| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
The Endocrine Society |
 |
Endocrine Discovery |
|---|
 Top Endocrine Discovery Endocrine PolicyEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
|---|
Patients receiving levothyroxine therapy after undergoing near-total or total thyroidectomy achieved normal T3 levels without T3 supplementation, suggesting that combination therapy may not be warranted. (JAMA [February 20, 2008] 299 (7):769)
In the Diabetes Prevention Project cohort of 3,187 individuals at risk for the development of diabetes, the presence of depression initially or later during the study was unassociated with diabetes risk. While antidepressant use was associated with diabetes risk in the placebo and lifestyle arms of the study, it was not in those on metformin. (Diabetes Care [March 2008] 31 (3):420)
In overweight Hispanic children and adolescents with normal glucose tolerance, plasma markers of endothelial dysfunction and subclinical inflammation increased in parallel with their degrees of excess body fat and increased insulin resistance, possibly contributing to their greater risk of developing type 2 diabetes and cardiovascular disease. (Diabetes Care [March 2008] 31 (3):576)
In a prospective study of 50 individuals undergoing total thyroidectomy, normal serum T3 levels similar to the patients’ baseline values were achieved with L-thyroxine therapy alone in most patients, suggesting that T3 administration would be of no additional benefit. (JAMA [February 20, 2008] 299 (7):769)
In a meta analysis of 42 trials assessing statin therapy for all-stroke prevention (n = 121,285), the relative risk (RR) for stroke was reduced (RR = 0.84; 95% CI, 0.79–0.91). The RR of statin therapy for all-cause mortality (n = 116,080) was also less (0.88; 95% CI, 0.83–0.93). (Am J Med [January 2008] 121 (1):24)
NALP5 appears to be a tissue-specific autoantigen involved in hypoparathyroidism in patients with APS-1. Autoantibodies against NALP5 appear to be highly specific and may be diagnostic for this prominent component of APS-1. (N Engl J Med [March 6, 2008] 358 (10):1018)
In both insulin-deficient and insulin-resistant mice, diabetes-related impairment of hippocampus-dependent memory—as well as neurogenesis, synaptic plasticity, and learning—were all associated with elevated circulating corticosterone. These hippocampal changes in both models were reversed by maintenance of physiological corticosterone levels, suggesting that diabetes-related cognitive impairment might be glucocorticoid-mediated. (Nat Neurosci [March 2008] 11 (3):309)
β cell progenitors in the pancreatic duct lining of adult mice can be activated in the injured pancreas, a process dependent on neurogenin 3 expression, and one that generates β cells as well as all other islet cell types, implying that pluripotent progenitor cells do exist in the adult mouse pancreas and can be autonomously activated to expand β cell mass. (Cell [January 25, 2008] 132 (2): 197)
A novel phosphoinositide-binding domain in O-GlcNAc transferase (OGT) has been shown to modify the insulin signaling pathway, with hepatic overexpression of OGT inhibiting expression of insulin-responsive genes and causing insulin resistance and dyslipidemia. This represents a new molecular mechanism for nutritional signals to regulate insulin signalling through O-GlcNAc. (Nature [February 21, 2007] 451 (7181):964)
Osteoblast-specific Notch function gain increased proliferation of immature osteoblasts, causing osteosclerosis, an action mediated by up-regulation of the cyclin D, cyclin E, and Sp7 (osterix) genes; loss of osteoblastic Notch signaling was associated with age-related osteoporosis. (Nat Med [March 2008] 14 (3):299)
Intermittent TSH administration to mice and rats exerted antiresorptive actions in vivo, preventing bone loss and restoring previously lost bone after ovariectomy. Inhibition of osteoclast action was also observed in cells overexpressing a constitutively active TSH receptor, whereas a mouse model with a dysfunction TSH receptor mutant showed increased osteoclast differentiation–all implying that TSH receptors play a role in regulation of bone remodeling. (Proc Natl Acad Sci U S A [March 18, 2008] 105 (11):4289)
Unliganded thyroid hormone receptor 
1 in maternal mice causes locomotor deficiencies and aberrant development of parvalbumin-immunoreactive GABAergic interneurons in the neocortex of their offspring, implying there may be a previously unknown basis for endemic cretinism and untreated congenital hypothyroidism.
