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  • 1. THE JOURNALS of The Endocrine Society World leaders in diabetes, endocrinology & metabolism Renew Now or Begin Your Free Trial! Endocrine Reviews An In-Depth, Enduring Resource Free Trial Offer for New Institutional Subscribers— Each issue presents in-depth reviews on clinical and Get 3 months of free online access to any of our four journals. research topics in endocrinology, including diabetes, Offer expires June 30, 2009. Available to new institutional thyroid disorders, pediatric endocrinology, growth subscribers and qualified former institutional subscribers. factors and reproductive medicine. Its impact factor Two-for-One Offer for Institutional Subscribers— of 18.493 was the highest among all endocrinology and Endocrinology and Molecular Endocrinology are sold as a metabolism journals in 2007. bundle, giving you the value of two high impact journals at a discounted rate. Endocrinology & Molecular Endocrinology Essential Resources for Researchers Tailor-Made Pricing for Institutional Subscribers— Endocrinology has defined the science of endocrinology for y Subscription prices for institutional and multi-site subscribers over 90 years, publishing a broad spectrum of the highest will be based on the type of organization (tiered pricing). quality basic research related to the endocrine glands and For more information about these offers or a tailor-made price their hormones. quote, contact societyservices @ endo-society.org. Molecular Endocrinology focuses on how receptors and hormones signal to regulate gene expression, The Journal of Clinical Endocrinology development, physiological function and disease. & Metabolism With impact factors of 5.045 and 5.337, both The Must-Read Clinical Journal in the Field Endocrinology and Molecular Endocrinology are y In-depth coverage of the latest developments in diabetes, ranked among the top 5% of all biomedical journals. obesity, thyroid disorders, reproductive endocrinology, growth hormone therapy and other critical areas of endocrinology and metabolism. © 2009 The Endocrine Society ® View subscription information at www.endo-society.org/journals ANNOUNCING THE 2009 ELECTION RESULTS The Endocrine Society’s Nominating Committee is pleased to announce the results of the 2009 Election that concluded on March 9, 2009. Congratulations to the following Society leaders who will assume their new positions at the Society’s Congratulations! Annual Business Meeting on June 13, 2009, during ENDO 2009 in Washington, DC. President-Elect (Basic Scientist) Kelly E. Mayo, Ph.D. Vice President (Clinical Scientist) Nannette F. Santoro, M.D. Secretary Treasurer-Elect John C. Marshall, M.D., Ph.D. Council (Physician-in-Practice seat) Susan J. Mandel, M.D. Council (At Large seat) Jennifer L. Larsen, M.D.
  • 2. The History of Endocrinology comes alive in the Clark T. Sawin Memorial Library Visit the online library www.endo-society.org/about/sawin. Consult with the librarian. View the numerous oral/video histories. Make a contribution to the ongoing library endowment. The Clark T. Sawin Memorial Library boasts thousands of written works and rare artifacts dating back over 100 years—along with a growing collection of oral and video histories. You’re invited to nominate key thought leaders to record their experiences and expand this anthology. Please consider making a contribution to the Clark T. Sawin Memorial Library endowment. Your gift will ensure endocrinology takes its proper place in the annals of medicine for generations to come. To discuss your tax-deductible gift or nominate a thought leader, contact Anna Meenan at 301.951.2619 or ameenan@endo-society.org. © 2009 The Endocrine Society®
  • 3. T R A N S L A T I O N A L H I G H L I G H T S F R O M E N D O C R I N O L O G Y A b s t r a c t s The following abstracts from Endocrinology have been selected by the editors of JCEM as being particularly relevant to readers interested in translational science. Minireview: Hormonal and Metabolic Mechanisms of Diabetes Remission after Gastrointestinal Surgery Joshua P. Thaler and David E. Cummings (Endocrinology, published April 16, 2009, 10.1210/en.2009-0367) ABSTRACT Bariatric surgery is the most effective available treatment for obesity. The most frequently performed operation, Roux-en-Y gastric bypass (RYGB), causes profound weight loss and ameliorates obesity-related comorbid conditions, especially type 2 diabetes mellitus (T2DM). Approximately 84% of diabetic patients experience complete remission of T2DM after undergoing RYGB, often before significant weight reduction. The rapid time course and disproportional degree of T2DM improvement after RYGB com- pared with equivalent weight loss from other interventions suggest surgery-specific, weight-independent effects on glucose homeostasis. Potential mechanisms underlying the direct antidiabetes impact of RYGB include enhanced nutrient stimulation of lower intestinal hormones (e.g. glucagon-like peptide-1), altered physiology from excluding ingested nutrients from the upper intestine, compromised ghrelin secretion, modulations of intestinal nutrient sensing and regulation of insulin sensitivity, and other changes yet to be fully characterized. Research aimed at determining the relative importance of these effects and identifying additional mechanisms promises not only to improve surgical design but also to identify novel targets for diabetes medications. Minireview: Endocannabinoids and Their Receptors as Targets for Obesity Therapy Annette D. De Kloet and Stephen C. Woods (Endocrinology, published April 16, 2009, 10.1210/en.2009-0046) ABSTRACT As the incidence of obesity continues to increase, the development of effective therapies is a high priority. The endocannabinoid system has emerged as an important influence on the regulation of energy homeostasis. The endocannabinoids anandamide and 2-arachidonoylglycerol act on cannabinoid receptor-1 (CB1) in the brain and many peripheral tissues causing a net anabolic action. This includes increasing food intake, and causing increased lipogenesis and fat storage in adipose tissue and liver. The endocan- nabinoid system is hyperactive in obese humans and animals, and treating them with CB1 antagonists causes weight loss and improved lipid and glucose profiles. Although clinical trials with CB1 antagonists have yielded beneficial metabolic effects, concerns about negative affect have limited the therapeutic potential of the first class of CB1 antagonists available. 2208 jcem.endojournals.org J Clin Endocrinol Metab. June 2009, 94(6):2208 –2209
