Obesity: Wang C

Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC, Anonymous00084, Anonymous00085, Anonymous00086, Anonymous00087, Anonymous00088. · Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center, and Los Angeles BioMedical Research Institute, Torrance, CA 90509, USA. · J Androl. · Pubmed #18772485 No free full text.

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Sun Y, Xun K, Wang C, Zhao H, Bi H, Chen X, Wang Y. · School of Pharmacy, Chengdu Medical College, Chengdu, China. · Cardiovasc Ther. · Pubmed #19207481 No free full text.

Abstract: A large number of studies revealed that adiponectin, a protein secreted specifically by adipose tissue, exhibits antiinflammatory, antiatherogenic, and antidiabetic properties. This 247-amino acid protein contains four differentiable domains and exists in five different configurations, which binds three kinds of receptors. The plasma adiponectin concentration is at amazing microgram level and the gender difference is very clear. Obese subjects showed decreased plasma level of adiponectin while exercise seems to restore it. Many researchers demonstrated that it could be a reliable biomarker for multiple diseases. However, there is controversy about its role in inflammation since its plasma concentration decreases in some inflammatory diseases and increases under some other inflammatory conditions. The signal transduction pathway is still not very clear yet. Could adiponectin be a promising drug target?

Diaz-Arjonilla M, Schwarcz M, Swerdloff RS, Wang C. · Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA 90803, USA. · Int J Impot Res. · Pubmed #18843273 No free full text.

Abstract: Obesity is an important risk factor for many common diseases including cardiovascular disease (CVD), type 2 diabetes, cancer and erectile dysfunction (ED). Adipose tissues produce a number of adipokines and cytokines, which affect endothelial and metabolic function resulting in insulin resistance and the metabolic syndrome (risks factors for CVD). Both ED and metabolic syndrome improve with a reduction in body mass index (BMI). The relationships among obesity, metabolic syndrome, ED, sex hormone-binding globulin (SHBG) and serum total and free testosterone levels are complex and often confusing to the physician. It is known that BMI is inversely proportional to serum total testosterone concentrations; low serum SHBG levels in obesity contribute to the low serum total testosterone. Recent studies show that BMI is also inversely proportional to free testosterone concentration. The characteristic low serum testosterone concentrations observed in obese men are also present in men with the metabolic syndrome and type 2 diabetes mellitus. A small proportion of men with ED have hypogonadism; however, the proportion increases if these men are obese with manifestations of the metabolic syndrome or type 2 diabetes mellitus. ED is a common symptom in patients with type 2 diabetes who also have low testosterone levels. This review describes the relationships between low serum testosterone concentrations and ED in obese patients and those with metabolic syndrome and type 2 diabetes mellitus.

Keith SW, Redden DT, Katzmarzyk PT, Boggiano MM, Hanlon EC, Benca RM, Ruden D, Pietrobelli A, Barger JL, Fontaine KR, Wang C, Aronne LJ, Wright SM, Baskin M, Dhurandhar NV, Lijoi MC, Grilo CM, DeLuca M, Westfall AO, Allison DB. · Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA. · Int J Obes (Lond). · Pubmed #16801930 No free full text.

Abstract: OBJECTIVE: To investigate plausible contributors to the obesity epidemic beyond the two most commonly suggested factors, reduced physical activity and food marketing practices. DESIGN: A narrative review of data and published materials that provide evidence of the role of additional putative factors in contributing to the increasing prevalence of obesity. DATA: Information was drawn from ecological and epidemiological studies of humans, animal studies and studies addressing physiological mechanisms, when available. RESULTS: For at least 10 putative additional explanations for the increased prevalence of obesity over the recent decades, we found supportive (although not conclusive) evidence that in many cases is as compelling as the evidence for more commonly discussed putative explanations. CONCLUSION: Undue attention has been devoted to reduced physical activity and food marketing practices as postulated causes for increases in the prevalence of obesity, leading to neglect of other plausible mechanisms and well-intentioned, but potentially ill-founded proposals for reducing obesity rates.

Wang C, Wang L, Yang Z. · Beijing Institute of Geriatrics, Beijing Hospital, Key Laboratory of Genetics, Ministry of Health of PR China, Beijing 100730, China. · Yi Chuan. · Pubmed #15640130 No free full text.

Abstract: PTP1B is a ubiquitously expressed intracellular protein tyrosine phosphatase. Several lines of evidence support an important role for protein tyrosine phosphatase 1B(PTP1B) in metabolism, and specially in type 2 diabetes and obesity. Overexpression of PTP1B protein has been observed in insulin-resistant states associated with obesity. PTP1B is a negative regulator of insulin and leptin signaling, PTP1B inhibitors might be efficacious in the treatment of type 2 diabetes and obesity by increasing insulin and leptin sensitivity.

Yang D, Fontaine KR, Wang C, Allison DB. · Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA. · Obes Rev. · Pubmed #12608523 No free full text.

