Research Progresses on "Obesity and Diabetes"--1

1: Obesity (Silver Spring). 2008 Oct 2. [Epub ahead of print]
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TOF-SIMS Analysis of Lipid Accumulation in the Skeletal Muscle of ob/ob Mice.Magnusson YK, Friberg P, Sjövall P, Malm J, Chen Y.[1] 1Department of Molecular and Clinical Medicine/Clinical Physiology, The Sahlgrenska Academy and University Hospital, University of Gothenburg, Gothenburg, Sweden [2] 2Wallenberg Laboratory, The Sahlgrenska Academy and University Hospital, University of Gothenburg, Gothenburg, Sweden.Skeletal muscle lipid accumulation is associated with several chronic metabolic disorders, including obesity, insulin resistance (IR) and type 2 diabetes. The aim of this study is to evaluate whether static imaging time-of-flight-secondary-ion mass spectrometry (TOF-SIMS) equipped with a Bismuth-cluster ion source can be used for studying skeletal muscle lipid accumulation associated with obesity. Mouse gastrocnemius muscle tissues in 10-week-old obese ob/ob (n = 8) and lean wild-type C57/BL6 (n = 6) mice were analyzed by TOF-SIMS. Our results showed that signal intensities of fatty acids (FAs) and diacylglycerols (DAGs) were significantly increased in skeletal muscle of the obese ob/ob mice as compared to the lean wild-type mice. These differences were revealed through a global analytical approach, principal component analysis (PCA) of TOF-SIMS spectra, and ion-specific TOF-SIMS images. Region-of-interest (ROI) analysis showed that FA signal intensities within the muscle cell were significantly increased in ob/ob mice. Moreover, analysis of the ratio between different FA peaks revealed changes in monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs), which is in agreement with previous reports on obesity. These changes in FA composition were also reflected in the ratio of different DAGs or phosphatidylcholines (PCs) that contain different FA residues. Imaging TOF-SIMS together with PCA of TOF-SIMS spectra is a promising tool for studying skeletal muscle lipid accumulation associated with obesity.Obesity (2008) doi:10.1038/oby.2008.424.PMID: 18833214 [PubMed - as supplied by publisher]
2: Obesity (Silver Spring). 2008 Oct 2. [Epub ahead of print]
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Increased Myocardial Susceptibility to Repetitive Ischemia With High-fat diet-induced Obesity.Thakker GD, Frangogiannis NG, Zymek PT, Sharma S, Raya JL, Barger PM, Taegtmeyer H, Entman ML, Ballantyne CM.1Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol that results in the development of fibrotic cardiomyopathy. Cardiac lipids and candidate gene expression were analyzed at 3 days, and histology at 5 days of repetitive I/R. Total free fatty acids (FFAs) in the cardiac extracts of DIO mice were significantly elevated, reflecting primarily the dietary fatty acid (FA) composition. Compared with lean controls, cardiac FA oxidation (FAO) capacity of DIO mice was significantly higher, concurrent with increased expression of FA metabolism gene transcripts. Following 15 min of daily repetitive I/R for 3 or 5 days, DIO mice exhibited increased susceptibility to I/R and, in contrast to lean mice, developed microinfarction, which was associated with an exaggerated inflammatory response. Repetitive I/R in DIO mice was associated with more profound significant downregulation of FA metabolism gene transcripts and elevated FFAs and triglycerides. Maladaptive metabolic changes of FA metabolism contribute to enhanced myocardial injury in diet-induced obesity.Obesity (2008) doi:10.1038/oby.2008.414.PMID: 18833212 [PubMed - as supplied by publisher]
3: G Ital Dermatol Venereol. 2008 Oct;143(5):307-13.
