The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 7 17a
Copyright © 2007 by The Endocrine Society
Endocrinology & Metabolism News, July 2007
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Endocrine Discovery
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Rosiglitazone was associated with a significantly increased risk of myocardial infarction and borderline-significant increased risk of cardiovascular death, based on a meta-analysis of data from published literature, an FDA website, and the manufacturer’s clinical trials registry. Patients and providers were advised by FDA to consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes.
(N Engl J Med [June 14, 2007] 356 (24):2457)
A low glycemic load diet resulted in greater weight loss than a low fat diet in individuals with baseline insulin resistance (–5.8 vs. –1.2 kg, P = 0.04), while in insulin-sensitive obese individuals the two diets led to similar degrees of weight loss in a prospective randomized controlled trial lasting 18 months in obese young adults.
(JAMA [May 16, 2007] 297:2092)[CrossRef]
When weekly long-acting exenatide was added to metformin and/or diet and exercise, there were decreases in glycohemoglobin, fasting blood sugar, and body weight compared to placebo in a 15-week randomized placebo-controlled trial involving 45 diabetes patients with suboptimal glycemic control.
(Diabetes Care [June 2007] 30:1487)[CrossRef]
By analyzing almost 400,000 common single-nucleotide polymorphisms (SNPs) in 1464 type 2 diabetes patients and matched controls, investigators from Harvard, MIT, and Novartis identified three novel loci associated with diabetes in previously unsuspected genes as well as confirming the association of a SNP in an intron of glucokinase regulatory protein with serum triglycerides.
(Science [June 1, 2007] 316 (5829):1331)
A similar genome-wide association study of 1161 Finns with type 2 diabetes vs. 1174 controls identified diabetes-associated SNPs in the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, as well as confirming that previously reported variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 were associated with risk of diabetes.
(Science [June 1, 2007] 316 (5829):1336)
A role for the transcriptional coactivator PGC-1
in synchronization of energy metabolism was suggested by its rhythmic expression in liver and skeletal muscle, stimulation of expression of clock genes (Bmal1 [Arnt] and Rev-erb [Nr1d1]), and the observation that mice lacking PGC-1 have abnormal diurnal activity, body temperature, and metabolic rate rhythmicity. These were associated with abnormal expression of both clock genes and genes involved in energy metabolism.
(Nature [May 24, 2007] 447:477)[CrossRef]
The retinoic acid precursor retinaldehyde found in rodent fat binds retinol-binding proteins, inhibits adipogenesis, and suppresses PPAR-
and RXR responses. Mice lacking the retinaldehyde-catabolizing enzyme retinaldehyde dehydrogenase 1 were resistant to diet-induced obesity and insulin resistance and had increased energy expenditure. Conversely, administering retinaldehyde or a retinaldehyde dehydrogenase 1 inhibitor to ob/ob mice reduced their fat and increased their insulin sensitivity.
(Nat Med [June 2007] 13 (6):695)
Mitotane administered to adrenocortical cancer patients following radical surgical resection significantly prolonged recurrence-free survival in a retrospective analysis involving 177 patients who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005. Hazard ratios for recurrence were 2.91 (95% confidence interval [CI], 1.77 to 4.78; P < 0.001) and 1.97 (95% CI, 1.21 to 3.20; P = 0.005), respectively.
(N Engl J Med [June 7, 2007] 356 (23):2372)
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Endocrine Practice
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U.S. doctors and patients are avoiding diabetes medication rosiglitazone (Avandia®) after a recent New England Journal of Medicine study found an association between the drug and cardiovascular problems. There was a sharp decline in newly prescribed rosiglitazone from 10% of all oral antidiabetics to zero in the two days after publication of the study.
King Pharmaceuticals, which manufactures branded fludrocortisone acetate, Florinef®, will discontinue its production, but no shortage is anticipated as two other companies will still produce the mineralocorticoid. (For more information, see: http://www.fda.gov/cder/drug/shortages/florinef.pdf)
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Endocrinologists
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Herbert Fleisch, a pioneering bone researcher whose work led to the discovery of bisphosphonates as inhibitors of bone resorption, died at his home in Lausanne, Switzerland at age 74. Professor Fleisch was a founder of the International Bone and Mineral Society as well as the International Osteoporosis Foundation.
François Delange died in Brussels at age 72. His prolific accomplishments as a pediatric endocrinologist included describing myxedematous cretinism due to iodine deficiency, which he devoted his career to eradicating worldwide.
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Milestones in Endocrinology
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50 years ago, Arvid Carlsson showed that dopamine was a brain neurotransmitter and reported that the basal ganglia contained high levels.
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In the Journal 25 Years Ago
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Pituitary microadenomas causing Cushing’s disease respond to corticotropin-releasing factor. DN Orth, CR DeBold, GS DeCherney, RV Jackson, AN Alexander, J Rivier, C Rivier, J Spiess and W Vale.
(J Clin Endocrinol Metab [Nov. 1982] 55:1017)
"These results demonstrate that two microadenomas causing Cushing’s disease were responsive to CRF in situ and suggest that CRF may be involved in the etiology and/or the responses to changes in plasma glucocorticoid concentrations observed in patients with Cushing’s disease."
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Footnotes
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Readers are encouraged to suggest items for Endocrinology and Metabolism News by email (sherman{at}endo-society.org). Submissions will be considered based on their significance and timeliness.
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