B. Majtan, T. Zelinka, J. Rosa, O. Petrák, Z. Krátká, B. Štrauch, V. Tuka, A. Vránková, D. Michalský, K. Novák, D. Wichterle, J. Widimský, R. Holaj
Context Catecholamines may contribute to the accumulation of collagen fibers and extracellular matrix in the arterial and myocardial wall due to various mechanisms. Reversibility of this process has not been studied on both structures simultaneously. Objective To clarify the long-term effect of excess normalization of catecholamines on carotid and myocardial wall changes in patients with pheochromocytoma or functional paraganglioma (PHEO) after tumor removal. Design, Settings, and Patients Carotid intima-media thickness (IMT) and the left ventricular (LV) mass index were studied in 50 patients with PHEO before tumor removal and 5 years after tumor removal, and in 50 blood pressure- and age-matched essential hypertensive patients before follow-up and after 5 years of follow-up. Main Outcome Measures Common carotid artery (CCA)-IMT and LV mass indexed to lean body mass (LBM). Results Elimination of catecholamine excess in the PHEO group resulted in a significant decrease in CCA-IMT and LV mass index from 0.86 ± 0.17 to 0.83 ± 0.18 mm (P < 0.05) and from 3.2 ± 0.9 to 2.9 ± 0.9 g/LBM (P < 0.001), respectively. In contrast, CCA-IMT and LV mass index increased significantly from 0.78 ± 0.14 to 0.81 ± 0.15 mm (P < 0.05) and from 3.1 ± 0.7 to 3.2 ± 0.6 g/LBM (P < 0.05), respectively, in patients with essential hypertension. Conclusion In patients with PHEO, carotid IMT and LV mass index can significantly regress after tumor removal, in contrast to the impairment of these parameters in essential hypertensive patients during the same long-term period.
{"title":"Long-Term Effect of Adrenalectomy on Cardiovascular Remodeling in Patients With Pheochromocytoma","authors":"B. Majtan, T. Zelinka, J. Rosa, O. Petrák, Z. Krátká, B. Štrauch, V. Tuka, A. Vránková, D. Michalský, K. Novák, D. Wichterle, J. Widimský, R. Holaj","doi":"10.1210/jc.2016-2422","DOIUrl":"https://doi.org/10.1210/jc.2016-2422","url":null,"abstract":"Context\u0000Catecholamines may contribute to the accumulation of collagen fibers and extracellular matrix in the arterial and myocardial wall due to various mechanisms. Reversibility of this process has not been studied on both structures simultaneously.\u0000\u0000\u0000Objective\u0000To clarify the long-term effect of excess normalization of catecholamines on carotid and myocardial wall changes in patients with pheochromocytoma or functional paraganglioma (PHEO) after tumor removal.\u0000\u0000\u0000Design, Settings, and Patients\u0000Carotid intima-media thickness (IMT) and the left ventricular (LV) mass index were studied in 50 patients with PHEO before tumor removal and 5 years after tumor removal, and in 50 blood pressure- and age-matched essential hypertensive patients before follow-up and after 5 years of follow-up.\u0000\u0000\u0000Main Outcome Measures\u0000Common carotid artery (CCA)-IMT and LV mass indexed to lean body mass (LBM).\u0000\u0000\u0000Results\u0000Elimination of catecholamine excess in the PHEO group resulted in a significant decrease in CCA-IMT and LV mass index from 0.86 ± 0.17 to 0.83 ± 0.18 mm (P < 0.05) and from 3.2 ± 0.9 to 2.9 ± 0.9 g/LBM (P < 0.001), respectively. In contrast, CCA-IMT and LV mass index increased significantly from 0.78 ± 0.14 to 0.81 ± 0.15 mm (P < 0.05) and from 3.1 ± 0.7 to 3.2 ± 0.6 g/LBM (P < 0.05), respectively, in patients with essential hypertension.\u0000\u0000\u0000Conclusion\u0000In patients with PHEO, carotid IMT and LV mass index can significantly regress after tumor removal, in contrast to the impairment of these parameters in essential hypertensive patients during the same long-term period.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"33 1","pages":"1208–1217"},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74855547","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}
Thiago Gagliano-Jucá, Tevhide Betul Icli, K. Pencina, Zhuoying Li, J. Tapper, Grace Huang, T. Travison, P. Tsitouras, S. Harman, T. Storer, S. Bhasin, S. Basaria
Context Endogenous testosterone levels have been negatively associated with QTc interval in small case series; the effects of testosterone therapy on electrocardiographic parameters have not been evaluated in randomized trials. Objective To evaluate the effects of testosterone replacement on corrected QT interval (QTcF) in two randomized controlled trials. Participants Men with pre- and postrandomization electrocardiograms (ECGs) from the Testosterone and Pain (TAP) and the Testosterone Effects on Atherosclerosis in Aging Men (TEAAM) Trials. Interventions Participants were randomized to either placebo or testosterone gel for 14 weeks (TAP) or 36 months (TEAAM). ECGs were performed at baseline and at the end of interventions in both trials; in the TEAAM trial ECGs were also obtained at 12 and 24 months. Outcomes Difference in change in the QTcF between testosterone and placebo groups was assessed in each trial. Association of changes in testosterone levels with changes in QTcF was analyzed in men assigned to the testosterone group of each trial. Results Mean total testosterone levels increased in the testosterone group of both trials. In the TAP trial, there was a nonsignificant reduction in mean QTcF in the testosterone group compared with placebo (effect size = -4.72 ms; P = 0.228) and the changes in QTcF were negatively associated to changes in circulating testosterone (P = 0.036). In the TEAAM trial, testosterone attenuated the age-related increase in QTcF seen in the placebo group (effect size= -6.30 ms; P < 0.001). Conclusion Testosterone replacement attenuated the age-related increase in QTcF duration in men. The clinical implications of these findings require further investigation.