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Cardiovascular morbidity in psoriasis: epidemiology, pathomechanisms, and clinical consequences.Boehncke WH, Boehncke S.Department of Dermatology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany Boehncke@em.uni-frankfurt.de.Psoriasis is a common inflammatory skin condition. Around 25% of patients develop joint involvement in the form of psoriatic arthritis as well. Recent epidemiologic studies demonstrated an increased cardiovascular morbidity among psoriasis patients. Although the association of psoriasis with cardiovascular diseases such as hypertension, myocardial infarction, and heart failure, is now widely accepted, the pathogenetic link remains yet unclear. High prevalence of the metabolic syndrome as well as adverse effects of systemic anti-psoriatic therapies may contribute to the observed association. Several pilot studies suggest that insulin resistance may contribute to the development of cardiovascular diseases in psoriasis patients who exhibit metabolic parameters like patients developing diabetes. Retrospective data provide evidence that continuous systemic therapy may reduce the risk of cardiovascular mortality in psoriasis patients. The consequences for the management of psoriasis at this point are two-fold: as co-morbidity goes along with co-medication, potential drug interactions need to be kept in mind when choosing a systemic anti-psoriatic therapy. Moreover, as psoriasis itself is a risk factor for cardiovascular morbidity, patients must avoid other known risk factors such as obesity or smoking. Dermatologists need to communicate this additional risk to their patients and support them accordingly.PMID: 18833072 [PubMed - in process]
4: Diabetes Educ. 2008 Sep-Oct;34(5):799-806.
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Low testosterone and the association with type 2 diabetes.Farrell JB, Deshmukh A, Baghaie AA.Medical Affairs, Men's Health, Solvay Pharmaceuticals, Inc, 901 Sawyer Road, Marietta, GA 30062. joanne.farrell@solvay.com.PURPOSE: The purpose of this article is to describe androgen deficiency in men, the consequences of this clinically underdiagnosed endocrine disorder, and its relationship to the metabolic syndrome and the association with type 2 diabetes. An overview of prevalence, screening, diagnosis, treatment, and monitoring of male hypogonadism is presented. Method Established guidelines were used to provide definition, diagnosis, treatment, and monitoring information for male hypogonadism. A literature review from 1990 to 2007 revealed study findings that identify the link between low testosterone in men and the development of type 2 diabetes. The following databases were used to review and analyze the current literature: CINAHL, PubMed, and MEDLINE. RESULTS: An analysis of 26 studies was completed. The key findings in all of these studies show that there is a link between low levels of testosterone and an adverse metabolic profile (ie, obesity and insulin resistance). There is evidence that hypogonadism is associated with metabolic syndrome and type 2 diabetes in men. CONCLUSION: Male hypogonadism is a clinical condition that affects a significant number of men in the United States and can affect up to 50% of men diagnosed with type 2 diabetes. The implications for diabetes educators are two-fold: first, there is a high prevalence of low testosterone in men with type 2 diabetes, and second, educators need to have a better understanding of this disease state to provide instructional guidance for their patients and to coordinate care with other clinicians.PMID: 18832284 [PubMed - in process]
5: Diabetes Educ. 2008 Sep-Oct;34(5):766-76.
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Development of an Online University-based Physical Activity and Obesity Education Program.McFarlin BK, Jackson AS.University of Houston, Department of Health and Human Performance, 3855 Holman Street, 104U Garrison, Houston, Texas 77204-6015. bmcfarlin@uh.edu.PURPOSE: The purpose of this article is to describe the development and implementation of an undergraduate university core course titled, Public Health Issues in Physical Activity and Obesity (KIN1304) at a diverse, urban university. METHODS: The course was designed to provide the scientific and public health information on obesity with a goal of prevention. Whereas the course was administered to college students, there are several applications within diabetes education where its content may be useful. RESULTS: The course is entirely Internet based (by means of WebCT Vista) and is a university core requirement for all undergraduate degree programs on campus. Development of such a course provides an opportunity to reach a large portion of the undergraduate population. CONCLUSION: Development of the Internet-based course, Public Health Issues in Physical Activity and Obesity (KIN1304) may be useful for educating a wide variety of people regarding the risks and prevention associated with obesity and diabetes.PMID: 18832283 [PubMed - in process]
