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Background: Current evidence supports the use of wearable trackers by people with cardiometabolic conditions. However, as the health benefits are small and confounded by heterogeneity, there remains uncertainty as to which patient groups are most helped by wearable trackers., Objective: This study examined the effects of wearable trackers in patients with cardiometabolic conditions to identify subgroups of patients who most benefited and to understand interventional differences., Methods: We obtained individual participant data from randomized controlled trials of wearable trackers that were conducted before December 2020 and measured steps per day as the primary outcome in participants with cardiometabolic conditions including diabetes, overweight or obesity, and cardiovascular disease. We used statistical models to account for clustering of participants within trials and heterogeneity across trials to estimate mean differences with the 95% CI., Results: Individual participant data were obtained from 9 of 25 eligible randomized controlled trials, which included 1481 of 3178 (47%) total participants. The wearable trackers revealed that over the median duration of 12 weeks, steps per day increased by 1656 (95% CI 918-2395), a significant change. Greater increases in steps per day from interventions using wearable trackers were observed in men (interaction coefficient -668, 95% CI -1157 to -180), patients in age categories over 50 years (50-59 years: interaction coefficient 1175, 95% CI 377-1973; 60-69 years: interaction coefficient 981, 95% CI 222-1740; 70-90 years: interaction coefficient 1060, 95% CI 200-1920), White patients (interaction coefficient 995, 95% CI 360-1631), and patients with fewer comorbidities (interaction coefficient -517, 95% CI -1188 to -11) compared to women, those aged below 50, non-White patients, and patients with multimorbidity. In terms of interventional differences, only face-to-face delivery of the tracker impacted the effectiveness of the interventions by increasing steps per day., Conclusions: In patients with cardiometabolic conditions, interventions using wearable trackers to improve steps per day mostly benefited older White men without multimorbidity., Trial Registration: PROSPERO CRD42019143012; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=143012., (©Alexander Hodkinson, Evangelos Kontopantelis, Salwa S Zghebi, Christos Grigoroglou, Brian McMillan, Harm van Marwijk, Peter Bower, Dialechti Tsimpida, Charles F Emery, Mark R Burge, Hunter Esmiol, Margaret E Cupples, Mark A Tully, Kaberi Dasgupta, Stella S Daskalopoulou, Alexandra B Cooke, Ayorinde F Fayehun, Julie Houle, Paul Poirier, Thomas Yates, Joseph Henson, Derek R Anderson, Elisabeth B Grey, Maria Panagioti. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 30.08.2022.)

The Mountain West Clinical Translational Research - Infrastructure Network (MW CTR-IN), established in 2013, is a research network of 13 university partners located among seven Institutional Development Award (IDeA) states targeting health disparities. This is an enormous undertaking because of the size of the infrastructure network (encompassing a third of the US landmass and spanning four time zones in predominantly rural and underserved areas, with populations that have major health disparities issues). In this paper, we apply the barriers, strategies, and metrics to an adapted educational conceptual model by Fink (2013). Applying this model, we used four tailored approaches across this regional infrastructure network to: (1) assess individual faculty specific needs, (2) reach out and engage with faculty, (3) provide customized services to meet the situational needs of faculty, and (4) utilize a "closed communication feedback loop" between Professional Development (PD) core and MW CTR-IN faculty within the context of their home institutional environment. Summary statement results from participating faculty show that these approaches were positive. Grounded in best educational practice approaches, we have an opportunity to refine and build from this sound foundation with implications for future use in other CTR-IN networks and institutions in the IDeA states., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2022.)

Objective: To assess the risk of new-onset type 1 diabetes mellitus (T1D) diagnosis following COVID-19 diagnosis and the impact of COVID-19 diagnosis on the risk of diabetic ketoacidosis (DKA) in patients with prior T1D diagnosis., Research Design and Methods: Retrospective data consisting of 27,292,879 patients from the Cerner Real-World Data were used. Odds ratios, overall and stratified by demographic predictors, were calculated to assess associations between COVID-19 and T1D. Odds ratios from multivariable logistic regression models, adjusted for demographic and clinical predictors, were calculated to assess adjusted associations between COVID-19 and DKA. Multiple imputation with multivariate imputation by chained equations (MICE) was used to account for missing data., Results: The odds of developing new-onset T1D significantly increased in patients with COVID-19 diagnosis (OR: 1.42, 95% CI: 1.38, 1.46) compared to those without COVID-19. Risk varied by demographic groups, with the largest risk among pediatric patients ages 0-1 years (OR: 6.84, 95% CI: 2.75, 17.02) American Indian/Alaskan Natives (OR: 2.30, 95% CI: 1.86, 2.82), Asian or Pacific Islanders (OR: 2.01, 95% CI: 1.61, 2.53), older adult patients ages 51-65 years (OR: 1.77, 95% CI: 1.66, 1.88), those living in the Northeast (OR: 1.71, 95% CI: 1.61, 1.81), those living in the West (OR: 1.65, 95% CI: 1.56, 1.74), and Black patients (OR: 1.59, 95% CI: 1.47, 1.71). Among patients with diagnosed T1D at baseline (n = 55,359), 26.7% (n = 14,759) were diagnosed with COVID-19 over the study period. The odds of developing DKA for those with COVID-19 were significantly higher (OR 2.26, 95% CI: 2.04, 2.50) than those without COVID-19, and the largest risk was among patients with higher Elixhauser Comorbidity Index., Conclusions: COVID-19 diagnosis is associated with significantly increased risk of new-onset T1D, and American Indian/Alaskan Native, Asian/Pacific Islander, and Black populations are disproportionately at risk. In patients with pre-existing T1D, the risk of developing DKA is significantly increased following COVID-19 diagnosis., Competing Interests: The authors have declared that no competing interests exist.