{"title":"Effects of Testosterone Replacement on Electrocardiographic Parameters in Men: Findings From Two Randomized Trials","authors":"Thiago Gagliano-Jucá, Tevhide Betul Icli, K. Pencina, Zhuoying Li, J. Tapper, Grace Huang, T. Travison, P. Tsitouras, S. Harman, T. Storer, S. Bhasin, S. Basaria","doi":"10.1210/jc.2016-3669","DOIUrl":"https://doi.org/10.1210/jc.2016-3669","url":null,"abstract":"Context\u0000Endogenous testosterone levels have been negatively associated with QTc interval in small case series; the effects of testosterone therapy on electrocardiographic parameters have not been evaluated in randomized trials.\u0000\u0000\u0000Objective\u0000To evaluate the effects of testosterone replacement on corrected QT interval (QTcF) in two randomized controlled trials.\u0000\u0000\u0000Participants\u0000Men with pre- and postrandomization electrocardiograms (ECGs) from the Testosterone and Pain (TAP) and the Testosterone Effects on Atherosclerosis in Aging Men (TEAAM) Trials.\u0000\u0000\u0000Interventions\u0000Participants were randomized to either placebo or testosterone gel for 14 weeks (TAP) or 36 months (TEAAM). ECGs were performed at baseline and at the end of interventions in both trials; in the TEAAM trial ECGs were also obtained at 12 and 24 months.\u0000\u0000\u0000Outcomes\u0000Difference in change in the QTcF between testosterone and placebo groups was assessed in each trial. Association of changes in testosterone levels with changes in QTcF was analyzed in men assigned to the testosterone group of each trial.\u0000\u0000\u0000Results\u0000Mean total testosterone levels increased in the testosterone group of both trials. In the TAP trial, there was a nonsignificant reduction in mean QTcF in the testosterone group compared with placebo (effect size = -4.72 ms; P = 0.228) and the changes in QTcF were negatively associated to changes in circulating testosterone (P = 0.036). In the TEAAM trial, testosterone attenuated the age-related increase in QTcF seen in the placebo group (effect size= -6.30 ms; P < 0.001).\u0000\u0000\u0000Conclusion\u0000Testosterone replacement attenuated the age-related increase in QTcF duration in men. The clinical implications of these findings require further investigation.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"161 1","pages":"1478–1485"},"PeriodicalIF":0.0,"publicationDate":"2016-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72722135","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}
Z. Hannoush, Herminia Puerta, M. Bauer, R. Goldberg
Context: Alagille syndrome is a rare autosomal-dominant genetic disorder caused by defects in the Notch signaling pathway, which involves multiple organ systems. Bile duct paucity is the main characteristic feature of the disease, which often leads to cholestatic hypercholesterolemia. Case Description: We report the case of a male infant who had developed failure to thrive, jaundice, intermittent pruritus, and multiple diffuse symmetrical skin xanthomas at 1 year of age. He was diagnosed with pulmonary stenosis, butterfly vertebrae of T4, T6, and T8; horseshoe kidney, and embryotoxon in the left eye. Laboratory workup revealed severe hypercholesterolemia. Alagille syndrome was suspected and confirmed by genetic testing, which identified a previously undescribed frameshift pathogenic heterozygous variant in the JAG1 gene, p.Arg486Lysfs*5. Conclusions: Here, we report a unique case of a patient diagnosed with Alagille syndrome who was found to have a previously undescribed frameshift pathogenic mutation in the JAG1 gene and who presented with xanthomatosis and levels of hypercholesterolemia more than 2 times higher than those previously reported in the literature. We also provide a review of the different pathophysiologic mechanisms associated with the increase in serum cholesterol and low-density lipoprotein cholesterol concentrations seen in cholestatic liver disease in general and in Alagille syndrome in particular.
