Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Glargine (Gan & Lee Glargine) Compared with Originator Insulin Glargine (Lantus®) in Patients with Type 1 Diabetes after 26 Weeks Treatment.

OBJECTIVES: To compare the immunogenicity, safety, and efficacy of GL Glargine with that of the reference product (Lantus®) in patients with type 1 diabetes mellitus (T1DM). METHODS: This was a Phase 3, multicenter, randomized, open-label, equivalence study. 576 subjects with T1DM were randomized 1:1 to receive either GL Glargine or Lantus® treatment for 26 weeks. The primary endpoint was the percentage of subjects in each treatment group who developed treatment-induced anti-insulin antibody (AIA) after baseline and up to visit Week 26, which was evaluated using a country-adjusted logistic regression model. The study also compared the changes in glycated hemoglobin (HbA1c), and adverse events (AEs) including hypoglycemia. RESULTS: The percentage of subjects positive for treatment-induced AIA by Week 26 was 25.8% in the GL Glargine treatment group and 25.3% in the Lantus® treatment group, with a 90% confidence interval [CI] (-5.4, 6.5) of the difference in proportions that fell completely between the similarity margins (-11.3, 11.3). The least squares (LS) mean difference between treatment groups for changes in HbA1c was -0.08 (90% CI: -0.23, 0.06), and the other immunogenicity and safety profiles were comparable. CONCLUSION: GL Glargine demonstrated similar immunogenicity, efficacy, and safety compared to Lantus® over 26 weeks in patients with T1DM.

Assessing the quality and reliability of patient information regarding aesthetic fat grafting on YouTube.

PURPOSE: Patients increasingly consult social media regarding aesthetic surgery. Given the popularity of fat transfer operations, this study assesses the quality and reliability of patient information available on YouTube regarding aesthetic fat grafting. METHODS: The terms "fat grafting" and "fat transfer" were searched on YouTube with respect to the terms "face", "breast", "buttock", and "Brazilian butt lift". Filtered by view count, the top 20 unique, English language, aesthetic surgery-related videos for each search combination were reviewed by three independent reviewers for demographic and descriptive characteristics. Videos were rated for information reliability and quality using the modified DISCERN (MD) tool (1 = low, 5 = high) and global quality scale (GQS) (1 = poor, 5 = excellent). RESULTS: Out of 80 total videos, 76% were authored by physicians and 24% by laypersons. The overall mean MD score was 1.5 and the mean GQS was 2.6. Videos authored by physicians outscored those by non-medical authors (MD: 1.6 vs. 1.3; GQS 2.7 vs. 2.2). Board-certified plastic surgeon videos (N = 30) scored higher on both the MD (1.7 vs 1.3) and GQS (3.1 vs 2.2) than those of non-medical authors. On the contrary, videos by laypersons and non-plastic surgeons had 40% more views, twice as many "likes" and nearly double as many subscribers. CONCLUSION: The overall quality of information presented in aesthetic fat grafting procedures videos on YouTube is low and from unreliable sources. Surgeons should educate patients regarding potentially inaccurate information, and professional societies should disseminate high-quality media.

Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes.

Currently, no oral medications are available for type 1 diabetes (T1D). While our recent randomized placebo-controlled T1D trial revealed that oral verapamil had short-term beneficial effects, their duration and underlying mechanisms remained elusive. Now, our global T1D serum proteomics analysis identified chromogranin A (CHGA), a T1D-autoantigen, as the top protein altered by verapamil and as a potential therapeutic marker and revealed that verapamil normalizes serum CHGA levels and reverses T1D-induced elevations in circulating proinflammatory T-follicular-helper cell markers. RNA-sequencing further confirmed that verapamil regulates the thioredoxin system and promotes an anti-oxidative, anti-apoptotic and immunomodulatory gene expression profile in human islets. Moreover, continuous use of oral verapamil delayed T1D progression, promoted endogenous beta-cell function and lowered insulin requirements and serum CHGA levels for at least 2 years and these benefits were lost upon discontinuation. Thus, the current studies provide crucial mechanistic and clinical insight into the beneficial effects of verapamil in T1D.

Incorporation of a genetics-based information module into standardized diabetes patient education.

