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1.  Mass spectrometry-based proteomics in Chest Medicine, Gerontology, and Nephrology: subgroups omics for personalized medicine 
Biomedicine  2014;4:25.
Mass spectrometry (MS) is currently the most promising tool for studying proteomics to investigate largescale proteins in a specific proteome. Emerging MS-based proteomics is widely applied to decipher complex proteome for discovering potential biomarkers. Given its growing usage in clinical medicine for biomarker discovery to predict, diagnose and confer prognosis, MS-based proteomics can benefit study of personalized medicine. In this review we introduce some fundamental MS theory and MS-based quantitative proteomic approaches as well as several representative clinical MS-based proteomics issues in Chest Medicine, Gerontology, and Nephrology.
doi:10.7603/s40681-014-0025-y
PMCID: PMC4264973  PMID: 25520938
Mass spectrometry;; Personalized medicine;; Proteomics;; Chest Medicine;; Nephrology;; Gerontology
2.  Correlation between reduction of superior interventricular groove epicardial fat thickness and improvement of insulin resistance after weight loss in obese men 
Background
It has been recognized that reduction of abdominal visceral fat and subcutaneous fat are associated with improvement in insulin-resistance (IR) after weight loss. However, few studies have investigated the correlation of reduction in epicardial adipose tissue (EAT) with improvement of IR index after weight loss in obese non-diabetic men with metabolic syndrome (MetS).
Methods and results
We prospectively enrolled 32 non-diabetic men with MetS for a 3-month weight reduction program mainly by diet control and exercise. Magnetic resonance imaging (MRI) examinations were used to measure EAT, subcutaneous fat, and abdominal visceral fat. Anthropometric parameters, oral glucose tolerance test (OGTT), and serum adipokines were assessed before and after the weight loss program. After a 3-month weight loss program, 27 obese MetS men had significant weight loss >5% (97 ± 14 to 87 ± 14 kg, with a 10.7 % decrease, p < 0.001). Multivariate analysis revealed that the decrement ratio of superior interventricular groove (SIVG) EAT thickness (r = 0.322, p = 0.044) and serum leptin (r = 0.626, p < 0.001) significantly correlated with the percentage improvements of fasting HOMA-IR index. Furthermore, the decrement ratio of SIVG EAT thickness (r = −0.370, p = 0.017) and decrement ratio of subcutaneous fat area (r = −0.673, p = 0.006) were significantly correlated with improvement of OGTT-derived Matsuda insulin-sensitivity index.
Conclusions
The decrement ratio of SIVG EAT correlated with improvement of both HOMA-IR and OGTT-derived Matsuda insulin-sensitivity indexes after weight loss in obese non-diabetic men with MetS.
Clinical trial registration
(Multi-faceted Evaluations Following Weight Reduction in Subjects with Metabolic Syndrome NCT 01065753 on Feb 8, 2010).
doi:10.1186/1758-5996-6-115
PMCID: PMC4223841  PMID: 25383099
Epicardial adipose tissue; Insulin resistance; Leptin; Matsuda index; Metabolic syndrome; Obesity
3.  Reduced Health-Related Quality of Life in Body Constitutions of Yin-Xu, and Yang-Xu, Stasis in Patients with Type 2 Diabetes: Taichung Diabetic Body Constitution Study 
Aim. To evaluate how health-related quality of life (HRQOL) and traditional Chinese medicine (TCM) constitutions of Yin-Xu, Yang-Xu, and Stasis are related in type 2 diabetes patients. Method. Seven hundred and five subjects were recruited in 2010 for this study from a Diabetes Shared Care Network in Taiwan. Generic and disease-specific HRQOL were assessed by the short form 36 (SF-36) and the diabetes impact measurement scale (DIMS). Constitutions of Yin-Xu, Yang-Xu, and Stasis were then assessed by the body constitution questionnaire (BCQ), a questionnaire consisting of 44 items that evaluate the physiological state based on subjective symptoms and signs. Results. Estimated effects of the Ying-Xu and Stasis on all scales of the SF-36 were significantly negative, while estimated effects of the Yang-Xu on all scales (except for SF, RE, MH, and MCS) were significantly negative. For DIMS, the estimated effects of the Ying-Xu and Stasis on all scales were significantly negative except for Stasis on well-being, while Yang-Xu has a significantly negative effect only on symptoms. Conclusions. This study demonstrates that TCM constitutions of Yin-Xu, Yang-Xu, and Stasis are closely related to a reduction in HRQOL. These findings support the need for further research into the impact of intervention for TCM constitutions on HRQOL in patients with type 2 diabetes.
doi:10.1155/2014/309403
PMCID: PMC4100449  PMID: 25093025
4.  Post-meal β-cell function predicts the efficacy of glycemic control in patients with type 2 diabetes inadequately controlled by metformin monotherapy after addition of glibenclamide or acarbose 
Background
This study aimed to explore parameters which will predict good control of HbA1c after adding a second anti-diabetic drug in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy.