{"title":"New JAG1 Mutation Causing Alagille Syndrome Presenting With Severe Hypercholesterolemia: Case Report With Emphasis on Genetics and Lipid Abnormalities","authors":"Z. Hannoush, Herminia Puerta, M. Bauer, R. Goldberg","doi":"10.1210/jc.2016-3171","DOIUrl":"https://doi.org/10.1210/jc.2016-3171","url":null,"abstract":"Context: Alagille syndrome is a rare autosomal-dominant genetic disorder caused by defects in the Notch signaling pathway, which involves multiple organ systems. Bile duct paucity is the main characteristic feature of the disease, which often leads to cholestatic hypercholesterolemia. Case Description: We report the case of a male infant who had developed failure to thrive, jaundice, intermittent pruritus, and multiple diffuse symmetrical skin xanthomas at 1 year of age. He was diagnosed with pulmonary stenosis, butterfly vertebrae of T4, T6, and T8; horseshoe kidney, and embryotoxon in the left eye. Laboratory workup revealed severe hypercholesterolemia. Alagille syndrome was suspected and confirmed by genetic testing, which identified a previously undescribed frameshift pathogenic heterozygous variant in the JAG1 gene, p.Arg486Lysfs*5. Conclusions: Here, we report a unique case of a patient diagnosed with Alagille syndrome who was found to have a previously undescribed frameshift pathogenic mutation in the JAG1 gene and who presented with xanthomatosis and levels of hypercholesterolemia more than 2 times higher than those previously reported in the literature. We also provide a review of the different pathophysiologic mechanisms associated with the increase in serum cholesterol and low-density lipoprotein cholesterol concentrations seen in cholestatic liver disease in general and in Alagille syndrome in particular.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"42 1","pages":"350–353"},"PeriodicalIF":0.0,"publicationDate":"2016-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86048628","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}
W. Oliva-Olivera, L. Coín‐Aragüez, S. Lhamyani, M. Clemente-Postigo, J. A. Torres, M. Bernal-López, R. El Bekay, F. Tinahones
Context: The decreased expansion capacity of adipose tissue plays a crucial role in the onset of disorders associated with metabolic syndrome. Objective: The aim of this study was to examine the state of adipose tissue-derived mesenchymal stem cells (ASCs) from obese subjects with different metabolic profiles. Design: This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Setting: University Hospital. Patients and Intervention: Patients who underwent either bariatric surgery (20 morbidly obese) or cholecystectomy (40 subjects) participated in the study. Main Outcome Measures: ASCs were obtained from both visceral and subcutaneous adipose tissue. Adipogenic, fibrotic gene expression was quantified by quantitative polymerase chain reaction; Smad7 and fibroblast growth factor 2 were quantified by western blotting and enzyme-linked immunosorbent assay, respectively. The susceptibility of ASCs to apoptosis, their population doubling time, and their clonogenic potential were evaluated. Results: The worsening metabolic profile of the patients was accompanied by a decrease in the intrinsic levels of adipogenic gene expression, reduced proliferation rate, clonogenic potential, and exportation of fibroblast growth factor 2 to the cell surface of the ASCs derived from both tissues. In addition, the ASCs from patients without metabolic syndrome showed differences in susceptibility to apoptosis and expression of TGF&bgr;-signaling inhibitory protein Smad7 with respect to the ASCs from patients with metabolic syndrome. Conclusion: Our results suggest that the decrease in adipogenic-gene mRNA and clonogenic potential, as well as the accumulation of fibrotic proteins with metabolic alterations, could be a relevant mechanism controlling the number and size of neogenerated adipocytes and involved in alteration of adipose-tissue expansion.
{"title":"Adipogenic Impairment of Adipose Tissue–Derived Mesenchymal Stem Cells in Subjects With Metabolic Syndrome: Possible Protective Role of FGF2","authors":"W. Oliva-Olivera, L. Coín‐Aragüez, S. Lhamyani, M. Clemente-Postigo, J. A. Torres, M. Bernal-López, R. El Bekay, F. Tinahones","doi":"10.1210/jc.2016-2256","DOIUrl":"https://doi.org/10.1210/jc.2016-2256","url":null,"abstract":"Context: The decreased expansion capacity of adipose tissue plays a crucial role in the onset of disorders associated with metabolic syndrome. Objective: The aim of this study was to examine the state of adipose tissue-derived mesenchymal stem cells (ASCs) from obese subjects with different metabolic profiles. Design: This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Setting: University Hospital. Patients and Intervention: Patients who underwent either bariatric surgery (20 morbidly obese) or cholecystectomy (40 subjects) participated in the study. Main Outcome Measures: ASCs were obtained from both visceral and subcutaneous adipose tissue. Adipogenic, fibrotic gene expression was quantified by quantitative polymerase chain reaction; Smad7 and fibroblast growth factor 2 were quantified by western blotting and enzyme-linked immunosorbent assay, respectively. The susceptibility of ASCs to apoptosis, their population doubling time, and their clonogenic potential were evaluated. Results: The worsening metabolic profile of the patients was accompanied by a decrease in the intrinsic levels of adipogenic gene expression, reduced proliferation rate, clonogenic potential, and exportation of fibroblast growth factor 2 to the cell surface of the ASCs derived from both tissues. In addition, the ASCs from patients without metabolic syndrome showed differences in susceptibility to apoptosis and expression of TGF&bgr;-signaling inhibitory protein Smad7 with respect to the ASCs from patients with metabolic syndrome. Conclusion: Our results suggest that the decrease in adipogenic-gene mRNA and clonogenic potential, as well as the accumulation of fibrotic proteins with metabolic alterations, could be a relevant mechanism controlling the number and size of neogenerated adipocytes and involved in alteration of adipose-tissue expansion.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"17 1","pages":"478–487"},"PeriodicalIF":0.0,"publicationDate":"2016-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87587167","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}