OBJECTIVE: The purpose of this study is to investigate the effectiveness of a genetics educational module created to improve understanding about the genetics of diabetes, assess motivation to engage in healthy lifestyle behaviors, and gauge interest in genetic testing for diabetes. METHODS: Participants were recruited from the Multidisciplinary Comprehensive Diabetes Clinic at the University of Alabama at Birmingham. Participants completed a pre-survey to assess three domains: (1) knowledge about diabetes etiology and testing, (2) healthy lifestyle behaviors, and (3) interest in genetic testing. Participants viewed a short, recorded educational module, then completed a post-survey to re-assess the domains. RESULTS: Participants increased knowledge about genetics of diabetes (p < 0.0001) and genetic testing (p = 0.0184), demonstrated motivation to adopt healthy behaviors (p < 0.0001), and decreased interest in genetic testing (p = 0.0833) after viewing the module. CONCLUSIONS: The educational module increased understanding of diabetes and increased motivation to adopt healthy behaviors. The need for patient-friendly educational modules explaining the genetics of diabetes will likely increase with continued discoveries of how genetics contributes to diabetes risk and outcomes. This short, educational module has the potential to provide genetic information in an effective way that is easily adapted in a routine clinic setting.

METFORMIN USE IS ASSOCIATED WITH REDUCED MORTALITY IN A DIVERSE POPULATION WITH COVID-19 AND DIABETES.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a growing pandemic with an increasing death toll that has been linked to various comorbidities as well as racial disparity. However, the specific characteristics of these at-risk populations are still not known and approaches to lower mortality are lacking. METHODS: We conducted a retrospective electronic health record data analysis of 25,326 subjects tested for COVID-19 between 2/25/20 and 6/22/20 at the University of Alabama at Birmingham Hospital, a tertiary health care center in the racially diverse Southern U.S. The primary outcome was mortality in COVID-19-positive subjects and the association with subject characteristics and comorbidities was analyzed using simple and multiple linear logistic regression. RESULTS: The odds ratio of contracting COVID-19 was disproportionately high in Blacks/African-Americans (OR 2.6; 95%CI 2.19-3.10; p<0.0001) and in subjects with obesity (OR 1.93; 95%CI 1.64-2.28; p<0.0001), hypertension (OR 2.46; 95%CI 2.07-2.93; p<0.0001), and diabetes (OR 2.11; 95%CI 1.78-2.48; p<0.0001). Diabetes was also associated with a dramatic increase in mortality (OR 3.62; 95%CI 2.11-6.2; p<0.0001) and emerged as an independent risk factor in this diverse population even after correcting for age, race, sex, obesity and hypertension. Interestingly, we found that metformin treatment was independently associated with a significant reduction in mortality in subjects with diabetes and COVID-19 (OR 0.33; 95%CI 0.13-0.84; p=0.0210). CONCLUSION: Thus, these results suggest that while diabetes is an independent risk factor for COVID-19-related mortality, this risk is dramatically reduced in subjects taking metformin, raising the possibility that metformin may provide a protective approach in this high risk population.

Infections Associated with Resterilized Pacemakers and Defibrillators.

BACKGROUND: Access to pacemakers and defibrillators is problematic in places with limited resources. Resterilization and reuse of implantable cardiac devices obtained post mortem from patients in wealthier nations have been undertaken, but uncertainty around the risk of infection is a concern. METHODS: A multinational program was initiated in 1983 to provide tested and resterilized pacemakers and defibrillators to underserved nations; a prospective registry was established in 2003. Patients who received reused devices in this program were matched in a 1:3 ratio with control patients who received new devices implanted in Canada. The primary outcome was infection or device-related death, with mortality from other causes modeled as a competing risk. RESULTS: Resterilized devices were implanted in 1051 patients (mean [±SD] age, 63.2±18.5 years; 43.6% women) in Mexico (36.0%), the Dominican Republic (28.1%), Guatemala (26.6%), and Honduras (9.3%). Overall, 85% received pacemakers and 15% received defibrillators, with one (55.5%), two (38.8%), or three (5.7%) leads. Baseline characteristics did not differ between these patients and the 3153 matched control patients. At 2 years of follow-up, infections had occurred in 21 patients (2.0%) with reused devices and in 38 (1.2%) with new devices (hazard ratio, 1.66; 95% confidence interval, 0.97 to 2.83; P = 0.06); there were no device-related deaths. The most common implicated pathogens were Staphylococcus aureus and S. epidermidis. CONCLUSIONS: Among patients in underserved countries who received a resterilized and reused pacemaker or defibrillator, the incidence of infection or device-related death at 2 years was 2.0%, an incidence that did not differ significantly from that seen among matched control patients with new devices in Canada.