Abstract: Short-term studies indicate that intentional weight loss (IWL) among obese persons significantly improves health variables that are often precursors or markers of chronic diseases (e.g. heart diseases, type-2 diabetes). Hence, it is logical to assume that IWL among obese persons would lead to increased longevity. On the whole, epidemiological studies, including recent ones that use conservative analytic approaches such as distinguishing between apparently IWL and unintentional weight loss (UWL), adjusting for potential confounders and excluding apparently unhealthy subjects, indicate that apparently IWL appears to neither increase nor decrease mortality rate. However, it is important to note that none of the existing studies were designed specifically to test the hypothesis that IWL reduces mortality rate, and given methodological problems, these studies do not provide a satisfactory way to address the body mass index (BMI)-mortality question. Several controlled clinical trials suggest that IWL may reduce mortality rate. However, even in these studies, it is important to acknowledge that subjects are randomized to conditions that produce more or less weight loss and not to distinct levels of weight loss per se. Nevertheless, while we await additional data from better designed studies, given our incomplete knowledge, we conclude that it seems more likely than not that IWL achieved by medically recommended methods does not increase and probably decreases mortality rate.

Xiang AH, Peters RK, Kjos SL, Ochoa C, Marroquin A, Goico J, Tan S, Wang C, Azen SP, Liu CR, Liu CH, Hodis HN, Buchanan TA. · Department of Preventive Medicine, University of Southern California Keck School of Medicine, Room 6602 GNH, 1200 North State Street, Los Angeles, California 90089-9317, USA. · J Clin Endocrinol Metab. · Pubmed #15623809 links to  free full text

Abstract: We tested the effects of treatment with a thiazolidinedione drug on rates of progression of carotid intima-media thickness (CIMT) and some putative determinants of CIMT in young women at high risk for type 2 diabetes. A total of 266 nondiabetic, Hispanic women with recent gestational diabetes were randomized to placebo or troglitazone. CIMT measurements were made at baseline, annually, and at study end, together with measurements of obesity, serum lipids, and glucose and insulin levels during oral glucose tolerance tests. Insulin sensitivity (minimal model analysis) was measured at baseline and 3 months later. Data were analyzed to compare CIMT progression rates between treatment groups and investigate potential determinants of differences in CIMT progression. One hundred ninety-two women had a CIMT measurement at baseline and at least one follow-up visit. The mean rate of CIMT change was 31% lower in women assigned to troglitazone (P = 0.048). This intergroup difference was not explained by baseline or on-trial differences in obesity, lipids, glucose, or insulin. The reduction in CIMT progression developed gradually, occurred only in women who had an increase in insulin sensitivity, and was unrelated to the presence of the metabolic syndrome at baseline. Troglitazone reduced the progression of subclinical atherosclerosis via a mechanism that involved unmeasured mediators of atherosclerosis, either in the circulation or directly in the arterial wall.

Wang C, Li Y, Zhu K, Dong YM, Sun CH. · Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, P. R. China. · Asia Pac J Clin Nutr. · Pubmed #19329405 No free full text.

Abstract: OBJECTIVE: To investigate the effect of supplementation with multivitamin and mineral on blood pressure and C-reactive protein (CRP) in obese women with increased cardiovascular disease risk as having hypertension, hyperglycemia or hyperlipemia. SUBJECTS AND METHODS: 128 obese Chinese women aged 18-55 years with increased cardiovascular disease risk participated in a 26-week randomized, double-blind, placebo-controlled trial. Subjects were randomized to four groups, and received either one tablet of high-dose multivitamin and mineral supplement (MMS), or one tablet of low-dose MMS (Low MMS), or calcium 162 mg (Calcium) or identical placebo (Placebo) daily during the study. Diastolic blood pressure (DBP), systolic blood pressure (SBP) and serum concentrations of CRP were measured at baseline and end-trial. RESULTS: At baseline, the subjects had an average age of 42.0+/-7.1 years and BMI of 30.9+/-2.8 kg/m2. There were no significant differences between the four groups in baseline characteristics. One hundred and seventeen subjects completed the study. After 26-week supplementation, both SBP and DBP were significantly lower in the MMS group compared to the placebo group (p < 0.05). There was also a non-significant trend of lower DBP at 26-week in the MMS and calcium groups compared to baseline (p < 0.08). At 26-week, the MMS group also had significantly lower serum concentrations of CRP compared with that of baseline and the placebo group (p < 0.05). CONCLUSIONS: Our results showed that supplementation with adequate multivitamin and mineral supplement could reduce blood pressure and serum CRP in obese women with increased cardiovascular disease risk.

Winters SJ, Chennubhatla R, Wang C, Miller JJ. · Division of Endocrinology, Metabolism and Diabetes, University of Louisville, Louisville, KY 40202, USA. · Metabolism. · Pubmed #19303961 No free full text.

