The Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Effects of Cholecalciferol vs Calcifediol on Total and Free 25-Hydroxyvitamin D and Parathyroid Hormone","authors":"Albert Shieh, Christina Ma, R. Chun, Sten Witzel, Brandon Rafison, H. Contreras, Jonas Wittwer-Schegg, L. Swinkels, Tonnie Huijs, M. Hewison, J. Adams","doi":"10.1210/jc.2016-3919","DOIUrl":"https://doi.org/10.1210/jc.2016-3919","url":null,"abstract":"Context\u0000Vitamin D deficiency disproportionately affects nonwhite individuals. Controversy persists over how to best restore low 25D levels, and how to best define vitamin D status [total (protein bound plus free) vs free 25D].\u0000\u0000\u0000Objective\u0000To assess the effects of vitamin D3 (cholecalciferol, or D3) vs 25-hydroxyvitamin D3 (calcifediol, or 25D3) on total and free 25D in a multiethnic cohort of adults, and whether change in parathyroid hormone (PTH) is more strongly associated with total vs free 25D.\u0000\u0000\u0000Design\u0000Sixteen-week randomized controlled trial. Biochemistries at 0, 4, 8, and 16 weeks.\u0000\u0000\u0000Setting\u0000Academic medical center.\u0000\u0000\u0000Participants\u0000Thirty-five adults ≥18 years of age with 25D levels <20 ng/mL.\u0000\u0000\u0000Intervention\u0000Sixty micrograms (2400 IU)/d of D3 or 20 μg/d of 25D3.\u0000\u0000\u0000Main Outcome Measures\u0000Total and free 25D, and PTH.\u0000\u0000\u0000Results\u0000Baseline total (16.2 ± 3.7 vs 17.0 ± 2.5 ng/mL; P = 0.4) and free (4.2 ± 0.8 vs 4.7 ± 1.0 pg/mL; P = 0.2) 25D were similar between D3 and 25D3 groups, respectively; 25D3 increased total (+25.5 vs +13.8 ng/mL; P = 0.001) and free (+6.6 vs +3.5 pg/mL; P = 0.03) 25D more than D3. By 4 weeks, 87.5% of 25D3 participants had total 25D levels ≥30 ng/mL, compared with 23.1% of D3 participants (P = 0.001). Change in PTH was associated with both total (P = 0.01) and free 25D (P = 0.04).\u0000\u0000\u0000Conclusions\u000025D3 increased total and free 25D levels more rapidly than D3, regardless of race/ethnicity. Free and total 25D were similarly associated with change in PTH.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"120 1","pages":"1133–1140"},"PeriodicalIF":0.0,"publicationDate":"2017-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79632832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiinflammatory and ROS Suppressive Effects of the Addition of Fiber to a High-Fat High-Calorie Meal","authors":"H. Ghanim, M. Batra, S. Abuaysheh, K. Green, A. Makdissi, Nitesh D Kuhadiya, A. Chaudhuri, P. Dandona","doi":"10.1210/jc.2016-2669","DOIUrl":"https://doi.org/10.1210/jc.2016-2669","url":null,"abstract":"Background\u0000Fiber intake is associated with a reduction in the occurrence of cardiovascular events and diabetes.\u0000\u0000\u0000Objective\u0000To investigate whether the addition of fiber to a high-fat, high-calorie (HFHC) meal prevents proinflammatory changes induced by the HFHC meal.\u0000\u0000\u0000Design\u0000Ten normal fasting subjects consumed an HFHC meal with or without an additional 30 g of insoluble dietary fiber on 2 separate visits. Blood samples were collected over 5 hours, and mononuclear cells (MNCs) were isolated.\u0000\u0000\u0000Results\u0000Fiber addition to the HFHC meal significantly lowered glucose excursion in the first 90 minutes and increased insulin and C-peptide secretion throughout the 5-hour follow-up period compared with the meal alone. The HFHC meal induced increases in lipopolysaccharide (LPS) concentrations, MNC reactive oxygen species generation, and the expression of interleukin (IL)-1β, tumor necrosis factor α (TNF-α), Toll-like receptor (TLR)-4, and CD14. The addition of fiber prevented an increase in LPS and significantly reduced the increases in ROS generation and the expression of IL-1β, TNF-α, TLR-4, and CD14. In addition, the meal increased Suppressor of cytokine signaling (SOCS)-3 and protein tyrosine phosphatase 1B (PTP-1B) messenger RNA and protein levels, which were inhibited when fiber was added.\u0000\u0000\u0000Conclusions\u0000The addition of fiber to a proinflammatory HFHC meal had beneficial anti-inflammatory and metabolic effects. Thus, the fiber content of the American Heart Association meal may contribute to its noninflammatory nature. If these actions of dietary fiber are sustained following long-term intake, they may contribute to fiber's known benefits in the prevention of insulin resistance, type 2 diabetes, and atherosclerosis.