Y. Gu, Huihui Li, X. Bao, Qing Zhang, Li Liu, G. Meng, Hongmei Wu, H. Du, Hongbin Shi, Yang Xia, Q. Su, L. Fang, F. Yu, Huijun Yang, Bin Yu, Shaomei Sun, Xing Wang, Ming Zhou, Q. Jia, Q. Guo, Hong Chang, Guolin Wang, Guowei Huang, K. Song, K. Niu
Purpose: Thyroid hormones (THs) are primarily responsible for the regulation of energy balance and metabolism, suggesting that TH levels may contribute to the development of type 2 diabetes mellitus (T2DM). However, few studies have investigated the relationship between TH and T2DM in a general population. The aim of this study was to evaluate whether serum TH levels within the reference range are related to T2DM. Methods: A cross-sectional study (n = 15,296) was performed in Tianjin, China. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels were measured by chemiluminescence immunoassay, and T2DM was defined according to the American Diabetes Association criteria. Multiple logistic regression models were used to assess the sex-specific relationships between FT3, FT4, FT3/FT4 ratios, and TSH quintiles and T2DM. Results: The prevalence of T2DM was 16.2% in males and 7.7% in females. In males, the multivariable-adjusted odds ratios (95% confidence interval) of T2DM for increasing quintiles of FT3, FT4, and FT3/FT4 ratios were 1.00, 0.75(0.63 to 0.89), 0.70(0.58 to 0.84), 0.63(0.52 to 0.76), 0.56(0.46 to 0.68; P for trend < 0.0001); 1.00, 1.05(0.87 to 1.27), 1.16(0.96 to 1.40), 1.09(0.90 to 1.31), 1.29(1.07 to 1.56; P for trend = 0.01); and 1.00, 0.69(0.58 to 0.83), 0.72(0.60 to 0.86), 0.59(0.48 to 0.71), and 0.55(0.46 to 0.66; P for trend < 0.0001), respectively. Similar results also were observed in females. In contrast, a strong negative correlation between TSH and T2DM was observed in males, but not in females. Conclusions: This study demonstrated that decreased FT3, FT3/FT4 ratios, and increased FT4 levels are independently related to a higher prevalence of T2DM in both males and females, and TSH is inversely related to T2DM in males only.
{"title":"The Relationship Between Thyroid Function and the Prevalence of Type 2 Diabetes Mellitus in Euthyroid Subjects","authors":"Y. Gu, Huihui Li, X. Bao, Qing Zhang, Li Liu, G. Meng, Hongmei Wu, H. Du, Hongbin Shi, Yang Xia, Q. Su, L. Fang, F. Yu, Huijun Yang, Bin Yu, Shaomei Sun, Xing Wang, Ming Zhou, Q. Jia, Q. Guo, Hong Chang, Guolin Wang, Guowei Huang, K. Song, K. Niu","doi":"10.1210/jc.2016-2965","DOIUrl":"https://doi.org/10.1210/jc.2016-2965","url":null,"abstract":"Purpose: Thyroid hormones (THs) are primarily responsible for the regulation of energy balance and metabolism, suggesting that TH levels may contribute to the development of type 2 diabetes mellitus (T2DM). However, few studies have investigated the relationship between TH and T2DM in a general population. The aim of this study was to evaluate whether serum TH levels within the reference range are related to T2DM. Methods: A cross-sectional study (n = 15,296) was performed in Tianjin, China. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels were measured by chemiluminescence immunoassay, and T2DM was defined according to the American Diabetes Association criteria. Multiple logistic regression models were used to assess the sex-specific relationships between FT3, FT4, FT3/FT4 ratios, and TSH quintiles and T2DM. Results: The prevalence of T2DM was 16.2% in males and 7.7% in females. In males, the multivariable-adjusted odds ratios (95% confidence interval) of T2DM for increasing quintiles of FT3, FT4, and FT3/FT4 ratios were 1.00, 0.75(0.63 to 0.89), 0.70(0.58 to 0.84), 0.63(0.52 to 0.76), 0.56(0.46 to 0.68; P for trend < 0.0001); 1.00, 1.05(0.87 to 1.27), 1.16(0.96 to 1.40), 1.09(0.90 to 1.31), 1.29(1.07 to 1.56; P for trend = 0.01); and 1.00, 0.69(0.58 to 0.83), 0.72(0.60 to 0.86), 0.59(0.48 to 0.71), and 0.55(0.46 to 0.66; P for trend < 0.0001), respectively. Similar results also were observed in females. In contrast, a strong negative correlation between TSH and T2DM was observed in males, but not in females. Conclusions: This study demonstrated that decreased FT3, FT3/FT4 ratios, and increased FT4 levels are independently related to a higher prevalence of T2DM in both males and females, and TSH is inversely related to T2DM in males only.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"6 1","pages":"434–442"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89851900","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}
J. Vangipurapu, A. Stančáková, R. Jauhiainen, J. Kuusisto, M. Laakso
Context: Recent studies have highlighted the role of height in complex diseases, but conflicting information has been reported on height as a predictor of changes in glycemia and risk of type 2 diabetes. Objective: Our aim was to investigate the association of height with insulin sensitivity, insulin secretion, glycemia, type 2 diabetes, and cardiovascular disease (CVD) in a large prospective population-based study. Design: The study included 8746 Finnish men (mean ± standard deviation, age 57.2 ± 7.1 years, body mass index, 26.8 ± 3.8 kg/m2) selected from a population-based Metabolic Syndrome in Men (METSIM) study. Setting: The study was conducted at Kuopio University Hospital and University of Eastern Finland. Participants: The participants were nondiabetic at the recruitment, and 5401 subjects have participated in the follow-up study. During the follow-up, a total of 693 subjects converted to type 2 diabetes and 351 were diagnosed with a new CVD event during the follow-up. Main Outcome Measures: The main outcome measures were incidence of type 2 diabetes and CVD. Results: Height measured at baseline was significantly associated with lower levels of 2-hour glucose in an oral glucose tolerance test, an increase in insulin secretion, a decrease in the risk of type 2 diabetes [hazard ratio (HR) = 0.83(confidence interval [CI] 0.77 to 0.90)] and CVD [HR = 0.75(CI 0.67 to 0.83)] during the follow-up. Conclusion: Short stature is associated with unfavorable changes in glucose metabolism and predicts an increase in the risk of type 2 diabetes and cardiovascular events.
