Molecular Aspects in the Potential of Vitamins and Supplements for Treating Diabetic Neuropathy

PURPOSE OF REVIEW: To discuss and provide evidence-based data on dietary supplements as part of treating diabetic neuropathy RECENT FINDINGS: Few randomized controlled trials are available, but some have shown beneficial efficacy of various dietary supplements on objective primary endpoints including nerve conduction velocities and axon potentials as well as subjective patient-reported outcomes. SUMMARY: No medical cure for diabetic neuropathy exists, and prevention is therefore crucial. Tight glucose control slows the progression of nerve damage in diabetes, but an unmet clinical need for effective interventions is warranted. Consequently, a growing number of patients turn to dietary supplements proposed to possess neuroprotective properties. However, the postulated effects are often not evidence-based as they have not been tested scientifically. Taken together, this review will focus on dietary supplements investigated in clinical trials for their potential capabilities in targeting the molecular mechanisms involved in the underlying pathogenesis of diabetic neuropathy

Low-grade inflammation in type 2 diabetes:a cross-sectional study from a Danish diabetes outpatient clinic

OBJECTIVES: To investigate low-grade inflammation in type 2 diabetes and explore associations to clinical aspects as well as microvascular and macrovascular complications. DESIGN: Cross-sectional analysis. SETTING: The outpatient diabetes clinic at the Department of Endocrinology at Aalborg University Hospital, Denmark. PARTICIPANTS: 100 participants with type 2 diabetes confirmed by a haemoglobin A1c (HbA1c)≥6.5% for a minimum of 1 year and 21 healthy controls. OUTCOME MEASURES: Serum levels of 27 inflammation-related biomarkers measured by immunoassay. Associations with microvascular and macrovascular complications, body weight, glycaemic control, medication and sex were investigated in the diabetes cohort. RESULTS: Serum levels of tumour necrosis factor (TNF)-α and eotaxin were elevated in type 2 diabetes (p<0.05), while interleukin (IL)-7 was decreased (p<0.001). IL-12/IL-23p40, IL-15, macrophage-derived chemokine (MDC) and C reactive protein (CRP) levels were increased with body weight (p<0.05), while eotaxin and TNF-α were increased with elevated HbA1c levels (p<0.04). Dipeptidyl peptidase-4 inhibitor therapy was associated with lower levels of induced protein-10, MDC and thymus and activation regulated chemokine (p<0.02), while females had higher levels of MDC (p=0.027). Individuals with ≥3 diabetic complications had elevated levels of IL-6, IL-10, IL-12/IL-23p40, IL-15 and CRP compared with those with ≤3 (p<0.05). CONCLUSION: The level of low-grade inflammation in type 2 diabetes is associated with obesity, glycaemic regulation, therapeutical management, sex and complications. Our results underline the importance of addressing inflammatory issues in type 2 diabetes, as these may predispose for crippling comorbidities

Circulating Inflammatory Markers Are Inversely Associated with Heart Rate Variability Measures in Type 1 Diabetes

Introduction. A neuroimmune communication exists, and compelling evidence suggests that diabetic neuropathy and systemic inflammation are linked. Our aims were (1) to investigate biomarkers of the ongoing inflammation processes including cytokines, adhesion molecules, and chemokines and (2) to associate the findings with cardiovascular autonomic neuropathy in type 1 diabetes by measuring heart rate variability and cardiac vagal tone. Materials and Methods. We included 104 adults with type 1 diabetes. Heart rate variability, time domain, and frequency domains were calculated from a 24-hour Holter electrocardiogram, while cardiac vagal tone was determined from a 5-minute electrocardiogram. Cytokines (interleukin- (IL-) 1α, IL-4, IL-12p70, IL-13, IL-17, and tumor necrosis factor- (TNF-) α), adhesion molecules (E-selectin, P-selectin, and intercellular adhesion molecule- (ICAM-) 1), and chemokines (chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4, and C-X-C motif chemokine (CXCL)10) were assessed using a Luminex multiplexing technology. Associations between concentrations of inflammatory biomarkers and continuous variables of heart rate variability and cardiac vagal tone were estimated using multivariable linear regression adjusting for age, sex, disease duration, and smoking. Results. Participants with the presence of cardiovascular autonomic neuropathy had higher systemic levels of IL-1α, IL-4, CCL2, and E-selectin than those without cardiovascular autonomic neuropathy. IL-1α, IL-4, IL-12, TNF-α, and E-selectin were inversely associated with both sympathetic and parasympathetic heart rate variability measures (p>0.01). Discussion. Our results show that several pro- and anti-inflammatory factors, believed to be involved in the progression of diabetic polyneuropathy, are associated with cardiovascular autonomic neuropathy, suggesting that these factors may also contribute to the pathogenesis of cardiovascular autonomic neuropathy. Our findings emphasize the importance of the neuroimmune regulatory system in the pathogenesis of neuropathy in type 1 diabetes