Abstract: 25-Hydroxy vitamin D (25OHD) is lipophilic and highly bound to vitamin D-binding protein (VDBP) in plasma. In the present study, we examined VDBP and 25OHD levels by race and body mass index (BMI) in young adult women to determine whether circulating VDBP plays a role in the low levels of 25OHD with obesity and among African Americans. In agreement with previous studies, mean 25OHD levels were lower in African American women than in whites (P < .01). In a hierarchical multiple regression model, BMI was associated with 25OHD after adjustment for age in white women (P = .02, R(2) = .10) but not in African American women. The VDBP levels, by contrast, were similar in African Americans and whites, and were unrelated to BMI in either racial group. Furthermore, VDBP was unrelated to the plasma level of 25OHD. These data confirm an interaction between race and obesity in vitamin D metabolism, and imply that the carrier protein is not an important determinant of circulating 25OHD in women, nor is it affected by race or adiposity.

Kalaitzidis R, Li S, Wang C, Chen SC, McCullough PA, Bakris GL. · Department of Medicine, Hypertensive Diseases Unit, Section of Endocrinology, Diabetes and Metabolism, University of Chicago, Pritzker School of Medicine, Chicago, IL 60637, USA. · Am J Kidney Dis. · Pubmed #19285608 No free full text.

Abstract: BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health problem. Systolic blood pressure as an associated feature of CKD has not been fully explored in community volunteer and nationally representative samples of the US population. METHODS: This cross-sectional analysis evaluated hypertension and early-stage CKD in participants in the Kidney Early Evaluation Program (KEEP), a voluntary community-based health screening program administered by the National Kidney Foundation, and the National Health and Nutrition Examination Survey (NHANES) data to assess similarities and differences between these populations. Participants in both databases were 18 years or older. RESULTS: The KEEP database included 88,559 participants and the NHANES included 20,095. Hypertension prevalence was greater in KEEP (69.6%) than NHANES (38.1%; P < 0.001). Compared with NHANES participants, KEEP participants had greater rates of obesity (79.5% versus 51.5%; P < 0.001) and diabetes (28.0% versus 8.9%; P < 0.001). In participants with diabetes, KEEP had slightly greater rates of prevalent hypertension (88.5% versus 85.7%; P = 0.03). In participants with hypertension, CKD stages 3 and 4 were more prevalent in KEEP than NHANES (79.1% versus 69.3%; P < 0.001). Rates of CKD stages 3 and 4 were greater in KEEP than NHANES for the following subgroups: African Americans (72.4% versus 57.4%; P < 0.001), smokers (69.1% versus 55.6%; P = 0.002), and participants with hypercholesterolemia (80.2% versus 71.9%; P < 0.001). CONCLUSIONS: In the volunteer KEEP population, rates of hypertension and CKD were greater than in NHANES, most prominently in African Americans and participants with increased cardiovascular risk.

Whaley-Connell A, Sowers JR, McCullough PA, Roberts T, McFarlane SI, Chen SC, Li S, Wang C, Collins AJ, Bakris GL, Anonymous00040. · Department of Internal Medicine, University of Missouri-Columbia School of Medicine and Harry S. Truman VA Medical Center, Columbia, MO 65212, USA. · Am J Kidney Dis. · Pubmed #19285607 No free full text.

Abstract: BACKGROUND: Diabetes contributes to increased morbidity and mortality in patients with chronic kidney disease (CKD). We sought to describe CKD awareness and identify factors associated with optimal glycemic control in diabetic and nondiabetic individuals both aware and unaware of CKD. METHODS: This cross-sectional analysis compared Kidney Early Evaluation Program (KEEP) and National Health and Nutrition and Examination Survey (NHANES) 1999 to 2006 participants with diabetes and CKD. CKD was defined and staged using glomerular filtration rate (estimated by using the 4-variable Modification of Diet in Renal Disease Study equation) and urine albumin-creatinine ratio. NHANES defined diabetes as self-reported diabetes or fasting plasma blood glucose level of 126 mg/dL or greater, and KEEP as self-reported diabetes or diabetic retinopathy, use of diabetes medications, fasting blood glucose level of 126 mg/dL or greater, or nonfasting glucose level of 200 mg/dL or greater. RESULTS: Of 77,077 KEEP participants, 20,200 (26.2%) were identified with CKD and 23,082 (29.9%) were identified with diabetes. Of 9,536 NHANES participants, 1,743 (18.3%) were identified with CKD and 1,127 (11.8%) were identified with diabetes. Of KEEP participants with diabetes and CKD (n = 7,853), 736 (9.4%) were aware of CKD. Trends in lack of CKD awareness were similar for KEEP participants with and without diabetes. Unaware participants with and without diabetes identified with stages 1 and 2 CKD were less likely to reach target glucose levels, defined as fasting glucose level less than 126 mg/dL or nonfasting glucose level less than 140 mg/dL, than those with stages 3 to 5 (odds ratio, 0.69; 95% confidence interval, 0.62 to 0.78; odds ratio, 0.69; 95% confidence interval, 0.58 to 0.81; P < 0.001, respectively). CONCLUSION: Our data support that KEEP, as a targeted screening program, is a more enriched population with CKD and comorbid diabetes than NHANES. In addition, our findings highlight the relationship between dysglycemia and early stages of unidentified CKD.