Prior single-institution studies suggest that preoperative vitamin D deficiency (VDD) is associated with postoperative hypocalcemia and a prolonged length of hospital stay following total thyroidectomy. In this study, we employ a multi-institutional, de-identified electronic health records database to address this issue. We hypothesize that total thyroidectomy patients with preoperative VDD will be at an increased associated risk of postoperative hypocalcemia and hospitalization. Using Cerner Health Facts, we identified 2447 patients who underwent total or subtotal thyroidectomy between 2008 and 2016 and who had a documented 25-hydroxyvitamin D concentration obtained within 12 months of the surgery date using International Classification of Diseases 9/10, Current Procedural Terminology and Healthcare Common Procedure Coding System codes. Data from 984 patients who underwent total thyroidectomy were analyzed. Analysis of variance models estimated the effect of VDD on postoperative numerical variables. Multiple logistic regression estimated the risk of postoperative hypocalcemia and hospital stay, adjusting for any imbalanced demographic variables and operative characteristics. On average, postoperative total calcium concentrations in the VDD group were lower by 0.3 mg/dL compared with that of the non-VDD group (p<0.01). The risk of postoperative hypocalcemia was 2.2 times higher in the VDD group compared with the non-VDD group (p<0.01). Although the length of hospital stay after thyroidectomy was longer in the VDD group compared with the non-VDD group (p=0.03), VDD is not an independent risk factor for prolonged hospitalization following thyroidectomy (p=0.13). VDD is associated with a higher risk of hypocalcemia following total thyroidectomy. Prethyroidectomy operative screening for VDD should be considered., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Lysosomal damage activates AMPK, a regulator of macroautophagy/autophagy and metabolism, and elicits a strong ubiquitination response. Here we show that the cytosolic lectin LGALS9 detects lysosomal membrane breach by binding to lumenal glycoepitopes, and directs both the ubiquitination response and AMPK activation. Proteomic analyses have revealed increased LGALS9 association with lysosomes, and concomitant changes in LGALS9 interactions with its newly identified partners that control ubiquitination-deubiquitination processes. An LGALS9-inetractor, deubiquitinase USP9X, dissociates from damaged lysosomes upon recognition of lumenal glycans by LGALS9. USP9X's departure from lysosomes promotes K63 ubiquitination and stimulation of MAP3K7/TAK1, an upstream kinase and activator of AMPK hitherto orphaned for a precise physiological function. Ubiquitin-activated MAP3K7/TAK1 controls AMPK specifically during lysosomal injury, caused by a spectrum of membrane-damaging or -permeabilizing agents, including silica crystals, the intracellular pathogen Mycobacterium tuberculosis , TNFSF10/TRAIL signaling, and the anti-diabetes drugs metformin. The LGALS9-ubiquitin system activating AMPK represents a novel signal transduction system contributing to various physiological outputs that are under the control of AMPK, including autophagy, MTOR, lysosomal maintenance and biogenesis, immunity, defense against microbes, and metabolic reprograming., Abbreviations: AMPK: AMP-activated protein kinase; APEX2: engineered ascorbate peroxidase 2; ATG13: autophagy related 13; ATG16L1: autophagy related 16 like 1; BMMs: bone marrow-derived macrophages; CAMKK2: calcium/calmodulin dependent protein kinase kinase 2; DUB: deubiquitinase; GPN: glycyl-L-phenylalanine 2-naphthylamide; LLOMe: L-leucyl-L-leucine methyl ester; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MERIT: membrane repair, removal and replacement; MTOR: mechanistic target of rapamycin kinase; STK11/LKB1: serine/threonine kinase 11; TNFSF10/TRAIL: TNF superfamily member 10; USP9X: ubiquitin specific peptidase 9 X-linked.

In this work, we demonstrate a novel approach to assessing the risk of Diabetic Peripheral Neuropathy (DPN) using only the retinal images of the patients. Our methodology consists of convolutional neural network feature extraction, dimensionality reduction and feature selection with random projections, combination of image features to case-level representations, and the training and testing of a support vector machine classifier. Using clinical diagnosis as ground truth for DPN, we achieve an overall accuracy of 89% on a held-out test set, with sensitivity reaching 78% and specificity reaching 95%.

Purpose: Aberrant thyroid function causes dysregulated metabolic homeostasis. Literature has demonstrated hypercoagulability in hypothyroidism, suggesting a risk for thromboembolic events (TEE). We hypothesize that individuals with hypothyroidism will experience more clinically-diagnosed TEE than euthyroid individuals., Methods: De-identified patient data from the University of New Mexico Health Sciences Center were retrieved using thyrotropin (TSH; thyroid-stimulating hormone) for case-finding from 2005 to 2007 and ICD billing codes to identify TEE during the follow-up period of 10 to 12 years. Diagnoses affecting coagulation were excluded and 12 109 unique enrollees were categorized according to TSH concentration as Hyperthyroid (n = 510), Euthyroid (n = 9867), Subclinical Hypothyroid (n = 1405), or Overtly Hypothyroid (n = 327). Analysis with multiple logistic regression provided the odds of TEE while adjusting for covariates., Results: There were 228 TEEs in the cohort over 5.1 ± 4.3 years of follow-up. Risk of TEE varied significantly across study groups while adjusting for sex, race/ethnicity, levothyroxine, oral contraceptive therapy, and visit status (outpatient vs non-outpatient), and this risk was modified by age. Overt Hypothyroidism conferred a significantly higher risk of TEE than Euthyroidism below age 35, and Hyperthyroidism conferred an increased risk for TEE at age 20. Analysis also demonstrated a higher age-controlled risk for a subsequent TEE in men compared with women (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.02-1.81). Subanalysis of smoking status (n = 5068, 86 TEE) demonstrated that smokers have 2.21-fold higher odds of TEE relative to nonsmokers (95% CI, 1.41-3.45)., Conclusions: In this retrospective cohort study, Overt Hypothyroidism conferred increased risk of TEE over the next decade for individuals younger than 35 years of age, as compared with Euthyroidism., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

AMPK is a central regulator of metabolism and autophagy. Here we show how lysosomal damage activates AMPK. This occurs via a hitherto unrecognized signal transduction system whereby cytoplasmic sentinel lectins detect membrane damage leading to ubiquitination responses. Absence of Galectin 9 (Gal9) or loss of its capacity to recognize lumenal glycans exposed during lysosomal membrane damage abrogate such ubiquitination responses. Proteomic analyses with APEX2-Gal9 have revealed global changes within the Gal9 interactome during lysosomal damage. Gal9 association with lysosomal glycoproteins increases whereas interactions with a newly identified Gal9 partner, deubiquitinase USP9X, diminishes upon lysosomal injury. In response to damage, Gal9 displaces USP9X from complexes with TAK1 and promotes K63 ubiquitination of TAK1 thus activating AMPK on damaged lysosomes. This triggers autophagy and contributes to autophagic control of membrane-damaging microbe Mycobacterium tuberculosis. Thus, galectin and ubiquitin systems converge to activate AMPK and autophagy during endomembrane homeostasis., Competing Interests: Declaration of Interests M.Z. was an employee of Human Metabolome Technologies America, Boston, MA, USA., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Research participants want to receive results from studies in which they participate. However, health researchers rarely share the results of their studies beyond scientific publication. Little is known about the barriers researchers face in returning study results to participants., Methods: Using a mixed-methods design, health researchers ( N = 414) from more than 40 US universities were asked about barriers to providing results to participants. Respondents were recruited from universities with Clinical and Translational Science Award programs and Prevention Research Centers., Results: Respondents reported the percent of their research where they experienced each of the four barriers to disseminating results to participants: logistical/methodological, financial, systems, and regulatory. A fifth barrier, investigator capacity, emerged from data analysis. Training for research faculty and staff, promotion and tenure incentives, and funding agencies supporting dissemination of results to participants were solutions offered to overcoming barriers., Conclusions: Study findings add to literature on research dissemination by documenting health researchers' perceived barriers to sharing study results with participants. Implications for policy and practice suggest that additional resources and training could help reduce dissemination barriers and increase the return of results to participants., (© The Association for Clinical and Translational Science 2019.)

The NIH-funded center for autophagy research named Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence, located at the University of New Mexico Health Science Center is now completing its second year as a working center with a mission to promote autophagy research locally, nationally, and internationally. The center has thus far supported a cadre of 6 junior faculty (mentored PIs; mPIs) at a near-R01 level of funding. Two mPIs have graduated by obtaining their independent R01 funding and 3 of the remaining 4 have won significant funding from NIH in the form of R21 and R56 awards. The first year and a half of setting up the center has been punctuated by completion of renovations and acquisition and upgrades for equipment supporting autophagy, inflammation and metabolism studies. The scientific cores usage, and the growth of new studies is promoted through pilot grants and several types of enablement initiatives. The intent to cultivate AIM as a scholarly hub for autophagy and related studies is manifested in its Vibrant Campus Initiative, and the Tuesday AIM Seminar series, as well as by hosting a major scientific event, the 2019 AIM symposium, with nearly one third of the faculty from the International Council of Affiliate Members being present and leading sessions, giving talks, and conducting workshop activities. These and other events are often videostreamed for a worldwide scientific audience, and information about events at AIM and elsewhere are disseminated on Twitter and can be followed on the AIM web site. AIM intends to invigorate research on overlapping areas between autophagy, inflammation and metabolism with a number of new initiatives to promote metabolomic research. With the turnover of mPIs as they obtain their independent funding, new junior faculty are recruited and appointed as mPIs. All these activities are in keeping with AIM's intention to enable the next generation of autophagy researchers and help anchor, disseminate, and convey the depth and excitement of the autophagy field.