Methods
Fifty-one patients (M/F: 25/26, mean age: 53.7 ± 8.2 years, mean glycated hemoglobin [HbA1c] 8.4 ± 1.2%) with T2DM inadequately controlled with metformin were randomized to add-on glibenclamide or acarbose for 16 weeks. Before and after combination therapy, the subjects underwent a 2-hour liquid mixed meal tolerance test to determine insulin secretion (HOMA-β, insulinogenic index, and disposition index [DI]) and insulin sensitivity (HOMA-IR and Matsuda insulin sensitivity index).
Results
At baseline, there was a significant inverse relationship between DI120 and HbA1c (p = 0.001) in all subjects. The addition of glibenclamide and acarbose improved HbA1c significantly from 8.6 ± 1.6% to 7.4 ± 1.2% (p < 0.001), and from 8.2 ± 0.8% to 7.5 ± 0.8% (p < 0.001), respectively. In the glibenclamide group, DI120 significantly increased from 51.2 ± 24.2 to 74.9 ± 41.9 (p < 0.05), and in the acarbose group, from 62.5 ± 31.4 to 91.7 ± 36.2 (p < 0.05), respectively. Multiple regression analyses showed that both baseline HbA1c and DI120 independently predicted reduction of HbA1c as well as final HbA1c after combination therapy.
Conclusions
In patients with T2DM inadequately controlled with metformin, add-on oral anti-diabetic agent with glibenclamide or acarbose resulted in the significant HbA1c reduction and improvement of β-cell function. Subjects with greater baseline β-cell function reserve displayed better glycemic response in the combination therapy of metformin with glibenclamide or acarbose.
Trial registration
This study was registered in the ClinicalTrials.gov with registration number of NCT00417729.
doi:10.1186/1758-5996-6-68
PMCID: PMC4057801  PMID: 24932223
Beta-cell function; Disposition index; Glycated hemoglobin; Glycemic control; Metformin
5.  Performance of HbA1c and Fasting Plasma Glucose in Screening for Diabetes in Patients Undergoing Coronary Angiography 
Diabetes Care  2013;36(5):1138-1140.
OBJECTIVE
The performance of glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) was compared in screening for diabetes by an oral glucose tolerance test (OGTT) in patients undergoing coronary angiography (CAG).
RESEARCH DESIGN AND METHODS
Patients without known diabetes admitted for CAG were eligible. OGTT and HbA1c were assessed 2–4 weeks after hospital discharge. The performance of HbA1c and FPG was evaluated by using receiver operating characteristic (ROC) analysis.
RESULTS
Diabetes was diagnosed in 83 of 400 patients (20.8%). The area under the ROC curve was higher for FPG than for HbA1c (0.81 vs. 0.73, P = 0.032). We proposed a screening algorithm and validated it in another 170 patients. Overall, this algorithm reduced the number of OGTTs by 71.4% (sensitivity 74.4%, specificity 100%).
CONCLUSIONS
FPG performed better than HbA1c in screening for diabetes in patients undergoing CAG. A screening algorithm might help to reduce the number of OGTTs.
