Albert Shieh, Christina Ma, R. Chun, Sten Witzel, Brandon Rafison, H. Contreras, Jonas Wittwer-Schegg, L. Swinkels, Tonnie Huijs, M. Hewison, J. Adams
Context Vitamin 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]. Objective To 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. Design Sixteen-week randomized controlled trial. Biochemistries at 0, 4, 8, and 16 weeks. Setting Academic medical center. Participants Thirty-five adults ≥18 years of age with 25D levels <20 ng/mL. Intervention Sixty micrograms (2400 IU)/d of D3 or 20 μg/d of 25D3. Main Outcome Measures Total and free 25D, and PTH. Results Baseline 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). Conclusions 25D3 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.
维生素D缺乏症对非白人的影响尤为严重。关于如何最好地恢复低25D水平，以及如何最好地定义维生素D状态[总(蛋白质结合加上游离)vs游离25D]的争议一直存在。目的评估维生素D3(胆钙化醇，或D3)与25-羟基维生素D3(钙化二醇，或25D3)对多种族成人总25D和游离25D的影响，以及甲状旁腺激素(PTH)的变化是否与总25D和游离25D有更强的相关性。设计16周随机对照试验。第0、4、8、16周的生化课。学术医疗中心。参与者:35名年龄≥18岁且25D水平<20 ng/mL的成年人。干预:服用60微克(2400国际单位)/天的D3或20微克/天的25D3。主要观察指标:总25D、游离25D、甲状旁腺激素。结果基线总浓度(16.2±3.7 vs 17.0±2.5 ng/mL);P = 0.4)和游离(4.2±0.8 vs 4.7±1.0 pg/mL;P = 0.2) 25D在D3组和25D3组之间差异无统计学意义;25D3增加总剂量(+25.5 vs +13.8 ng/mL);P = 0.001)和游离(+6.6 vs +3.5 pg/mL;P = 0.03) 25D以上。到4周时，87.5%的25D3参与者的总25D水平≥30 ng/mL，而D3参与者的比例为23.1% (P = 0.001)。PTH的变化与总25D (P = 0.01)和游离25D (P = 0.04)相关。结论无论种族/民族，25d3均比D3更快地提高总25D和游离25D水平。游离和总25D与PTH的变化相似。
{"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}
H. Ghanim, M. Batra, S. Abuaysheh, K. Green, A. Makdissi, Nitesh D Kuhadiya, A. Chaudhuri, P. Dandona
Background Fiber intake is associated with a reduction in the occurrence of cardiovascular events and diabetes. Objective To investigate whether the addition of fiber to a high-fat, high-calorie (HFHC) meal prevents proinflammatory changes induced by the HFHC meal. Design Ten 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. Results Fiber 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. Conclusions The 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.
{"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}
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
Context The 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. Objective To 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. Design/Setting/Participants Patients with GD and healthy donors in an academic medical center clinical practice were recruited. Main Outcome Measures Liquid chromatography-tandem mass spectrometry, autoradiography, real-time polymerase chain reaction, hyaluronan immunoassay. Results Serum 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. Conclusion TA4 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.
{"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}
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
Context We 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. Objective To examine whether methylation at SNP-420 affects plasma resistin, we analyzed plasma resistin and methylation at RETN SNP-420. Design and Methods Genomic DNA was extracted from peripheral white blood cells in 2078 Japanese subjects. Quantification of the methylation was performed by pyrosequencing after DNA bisulfite conversion. Results Methylation 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. Conclusions Plasma 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.
