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Endocrine Discovery |
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 Top Endocrine Discovery Most Americans Need More...Latest Clinical Trial Favors...Endocrine TrainingEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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400 IU/day) should further reduce these fractures by at least 20% and hip fractures by 18%, according to a meta-analysis of 20 randomized controlled trials involving 83,165 patients aged 65 years or older.
(Arch Intern Med [March 23, 2009] 169 (6):551) In a study of 2776 patients with end-stage renal disease, rosuvastatin treatment lowered LDL cholesterol and high-sensitivity C-reactive protein, but had no effect on the composite primary end point based on cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (New Engl J Med [April 2, 2009] 360:1395)[CrossRef]
Compared to conventional therapy for diabetes management, surgically induced weight loss was found to be more cost-effective for managing recently diagnosed type 2 diabetes in class I/II obese patients in Australia. (Diabetes Care [April 2009] 32 (4):567 and 580)
Mutated steroidogenic factor 1 gene (NR5A1) is associated with progressive loss of reproductive capacity, based on a pedigree and genetic analysis of four families with histories of both 46,XY disorders of sex development and 46,XX primary ovarian insufficiency, indicating that this gene may be useful as a diagnostic gene marker for primary ovarian insufficiency. (N Engl J Med [March 19, 2009] 360:1200)[CrossRef]
Metformin therapy led to a decrease in macrovascular but not microvascular disease, an effect partially explained by improved glycemic control and lower weight, in a prospective study of 390 patients treated with insulin and randomized to metformin or placebo with a follow-up period of 4.3 years. (Arch Intern Med [March 23, 2009] 169 (6):616)
A prospective, randomized, stratified, double-blind, placebo-controlled study of 892 patients with familial hypercholesterolemia found that pactimibe had no effect on atherosclerosis, but was associated with an increase in mean carotid intima-media thickness and incidence of major cardiovascular events. (JAMA [March 18, 2009] 301 (11):1131)
Fenofibrate treatment reduced the risk of heart disease in a study among 9795 patients with type 2 diabetes and components of the metabolic syndrome. (Diabetes Care [March 2009] 32 (3):493)
A single nucleotide polymorphism in the visfatin gene, rs10487818, has been linked to protection from obesity, according to genotype data analysis from 6926 severely obese individuals and controls. (Obesity [published online March 19, 2009])
In a prospective cohort study of 559 children, more rapid increases in weight for length in the first 6 months of life were linked to sharply increased risk of obesity at 3 years of age, indicating that changes in weight status in infancy may influence risk of later obesity more than weight status at birth. (Pediatrics [April 2009] 123 (4):1177)
After ingestion of 13C labeled glucose, breath 13CO2 was higher in normal individuals versus individuals with pre- or early diabetes, suggesting the possibility of breath tests to recognize early diabetes. (Diabetes Care [March 2009] 32 (3):430)
In a cross-sectional study of 355 men with type 2 diabetes treated with statins, statin usage, particularly that of atorvastatin, was linked with lower testosterone levels and a trend toward lower sex hormone-binding globulin, but bioavailable testosterone, free testosterone, estradiol, and hypogonadal symptoms were not affected. (Diabetes Care [April 2009] 32 (4):541)
Adults with type 1 diabetes reported more symptoms of depression and more antidepressant medication usage compared to those without this disease. (Diabetes Care [April 2009] 32 (4):575)
Daily consumption of diet soda was associated with greater risks of two metabolic syndrome components (incident high waist circumference and fasting glucose) and type 2 diabetes, according to an observational study of 6814 Caucasian, African American, Hispanic, and Chinese adults, aged 45–84 years. (Diabetes Care [April 2009] 32 (4):688)
Decreased mental efficiency occurred with naturally-occurring hypo- and hyperglycemic glucose fluctuations in children with type 1 diabetes, according to a field procedure using Personal Digital Assistance technology. (Diabetes Care [published online March 26, 2009])
Chlorogenic acid and trigonelline reduced early glucose and insulin responses during the oral glucose tolerance test, indicating that these compounds may contribute to the preventative effect of coffee on the development of diabetes. (Diabetes Care [published online March 26, 2009])
An international study comparing type 2 diabetes patients on starter insulin therapy with either twice-daily lispro mix 75/25 or once-daily glargine, in combination with oral antihyperglycemic drugs, revealed that those on LM 75/25 had slightly lower A1C at 24 weeks and a moderately higher percentage of reaching an A1C target of <7.0%. These same patients also gained more weight and had higher rates of overall hypoglycemia, but lower rates of nocturnal hypoglycemia. (Diabetes Care [published online March 31, 2009])
A meta-analysis of 10 randomized controlled trials involving 7812 patients with multivessel coronary artery disease suggests that older patients or those with diabetes might enjoy a significant survival advantage if treated with coronary artery bypass graft compared to percutaneous coronary intervention. (Lancet [April 4, 2009] 373:1190)[CrossRef]
A retrospective study of 38 pregnant women with hypothyroidism showed that its etiology determined the timing and magnitude of thyroid hormone adjustments required during pregnancy. (Thyroid [March 2009] 19:269)[CrossRef]
In vivo mouse studies revealed that C-C chemokine receptor-2 is involved in receptor activator of NF-
B (RANK) ligand-induced osteoclastogenesis, providing a new treatment target for osteoporosis.
