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Endocrine Discovery |
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 Top Endocrine Discovery Endocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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Higher total and high-molecular-weight adiponectin levels were associated with lower risk of type 2 diabetes in healthy women, independent of body mass index. (Ann Intern Med [September 2, 2008] 149 (5):307)
Individuals in the lowest quartile for serum 25-hydroxyvitamin D level (<18 ng/mL) had a 26% increase in all-cause mortality (mortality rate ratio, 1.3; 95% CI, 1.1–1.5) compared with the highest quartile (
24 ng/ml) in the NHANES III cohort (1988–1994) of over 13,000 adults followed for a median of 9 years. (Arch Intern Med [August 11, 2008] 168 (15):1629)
In a prospective randomized trial among 580 women treated for infertility, those randomized to expectant management (n=193), oral clomifene citrate (n=194), or unstimulated intrauterine insemination (n=193) for six months had similar live birth rates of 17%, 14%, and 23%, respectively (P = NS). (BMJ [August 16, 2008] 337 (7666):a716)
In a prospective study of 1025 persons mean age 13 years with type 1 diabetes without retinopathy and albuminuria at baseline, development of retinopathy at 10 years of follow up was associated with systolic and diastolic blood pressure above the 90th percentile, independent of nephropathy. (BMJ [August 30, 2008]337 (7668):a918)
Postmenopausal women who started combination hormone replacement therapy many years after menopause had an overall increase in quality of life compared to controls, with fewer women reporting hot flashes (9% vs. 25%), night sweats (14% vs. 23%), aching joints and muscles (57% vs. 63%), insomnia (35% vs. 41%), and vaginal dryness (14% vs. 19%). However, more women on treatment reported breast tenderness (16% vs. 7%) and vaginal discharge (14% vs. 5%). (BMJ [published online August 21, 2008])
In a cross-sectional study of 788 adults, those with diabetes had a 26% higher level of total urinary arsenic (95% confidence interval [CI], 2%–56%) compared to those without diabetes. (JAMA [August 20, 2008] 300 (7):814)
In a meta analysis of 29 randomized controlled trials totaling 8432 patients randomized to tight glucose control vs. usual care, tight glucose control was not associated with lesser hospital mortality, but was with hypoglycemia. (JAMA [August 27, 2008] 300 (8):933)
Postmenopausal women taking tibolone had a decreased risk of vertebral fracture, nonvertebral fracture, invasive breast cancer and colon cancer, but an increased risk of stroke in a randomized controlled trial including 4538 women with osteoporosis treated for a median of 34 months, (relative hazard, 2.19; 95% CI, 1.14 to 4.23; P=0.02), prompting discontinuation of the study by the data and safety monitoring board. (N Engl J Med [August 14, 2008] 359 (7):697)
Single-nucleotide polymorphisms in SLCO1B1 are strongly associated with increased risk of simvastatin-induced myopathy, based on a genome-wide association study. Identifying these polymorphisms may be useful in tailoring both statin dose and safety monitoring. (N Engl J Med [August 21, 2008] 359 (8):789)
Brain-derived neurotrophic factor (BDNF) haploinsufficiency is associated with lower levels of serum BDNF and childhood-onset obesity in individuals with Wilms’ tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome, suggesting that BDNF may be important for energy homeostasis. (N Engl J Med [August 28, 2008] 359:918)[CrossRef]
Three trials did not provide credible evidence of any adverse effect of ezetimibe on cancer rates. (New Engl J Med [published online September 2, 2008])
In patients with mild-to-moderate aortic-valve stenosis, long-term intensive lipid-lowering therapy with simvastatin and ezetimibe had no overall effect on the course of valvular stenosis, but was associated with reduced risk of ischemic cardiovascular events and an increased incidence of cancer . (New Engl J Med [published online September 2, 2008])
Increased vitamin D from sunlight and diet was associated with a reduced risk of breast cancer regardless of the estrogen/progesterone receptor status of the tumor. (Am J Epidemiol [published online August 27, 2008])
Women on oral contraceptive agent may have a distorted sense of smell that causes them to choose a mate similar in smell, and hence genes, to their own, thus reducing the possibility of offspring heterozygosity. (Proc Roy Soc B Biol [published online August 13, 2008])