Background: Although research participants are generally interested in receiving results from studies in which they participate, health researchers rarely communicate study findings to participants. The present study was designed to provide opportunity for a broad group of health researchers to describe their experiences and concerns related to sharing results (i.e. aggregate study findings) with research participants., Methods: We used a mixed-methods concurrent triangulation design, relying on an online survey to capture health researchers' experiences, perceptions and barriers related to sharing study results with participants. Respondents were health researchers who conduct research that includes the consent of human subjects and hold a current appointment at an accredited academic medical institution within the United States. For quantitative data, the analytic strategy focused on item-level descriptive analyses. For the qualitative data, analyses focused on a priori themes and emergent subthemes., Results: Respondents were 414 researchers from 44 academic medical institutions; 64.5% reported that results should always be shared with participants, yet 60.8% of respondents could identify studies in which they had a leadership role where results were not shared. Emergent subthemes from researchers' reasons why results should be shared included participant ownership of findings and benefits of results sharing to science. Reasons for not sharing included concerns related to participants' health literacy and participants' lack of desire for results. Across all respondents who described barriers to results sharing, the majority described logistical barriers., Conclusions: Study findings contribute to the literature by documenting researchers' perspectives and experiences about sharing results with research participants, which can inform efforts to improve results sharing. Most respondents indicated that health research results should always be shared with participants, although the extent to which many respondents described barriers to results sharing as well as reported reasons not to share results suggests difficulties with a one-size-fits-all approach to improving results sharing.

Background: Posttraumatic stress disorder (PTSD) is a common and debilitating disorder among war veterans. Although complementary and alternative therapies are gaining acceptance in the treatment of PTSD, the efficacy of animal-based therapies in this disorder is unknown. The goal of equine-assisted psychotherapy (EAP) is to improve the social, emotional, and/or cognitive functions of individuals with PTSD., Objective: This study aims to explore the effects of EAP on PTSD symptoms. We hypothesized that veterans with PTSD who participate in a standardized EAP program for 1 h per week for 6 weeks would experience decreased PTSD symptoms and would demonstrate increased resilience as compared with individuals who do not receive EAP intervention., Design, Setting, Participants and Interventions: We conducted a sequentially assigned, two-arm parallel group trial comparing 6 weeks of EAP with standard, previously established, ongoing PTSD therapy. Therapy was conducted at a community EAP facility in conjunction with an academic University Hospital. Twenty adult veterans with symptomatic PTSD completed the study. Ten adult veterans with previously diagnosed PTSD were assigned to EAP and received directed interaction with trained horses for one hour a week in groups of 3 or 4 individuals, while also continuing their previously established therapies. A certified therapist supervised the sessions, and a professional horse handler was also present. Results were compared with those from 10 adult veterans who only received their standard previously established PTSD care as prescribed by their provider., Main Outcome Measures: Changes in salivary cortisol, scores for the PTSD Check List-Military Version (PCL-M) and the Connor-Davidson Resilience Scale (CD-RISC) after 6 weeks of study were measured., Results: Of the 20 enrolled patients, 10 served in Afghanistan, 5 served in Iraq, and 3 served in Vietnam. Subjects were (47 ± 14) years old, were predominantly male, and had a body mass index of (29 ± 7) kg/m 2 . They had (9.2 ± 6.1) years of military service and carried 66% ± 37% service-connected disability. PCL-M scores declined significantly in both groups and CD-RISC scores increased significantly in the EAP group. There was no difference between the groups with respect to the magnitude of change., Conclusion: As compared to the control group, a 6-week EAP program did not produce a statistically significant difference with respect to PCL-M and CD-RISC scores, or salivary cortisol. However, our results suggest that EAP may work as well as standard therapy with respect to these parameters. This study supports further inquiry into EAP as a potentially efficacious alternative for veterans suffering from PTSD., Trial Registration: ClinicalTrials.gov NCT #03039361., (Copyright © 2018 Shanghai Changhai Hospital. All rights reserved.)

In this article, we present an exceptional case of pituitary apoplexy in which a patient presented with meningeal symptoms of headache, stiff neck, and nausea rather than the classical findings of ophthalmoplegia and/or vision loss. The patient has had 2 similar presentations with cerebrospinal fluid showing neutrophilic pleocytosis, as well as a computed tomography scan showing a prominent pituitary gland. On current presentation, the patient's vital signs were stable and the physical examination was remarkable for nuchal rigidity. Magnetic resonance imaging of the head revealed an expansile pituitary gland lesion measuring 2.0 × 1.7 × 1.5 cm with upward displacement of the overlying optic chiasm. Cerebrospinal fluid showed neutrophilic pleocytosis, low glucose, high protein content, and negative bacterial and fungal cultures. Surgical decompression subsequently revealed findings consistent with pituitary apoplexy. This is the first known case in which a patient had recurrent episodes of meningitis due to pituitary apoplexy in the absence of a clinical deterioration. Early identification of apoplexy masquerading as meningitis will allow early surgical intervention, if necessary, to prevent complications, recurrence, and morbidity. As such, the presence of sterile meningitis in patients with a known pituitary adenoma should be considered for prompt surgical evaluation., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Beige adipocytes are present in white adipose tissue (WAT) and have thermogenic capacity to orchestrate substantial energy metabolism and counteract obesity. However, adipocyte-derived signals that act on progenitor cells to control beige adipogenesis remain poorly defined. Here, we show that adipose-specific depletion of Raptor, a key component of mTORC1, promoted beige adipogenesis through prostaglandins (PGs) synthesized by cyclooxygenase-2 (COX-2). Moreover, Raptor-deficient mice were resistant to diet-induced obesity and COX-2 downregulation. Mechanistically, mTORC1 suppressed COX-2 by phosphorylation of CREB-regulated transcription coactivator 2 (CRTC2) and subsequent dissociation of CREB to cox-2 promoter in adipocytes. PG treatment stimulated PKA and promoted differentiation of progenitor cells to beige adipocytes in culture. Ultimately, we show that pharmacological inhibition or suppression of COX-2 attenuated mTORC1 inhibition-induced thermogenic gene expression in inguinal WAT in vivo and in vitro. Our study identifies adipocyte-derived PGs as key regulators of white adipocyte browning, which occurs through mTORC1 and CRTC2., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Recruitment and engagement for clinical and translational research is challenging, especially among medically underserved and ethnic or racial minority populations., Methods: We present a comprehensive model developed through the Clinical and Translational Science Center at the University of New Mexico Health Sciences Center that addresses three critical aspects of participant recruitment., Results: The components of the model are: 1) Recruitment from within UNM to UNM-centered studies, 2) recruitment from within UNM to community-based studies, and 3) recruitment from outside UNM to UNM-centered studies., Conclusions: This model has increased research participant recruitment, especially among medically underserved populations, and offers generalizable translational solutions to common clinical and translational research challenges, especially in settings with similar demographic and geographic characteristics., Competing Interests: Conflicts of Interest: The authors do not have any conflicts of interest to report.