Cao L, Lin EJ, Cahill MC, Wang C, Liu X, During MJ. · Cancer Genetics and Neuroscience Program, Department of Molecular Virology, Immunology and Medical Genetics, and the Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA. · Nat Med. · Pubmed #19270710 No free full text.

Abstract: Hypothalamic brain-derived neurotrophic factor (BDNF) is a key element in the regulation of energy balance. Here we investigated the therapeutic efficacy of BDNF by gene transfer in mouse models of obesity and diabetes. Gene transfer of BDNF led to marked weight loss and alleviation of obesity-associated insulin resistance. To facilitate clinical translation and ensure that BDNF protein expression was appropriately decreased as weight loss progressed, thus preventing cachexia, we developed a molecular autoregulatory system involving a single recombinant adeno-associated virus vector harboring two expression cassettes, one constitutively driving BDNF and the other driving a specific microRNA targeting BDNF. The microRNA element was controlled by a promoter (that controlling the Agrp gene encoding agouti-related peptide) responsive to BDNF-induced physiological changes. Hence, as body weight decreased and agouti-related protein is induced, microRNA expression was activated, inhibiting transgene expression. In contrast to the progressive weight loss associated with a nonregulated approach, this microRNA-approach led to a sustainable plateau of body weight after notable weight loss was achieved. This strategy mimics the body's endogenous physiological feedback mechanisms, thereby resetting the hypothalamic set point to reverse obesity and metabolic syndrome.

Gao F, Fang Q, Zhang R, Lu J, Lu H, Wang C, Ma X, Xu J, Jia W, Xiang K. · Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Medicine Center for Diabetes, Shanghai, PR China. · Endocr J. · Pubmed #19225211 links to  free full text

Abstract: Disulfide-bond-A oxidoreductase-like protein (DsbA-L) has been suggested to take part in the disulfide bond formation progress of proteins, including insulin and adiponectin. Recent study has demonstrated that expression of DsbA-L was decreased in obese mice and human subject, indicating that DsbA-L might be a potential target for treatment of metabolic diseases. We investigated the association of SNP-1308G/T (rs1917760) of DsbA-L gene with metabolic diseases. 589 normal glucose tolerance (NGT) subjects and 556 type 2 diabetes (T2DM) subjects were recruited. Each group was divided into normal weight (NW) (BMI<24 kg/m(2)) subgroup and overweight/obesity (OW/OB) (BMI>/=24 kg/ m(2)) subgroup. Genotype distributions and allele frequencies of SNP (-1308G/T) in DsbA-L gene were not associated with T2DM and obesity. However, it was observed that T allele carriers had better insulin secretion function compared with non-T allele carriers in NGT-NW group, not only the first phase insulin secretion (P=0.007) but also the second phase insulin secretion (P=0.031). Multiple linear regression analysis revealed that SNP-1308G/T polymorphism (rs1917760) was independently correlated with both first and second phase insulin secretion in NGT-NW group (R(2)=0.055, P=0.007; R(2)=0.029, P=0.041). Otherwise, T carriers had more visceral fat than non-T carriers (P=0.020) in NGT-OW/OB group. In conclusion, the SNP-1308G/T (rs1917760) genotypes of DsbA-L gene might participate in insulin secretion and body fat distribution. It is possible that polymorphisms of DsbA-L gene associated with metabolic diseases.

Wang C, Liu M, Riojas RA, Xin X, Gao Z, Zeng R, Wu J, Dong LQ, Liu F. · Department of Pharmacology, Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78229, USA. · J Biol Chem. · Pubmed #19047061 No free full text.

Abstract: Clinical, epidemiological, and biochemical studies have highlighted the role of obesity-induced insulin resistance in various metabolic diseases. However, the underlying molecular mechanisms remain to be established. In the present study, we show that palmitate-induced serine phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1) negatively regulates insulin signaling. PDK1-mediated Akt phosphorylation at Thr308 in the activation loop is reduced in C2C12 myotubes treated with palmitate or overexpressing protein kinase C theta (PKCtheta), a kinase that has been implicated in hyperlipidemia-induced insulin resistance. Palmitate treatment also inhibited platelet-derived growth factor-stimulated Akt phosphorylation, suggesting that the inhibition could occur at a site independent of IRS1/2. The inhibitory effect of palmitate on PDK1 and Akt was diminished in PKCtheta-deficient mouse embryonic fibroblasts (MEFs) by treating C2C12 myotubes with PKCtheta pseudosubstrates. In vivo labeling studies revealed that PDK1 undergoes palmitate-induced phosphorylation at two novel sites, Ser504 and Ser532. Replacing Ser504/532 with alanine disrupted PKCtheta-catalyzed PDK1 phosphorylation in vitro and palmitate-induced PDK1 phosphorylation in cells. PDK1-deficient MEFs transiently expressing PDK1S504A/S532A but not PDK1S504E/S532D showed increased basal and insulin-stimulated Akt phosphorylation at Thr308 when compared with MEFs expressing wild-type PDK1. Taken together, our results identify PDK1 as a novel target in free fatty acid-induced insulin resistance and PKCtheta as the kinase mediating the negative regulation.

