The following studies, among others, will be published in Endocrine Society journals. Before print, they are edited and posted online in each journal’s Early Release section. You can access the journals at www.endocrine.org
Relationship of Bone Metabolism Biomarkers and Periodontal Disease: The Osteoporotic Fractures in Men (MrOS) Study • Ulrike Schulze-Späte, Ryan Turner, Ying Wang, Raylien Chao, P. Christian Schulze, Kathy Phipps, Eric Orwoll, Thuy-Tien Dam, and for the Osteoporotic Fractures in Men (MrOS) Research Group • This study suggests that a distinct set of biomarkers of bone metabolism are associated with more severe periodontal disease (PTH, 25(OH)D) and periodontal progression (alpha-CTX, beta-CTX, and CTX)over time.
Impact of Male and Female Weight, Smoking, and Intercourse Frequency on Live Birth in Women with Polycystic Ovary Syndrome • Alex J. Polotsky, Amanda A. Allshouse, Peter R. Casson, Christos Coutifaris, Michael P. Diamond, Gregory M. Christman, William D. Schlaff, Ruben Alvero, J.C. Trussell, Stephen A. Krawetz, Nanette Santoro, Esther Eisenberg, Heping Zhang, and Richard S. Legro • In this large cohort of obese women with PCOS, impact of male obesity was explained by female BMI. Lower chance of success was seen among couples where both partners smoked. Obesity and smoking are common among women with PCOS and their partners and contribute to a decrease in fertility treatment success.
Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis • Layal Chaker, Christine Baumgartner, Wendy P. J. den Elzen, M. Arfan Ikram, Manuel R. Blum, Tinh-Hai Collet, Stephan J. L. Bakker, Abbas Dehghan, Christiane Drechsler, Robert N. Luben, Albert Hofman, Marileen L. P. Portegies, Marco Medici, Giorgio Iervasi, David J. Stott, Ian Ford, Alexandra Bremner, Christoph Wanner, Luigi Ferrucci, Anne B. Newman, Robin P. Dullaart, José A. Sgarbi, Graziano Ceresini, Rui M. B. Maciel, Rudi G. Westendorp, J. Wouter Jukema, Misa Imaizumi, Jayne A. Franklyn, Douglas C. Bauer, John P. Walsh, Salman Razvi, Kay-Tee Khaw, Anne R. Cappola, Henry Völzke, Oscar H. Franco, Jacobijn Gussekloo, Nicolas Rodondi, and Robin P. Peeters • Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.
Effects of Dulaglutide on Thyroid C-Cells and Serum Calcitonin in Male Monkeys • John L. Vahle, Richard A. Byrd, Jamie L. Blackbourne, Jennifer A. Martin, Steven D. Sorden, Thomas Ryan, Thomas Pienkowski, John A. Wijsman, Holly W. Smith, and Thomas J. Rosol • This study represents a comprehensive evaluation of monkey thyroid C-cells following dosing with a GLP-1 receptor agonist, with a large group size, and measurement of multiple relevant parameters. The lack of effect of dulaglutide on C-cells is consistent with other studies in monkeys using GLP-1 receptor agonists and suggests that non-human primates are less sensitive than rodents to the induction of proliferative changes in thyroid C-cells by GLP-1 receptor agonists.
Chronic Toxicity and Carcinogenicity Studies of the LongActing GLP-1 Receptor Agonist Dulaglutide in Rodents • Richard A. Byrd, Steven D. Sorden, Thomas Ryan, Thomas Pienkowski, Richard LaRock, Ricardo Quander, John A. Wijsman, Holly W. Smith, Jamie L. Blackbourne, Thomas J. Rosol, Gerald G. Long, Jennifer A. Martin, and John L. Vahle • Consistent with the lack of morphometric changes in C-cell mass, dulaglutide did not affect the incidence of diffuse C-cell hyperplasia or basal- or calcium-stimulated plasma calcitonin, suggesting that diffuse increases in C-cell mass did not occur during the initial 52 weeks of the rat carcinogenicity study.
Role of Complement and Complement Regulatory Proteins in the Complications of Diabetes • Pamela Ghosh, Rupam Sahoo, Anand Vaidya, Michael Chorev, and Jose A. Halperin • The authors discuss a pathogenic model of human diabetic complications in which a combination of CD59 inactivation by glycation and hyperglycemia-induced complement activation increase MAC deposition, activates pathways of intracellular signaling, and induces the release of proinflammatory, prothrombotic cytokines, and growth factors. Combined, complement-dependent and complement-independent mechanisms induced by high glucose, promote inflammation, proliferation, and thrombosis as characteristically seen in the target organs of diabetes complications.
TLR4 at the Crossroads of Nutrients, Gut Microbiota, and Metabolic Inflammation • Licio A. Velloso, Franco Folli, and Mario J. Saad • The authors review the data that place TLR4 in the center of the events that connect the consumption of dietary fats with metabolic inflammation and insulin resistance. Changes in the gut microbiota can lead to reduced integrity of the intestinal barrier, leading to increased leakage of LPS and fatty acids, which can act upon TLR4 to activate systemic inflammation. Fatty acids can also trigger endoplasmic reticulum stress, which can be further stimulated by cross-talk with active TLR4. Thus, the current data support a connection among the three main triggers of metabolic inflammation, and TLR4 emerges as a link among all of these mechanisms.