Including patient stakeholders as active members of the research team is essential to a patient-engaged research design. To hire community-based research staff for a study comparing the effectiveness of diabetes self-management programs for Latinos, we had to provide phlebotomy training which was not allowed under the fiscal guidelines of our funders. By collaborating with partners at the Clinical and Translational Science Center, we were not only able to find a creative solution and provide phlebotomy training to our research staff but the process of creating the training also contributed to improved infrastructure for patient-engaged research at our institution., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The highest incidence of relapse to smoking occurs within the first 2 weeks of a cessation attempt. In addition to enhanced nicotine craving, this phase of smoking cessation is also marked by learning and memory dysfunction. Many smokers are not able to overcome these symptoms, and they relapse to smoking shortly after trying to quit. In two clinical studies, we evaluated intranasal insulin for efficacy in improving learning and memory function during nicotine withdrawal. Our first study was a crossover evaluation (N = 19) following 20 hr of smoking abstinence. Study 2 was a parallel design study (N = 50) following 16 hr of abstinence. Intranasal insulin (60 IU) dose was administered in both studies and cognitive function was measured using California Verbal Learning Test-II. Intranasal insulin did not improve learning over the 5 verbal learning trials. In addition, intranasal insulin did not improve either short- or long-delay recall in either study. In summary, the one-time administration of intranasal insulin does not improve verbal learning and memory in smokers. Whether longer administration schedules may be of benefit should be evaluated in future studies., (Copyright © 2018 John Wiley & Sons, Ltd.)

Thionamides are anti-thyroid drugs (ATD) used to treat autonomous thyrotoxicosis. Although efficacious, these medications carry a risk of neutropenia or agranulocytosis. Some risk factors for ATD-induced neutropenia have been identified, including dose, age, and female sex, but the role of race and ethnicity has not been well studied. We hypothesize that there will be no effect of race or ethnicity on the change in Absolute Neutrophil Count (ANC) following initiation of ATD therapy. Data from the Electronic Medical Record at UNM HSC were obtained using a standard database query. Inclusion criteria were the prescription of an ATD, an ANC recorded within 30 days of initiating ATD therapy (Pre-ATD), and an ANC recorded 75 - 365 days after starting an ANC (Post-ATD). Patients taking other agents known to cause neutropenia were excluded. Racial and ethnic groups were assigned as follows: Hispanic, Non-Hispanic White, Native American, Black/African American, and Asian/Pacific Islander. Post-ATD ANC was defined as the nadir ANC after ATD initiation. "Delta ANC" was defined as ((Post-ATD ANC) - (Pre-ATD ANC)). ANOVA analysis with Bonferroni-adjusted post-hoc testing and multiple regression were performed to examine differences in the mean changes in ANC across ethnic groups. One hundred and twenty-three adult patients met inclusion and exclusion criteria and were included in the analysis. The Native American group showed a significantly greater Post-ATD ANC and Delta-ANC as compared to the other groups (p<0.001). In this cohort of New Mexicans with thyrotoxicosis, Native American race was protective against thionamide-induced neutropenia., Competing Interests: Disclosure Statement The authors have no conflicts of interest to disclose

Background: Diabetes risk is extremely high for Latinos from low-income households. Health guidelines recommend that individuals learn strategies to self-manage their diabetes, but getting people to adopt required lifestyle changes is challenging and many people are not able to prevent their pre-diabetes from escalating or effectively control their diabetes. Systematic reviews show that culturally competent self-management programs can significantly improve diabetes outcomes and different models for culturally competent programming have been developed., Methods: This patient-engaged study will compare the effectiveness of two distinct evidence-based models for culturally competent diabetes health promotion at two sites that serve a large Latino patient population from low-income households: 1) The Diabetes Self-Management Support Empowerment Model, an educational session approach, and 2) The Chronic Care Model, a holistic community-based program. Data collection will involve interviews, focus groups, surveys and assessments of each program; and testing of patient participants for A1c, depression, Body Mass Index (BMI), and chronic stress with hair cortisol levels. We will recruit a total of 240 patient-social support pairs: Patients will be adults (men and women over the age of 18) who: 1.) Enter one of the two diabetes programs during the study; 2.) Self-identify as "Latino;" 3.) Are able to identify a social support person or key member of their social network who also agrees to participate with them; 4.) Are not pregnant (participants who become pregnant during the study will be excluded); and 5.) Have household income 250% of the Federal Poverty Level (FPL) or below. Social supports will be adults who are identified by the patient participants., Primary Outcome: Improved capacity for diabetes self-management measured through improvements in diabetes knowledge and diabetes-related patient activation., Secondary Outcome: Successful diabetes self-management as measured by improvements in A1c, depression scale scores, BMI, and circulating levels of cortisol to determine chronic stress., Discussion: Our hypothesis is that the program model that interfaces most synergistically with patients' culture and everyday life circumstances will have the best diabetes health outcomes., Trial Registration: This study was registered with ClinicalTrials.gov on December 16, 2016 (Registration # NCT03004664 ).

Background: The widespread availability of the coronary artery calcium scan to diagnose coronary artery atheroma semiquantitatively and its prognostic significance has frequently resulted in a difficult therapeutic decision for physicians caring for asymptomatic patients., Patients and Risk Factors: Of particular concern are patients over 40 years of age and young adults characterized by multiple cardiovascular risk factors. The correct prognostic interpretation of coronary artery calcium scores and the potential benefits and risks of various therapeutic modalities need to be understood., Conclusion: This review describes the therapeutic choices available to endocrinologists and provides recommendations for various treatment options.

Objective: The goal of insulin therapy in type 1 diabetes (T1D) is to reduce hemoglobin A1C (A1C) to ≤7.0% (53 mmol/mol) with minimal hypoglycemia. We investigated the possibility that "insulin timing" would improve A1C without incurring severe hypoglycemia in volunteers with T1D over a 6-month observation period., Methods: Forty healthy adult volunteers with T1D were randomly assigned for 6 months to either a control group or an insulin timing group. The primary endpoint was the difference in A1C between the two groups. As a secondary endpoint, both groups were further divided to assess the importance of the baseline A1C in determining the response to timing. The insulin timing algorithm altered the time when the meal dose of insulin was injected or infused from 30 minutes before the meal to 15 minutes after the meal, depending upon the premeal blood glucose concentration., Results: An improvement in mean A1C was observed in the timing group compared with no change in the control group, but this improvement did not reach statistical significance (P>.05). In contrast, when the two groups were analyzed according to baseline A1C, the timing volunteers with baseline A1C values in the upper half (separated by the A1C median of 7.45% [57.9 mmol/mol]) of the timing group had a more robust response to timing (decline in A1C) than the upper half of the control group (P<.05)., Conclusion: Insulin timing is a patient-centered translational approach that is safe and effective in improving A1C in individuals with T1D with an elevated A1C., Abbreviations: A1C = hemoglobin A1C ANOVA = analysis of variance CGM = continuous glucose monitoring CSII = continuous subcutaneous insulin infusion MDI = multiple daily injection T1D = type 1 diabetes.

Smoking is the leading cause of avoidable death and is associated with type 2 diabetes (T2D) risk. Previous studies on the impact of passive smoking have not been applied to a Hispanic-majority population. We investigated the association between active smoking, exposure to environmental tobacco smoke (ETS), and pre-diabetes risk in a New Mexico population. We hypothesized that pre-diabetes risk increases with increasing smoking status after adjustment for important covariates. We screened 219 adults from an ongoing study who were categorized according to their smoking status (never smoker, current smoker, previous smoker) and their exposure to ETS (exposed or unexposed). Glucose homeostasis status was assigned using A1c: no diabetes (A1c <5.7%), pre-diabetes (A1c 5.7-6.4%), and T2D (A1c >6.4%). Among 160 patients with complete data, 51.6% had no diabetes and 48.4% had pre-diabetes. The mean age was 44.8±13.5 years. The study population was predominantly female (64.4%), and the ethnic composition was 44.4% Hispanic, 39.4% non-Hispanic White (NHW), 10.6% American Indian, 2.5% African-American, and 3.1% other. Using a logistic model with 2-way interactions, all predicted probabilities for being at risk for pre-diabetes were significant at the 0.001 level for smoking status and ETS exposure after adjusting for age, sex, ethnicity, family history of diabetes, alcohol consumption, BMI, and blood pressure. Active or passive smoking is independently associated with pre-diabetes risk., (Copyright © 2016 American Federation for Medical Research.)