  • 4. J Clin Endocrinol Metab, June 2009, 94(6):2208 –2209 jcem.endojournals.org 2209 Pegylated Leptin Antagonist Is a Potent Orexigenic Agent: Preparation and Mechanism of Activity Eran Elinav, Leonora Niv-Spector, Meirav Katz, Tulin O. Price, Mohammed Ali, Michal Yacobovitz, Gili Solomon, Shay Reicher, Jessica L. Lynch, Zamir Halpern, William A. Banks, and Arieh Gertler (Endocrinology, published April 2, 2009, 10.1210/en.2008-1706) ABSTRACT Leptin, a pleiotropic adipokine, is a central regulator of appetite and weight and a key immunomodulatory protein. Although inborn leptin deficiency causes weight gain, it is unclear whether induced leptin deficiency in adult wild-type animals would be orexigenic. Previous work with a potent competitive leptin antagonist did not induce a true metabolic state of leptin deficiency in mice because of a short circulating half-life. In this study, we increased the half-life of the leptin antagonist by pegylation, which resulted in significantly increased bioavailability and retaining of antagonistic activity. Mice administered the pegylated antag- onist showed a rapid and dramatic increase in food intake with weight gain. Resulting fat was confined to the mesenteric region with no accumulation in the liver. Serum cholesterol, triglyceride, and hepatic aminotransferases remained unaffected. Weight changes were reversible on cessation of leptin antagonist treatment. The mechanism of severe central leptin deficiency was found to be primarily caused by blockade of transport of circulating leptin across the blood-brain barrier with antagonisms at the arcuate nucleus playing a more minor role. Altogether we introduce a novel compound that induces central and peripheral leptin deficiency. This compound should be useful in exploring the involvement of leptin in metabolic and immune processes and could serve as a therapeutic for the treatment of cachexia.
  • 5. T R A N S L A T I O N A L H I G H L I G H T S F R O M M O L E C U L A R E N D O C R I N O L O G Y A b s t r a c t s The following abstracts from Molecular Endocrinology have been selected by the editors of JCEM as being particularly relevant to readers interested in translational science. MBX-102/JNJ39659100, a Novel Peroxisome Proliferator Activated Receptor- Ligand with Weak Transactivation Activity Retains Full Anti-Diabetic Properties in the Absence of Side Effects Francine M. Gregoire, Fang Zhang, Holly J. Clarke, Thomas A. Gustafson, Dorothy D. Sears, Svetlana Favelyukis, James Lenhard, Dennis Rentzeperis, L. Edward Clemens, Yi Mu, and Brian E. Lavan (Mol Endocrinol, published April 23, 2009, 10.1210/me.2008-0473) ABSTRACT MBX-102/JNJ39659100 (MBX-102) is in clinical development as an oral glucose lowering agent for the treatment of type 2 diabetes. MBX-102 is a non-thiazolidinedione (TZD) selective partial agonist of PPAR- that is differentiated from the TZDs structurally, mechanistically, pre-clinically and clinically. In diabetic rodent models, MBX-102 has insulin sensitizing and glucose lowering properties comparable to TZDs without dose-dependent increases in body weight. In vitro, in contrast with full PPAR- agonist treatment, MBX-102 fails to drive human and murine adipocyte differentiation and selectively modulates the expression of a subset of PPAR- target genes in mature adipocytes. Moreover, MBX-102 does not inhibit oteoblastogenesis of murine mesen- chymal cells. Compared to full PPAR- agonists, MBX-102 displays differential interactions with the PPAR- ligand binding domain (LBD) and possesses reduced ability to recruit coactivators. Interestingly, in primary mouse macrophages, MBX-102 displays enhanced anti-inflammatory properties compared to other PPAR- or / agonists suggesting that MBX-102 has more potent transrepression activity. In summary, MBX-102 is a selective PPAR- modulator with weak transactivation but robust transrepres- sion activity. MBX-102 exhibits full therapeutic activity without the classical PPAR- side effects and may represent the next generation insulin sensitizer. Fasting-Induced Hepatic Production of DHEA is Regulated by PGC-1 , ERR and HNF4 Linda L. Grasfeder, Stephanie Gaillard, Stephen R. Hammes, Olga Ilkayeva, Christopher B. Newgard, Richard B. Hochberg, Mary A. Dwyer, Ching-yi Chang, and Donald P. McDonnell (Mol Endocrinol, published April 23, 2009, 10.1210/me.2009-0024) ABSTRACT The transcriptional coactivator PGC-1 is involved in the coordinate induction of changes in gene expression in the liver that enable a homeostatic response to alterations in metabolic state, environmental cues and nutrient availability. In exploring the specific pathways under PGC-1 regulation in the liver, we have made the surprising observation that this coactivator can induce the expression of CYP11A1 and CYP17A1, key rate limiting enzymes involved in the initial steps of steroidogenesis. Both of these enzymes function to produce C19-steroids, converting cholesterol into pregnenolone, and then to DHEA. ERRa mediates PGC-1 ’s induction of CYP11A1 and binds within the first intron of the CYP11A1 gene. Both ERRa and HNF4a are required for PGC-1 - mediated induction of CYP17A1 and specific binding sites for these receptors have been identified in the regulatory regions of this gene. The potential physiological significance of these observations was highlighted in rats where fasting induced hepatic expression of PGC-1 and CYP17A1 and was associated with an increase in hepatic levels of DHEA. These data suggest that DHEA could be playing a role as an intracellular signaling molecule involved in modulating hepatic activity in response to fasting conditions. 2210 jcem.endojournals.org J Clin Endocrinol Metab. June 2009, 94(6):2210 –2211