Study protocol for a multicentre, randomised, parallel group, sham-controlled clinical trial investigating the effect of transcutaneous vagal nerve stimulation on gastrointestinal symptoms in people with diabetes complicated with diabetic autonomic neuropathy:The DAN-VNS Study

Introduction A high proportion of people with diabetes experience gastrointestinal (GI) symptoms, which may be manifestations of diabetic autonomic neuropathy (DAN). The current treatment regime is ineffective and associated with major side effects. Transcutaneous vagal nerve stimulation (tVNS) is a new therapeutic option, which has been shown to increase GI motility and reduce inflammatory responses. As vagus is the main neuronal pathway for extrinsic coordination of GI secretion and motility, we hypothesise that tVNS will improve DAN-induced GI symptoms in subjects with diabetes.Methods and analysis The DAN-VNS study is a randomised multicentre clinical trial investigating the effect of short-term, high intensity as well as long-term, medium-intensity tVNS on GI symptom alleviation in 120 subjects with diabetes. The primary outcome consists of changes from baseline in subjective ratings of symptom severity. Secondary outcomes include changes in gastric motility and GI transit time measured by MRI and wireless motility capsule. Moreover, cardiovascular and sudomotor function, glycaemic control, brain sensory processing and presence of low-grade inflammation will be investigated as secondary outcome measures. Lastly, 15 responders of tVNS treatment will be included in an explorative, randomised, cross-over study, in which the acute endocrine and metabolic response to short-term tVNS will be investigated.Ethics and dissemination The study has been approved by the North Denmark Region Committee on Health Research Ethics (N-20190020). Results will be published in relevant international peer-reviewed journals.Trial registration number NCT04143269

Entrustable Professional Activities (EPAs) for Global Health

Purpose As global health education and training shift toward competency-based approaches, academic institutions and organizations must define appropriate assessment strategies for use across health professions. The authors aim to develop entrustable professional activities (EPAs) for global health to apply across academic and workplace settings. Method In 2019, the authors invited 55 global health experts from medicine, nursing, pharmacy, and public health to participate in a multiround, online Delphi process; 30 (55%) agreed. Experts averaged 17 years of global health experience, and 12 (40%) were from low-to middle-income countries. In round one, participants listed essential global health activities. The authors used in vivo coding for round one responses to develop initial EPA statements. In subsequent rounds, participants used 5-point Likert-Type scales to evaluate EPA statements for importance and relevance to global health across health professions. The authors elevated statements that were rated 4 (important/relevant to most) or 5 (very important/relevant to all) by a minimum of 70% of participants (decided a priori) to the final round, during which participants evaluated whether each statement represented an observable unit of work that could be assigned to a trainee. Descriptive statistics were used for quantitative data analysis. The authors used participant comments to categorize EPA statements into role domains. Results Twenty-Two EPA statements reached at least 70% consensus. The authors categorized these into 5 role domains: partnership developer, capacity builder, data analyzer, equity advocate, and health promoter. Statements in the equity advocate and partnership developer domains had the highest agreement for importance and relevance. Several statements achieved 100% agreement as a unit of work but achieved lower levels of agreement regarding their observability. Conclusions EPAs for global health may be useful to academic institutions and other organizations to guide the assessment of trainees within education and training programs across health professions

To address emerging infections, we must invest in enduring systems: The kinetics and dynamics of health systems strengthening

Clinical pharmacology uses foundational principles of pharmacokinetics (PK) and pharmacodynamics (PD) to address medication use spanning a continuum from molecules to the masses. In the realm of infectious diseases, PK/PD attributes are considered especially important, because subtherapeutic dosing of antibiotics has been associated with poorer clinical outcomes in patients and increased incidences of drug resistance in populations. In consideration of these PK/PD principles, we will describe the analogous relationship between health systems strengthening, including for educating healthcare providers about emerging infections, and the tenets of therapeutic drug monitoring