Hand and Upper Extremity Infections in Intravenous Drug Users: Epidemiology and Predictors of Outcomes.

PURPOSE: Injectable drug use (IDU) is a national epidemic, public health problem, and common cause of hand and upper extremity (UE) infections. This study assesses the epidemiology of the IDU patient population presenting to a Midwestern academic medical center emergency department (ED) and examines predictors influencing morbidity and outcomes. METHODS: A retrospective review was performed using International Classification of Diseases, Ninth Revision (ICD-9) codes to identify all adult patients presenting to the ED with hand/UE infections, with and without concurrent IDU diagnoses, over a period of 2.5 years. Demographics and clinical factors were examined utilizing bivariate and multivariable analyses to identify predictors of outcomes, including not completing outpatient follow-up and leaving against medical advice (AMA). RESULTS: A total of 1,482 patients with 1,754 ED visits for hand/UE infections were identified, including 308 patients with IDU-acquired infections (396 visits) and 1,174 patients with non-IDU infections (1,358 visits). Psychiatric comorbidities and hepatitis C were common in the IDU group (51% and 39%, respectively), and 31% of IDU patients were uninsured. Heroin use was identified in 96% of visits. The IDU infections were more likely to have surgical intervention than those in non-IDU patients (16% vs 6%), and a longer mean length hospital stay (2.4 vs 0.9 days). The IDU patients were more likely than non-IDU patients to leave AMA. In multivariable analysis, IDU, psychiatric comorbidity, and insurance status were independent predictors (P < .05) for leaving AMA. CONCLUSIONS: In the setting of a national epidemic, hand/UE infections due to IDU are a common problem seen by hand surgeons. This study characterizes the growing IDU patient population at an urban academic medical center, examining the largest cohort of these patients to date. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes.

Background: Coronavirus disease-2019 (COVID-19) is a growing pandemic with an increasing death toll that has been linked to various comorbidities as well as racial disparity. However, the specific characteristics of these at-risk populations are still not known and approaches to lower mortality are lacking. Methods: We conducted a retrospective electronic health record data analysis of 25,326 subjects tested for COVID-19 between 2/25/20 and 6/22/20 at the University of Alabama at Birmingham Hospital, a tertiary health care center in the racially diverse Southern U.S. The primary outcome was mortality in COVID-19-positive subjects and the association with subject characteristics and comorbidities was analyzed using simple and multiple linear logistic regression. Results: The odds ratio of contracting COVID-19 was disproportionately high in Blacks/African-Americans (OR 2.6; 95% CI 2.19-3.10; p<0.0001) and in subjects with obesity (OR 1.93; 95% CI 1.64-2.28; p<0.0001), hypertension (OR 2.46; 95% CI 2.07-2.93; p<0.0001), and diabetes (OR 2.11; 95% CI 1.78-2.48; p<0.0001). Diabetes was also associated with a dramatic increase in mortality (OR 3.62; 95% CI 2.11-6.2; p<0.0001) and emerged as an independent risk factor in this diverse population even after correcting for age, race, sex, obesity, and hypertension. Interestingly, we found that metformin treatment prior to diagnosis of COVID-19 was independently associated with a significant reduction in mortality in subjects with diabetes and COVID-19 (OR 0.33; 95% CI 0.13-0.84; p=0.0210). Conclusion: Thus, these results suggest that while diabetes is an independent risk factor for COVID-19-related mortality, this risk is dramatically reduced in subjects taking metformin prior to diagnosis of COVID-19, raising the possibility that metformin may provide a protective approach in this high risk population.

Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC.

OBJECTIVE: The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS: Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS: The strongest associations in the MHC class II region (rs3957146, ß [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (ß [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, ß [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS: In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.

The Role of Perceived Discrimination and Other Psychosocial Factors in Explaining Diabetes Distress Among Older African American and White Adults.