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"4 1","pages":"858–869"},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78446265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Serum Tetrac in Graves Disease: Potential Pathogenic Role in Thyroid-Associated Ophthalmopathy","authors":"R. Fernando, Ekaterina A. Placzek, E. A. Reese, Andrew T. Placzek, S. Schwartz, Aaron Trierweiler, Leslie Niziol, N. Raychaudhuri, S. Atkins, T. Scanlan, Terry J. Smith","doi":"10.1210/jc.2016-2762","DOIUrl":"https://doi.org/10.1210/jc.2016-2762","url":null,"abstract":"Context\u0000The sources and biological impact of 3,3',5,5' tetraiodothyroacetic acid (TA4) are uncertain. CD34+ fibrocytes express several proteins involved in the production of thyroid hormones. They infiltrate the orbit in Graves disease (GD), an autoimmune process known as thyroid-associated ophthalmopathy. It appears that the thyrotropin receptor plays an important role in the pathogenesis of thyroid-associated ophthalmopathy.\u0000\u0000\u0000Objective\u0000To quantify levels of TA4 in healthy participants and those with GD, determine whether fibrocytes generate this thyroid hormone analogue, and determine whether TA4 influences the actions of thyroid-stimulating hormone and thyroid-stimulating immunoglobulins in orbital fibroblasts.\u0000\u0000\u0000Design/Setting/Participants\u0000Patients with GD and healthy donors in an academic medical center clinical practice were recruited.\u0000\u0000\u0000Main Outcome Measures\u0000Liquid chromatography-tandem mass spectrometry, autoradiography, real-time polymerase chain reaction, hyaluronan immunoassay.\u0000\u0000\u0000Results\u0000Serum levels of TA4 are elevated in GD. TA4 levels are positively correlated with those of thyroxine and negatively correlated with serum levels of triiodothyronine. Several cell types in culture generate TA4 from ambient thyroxine, including fibrocytes, HELA cells, human Müller stem cells, and retinal pigmented epithelial cells. Propylthiouracil inhibits TA4 generation. TA4 enhances the induction by thyrotropin and thyroid-stimulating immunoglobulins of several participants in the pathogenesis of thyroid-associated ophthalmopathy, including interleukin 6, hyaluronan synthase 1, prostaglandin endoperoxide H synthase 2, and haluronan production.\u0000\u0000\u0000Conclusion\u0000TA4 may be ubiquitously generated in many tissues and enhances the biological impact of thyrotropin and thyroid-stimulating immunoglobulins in orbital connective tissue. These findings may identify a physiologically important determinant of extrathyroidal thyroid-stimulating hormone action.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"69 1","pages":"776–785"},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77599157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Effects of a RETN Single Nucleotide Polymorphism (SNP) at –420 on Plasma Resistin: Genotype and DNA Methylation","authors":"H. Onuma, Y. Tabara, R. Kawamura, J. Ohashi, Wataru Nishida, Y. Takata, M. Ochi, T. Nishimiya, Y. Ohyagi, R. Kawamoto, K. Kohara, T. Miki, H. Osawa","doi":"10.1210/jc.2016-2417","DOIUrl":"https://doi.org/10.1210/jc.2016-2417","url":null,"abstract":"Context\u0000We previously reported that single nucleotide polymorphism (SNP)-420 C>G (rs1862513) in the promoter region of RETN was associated with type 2 diabetes. Plasma resistin was tightly correlated with SNP-420 genotypes. SNP-420 is a CpG-SNP affecting the sequence of cytosine-phosphate-guanine dinucleotides.\u0000\u0000\u0000Objective\u0000To examine whether methylation at SNP-420 affects plasma resistin, we analyzed plasma resistin and methylation at RETN SNP-420.\u0000\u0000\u0000Design and Methods\u0000Genomic DNA was extracted from peripheral white blood cells in 2078 Japanese subjects. Quantification of the methylation was performed by pyrosequencing after DNA bisulfite conversion.\u0000\u0000\u0000Results\u0000Methylation at SNP-420 was highest in the C/C genotype (36.9 ± 5.7%), followed by C/G (21.4 ± 3.5%) and G/G (2.9 ± 1.4%; P < 0.001). When assessed in each genotype, methylation at SNP-420 was inversely associated with plasma resistin in the C/C (β = -0.134, P < 0.001) or C/G (β = -0.227, P < 0.001) genotype. In THP-1 human monocytes intrinsically having the C/C genotype, a demethylating reagent, 5-aza-dC, decreased the methylation at SNP-420 and increased RETN messenger RNA. SNP+1263 (rs3745369), located in the 3' untranslated region of RETN, was also associated with methylation at SNP-420. In addition, highly sensitive C-reactive protein was inversely associated with methylation at SNP-420 in the C/C genotype, whereas body mass index was positively associated.