Obesity

With obesity rising dramatically in China, CCEMD is exploring novel causal genes, molecular mechanisms, preventions, and therapies. In 2009, the Genetics of Obesity in

Chinese Youth (GOCY) study was established with the goal of exploring the pathogenesis and

genetic susceptibility of patients with obesity. This cohort study has enrolled over 1,000 patients with obesity and 1,000 control subjects, and is registered on the U.S. ClinicalTrials.gov web-site.

The center was one of the first to investigate the causal role of obesity in cardiovascular disease using the principle of Mendelian randomiza-tion, a way of ensuring that any difference in the outcome is because of the genetic variant being studied. CCEMD researchers are using whole-exome sequencing to identify novel rare genetic variants in the human genome as well as metagenomics to investigate our ‘other ge-nome’—the collective genome of the microorganisms inhabiting our body, known as the microbiome.

The obesity study group also conducts basic studies that examine the molecular mechanisms underlying energy balance, including which genes regulate adipocyte (fat cell) differentiation, and investigate how bariatric (weight loss) surgery alters the microbiome and neural path-ways. They believe that a better understanding of these processes will pave the way for developing new drugs to combat the obesity epidemic.

T he Shanghai Clinical Center for Endocrine and Metabolic Diseases (CCEMD) at Ruijin Hospital in the heart of downtown Shanghai is a large complex housing both the Shanghai Institute of Endo-

crine and Metabolic Diseases and the Department of Endocrine and Metabolic Diseases.

CCEMD supports 100 staff, including a faculty of 30. A total of 149 doctoral degrees and 270 postgraduate degrees have been awarded at the center since 1978.

“CCEMD has the best research talent in China right now,” says Pro-fessor Guang Ning, the center’s director. “Our vision is to become the leading endocrine and metabolic disease center in the Asia Pacific region; our mission is to take care of people’s health with our hearts.”

Ning joined the Department of Endocrine and Metabolic Diseas-es as chief resident in 1994 and has been the director of CCEMD since 2007. He is an executive committee member of the Interna-tional Society of Endocrinology, has published more than 180 sci-entific papers in peer-reviewed journals, and created the Journal of Diabetes.

Professor Ning’s strong leadership style is characterized by open-ness and engagement. He strives to create a working environment where, he says, “we are all happy to come to work every day, and at the end of the day we don’t want to leave.”

The best medical students across China compete fiercely for a place at CCEMD, where they are afforded access to some of the most knowledgeable minds in the field and the opportunity to be part of cutting-edge research. Every year, a select few are chosen to study abroad in the Unites States, Europe, Japan, or Australia.

The Shanghai Clinical Center for Endocrine and Metabolic DiseasesA Wealth of Research from China for the World

Endocrine System ResearchEstablished in the 1960s, the adrenal gland disease study group reported the very first primary aldosteronism (PA) patient in China. Today, the center holds the largest collection of adrenal tumors in China and leads a nationwide cross-sectional survey on the prevalence of PA in resistant hypertension patients in China. In addition to PA, the adrenal gland disease study group has been focusing on pheochromocytoma, Cushing syndrome, endocrine-related hypertension, and hypokalemia.

The thyroid research team, meanwhile, studies the most common diseases affecting the thyroid. Specific areas of investigation include elu-cidating genetic and environmental factors and immunity pathways in-volved in autoimmune thyroid disease, identifying molecular biomark-ers for improving the diagnosis and prognosis of thyroid cancer, and ultimately discovering new therapies for treating thyroid diseases.

Diabetes “The prevalence of metabolic diseases such as diabetes is growing very fast in China,” says Ning. “We must look for the best ways to prevent and treat diabetes, both so it is effective and so that the cost of treatment can be lowered and rolled out across China.”

CCEMD research groups are conducting major studies on the mo-lecular mechanism of pancreatic beta cell expansion and compensation in response to different stimuli to find a remedy for beta cell loss in type 1 and type 2 diabetes.

Other areas of great interest include the molecular mechanisms un-derlying metabolic disorders in the liver, in particular the function of nuclear receptors and adaptor proteins in the pathogenesis of nonalco-holic fatty liver disease and insulin resistance.

