The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 3 17a
Copyright © 2006 by The Endocrine Society
Endocrinology & Metabolism News March 2006
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Endocrine Discovery
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Type 2 diabetes was strongly associated with a variant transcription factor 7-like 2 gene (TCF7L2) in an Icelandic population, a finding replicated in Danish and U.S. cohorts. Heterozygous and homozygous carriers of the variant allele(s) had relative risks of 1.45 and 2.41, respectively. TCF7L2 is a transcription factor believed to regulate expression of the proglucagon gene in enteroendocrine cells.
(Nat Genet (January 15, 2006))
In a randomized controlled trial, intensive insulin therapy in 1200 patients did not significantly lessen the overall group’s in-hospital mortality, although lower incidences of new renal injury, faster weaning from mechanical ventilation, and earlier ICU discharge were seen. Among patients who ultimately stayed in the ICU for more than three days, mortality was lower (43% vs. 53%, P = 0.009), but they could not be distinguished in advance from those with shorter stays, in whom mortality was actually increased.
(N Engl J Med (Feb. 2, 2006) 354:449)[Abstract/Free Full Text]
Patients in the DCCT intensive therapy group had decreased symptoms (–51%) and signs (–43%) of neuropathy compared to the conventional treatment group after a mean 6
years of intensive therapy during the study and 8 or more years of follow up.
(Diabetes Care (Feb. 2006) 29:340)[Abstract/Free Full Text]
In type 2 diabetic subjects with coronary artery disease, short-term insulin infusion during a euglycemic-hyperinsulinemic clamp improved myocardial blood flow in both ischemic and nonischemic regions, based on PET scan and coronary angiographic observations.
(Diabetes (Feb. 2006) 55:511)[Abstract/Free Full Text]
In more than 2100 men prescribed warfarin for more than 1 year, an increased risk of osteoporotic fractures (OR 1.6, 95% CI 1.3–2.1) was observed compared to non-warfarin-treated controls, but there was no significant association in women or men treated for less than 1 year.
(Arch Intern Med (Jan. 23, 2006) 166:241)[Abstract/Free Full Text]
Coronary artery disease patients receiving statin therapy had a lower rate of subsequently developing sepsis compared to patients not receiving statins (OR 0.81, 95% CI 0.72–0.91) in a cohort of 69,000 hospitalized patients. This effect was present in patients with diabetes, and was not observed with other lipid-lowering agents.
(Lancet (Feb. 4, 2006) 367:413)[CrossRef][Medline]
Small-molecule inhibitors of MEK selectively repressed growth of cultured BRAF mutant cells compared to wild-type or RAS mutant cells—down-regulating cyclin D1 expression and inducing G1 arrest. Pharmacological MEK inhibition also prevented growth of BRAF mutant tumor xenografts.
(Nature (Jan. 19, 2006) 439:358)[CrossRef][Medline]
Bile acids administration increased energy expenditure by brown fat in mice, an effect that was dependent on a local increase in type 2 iodothyronine deiodinase activity. The effect was mediated by bile acid binding to a G protein-coupled receptor (TGR5) and increased cyclic AMP.
(Nature (Jan. 26, 2006) 439:484)[CrossRef][Medline]
Afferent pathways to murine GnRH-producing neurons were identified projecting from a discrete population of olfactory sensory neurons. In the absence of olfactory function, chemosensory modulation of LHRH neuronal activity and mating behavior was impaired.
(Cell (Nov. 18, 2005) 123:669)[CrossRef][Medline]
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Endocrine Practice
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The American Thyroid Association published updated guidelines for the management of patients with thyroid nodules and thyroid cancer
(Thyroid (Feb. 2006) 16:1).[CrossRef][Medline]
A complete table of contents and free sample issue is available online at: www.liebertpub.com/thy.
FDA approved the first inhalable insulin preparation (Exubera®) for treatment of type 1 and 2 diabetes in adults. Candidates for the drug should not have chronic lung disease or smoked within 6 months. (For more information, see: http://www.pfizer.com/pfizer/are/news_releases/2006pr/mn_2006_0127a.jsp)
An inhibitor of VEGF and EGF receptors and RET kinase, ZD6474 (Zactima®), has been granted fast track review by FDA for treatment of medullary thyroid cancer. (For more information, see: http://www.astrazeneca.com/pressrelease/5182.aspx)
FDA approved the dual V1a-V2 receptor AVP antagonist conivaptan (Vaprisol®) as the first pharmacologic agent for treatment of euvolemic hyponatremia. (For more information, see: http://www.astellas.com/global/about/news/2006/pdf/060104_eg.pdf)
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Endocrine Policy
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A newly announced NIH Pathway to Independence Award program will support postdoctoral scientists during the transition from mentored (1–2 years) to independent research (3–5 years). (For more information, visit: http://grants.nih.gov/grants/new_investigators/pathway_independence.htm)
A New York City Board of Health code would require medical laboratories to submit hemoglobin A1c data for individuals with diabetes for epidemiological surveillance and so physicians could be notified about poorly controlled patients. The as-yet-unfunded program has engendered privacy concerns.
(Nature Medicine 12:155 (2006) (Published online 31 January 2006))[Medline]
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Endocrinologists
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Gideon Rodan, a pioneer in bone research who helped develop widely-used treatments for osteoporosis, died at his home in Bryn Mawr, Pennsylvania at age 71.
Christian Koch will become director of the Division of Endocrinology, Diabetes, and Metabolism at the University of Mississippi in Jackson, Mississippi.
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Milestones in Endocrinology
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Fifty years ago, Bromer and colleagues discovered the structure of glucagon.
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In the Journal 50 Years Ago
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The effect of iodide on the release of thyroid hormone in hyperthyroidism. Goldsmith RE and Eisele ML.
J Clin Endocrinol Metab
1956;16:130–137.
"The data suggest that, in hyperthyroid man, iodide ion slows of the rate of secretion of thyroid hormone, and that this slowing results from interference with release of hormone from the gland rather than with hormone synthesis."
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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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