doi:10.2337/dc12-1434
PMCID: PMC3631876  PMID: 23238660
6.  Discovery and Refinement of Loci Associated with Lipid Levels 
Willer, Cristen J. | Schmidt, Ellen M. | Sengupta, Sebanti | Peloso, Gina M. | Gustafsson, Stefan | Kanoni, Stavroula | Ganna, Andrea | Chen, Jin | Buchkovich, Martin L. | Mora, Samia | Beckmann, Jacques S. | Bragg-Gresham, Jennifer L. | Chang, Hsing-Yi | Demirkan, Ayşe | Den Hertog, Heleen M. | Do, Ron | Donnelly, Louise A. | Ehret, Georg B. | Esko, Tõnu | Feitosa, Mary F. | Ferreira, Teresa | Fischer, Krista | Fontanillas, Pierre | Fraser, Ross M. | Freitag, Daniel F. | Gurdasani, Deepti | Heikkilä, Kauko | Hyppönen, Elina | Isaacs, Aaron | Jackson, Anne U. | Johansson, Åsa | Johnson, Toby | Kaakinen, Marika | Kettunen, Johannes | Kleber, Marcus E. | Li, Xiaohui | Luan, Jian’an | Lyytikäinen, Leo-Pekka | Magnusson, Patrik K.E. | Mangino, Massimo | Mihailov, Evelin | Montasser, May E. | Müller-Nurasyid, Martina | Nolte, Ilja M. | O’Connell, Jeffrey R. | Palmer, Cameron D. | Perola, Markus | Petersen, Ann-Kristin | Sanna, Serena | Saxena, Richa | Service, Susan K. | Shah, Sonia | Shungin, Dmitry | Sidore, Carlo | Song, Ci | Strawbridge, Rona J. | Surakka, Ida | Tanaka, Toshiko | Teslovich, Tanya M. | Thorleifsson, Gudmar | Van den Herik, Evita G. | Voight, Benjamin F. | Volcik, Kelly A. | Waite, Lindsay L. | Wong, Andrew | Wu, Ying | Zhang, Weihua | Absher, Devin | Asiki, Gershim | Barroso, Inês | Been, Latonya F. | Bolton, Jennifer L. | Bonnycastle, Lori L | Brambilla, Paolo | Burnett, Mary S. | Cesana, Giancarlo | Dimitriou, Maria | Doney, Alex S.F. | Döring, Angela | Elliott, Paul | Epstein, Stephen E. | Ingi Eyjolfsson, Gudmundur | Gigante, Bruna | Goodarzi, Mark O. | Grallert, Harald | Gravito, Martha L. | Groves, Christopher J. | Hallmans, Göran | Hartikainen, Anna-Liisa | Hayward, Caroline | Hernandez, Dena | Hicks, Andrew A. | Holm, Hilma | Hung, Yi-Jen | Illig, Thomas | Jones, Michelle R. | Kaleebu, Pontiano | Kastelein, John J.P. | Khaw, Kay-Tee | Kim, Eric | Klopp, Norman | Komulainen, Pirjo | Kumari, Meena | Langenberg, Claudia | Lehtimäki, Terho | Lin, Shih-Yi | Lindström, Jaana | Loos, Ruth J.F. | Mach, François | McArdle, Wendy L | Meisinger, Christa | Mitchell, Braxton D. | Müller, Gabrielle | Nagaraja, Ramaiah | Narisu, Narisu | Nieminen, Tuomo V.M. | Nsubuga, Rebecca N. | Olafsson, Isleifur | Ong, Ken K. | Palotie, Aarno | Papamarkou, Theodore | Pomilla, Cristina | Pouta, Anneli | Rader, Daniel J. | Reilly, Muredach P. | Ridker, Paul M. | Rivadeneira, Fernando | Rudan, Igor | Ruokonen, Aimo | Samani, Nilesh | Scharnagl, Hubert | Seeley, Janet | Silander, Kaisa | Stančáková, Alena | Stirrups, Kathleen | Swift, Amy J. | Tiret, Laurence | Uitterlinden, Andre G. | van Pelt, L. Joost | Vedantam, Sailaja | Wainwright, Nicholas | Wijmenga, Cisca | Wild, Sarah H. | Willemsen, Gonneke | Wilsgaard, Tom | Wilson, James F. | Young, Elizabeth H. | Zhao, Jing Hua | Adair, Linda S. | Arveiler, Dominique | Assimes, Themistocles L. | Bandinelli, Stefania | Bennett, Franklyn | Bochud, Murielle | Boehm, Bernhard O. | Boomsma, Dorret I. | Borecki, Ingrid B. | Bornstein, Stefan R. | Bovet, Pascal | Burnier, Michel | Campbell, Harry | Chakravarti, Aravinda | Chambers, John C. | Chen, Yii-Der Ida | Collins, Francis S. | Cooper, Richard S. | Danesh, John | Dedoussis, George | de Faire, Ulf | Feranil, Alan B. | Ferrières, Jean | Ferrucci, Luigi | Freimer, Nelson B. | Gieger, Christian | Groop, Leif C. | Gudnason, Vilmundur | Gyllensten, Ulf | Hamsten, Anders | Harris, Tamara B. | Hingorani, Aroon | Hirschhorn, Joel N. | Hofman, Albert | Hovingh, G. Kees | Hsiung, Chao Agnes | Humphries, Steve E. | Hunt, Steven C. | Hveem, Kristian | Iribarren, Carlos | Järvelin, Marjo-Riitta | Jula, Antti | Kähönen, Mika | Kaprio, Jaakko | Kesäniemi, Antero | Kivimaki, Mika | Kooner, Jaspal S. | Koudstaal, Peter J. | Krauss, Ronald M. | Kuh, Diana | Kuusisto, Johanna | Kyvik, Kirsten O. | Laakso, Markku | Lakka, Timo A. | Lind, Lars | Lindgren, Cecilia M. | Martin, Nicholas G. | März, Winfried | McCarthy, Mark I. | McKenzie, Colin A. | Meneton, Pierre | Metspalu, Andres | Moilanen, Leena | Morris, Andrew D. | Munroe, Patricia B. | Njølstad, Inger | Pedersen, Nancy L. | Power, Chris | Pramstaller, Peter P. | Price, Jackie F. | Psaty, Bruce M. | Quertermous, Thomas | Rauramaa, Rainer | Saleheen, Danish | Salomaa, Veikko | Sanghera, Dharambir K. | Saramies, Jouko | Schwarz, Peter E.H. | Sheu, Wayne H-H | Shuldiner, Alan R. | Siegbahn, Agneta | Spector, Tim D. | Stefansson, Kari | Strachan, David P. | Tayo, Bamidele O. | Tremoli, Elena | Tuomilehto, Jaakko | Uusitupa, Matti | van Duijn, Cornelia M. | Vollenweider, Peter | Wallentin, Lars | Wareham, Nicholas J. | Whitfield, John B. | Wolffenbuttel, Bruce H.R. | Ordovas, Jose M. | Boerwinkle, Eric | Palmer, Colin N.A. | Thorsteinsdottir, Unnur | Chasman, Daniel I. | Rotter, Jerome I. | Franks, Paul W. | Ripatti, Samuli | Cupples, L. Adrienne | Sandhu, Manjinder S. | Rich, Stephen S. | Boehnke, Michael | Deloukas, Panos | Kathiresan, Sekar | Mohlke, Karen L. | Ingelsson, Erik | Abecasis, Gonçalo R.
Nature genetics  2013;45(11):10.1038/ng.2797.
Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and total cholesterol are heritable, modifiable, risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,578 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5×10−8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian, and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipids are often associated with cardiovascular and metabolic traits including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio, and body mass index. Our results illustrate the value of genetic data from individuals of diverse ancestries and provide insights into biological mechanisms regulating blood lipids to guide future genetic, biological, and therapeutic research.
doi:10.1038/ng.2797
PMCID: PMC3838666  PMID: 24097068
7.  Common variants associated with plasma triglycerides and risk for coronary artery disease 
Do, Ron | Willer, Cristen J. | Schmidt, Ellen M. | Sengupta, Sebanti | Gao, Chi | Peloso, Gina M. | Gustafsson, Stefan | Kanoni, Stavroula | Ganna, Andrea | Chen, Jin | Buchkovich, Martin L. | Mora, Samia | Beckmann, Jacques S. | Bragg-Gresham, Jennifer L. | Chang, Hsing-Yi | Demirkan, Ayşe | Den Hertog, Heleen M. | Donnelly, Louise A. | Ehret, Georg B. | Esko, Tõnu | Feitosa, Mary F. | Ferreira, Teresa | Fischer, Krista | Fontanillas, Pierre | Fraser, Ross M. | Freitag, Daniel F. | Gurdasani, Deepti | Heikkilä, Kauko | Hyppönen, Elina | Isaacs, Aaron | Jackson, Anne U. | Johansson, Åsa | Johnson, Toby | Kaakinen, Marika | Kettunen, Johannes | Kleber, Marcus E. | Li, Xiaohui | Luan, Jian'an | Lyytikäinen, Leo-Pekka | Magnusson, Patrik K.E. | Mangino, Massimo | Mihailov, Evelin | Montasser, May E. | Müller-Nurasyid, Martina | Nolte, Ilja M. | O'Connell, Jeffrey R. | Palmer, Cameron D. | Perola, Markus | Petersen, Ann-Kristin | Sanna, Serena | Saxena, Richa | Service, Susan K. | Shah, Sonia | Shungin, Dmitry | Sidore, Carlo | Song, Ci | Strawbridge, Rona J. | Surakka, Ida | Tanaka, Toshiko | Teslovich, Tanya M. | Thorleifsson, Gudmar | Van den Herik, Evita G. | Voight, Benjamin F. | Volcik, Kelly A. | Waite, Lindsay L. | Wong, Andrew | Wu, Ying | Zhang, Weihua | Absher, Devin | Asiki, Gershim | Barroso, Inês | Been, Latonya F. | Bolton, Jennifer L. | Bonnycastle, Lori L | Brambilla, Paolo | Burnett, Mary S. | Cesana, Giancarlo | Dimitriou, Maria | Doney, Alex S.F. | Döring, Angela | Elliott, Paul | Epstein, Stephen E. | Eyjolfsson, Gudmundur Ingi | Gigante, Bruna | Goodarzi, Mark O. | Grallert, Harald | Gravito, Martha L. | Groves, Christopher J. | Hallmans, Göran | Hartikainen, Anna-Liisa | Hayward, Caroline | Hernandez, Dena | Hicks, Andrew A. | Holm, Hilma | Hung, Yi-Jen | Illig, Thomas | Jones, Michelle R. | Kaleebu, Pontiano | Kastelein, John J.P. | Khaw, Kay-Tee | Kim, Eric | Klopp, Norman | Komulainen, Pirjo | Kumari, Meena | Langenberg, Claudia | Lehtimäki, Terho | Lin, Shih-Yi | Lindström, Jaana | Loos, Ruth J.F. | Mach, François | McArdle, Wendy L | Meisinger, Christa | Mitchell, Braxton D. | Müller, Gabrielle | Nagaraja, Ramaiah | Narisu, Narisu | Nieminen, Tuomo V.M. | Nsubuga, Rebecca N. | Olafsson, Isleifur | Ong, Ken K. | Palotie, Aarno | Papamarkou, Theodore | Pomilla, Cristina | Pouta, Anneli | Rader, Daniel J. | Reilly, Muredach P. | Ridker, Paul M. | Rivadeneira, Fernando | Rudan, Igor | Ruokonen, Aimo | Samani, Nilesh | Scharnagl, Hubert | Seeley, Janet | Silander, Kaisa | Stančáková, Alena | Stirrups, Kathleen | Swift, Amy J. | Tiret, Laurence | Uitterlinden, Andre G. | van Pelt, L. Joost | Vedantam, Sailaja | Wainwright, Nicholas | Wijmenga, Cisca | Wild, Sarah H. | Willemsen, Gonneke | Wilsgaard, Tom | Wilson, James F. | Young, Elizabeth H. | Zhao, Jing Hua | Adair, Linda S. | Arveiler, Dominique | Assimes, Themistocles L. | Bandinelli, Stefania | Bennett, Franklyn | Bochud, Murielle | Boehm, Bernhard O. | Boomsma, Dorret I. | Borecki, Ingrid B. | Bornstein, Stefan R. | Bovet, Pascal | Burnier, Michel | Campbell, Harry | Chakravarti, Aravinda | Chambers, John C. | Chen, Yii-Der Ida | Collins, Francis S. | Cooper, Richard S. | Danesh, John | Dedoussis, George | de Faire, Ulf | Feranil, Alan B. | Ferrières, Jean | Ferrucci, Luigi | Freimer, Nelson B. | Gieger, Christian | Groop, Leif C. | Gudnason, Vilmundur | Gyllensten, Ulf | Hamsten, Anders | Harris, Tamara B. | Hingorani, Aroon | Hirschhorn, Joel N. | Hofman, Albert | Hovingh, G. Kees | Hsiung, Chao Agnes | Humphries, Steve E. | Hunt, Steven C. | Hveem, Kristian | Iribarren, Carlos | Järvelin, Marjo-Riitta | Jula, Antti | Kähönen, Mika | Kaprio, Jaakko | Kesäniemi, Antero | Kivimaki, Mika | Kooner, Jaspal S. | Koudstaal, Peter J. | Krauss, Ronald M. | Kuh, Diana | Kuusisto, Johanna | Kyvik, Kirsten O. | Laakso, Markku | Lakka, Timo A. | Lind, Lars | Lindgren, Cecilia M. | Martin, Nicholas G. | März, Winfried | McCarthy, Mark I. | McKenzie, Colin A. | Meneton, Pierre | Metspalu, Andres | Moilanen, Leena | Morris, Andrew D. | Munroe, Patricia B. | Njølstad, Inger | Pedersen, Nancy L. | Power, Chris | Pramstaller, Peter P. | Price, Jackie F. | Psaty, Bruce M. | Quertermous, Thomas | Rauramaa, Rainer | Saleheen, Danish | Salomaa, Veikko | Sanghera, Dharambir K. | Saramies, Jouko | Schwarz, Peter E.H. | Sheu, Wayne H-H | Shuldiner, Alan R. | Siegbahn, Agneta | Spector, Tim D. | Stefansson, Kari | Strachan, David P. | Tayo, Bamidele O. | Tremoli, Elena | Tuomilehto, Jaakko | Uusitupa, Matti | van Duijn, Cornelia M. | Vollenweider, Peter | Wallentin, Lars | Wareham, Nicholas J. | Whitfield, John B. | Wolffenbuttel, Bruce H.R. | Altshuler, David | Ordovas, Jose M. | Boerwinkle, Eric | Palmer, Colin N.A. | Thorsteinsdottir, Unnur | Chasman, Daniel I. | Rotter, Jerome I. | Franks, Paul W. | Ripatti, Samuli | Cupples, L. Adrienne | Sandhu, Manjinder S. | Rich, Stephen S. | Boehnke, Michael | Deloukas, Panos | Mohlke, Karen L. | Ingelsson, Erik | Abecasis, Goncalo R. | Daly, Mark J. | Neale, Benjamin M. | Kathiresan, Sekar
Nature genetics  2013;45(11):1345-1352.
Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P<5×10−8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
doi:10.1038/ng.2795
PMCID: PMC3904346  PMID: 24097064
8.  Brain-derived neurotrophic factor, but not body weight, correlated with a reduction in depression scale scores in men with metabolic syndrome: a prospective weight-reduction study 
Background
Obesity, a critical component of metabolic syndrome (MetS), is associated with depression. Deficiency of brain-derived neurotrophic factor (BDNF) is involved in the mechanism of depression. We hypothesized that weight reduction would improve depressive symptoms via increasing BDNF levels in obese men.
Methods
Male adults with obesity were enrolled in a weight-reduction program for twelve weeks. All subjects underwent daily caloric restriction and an exercise program which was regularly assessed in group classes. Fasting blood samples and Zung Self-Rating Depression Scale (Zung SDS) scores were collected for assessments before and after the study.
Results
A total of 36 subjects completed this program. The average reduction in body weight was 8.4 ± 5.1 kg (8.8 ± 5.1%, P < 0.001). Fasting serum BDNF significantly increased after the study (from 40.4 ± 7.8 to 46.9 ± 8.9 ng/ml, P < 0.001). However, the depression symptoms, as assessed by the Zung Self-Rating Depression Scale (Zung SDS), did not reduce significantly (P = 0.486). Divided into subgroups based on changes in BDNF, Zung SDS scores were significantly reduced in subjects with greater BDNF increase than in those with minor BDNF change (-3.9 ± 6.2 vs. 2.3 ± 6.7, P = 0.009). The increased percentage of BDNF was inversely correlated with the change in Zung SDS (r = -0.380, P = 0.022). Multivariate regression analysis showed that reduction in BDNF was independently associated with change in Zung SDS (95% confidence interval -0.315 to -0.052, P = 0.008).
Conclusion
Zung SDS only significantly improved in men with increased fasting BDNF levels after a lifestyle intervention.
Trial registration
(NCT01065753, ClinicalTrials.gov)
doi:10.1186/1758-5996-6-18
PMCID: PMC3925444  PMID: 24524285
Exercise; Lifestyle intervention; Obesity; Zung self-rating depression scale
9.  Chinese Medicinal Formula (MHGWT) for Relieving Diabetic Neuropathic Pain: A Randomized, Double-Blind, Placebo-Controlled Trial 
Objective. To investigate the effects of modified Hungqi Guizhi Wuwu Tang (MHGWT), a formula that comprises Chinese medicinal herbs, in relieving neuropathic pain in diabetics. Method. Between March 2008 and April 2009, 112 participants were randomly assigned to either the MHGWT group, whose members received MHGWT (n = 56), or the control group, whose members received a placebo (n = 56). Diabetic neuropathic pain (DNP) was rated using the 15-item Short-Form Brief Pain Inventory (SF-BPI), the 17-item Short-Form McGill Pain Questionnaire (SF-MPQ), the 13-item Modified Michigan Neuropathy Screening Instrument (MMNSI), and the 36-item “SF-36.” Nerve conduction studies (NCSs) were performed before and after treatment. Results. After 12 weeks of treatment, the SF-MPQ and SF-BPI scores of the MHGWT group were significantly (P < 0.05) reduced and a significant difference between the groups was observed (P < 0.05). The levels of NCS in the MHGWT group were nonsignificantly (P > 0.05) reduced, and no significant difference in NCS level was observed between the groups (P > 0.05). Conclusions. MHGWT shows promise in relieving DNP and deserves further investigation.
doi:10.1155/2013/767498
PMCID: PMC3766986  PMID: 24062790
10.  The effect of removing plugs and adding arch support to foam based insoles on plantar pressures in people with diabetic peripheral neuropathy 
Background
Removable plug insoles appear to be beneficial for patients with diabetic neuropathic feet to offload local plantar pressure. However, quantitative evidence of pressure reduction by means of plug removal is limited. The value of additional insole accessories, such as arch additions, has not been tested. The purpose of this study was to evaluate the effect of removing plugs from foam based insoles, and subsequently adding extra arch support, on plantar pressures.
Methods
In-shoe plantar pressure measurements were performed on 26 patients with diabetic neuropathic feet at a baseline condition, in order to identify the forefoot region with the highest mean peak pressure (MPP). This was defined as the region of interest (ROI) for plug removal.The primary outcome was measurement of MPP using the pedar® system in the baseline and another three insole conditions (pre-plug removal, post-plug removal, and post-plug removal plus arch support).
