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Endocrine Discovery |
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In a study of nearly 8000 Caucasians looking for genetic loci associated with bone mineral density, SNPs near or within the receptor activator of nuclear factor-B ligand gene (RANKL), the osteoprotegerin gene (OPG), and the estrogen receptor 1 gene (ESR1) were significantly associated with bone density and fracture. (N Engl J Med [published electronically ahead of print April 29, 2008])
Homozygous mutations in DEHAL1 in patients with hypothyroidism appeared to cause human iodotyrosine deiodinase deficiency, leading to goiter with a varying time of onset of hypothyroidism. Consequently, infants with DEHAL1 defects may be missed by neonatal screening programs for congenital hypothyroidism because some have a normal thyroid function at birth. (N Engl J Med [April 24, 2008] 358 (17):1811)
Among 23,316 pregnant women, even modest increases (+1 SD) in fasting plasma glucose and in the 1-hour and 1-hour plasma glucose levels after a 75 gm glucose load were associated with increased odds of adverse pregnancy outcomes, including birth weight >90th percentile for gestational age, primary cesarean delivery, neonatal hypoglycemia, and cord-blood C-peptide >90th percentile. There were no clear thresholds above which these risks increased. (N Engl J Med [May 8, 2008] 358:1991)[CrossRef]
In 751 women with gestational diabetes mellitus at 20 to 33 weeks treated with metformin (and insulin supplementation if needed) or insulin alone, the rate of the composite neonatal outcome (including hypoglycemia, respiratory distress, phototherapy requirement, birth trauma, 5-min Apgar <7, or prematurity) was 32.0% in metformin-treated and 32.2% in insulin-treated women. Furthermore, more women assigned to metformin than insulin said they would choose the same treatment again (77% vs. 27%, P<0.001). (N Engl J Med [May 8, 2008] 358:2003)[CrossRef]
Scanning electron microscopy of bone samples in patients with bisphosphonate-related jaw osteonecrosis revealed microbial biofilms in affected areas, implying a possible role for bacteria in this disease process. (J Oral Maxillofac Surg [April 2008] 66:767)[CrossRef]
Associations between dementia and both low and high BMI were found in a meta-analysis of 10 relevant prospective cohort studies of older adults. (Obes Res [May 2008] 9 (3):204)
Adult stem cells in the mouse anterior pituitary permit gland growth after birth, suggesting that there may be two types of hypophyseal stem cells—one that grows in the developing embryo and one appearing later, perhaps to help the gland respond to changing metabolic conditions. (Proc Natl Acad Sci USA [April 29, 2008] 105 (17):6332)
A G6PC2/IGRP gene polymorphism was associated with high fasting plasma glucose in an analysis of 392,935 single nucleotide polymorphisms in 654 normoglycemic non-obese individuals, and replicated in 9,353 separate subjects. (Science [May 23, 2008] 320 (5879):1085)
Consumption of a low glycemic index diet improved blood sugar control in children and adolescents with type 1 diabetes. (Diabetes Care [April 2008] 31:695)[CrossRef]
Glutamate decarboxylase 65 autoantibodies (GAD65AB) were found in 238 healthy individuals and first-degree relatives of patients with type 1 diabetes, but they were masked by specific anti-idiotypic antibodies absent in patients with the disease. (Proc Natl Acad Sci USA [April 8, 2008] 105 (14):5471)
Patients with diabetes who either took diabetes education classes or saw a nutritionist had fewer hospitalizations and lower medical costs. (Diabetes Care [April 2008] 31:655)[CrossRef]
New Findings Implicate Thiazolidinediones as Risk Factors for Bone Disease
Long-term treatment of thiazolidinediones (TZD) nearly doubles the risk of bone fractures in patients with type 2 diabetes, according to recent published results from two independent research groups. This TZD-related bone effect might also exacerbate the already known association between increased fracture risk—particularly at the hip, arm, and foot—and the duration of the disease.
