) and Fructosamine (FA) with CGM data. Patients-Data: A total of 36 well-controlled patients with type 2 Diabetes Mellitus (T2DM) underwent 7-day CGM with PHI and subsequently with BiAsp30. GA and FA were measured at the first and last day of each week of CGM. Results: BiAsp30 was associated with lower Average Blood Glucose (ABG) during the 23:00-03:00 period (PHI: 135.08 +/- 28.94 mg/dL, BiAsp30: 117.75 +/- 21.24 mg/dL, p &lt; 0.001) and the 00:00-06:00 period (PHI: 120.42 +/- 23.13 mg/dL, BiAsp30: 111.17 +/- 14.74 mg/dL, p = 0.008), as well as with more time below range (&lt;70 mg/dL) (TBR) during the 23:00-03:00 period in the week (PHI: 3.65 +/- 5.93%, BiAsp30: 11.12 +/- 16.07%, p = 0.005). PHI was associated with lower ABG before breakfast (PHI: 111.75 +/- 23.9 mg/dL, BiAsp30: 128.25 +/- 35.9 mg/dL, p = 0.013). There were no differences between the two groups in ABG, Time In Range and Time Below Range during the entire 24-h period for 7 days, p = 0.502, p = 0.534, and p = 0.258 respectively, and in TBR for the 00:00-06:00 period p = 0.253. Total daily insulin requirements were higher for BiAsp30 (PHI: 47.92 +/- 12.18 IU, BiAsp30: 49.58 +/- 14.12 IU, p = 0.001). GA and FA correlated significantly with ABG (GA: r = 0.512, p = 0.011, FA: r = 0.555, p = 0.005). Conclusions: In well-controlled patients with T2DM, BiAsp30 is an equally effective alternative to PHI

Exploring the Role of ACE2 as a Connecting Link between COVID-19 and Parkinson’s Disease

Coronavirus disease 2019 (COVID-19) is frequently accompanied by neurological manifestations such as headache, delirium, and epileptic seizures, whereas ageusia and anosmia may appear before respiratory symptoms. Among the various neurological COVID-19-related comorbidities, Parkinson’s disease (PD) has gained increasing attention. Some cases of PD disease have been linked to COVID-19, and both motor and non-motor symptoms in Parkinson’s disease patients frequently worsen following SARS-CoV-2 infection. Although it is still unclear whether PD increases the susceptibility to SARS-CoV-2 infection or whether COVID-19 increases the risk of or unmasks future cases of PD, emerging evidence sheds more light on the molecular mechanisms underlying the relationship between these two diseases. Among them, angiotensin-converting enzyme 2 (ACE2), a significant component of the renin-angiotensin system (RAS), seems to play a pivotal role. ACE2 is required for the entry of SARS-CoV-2 to the human host cells, and ACE2 dysregulation is implicated in the severity of COVID-19-related acute respiratory distress syndrome (ARDS). ACE2 imbalance is implicated in core shared pathophysiological mechanisms between PD and COVID-19, including aberrant inflammatory responses, oxidative stress, mitochondrial dysfunction, and immune dysregulation. ACE2 may also be implicated in alpha-synuclein-induced dopaminergic degeneration, gut–brain axis dysregulation, blood–brain axis disruption, autonomic dysfunction, depression, anxiety, and hyposmia, which are key features of PD

COVID-19 and liver injury in individuals with obesity

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations, including liver damage commonly detected by a hepatocellular pattern from liver function tests. Liver injury is associated with a worse prognosis overall. Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities, which are also associated with nonalcoholic fatty liver disease (NAFLD). The presence of NAFLD, similarly to obesity, is associated with an unfavourable impact on the coronavirus disease 2019 outcome. Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity, systemic inflammation, ischemic or hypoxic liver damage or drug side effects. However, liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals. Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection, which embodies a second hit to the underestimated liver damage

A comparative assessment of cardiovascular autonomic reflex testing and cardiac 123I-metaiodobenzylguanidine imaging in patients with type 1 diabetes mellitus without complications or cardiovascular risk factors

Aim. To compare the cardiovascular autonomic reflex tests (CARTs) with cardiac sympathetic innervation imaging with 123Imetaiodobenzylguanidine (MIBG) in patients with type 1 diabetes mellitus (T1DM). Patients and Methods. Forty-nine patients (29 males, mean age 36 ± 10 years, mean T1DM duration 19 ± 6 years) without cardiovascular risk factors were prospectively enrolled. Participants were evaluated for autonomic dysfunction by assessing the mean circular resultant (MCR), Valsalva maneuver (Vals), postural index (PI), and orthostatic hypotension (OH). Within one month from the performance of these tests, patients underwent cardiac MIBG imaging and the ratio of the heart to upper mediastinum count density (H/M) at 4 hours postinjection was calculated (abnormal values, H/M &lt; 1.80). Results. Twenty-nine patients (59%) had abnormal CARTs, and 37 (76%) patients had an H/M-4 &lt; 1.80 (p = 0 456). MCR, PI, Vals, and OH were abnormal in 29 (59%), 8 (16%), 5 (10%), and 11 (22%) patients, respectively. When using H/M-4 &lt; 1.80 as the reference standard, a cutoff point of ≥2 abnormal CARTs had a sensitivity of 100% but a specificity of only 33% for determining CAN. Conclusions. CARTs are not closely associated with 123I-MIBG measurements, which can detect autonomic dysfunction more efficiently than the former. In comparison to semiquantitative cardiac MIBG assessment, the recommended threshold of ≥2 abnormal CARTs to define cardiovascular autonomic dysfunction is highly sensitive but of limited specificity and is independently determined by the duration of T1DM. Copyright © 2018 Triantafyllos Didangelos et al

Effect of Calcium and Vitamin D Supplementation With and Without Collagen Peptides on Volumetric and Areal Bone Mineral Density, Bone Geometry and Bone Turnover in Postmenopausal Women With Osteopenia

Collagen peptides (CPs) have been shown to potentially have a role as a treatment option in osteopenia. In the present randomized prospective study, we examined the effect of calcium, vitamin D with and without CPs supplementation on changes in volumetric bone mineral density (vBMD) and bone geometry assessed by peripheral quantitative computed tomography at the tibia, areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry at the lumbar spine and the hip and bone turnover markers over 12-mo. Fifty-one postmenopausal women with osteopenia were allocated to Group A who received orally 5 g CPs, 500 mg calcium and 400 IU vitamin D3 and Group B who received the same dose of calcium and vitamin D3 per day. The primary endpoint was the change of trabecular bone mineral content (BMC) and vBMD after 12-mo supplementation in Groups A and B. At the trabecular site (4% of the tibia length), Group A had a significant increase of total BMC by 1.96 ± 2.41% and cross-sectional area by 2.58 ± 3.91%, trabecular BMC by 5.24 ± 6.48%, cross-sectional area by 2.58 ± 3.91% and vBMD by 2.54 ± 3.43% and a higher % change of these parameters at 12 mo in comparison to Group B (p &lt; 0.01, p = 0.04, p &lt; 0.01, p = 0.04, p = 0.02, respectively). At the cortical site (38% of the tibia length), total and cortical vBMD increased by 1.01 ± 2.57% and 0.67 ± 1.71%. Furthermore, the mean aBMD at the spine was higher (p = 0.01), while bone markers decreased in Group A compared to Group B. The present study shows improvement of trabecular and cortical parameters as assessed by peripheral quantitative computed tomography at the tibia, prevention of aBMD decline and decrease of bone turnover after 12-mo supplementation with calcium, vitamin D with CPs. © 2021 The International Society for Clinical Densitometr