Traditional Chinese medicine (TCM) has long been used in diabetes treatment in China, and the center has been driving TCM experiments since the 1980s. CCEMD scientists have found evidence supporting the benefits of ingredients such as berberine, Panax ginseng, and androgra-pholide for treating diabetes and are creating a storage bank of TCM molecular ingredients and exploring ways to incorporate these into treatment regimens.

CCEMD is pioneering both basic and translational science, housing research teams dedicated to studying endocrine tumors, diabetes, and obesity, among other areas.

Key Research Areas

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An International Player

One of the major focuses of CCEMD is conducting massive cohort studies, which are of fundamental importance to new discoveries within translational medicine.

“We not only focus on the basic understanding of diseases, but also put the results back into our clinical work,” says Ning. “Many labs in the U.S. are like this, but our center is the only one in China.”

“We have several huge cohort studies on type 2 diabetes and endo-crine tumors, each with a large number of research subjects,” he ex-plains, “and we are keen to share our findings with researchers across the world.”

CCEMD has conducted three major epidemiological studies in the last five years. In June 2008, 40,000 participants were recruited as part of the Shanghai Community Metabolic Diseases Survey investigating the influence of urbanization on the prognoses of metabolic diseases in sub-jects over the age of 40.

The 2010 China Noncommunicable Disease Surveillance study was set up to assess and monitor the prevalence of and risk factors for non-communicable diseases in Chinese adults. The team recruited 98,658 participants over the age of 18 in 162 cities across mainland China and has recently published a paper based on the survey’s findings in the Jour-nal of the American Medical Association.

A third noteworthy study is the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal Study (REACTION). Set up in 2011, the multicenter prospective cohort recruited a total of 259,657 individuals aged 40 and over from 25 research centers and will follow up with them every five years.

As part of the large Shanghai Community Metabolic Diseases Survey, the center created an additional prospective-cohort to study whether Bisphenol A (BPA) exposure affects human health. “In 2009, CCEMD recruited 3,423 middle-aged and elderly subjects and followed them for four years. The cross-sectional analysis revealed a significant association between BPA-exposure levels and the prevalence of metabolic disor-ders, including diabetes, obesity, and thyroid dysfunctions.”

AdiposeTissue

Clinical Studies

Founded in 1950 by a team of four doctors, the Shanghai Clinical Center for Endocrine and Metabolic Diseases was one of the earliest endocrine and metabolic disease units in China. It has grown to become the most important clinical, research, and education center in the field of endocrine and metabolic diseases in the country. Ranked first in the “Comprehensive Ranking of China’s Best Hospitals” report from the Hospital Management Insti-tute of Fudan University in 2011 and 2012, the center is the only National Glycohemoglobin Standardization Program (NGSP) certified and College of American Pathologists (CAP)-accredited clinical laboratory for endocrine and metabolic diseases in China.

College of American Pathologists-Accredited Lab Pancreatic Islets

Doctors and Nurses at CCEMD

http://english.shsmu.edu.cn

Patient Statistics •280,000 out-patient consultations •16,200 out-patient follow-up visits (12 specialized disease clinics every week)•5,210 in-patient consultations •19 clinical trials

2012 Data

Professor Guang Ning is an advocate of global collaboration, and the CCEMD enjoys ex-cellent relationships with many international hospitals and research facilities, including the MD Anderson Cancer Center in the United States, where some of the center’s young staff members have been sent during their postdoctoral training.

Every two years, the center hosts the International Ruijin Endocrine and Metabolic Forum, where they invite world-renowned experts to discuss research, treatment, and future developments in the field of endocrinology and metabolism.

“As our center grows, we should become the leader in endocrine and metabolic disease, and create clinical therapy and diagnostic techniques that allow us to take care of patients at a very high level—and hopefully attract doctors and students from all over the world to participate in our research,” says Ning.

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Prevalence of Diabetes Among Adults in China

Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The journal has established a specific “Asia Track” to further this endeavor by bringing to the international community articles which focus on aspects of diabetes of particular relevance to Asia. The Editorial team is international with a unique mix of Asian and Western participation.

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