\u0000\u0000\u0000Conclusions\u0000Plasma resistin was inversely associated with the extent of methylation at SNP-420 mainly dependent on the SNP-420 genotype. The association can also be explained partially independent of SNP-420 genotypes. SNP-420 could have dual, genetic and epigenetic effects on plasma resistin.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"22 1","pages":"884–892"},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75933188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality Among Hospitalized Patients With Hypoglycemia: Insulin Related and Noninsulin Related","authors":"A. Akirov, A. Grossman, T. Shochat, I. Shimon","doi":"10.1210/jc.2016-2653","DOIUrl":"https://doi.org/10.1210/jc.2016-2653","url":null,"abstract":"Context: Hypoglycemia is common among hospitalized patients with and without diabetes mellitus. Objective: Investigate the association between spontaneous or insulin-related hypoglycemia and mortality in hospitalized patients. Design: Hypoglycemia was defined as blood glucose <70 mg/dl (3.9 mmol/l), including moderate (40 to 70 mg/dl, 2.2 to 3.9 mmol/l) and severe hypoglycemia (<40 mg/dl, 2.2 mmol/l). Use of insulin during hospitalization defined insulin-related hypoglycemia, thus patients were classified into 6 groups: non-insulin treated (NITC) and insulin-treated controls (ITC), insulin-related hypoglycemia (IH) or severe hypoglycemia (ISH), and non insulin-related hypoglycemia (NIH) and severe hypoglycemia (NISH). Setting and Patients: Historical prospectively data of patients ≥ 18 years of age, hospitalized in medical wards for any cause between January 2011 and December 2013. Main Outcome Measure: All-cause mortality at the end of follow-up. Results: The cohort included 33,675 patients, including 2605 with moderate hypoglycemia (IH, 1011; NIH, 1594) and 342 with severe hypoglycemia (ISH, 201; NISH,141). Overall end-of-follow-up mortality was 31.9% (NITC, 28.0%; ITC, 42.9%; NIH, 50.7%; IH, 55.3%; NISH, 70.9%; ISH, 69.1%). Compared with NITC, unadjusted hazard ratios (95% confidence intervals) for mortality were as follows: ITC, 1.7 (1.6 to 1.8), NIH, 2.2 (2.0 to 2.4), IH, 2.5 (2.2 to 2.7), NISH, 4.2 (3.5 to 5.2), and ISH, 3.8 (3.2 to 4.5); with P < 0.001. Following multivariate analysis, respective hazard ratios were 1.8, 2.1, 2.4, 3.2, and 3.6 (P < 0.001). Cause of admission did not affect the association. Conclusions: In hospitalized patients, hypoglycemia, either with insulin use or spontaneous, is associated with increased short- and long-term mortality.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"55 1","pages":"416–424"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80213686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and Function of the Costimulatory Receptor SLAMF1 Is Altered in Lymphocytes From Patients With Autoimmune Thyroiditis","authors":"M. Vitales-Noyola, A. Ramos-Leví, Ana Serrano-Somavilla, Rebeca Martínez-Hernández, M. Sampedro-Nuñez, C. Di Pasquale, R. González-Amaro, M. Marazuela","doi":"10.1210/jc.2016-2322","DOIUrl":"https://doi.org/10.1210/jc.2016-2322","url":null,"abstract":"Context\u0000Signaling lymphocytic activation molecule family 1 (SLAMF1) is a costimulatory receptor expressed by most immune cells. Its role in autoimmune thyroid disease (AITD) is not well known.\u0000\u0000\u0000Objective\u0000To analyze the expression and function of the costimulatory receptor SLAMF1 in lymphocytes of patients with AITD.\u0000\u0000\u0000Design\u0000Cross-sectional, prospective, single-center study.\u0000\u0000\u0000Setting\u0000Department of Endocrinology, Hospital Universitario de la Princesa, Madrid.\u0000\u0000\u0000Patients\u0000Twenty-eight patients with AITD (17 with Graves disease and 11 with Hashimoto thyroiditis) and 21 controls.\u0000\u0000\u0000Intervention\u0000Multiparametric flow cytometry and immunofluorescence techniques to analyze the expression of SLAMF1 in peripheral blood (n = 28) and thyroid tissue (n = 5) mononuclear cells. Assay of inhibition of cellular proliferation to study the function of SLAMF1 in CD4+CD25+ T regulatory (Treg) cells.\u0000\u0000\u0000Main Outcome Measure\u0000Expression levels and the function of SLAMF1 in lymphocytes in AITD patients and controls.\u0000\u0000\u0000Results\u0000Expression of SLAMF1 was significantly increased in peripheral blood CD4+, T helper 17, and CD19+ B cells from AITD patients. Immunofluorescence microscopy detected the presence of SLAMF1+ lymphocytes in thyroid inflammatory cell infiltrate. Functional studies showed that SLAMF1 engagement in Treg cells increased their suppressive function in healthy controls but not in AITD patients.