(J Neurosci [Feb. 20, 2008] 28 (8):1904)
In patients with chronic hepatitis C, insulin resistance is associated with viral genotypes 1 and 4, high serum HCV RNA level, and significant liver fibrosis. (Gastroenterology [Feb. 2008] 134:416)[CrossRef]
In a meta-analysis of studies examining the relationship between body mass index and risk of cancers (141 articles with 282,137 subjects), the risks of several common and less common cancers—including thyroid, endometrial, and renal cancer—increased with higher body mass index, with the degree of risk differing among genders and different ethnic groups. (Lancet [Feb. 16, 2008] 317:569)
Calcitriol treatment of patients with chronic kidney disease not yet receiving dialysis was associated with better short-term survival in a study of 520 male patients with chronic renal disease stages 3 to 5 followed for 2 years. (Arch Intern Med [Feb. 25, 2008] 168 (4):397)
Largest Type 2 Diabetes Trial Affirms Aggressive Serum Glucose Treatment
New data from an international trial has heightened controversy about the cardiovascular value and risks of very tight glycemic control for individuals with type 2 diabetes. In February, the ACCORD trial run by the U.S. National Heart, Lung, and Blood Institute revealed that lowering A1c levels to 6.0% was associated with excess deaths—257, compared to 203 in the standard treatment group—resulting in premature termination of that study arm.
Now results recently released from the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial finds no evidence that aggressive treatment increases their risk of death. ADVANCE is a randomized control study that enrolled 11,140 type 2 diabetes patients at high risk for heart disease from about 200 clinical centers in 20 countries in Asia, Australia, Europe, and North America. As in the ACCORD trial, this study aimed to reduce hemoglobin A1c levels, but only to less than 6.5%, through an intensive, modified-release glicazide-based regimen. This study has longer follow-up time than the ACCORD trial.
Due to the similar treatment arms of both studies, the ADVANCE mortality data was reviewed by the Data and Safety Monitoring Committee to determine if similar increase in mortality would also have been seen. "At this stage, the Data Monitoring and Safety Committee have reviewed results that are more than 99% complete, so we are confident that the interim findings are a reliable guide to the final results," said Anushka Patel, FRACP, ADVANCE study leader at The George Institute in Sydney, cautioning that "until we have the final results of both studies, it would be most reasonable to advise patients and doctors to continue to follow current guidelines."
The final results of the ADVANCE trial will be presented this June at the American Diabetes Association annual meeting, with a resulting publication to follow soon thereafter. In the meantime, endocrinologists can only speculate as to what will be the final resolution of the controversy arising from these conflicting trial results.
"It appears, from the data now available, that hypoglycemia has a different impact on different populations. For those with advanced vascular disease, it seems that hypoglycemia is more dangerous than those without," said Irl Hirsch, M.D., professor at the University of Washington School of Medicine in Seattle. "Furthermore, for this population, it appears that control of blood pressure and cholesterol seems more important."
Some research clinicians have postulated that the differences seen between the two studies could be due to the American patients being heavier and thus more at risk for heart disease, or that the ADVANCE trial patients received gliclazide, a drug unavailable in the United States. Most, however, agree that for the time being, patients should have treatments developed with an eye toward their personal medical history.
"As medical professionals, but especially as endocrinologists, we are going to have to do a better job of individualizing A1c targets– different populations handle A1c levels differently," said Hirsch.
Women’s Health Initiative Study Shows Overall Risks Outweigh Benefits in Short-Term Combined Hormone Replacement Therapy
The latest results from the Women’s Health Initiative (WHI) indicate that even halting combination hormone therapy after a couple of years following menopause, overall risks still outweigh the benefits.
Launched in 1991 and sponsored by the National Heart, Lung, and Blood Institute at the National Institutes of Health, the WHI consisted of a set of clinical trials and an observational study investigating the quality of life and risk for cardiovascular disease, cancer, stroke, and bone fractures on generally healthy postmenopausal women either on placebo, estrogen, or a combination of estrogen and progestin. The combined therapy trial was limited to 16,608 women with a uterus.
The trials looking at the effects of combined therapy were stopped in 2002, after it was found that women on these treatments had higher risks of breast cancer, stroke, blood clots, and heart disease, while the risk of colorectal cancer and hip fractures were lower compared to women who did not take the therapy. Since then, the U.S. Food and Drug Administration have emphasized that those who are prescribed this type of medication should only take it at the smallest effective dose for the shortest time possible.