Bao Y, Lu J, Wang C, Yang M, Li H, Zhang X, Zhu J, Lu H, Jia W, Xiang K. · Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai, China. · Atherosclerosis. · Pubmed #18417137 No free full text.

Abstract: OBJECTIVE: To determine the appropriate cutoffs for visceral fat area (VFA) measured by magnetic resonance imaging linking to risk of the metabolic syndrome (MetS) and the corresponding waist circumference in Chinese. METHODS AND RESULTS: Totally 1,140 individuals (men 525, women 615) aged from 35 to 75 years were included. The components of the MetS were defined by International Diabetes Federation (IDF) and Chinese Diabetes Society (CDS) definition, respectively. Receive operating characteristic curve analyses were used to determine the appropriate cutoffs of VFA and corresponding waist circumference in the prediction of the MetS. The optimal VFA cutoff was near 80 cm(2) in identifying the MetS with two or more components but not including overweight/obesity by either of the two definitions in all subjects. There was no difference in men by ages while women aged < 50 years tended to have lower VFA cutoff than those aged > or = 50 years by the two definitions. The appropriate waist circumference cutoffs were 90 cm in men and 85 cm in women for the MetS. CONCLUSION: The optimal cutoff of waist circumference for abdominal obesity is 90 cm for men and 85 cm for women in Chinese.

Wang C, Ren Y, Chen J, Hu Y, Yang J, Xu P, Pan Y, Li J. · The Center of Minimally Invasive Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. · Obes Surg. · Pubmed #18369682 No free full text.

Abstract: Current widespread application of laparoscopic techniques in Roux-en-Y gastric bypass (RYGBP) is making surgical safety an increasingly important issue. We report one case that resulted in death due to postoperative fulminant acute pancreatitis after laparoscopic RYGBP was performed when this procedure was still relatively new in China. The patient was a chronically obese 19-year-old male. Weight loss medications had been ineffective, and preoperative body mass index was 40.7. Preoperative examination revealed moderate steatohepatitis. Laparoscopic RYGBP (LRYGBP) was performed. Early manifestations of clinical shock appeared 13 h after the laparoscopic surgery. A second laparoscopic examination showed small-vessel hemorrhage at the posterior wall of the jejunojejunal anastomosis, with blood clot formation resulting in Roux limb and afferent loop obstruction. Fulminant acute pancreatitis developed in the patient 18 h after the second surgery. The patient died 15 days later from systemic multiorgan insufficiency. LRYGBP (postcolon) is a technically demanding procedure for surgeons who are not experienced in this operation. In addition, surgical tolerance is reduced in morbidly obese patients. Therefore, special care should be taken during surgery, and hemostasis must be achieved at all bleeding sites. Increased perioperative surveillance allows for early detection and management of severe complications.

Rao MV, Qiu Y, Wang C, Bakris G. · Department of Medicine, Section of Nephrology, University of Chicago, Pritzker School of Medicine, Chicago, IL 60637, USA. · Am J Kidney Dis. · Pubmed #18359406 No free full text.

Abstract: BACKGROUND: The prevalence and incidence of hypertension are increasing, and they correlate with the chronic kidney disease rate in the United States. Early identification and achievement of blood pressure goals may improve chronic kidney disease outcomes. METHODS: In this cross-sectional study, subjects were participants in the Kidney Early Evaluation Program (KEEP), a voluntary community-based health-screening program enrolling individuals 18 years and older with diabetes, hypertension, or family history of kidney disease, diabetes, or hypertension, administered by the National Kidney Foundation; and the National Health and Nutrition Examination Survey (NHANES), administered by the National Center for Health Statistics. All studied individuals in both databases were US residents aged 18 years or older. We evaluated multiple variables for participants in KEEP 2000-2006 and participants in NHANES 1999-2004 in this logistic analysis. RESULTS: Although distributions of hypertension were similar between databases, KEEP participants with cardiovascular risk factors, especially current smoking, have a greater prevalence of hypertension than similar NHANES participants. Of hypertensive participants, 35.8% were African American in KEEP data, and 13.2% in NHANES data. Associations with increased prevalence of hypertension were decreasing estimated glomerular filtration rate by increments of 10 mL/min/1.73 m(2), increasing age, obesity, African American race, and microalbuminuria. In both KEEP and NHANES data, study group participants younger than 46 years were more likely to have achieved goal blood pressure. CONCLUSION: Several elements were identified by both registries as risk factors for linearly associated worsening of hypertension. In addition to the traditional risk factors of age, race, and geographic residence, such novel markers as microalbuminuria may also increase the risk.