6: Proc Natl Acad Sci U S A. 2008 Oct 1. [Epub ahead of print]
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A Drosophila orphan G protein-coupled receptor BOSS functions as a glucose-responding receptor: Loss of boss causes abnormal energy metabolism.Kohyama-Koganeya A, Kim YJ, Miura M, Hirabayashi Y.Hirabayashi Research Unit, Chemical Neuroscience Group, Brain Science Institute, RIKEN, Wako-shi, Saitama 351-0198, Japan;Glucose, one of the most important nutrients for animals, acts as a regulatory signal that controls the secretion of hormones, such as insulin, by endocrine tissues. However, how organisms respond to extracellular glucose and how glucose controls nutrient homeostasis remain unknown. Here, we show that a putative Drosophila melanogaster G protein-coupled receptor, previously identified as Bride of sevenless (BOSS), responds to extracellular glucose and regulates sugar and lipid metabolism. We found that BOSS was expressed in the fat body, a nutrient-sensing tissue equivalent to mammalian liver and adipose tissues, and in photoreceptor cells. Boss null mutants had small bodies, exhibited abnormal sugar and lipid metabolism (elevated circulating sugar and lipid levels, impaired lipid mobilization to oenocytes), and were sensitive to nutrient deprivation stress. These phenotypes are reminiscent of flies defective in insulin signaling. Consistent with these findings are the observations that boss mutants had reduced PI3K activity and phospho-AKT levels, which indicates that BOSS is required for proper insulin signaling. Because human G protein-coupled receptor 5B and the seven-transmembrane domain of BOSS share the same sequence, our results also have important implications for glucose metabolism in humans. Thus, our study provides insight not only into the basic mechanisms of metabolic regulation but also into the pathobiological basis for diabetes and obesity.PMID: 18832180 [PubMed - as supplied by publisher]
7: Am J Physiol Regul Integr Comp Physiol. 2008 Oct 1. [Epub ahead of print]
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Development and Characterization of a Novel Rat Model of Type 2 Diabetes Mellitus: The UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rat.Cummings BP, Digitale EK, Stanhope KL, Graham JL, Baskin DG, Reed BJ, Sweet IR, Griffen SC, Havel PJ.University of California, Davis.The prevalence of type 2 diabetes (T2DM) is increasing, creating a need for T2DM animal models for the study of disease pathogenesis, prevention and treatment. The purpose of this project was to develop a rat model of T2DM that more closely models the pathophysiology of T2DM in humans. The model was created by crossing obese Sprague-Dawley rats with insulin resistance resulting from polygenic adult-onset obesity with ZDF-lean rats that have a defect in pancreatic beta-cell function, but normal leptin signaling. We have characterized the model with respect to diabetes incidence, age of onset, and longitudinal measurements of glucose, insulin, and lipids, and glucose tolerance. Longitudinal fasting glucose and insulin data demonstrated progressive hyperglycemia (with fasting and fed glucose concentrations >250 mg/dl and >450 mg/dl, respectively) after onset along with hyperinsulinemia resulting from insulin resistance at onset followed by a progressive decline in circulating insulin concentrations, indicative of beta-cell decompensation. The incidence of diabetes in male and female rats is 92% and 43% respectively with an average age of onset of 6 months in males and 9.5 months in females. Results from intravenous glucose tolerance tests, pancreas immunohistochemistry and islet insulin content further support a role for beta-cell dysfunction in the pathophysiology of T2DM in this model. Diabetic animals also exhibit glycosuria, polyuria, and hyperphagia. Thus, diabetes in the UCD-T2DM rat is more similar to clinical T2DM in humans than in other existing rat models and provides a useful model for future studies of the pathophysiology, treatment and prevention of T2DM. Key words: Type 2 Diabetes Mellitus, rodent model, hyperglycemia, hyperinsulinemia.PMID: 18832086 [PubMed - as supplied by publisher]
8: Indian J Physiol Pharmacol. 2008 Jan-Mar;52(1):43-52.