The latest study, published in the March 5, 2008 issue of JAMA, followed 15,730 women, aged 50 to 70 years with an intact uterus, for approximately 3 years after they stopped taking estrogen-plus-progestin. The participants underwent a yearly health exam and mammogram, with biopsies performed as needed. After three years, the previously established risk of heart disease was diminished, but overall risks, including that of stroke, blood clots, and cancer, remained. Specifically, the risk of breast cancer continued at a rate similar to that seen during treatment; women who had stopped taking combined therapy were 27% more likely to develop breast cancer than those on placebo. The study also found that other effects of combined therapy, such as decreased risk of colorectal cancer and hip fractures, also stopped when therapy ended. In sum, the global risk index was 12% higher in women assigned to combined hormonal therapy than placebo.
Elizabeth G. Nabel, M.D., NHLBI director, said the article "confirms the study’s primary conclusion that combination hormone therapy should not be used to prevent disease in healthy, premenopausal women." Added Michael Lauer, M.D., director of the NHLBI Division of Prevention and Population Sciences: "All the accumulated risks do not simply disappear."
Yet outside physicians did not draw as negative a conclusion. "The take-home message is that there are risks while you’re taking it and most of those risks appear to go away when you stop," said Elizabeth Barrett-Connor, M.D., professor and division chief of epidemiology at the University of California in San Diego. "The not-so-good news is that the risk of cancer doesn’t go away." The bottom line, she said, is that, "The risks of combined hormone therapy are very small and the benefits are very small. The trick here is how to advise women in the way that is best for their health and quality of life and not to scare them."
Similarly, in his practice, Robert Barbieri, M.D., gynecology and reproductive biology professor at Harvard Medical School in Boston, Massachusetts, takes the age of his patients under consideration. "I think the risks are quite modest with someone in their 40s and 50s," he said. "If I see people in their 60s with hormone replacement therapy, I take a more active stance in trying to get them to stop it." (JAMA [March 5, 2008] 299 (9):1036)
Restricting Insulin Doses Increases Mortality Risk
Women with type 1 diabetes who reported taking less insulin than prescribed had a three-fold greater risk of death and higher rates of complications than those who did not skip needed insulin shots, researchers at the Joslin Diabetes Center report in the March issue of Diabetes Care. This reported danger casts further light onto what is referred to in the popular press as "diabulimia," an eating disorder in which people with type 1 diabetes deliberately take less insulin than they need for the purposes of weight loss. The attention to diet, weight, and glycemic control associated with diabetes management can trigger this behavior, observed more often in younger females.
In their study, 234 women from age 13 to 60 with type 1 diabetes were followed for 11 years. At the study’s onset, 30% of these women reported taking less insulin than they should for a number of reasons, including weight concerns and related eating disorders, as well as other psychological symptoms such as depression, anxiety, or fear of hypoglycemia. Researchers found that, compared to those who regularly took insulin, the insulin restrictors had increased mortality along with higher rates of nephropathy and foot problems. This was true even though the mean age of death was actually younger for insulin restrictors compared to insulin takers: 45 years versus 58 years.
"There is a subset of women for whom their fears of weight gain and their extreme desire for thinness interferes with appropriate diabetes self-care," said lead author, Ann Goebel-Fabbri, Ph.D., psychologist and instructor at Harvard Medical School, who noted that other studies have shown women with diabetes are nearly 2.5 times more likely to develop an eating disorder than women without diabetes. Goebel-Fabbri and her team propose a screening question appropriate for routine diabetes care—"Do you take less insulin than you should"—to increase the likelihood of earlier detection of this problem and improve access to specialty treatment referrals for these high-risk patients.
"Raising awareness of the impact of insulin restriction among clinicians who treat type 1 diabetes is extremely important so that they can make appropriate assessments and referrals to mental health professionals who are experienced in the treatment of people with diabetes," said study co-author Katie Weinger, Ed.D., R.N., and assistant professor of psychiatry at Harvard Medical School.
Warning signs of insulin restriction can include unexplainable spikes in their hemoglobin A1c; weight loss; unusual pattern of intense exercise; lack of marks from finger sticks; lack of prescription refills for diabetes medications; repeated problems with diabetic ketoacidosis; amenorrhea; and blood glucose records that do not match hemoglobin A1c.
