BY : - MEDIPLEX RESEARCH GROUP WWW.MEDIPLEX.IN

1. OBESITY AND ASSOCIATED DISEASES: SUCH AS DIABETES BY : - MEDIPLEX RESEARCH GROUP WWW.MEDIPLEX.IN

2. What are overweight and obesity? • Overweight and obesity are defined as abnormal or excessive fat accumulation that may impair health. • Body mass index (BMI) is a simple index of weight-for-height that is commonly used in classifying overweight and obesity in adult populations and individuals. It is defined as the weight in kilograms divided by the square of the height in meters (kg/m2). • BMI provides the most useful population-level measure of overweight and obesity as it is the same for both sexes and for all ages of adults. However, it should be considered as a rough guide because it may not correspond to the same degree of fatness in different individuals. REFERENCE - http://www.who.int/dietphysicalactivity/publications/facts/obesity/en/

3. SUMMARIES OF SOME OF THE RESEARCH PAPERS WE HAVE READ

4. Obesity and Diabetes in the Developing World — A Growing ChallengeParvez Hossain, M.D., Bisher Kawar, M.D., and Meguid El Nahas, M.D., Ph.D. 2007 • About 18 million people die every year from cardiovascular disease, for which diabetes and hypertension are major predisposing factors. Propelling the upsurge in cases of diabetes and hypertension is the growing prevalence of overweight and obesity. More than 1.1 billion adults worldwide are overweight, and 312 million of them are obese. In addition, at least 155 million children worldwide are overweight or obese. a higher body-mass index (the weight in kilograms divided by the square of height in meters) has been shown to account for up to 16% of the global burden of disease. About 90% of type 2 diabetes is attributable to excess weight. Obesity, diabetes, and hypertension also affect the kidneys. Diabetic nephropathy develops in about one third of patients with diabetes. Preventing obesity, diabetes, and hypertension will require fundamental social and political changes. Public health initiatives will be required to make affordable, healthful foods available, and initiatives in education and community planning will be needed to encourage and facilitate exercise.

5. How Does Obesity Cause Diabetes? • Understanding Diabetes When we eat, the pancreas releases insulin, which sits on receptors in the cells, allowing blood sugar to enter the cells for use in energy production. Diabetes mellitus is a condition where the cells are unable to use insulin to convert sugar into energy, so the sugar remains in the blood stream. There are three types of diabetes: type 1, type 2 and gestational. Type 1 diabetes is not linked to obesity and occurs when the islet cells in the pancreas stop producing insulin. Type 2 and gestational diabetes are both conditions where the body produces insulin, but the cell receptors do not respond properly. Gestational diabetes is linked to hormonal changes during pregnancy and type 2 diabetes is linked to obesity. Medical science is not exactly clear how obesity causes type 2 diabetes, but there are several theories.

6. ER Stress and Overnutrition The endoplasmic reticulum (ER) is a specialized membrane, inside the cell, that synthesizes proteins and processes blood fats. Overnutrition is a state where the body has more calories and fat that it can process at one time. When the body enters a state of overnutrition, this puts stress on the ER, causing it to signal the insulin receptors to stop responding to insulin. Temporarily reducing insulin receptivity allows the ER to catch up with its workload. If the body repeatedly enters a state of overnutrition, the ER continually signals the cells to dampen their insulin receptors. Over time, the body is no longer able to respond to insulin properly.

7. IRS Suppression Insulin receptor substrates (IRS) are proteins, inside the cell, that rest against the insulin receptors. When insulin activates the receptors, the receptors release chemicals onto the IRS, causing them to activate the glucose transporter machinery within the cell. In studies with mice, scientists disabled IRS function, resulting in type 2 diabetes. While studies in human subjects with inherited type 2 diabetes showed no abnormality in IRS genes, scientists believe the link between obesity and impaired IRS function lies with a hormone called resistin.

8. Resistin Resistin is produced by fat cells and causes the body to resist insulin. It is believed that resistin production evolved as a response to famine, allowing the body to survive by conserving energy stores. In laboratory studies, mice that were given resistin lost the ability to transport glucose. High levels of resistin were also found in mice that were obese from overeating. In the mice that were given resistin, resistin-lowering drugs reversed the effect, and they were able to transport glucose.

9. Does visceral fat produce insulin?Jo¨rg Do¨tsch, Wolfgang Rascher and Udo MeißnerDepartment of Pediatrics, University of Erlangen-Nu¨rnberg, Loschgestrasse 15, Erlangen, 91054, Germany Obesity is associated with an increased risk for the development of type 2 diabetes mellitus. Adipose tissue serves as an endocrine organ, producing a variety of factors that may favour the development of insulin resistance and type 2 diabetes mellitus. Some are leptin, adiponectin, resistin, tumor necrosis factor. Production of an insulin-mimetic in human adipose tissue might possibly lengthen the phase until hyperinsulinaemia meets with type 2 diabetes. Fukuhara and co-workers have now introduced a new adipokine derived predominantly from visceral adipose tissue, functioning as an insulin-mimetic in various tissues and organs called visfatin. • It exerted a glucose lowering effect on mice. • It acts independent of glucose. • It uses a system of tyrosine phosphorylation dependent signaling. • Concentration did not change upon fasting or feeding. • Visfatin and insulin shared an equal binding affinity for insulin receptor.