Christian Meier, M.D., head of the pharmacoepidemiology unit of University Hospital Basel, in Switzerland, and his team performed an 11-year case-control study of 4,748 type 2 diabetes patients, aged 30 to 89 years. They found that individuals currently taking rosiglitazone or pioglitazone had approximately 2 to 3 time greater odds of having a hip and other non-spine fracture than those who had not taken take these drugs. The fracture risk was highest for those who took the drugs for 2 or more years, and the odds slightly increased for those only on the medication for 12 to 18 months. Their results are published in April 28, 2008 issue of the Archives of Internal Medicine.
Similar results were seen in a May 2008 Diabetes Care article written by Steven Kahn, M.D., associate director of the Diabetes Endocrinology Research Center at the University of Washington in Seattle, and his team. They followed 1,840 women and 2,511 men from the ADOPT trial over 4 years for fractures. They found in women treated with rosiglitazone for more than 12 months, there was doubling of fracture risk compared to metformin or glyburide. However, no skeletal effects were seen in men.
"...if you’re going to take this medication you might get better glucose control, but there is an increased risk of getting bone fractures with these drugs," said Steven Kahn, M.D., on the latest findings that long-term treatment of thiazolidinediones nearly doubles the risk of bone fractures in patients with type 2 diabetes.
These results are forcing diabetologists to reevaluate their approach to treatment. "There is a growing awareness that this needs to be looked at," said Ann Schwartz, Ph.D., MPH, assistant professor of epidemiology and biostatistics at the University of California, San Francisco, who added that the results of Dr. Kahn’s controlled, randomized trial lends further credence to Dr. Meier’s observational trial.
Indeed, many endocrinologists are now informing their patients considering TZD therapy of these medications’ beneficial and harmful effects. "The decision needs to be taken by the patient in consultation with their physician and with the understanding that if you’re going to take this medication you might get better glucose control, but there is an increased risk of getting bone fractures with these drugs," said Dr. Kahn.
Similarly, Dr. Meier stressed caution when consulting with patients. "These findings don’t change current treatment guidelines," he said. "All the heavily used oral diabetes drugs have adverse effects. ...It’s really a matter of the individual situation and the diabetologist looking at the situation together."
Thiazolidinediones are ligands for peroxisome proliferators-activated receptor 
(PPAR), a family of nuclear receptors that regulate gene transcription. While they are predominantly found in adipocytes, PPARs also inhibit osteoblastic function, providing evidence to the claims found in the above mentioned articles.
The effects of TZDs and the skeleton will be further discussed at the June annual meetings of the American Diabetes Association and The Endocrine Society. (Arch Intern Med [April 28, 2008] 168 (8):820) and (Diabetes Care [May 2008] 31(5):845)
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TopEndocrine DiscoveryEndocrinologistsEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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Endocrine Practice |
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TopEndocrine DiscoveryEndocrinologistsEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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A 10-year review of insulin pump usage in patients aged 12 to 21 years with type 1 diabetes by the U.S Food and Drug Administration revealed 13 deaths and more than 1,500 injuries connected with use of the pumps, suggesting possible misuse by adolescents. (Pediatrics [May 2008] 121 (5):1133)
The Society for Assisted Reproductive Technology has placed its latest 2006 Success Rate Reports online. The reports include data from 343 clinics on 126,397 treatment cycles that resulted in the births of 50,769 babies. The clinic summary pages on the site allow users to customize and sort data—for diagnoses and treatment types—so that they can see what is relevant to their own experience. To view the reports, go to http://www.sart.org and click onto the "IVF Success Rate Reports" box.
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Milestones in Endocrinology |
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TopEndocrine DiscoveryEndocrinologistsEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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In the Journal 25 Years Ago |
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TopEndocrine DiscoveryEndocrinologistsEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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"The demonstration of 1, 25-(OH)2D3receptors in human monocytes and activated T lymphocytes suggests an expanded role for 1,25-(OH)2D3 in inflammation and immune cell interactions."
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