  • 6. J Clin Endocrinol Metab, June 2009, 94(6):2210 –2211 jcem.endojournals.org 2211 Characterization of ASC-2 as an Anti-Atherogenic Transcriptional Coactivator of Liver X Receptors in Macrophages Geun Hyang Kim, Keunhee Park, Seon-Yong Yeom, Kyung Jin Lee, Gukhan Kim, Jesang Ko, Dong-Kwon Rhee, Young Hoon Kim, Hye Kyung Lee, Hae Won Kim, Goo Taeg Oh, Ki-Up Lee, Jae W. Lee, and Seung-Whan Kim (Mol Endocrinol, published April 2, 2009, 10.1210/me.2008-0308) ABSTRACT Activating signal cointegrator-2 (ASC-2) functions as a transcriptional coactivator of many nuclear receptors and also plays im- portant roles in the physiology of the liver and pancreas by interacting with liver X receptors (LXRs), which antagonize the development of atherosclerosis. This study was undertaken to establish the specific function of ASC-2 in macrophages and atherogenesis. Intriguingly, ASC-2 was more highly expressed in macrophages than in the liver and pancreas. To inhibit LXR-specific activity of ASC-2, we used DN2, which contains the C-terminal LXXLL motif of ASC-2 and thereby acts as an LXR-specific, dominant- negative mutant of ASC-2. In DN2-overexpressing transgenic (Tg) macrophages, cellular cholesterol content was higher and cholesterol efflux lower than in control macrophages. DN2 reduced LXR ligand-dependent increases in the levels of ABCA1, ABCG1, and apoE transcripts, as well as the activity of luciferase reporters driven by the LXR response elements (LXREs) of ABCA1, ABCG1, and apoE genes. These inhibitory effects of DN2 were reversed by overexpression of ASC-2. Chromatin immunoprecipitation analysis demonstrated that ASC-2 was recruited to the LXREs of the ABCA1, ABCG1, and apoE genes in a ligand-dependent manner and that DN2 interfered with the recruitment of ASC-2 to these LXREs. Furthermore, low density lipoprotein receptor (LDLR)-null mice receiving bone marrow transplantation from DN2-Tg mice showed accelerated atherogenesis when administered a high-fat diet. Taken together, these results indicate that suppression of the LXR-specific activity of ASC-2 results in both defective cho- lesterol metabolism in macrophages and accelerated atherogenesis, suggesting that ASC-2 is an anti-atherogenic coactivator of LXRs in macrophages.
  • 7. Employment Opportunities MAINE: Central Maine Medical Center’s multi-specialty group practice is seeking a third BC/BE endocrinologist to join the endocrinology section of this growing practice. This exciting opportunity offers a competitive salary and excel- lent benefits package. Enjoy the professional challenge of- Discover this beautiful mountainous region with 50+ lakes, a mild four- fered in a sophisticated medical community along with the season climate (averaging 260 sunny days)…the perfect formula for wonderful recreational opportunities and quality of life in unlimited year-round recreational enjoyment. Maine. For more information, please send CV to Julia Lau- Spokane, Washington, is a progressive and vibrant place! This fine community offers regional arts organizations, excellent schools, four ver, Central Maine Medical Center, 300 Main Street, universities, and affordable housing in friendly neighborhoods. Lewiston, ME 04240. Call: 800/445-7431; fax: 207/795-5696; or Great practice opportunity available for a BC/BE adult endocrinologist to email: jlauver@cmhc.org. Not a J-1 opportunity. join our prominent and respected endocrinology team. Our consultative practice offers a full service ADA certified ED Center with RD’s and CDE’s; participation and support with research projects; and teaching GROWING ENDOCRINOLOGY PRACTICE/MANCHESTER, opportunities. Rockwood, a physician owned/directed multi-specialty NEW HAMPSHIRE: Elliot Health System seeks an addi- group provides a collegial practice environment, sophisticated on- site Imaging Services, laboratory, DXA, nuclear medicine services, and tional BE/BC endocrinologist to join our growing practice. electronic health record. We offer an attractive benefit and compensation The preferred must have a passion for clinical excellence. package with early shareholder status. We provide specialized care in diabetes, thyroid and para- For additional details contact: thyroid conditions, osteoporosis, pituitary and adrenal Colleen Mooney, Physician Recruiter 1-800-776-4048 / practice@rockwoodclinic.com disorders, polycystic ovary syndrome, and other hormone conditions. Located in Manchester, New Hampshire, the fully Meet us during the AACE and Endo Society Meetings! equipped office includes ultrasound machine that allows ul- trasound guided thyroid biopsies on site. We are proud to offer an excellent compensation and benefit package. The www.rockwoodclinic.com / www.visitspokane.com Elliot Health System invites you to explore the rich heritage, breathtaking beauty and four-season attractions of (tax-free) New Hampshire. Contact Selena Dickherber at 800-678-7858 x63755 or email selenad@elliotphysicians.org. ID#31697CF. ENDOCRINOLOGIST COOPER UNIVERSITY HOSPITAL, CAMDEN, NEW JERSEY Excellent