我们之前报道过RETN启动子区域的单核苷酸多态性(SNP)-420 C>G (rs1862513)与2型糖尿病相关。血浆抵抗素与SNP-420基因型密切相关。SNP-420是影响胞嘧啶-磷酸-鸟嘌呤二核苷酸序列的CpG-SNP。目的探讨SNP-420位点甲基化对血浆抵抗素的影响，分析RETN SNP-420位点甲基化对血浆抵抗素的影响。设计与方法从2078名日本受试者外周血中提取基因组DNA。DNA亚硫酸氢盐转化后，通过焦磷酸测序进行甲基化定量。结果C/C基因型SNP-420位点甲基化率最高(36.9±5.7%)，其次是C/G基因型(21.4±3.5%)和G/G基因型(2.9±1.4%);P < 0.001)。当对每种基因型进行评估时，SNP-420甲基化与C/C (β = -0.134, P < 0.001)或C/G (β = -0.227, P < 0.001)基因型的血浆抵抗素呈负相关。在本质上具有C/C基因型的THP-1人单核细胞中，一种去甲基化试剂5-aza-dC降低了SNP-420的甲基化，增加了RETN信使RNA。位于RETN 3'非翻译区的SNP+1263 (rs3745369)也与SNP-420位点的甲基化有关。此外，在C/C基因型中，高度敏感的C反应蛋白与SNP-420位点的甲基化呈负相关，而体重指数呈正相关。结论血浆抵抗素与SNP-420位点甲基化程度呈负相关，主要依赖于SNP-420基因型。这种关联也可以部分独立于SNP-420基因型来解释。SNP-420可能对血浆抵抗素具有遗传和表观遗传双重作用。
{"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}
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.
{"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}
M. Vitales-Noyola, A. Ramos-Leví, Ana Serrano-Somavilla, Rebeca Martínez-Hernández, M. Sampedro-Nuñez, C. Di Pasquale, R. González-Amaro, M. Marazuela
Context Signaling 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. Objective To analyze the expression and function of the costimulatory receptor SLAMF1 in lymphocytes of patients with AITD. Design Cross-sectional, prospective, single-center study. Setting Department of Endocrinology, Hospital Universitario de la Princesa, Madrid. Patients Twenty-eight patients with AITD (17 with Graves disease and 11 with Hashimoto thyroiditis) and 21 controls. Intervention Multiparametric 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. Main Outcome Measure Expression levels and the function of SLAMF1 in lymphocytes in AITD patients and controls. Results Expression 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. Conclusions The 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.
{"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}
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.
{"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}
D. Gómez-Arbeláez, D. Bellido, A. Castro, Lucía Ordóñez-Mayán, J. Carreira, C. Galbán, M. Martínez-Olmos, A. Crujeiras, I. Sajoux, F. Casanueva
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.
背景:当使用低热量饮食作为肥胖治疗时，常见的问题是无脂肪量(主要是肌肉量)的减少，这与脂肪量(FM)的减少一起发生，以及确定评估身体成分变化的最佳方法。目的:本研究旨在评估极低热量生酮(VLCK)饮食引起的肥胖患者身体成分的变化，并比较用于评估这些变化的3种不同方法。设计:20例肥胖患者遵循VLCK饮食4个月。采用双能x线吸收仪(DXA)、多频生物电阻抗(nf - bia)和空气置换体积脉搏波(ADP)技术进行体成分评估。肌肉力量也被评估。在与酮症相匹配的4个点(基础、最大酮症、酮症下降和脱离酮症)进行测量。结果:4个月后，VLCK饮食导致体重减轻- 20.2±4.5 kg，脂肪量(FM)减少- 16.5±5.1 kg (DXA)， - 18.2±5.8 kg (MF-BIA)和- 17.7±9.9 kg (ADP)。内脏FM也明显下降。在酮症最严重时，无脂肪量出现了轻微但显著的减少，主要是由于体内总水分的变化，此后恢复。没有观察到肌肉力量的变化。这三种评估身体成分的方法之间有很强的相关性。结论:VLCK饮食引起的体重减轻主要以牺牲脂肪和内脏质量为代价;肌肉质量和力量得以保留。在使用的3种体成分技术中，MF-BIA法在临床环境中似乎更方便。
{"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}
O. Lamy, Elena Gonzalez‐Rodriguez, D. Stoll, D. Hans, B. Aubry-Rozier
Context Denosumab 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. Cases Description We 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. Conclusion Studies 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.
{"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}
G. Parthasarathy, Y. Kudva, P. Low, M. Camilleri, A. Basu, A. Bharucha
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.
{"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}
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