Injection of angiotensin autoantibodies from women with pre-eclampsia into pregnant mice induced this disorder, suggesting that pre-eclampsia may be an autoimmune disease. (Nat Med [August 2008] 14 (8):855)
Decreasing brain-type creatine kinase expression via RNA interference, its pharmacological inhibitor cylcocreatine, or through in vivo knock out mice, suppressed the bone-resorbing activity of osteoclasts, suggesting this enzyme as a potential new target for antiresportive drug treatment. (Nat Med [September 2008] 14 (9):966)
Two mouse models indicated that the cyclic AMP responsive element-binding protein-1 (Creb-1)-regulated transcription coactivator-1 (Crtc1) is required for energy balance and reproduction. Crtc1-/- mice are hyperphagic, obese, and infertile, whereas hypothalamic Crtc1 was phosphorylated and inactive in leptin-deficient ob/ob mice. The dephosphorylated Crtc1 in the latter mouse model stimulated expression of the Cartpt and Kiss1 genes, which encode hypothalamic neuropeptides that mediate leptin’s effects on satiety and fertility. (Nat Med [published online August 31, 2008])
Fully differentiated exocrine cells in adult mice can be directly reprogrammed into cells that closely resemble β-cells through the stimulation of three transcription factors—Ngn3, Pdx1, and Mafa. (Nature [published online August 27, 2008])
An increased cumulative incidence of type 2 diabetes was seen among Yucheng women who had been exposed to polychlorinated biphenyls and dioxins, particularly among those diagnosed with chloracne. (Diabetes Care [August 2008] 31 (8):1574)
A case–control study of 8191 women with gestational diabetes and 81,262 without it found that young women with gestational diabetes have an increased risk for cardiovascular disease compared to women without the condition, and that much of this risk is attributable to the subsequent development of type 2 diabetes. (Diabetes Care [August 2008] 31 (8):1668)
Combination therapy of metformin and sulfonylurea increased risk of cardiovascular hospitalization or mortality, but did not increase cardiovascular or all-cause mortality. (Diabetes Care [August 2008] 31 (8):1672)
Obesity does not increase the likelihood that an individual’s diabetes will be diagnosed, according to an analysis of 5514 U.S adults. (Diabetes Care [September 2008]31 (9):1813)
Among atomic bomb survivors, individuals with papillary thyroid cancer harboring RET/PTC rearrangements developed their cancers earlier than those with BRAFV600E mutations. (Cancer Res [September 1, 2008] 68 (17):7176)
Low vitamin D status predicted development of type 2 diabetes in two nested case-control studies of men and women aged 40–74 years and followed for 22 years. (Epidemiology [September 2008] 19 (5):666)
Use of proton pump inhibitors increased the risk of hip and any osteoporotic fractures after 5 years and 7 years, respectively, of continuous exposure. (CMAJ [August 12, 2008]179 (4):319)
In premenopausal women with early-stage breast cancer taking combined endocrine therapy for 3 years followed by 2 years with zoledronic acid, bone mineral density remained stable and improved over time, with 4% increases in both lumbar spine and trochanter bone densities; whereas in patients who did not receive this bisphosphonate, lumbar spine and trochanter bone densities remained 6% and 4%, respectively, below baseline. (Lancet Oncol [September 2008] 9:840)[CrossRef]
Entero–gastro anastomosis procedures in mice reduced food intake and increased insulin sensitivity by raising intestinal gluconeogenesis and stimulating the hepatoportal glucose sensor via a GLUT-2-dependent pathway. (Cell Metab [September 3, 2008] 8:201)[CrossRef]
A transgenic mouse line designed to report leptin gene expression demonstrated that weight loss by fasting or leptin treatment results in the persistence of lipid-depleted adipocytes in the adipose depot. Low leptin levels stimulated the recovery of adipose tissue mass by activating genes that facilitate the conversion of glucose into acetyl-CoA and glycerol, key substrates in triglycerides synthesis. (Proc Natl Acad Sci USA [September 2, 2008] 105 (35):12985)
The hypotensive effects of olive-oil-enriched diets can be explained by its high oleic acid content, which, in rats, regulates membrane lipid structure to control G protein-mediated signaling. (Proc Natl Acad Sci USA [September 16, 2008] 105 (37):13811)
Tight Glucose Control in ICU: Do the Risks Outweigh the Benefits?
A recently published meta-analysis has critical care physicians trying to reset the bar for how tightly blood glucose control in their patients should be monitored.