opportunity to join the growing Endocrine division of a 180-member Department of Medicine multi-specialty faculty group of an academic medical center with an excellent reputation. The Department of Medicine of Cooper University Hospital, is affiliated with the University of Medicine and Dentistry of New Jersey (UMDNJ)/ Robert Wood Johnson Medical School (RWJMS) in Camden, New Jersey. We are seeking a full time faculty physician in the Division of Endocrinology and Metabolism. Cooper University Hospital is a 570-bed, tertiary care facility, located one-mile from Philadelphia, serves southern New Jersey and the Delaware Valley. Services provided by the endocrine division include inpatient and outpatient services at Cooper University Hospital. A large division practice location is also maintained minutes from Philadelphia, in Cherry Hill, NJ. Cooper/ RWJMS is experiencing exponential growth in its clinical practice and clinical research programs. The successful candidate will be an experienced clinical and academic physician with a demonstrated commitment to patient care and education of medical stu- dents and residents. There is ample opportunity for collaboration in major clinical research, including NIH diabetes research. Candidates are eligible for faculty appointments at UMDNJ/Robert Wood Johnson Medical School. Salary will be commensurate with qualifications and experience. To apply in complete confidentiality, please forward CV, or requests for additional information via e-mail to: Haddad-Ghada@cooperhealth.edu. Principals only. No Third Party Inquiries Accepted. Equal Opportunity Employer M/F/D/V. 2212 jcem.endojournals.org J Clin Endocrinol Metab. June 2009, 94(6):2212–2213
  • 8. J Clin Endocrinol Metab, June 2009, 94(6):2212–2213 jcem.endojournals.org 2213 S ET YOUR SIGH T S H IGH ENDOCRINOLOGY Geisinger Health System seeks two Endocrinologists to join its growing program in Endocrinology, Diabetes and Metabolism. About the positions: About the positions: Endocrinologist, Geisinger Medical Center, Danville, PA Clinical Endocrinologist, State College, PA—Home to Penn State University • Provide outpatient/inpatient care in the group practice academic setting of our • Exciting opportunity to develop an endocrinology practice in this thriving, tertiary/quaternary care hospital, resident education and help develop quality multi-specialty group practice in a progressive university town programs • Provide outpatient care and inpatient consultations • Department has full-time Dietitian, CDE & Nurse CDE on site • Cross-coverage supported by our Hospitalist Program • Clinical research opportunities available Geisinger Health System: • Is a physician-led, academic, multi-specialty group practice • Provides care to nearly one-third of Pennsylvania, almost 3 million residents • Utilizes a mature, fully integrated electronic health record, connecting a comprehensive network of 40 community medical groups and more than 700 Geisinger primary and specialty physicians • Includes 75 medical and surgical specialties and hosts 31 accredited residency and fellowship programs For more information about either of these positions, please contact John Kennedy, MD C/O Kathy Kardisco, Physician Recruiter, at 1-800-845-7112, email: kkardisco@geisinger.edu or visit www.Join-Geisinger.org/798/Endocrinology W E L C O M I N G A N D W O R L D - C L A S S Endocrine News classifieds are your “... an environment that is both caring What They’re Saying About Winthrop... BEST recruiting tool! and academically enriching.” Your ad is seen by Winthrop-University Hospital’s Division of Adult Endocrinology, 27,000 Endocrine Diabetes and Metabolism has close association with Winthrop-University Hospital Diabetes Education Center and is leading a hospital wide Society journal effort to establish an institute for basic Diabetes research. subscribers, members, fellows, students, and ACADEMIC meeting attendees. We offer FREE ENDOCRINOLOGIST color, FREE Web site posting and 10% Division of Adult Endocrinology, off when you advertise in Endocrine Diabetes and Metabolism Applicants are requested for an academic endocrinologist to join our News and a Society journal. staff of five full time faculty. We are seeking individuals with current research interests in Diabetes, Obesity, Diseases of the Thyroid, and Metabolic bone diseases. The applicant must have the desire, abili- Recruiting endocrinologists ty and accomplishments to pursue a challenging career in teaching, research and faculty practice. Salary will be commensurate with just got easier! experience and career accomplishments. Winthrop-University Hospital is affiliated with SUNY at Stony Brook. Winthrop is located in suburban Long Island, 30 miles from NYC on the LIRR, just one block from the Mineola train station. Please contact Contact Christine Whorton at: Dr. Lawrence Shapiro, 516 663-4775; lshapiro@winthrop.org placement@endo-society.org Visit us at: www.winthrop.org EOE-m/f/d/v Or call: 800-361-3906. Visit our Web site at www.endo-society.org/placementservices Institute for Institute for Institute for Cancer Care Digestive Care Family Care Institute for Institute for Institute for Institute for Heart Care Neurosciences Lung Care Specialty Care
  • 9. Board Review “Don’t miss this year’s Board Review! Not only will you have the opportunity to interact with and ask questions of some the most respected experts in endocrinology, you will get immediate feedback of your performance 09 in all key areas of Endocrinology, which will help you in your preparation for the Board Examination, even after you’ve left the course.” What: When: Where: Who Attends: Featured Faculty: Register: Register for The Endocrine Society’s Board Review and receive a discounted rate for ESAP 09 and for CEU 2009.