{"title":"Short Adult Stature Predicts Impaired &bgr;-Cell Function, Insulin Resistance, Glycemia, and Type 2 Diabetes in Finnish Men","authors":"J. Vangipurapu, A. Stančáková, R. Jauhiainen, J. Kuusisto, M. Laakso","doi":"10.1210/jc.2016-2933","DOIUrl":"https://doi.org/10.1210/jc.2016-2933","url":null,"abstract":"Context: Recent studies have highlighted the role of height in complex diseases, but conflicting information has been reported on height as a predictor of changes in glycemia and risk of type 2 diabetes. Objective: Our aim was to investigate the association of height with insulin sensitivity, insulin secretion, glycemia, type 2 diabetes, and cardiovascular disease (CVD) in a large prospective population-based study. Design: The study included 8746 Finnish men (mean ± standard deviation, age 57.2 ± 7.1 years, body mass index, 26.8 ± 3.8 kg/m2) selected from a population-based Metabolic Syndrome in Men (METSIM) study. Setting: The study was conducted at Kuopio University Hospital and University of Eastern Finland. Participants: The participants were nondiabetic at the recruitment, and 5401 subjects have participated in the follow-up study. During the follow-up, a total of 693 subjects converted to type 2 diabetes and 351 were diagnosed with a new CVD event during the follow-up. Main Outcome Measures: The main outcome measures were incidence of type 2 diabetes and CVD. Results: Height measured at baseline was significantly associated with lower levels of 2-hour glucose in an oral glucose tolerance test, an increase in insulin secretion, a decrease in the risk of type 2 diabetes [hazard ratio (HR) = 0.83(confidence interval [CI] 0.77 to 0.90)] and CVD [HR = 0.75(CI 0.67 to 0.83)] during the follow-up. Conclusion: Short stature is associated with unfavorable changes in glucose metabolism and predicts an increase in the risk of type 2 diabetes and cardiovascular events.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"287 1","pages":"443–450"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91476910","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}
A. Anisimova, P. Rubtsov, K. A. Akulich, S. Dmitriev, E. Frolova, A. Tiulpakov
Context: Loss-of-function mutations in the POMC gene are associated with a syndrome with the characteristics of adrenal insufficiency, obesity, and red hair. We describe here a case of pro-opiomelanocortin (POMC) deficiency in which adrenal insufficiency was not treated until the fourth year of life. One of the disease-causative POMC mutations was characterized in vitro using a unique approach. Case Description: A boy presented in the first year of life with red hair, growth acceleration, moderate obesity, and recurrent cholestasis, which was followed by 2 episodes of hypoglycemia at the ages of 1.5 and 3 years. The diagnosis was suspected at the age of 3.6 years after documentation of undetectable levels of plasma adrenocorticotropic hormone and serum cortisol, after which replacement with hydrocortisone was initiated. Sequencing of the POMC gene revealed compound heterozygosity for c.-11C>A/p.W84X mutations. The p.W84X mutation is predicted to result in a marked truncation of preprohormone. Using a messenger RNA transfection approach followed by an in vitro translation assay, we could directly demonstrate that the transcript with c.-11C>A substitution is predominantly translated within a new open reading frame; however, translation of the POMC main reading frame is preserved, with translation efficiency being ∼17% of the wild-type transcript. Conclusions: The current report provides important information on the natural course of POMC deficiency. In vitro translation studies demonstrated residual translation of the main coding region from an allele with the c.-11C>A mutation, which at least partially explains a relatively late presentation of adrenal insufficiency in the patient.