The American Diabetes Association and the Surviving Sepsis Campaign have each recommended tight blood glucose control for critically ill patients—at levels of 110 mg/dL and lower than 150 mg/dL, respectively. Both recommendations stemmed from the outcome of a 2001 randomized controlled trial which found that tight glucose control reduced hospital mortality among critically ill surgical patients by one-third. Subsequent trials attempting to replicate these results, however, have yielded mixed results.
"As a practicing critical care physician, I was struck by how quickly tight glucose control became a standard of care for all critically ill patients based on the results of one clinical study," said Renda Wiener, M.D., M.P.H., assistant professor of medicine at Dartmouth Medical School in Hanover, New Hampshire.
Seeking a consensus, Dr. Wiener and her colleagues performed a meta-analysis of 29 trials involving 8,432 patients in medical, surgical, and mixed medical-surgical intensive care unit (ICU) settings. Two tight glucose control groups, one at less than 110 mg/dL and the other at less than 150 mg/dL, were compared to usual ICU care, which achieves glucose levels of approximately 180 mg/dL).
They found that hospital mortality did not differ between usual care and either of the tight glucose control groups. While surgical ICU patients assigned to the tight glucose group had fewer cases of septicemia (11% vs. 13%), they had five times as many hypoglycemic patients with glucose levels less than 40 mg/dL (14% vs. 3%).
"Our results show that the time has come to reconsider whether tight glucose control should be the standard of care recommended by medical societies for all critically ill adults," said Dr. Wiener.
Frank Brunkhorst, M.D., manager of the German Sepsis Society and senior physician of the Clinic for Anesthesiology and Intensive Care at the Friedrich Schiller University of Jena in Germany, expressed concern: "Most societies for endocrinology aren’t well aware that 90% of ICU patients are sedated and don’t develop clinical signs of hypoglycemia."
Many ICU physicians are looking forward to the day in which continuous glucose monitoring, a technology still in its developmental stages, will aid in blood glucose control. "Several of the studies in the meta-analysis used morning glucose values which are less relevant," commented Jean-Charles Preiser, M.D., Ph.D, professor in the Department of Intensive Care at the Liege University Hospital Center in Belgium. "An emerging and promising issue is the variability of blood glucose that could represent a better target than the absolute values."
Constant manual monitoring, pointed out Dr. Brunkhorst, is not feasible in the ICU. "We should be recording glucose level every hour, but it’s not possible," said Dr. Brunkhorst who pointed out that European ICU nurses are outnumbered by patients 3 to 1.
Dr. Greet Van den Berghe, head of the Department of Intensive Care Medicine at the Catholic University of Leuven in Belgium, and author of the contested 2001 randomized control trial, contended that the current evidence is still in favor of tight glucose control. The pooled studies, she explained, defined tight glucose control as anything below the 150 mg/dL cut-off and, therefore, do not entirely replicate her tighter glucose control group with levels below 110 mg/dL.
The final verdict may come next year, when the much-anticipated multi-center, randomized control trial, NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation), will publish their results.
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Endocrine Practice |
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TopEndocrine DiscoveryEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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U.S. adult obesity rates increased in 37 states in the past year. More than 20 percent of adults are obese in every state except Colorado, according to the fifth annual F as in Fat; How Obesity Policies Are Failing in America, 2008 report from the Trust for America’s Health and the Robert Wood Johnson Foundation. A follow-up analysis of the annual Behavioral Risk Factor Surveillance Survey by the U.S. Centers for Disease Control and Prevention, the report also provides an annual review of state and federal policies aimed at reducing or preventing obesity in children and adults, and provides key policy recommendations. The report can be viewed at www.healthyamericans.org and www.rwif.org
The U.S. Food and Drug Administration approved a generic human growth hormone preparation (Novartis’ Omnitrope® Pen 10 [somatropin [rDNA origin] injection), for long-term treatment of children with growth failure and long-term replacement therapy in adults with growth hormone deficiency. (For more info, see: http://www.novartis.com/newsroom/media-releases/en/2008/1248342.shtml)
The U.S. Food and Drug Administration recommended physicians discontinue use of Byetta in patients suspected to be suffering from pancreatitis. Since October 2007, the FDA has received reports of 6 cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta; two of which died and four are recovering at the time of reporting. The complete safety summary can be read at: http://fda.gov/medwatch/safety/2007/safety07.htm#Byetta.
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Milestones in Endocrinology |
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In the Journal 25 Years Ago |
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