(Nat Med [published online March 29, 2009])
Analysis of 5 human osteosarcoma cell lines identified Wnt inhibitory factor, which encodes an endogenous secreted Wnt pathway antagonist, as a candidate tumor suppressor gene. (J Clin Invest [April 1, 2009] 119 (4):837)
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Most Americans Need More Vitamin D |
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TopEndocrine DiscoveryMost Americans Need More...Latest Clinical Trial Favors...Endocrine TrainingEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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Once thought to be solely affiliated with bone health, recent studies show that vitamin D is important in other diseases such as cardiovascular disease, diabetes, and cancer.
"Vitamin D deficiency has enormous health implications for the population at large," said Michael F. Holick, M.D., Ph.D., Director of the General Clinical Research Unit at Boston University Medical Center in Massschusetts and a leading vitamin D expert who wasn’t involved with the study.
Current dosage recommendations cannot quell the tide of vitamin D insufficiency currently seen in the population. The Institute of Medicine (IOM) now recommends vitamin D supplementation of 200 IU/d from birth to 50 years of age, 400 IU/d for adults aged 51–70 years, and 600 IU/d for seniors 71 years or older. Until recently, serum 25-hydroxyvitamin D (25[OH]D) levels of 20 ng/mL appeared adequate based on skeletal outcomes, but recent evidence suggests that 30–40 ng/mL may be required for optimum bone health.
"We still need to figure out what the optimal dose is, yet the current recommendations are 10 years old and need to be updated," said Adit Ginde, M.D., M.P.H., assistant professor of surgery at the University of Colorado Denver School of Medicine and lead author of this recent study. He added that the IOM convened in March 2009 in Washington DC to review current data and is expected to make final recommendations by 2010.
Dr. Ginde and his team compared serum 25(OH)D levels of two time periods—1988–1994 and 2001–2004— from the U.S. federal government’s National Health and Nutrition Examination Survey (NHANES). They found that the prevalence of serum 25(OH)D levels at or above the recommended 30 ng/mL dropped by half among the two surveys—down to 23% in 2001–2004 compared with 45% in 2001–2004. Furthermore, their study found that vitamin D insufficiency, reported as <30 ng/mL serum 25(OH)D, was nearly universal in the more recent survey among non-Hispanic blacks (97%) and Mexican-Americans in the U.S. (90%).
"It’s not as dire as his paper would indicate," said Mary Francis Picciano, Ph.D., senior nutrition scientist at the National Institutes of Health’s Office of Dietary Supplements (ODS), attributing these differences to shifts over time in the assay that was used to measure the blood levels. She points out that a new and improved standard reference material for serum 25(OH)D levels—SRM 972 Vitamin D in Human Serum—will soon be available to researchers from the ODS and the National Institutes of Standards and Technology.
Until the IOM hammers out the recommended levels of vitamin D, Drs. Ginde and Holick recommend that patients consult with their doctors, get their serum blood levels tested for 25(OH)D, and consider taking supplements of 1,000 IU/d. Dr. Holick personally takes 2700 IU/d and has a blood level of 50 ng/mL.
Dr. Picciano cautioned that too much vitamin D could also be toxic and lead to hypercalcemia and calcification of soft tissue. "Women even receiving the low dose of 400 IU/d of vitamin D in the Women’s Health Initiative Study experienced a 17% increase in kidney stones," she said. She believes that the current guidelines should still be upheld until the new IOM results are released next year. (Arch Intern Med [March 23, 2009]169 (6):626)
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Latest Clinical Trial Favors Conventional Over Intensive Glucose Control in Critically Ill Patients |
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TopEndocrine DiscoveryMost Americans Need More...Latest Clinical Trial Favors...Endocrine TrainingEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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Hyperglycemia is common in intensive care unit (ICU) patients and is associated with increased morbidity and mortality. One solution has been intensive glucose control, in which blood sugar is rigorously checked and held at bay with insulin and other medications. Unfortunately, this approach can quickly swing a patient toward hypoglycemia, leading to coma and even death.