{"title":"Late Diagnosis of POMC Deficiency and In Vitro Evidence of Residual Translation From Allele With c.-11C>A Mutation","authors":"A. Anisimova, P. Rubtsov, K. A. Akulich, S. Dmitriev, E. Frolova, A. Tiulpakov","doi":"10.1210/jc.2016-3318","DOIUrl":"https://doi.org/10.1210/jc.2016-3318","url":null,"abstract":"Context: Loss-of-function mutations in the POMC gene are associated with a syndrome with the characteristics of adrenal insufficiency, obesity, and red hair. We describe here a case of pro-opiomelanocortin (POMC) deficiency in which adrenal insufficiency was not treated until the fourth year of life. One of the disease-causative POMC mutations was characterized in vitro using a unique approach. Case Description: A boy presented in the first year of life with red hair, growth acceleration, moderate obesity, and recurrent cholestasis, which was followed by 2 episodes of hypoglycemia at the ages of 1.5 and 3 years. The diagnosis was suspected at the age of 3.6 years after documentation of undetectable levels of plasma adrenocorticotropic hormone and serum cortisol, after which replacement with hydrocortisone was initiated. Sequencing of the POMC gene revealed compound heterozygosity for c.-11C>A/p.W84X mutations. The p.W84X mutation is predicted to result in a marked truncation of preprohormone. Using a messenger RNA transfection approach followed by an in vitro translation assay, we could directly demonstrate that the transcript with c.-11C>A substitution is predominantly translated within a new open reading frame; however, translation of the POMC main reading frame is preserved, with translation efficiency being ∼17% of the wild-type transcript. Conclusions: The current report provides important information on the natural course of POMC deficiency. In vitro translation studies demonstrated residual translation of the main coding region from an allele with the c.-11C>A mutation, which at least partially explains a relatively late presentation of adrenal insufficiency in the patient.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"2 1","pages":"359–362"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86939959","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}
Jieli Lu, Limin Wang, Mian Li, Yu Xu, Yong Jiang, Weiqing Wang, Jian-hong Li, S. Mi, Mei Zhang, Yichong Li, Tiange Wang, Min Xu, Zhiyun Zhao, M. Dai, S. Lai, Wenhua Zhao, Linhong Wang, Y. Bi, G. Ning
Context: In China, data on the prevalence of metabolic syndrome have been rare recently. Objective: The objective of the study was to evaluate the prevalence of metabolic syndrome and its components in 2010. Design, Setting, and Participants: The study covered all 31 provinces of mainland China and consisted of a nationally representative population sample of 98,658 Chinese adults aged ≥18 years. Of these, 97,098 participants were eligible for the data analysis reported here. Main Outcome Measures: Estimates of the prevalence of metabolic syndrome and its components were calculated. To further explore whether metabolic syndrome is associated with the 10-year coronary heart disease risk, sex-stratified logistic regression models were used. Results: The prevalence of the metabolic syndrome was 33.9% (31.0% in men and 36.8% in women), which indicates that metabolic syndrome affects approximately 454 million adults in China. More than half of total adult population was suffering from low high-density lipoprotein cholesterol (HDL-C), and nearly half of participants had high blood pressure. Abdominal obesity and low HDL-C were more prevalent in women than in men, whereas high blood pressure, high blood glucose, and high triglycerides were more common in men. Metabolic syndrome was associated with a higher 10-year coronary heart disease risk after adjustment for potential risk factors and each component of metabolic syndrome as continuous variables. Conclusion: Our results showed a high prevalence of metabolic syndrome and its components in the general adult population in mainland China. Metabolic syndrome was independently associated with a higher 10-year risk of developing coronary heart disease.
{"title":"Metabolic Syndrome Among Adults in China: The 2010 China Noncommunicable Disease Surveillance","authors":"Jieli Lu, Limin Wang, Mian Li, Yu Xu, Yong Jiang, Weiqing Wang, Jian-hong Li, S. Mi, Mei Zhang, Yichong Li, Tiange Wang, Min Xu, Zhiyun Zhao, M. Dai, S. Lai, Wenhua Zhao, Linhong Wang, Y. Bi, G. Ning","doi":"10.1210/jc.2016-2477","DOIUrl":"https://doi.org/10.1210/jc.2016-2477","url":null,"abstract":"Context: In China, data on the prevalence of metabolic syndrome have been rare recently. Objective: The objective of the study was to evaluate the prevalence of metabolic syndrome and its components in 2010. Design, Setting, and Participants: The study covered all 31 provinces of mainland China and consisted of a nationally representative population sample of 98,658 Chinese adults aged ≥18 years. Of these, 97,098 participants were eligible for the data analysis reported here. Main Outcome Measures: Estimates of the prevalence of metabolic syndrome and its components were calculated. To further explore whether metabolic syndrome is associated with the 10-year coronary heart disease risk, sex-stratified logistic regression models were used. Results: The prevalence of the metabolic syndrome was 33.9% (31.0% in men and 36.8% in women), which indicates that metabolic syndrome affects approximately 454 million adults in China. More than half of total adult population was suffering from low high-density lipoprotein cholesterol (HDL-C), and nearly half of participants had high blood pressure. Abdominal obesity and low HDL-C were more prevalent in women than in men, whereas high blood pressure, high blood glucose, and high triglycerides were more common in men. Metabolic syndrome was associated with a higher 10-year coronary heart disease risk after adjustment for potential risk factors and each component of metabolic syndrome as continuous variables. Conclusion: Our results showed a high prevalence of metabolic syndrome and its components in the general adult population in mainland China. Metabolic syndrome was independently associated with a higher 10-year risk of developing coronary heart disease.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"175 1","pages":"507–515"},"PeriodicalIF":0.0,"publicationDate":"2016-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78739169","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}