Jurkovitz CT, Qiu Y, Wang C, Gilbertson DT, Brown WW. · Christiana Care Center for Outcomes Research, Christiana Care Health System, Newark, DE 19713, USA. · Am J Kidney Dis. · Pubmed #18359405 No free full text.

Abstract: BACKGROUND: Chronic kidney disease (CKD) recently was identified as a public health problem requiring a public health prevention approach. The National Kidney Foundation Kidney Early Evaluation Program (KEEP), initiated in 2000, meets the definition of a public health program, offering surveillance and early detection of CKD. This report aims to detail demographic characteristics of KEEP participants and compare them with characteristics of participants in the National Health and Nutrition Examination (NHANES) 1999-2004. METHODS: KEEP is a CKD screening program enrolling individuals 18 years and older with a family history of kidney disease or personal or family history of diabetes or hypertension. Simple descriptive statistics were used in the analysis. For comparison, the NHANES sample was restricted to participants with hypertension or diabetes or a family history of hypertension or diabetes. RESULTS: The number of KEEP participants grew exponentially over time. Most participants were aged 46 to 60 years. KEEP enrolled twice as many women as men (68.4% versus 31.5%). Minorities were well represented (33.4% African American, 12.3% Hispanic). Almost 58% of participants had some college or more education, and close to 85.0% had a physician. Compared with NHANES, the KEEP population was older and included a larger proportion of women and African Americans. Self-reported hypertension, self-reported diabetes, obesity, and CKD were higher in KEEP (52.9% versus 38.5%, 26.6% versus 9.9%, 43.6% versus 35.5%, and 22.8% versus 17.6%, respectively). CONCLUSIONS: KEEP has been successful in enrolling individuals at risk of kidney disease, evidenced by the high levels of self-reported hypertension and diabetes.

Whaley-Connell AT, Sowers JR, McFarlane SI, Norris KC, Chen SC, Li S, Qiu Y, Wang C, Stevens LA, Vassalotti JA, Collins AJ, Anonymous00276. · University of Missouri-Columbia School of Medicine and Harry S Truman VA Medical Center, Columbia, MO 65212, USA. · Am J Kidney Dis. · Pubmed #18359404 No free full text.

Abstract: BACKGROUND: Diabetes mellitus is the leading cause of chronic kidney disease (CKD) and contributes to increased morbidity and mortality in the CKD population. Early diabetes identification through targeted screening programs is important for the development of preventive strategies. METHODS: This is a cross-sectional analysis of the National Kidney Foundation Kidney Early Evaluation Program (KEEP) data and National Health and Nutrition and Examination Survey (NHANES) 1999-2004 data. KEEP is a community-based health-screening program enrolling individuals 18 years or older with diabetes, hypertension, or family history of kidney disease, diabetes, or hypertension. Study participants were those identified as meeting these inclusion criteria. Participants who had received kidney transplants or were currently receiving dialysis therapy were excluded. RESULTS: Of 73,460 KEEP participants, 20,562 (28.0%) had diabetes compared with 1,545 of 17,049 (6.7%) NHANES participants. Age, obesity, high cholesterol level, hypertension, and cardiovascular disease distributions were similar for patients with diabetes in both populations, whereas women and African Americans were overrepresented in KEEP. The prevalence of diabetes in KEEP progressively increased with increasing stage of CKD, and this relationship persisted in subgroup analyses of older participants (age > 46 years), as well as in analyses stratified by sex, race, and other CKD risk factors: current tobacco use, obesity, hypertension, cardiovascular disease, and increased cholesterol level. KEEP participants with CKD who reported having diabetes were unlikely to have met target blood glucose levels (odds ratio, 0.71; 95% confidence interval, 0.66 to 0.77; P < 0.001). Reporting not having diabetes was associated with the likelihood of increased blood glucose levels (odds ratio, 1.28; 95% confidence interval, 1.16 to 1.41; P < 0.001). CONCLUSION: KEEP is congruent with NHANES regarding a greater prevalence of diabetes in patients with CKD. As a targeted screening program, KEEP may represent a higher risk and more motivated patient population.

Whaley-Connell AT, Sowers JR, Stevens LA, McFarlane SI, Shlipak MG, Norris KC, Chen SC, Qiu Y, Wang C, Li S, Vassalotti JA, Collins AJ, Anonymous00275. · University of Missouri-Columbia School of Medicine and the Harry S. Truman VA Medical Center, Columbia, MO 65212, USA. · Am J Kidney Dis. · Pubmed #18359403 No free full text.