Background: Diabetes distress, also referred to as diabetes-related emotional distress, has been shown to contribute to worsening diabetes status over time as well as increased depressive symptoms. Other psychosocial factors, including perceived discrimination, are also related to poorer diabetes outcomes. This study explores the relationships between diabetes distress and several psychosocial variables relevant to health disparities (i.e., race, cognition, social support, physician trust, and perceived discrimination) among older adults with type 2 diabetes mellitus. Design and Method: Structured telephone interviews were conducted with 148 African American and White adults (age ≥65) with type 2 diabetes mellitus. Results: Perceived discrimination and physician trust partially explain the relationship between African American race and diabetes distress. Younger age, less satisfaction with social support, and lower physician trust were associated with higher levels of diabetes distress. Conclusion: These results highlight the need to address unique stressors, such as perceived discrimination, among racial/ethnic minorities to improve diabetes-related outcomes.

A randomized cross-over trial to determine the effect of a protein vs. carbohydrate preload on energy balance in ad libitum settings.

BACKGROUND: Although high protein diets have been tested in controlled environments for applications to weight management, it is not understood if adding high protein foods to the diet would impact ad libitum energy balance in the absence of other lifestyle changes. METHODS: This double-blinded randomized crossover trial compared the effects of a protein shake (PS) to a carbohydrate shake (CS), consumed prior to each major meal to equate to 20% of total energy needs over the course of the day, on energy balance over two 5-day treatment periods in healthy adults with BMI 20-30 kg/m2. Tri-axial accelerometers estimated physical activity energy expenditure. Ad libitum energy intake was measured in a laboratory kitchen. RESULTS: Energy balance was positive during both treatment periods but was not different between periods. There were no interactions between treatment and preload caloric dose or treatment and BMI status on energy balance. Satiety ratings did not differ for any pairwise comparisons between treatment and caloric dose. Controlling for gender and basal metabolic rate, thermic effect of food was greater for PS than CS. CONCLUSIONS: Preload periods significantly altered the macronutrient composition of the overall diet. This study found limited evidence that carbohydrate or protein preloads have differential effects on energy balance in short-term ad libitum settings. TRIAL REGISTRATION: This trial was pre-registered on clinicaltrials.gov as NCT02613065 on 11/30/2015.

Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial.

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body mass (p = .003) and thigh muscle mass (p < .001) than metformin. CT scan showed that increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin. There was a trend for blunted strength gains in metformin that did not reach statistical significance. Analyses of vastus lateralis muscle biopsies showed that metformin did not affect fiber hypertrophy, or increases in satellite cell or macrophage abundance with PRT. However, placebo had decreased type I fiber percentage while metformin did not (p = .007). Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT. These results underscore the benefits of PRT in older adults, but metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. ClinicalTrials.gov Identifier: NCT02308228.

Serum miR-204 is an early biomarker of type 1 diabetes-associated pancreatic beta-cell loss.

Pancreatic beta-cell death is a major factor in the pathogenesis of type 1 diabetes (T1D), but straightforward methods to measure beta-cell loss in humans are lacking, underlining the need for novel biomarkers. Using studies in INS-1 cells, human islets, diabetic mice, and serum samples of subjects with T1D at different stages, we have identified serum miR-204 as an early biomarker of T1D-associated beta-cell loss in humans. MiR-204 is a highly enriched microRNA in human beta-cells, and we found that it is released from dying beta-cells and detectable in human serum. We further discovered that serum miR-204 was elevated in children and adults with T1D and in autoantibody-positive at-risk subjects but not in type 2 diabetes or other autoimmune diseases and was inversely correlated with remaining beta-cell function in recent-onset T1D. Thus, serum miR-204 may provide a much needed novel approach to assess early T1D-associated human beta-cell loss even before onset of overt disease.

American Diabetes Association 2019 Conference Podcast With the Editor-in-Chief: What Are the Outcomes from ADA This Year and What Are the Future Developments in Diabetes?

Podcast recording of Fernando Ovalle live from the ADA 2019 conference in San Francisco (MP4 177883 kb).

Publishing Conversion Rates and Trends in Abstracts Presented at the American Association for Hand Surgery Annual Meeting: A Five-Year Review.