Objective: Postoperative hypocalcemia is frequent after total thyroidectomy. The role of pre-operative vitamin D levels in the pathogenesis of this condition has not been studied under the most current guidelines for evaluation of the role of vitamin D in calcium homeostasis. We hypothesized that patients who are vitamin D deficient (VDD) pre-operatively are more likely to suffer from postoperative hypocalcemia, thereby requiring prolonged hospitalization., Methods: A retrospective chart review of patients undergoing total thyroidectomy at the University of New Mexico Hospital between 2005 and 2014 was performed. Patients who underwent intentional parathyroidectomy were excluded. The study included 30 patients who had a 25-hydroxyvitamin D levels obtained within 12 months before surgery., Results: Twelve patients who were VDD (25-hydroxyvitamin D ≤20 ng/mL) were compared to 18 patients who did not have VDD (non-VDD; 25-hydroxyvitamin D >20 ng/mL). The mean nadir postoperative ionized calcium concentration was lower in the VDD group (0.99 ± 0.10 vs. 1.06 ± 0.06 mmol/L, P = .04) (reference range = 1.15-1.27 mmol/L), as was the postoperative concentration of phosphorus (3.48 ± 0.60 vs. 4.17 ± 0.84 mg/dL, P = .03). VDD patients had a longer length of stay (4.3 ± 4.4 vs. 1.7 ± 1.5 days, P = .03). Three patients in the VDD group required intravenous calcium for treatment of symptomatic hypocalcemia, but none of the non-VDD patients required this intervention (P = .054)., Conclusion: Pre-operative vitamin D deficiency is associated with an increased risk of postoperative hypocalcemia and a prolonged length of stay in patients undergoing total thyroidectomy. Vitamin D replacement before thyroidectomy may improve postsurgical outcomes in VDD patients., Abbreviations: BMI = body mass index non-VDD = non-vitamin D deficient PTH = parathyroid hormone VDD = vitamin D deficient.

Objective: Reliable identification of individuals at risk for developing diabetes is critical to instituting preventative strategies. Studies suggest that the accuracy of using hemoglobin A1c as a sole diagnostic criterion for diabetes may be variable across different ethnic groups. We postulate that there will be lack of concordance between A1c and the oral glucose tolerance test (OGTT) for diagnosing prediabetes across Hispanic and non-Hispanic white (NHW) populations., Methods: A total of 218 asymptomatic adults at risk for type 2 diabetes (T2D) were assessed with A1c and OGTT for the diagnosis of prediabetes. Glucose homeostasis status was assigned as no diabetes (A1c <5.7% [39 mmol/mol]), prediabetes (A1c 5.7 to 6.4% [46 mmol/mol]), and T2D (A1c >6.4% [46 mmol/mol]). Inclusion criteria were age >18 years and at least one of the following: a family history of diabetes, a history of gestational diabetes, Hispanic ethnicity, non-Caucasian race, or obesity. Subjects received a fasting 75-g OGTT and A1c on the same day. Bowker's test of symmetry was employed to determine agreement between the tests., Results: Data from 99 Hispanic patients and 79 NHW patients were analyzed. There was no concordance between A1c and OGTT for Hispanic (P = .002) or NHW individuals (P = .003) with prediabetes., Conclusion: A1c is discordant with OGTT among Hispanic and NHW subjects for the diagnosis of prediabetes. Sole use of A1c to designate glycemic status will result in a greater prevalence of prediabetes among Hispanic and NHW New Mexicans., Abbreviations: A1c = hemoglobin A1c BMI = body mass index CDC = Centers for Disease Control CI = confidence interval FPG = fasting plasma glucose NHW = non-Hispanic white OGTT = oral glucose tolerance test T2D = type 2 diabetes WHO = World Health Organization., Competing Interests: Statement: The authors have no conflicts of interest to disclose

The coronary artery calcium (CAC) scan has recently emerged as a reproducible noninvasive test to detect asymptomatic atherosclerotic coronary artery disease. It has several advantages over the traditional cardiac stress testing modalities, including lower cost, greater sensitivity for nonobstructing coronary artery lesions, and excellent prognostic value when combined with the Framingham risk parameters. Its chief disadvantage is that it does not identify obstructing coronary artery lesions or noncalcified coronary artery plaque. A CAC scan utilizes a chest computed tomogram and computer software to calculate the amount of calcium in the four main coronary vessels. Calcium is deposited in coronary plaques so that the greater the calcium score, the greater the plaque burden. This, in turn, is the basis for predicting a 10-15-year risk of a cardiovascular event. Individuals with a zero calcium score have a very low 10-year risk of a cardiovascular event. Obtaining a calcium score in a diabetic patient permits rational decisions for prescribing statin therapy. In patients with a zero score, the initiation of statin therapy is not recommended because the 5-year incidence of atherosclerotic cardiovascular disease is so low. In patients with diabetes, it is recommended to repeat the calcium scan in 4-5 years to permit timely therapy in the event that the score becomes positive. Since statins mildly increase coronary calcium as part of the stabilization of plaque, a reduction in the calcium score should not be anticipated. However, progression of the calcium score by more than 15%/year (calculated from a repeat CAC scan) provides additional prognostic information of an indication of progression of atherosclerosis. In summary, the coronary calcium score is a major clinical advance for noninvasively detecting coronary artery disease and managing antiatherosclerotic therapy in type 1 diabetes., Competing Interests: Author Disclosure Statement No competing financial interests exist.

Introduction/purpose: The Southwestern American Indian population carries a high prevalence of metabolic syndrome and obesity, placing this group at higher risk than the general population for developing early type 2 diabetes and cardiovascular disease, likely impacting overall lifespan. This study aims to evaluate the impact of early lifestyle interventions which promote healthy eating and regular exercise on risk factors contributing to the development of the metabolic syndrome among the adolescent Zuni Pueblo population., Materials and Methods: We describe a prospective, single site, community-based cohort study performed among sixty-five adolescent Zuni Indians aged 13.9 ± 1.7 years who were recruited between March 2011 and January 2014. The study intervention consisted of a targeted, tri-weekly exercise regimen with nutritional counselling, and the primary study outcomes included changes from baseline in metabolic profile (fasting lipids, A1c), vital signs (blood pressure, resting heart rate) and anthropometric characteristics of the study group., Results: 41 participants have anthropometric data measured at baseline and after completion, biochemical data are available from 30 participants, and body composition data from 26 patients. Using the paired Student's t-test with Bonferroni correction, significant improvements were shown in pediatric BMI percentile, fasting lipid profile, A1C, total body fat, and fat free mass after six months of exercise and nutritional intervention., Conclusions: A simple, standardized fitness program among Southwest American Indian adolescents was effective at reducing fasting lipids and adiposity, as well as improving glycemic indices over the course of six months., Competing Interests: Conflict of Interest: No potential conflicts of interest relevant to this original article were reported by authors. Results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and that the results of the present study do not constitute endorsement by the journal.