  • 10. NEWS E N D O C R I N O L O G Y & M E T A B O L I S M N E W S Endocrine Discovery therapy found similar reductions in depres- sion among these therapies, but a worsen- In a longitudinal cohort study of 16,667 ing of mood in 13.9% of all patients. (Obesity older patients with type 2 diabetes fol- [May 2009] 17(5):1009) lowed for up to 27 years, patients with sin- gle or multiple episodes of hypoglycemia Night eating was found to be 2.5 and 2.8 had a graded increase risk of dementia with times more common in obese men and increasing numbers of hypoglycemic events women compared to normal weight con- (for 3 or more episodes the hazard ratio was 1.94; trols and associated with binge eating and 95% CI, 1.42–2.64), with an attributable risk of sleep-related problems, according to a study dementia between individuals with and without of 21,741 Swedish twins aged 20 – 47 years old. a history of hypoglycemia of 2.39% per year (Obesity [May 2009] 17(5):1050) (95% CI, 1.72%–3.01%). (JAMA [April 15, 2009] 301(15):1565) Oxytocin was found to be a direct anabolic regulator of bone mass, based on comple- In a 1-year randomized, double-blind study of mentary genetic and pharmacologic ap- 5 mg intravenous zoledronic acid versus 5 mg proaches, pointing to possible implications for oral risedronate for both prevention and osteoporosis therapy. (Proc Natl Acad Sci USA treatment of glucocorticoid-induced osteo- [April 28, 2009] 106(17):7149) porosis, zoledronic acid was superior to risedronate in increasing lumbar spine bone mineral density, but there were more adverse Pyrvinium pamoate and harmol hydrochlo- events in patients given zoledronic acid as a result of ride, two non-ligand inhibitors of androgen transient symptoms during the first 3 days after in- receptor activity, were found to be likely fusion. (Lancet [April 11, 2009] 373(9671):1253) therapeutic candidates for such diseases as hirsutism, benign prostatic hypertrophy, A genetic risk score (GRS), calculated on the and prostate cancer. (Proc Natl Acad Sci USA basis of 10 polymorphisms in 9 loci, was [April 28, 2009] 106(17):7233) found to confer increasing risk of type 2 diabetes with each quintile of GRS, espe- Aspirin usage of 325 mg every other day cially in individuals with BMI > 30 kg/m2, was linked to a lower risk of diabetes, ac- and a positive family history of diabetes, but cording to a 22-year longitudinal study of 22,071 addition of the GRS to a model of conventional healthy male physicians. (Am J Med [April 2009] risk factors improved discrimination by only 1%, 122(4):374) in a study of 2809 patients with type 2 diabetes and 3501 healthy controls. (Ann Intern Med Examination of 70,781 men and women [April 21, 2009] 150(8):541) aged 66 years or older with stages I through III breast cancer found that those with Mice lacking the intestinal lipid synthesis breast cancer and diabetes are at increased enzyme acyl CoA:monoacylglycerol acyl- risk of chemotherapy-related toxicities and transferase-2 and fed a high-fat diet were have higher all-cause mortality than those protected against developing obesity, glu- who just had cancer alone. (J Clin Oncol [May cose intolerance, hypercholesterolemia, 1, 2009] 27(13):2170) and fatty livers, suggesting that inhibition of this enzyme may be a useful treatment strategy Rosuvastatin significantly reduced the oc- NEWS for obesity and other metabolic diseases associ- currence of symptomatic venous thrombo- ated with excessive fat intake. (Nat Med [pub- embolism, according to a clinical trial of 17,802 lished online March 15, 2009]) healthy men and women who received either a 20 mg daily dose of the drug or placebo. (N Engl A 1-year randomized trial among 194 obese J Med [April 30, 2009] 360(18):1851) participants of lifestyle versus sibutramine A 10-year prospective analysis among 4883 Readers are encouraged to suggest items for Endocrinology and Metabolism News by email (sherman@endo-society.org). men and women 65 years or older revealed Submissions will be considered based on their significance and that even later in life, combined lifestyle timeliness. factors—including physical activity level, J Clin Endocrinol Metab, June 2009, 94(6):17A–20A jcem.endojournals.org 17A
  • 11. E N D O C R I N O L O G Y & M E T A B O L I S M N E W S “It’s interesting as an dietary habits, smoking habits, alcohol 1 had few symptoms, normal A1C, rare ke- use, and adiposity measures—are associ- tosis, and evidence for insulin production at indication that this ated with a lowered incidence of new- the time of diagnosis, suggesting that inter- tissue is still present onset diabetes mellitus. (Arch Intern Med mittent screening and follow-up of islet autoan- [April 27, 2009] 169(8):798) tibody-positive subjects may allow for early diag- and chemically active nosis and that sole screening of A1C may not be Combined with lifestyle modification, vo- adequate. (Diabetes Care [May 2009] 32(5):769) in adult humans,” glibose, an -glucosidase inhibitor, reduced said Rudolph Leibel, the development of type 2 diabetes in high- Examination of 652 women with type 1 di- risk Japanese individuals with impaired glucose abetes revealed that female sexual dysfunc- M.D., about the tolerance. (Lancet [published online April 22, tion was common, with depression being 2009]) the major predictor for this disorder. (Dia- recent series of betes Care [May 2009] 32(5):780) articles verifying the A randomized controlled trial of 1123 par- ticipants with type 2 diabetes and no symp- Metabolic profiling of obese versus lean humans existence of brown toms of coronary artery disease found that and examination of rats fed on high-fat, high-fat adipose fat in adults. cardiac event rates were low in this patient with supplemented branched-chain amino acid group and were not significantly reduced (BCAA), or standard chow, revealed that BCAA by MRI screening for myocardial ischemia. contributes to the development of obesity- (JAMA [April 15, 2009] 301(15):1547) associated insulin resistance. (Cell Metab [April 8, 2009] 9:311) According to a retrospective cohort study of 7820 patients hospitalized with acute Two new studies indicated that bisphos- myocardial infarction and hyperglycemic phonates may not raise the risk of esopha- on admission, spontaneous development geal cancer. (N Engl J Med [April 23, 2009] of hypoglycemia was