Sustainable Pharmacy: Piloting a Session on Pharmaceuticals, Climate Change, and Sustainability within a U.S. Pharmacy Curriculum

Objective: To design and assess an innovative session for pharmacy students that addresses the role of pharmaceuticals with climate change and sustainability. Innovation: One hundred and sixteen third-year students at the University of California, San Francisco School of Pharmacy participated during their required Health Policy course. This 3-hour session included guided pre-course activities, an interactive lecture, a panel of healthcare professionals discussing complex decision-making and small group case-based learning. Curricular assessment was conducted through pre-/post-test measures of knowledge acquisition, student evaluations, and course projects. Critical Analysis: One hundred and two students (response rate 88%) completed the pre-test and 115 students (response rate 99%) completed the post-test assessment. We identified a significant increase in the proportion of correct answers on post-test questions addressing drug disposal legislation (75% pre-test vs 91% post-test, p=0.002) and the predicted effects of climate change on health (55% pre-test vs 90% post-test, p < 0.001). The session was also well received; average student evaluation scores were above 4 in all areas of course evaluation (where 5=ideal). In addition, 17% of student groups (relative to 0% in 2015) proposed a sustainability-related policy as their final coursework project. Next Steps: The development and implementation of this brief session resulted in knowledge gain and favorable student response. This project is feasible for other Schools of Pharmacy to adapt and implement. Conflict of Interest: None   Type: Not

Sustainable Pharmacy: Piloting a Session on Pharmaceuticals, Climate Change, and Sustainability within a U.S. Pharmacy Curriculum

Objective: To design and assess an innovative session for pharmacy students that addresses the role of pharmaceuticals with climate change and sustainability. Innovation: One hundred and sixteen third-year students at the University of California, San Francisco School of Pharmacy participated during their required Health Policy course. This 3-hour session included guided pre-course activities, an interactive lecture, a panel of healthcare professionals discussing complex decision-making and small group case-based learning. Curricular assessment was conducted through pre-/post-test measures of knowledge acquisition, student evaluations, and course projects. Critical Analysis: One hundred and two students (response rate 88%) completed the pre-test and 115 students (response rate 99%) completed the post-test assessment. We identified a significant increase in the proportion of correct answers on post-test questions addressing drug disposal legislation (75% pre-test vs 91% post-test, p=0.002) and the predicted effects of climate change on health (55% pre-test vs 90% post-test, p &lt; 0.001). The session was also well received; average student evaluation scores were above 4 in all areas of course evaluation (where 5=ideal). In addition, 17% of student groups (relative to 0% in 2015) proposed a sustainability-related policy as their final coursework project. Next Steps: The development and implementation of this brief session resulted in knowledge gain and favorable student response. This project is feasible for other Schools of Pharmacy to adapt and implement. Conflict of Interest: None &nbsp; Type:&nbsp;Not

The WHO UNESCO FIP Pharmacy Education Taskforce: enabling concerted and collective global action

Pharmacy Education is a priority area for the International Pharmaceutical Federation (FIP), the global federation representing pharmacists and pharmaceutical scientists worldwide that is spearheading the Global Pharmacy Education Taskforce. This paper describes the work of the Taskforce that was established in March 2008, explores key issues in pharmacy education development, and describes the Global Pharmacy Action Plan 2008-2010. Given the significance of pharmacy education to the diverse practice of contemporary pharmacists and pharmacy support personnel, there is a need for pharmacy education to attain greater visibility on the global human resources for health agenda. From this perspective, FIP is steering the development of holistic and comprehensive pharmacy education and pharmacy workforce action to support and strengthen regional, national, and local efforts. The role of a global organization such as FIP is to facilitate, catalyze, and share efforts to maximize pharmacy education development and stimulate international research to develop guidance, tools, and better understanding of key issues. To achieve this goal, FIP has (1) established a formal collaborative partnership with the 2 United Nations agencies representing the education and health sectors, United Nations Educational, Scientific and Cultural Organization (UNESCO) and the World Health Organization (WHO); and (2) established the Global Pharmacy Education Taskforce to serve as the coordinating body of these efforts. The initial effort will serve to leverage strategic leadership and maximize the impact of collective actions at global, regional, and national levels. Three project teams have been convened to conduct research, consultations and develop guidance in the domains of vision for pharmacy education, competency, quality assurance, academic workforce, and institutional capacity