Introduction: One in three people will be diagnosed with diabetes by 2050, and the proportion will likely be higher among Native Americans. Diabetes control is currently suboptimal in underserved populations despite a plethora of new therapies. Patient empowerment is a key determinant of diabetes control, but such empowerment can be difficult to achieve due to resource limitation and cultural, language and health literacy barriers. We describe a home-based educational intervention using Community Health Representatives (CHRs), leading to improvement in Patient Activation Measures scores and clinical indicators of diabetes control., Methods: Sixty participants with type 2 diabetes (T2D) completed a baseline evaluation including physical exam, Point of Care (POC) testing, and the Patient Activation Measure (PAM) survey. Participants then underwent a one hour group didactic session led by Community Health Representatives (CHRs) who subsequently carried out monthly home-based educational interventions to encourage healthy lifestyles, including diet, exercise, and alcohol and cigarette avoidance until follow up at 6 months, when clinical phenotyping and the PAM survey were repeated., Results: PAM scores were increased by at least one level in 35 (58%) participants, while 24 participants who started at higher baseline score did not change. Six months after intervention, mean levels of A1C decreased by 0.7 ± 1.2%; fasting blood glucose decreased by 24.0 ± 38.0 mg/dl; BMI decreased by 1.5 ± 2.1 kg/m2; total cholesterol decreased by 12.0 ± 28.0 mg/dl; and triglycerides decreased by 52.0 ± 71.0 mg/dl. All of these changes were statistically significant (p < 0.05)., Conclusion: This six month, CHR led and community-oriented educational intervention helps inform standards of practice for the management of diabetes, engages diabetic populations in their own care, and reduces health disparities for the underserved population of Zuni Indians., Trial Registration: ClinicalTrials.gov NCT02339311.

Objective. We present the clinical, biochemical, and imaging findings of a woman with vitamin D deficiency and severe osteomalacia related to intravenous heroin addiction. Results. A 54-year-old woman with a medical history significant for long-standing heroin abuse presented with complaints of bone pain, muscle cramping, and a left hip ulcer. She had been bed bound for approximately 1 year secondary to pain of uncertain etiology, and her husband was bringing her both food and drugs. She was admitted to the hospital for debridement of a right ischial ulcer. Further workup revealed osteomyelitis of the left hip and severe vitamin D deficiency. Radiologic evaluation demonstrated diffuse osteopenia with pseudofractures, as well as true fractures. Conclusion. This is the first case reported in the English literature of advanced osteomalacia resulting from a debilitating narcotic dependency. Vitamin D deficiency should be considered in patients with poor nutrition and prolonged sunlight deprivation from any cause.

Background: The masked continuous glucose monitoring system (Masked-CGMS) differs from standard CGMSs in three ways: (1) there is no feedback to the user so that no immediate regimen changes can be made; (2) it can only be worn for up to 5 days; and (3) there are no alarms to warn of hyperglycemia or hypoglycemia. Since 2008 masked-CGMS has become popular for identifying reasons that a patient's hemoglobin A1C does not correlate closely with his or her capillary blood glucose measurements. To date only one study addressing the clinical utility of Masked-CGMS for improving A1C in diabetes has been published. No studies are available specifically examining the variability and correlation of Masked-CGMS and A1C., Subjects and Methods: We performed 156 Masked-CGMS studies (40 patients studied sequentially a maximum of four times each) in type 1 diabetes patients. We then analyzed the resulting interstitial glucose levels obtained from the Masked-CGMS compared with an A1C measurement performed within 1 week of the Masked-CGMS study., Results: There was a very low correlation between the A1C and the Masked-CGMS-derived mean interstitial glucose level. This statistic did not provide sufficiently predictive information to be clinically useful for changing an individual patient's intensive insulin therapy regimen., Conclusions: Our data demonstrate that a very weak correlation exists between 5 days of masked CGMS and a concurrently measured A1C level. For the individual type 1 diabetes patient, this relationship would unlikely to be clinically useful in altering the individual's treatment regimen.

Context: Abnormal cortisol levels are a key pathophysiological indicator of post-traumatic stress disorder (PTSD). Endogenous normalization of cortisol concentration through exercise may be associated with PTSD symptom reduction., Objective: The aim of the study was to determine whether mindfulness-based stretching and deep breathing exercise (MBX) normalizes cortisol levels and reduces PTSD symptom severity among individuals with subclinical features of PTSD., Design and Setting: A randomized controlled trial was conducted at the University of New Mexico Health Sciences Center., Participants: Twenty-nine nurses (28 female) aged 45-66 years participated in the study., Intervention: Sixty-minute MBX sessions were conducted semiweekly for 8 weeks., Main Outcome Measures: Serum cortisol was measured, and the PTSD Checklist-Civilian version (PCL-C) was performed at baseline and weeks 4, 8, and 16., Results: Twenty-nine participants completed the study procedures, 22 (79%) with PTSD symptoms (MBX, n = 11; control, n = 11), and 7 (21%) without PTSD (BASE group). Eight-week outcomes for the MBX group were superior to those for the control group (mean difference for PCL-C scores, -13.6; 95% confidence interval [CI], -25.6, -1.6; P = .01; mean difference for serum cortisol, 5.8; 95% CI, 0.83, 10.8; P = .01). No significant differences were identified between groups in any other items. The changes in the MBX group were maintained at the 16-week follow-up (P = .85 for PCL-C; P = .21 for cortisol). Our data show that improved PTSD scores were associated with normalization of cortisol levels (P < .05)., Conclusions: The results suggest that MBX appears to reduce the prevalence of PTSD-like symptoms in individuals exhibiting subclinical features of PTSD.

Background: Mind-body practices are increasingly used to provide stress reduction for posttraumatic stress disorder (PTSD). Mind-body practice encompasses activities with the intent to use the mind to impact physical functioning and improve health., Methods: This is a literature review using PubMed, PsycINFO, and Published International Literature on Traumatic Stress to identify the effects of mind-body intervention modalities, such as yoga, tai chi, qigong, mindfulness-based stress reduction, meditation, and deep breathing, as interventions for PTSD., Results: The literature search identified 92 articles, only 16 of which were suitable for inclusion in this review. We reviewed only original, full text articles that met the inclusion criteria. Most of the studies have small sample size, but findings from the 16 publications reviewed here suggest that mind-body practices are associated with positive impacts on PTSD symptoms. Mind-body practices incorporate numerous therapeutic effects on stress responses, including reductions in anxiety, depression, and anger, and increases in pain tolerance, self-esteem, energy levels, ability to relax, and ability to cope with stressful situations. In general, mind-body practices were found to be a viable intervention to improve the constellation of PTSD symptoms such as intrusive memories, avoidance, and increased emotional arousal., Conclusions: Mind-body practices are increasingly used in the treatment of PTSD and are associated with positive impacts on stress-induced illnesses such as depression and PTSD in most existing studies. Knowledge about the diverse modalities of mind-body practices may provide clinicians and patients with the opportunity to explore an individualized and effective treatment plan enhanced by mind-body interventions as part of ongoing self-care.