linked to increased 360(17):1789) mortality whereas iatrogenic hypoglycemia after insulin therapy was not. (JAMA [April 15, 2009] 301(15):1556) A prospective observational study of 4006 men and women showed that daily nitrate use was associated with increased bone A prospective phase I/II study of 23 patients mineral density at the hip and spine of both with newly diagnosed type 1 diabetes mel- groups. (Osteoporos Int [May 2009] 20:737) litus, aged 13–31 years, who underwent au- tologous nonmyeloablative hematopoietic stem cell transplantation found that these Brown Adipose Tissue Found in Adults patients had increased C-peptide levels and Three recent studies in The New England Jour- that most achieved insulin independence nal of Medicine confirmed the presence of ener- with good glycemic control. (JAMA [April 15, gy-burning brown adipose tissue in adults, pav- 2009] 301(15):1573) ing the way for exploiting this fat in weight control. A study of 69 metformin-treated patients Once thought only to exist in small mammals with type 2 diabetes who were randomly and newborns, and then to completely dwindle treated for 1 year with exenatide or insulin upon human adulthood, brown fat differs from glargine found that exenatide significantly white fat in its appearance and function. For one, NEWS improved -cell function compared to insu- the presence of more mitochondria lends to its lin glargine. Once treatment with either drug brown color. Also, these cells contain multiple was stopped however, -cell function and gly- lipid droplets as opposed to the one fat lipid drop- cemic control returned to pretreatment values, let seen in regular fat. Whereas white fat primar- suggesting that ongoing treatment with either of ily stores fat, brown fat helps to regulate body these drugs is necessary. (Diabetes Care [May temperature by non-shivering thermogenesis. 2009] 32(5):762) Mounting evidence over the years suggests brown fat’s presence in adults. Brown fat depots Patients diagnosed with type 1 diabetes appeared in adult patients with catecholamine- through the Diabetes Prevention Trial-Type secreting tumors such as pheochromocytomas 18A jcem.endojournals.org J Clin Endocrinol Metab. June 2009, 94(6):17A–20A
  • 12. NEWS E N D O C R I N O L O G Y & M E T A B O L I S M N E W S and paragangliomas. Furthermore, radiologists reduced activity of brown adipose tissue will be “The tide is rising reported the presence of increased “noise” in one of the factors causing obesity remains to be their 18F-fluorodeoxyglucose positron-emission seen.” He further pointed out that thyroid hor- and appears to be tomographic and computed tomographic (PET/ mone and adrenergic agents stimulate this tis- lifting all boats, but CT) scans in the neck, chest, and abdomen—all sue. Dr. Garg suggested that a thyroid hormone areas where brown fat lurks in infants— during analogue or adrenergic receptor stimulating there are still many the winter months that would dampen when the agent may be developed that acts solely on patients were placed in warmer environments. brown fat and not on other tissues. (N Engl J Med racial and ethnic Exploiting the latter phenomena, all three [April 9, 2009]360 (15):1500; N Engl J Med [April minorities and adults NEJM articles prospected for brown fat. Wouter 9, 2009] 360(15):1509; N Engl J Med [April 9, van Marken Lichtenbelt, Ph.D., of the University 2009] 360(15):1518) of lower of Masstricht in The Netherlands, and his group, socioeconomic status compared PET/CT scans in 24 men, who were Medicare Linked to Improved either lean or obese, during exposure to cold Cardiovascular and Diabetes Outcomes being left behind,” temperature and room temperature conditions. They found that the leaner men had increased More Americans may be in control of their car- said J. Michael amounts of more active brown adipose tissue diovascular disease and diabetes, but racial, eth- McWilliams, M.D., than those who were obese, and that this activity nic, and socioeconomic differences continue to disappeared in individuals at room temperature. persist, calling to question the idea of universal or Ph.D., on his study Similarly, C. Ronald Kahn, M.D., of Harvard expanded health care coverage for adults before they can receive Medicare coverage. showing that near Medical School in Boston, and his colleagues pored over PET/CT scans of nearly 2000 patients Racial and ethnic minorities and less educated universal Medicare and found that more women than men had pos- adults are more likely to be uninsured or under- itive scans showing active brown fat—7.5% vs. insured, making it less likely that they receive ba- coverage improves 3.1% or a ratio of 2:1—and that the amount sic clinical services for these conditions. Essen- tially these groups may end up playing a waiting cardiovascular and declined with age. The third group, led by Sven Enerback, M.D., ¨ game in which they address their health issues diabetes treatment. Ph.D., at the University of Goteborg, Sweden, ¨ once they reach age 65 and are eligible for Medi- used PET/CT scans to pinpoint brown adipose care. While this may work for some, for others it tissue deposits in subjects exposed to cold, and may be too late. confirmed the tissue’s identity by looking at A recent study published in the Annals of Internal brown adipose tissue-specific genes such as un- Medicine used data from the 1999 –2006 National coupling protein 1. Health and Nutrition Examination Survey to mea- Researchers and clinicians remain cautiously sure changes in disease control over time as well as optimistic about this finding. “It’s interesting as the possible association of improved control with an indication that this tissue is still present and near-universal Medicare coverage after age 65. Us- chemically active in adult humans,” said Rudolph ing a serial cross-sectional study design, the authors Leibel, M.D., co-director of the Naomi Berrie Di- focused on people who reported having diabetes, abetes Center at Columbia University. “Whether hypertension, coronary heart disease, or stroke. this tissue will be exploitable as a therapeutic de- The authors defined disease control in the follow- vice will need to be readdressed,” he said, adding ing fashion: hemoglobin A1C levels 7% among that previously, investigators had reported that patients with diabetes; average blood pressure