\u0000\u0000\u0000Conclusions\u0000The altered expression of SLAMF1, as well as its defective function observed in patients with AITD, may have a relevant role in the defective immune-regulatory function observed in this condition.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"61 1","pages":"672–680"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76051655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Premature Mortality on the Link Between Type 2 Diabetes and Hip Fracture: The Fremantle Diabetes Study","authors":"E. Hamilton, W. Davis, D. Bruce, T. Davis","doi":"10.1210/jc.2016-3570","DOIUrl":"https://doi.org/10.1210/jc.2016-3570","url":null,"abstract":"Context: Studies of hip fracture complicating diabetes have not considered the effect of premature mortality. Objective: The aim of our study was to determine influence of the competing risk of death on the association between type 2 diabetes and hip fracture. Design: The study was designed as a longitudinal observational study. Setting: The study setting was an urban community. Patients: Participants included 1291 patients with type 2 diabetes (mean age 64.0 years) and 5159 matched residents without diabetes. Main Outcome Measures: Primary outcome measures were incident hip fracture hospitalizations and deaths. Hip fracture risk was assessed using proportional hazards and competing risk regression modeling. Results: During a mean of 14.1 years of follow-up, the incidence rate ratio for first hip fracture hospitalization in participants with vs without diabetes was 1.33 [95% confidence interval (CI), 1.05 to 1.68; P = 0.013]. Type 2 diabetes was associated with a cause-specific hazard ratio (csHR) for hip fracture of 1.50 (95% CI, 1.19 to 1.89; P < 0.001) and a subdistribution hazard ratio (sdHR) of 1.21 (95% CI, 0.96 to 1.52; P = 0.11) after adjustment for age, sex, and comorbidities. In patients with diabetes, significant csHRs for incident hip fracture were male sex (protective), body mass index (protective), insulin use, and renal impairment. These variables, with increasing age, also had significant sdHRs. Conclusions: The diabetes-associated risk of hip fracture is attenuated after allowing for the competing risk of death. Risk factors for hip fracture in diabetes were those in reported in general population studies plus insulin use.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"137 1","pages":"551–559"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79727162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body Composition Changes After Very-Low-Calorie Ketogenic Diet in Obesity Evaluated by 3 Standardized Methods","authors":"D. Gómez-Arbeláez, D. Bellido, A. Castro, Lucía Ordóñez-Mayán, J. Carreira, C. Galbán, M. Martínez-Olmos, A. Crujeiras, I. Sajoux, F. Casanueva","doi":"10.1210/jc.2016-2385","DOIUrl":"https://doi.org/10.1210/jc.2016-2385","url":null,"abstract":"Context: Common concerns when using low-calorie diets as a treatment for obesity are the reduction in fat-free mass, mostly muscular mass, that occurs together with the fat mass (FM) loss, and determining the best methodologies to evaluate body composition changes. Objective: This study aimed to evaluate the very-low-calorie ketogenic (VLCK) diet-induced changes in body composition of obese patients and to compare 3 different methodologies used to evaluate those changes. Design: Twenty obese patients followed a VLCK diet for 4 months. Body composition assessment was performed by dual-energy X-ray absorptiometry (DXA), multifrequency bioelectrical impedance (MF-BIA), and air displacement plethysmography (ADP) techniques. Muscular strength was also assessed. Measurements were performed at 4 points matched with the ketotic phases (basal, maximum ketosis, ketosis declining, and out of ketosis). Results: After 4 months the VLCK diet induced a −20.2 ± 4.5 kg weight loss, at expenses of reductions in fat mass (FM) of −16.5 ± 5.1 kg (DXA), −18.2 ± 5.8 kg (MF-BIA), and −17.7 ± 9.9 kg (ADP). A substantial decrease was also observed in the visceral FM. The mild but marked reduction in fat-free mass occurred at maximum ketosis, primarily as a result of changes in total body water, and was recovered thereafter. No changes in muscle strength were observed. A strong correlation was evidenced between the 3 methods of assessing body composition. Conclusion: The VLCK diet-induced weight loss was mainly at the expense of FM and visceral mass; muscle mass and strength were preserved. Of the 3 body composition techniques used, the MF-BIA method seems more convenient in the clinical setting.