J. Yoo, Y. Ha, H. Ryu, Geunwu Chang, Young-Kyun Lee, Moon-jib Yoo, K. Koo
Context and Objective: Pain-related immobility because of insufficiency fractures may result in serious complications and a high mortality rate in senile patients with preexisting comorbidities. This study aimed to evaluate the efficacy of teriparatide in patients with sacral insufficiency fractures. Design, Setting, and Participants: This retrospective, case-controlled, single center study, performed from 2009 to 2014, included 41 patients who underwent radiographs, magnetic resonance imaging, and/or bone scans to document sacral insufficiency fractures. Intervention: The intervention involved teriparatide at a once-daily subcutaneous dose of 20 &mgr;g within 2 days of hospital admission (21 patients). Twenty patients (control group) did not receive teriparatide. Main Outcome Measures: Functional outcome was assessed using a visual analog scale for pain and the time to mobilization. Pelvic anteroposterior radiographs were repeated at 0, 1, 4, 8, 12, and 16 weeks until radiographic evidence of cortical bridging at the fracture site was confirmed. Results: From the date of admission to 4 weeks, the mean visual analog scale score improved between the 2 groups. The mean time to mobilization was 1.2 ± 0.4 weeks in patients who received teriparatide treatment, compared with 2.0 ± 0.3 weeks in controls (P < 0.001). At 8 weeks, all fractures in the teriparatide treatment group and 4 fractures in the control group had healed. Conclusions: In senile patients with preexisting comorbidities who have sacral insufficiency fractures, teriparatide treatment may achieve earlier pain reduction and mobilization and reduce healing time.
{"title":"Teriparatide Treatment in Elderly Patients With Sacral Insufficiency Fracture","authors":"J. Yoo, Y. Ha, H. Ryu, Geunwu Chang, Young-Kyun Lee, Moon-jib Yoo, K. Koo","doi":"10.1210/jc.2016-3582","DOIUrl":"https://doi.org/10.1210/jc.2016-3582","url":null,"abstract":"Context and Objective: Pain-related immobility because of insufficiency fractures may result in serious complications and a high mortality rate in senile patients with preexisting comorbidities. This study aimed to evaluate the efficacy of teriparatide in patients with sacral insufficiency fractures. Design, Setting, and Participants: This retrospective, case-controlled, single center study, performed from 2009 to 2014, included 41 patients who underwent radiographs, magnetic resonance imaging, and/or bone scans to document sacral insufficiency fractures. Intervention: The intervention involved teriparatide at a once-daily subcutaneous dose of 20 &mgr;g within 2 days of hospital admission (21 patients). Twenty patients (control group) did not receive teriparatide. Main Outcome Measures: Functional outcome was assessed using a visual analog scale for pain and the time to mobilization. Pelvic anteroposterior radiographs were repeated at 0, 1, 4, 8, 12, and 16 weeks until radiographic evidence of cortical bridging at the fracture site was confirmed. Results: From the date of admission to 4 weeks, the mean visual analog scale score improved between the 2 groups. The mean time to mobilization was 1.2 ± 0.4 weeks in patients who received teriparatide treatment, compared with 2.0 ± 0.3 weeks in controls (P < 0.001). At 8 weeks, all fractures in the teriparatide treatment group and 4 fractures in the control group had healed. Conclusions: In senile patients with preexisting comorbidities who have sacral insufficiency fractures, teriparatide treatment may achieve earlier pain reduction and mobilization and reduce healing time.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"1 1","pages":"560–565"},"PeriodicalIF":0.0,"publicationDate":"2016-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89499952","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}
L. Mañé, J. F. Flores-Le Roux, D. Benaiges, Marta Rodríguez, Irene Marcelo, J. Chillarón, J. Pedro-botet, Gemma Llauradó, Lucía Gortazar, R. Carreras, A. Payà
Context Risk of obstetric complications increases linearly with rising maternal glycemia. Testing hemoglobin A1c (HbA1c) is an effective option to detect hyperglycemia, but its association with adverse pregnancy outcomes remains unclear. Emerging data sustain that an early HbA1c ≥5.9% could act as a pregnancy risk marker. Objective To determine, in a multiethnic cohort, whether an early ≥5.9% HbA1c could be useful to identify women without diabetes mellitus at increased pregnancy risk. Design and Setting A prospective study was conducted at Hospital del Mar, Barcelona, between April 2013 and September 2015. Patients and Intervention A total of 1631 pregnant women had an HbA1c measurement added to their first antenatal blood tests and were screened for gestational diabetes mellitus at 24 to 28 weeks' gestation. Outcome Measures Primary outcome was macrosomia. Secondary outcomes were preeclampsia, preterm birth, and cesarean section rate. Results A total of 1228 pregnancies were included for outcome analysis. Women with HbA1c ≥5.9% (n = 48) showed a higher rate of macrosomia (16.7% vs 5.9%, P = 0.008) and a tendency toward a higher rate of preeclampsia (9.32% vs 3.9%, P = 0.092). There were no statistically significant differences in other pregnancy outcomes. After adjusting for potential confounders, an HbA1c ≥5.9% was independently associated with a 3-fold increased risk of macrosomia (95% confidence interval, 1.127 to 8.603, P = 0.028) and preeclampsia (95% confidence interval, 1.086 to 11.532, P = 0.036). Conclusions In a multiethnic population, an early HbA1c ≥5.9% measurement identifies women at high risk for poorer pregnancy outcomes independently of gestational diabetes mellitus diagnosis later in pregnancy. Further studies are required to establish cutoff points adapted to each ethnic group and to assess whether early detection and treatment are of benefit.