Adolescents Committed to Improvement of Nutrition and Physical Activity (ACTION) was undertaken to determine feasibility of a school-based health center (SBHC) weight management program. Two urban New Mexico SBHCs were randomized to deliver ACTION or standard care. ACTION consisted of eight visits using motivational interviewing to improve eating and physical activity behavior. An educational nutrition and physical activity DVD for students and a clinician toolkit were created for use as menu of options. Standard care consisted of one visit with the SBHC provider who prescribed recommendations for healthy weight. Sixty nondiabetic overweight/obese adolescents were enrolled. Measures included BMI percentile, waist circumference, insulin resistance by homeostasis model assessment (HOMA-IR), blood pressure, triglycerides, and HDL-C levels. Pre- to postchanges for participants were compared between groups. Fifty-one students (mean age 15 years, 62% female, 75% Hispanic) completed pre- and postmeasures. ACTION students (n = 28) had improvements in BMI percentile (P = 0.04) and waist circumference (P = 0.04) as compared with students receiving standard care (n = 23). No differences were found between the two groups in blood pressure, HOMA-IR, triglycerides, and HDL-C. The ACTION SBHC weight management program was feasible and demonstrated improved outcomes in BMI percentile and waist circumference.

Background: Acanthosis nigricans (AN) is a dermatologic condition associated with hyperinsulinemia, a marker of insulin resistance that is the principal abnormality in metabolic syndrome (MetS). We examined the association of AN with the clustering of MetS components., Methods: A cross-sectional study was conducted in an urban school-based health center in New Mexico. Students without diabetes were evaluated for AN, a family history of type 2 diabetes, body mass index (BMI), and MetS components. The clustering of MetS components by BMI category and AN status was assessed by comparing the group means of summed average z-scores of fasting insulin, triglycerides, high-density lipoprotein-cholesterol, and systolic blood pressure among the students. A multivariate model with BMI category and AN status controlling for Tanner stage was performed to identify the variables associated with the clustering of MetS components., Results: Complete data were available for 90 children (age, 9.7±1.4 years; 94% Hispanic; 60% female). In multivariate modeling of MetS cluster z-score, significant differences were found between the students with BMI <85th percentile [-0.27; 95% confidence interval (95% CI)=-0.42 to -0.11] and (a) the students with BMI 85th-94.9th percentile with AN (0.74; 95% CI=0.17-1.31) and (b) the students with BMI ≥95th percentile with AN (0.86; 95% CI=0.54-1.18). No significant differences in the MetS cluster z-score were seen between the students with BMI <85th percentile and those with BMI 85th-94.9th percentile without AN (0.24; 95% CI=-0.33 to 0.81) or those with BMI ≥95th percentile without AN (0.31; 95% CI=-0.13 to 0.75)., Conclusions: Overweight/obese Hispanic elementary school-aged children with AN exhibit clustering of MetS components and could benefit from early intervention.

The goal of this paper is to present a computer-based system for analyzing thermal images in the detection of preclinical stages of peripheral neuropathy (PN) or diabetic foot. Today, vibration perception threshold (VPT) and sensory tests with a monofilament are used as simple, noninvasive methods for identifying patients who have lost sensation in their feet. These tests are qualitative and are ineffective in stratifying risk for PN in a diabetic patient. In our system a cold stimulus applied to the foot causes a thermoregulatory and corresponding microcirculation response of the foot. A thermal video monitors the recovery of the microcirculation in the foot plantar. Thermal videos for 8 age-matched subjects were analyzed. Six sites were tracked and an average thermal emittance calculated. Characteristics of the recovery curve were extracted using coefficients from an exponential curve fitting process and compared among subjects. The magnitude of the recovery was significantly different for the two classes of subjects. Our system shows evidence of differences between both groups, which could lead to a quantitative test to screen and diagnose peripheral neuropathy.

Objective: To explore the hypothesis that CD36, a scavenger receptor and fatty acid translocase, is upregulated in peripheral blood mononuclear cells (PBMCs) among patients with type 2 diabetes and is a biomarker of PBMC activation and inflammation., Research Design and Methods: We used a cross-sectional observational design to study a multi-racial/ethnic population sample consisting of Caucasians, Hispanics, and Native Americans with type 2 diabetes (n = 33) and nondiabetic control subjects (n = 27). PBMC CD36 mRNA/protein and plasma high sensitivity (hs) C-reactive protein (hsCRP), hs-interleukin-6 (hsIL-6), and adiponectin were measured., Results: Unadjusted PBMC CD36 mRNA and protein were 1.56- and 1.63-fold higher, respectively, among type 2 diabetic subjects versus control subjects. PBMC CD36 protein was directly associated with CD36 mRNA, plasma hsCRP, and hsIL-6 and inversely associated with plasma adiponectin in both groups., Conclusions: Increased CD36 expression is a biomarker of PBMC activation and inflammation and may become a useful tool in cardiovascular disease risk stratification.

Objective: To examine the possibility of whether 2 days of strict hospitalized bed rest would alter the metabolic profile (including insulin resistance as calculated by the quantitative insulin sensitivity check index or QUICKI) in both normal subjects and patients with type 2 diabetes in comparison with 2 days of normal activity., Methods: The design of this pilot study was a randomized, crossover protocol that evaluated the effects of strict bed rest versus normal activity in 5 healthy normal subjects and 5 healthy patients with type 2 diabetes. All study participants completed a screening visit for assessment of baseline health., Results: All 10 study subjects completed the protocol without adverse events. Fasting plasma glucose, insulin, and C-peptide levels as well as several known risk factors for atherosclerosis were unchanged in both the subjects without diabetes and the patients with type 2 diabetes after 2 days of hospitalized bed rest. Insulin resistance demonstrated no significant change during the 48 hours of bed rest when compared with the mean value at baseline., Conclusion: This study demonstrates that 48 hours of bed rest has no significant effect on insulin resistance or standard metabolic variables in normal subjects and patients with type 2 diabetes. Therefore, achieving good glucose control in patients hospitalized for a period of 2 days or less does not necessitate early ambulation to prevent an increase in insulin resistance.

The aim of the study was to determine whether a recommendation to walk 10000 steps per day would result in significant improvements in glycemic control, insulin sensitivity, and cardiovascular risk in patients with type 2 diabetes mellitus. The study was a 6-week randomized controlled trial that included 30 patients with type 2 diabetes mellitus. After 10 days of baseline activity, patients were randomized into 2 groups: control and active. The control group (n = 15) was instructed to continue with their baseline activity for 6 weeks. The active group (n = 15) was instructed to walk at least 10000 steps per day 5 or more days per week, for 6 weeks. Data relevant to glycemic control and other parameters of health were collected at study weeks 0 and 6. There were no differences in the baseline activity between groups (P = .36). Subjects in the active group significantly increased physical activity by 69% during the intervention phase of the study (P = .002), whereas there was no change in the physical activity of the control group (P > .05). High-density lipoprotein cholesterol and resting energy expenditure significantly increased in the active group (P < .05). Finally, plasminogen activator inhibitor 1 (PAI-1) activity was reduced by exercise relative to the control group (P = .03). There were no differences in any other study parameters during the 6-week study. In conclusion, short-term intervention with a pedometer increased physical activity and positively affected plasminogen activator inhibitor 1 activity in previously inactive patients with type 2 diabetes mellitus. The use of a pedometer may prove to be an effective tool for promoting healthy lifestyle changes that include daily physical activity and self-monitoring of therapeutic goals.