Abstract: BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing in the United States, caused in part by older age and increasing prevalences of hypertension and type 2 diabetes. CKD is silent and undetected until advanced stages. The study of populations with earlier stages of kidney disease may improve outcomes of CKD. METHODS: The Kidney Early Evaluation Program (KEEP), a National Kidney Foundation program, is a targeted community-based health-screening program enrolling individuals 18 years and older with diabetes, hypertension, or family history of kidney disease, diabetes, or hypertension. Participants who had received transplants or were on regular dialysis treatment were excluded from this analysis. The National Health and Nutrition Examination Survey (NHANES) 1999-2004 was a nationally representative cross-sectional survey; participants were interviewed in their homes and/or received standardized medical examinations in mobile examination centers. RESULTS: Of the 61,675 KEEP participants, 16,689 (27.1%) were found to have CKD. In the NHANES sample of 14,632 participants, 2,734 (15.3%) had CKD. Older age, smoking, obesity, diabetes, hypertension, and cardiovascular disease were associated significantly with CKD in both KEEP and NHANES (P < 0.05 for all). Of note, the likelihood for CKD in African Americans differed between KEEP (odds ratio, 0.81; P < 0.001) and NHANES (odds ratio, 1.10; P = 0.2). CONCLUSION: A greater prevalence of CKD was detected in the KEEP screening than in the NHANES data. KEEP has the limitations common to population-screening studies and conclusions for population-attributable risk may be limited. The targeted nature of the KEEP screening program and the large sample size with clinical characteristics comparable to NHANES validates KEEP as a valuable cohort to explore health associations for the CKD and at-risk-for-CKD populations in the United States.

Kane MA, Folias AE, Wang C, Napoli JL. · Department of Nutritional Science and Toxicology, 119 Morgan Hall, MC#3104, University of California, Berkeley, Berkeley, California 94720-3104, USA. · Anal Chem. · Pubmed #18251521 No free full text.

Abstract: We report an improved tandem mass spectrometric assay for retinoic acid (RA) applicable to in vitro and in vivo biological samples. This liquid chromatography tandem mass spectrometric (LC/MS/MS) assay for direct RA quantification is the most sensitive to date, with a 62.5 attomol lower limit of detection and a linear range spanning greater than 4 orders of magnitude (from 250 attomol to 10 pmol). This assay resolves all-trans-RA (atRA) from its endogenous geometric isomers, is applicable to samples of limited size (10-20 mg of tissue), and functions with complex biological matrixes. Coefficients of variation are as follows: instrumental, < or =2.6%; intraday, 5.2% +/- 0.7%; interday, 6.7% +/- 0.9%. In vitro capabilities are demonstrated by quantification of endogenous RA and RA production (from retinol) in primary cultured astrocytes. Quantification of endogenous atRA and its geometric isomers in 129SV mouse serum and tissues (liver, kidney, adipose, muscle, spleen, testis, and brain) reveals in vivo utility of the assay. The ability to discriminate spatial concentrations of RA in vivo is illustrated with C57BL/6 mouse brain loci (hippocampus, cortex, olfactory bulb, thalamus, cerebellum, and striatum), as well as with Lewis rat proximal/distal mammary gland regions during various morphological stages: virgin, early pregnancy (e7), late pregnancy (e20), lactating (day 4), involuting day 1, and involuting day 11. This assay provides the sensitivity necessary for direct, endogenous RA quantification necessary to elucidate RA function, e.g., in neurogenesis, morphogenesis, and the contribution of altered RA homeostasis to diseases, such as Alzheimer's disease, type 2 diabetes, obesity, and cancer.

Keith SW, Wang C, Fontaine KR, Cowan CD, Allison DB. · Section on Statistical Genetics and Clinical Nutrition Research Center, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA. · Obesity (Silver Spring). · Pubmed #18239647 No free full text.

Abstract: OBJECTIVE: To evaluate the association between BMI (kg/m(2)) and headaches among women. METHODS AND PROCEDURES: Cross-sectional analysis of 11 datasets identified after searching for all large publicly available epidemiologic cohort study datasets containing relevant variables. Datasets included National Health Interview Survey (NHIS): 1997-2003, the first National Health Examination and Nutrition Survey, Alameda County Health Study (ACHS), Tecumseh Community Health Study (TCHS), and Women's Health Initiative (WHI). The women (220,370 in total) were aged 18 years or older and had reported their headache or migraine status. RESULTS: Using nonlinear regression techniques and models adjusted for age, race, and smoking, we found that increased BMI was generally associated with increased likelihood of headache or severe headache among women. A BMI of approximately 20 was associated with the lowest risk of headache. Relative to a BMI of 20, mild obesity (BMI of 30) was associated with roughly a 35% increase in the odds for experiencing headache whereas severe obesity (BMI of 40) was associated with roughly an 80% increase in odds. Results were essentially unchanged when models were further adjusted for socioeconomic variables, alcohol consumption, and hypertension. Being diagnosed with migraine showed no association with BMI. DISCUSSION: Among US women, a BMI of approximately 20 (about the 5th percentile) was associated with the lowest likelihood of headache. Consistently across studies, obese women had significantly increased risk for headache. By contrast, the risk for diagnosed migraine headache per se was not obviously related to BMI. The direction of causation and mechanisms of action remain to be determined.