Results
Among the 26 ROIs, a significant reduction in MPP (32.3%, P<0.001) was found after removing the insole plugs. With an arch support added, the pressure was further reduced (9.5%, P<0.001). There were no significant differences in MPP at non-ROIs between pre- and post-plug removal conditions.
Conclusions
These findings suggest that forefoot plantar pressure can be reduced by removing plugs and adding arch support to foam-based insoles. This style of insole may therefore be clinically useful in managing patients with diabetic peripheral neuropathy.
doi:10.1186/1757-1146-6-29
PMCID: PMC3750449  PMID: 23895323
Diabetic foot; Plantar pressure; Offloading; Insole
11.  Early utilization of hypertonic peritoneal dialysate and subsequent risks of non-traumatic amputation among peritoneal dialysis patients: a nationwide retrospective longitudinal study 
BMC Nephrology  2013;14:128.
Background
The hemodialysis (HD) population has a particularly high incidence of amputation, which is likely associated with decreased tissue oxygenation during HD. However, information about the risk factors leading to amputation in peritoneal dialysis (PD) patients is limited. Here, we have investigated the association between the use of hypertonic peritoneal dialysate (HPD) and subsequent amputation in PD patients.
Methods
Based on the data from the Taiwan National Health Insurance research database, this observational cohort study enrolled 203 PD patients who had received HPD early during treatment and had not undergone amputation and 296 PD controls who had not undergone amputation. Subjects were followed through until the end of 2009 and the event rates of new non-traumatic amputation were compared between groups.
Results
The incidence of amputation was 3 times higher for the HPD cohort than for the comparison cohort (23.68 vs. 8.01 per 1000 person-years). The hazard ratio (HR) for this group, estimated using a multivariable Cox model, was 2.48 (95% confidence interval [CI] = 1.06–5.79). The HR for patients with both diabetes and early adoption of HPD increased to 44.34 (95% CI = 5.51-357.03), compared to non-HPD non-diabetic PD controls.
Conclusion
Early utilization of HPD in PD patients is associated with increasing risk of amputation; this risk considerably increases for those with concomitant diabetes.
doi:10.1186/1471-2369-14-128
PMCID: PMC3691767  PMID: 23786634
Non-traumatic amputation; Hypertonic dialysate; Peritoneal dialysis
12.  Association between hypertensive disorders during pregnancy and end-stage renal disease: a population-based study 
Background:
Studies into the association between hypertensive disorders during pregnancy and end-stage renal disease are limited. We investigated the risk of end-stage renal disease after delivery among women with hypertensive disorders during pregnancy.
Methods:
We used insurance claims data from 1998 to 2009 to identify 26 651 women aged 19–40 years old who experienced hypertensive disorders during pregnancy; these women had no history of hypertension, diabetes, kidney disease or lupus. We also randomly selected 213 397 women without hypertensive disorders during pregnancy as a comparison cohort; the frequency was matched by age and index year of pregnancy. We compared the incidence of end-stage renal disease in the 2 cohorts. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) after controlling for demographic and clinical factors.
Results:
Women with hypertensive disorders during pregnancy had a greater risk of chronic kidney disease and end-stage renal disease, with adjusted HRs of 9.38 (95% CI 7.09–12.4) and 12.4 (95% CI 8.54–18.0), respectively, after controlling for urban status, coronary artery disease, congestive heart failure, hyperlipidemia and abruption. The HR for end-stage renal disease was 2.72 (95% CI 1.76–4.22) after we also controlled for hypertension and diabetes. Women with preeclampsia or eclampsia had a higher risk of end-stage renal disease (adjusted HR 14.0, 95% CI 9.43–20.7) than women who had gestational hypertension only (adjusted HR 9.03, 95% CI 5.20–15.7).
Interpretation:
Women with hypertensive disorders during pregnancy were at a high risk of end-stage renal disease. The risk was much greater for women who had preeclampsia or eclampsia than those who had gestational hypertension only.