Clinical hypothyroidism is associated with hyperhomocysteinemia, whereas the opposite is seen in hyperthyroidism. The effects of mild thyroid dysfunction on homocysteine concentrations are not known. We performed the following study to investigate this. Total homocysteine, vitamins B6 and B12, folate, fibrinogen, plasminogen activator inhibitor type 1, and lipids were measured in 11 subjects at baseline and after methionine loading. Subjects began methimazole (MMI), 40 mg daily, and were restudied during 2 stages of hypothyroidism. Liothyronine was added and subjects were restudied once thyrotropin normalized. Methimazole was stopped and studies were repeated during 2 stages of hyperthyroidism. Data were analyzed using repeated-measures analysis of variance. Post-methionine homocysteine decreased in each hypothyroid study compared with baseline (28.8+/-10.7, 27.5+/-9.9 vs 34.4+/-9.2 micromol/L, respectively). In addition, both fasting and post-methionine homocysteine decreased in the euthyroid/MMI study arm compared with baseline despite equivalent thyrotropin values (fasting, 7.5+/-3.0 vs 8.8+/-3.5 micromol/L, P<.05; and post-methionine, 27.2+/-10.6 vs 34.4+/-9.2 micromol/L, P<.05, respectively). Fasting homocysteine decreased in the first hyperthyroidism study arm compared with baseline (6.6+/-2.3 vs 8.8+/-3.5 micromol/L, P<.05) and post-methionine homocysteine decreased in both hyperthyroid arms compared with baseline (25.2+/-8.1, 24.2+/-10 vs 34.4+/-9.2 micromol/L, P<.05 respectively). In conclusion, mild thyroid dysfunction changes homocysteine metabolism. Unexpectedly, our results suggest a homocysteine-lowering effect of MMI.

Generalized insulin edema, although rare, is a well-recognized complication of insulin therapy. It is mainly appreciated in patients with newly diagnosed or poorly controlled diabetes mellitus after starting intensive insulin therapy. Although the condition is self-limiting, progression to overt cardiac failure and development of pleural effusion have been reported. With current trends toward intensive insulin therapy, clinicians should be aware of the existence of the insulin edema syndrome, and its occurrence should be documented and differentiated from other causes of edema. In this article, we present a recent case that illustrates the clinical features of insulin edema. Specifically, a young male with newly diagnosed type 1 diabetes mellitus developed significant, reversible peripheral edema after starting insulin therapy. A detailed case description is accompanied by the only known published photographs of insulin edema. The overall purpose of this article is to review the scanty existing medical literature surrounding the topic of insulin edema and to raise awareness about its continued occurrence.

Achieving target glycaemic goals while avoiding hypoglycaemia is a major challenge in the management of elderly patients with diabetes mellitus. Repeated episodes of hypoglycaemia may cause extreme emotional distress in such patients, even when the episodes are relatively mild. Moreover, evidence is mounting that hypoglycaemia among elderly patients is a very real and costly health concern. The strongest predictors of severe hypoglycaemia in the elderly are advanced age, recent hospitalisation and polypharmacy. Education is the key to preventing recurrent or severe hypoglycaemia. As such, there should be close coordination of care between the patient, physician and all other healthcare providers in identifying the cause of hypoglycaemia in elderly patients, and appropriate steps should be taken to prevent further episodes. Prevention of hypoglycaemia has the potential to improve psychosocial aspects of elderly health, including enhanced quality of life, boosted confidence, improved compliance with antidiabetic regimens and avoidance of long-term complications. Since the elderly population represents a unique group, it is imperative to focus on the aetiologies that are exclusive to this group. Advanced age itself is a risk factor for hypoglycaemia, and elderly patients with comorbidities are at increased risk when they are hospitalised. Elderly patients with diabetes often have compromised renal function, which intereferes with drug elimination and thus predisposes them to prolonged life-threatening hypoglycaemia. In addition, patients on five or more prescription medications are prone to drug-associated hypoglycaemia. Although sulfonylurea-associated hypoglycaemia is common, drugs such as ACE inhibitors and nonselective beta-adrenoceptor antagonists can also predispose patients to hypoglycaemia. Greater attention should be paid to the avoidance of hypgolycaemia in nursing home residents. Recurrent hypoglycaemia in elderly patients is not only detrimental to achieving good glycaemic control, it is also a substantial economic burden. Once the causes of hypoglycaemia have been identified, it is crucial to formulate and institute a prevention plan. Firstly, global evaluation of the patient should be carried out to identify possible predisposing risk factors. Secondly, target glycaemic goals should be tailored to each patient. Thirdly, selection of antidiabetic agents should be judicious, then patients and family should be educated to recognise and treat hypoglycaemia. Finally, coordinated care should be provided to identify, treat and prevent hypoglycaemia., (Copyright 2004 Adis Data Information BV)

Objective: To study the effects of ingestion of two different doses of supplemental kelp on the thyroid function of healthy euthyroid subjects., Methods: We conducted a double-blind prospective clinical trial involving 36 healthy euthyroid subjects, who were randomly assigned to receive placebo (4 alfalfa capsules per day), low-dose kelp (2 kelp capsules and 2 alfalfa capsules per day), or high-dose kelp (4 kelp capsules per day) for 4 weeks. Thyrotropin (thyroid-stimulating hormone or TSH), free thyroxine, and total triiodothyronine were assessed at weeks 0, 4, and 6. Response to thyrotropin-releasing hormone stimulation, urinary iodine excretion, and basal metabolic rate were determined at weeks 0 and 4., Results: TSH concentrations did not differ significantly between week 0 and week 4 in the placebo group (P = 0.16) but increased significantly in both the low-dose kelp (P = 0.04) and high-dose kelp (P = 0.002) groups. Free thyroxine concentrations decreased slightly but significantly after 4 weeks of placebo but were unchanged in the low-dose and the high-dose kelp groups. In contrast, total triiodothyronine levels did not differ significantly after 4 weeks of placebo or low-dose kelp therapy but were significantly decreased after high-dose kelp therapy (P = 0.04). Similarly, the thyrotropin-releasing hormone stimulation test showed no significant change in poststimulation TSH after 4 weeks in the placebo or low-dose kelp groups but revealed a significantly increased response after high-dose kelp therapy (P = 0.0002). The 24-hour urinary iodine excretion showed dose-dependent increases in the two kelp study groups. Basal metabolic rate did not change significantly in any study group during the 4-week study period. All thyroid laboratory values returned to baseline 2 weeks after cessation of kelp supplementation, except for TSH in the high-dose kelp group, which was significantly decreased., Conclusion: Short-term dietary supplementation with kelp significantly increases both basal and poststimulation TSH. These findings corroborate previous studies on the effects of supplemental iodide given to euthyroid subjects for a similar period. Further studies are needed to determine whether long-term kelp supplementation would cause clinically significant thyroid disease.

Objective: To describe a patient with severe thyrotoxicosis attributable to Graves' disease who had a thrombotic cerebrovascular accident and hyperhomocysteinuria, which resolved on correction of the thyrotoxicosis, and to present findings in a pilot study undertaken to investigate the relationship among thyrotoxicosis, homocysteine, folate, and vitamin B(12)., Methods: We present a case report of the index case, with clinical and laboratory details. For the investigative analysis, 21 patients who were 18 to 50 years old and had newly diagnosed, untreated Graves' disease and 10 age-and sex-matched euthyroid control subjects were studied. Of the patients with Graves' disease, 11 underwent studies both at diagnosis and after treatment. Fasting blood tests were performed for thyrotropin, free thyroxine, homocys-teine, vitamin B(12), folate, and methylmalonic acid, a marker of vitamin B(12) deficiency., Results: Vitamin B(12), folate, homocysteine, and methylmalonic acid levels were not significantly different between the thyrotoxic and control or posttreatment groups. In patients with thyrotoxicosis, however, free thyroxine was positively correlated with both homocysteine (r = 0.67; P = 0.03) and methylmalonic acid (r = 0.89; P = 0.003)., Conclusion: The positive correlation between free thyroxine levels and both homocysteine and methylmalonic acid suggests that thyrotoxicosis may be associated with functional vitamin B(12) deficiency. Such a deficiency may result in clinically important hyperhomocysteine-mia.