Hu C, Jia W, Zhang R, Wang C, Lu J, Wu H, Fang Q, Ma X, Xiang K. · Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. · Diabet Med. · Pubmed #18199128 No free full text.

Abstract: AIMS: Retinol binding protein 4 (RBP4) is a newly discovered adipokine, which plays a role in insulin resistance and obesity. The aim of this study was to determine the relationship between genetic variants of the RBP4 gene, circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism in the Chinese population. METHODS: We sequenced exons and the putative promoter region to identify single nucleotide polymorphisms (SNPs) in the RBP4 gene in 32 Chinese subjects. Additional SNPs were selected from a public database to increase marker density. Taking account of the pairwise linkage disequilibrium and minor allele frequencies, a subset of SNPs was further genotyped in 255 Type 2 diabetic patients and 372 normal control subjects. Circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism were measured. RESULTS: Ten SNPs were identified and five were further genotyped in the full sample. No individual SNP was significantly associated with Type 2 diabetes, but a rare haplotype CAA formed by +5388 C>T, +8201 T>A and +8204 T>A was more frequent in diabetic patients (P = 0.0343, empirical P = 0.0659 on 10 000 permutations). In both groups, non-coding SNPs were associated with circulating RBP4 concentrations (P < 0.05). In the normal control subjects, the SNP +5388 C>T was associated with serum C-peptide levels both fasting and 2 h after an oral glucose tolerance test (P = 0.0162 and P = 0.0075, respectively). CONCLUSION: Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism.

Johnen H, Lin S, Kuffner T, Brown DA, Tsai VW, Bauskin AR, Wu L, Pankhurst G, Jiang L, Junankar S, Hunter M, Fairlie WD, Lee NJ, Enriquez RF, Baldock PA, Corey E, Apple FS, Murakami MM, Lin EJ, Wang C, During MJ, Sainsbury A, Herzog H, Breit SN. · Centre for Immunology, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales 2010, Australia. · Nat Med. · Pubmed #17982462 No free full text.

Abstract: Anorexia and weight loss are part of the wasting syndrome of late-stage cancer, are a major cause of morbidity and mortality in cancer, and are thought to be cytokine mediated. Macrophage inhibitory cytokine-1 (MIC-1) is produced by many cancers. Examination of sera from individuals with advanced prostate cancer showed a direct relationship between MIC-1 abundance and cancer-associated weight loss. In mice with xenografted prostate tumors, elevated MIC-1 levels were also associated with marked weight, fat and lean tissue loss that was mediated by decreased food intake and was reversed by administration of antibody to MIC-1. Additionally, normal mice given systemic MIC-1 and transgenic mice overexpressing MIC-1 showed hypophagia and reduced body weight. MIC-1 mediates its effects by central mechanisms that implicate the hypothalamic transforming growth factor-beta receptor II, extracellular signal-regulated kinases 1 and 2, signal transducer and activator of transcription-3, neuropeptide Y and pro-opiomelanocortin. Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity.

Jia W, Wu H, Bao Y, Wang C, Lu J, Zhu J, Xiang K. · Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China. · J Clin Endocrinol Metab. · Pubmed #17550959 links to  free full text

Abstract: OBJECTIVE: Previous studies have shown that adipose-derived serum retinol-binding protein 4 (RBP4) levels are increased in insulin-resistant mouse models and in subjects with insulin resistance or type 2 diabetes. However, the association of visceral fat and serum RBP4 has not been studied. The purpose of this study was to investigate the relationship between serum RBP4 and regional fat distribution in Chinese subjects with and without type 2 diabetes. DESIGN: We measured serum RBP4 concentrations from 1033 Chinese subjects with various degrees of obesity and tested the association between visceral adiposity and serum RBP4. In a subgroup of this study, euglycemic-hyperinsulinemic clamp was performed to measure insulin sensitivity. The association between visceral adiposity and serum RBP4 was also determined in response to rosiglitazone treatment in a subgroup of patients with diabetes. RESULTS: Serum RBP4 level was positively correlated with visceral adipose area in male (r = 0.171; P < 0.001) and female (r = 0.215; P < 0.001) subjects. However, there was no correlation between serum RBP4 and body mass index. Subjects with visceral obesity had higher serum RBP4 concentrations than those without visceral obesity in both men and women. Rosiglitazone treatment in patients with diabetes resulted in a lower serum RBP4 level (35.2 +/- 10.2 vs. 24.9 +/- 5.6 microg/ml, before vs. after treatment). These changes were accompanied by improved insulin sensitivity and reductions in visceral fat area. The latter was found to be highly correlated with the decline of serum RBP4 levels (r = 0.471; P = 0.027). CONCLUSIONS: Serum RBP4 level is positively associated with visceral adiposity in both men and women. Our data suggest that RBP4 may contribute to the development of insulin resistance along with other adipokines.