doi:10.1503/cmaj.120230
PMCID: PMC3576438  PMID: 23339156
13.  Comparing Survival between Peritoneal Dialysis and Hemodialysis Patients with Subclinical Peripheral Artery Disease: a 6-Year Follow-Up 
Peripheral artery disease (PAD) is known to be an increased mortality risk in patients with end-stage renal disease (ESRD). The aim of this study was to compare patient survival between patients with subclinical PAD undergoing peritoneal dialysis (PD) and hemodialysis (HD). Subclinical peripheral artery was defined as an ankle-brachial index of less than 0.9. This study was conducted from April 2005, and the observation period ended on 30 June 2011. At the end of the follow-up, the status of all patients was assessed and data on mortality were obtained for the entire cohort. A total of 91 patients (61 HD and 30 PD) were included for analyses in this study. Mortality rate was 60.0% (18/30) for PD and 52.5% (32/61) for HD. Kaplan-Meier estimate demonstrate that PD patients had a higher mortality rate than those underwent HD (log-rank p = 0.0039). Cox regression model demonstrated that PD was an independent predictor for further mortality in ESRD patients with subclinical peripheral artery disease.(p = 0.012, HR: 1.776, 95% CI: 1.136-2.775). In multivariate analysis, the HD group still had a greater survival than PD group (p = 0.005, HR:1.916, 95% CI: 1.218-3.015). In patients with subclinical peripheral artery disease, the patient survival is better in HD patients as compared with PD patients.
doi:10.7150/ijms.5091
PMCID: PMC3590604  PMID: 23471522
Survival; hemodialysis; peritoneal dialysis; peripheral artery disease.
14.  Association of response to hepatitis B vaccination and survival in dialysis patients 
BMC Nephrology  2012;13:97.
Background
The status of immunocompromised patients is well recognized in end stage renal disease (ESRD). As described recently, this acquired immune dysfunction in the uremic milieu may be one of the main pathogenic factors for mortality in ESRD. The aim of this study was to determine the relationship between the immune response following a hepatitis B vaccination (HBV vaccination) and the survival of maintenance dialysis patients.
Methods
A total of 156 patients (103 on hemodialysis and 53 on continuous ambulatory peritoneal dialysis) were recruited. After receiving a full dose of the HBV vaccination, all patients were followed up for to 5 years to evaluate the association of patient survival, cause of mortality, and immune response.
Results
The response rate to the hepatitis B vaccination was 70.5%. There was no significant association between the immune response and the 5-year survival rate (p =0.600) or between the post-vaccination anti-HBs titers and the 5-year survival rate (p = 0.201). The logistic prediction model with the coefficient as non-response following HBV vaccination, diabetes mellitus, old age, and low albumin level could significantly predict infection-cause mortality (sensitivity = 0.842, specificity = 0.937).
Conclusion
There was no significant association between the immune response to HBV vaccination and the 5-year survival rate. However, non-response following HBV vaccination might be associated with infection-cause mortality in dialysis patients.
doi:10.1186/1471-2369-13-97
PMCID: PMC3471045  PMID: 22935561
Hepatitis B vaccination; Immune response; Post-vaccination anti-HBs titers
15.  The risk for chronic kidney disease in patients with heart diseases: a 7-year follow-up in a cohort study in Taiwan 
BMC Nephrology  2012;13:77.
Background
The worldwide increasing trend of chronic kidney disease (CKD) is of great concern and the role of heart disease deserves longitudinal studies. This study investigated the risk of developing CKD among patients with heart diseases.
Methods
From universal insurance claims data in Taiwan, we retrospectively identified a cohort of 26005 patients with newly diagnosed heart diseases and 52010 people without such disease from the 2000–2001 claims. We observed prospectively both cohorts until the end of 2007 to measure CKD incidence rates in both cohorts and hazard ratios (HR) of CKD.
Results
The incidence of CKD in the cohort with heart disease was 4.1 times greater than that in the comparison cohort (39.5 vs. 9.65 per 10,000 person-years). However, the HR changed into 2.37 (95% confidence interval (CI) = 2.05 – 2.74) in the multivariate Cox proportional hazard model after controlling for sociodemographic characteristics and comorbidity. Compared with individuals aged < 40 years, the HRs for CKD ranged from 2.70 to 4.99 in older age groups. Significant estimated relative risks of CKD observed in our patients were also independently associated with hypertension (HR = 2.26, 95% CI = 1.94 - 2.63) and diabetes mellitus (HR = 2.44, 95% CI = 2.13 - 2.80), but not with hyperlipidemia (HR =1.13, 95% CI = 0.99-1.30).
Conclusions
This population study provides evidence that patients with heart disease are at an elevated risk of developing CKD. Hypertension and diabetes mellitus are also comorbidity associated with increasing the CKD risk independently.
doi:10.1186/1471-2369-13-77
PMCID: PMC3437200  PMID: 22863289
16.  Differential White Blood Cell Count and Type 2 Diabetes: Systematic Review and Meta-Analysis of Cross-Sectional and Prospective Studies 
PLoS ONE  2010;5(10):e13405.
Objective
Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated.
Research Design and Methods
Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored.
Results
The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10−18). Substantial heterogeneity was present (I2 = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10−4), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10−13), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10−5). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference.
Conclusions
A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate.
doi:10.1371/journal.pone.0013405
PMCID: PMC2956635  PMID: 20976133

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