Background: Abstract presentation at scientific meetings grants attendees early access to innovation within the field, and ultimate journal publication serves as marker of research quality. This study aims to assess the publication conversion rate of abstracts presented at the American Association for Hand Surgery (AAHS) annual conference over 5 years and examine variables related to publication. Methods: Abstract information for oral and poster presentations from the 2012 to 2016 AAHS annual meetings was obtained through the AAHS website. A comprehensive literature search was conducted for journal publications correlating with abstracts based on titles, authors, and key words. Variables analyzed included study type, time to publication, and journal of publication. Results: In all, 1135 abstracts were reviewed from the 5-year period, consisting of 535 oral presentations and 600 posters. Overall, 532 articles (47%) were published. The publication conversion rate was 49% for oral presentations and 45% for posters. Mean time to publication was 11 months, with most publications occurring within 2 years (87%). The most common journals for publication were Journal of Hand Surgery (30%), HAND (21%), and Plastic and Reconstructive Surgery (7%). Conclusions: About half of the studies presented at the annual AAHS meeting become published, with similar rates between oral and poster formats. Most of the successful abstracts achieved publication within 2 years from presentation, demonstrating the need for timely completion of manuscripts. The publication conversion rate increased in recent years, emphasizing the continued improvement of the scientific quality of presentations at the AAHS meeting.

Global Contributions to Aesthetic Surgery Journal Over the Past Decade.

BACKGROUND: The Aesthetic Surgery Journal (ASJ) is a world-renowned publication with valuable contributions from around the globe. OBJECTIVES: To better characterize the journal's evolving representation of global contributions to aesthetic surgery, the authors examined the author affiliations of all articles published in ASJ over the last decade. METHODS: A PubMed search was performed for all journal articles published in ASJ from January 2008 to August 2018. For each article, the first author's primary affiliation as indexed in MEDLINE was recorded as the source country. Data were tabulated by source country and year. The authorless errata, corrigenda, and Cosmetic Surgery National Data Bank Statistics were excluded from analysis. RESULTS: A total of 1746 articles were published during this period, contributed from 49 distinct countries. All continents other than Antarctica were represented. Higher income countries where aesthetic surgery is more prevalent produced 87% of published articles. The total number of published articles in ASJ has climbed from 77 annually in 2008 to 318 in 2018 as of August. In 2008, 27.3% of articles were from non-US countries, whereas in 2018 this increased to 43.7%. In particular, Turkey, the United Kingdom, Australia, Brazil, and Italy demonstrate steady increases in contributions over the 10-year period. CONCLUSIONS: Publications in ASJ have increased in number over the past decade, and the journal has become increasingly global in its network of contributing authors. The increased global contribution to the ASJ may enhance readers' experience both in the United States and in the world beyond.

A Case Report of a Breast Implant-Associated Plasmacytoma and Literature Review of Non-ALCL Breast Implant-Associated Neoplasms.

Lymphomas associated with breast implants are rare, with the most common being anaplastic large cell lymphoma (ALCL). Non-ALCL breast implant-associated lymphomas are even more rare, with only a small handful of such neoplasms reported to date. Given the need to better understand these pathologies as well as the increasing clinical and media attention being paid to these diseases, we review the available literature of hematolymphoid neoplasms other than ALCL associated with breast implants and describe the first case of a patient diagnosed with a primary breast implant-associated plasmacytoma.

Acute Effects of Exercise Intensity on Insulin Sensitivity under Energy Balance.

Exercise is known to improve insulin sensitivity (SI); however, studies to date have been confounded by negative energy deficits after exercise. PURPOSE: The primary objective of this study was to assess the effect of 8 to 16 wk of aerobic exercise training on the SI of untrained women under rigorously controlled energy-balanced conditions. The secondary objective was to determine if one acute bout of moderate-intensity continuous (MIC) or high-intensity interval (HII) exercise further affected SI. METHODS: Insulin sensitivity was assessed in 28 untrained women at baseline, after 8 to 16 wk of training with no-exercise (NE) before assessment, 22 h after MIC (50% V˙O2peak), and 22 h after HII (84% V˙O2peak) using a hyperinsulinemic-euglycemic clamp. Participants were in a whole-room indirect calorimeter during each condition, and food intake was adjusted to ensure energy balance across 23 h before each clamp. RESULTS: There were no significant differences in acute energy balance between each condition. Results indicated a significant main effect of time, such that SI was higher during the HII condition compared with both baseline and NE (P < 0.05). No significant differences in SI were observed after NE or MIC. CONCLUSIONS: Widely reported improvements in SI in response to chronic exercise training may be mediated in part by shifts in energy balance. However, an acute bout of HII exercise may increase SI even in the context of energy balance.