overfed rats had increased activity of brown ad- 140/90 mm Hg among those with hypertension; ipose tissue, linking this fat not only to temper- and total cholesterol levels 5.2 mmol/L (200 mg/ NEWS ature regulation, but to calorie burning. The dL) among those with diabetes, coronary heart dis- pharmaceutical industry tried to activate thermo- ease, or stroke. genesis through -agonists in humans, but lim- Over these 8 years, the authors found that ited efficacy and elevations in blood pressure led disease control measures improved overall to abandonment of this approach to obesity from 10% to 21%. However, improvements in treatment. disease control were not associated with dis- Abhimanyu Garg, M.D., internal medicine pro- cernable reductions in racial, ethnic, or socioeco- fessor at the Center for Human Nutrition in The nomic differences in blood pressure or glyce- University of Texas Southwestern Medical Center mic control. An 8% difference was seen in at Dallas, concurred: “Whether the lack of it or hypertension control rates between white and J Clin Endocrinol Metab, June 2009, 94(6):17A–20A jcem.endojournals.org 19A
  • 13. E N D O C R I N O L O G Y & M E T A B O L I S M N E W S In an accompanying editorial in the same journal, Endocrinologists Ashwini R. Seghal, M.D., Director of the Center for Reducing Health Disparities, at Case Western Re- Walter Henry, former Chief of Endocrinology and serve University, Cleveland, Ohio, indicated a call to Head of the Department of Medicine at Howard action must be taken to expand health care cover- University Medical School, died at the age of 93. age, especially now that this is back on the current Among Dr. Henry’s many contributions were com- Administration’s political agenda. mitment to educating the African-American com- “As physicians and researchers, we have de- munity about diabetes, being the first black mem- scribed insurance-related health disparities and ber of the American Board of Internal Medicine, studied their mechanisms. Too seldom have we and two Bronze Stars for distinguished World War implemented interventions designed specifically II service in the U.S. Army Medical Corps. to reduce disparities,” he wrote. “A comprehen- sive universal health care intervention is desir- Walter Henry able, feasible, and necessary.” J. Maxwell McKenzie, former Chair of Medicine Harold Pollack, Ph.D., Chair of the Center for at the University of Miami Miller School of Medi- Health Administration Studies at the University of cine, died in Miami at age 81. Dr. McKenzie made Chicago, echoed the same sentiment. “The pivotal contributions to understanding the autoim- health reform debate often turns out to be a mune pathogenesis of Graves’ disease. He was a health financing debate. For instance, how do we past president of the American Thyroid Association. finance medical services? One of the issues that’s actually lost is would we be healthier if we cov- ered everyone?” (Ann Intern Med [April 21, 2009]150(8):505) J. Maxwell McKenzie Endocrine Practice African American adults, and a 15% difference The U.S. Food and Drug Administration an- in diabetes control rates was observed be- nounced a recall from Disetronic Medical Sys- tween high school graduates and nongradu- tems Inc. of the ACCU-CHEK® Spirit insulin ates. Gaps in glycemic control actually widened pumps, with serial numbers SN02119552 through between white and Hispanic adults. SN10006093, due to “up” and/or “down” button “The tide is rising and appears to be lifting all failures. (For more information, see www.fda.gov/ boats, but there are still many racial and ethnic oc/po/firmrecalls/disetronic04_09.html). minorities and adults of lower socioeconomic status being left behind,” said J. Michael McWil- liams, M.D., Ph.D., assistant professor at the De- Milestones in Endocrinology partment of Health Care Policy of Harvard, and 100 years ago, William Berkeley and S.P. Beebe the study’s lead author. showed that an extract of parathyroid gland could The numbers improved when McWilliams’ relieve hypocalcemic tetany in man. group analyzed the health disparities by age, spe- cifically before and after 65 years of age. Before age 65, African American patients had a 7.0 mm In the Journal 25 Years Ago Hg higher systolic blood pressure than white pa- Saad MF, Fritsche HA, Samaan NA. Diagnostic tients. But after this cut-off age, this difference and prognostic values of carcinoembryonic anti- NEWS was only 2.8 mm Hg. Similarly, the mean differ- gen in medullary carcinoma of the thyroid. J Clin ence in hemoglobin A1C levels between non- Endocrinol Metab 1984; 58:889 – 894. high school graduates and graduates was 0.6% before age 65 and 0.1% after age 65. “This implies that while current quality improve- “Peak calcitonin after pentagastrin stimulation ment may not be reducing disparities, we might remains the best diagnostic marker for medullary expect universal coverage to do so,” said Dr. Mc- thyroid cancer. However, CEA may be a better Williams. “Health disparities have existed for far too prognostic indicator, as it discriminated more ef- long in this country, and addressing uninsurance is ficiently between patients with and without me- likely to be a key part of the solution.” tastases.” 20A jcem.endojournals.org J Clin Endocrinol Metab. June 2009, 94(6):17A–20A
  • 14. Coming soon Discover how Endo Pharmaceuticals is taking testosterone therapy... ...further