产科并发症的风险随着产妇血糖升高呈线性增加。检测糖化血红蛋白(HbA1c)是检测高血糖的有效选择，但其与不良妊娠结局的关系尚不清楚。新出现的数据支持早期HbA1c≥5.9%可作为妊娠风险标志。目的在一项多民族队列研究中，确定早期HbA1c≥5.9%是否有助于识别无糖尿病的妊娠风险增加的女性。设计与环境一项前瞻性研究于2013年4月至2015年9月在巴塞罗那del Mar医院进行。患者和干预总共有1631名孕妇在第一次产前血液检查中增加了HbA1c测量，并在妊娠24至28周筛查妊娠糖尿病。主要结局为巨大儿。次要结局为先兆子痫、早产和剖宫产率。结果共纳入1228例妊娠进行结局分析。HbA1c≥5.9%的女性(n = 48)显示出较高的巨大儿发生率(16.7% vs 5.9%， P = 0.008)和较高的先兆子痫发生率(9.32% vs 3.9%， P = 0.092)。在其他妊娠结局方面没有统计学上的显著差异。在调整潜在混杂因素后，HbA1c≥5.9%与巨大儿(95%置信区间，1.127 ~ 8.603,P = 0.028)和先兆子痫(95%置信区间，1.086 ~ 11.532,P = 0.036)风险增加3倍独立相关。结论:在多民族人群中，早期HbA1c≥5.9%的检测可识别出妊娠结局较差的高危女性，与妊娠后期诊断妊娠糖尿病无关。需要进一步的研究来确定适合每个种族群体的临界值，并评估早期发现和治疗是否有益。
{"title":"Role of First-Trimester HbA1c as a Predictor of Adverse Obstetric Outcomes in a Multiethnic Cohort","authors":"L. Mañé, J. F. Flores-Le Roux, D. Benaiges, Marta Rodríguez, Irene Marcelo, J. Chillarón, J. Pedro-botet, Gemma Llauradó, Lucía Gortazar, R. Carreras, A. Payà","doi":"10.1210/jc.2016-2581","DOIUrl":"https://doi.org/10.1210/jc.2016-2581","url":null,"abstract":"Context\u0000Risk of obstetric complications increases linearly with rising maternal glycemia. Testing hemoglobin A1c (HbA1c) is an effective option to detect hyperglycemia, but its association with adverse pregnancy outcomes remains unclear. Emerging data sustain that an early HbA1c ≥5.9% could act as a pregnancy risk marker.\u0000\u0000\u0000Objective\u0000To determine, in a multiethnic cohort, whether an early ≥5.9% HbA1c could be useful to identify women without diabetes mellitus at increased pregnancy risk.\u0000\u0000\u0000Design and Setting\u0000A prospective study was conducted at Hospital del Mar, Barcelona, between April 2013 and September 2015.\u0000\u0000\u0000Patients and Intervention\u0000A total of 1631 pregnant women had an HbA1c measurement added to their first antenatal blood tests and were screened for gestational diabetes mellitus at 24 to 28 weeks' gestation.\u0000\u0000\u0000Outcome Measures\u0000Primary outcome was macrosomia. Secondary outcomes were preeclampsia, preterm birth, and cesarean section rate.\u0000\u0000\u0000Results\u0000A total of 1228 pregnancies were included for outcome analysis. Women with HbA1c ≥5.9% (n = 48) showed a higher rate of macrosomia (16.7% vs 5.9%, P = 0.008) and a tendency toward a higher rate of preeclampsia (9.32% vs 3.9%, P = 0.092). There were no statistically significant differences in other pregnancy outcomes. After adjusting for potential confounders, an HbA1c ≥5.9% was independently associated with a 3-fold increased risk of macrosomia (95% confidence interval, 1.127 to 8.603, P = 0.028) and preeclampsia (95% confidence interval, 1.086 to 11.532, P = 0.036).\u0000\u0000\u0000Conclusions\u0000In a multiethnic population, an early HbA1c ≥5.9% measurement identifies women at high risk for poorer pregnancy outcomes independently of gestational diabetes mellitus diagnosis later in pregnancy. Further studies are required to establish cutoff points adapted to each ethnic group and to assess whether early detection and treatment are of benefit.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"14 1","pages":"390–397"},"PeriodicalIF":0.0,"publicationDate":"2016-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86168644","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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