10. Monogenic disorders of obesity and body fat distributionDali Chen and Abhimanyu Garg • Identification of mutations in several genes in spontaneous monogenic animal models of obesity and development of transgenic models have indicated the physiological roles of many genes in the regulation of body fat distribution. In humans, mutations in leptin, leptin receptor, prohormone convertase 1 (PC1), pro-opiomelanocortin (POMC), melanocortin 4-receptor (MC4-R) genes have been described in patients with severe obesity. Most of these obesity disorders exhibit a distinct phenotype with varying degrees of hypothalamic and pituitary dysfunction and a recessive inheritance, whereas MC4-R mutation has a nonsyndromic phenotype with dominant inheritance. These mutations suggest the critical role of central signaling systems composed of leptin/ leptin receptor and alpha -melanocyte stimulating hormone/ MC4-R in human energy homeostasis. The advances in our knowledge of the phenotypic manifestations and underlying molecular mechanisms of genetic body fat disorders may lead to better treatment and prevention of obesity and other disorders of adipose tissue in the future.

12. Barsh and Schwartz

13. Obesity-related leptin receptor polymorphismsand gallstones diseaseNahum Méndez-Sánchez;1 Luisa Bermejo-Martínez;2 Norberto C. Chávez-Tapia;1 Daniel Zamora-Valdés;1Karla Sánchez-Lara;1 Martha H. Uribe-Ramos;1 Guadalupe Ponciano-Rodríguez;3 Hector A. Baptista-González;2Martha H. Ramos;1 Misael Uribe1 Leptin is the product of the ob gene, which encodes a 167 amino acid protein with a 21 amino acid signal peptide. Its crystal structure indicates that leptin is a member of the cytokine family and has four or possibly five helical segments. The human ob gene is localized on chromosome 7 and displays 84% homology with the mouse gene. Leptin have established an exciting pathway for the regulation of food ingestion and energy consumption. Leptin levels adapt to changes in energy balance; during fasting or weight loss, serum concentrations decrease, whereas they increase during overfeeding or weight gain. Leptin mRNA expression in fat cells correlates significantly with body fat mass. Hyperleptinemia is thought to be indicative of leptin resistance, and may play a role in the pathogenesis of obesity.

14. Leptin receptor (LEPR) is the product of the 1p31 gene and displays a 78% homology with the mouse db gene. LEPR spans over 70 kb and includes 20 exons which encode an 1,165 amino acid protein that belongs to the superfamily of cytokine receptors and requires all its extracellular subdomains functional for transmitting the signal. LEPR presents two basic isoforms, a short intracellular domain variant, unable to transmit a signal, which is present in a variety of tissues; and a second one with a long intracellular functional domain, capable of activating JAK2 and STAT3, and perhaps others signaling pathways. Leptin receptor gene polymorphisms had been previously associated with obesity and increased leptin levels, and might represent a common form of leptin resistance.

15. REFERENCES :- • Waist Circumference Is a Better Predictor than Body Mass Index of Coronary Heart Disease Risk in Overweight Premenopausal Women Ingrid Lofgren, Kristin Herron, Tosca Zern, Kristy West, Madhu Patalay, Neil S. Shachter,* Sung I. Koo, and Maria Luz Fernandez1 • Progress and Challenges in Metabolic Syndrome in Children and Adolescents Julia Steinberger, Stephen R. Daniels, Robert H. Eckel, Laura Hayman, Robert H. • The Obesity Paradox - Body Mass Index and Outcomes in Patients With Heart Failure Jeptha P. Curtis, MD; Jared G. Selter, MD; Yongfei Wang, MS; Saif S. Rathore, MPH; Ion S. Jovin, MD; Farid Jadbabaie, MD; Mikhail Kosiborod, MD; Edward L. Portnay, MD • Relationship of Childhood Obesity to Coronary Heart Disease Risk Factors in Adulthood: The Bogalusa Heart Study David S. Freedman, PhD*; Laura Kettel Khan, PhD*; William H Dietz, MD, PhD*; Sathanur R. Srinivasan, PhD‡; and Gerald S. Berenson, MD • Body Fat Distribution and Insulin Resistance: Beyond Obesity in Nonalcoholic Fatty Liver Disease among Overweight Men Seung Ha Park, MD, Byung Ik Kim, MD, Sang Hoon Kim, MD, Hong Joo Kim, MD, Dong Il Park, MD, Yong Kyun • Insulin Resistance Status - Predicting Weight Response in Overweight Children Doyle M. Cummings, PharmD, FCP, FCCP; Sarah Henes, MA, RD, LDN; Kathryn M. Kolasa, PhD, RD, LDN; John Olsson, MD; David Collier, MD, PhD • Diabesity: A Polygenic Model of Dietary-Induced Obesity from Ad Libitum Overfeeding of SpragueDawley Rats and Its Modulation by Moderate and Marked Dietary Restriction Kevin P. Keenan, Chao-Min Hoe, Lori Mixson, Carol L. Mccoy, John B. Coleman, Britta A. Mattson, Gordon A. Ballam