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Relationship between plasma leptin and plasma insulin levels in type-2 diabetic patients before and after treatment with glibenclamide and glimepiride.Bhattacharya SK, Madan M, Mahajan P, Paudel KR, Rauniar GP, Das BP, Roy RK.Department of Pharmacology, B.P. Koirala Institute of Health Sciences, Dharan, Nepal.Type 2 diabetes affects 100 million people throughout the world. Among the various factors implicated in the causation of this disease, the role of leptin, an obesity gene product, is increasingly being investigated. This especially assumes importance in the light of knowledge that obesity confers a minimum of 3-10 fold higher risk of diabetes. This study was planned to investigate the relationship between leptin and insulin levels in type 2 diabetic patients before and after treatment with glibenclamide or glimepiride. 60 type 2 diabetic patients were recruited for the study and were divided into 2 groups-one receiving glimepiride and the other group receiving glibenclamide for duration of 10 weeks. This study demonstrated a highly positive correlation of plasma leptin levels with BMI, plasma insulin and insulin resistance. No gender specific differences were observed in leptin concentrations. The study, however, failed to demonstrate any possible relationship between glycemic control as assessed by blood sugars/ glycosylated hemoglobin (HbAlc) and plasma leptin. The administration of glibenclamide or glimepiride significantly lowered blood glucose levels coupled with a decrease in (HbAlc). Both the drugs increased insulin concentrations. Glibenclamide increased leptin levels but they remained unaltered with glimepiride. Glibenclamide and glimepiride were found to be equally effective in their glucose lowering action. However, the patients receiving glibenclamide experienced higher episode of hypoglycaemic spells than those receiving glimepiride.PMID: 18831351 [PubMed - in process]
9: J Urban Health. 2008 Oct 2. [Epub ahead of print]
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Social Patterning of Chronic Disease Risk Factors in a Latin American City.Fleischer NL, Diez Roux AV, Alazraqui M, Spinelli H.Center for Social Epidemiology and Population Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA, nancyfl@umich.edu.Most studies of socioeconomic status (SES) and chronic disease risk factors have been conducted in high-income countries, and most show inverse social gradients. Few studies examine these patterns in lower- or middle-income countries. Using cross-sectional data from a 2005 national risk factor survey in Argentina (a middle-income country), we investigated the associations of individual- and area-level SES with chronic disease risk factors (body mass index [BMI], hypertension, and diabetes) among residents of Buenos Aires. Associations of risk factors with income and education were estimated after adjusting for age, sex (except in sex-stratified models), and the other socioeconomic indicators. BMI and obesity were inversely associated with education and income for women, but not for men (e.g., mean differences in BMI for lowest versus highest education level were 1.55 kg/m(2), 95%CI = 0.72-2.37 in women and 0.17 kg/m(2), 95%CI = -0.72-1.06 in men). Low education and income were also associated with increased odds of hypertension diagnosis in all adults (adjusted odds ratio [AOR] = 1.48, 95%CI = 0.99-2.20 and AOR = 1.50, 95%CI = 0.99-2.26 for the lowest compared to the highest education and income categories, respectively). Lower education was strongly associated with increased odds of diabetes diagnosis (AOR = 4.12, 95%CI = 1.85-9.18 and AOR = 2.43, 95%CI = 1.14-5.20 for the lowest and middle education categories compared to highest, respectively). Area-level education also showed an inverse relationship with BMI and obesity; these results did not vary by sex as they did at the individual level. This cross-sectional study of a major urban area provides some insight into the global transition with a trend toward concentrations of risk factors in poorer populations.PMID: 18830819 [PubMed - as supplied by publisher]
10: Obes Surg. 2008 Oct 2. [Epub ahead of print]
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Bariatric Surgery, Safety and Type 2 Diabetes.Spanakis E, Gragnoli C.Laboratory of Molecular Genetics of Complex & Monogenic Disorders, Department of Medicine and Cellular & Molecular Physiology, H044, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA.Obesity and type 2 diabetes (T2D) represent major health concerns in the USA. Weight loss is the most important aspect in T2D management, as it reduces both morbidity and mortality. Available lifestyle, behavioral, and pharmacological strategies provide just mild to moderate weight loss. The greatest degree of T2D prevention or T2D amelioration in obese subjects has been reported in subjects who underwent bariatric surgery. In the current review, we will describe various types of bariatric surgery, related safety profiles, and their effect on T2D, as well as the potential mechanisms involved in the remission of T2D. Finally, we hereby examine whether bariatric surgery may be considered a treatment for T2D in pregnant women, children, adolescents and subjects at least 65 years old.PMID: 18830788 [PubMed - as supplied by publisher]