"We need to find a happy median to really reduce risk but not cause harm," said Sherita Hill Golden, M.D., M.H.S., associate professor of medicine and epidemiology and director of the Inpatient Diabetes Management Program at the Johns Hopkins University School of Medicine.
Although labor intensive, intensive glucose control has been recommended as a standard of care for critically ill patients by many organizations, including the American Diabetes Association, the American Association of Clinical Endocrinology, and the Surviving Sepsis Campaign. This recommendation 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. The VISEP study performed in patients with septic shock published last year in NEJM found that intensive control carried no mortality benefits, yet was stopped early because of severe hypoglycemia observed in these patients. Similarly, a meta-analysis published last year in JAMA found no increase in mortality, but an increase in hypoglycemia in the intensive control-treated patients.
This current study, aptly called NICE-SUGAR (Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation) is the largest intensive insulin therapy trial to date. The trial set out to test the hypothesis whether intensive glucose control reduces mortality at 90 days. Over 6100 ICU adult patients were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81–108 mg/dL, or conventional glucose control, with a target of 
180 mg/dL. The primary endpoint was death from any cause within 90 days of randomization.
The group found that the absolute mortality rate was actually 3% higher (28% vs. 25%) in the tight control group, which achieved on average a blood glucose level of 118 mg/dL, than in the conventional control group, which reached a blood glucose average of 145 mg/dL, representing a 10% increase in relative mortality in the tight control group.
These results differ from the meta-analysis that showed no difference in mortality in these two groups, said Simon Finfer, F.R.C.P., F.J.F.I.C.M., professor of the George Institute for International Health at the University of Sydney, Australia, and corresponding author of the NICE-SUGAR study.
"At present, our data shows that targeting normal blood glucose cannot be recommended in critically ill patients at the moment," Dr. Finfer said.
In a related commentary in Canadian Medical Association Journal, Greet Van den Berghe, M.D., Ph.D., 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 intensive insulin therapy may be effective in lowering mortality risk among surgical patients in the ICU. She claimed that differences between the current study and her study may be due to duration of hyperglycemia before the start of the intervention, the target blood glucose ranges in the two groups (her study compared normal levels with no control for glucose except for levels that are excessively elevated, whereas NICE-SUGAR compared normal and intermediate levels of glucose control), and differences in feeding strategies and blood glucose monitoring (her study fed the patients enterally and parenterally and used blood gas analyzers whereas NICE-SUGAR fed almost all patients enterally and used multiple sets of glucometers, each with different accuracy levels).
"This issue is not closed," said Dr. Finfer. "No single trial answers the question completely." (N Engl J Med [March 26, 2009]360:1283)[CrossRef]
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Endocrine Training |
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TopEndocrine DiscoveryMost Americans Need More...Latest Clinical Trial Favors...Endocrine TrainingEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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Endocrine Practice |
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TopEndocrine DiscoveryMost Americans Need More...Latest Clinical Trial Favors...Endocrine TrainingEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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A standard reference material for circulating vitamin D analyses will be made available by the National Institutes of Standards and Technology and National Institutes of Health’s Office of Dietary Supplements. Named "SRM 972 Vitamin D in Human Serum," this material consists of four pools of fresh-frozen serum, with each pool containing a different level of 25(OH)D2, 25(OH)D3, or both, and one pool also containing 3-epi-25(OH)D3. (For more information, contact Karen Phinney, Ph.D., NIST, phone: 301-975-4457, email: karen.phinney{at}nist.gov)
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Milestones in Endocrinology |
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TopEndocrine DiscoveryMost Americans Need More...Latest Clinical Trial Favors...Endocrine TrainingEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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In the Journal 25 Years Ago |
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TopEndocrine DiscoveryMost Americans Need More...Latest Clinical Trial Favors...Endocrine TrainingEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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"We conclude that RU486 antagonize is the negative pituitary feedback of both the nocturnal endogenous cortisol rise and endogenously administered dexamethasone. These actions are consistent with an antiglucocorticoid activity of this compound in man."
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