  • 15. ESAP 2009 TWO OPTIONS FOR CAREER ADVANCEMENT ESAP ’09 & ESAP ’09 MOC—The most respected testing and training tools on the market. Based on the ABIM blueprint for endocrinology, diabetes and metabolism. ~ Case-based question, answer and discussion format. ~ ESAP ’09 has 160 case-based questions and ESAP ’09 MOC has 50 questions. Each question is associated with an Up-to-Date topic review. ~ Created by a distinguished panel of specialists to ensure that information is applicable to clinical practice. Seeking your initial ABIM certification or just looking for a refresher? ESAP ’09 is the tool for you. Ideal for fellows seeking initial certification or for practitioners seeking a review. Earn up to 50 AMA PRA Category 1 Credits™. 97% of questions are new relative to ESAP ’08. Available in print and web-based format. Certified after 1990 and seeking recertification? ESAP ’09 MOC is the tool for you. ESAP MOC is an ABIM-approved Self-Evaluation of Medical Knowledge Module in Endocrinology, Diabetes and Metabolism. 20 MOC credits toward Maintenance of Certification. All new questions. Earn up to 20 AMA PRA Category 1 Credits™. Available online only. ESAP 2009 MOC Fellows $199 — Member Discount $250 $200 For more information, please visit www.endo-society.org/education/esap/ Non-Members $350 $300 Earn up to 22 AMA PRA Category 1 CreditsTM s The Endocrine Society’s Clinical Practice Guidelines have been developed through a rigorous, multi-step, peer-review process to highlight key clinical content on the management of endocrine disorders. These nine guidelines are now available in a single volume collection that includes a 22 credit CME activity and 11 Hormone Foundation Patient Guides. Compendium of Clinical Practice Guidelines: $49* members and $59* non-members To order The Endocrine Society’s Compendium of Clinical Practice Guidelines, visit: www.endo-society.org/ custom_apps/Publication/index.cfm or call 888-363-6762 or fax 301-941-0257. *Price does not include shipping fee. © 2009 The Endocrine Society®
  • 16. The time is now! Register before July 16th and save Go to www.asbmr.org st ® ASBMR 31 Annual Meeting ASBMR 31st Annual Meeting September 11–15, 2009 Colorado Convention Center September 11–15, 2009 Colorado Convention USA Center Denver, CO, USA Denver, CO, A Review of Endocrinology: Diagnosis and Treatment September 8 – 12, 2009 Bethesda, Maryland Organizers: Smita Baid, M.D., Staff Clinician, NICHD, NIH Andrew Bauer, M.D., Program Director, Pediatric Endocrinology, NCC/USUHS David Harlan, M.D., Chief, Diabetes Branch, NIDDK, NIH Monica Skarulis, M.D., Senior Clinical Investigator, Division of Intramural Research, NIDDK, NIH Lee Weinstein, M.D., Chief Signal Transduction Section, Metabolic Diseases Branch, NIDDK, NIH Course Purpose: This review course is intended both for physicians who are preparing for the endocrinology subspecialty board examination and for physicians certified in endocrinology who wish to remain abreast of recent advances in the field. Objectives: To encourage an organized, efficient and cost-effective approach to the clinical, laboratory and radiologic diagnosis of endocrine disease, with emphasis on recent advances. After attending this activity, the participant should be able to: (1) evaluate and apply new treatments in the diagnosis of endocrine disorders, (2) look at the risks and benefits of each treatment. Tuition: $900 for physicians and $525 for residents, fellows, nurses and other medical professionals who verify their status. Registration, Accommodation, Course Information: www.faes.org Additional Information Contact: Carline Coote Phone: (301) 496-7975 Email: ccoote@mail.nih.gov PRESENTED BY: The Foundation for Advanced Education in the Sciences at the National Institutes of Health
  • 17. Coming Soon Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline Developed independently by a team of experts, evidence-based, Endocrine Society Clinical Guidelines and vetted through a rigorous, multi-step peer review process, the NOW AVAILABLE Endocrine Treatment of Transsexual Persons Guideline addresses: • Evaluation and Treatment of Adult Growth Hormone Deficiency • Diagnostic Procedures for the Treatment of Transsexuals • Testosterone Therapy in Adult Men • Treatment of Adolescent Transsexuals with Androgen Deficiency Syndromes • Hormonal Therapy for Transsexual Adults • Androgen Therapy in Women • Management of Thyroid Dysfunction • Adverse Outcome Prevention and Long-Term Care during Pregnancy & Postpartum • Surgery for Sex Reassignment • Evaluation and Treatment of Hirsutism in Premenopausal Women • The Diagnosis of Cushing’s Syndrome • Case Detection, Diagnosis, and Treatment of Patients with Primary Other Endocrine Society Guidelines COMING SOON Aldosteronism • Managing Patients Post-Bariatric • Hyperprolactinemia • Primary Prevention of Cardiovascular Surgery Disease and Type 2 Diabetes in • Hypertriglyceridemia Patients at Metabolic Risk • Continuous Glucose Monitoring • Prevention and Treatment of • Intensive Insulin Therapy of • Congenital Adrenal Hyperplasia Hospital Patients Pediatric Obesity • Evaluation and NEW • Pituitary Incidentaloma • Management of Anabolic Drugs Management of Adult for Osteoporosis in Men Hypoglycemic Disorders • Vitamin D & Bone To purchase the available guidelines visit: www.endo-society.org/guidelines/Current-Clinical-Practice-Guidelines.cfm. To view patient guides (companion pieces to the clinical guidelines), visit The Hormone Foundation’s Web site at www.hormone.org/public/patientguides.cfm.
  • 18. now available THE ENDOCRINE SOCIETY’S Compendium of Clinical Practice Guidelines This collection of clinical practice guidelines provides evidence-based content on key areas of interest in endocrinology. Each guideline developed independently by a team of experts was vetted through a rigorous, multi-step, peer-review process. The Compendium of Clinical Practice Guidelines offers the following features: weakness of the best available evidence using the GRADE system This valuable resource for reference and referral is essential for anyone involved in the care of patients with endocrine disorders. Order your copy today. Earn 22 CME Credits Compendium of Clinical Practice Guidelines $49* members $59* non-members Compendium of Clinical Practice Guidelines, https://www.endo-society.org/custom_apps/ Publication/index.cfm 888-363-6762 301-941-0257. *Price does not include shipping fee.
  • 19. Be among the best in the field. Become a member of The Endocrine Society and align yourself with endocrine thought leaders from around the world. With more than 14,000 members in over 100 countries, The Endocrine Society represents the entire endocrine community—scientists, educators and physicians—offering an unparalleled forum for cross-discipline collaboration. Membership in the Society unlocks an array of professional benefits including exclusive networking and educational opportunities; immediate access to peer-reviewed scientific journals; proactive advocacy efforts; ENDO, the world’s premier endocrinology meeting; essential practice resources and much more. For those dedicated to superior endocrine research and clinical care, membership is essential. Be among the best. Become a member today at www.endo-society.org/join.