Making an eating disorder diagnosis, however, can be somewhat tricky cautioned Jennifer Larsen, M.D., diabetes, endocrinology, and metabolism section chief at the University of Nebraska Medical Center. "It’s not so clear cut. Some tools used to identify eating disorders can be globally abnormal for many patients with diabetes." (Diabetes Care [March 2008] 31 (3):415)
Climate and Metabolic Syndrome
There may be a predisposition towards metabolic disorders and diabetes based on the climate in which people live, according to a recent population genetics study performed by University of Chicago researchers. The notion isn’t too far-fetched. Previously scientists have noted that humans inhabiting colder regions were stockier and had relatively shorter arms and legs compared to their sunnier southern and equatorial neighbors. Correlations have also been made between colder climates and increased body mass index.
In her study in the February issue of PLoS Genetics, genetics professor Anna Di Rienzo, Ph.D., examined 52 populations from 5 continents—about 1,000 people—for differences in allele patterning from 82 genes associated with energy metabolism. The genes were used as "bait" to fish out additional genes that may also be implicated. Among the "caught" genes, they found several single nucleotide polymorphisms associated with phenotypes related to cold tolerance such as those from the leptin receptor and fatty acid binding protein 2.
"Climate has been an important selective pressure during human evolution," said Di Rienzo. "Our earliest human ancestors lived in a hot, humid climate that placed a premium on dispersing heat. As some populations migrated out of Africa to much cooler climates, there would have been pressure to adapt to their new settings by boosting the processes that produce and retain heat.... The same variants that allowed humans to adapt to different climates also under some circumstances could increase the risk to some of these diseases."
Since then, she said, the consequences of climate have been attenuated by our modern lifestyle of nice heated and air conditioned homes. In short, our genes have yet to catch up to this lifestyle change.
"It’s a very provocative set of findings," said Nancy Cox, Ph.D., fellow geneticist at the University of Chicago who was not involved in this study. "We’re seeing in today’s genes things that occurred over 10,000 years ago when climate was a bigger deal."
Endocrinologist Puneet Arora, M.D., at Regions Hospital in St. Paul, Minnesota, concurred, and added that this study will spur future epidemiological studies. "This is mostly a statistical construct at this point," he said. "It would be interesting to see if these specific polymorphisms can now be localized to populations we already know to be more susceptible to metabolic disorders." (PLoS Genet [February 2008] 4 (2):e32)
|
Endocrine Policy |
|---|
|
TopEndocrine DiscoveryEndocrine PolicyEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
|---|
Students in the health professions will now be able to borrow up to $224,000 total in Stafford loans, an increase from the previous $189,125 limit, based on a decree from the U.S. Department of Education; the increase allows students to take on additional unsubsidized loans at a 6.8 percent interest rate. (For more information, see: http://www.aamc.org/advocacy/library/educ/corres/2008/022808hploanlimits.pdf)
|
Endocrine Practice |
|---|
|
TopEndocrine DiscoveryEndocrine PolicyEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
|---|
The National Osteoporosis Foundation has released a new guideline for treatment of people with low bone mass, "Clinician’s Guide to Prevention and Treatment of Osteoporosis," The document provides guidance regarding procedures for treating minority postmenopausal women and, for the first time, for men aged 50 and older. It also features the World Health Organization’s newly released algorithm on absolute fracture risk called FRAX®. (To view this guideline, see: http://www.nof.org/professionals/clinical.htm)
U.S. adults spent nearly $36 billion on prescription drugs to lower blood sugar, reduce cholesterol, or help manage other metabolic problems in 2005, with this class of drugs ranking first in terms of total prescription drug expenses, according to the latest information from the U.S. Department of Health and Human Services’s Agency for Healthcare Research and Quality. (For more information, go to: http://www.meps.ahrq.gov/mepsweb/data_files/publications/st198/stat198.pdf)
|
Milestones in Endocrinology |
|---|
|
TopEndocrine DiscoveryEndocrine PolicyEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
|---|
|
In the Journal 25 Years Ago |
|---|
|
TopEndocrine DiscoveryEndocrine PolicyEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
|---|
"The circadian rhythm in serum testosterone levels found in normal young men were markedly attenuated or absent in healthy elderly men; the early morning rise in testosterone levels characteristic of young men was not present in old age."
|
|
|
|
|
Footnotes |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