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"36 1","pages":"488–498"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90573885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: 9 Clinical Cases Report","authors":"O. Lamy, Elena Gonzalez‐Rodriguez, D. Stoll, D. Hans, B. Aubry-Rozier","doi":"10.1210/jc.2016-3170","DOIUrl":"https://doi.org/10.1210/jc.2016-3170","url":null,"abstract":"Context\u0000Denosumab inhibits bone resorption, increases bone mineral density, and reduces fracture risk. Denosumab was approved for the treatment of osteoporosis and the prevention of bone loss in some oncological situations. Denosumab discontinuation is associated with a severe bone turnover rebound (BTR) and a rapid loss of bone mineral density. The clinical consequences of the BTR observed after denosumab discontinuation are not known.\u0000\u0000\u0000Cases Description\u0000We report 9 women who presented 50 rebound-associated vertebral fractures (RAVFs) after denosumab discontinuation. A broad biological and radiological assessment excluded other causes than osteoporosis. These 9 cases are unusual and disturbing for several reasons. First, all vertebral fractures (VFs) were spontaneous, and most patients had a high number of VFs (mean = 5.5) in a short period of time. Second, the fracture risk was low for most of these women. Third, their VFs occurred rapidly after last denosumab injection (9-16 months). Fourth, vertebroplasty was associated with a high number of new VFs. All the observed VFs seem to be related to denosumab discontinuation and unlikely to the underlying osteoporosis or osteopenia. We hypothesize that the severe BTR is involved in microdamage accumulation in trabecular bone and thus promotes VFs.\u0000\u0000\u0000Conclusion\u0000Studies are urgently needed to determine 1) the pathophysiological processes involved, 2) the clinical profile of patients at risk for RAVFs, and 3) the management and/or treatment regimens after denosumab discontinuation. Health authorities, physicians, and patients must be aware of this RAVF risk. Denosumab injections must be scrupulously done every 6 months but not indefinitely.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"1 1","pages":"354–358"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76436643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship Between Gastric Emptying and Diurnal Glycemic Control in Type 1 Diabetes Mellitus: A Randomized Trial","authors":"G. Parthasarathy, Y. Kudva, P. Low, M. Camilleri, A. Basu, A. Bharucha","doi":"10.1210/jc.2016-2809","DOIUrl":"https://doi.org/10.1210/jc.2016-2809","url":null,"abstract":"Context: In type 1 diabetes (T1D), delayed gastric emptying (GE) may predispose to a mismatch between insulin delivery and glucose absorption. Previous studies evaluated, only partly, the relationship between delayed GE and postprandial, but not diurnal, glycemia. Objective: To assess the relationship between GE disturbances and glycemic control in T1D and the effects of accelerating GE on glycemic control. Design, Setting, and Participants: This was a randomized placebo-controlled trial in 30 patients with T1D on an insulin pump at an academic medical center. Intervention(s): GE was evaluated with a [13C]-Spirulina breath test at baseline (GEbaseline), during intravenous saline or erythromycin (2 or 3 mg/kg; GEiv), and after 7 days of oral erythromycin or placebo (GEoral). Weighed meals were provided throughout the study. Main Outcome Measure(s): These were GE and continuous glucose monitoring (CGM). Results: The baseline glycosylated hemoglobin was 7.6% ± 0.8% (60 ± 8.7 mmol/mol); 12 patients (40%) had delayed GE; faster GE was associated with a greater postprandial CGM-based glucose, but slower GE was not associated with postprandial hypoglycemia (<70 mg/dL). Intravenous (3 mg/kg) but not oral erythromycin accelerated GE. The relationship between GE and glycemia differed between the postprandial periods and the entire day. After adjusting for carbohydrate intake and insulin consumption, faster GE was associated with more hyperglycemia during the postprandial period but lower glucose values across the entire study. Conclusions: In T1D, pharmacologically mediated acceleration of GE increases postprandial CGM-based glucose. In contrast, delayed GE is associated with greater CGM-based glucose values over the entire day.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"10 1","pages":"398–406"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88440677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}