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Endocrine Discovery |
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 Top Endocrine Discovery Endocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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Regardless of smoking status, overweight and obesity in late adolescence increased the risk of adult mortality in a record linkage study of the Swedish military service conscription register. Obesity and overweight were found to be as hazardous as heavy and light smoking, respectively, but no interaction between BMI and smoking status was discovered. (BMJ [March 14, 2009] 338 (7695):b496)
In a meta-analysis of 108 randomized trials involving 299,310 participants at risk of cardiovascular events, the change in HDL-cholesterol explained little to none of the change in outcomes, whereas a 10 mg/dl reduction in LDL cholesterol led to a relative risk reduction of 7.2% for coronary heart disease deaths. (BMJ [February 28, 2009] 338 (7693):b92)
Increased risk of breast cancer declined markedly soon after discontinuation of combined estrogen plus progestin therapy and was unrelated to changes in mammography use. (N Engl J Med [February 5, 2009] 360 (6):573)
In 1803 premenopausal women with endocrine-responsive early breast cancer, after a 47.8 month median follow-up, goserelin plus anastrole resulted in clinical outcomes similar to those treated with goserelin plus Tamoxifen. The addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival. (N Engl J Med [February 12, 2009] 360 (7):679)
A survey of 20,211 overweight or obese individuals younger than 75 years and 7764 smokers found that new diagnoses can serve as a window of opportunity to prompt older adults to lose weight and stop smoking. (Arch Int Med [February 9, 2009] 169 (3):237)
Continuation of statin treatment provided an ongoing reduction in all-cause mortality for up to 9.5 years among patients with and without a history of cardiovascular heart disease, according to a retrospective cohort study of 229,918 adult participants in a health maintenance organization. (Arch Int Med [February 9, 2009] 169 (3):260)
Systematic delivery of IGF-1 significantly improved physiological behavior and survival and partially rescued immature synaptic function and organization in methyl CpG-binding protein 2 (MeCP2) mutant mice, suggesting the use of IGF-1 in the treatment of Rett Syndrome and other central nervous system disorders caused by delayed synapse maturation. (Proc Natl Acad Sci USA [February 10, 2009] 106 (6):2029)
Another Src family kinase, Lyn, has been found to affect osteoclast function by modulating differentiation, in a manner antithetical to c-Src, which regulates bone resorption by these cells, thus underscoring the necessity of specific targeting of these family members in designing antiresorptive agents. (Proc Natl Acad Sci USA [February 17, 2009] 106 (7):2325)
A prospective study of 1,295 women and men aged 60 years and over found that all low-trauma fractures were linked to increased mortality risk for 5–10 years, with subsequent fractures associated with increased mortality risk for an additional 5 years. (JAMA [February 4, 2009] 301 (5):513)
Low-income pregnant women with diabetes were twice as likely as those without diabetes to be diagnosed with depression during and after their pregnancy. (JAMA [February 25, 2009] 301 (8):842)
In 746 patients with early type 2 diabetes, liraglutide was found to be safe and effective as initial pharmacological therapy and led to greater decreases in weight, blood pressure, HbA1c, and hypoglycemic events than glimepiride. (Lancet [February 7, 2009] 373:473)[CrossRef]
Body mass index above and below the optimum range of 22.5–25 kg/m2 was a strong predictor of overall mortality—from vascular disease at above this range and from smoking-related diseases at below this range—according to a meta-analysis of 57 studies involving 894, 576 adults. People with a body mass index at 40–45 lost about 8–10 years of their lifespan, while those with a body mass index at 30–35 lost about 2–4 years. (Lancet [published online March 18, 2009])
Mouse models of diabetes revealed that downregulation of β-arrestin-2 contribute to insulin resistance and disturbance of insulin signaling, such that β-arrestin-2 cannot scaffold Akt and Src to the insulin receptor. Insight into this signaling pathway may provide new preventive and treatment strategies against insulin resistance and type 2 diabetes. (Nature [February 26, 2009] 457:1146)[CrossRef]
Sphingosine-1-phosphate, a lipid mediator enriched in blood, was found in vitro and in vivo to induce chemotaxis and regulate the migration of osteoclast precursors, thus contributing to bone homeostasis. (Nature [published ahead of print February 8,2009])
FTO-/- mice had a reduction in adiposity and were protected from diet-induced obesity, suggesting that variants in the human FTO gene might render individuals more susceptible to obesity. (Nature [published ahead of print February 22, 2009])
While low to moderate alcohol consumption in a study of 1,280,296 middle-aged women increased the risk of certain cancers such as breast cancer, the risks for other cancers were decreased, such as thyroid cancer and renal cell carcinoma. (J Natl Cancer Inst [March 4, 2009] 101 (5):296)
Treating patients with type 2 diabetes who had survived an acute myocardial infarction with prandial doses of insulin lispro, compared to basal doses of NPH, showed lower postprandial blood glucose, higher fasting blood glucose, similar levels of A1c, and no difference in risk for future cardiovascular event rates. (Diabetes Care [March 2009] 32 (3):381)
A study of 2955 participants aged 12–19 years found that black teens were twenty times more likely to be vitamin D deficient than white teens and that females were at double the risk than males. (Pediatrics [March 2009] 123 (3):797)
A genome-wide association study involving 30,000 subjects identified four rare gene variants that lowered type 1 diabetes risk in IFIH1, a gene encoding a cytoplasmic helicase that mediates the induction of interferon response to viral RNA. (Science [published ahead of print March 5, 2009])
Diet Comparisons Find Calories Count More Than Macronutrients
Diet fads may come and go, but which one is the most effective? Turns out any diet that reduces caloric intake will do as long as people stick to it, according to a recent research article published in The New England Journal of Medicine .
"Calories count. You can lose essentially the same amount of weight with any combo of macronutrients if you adhere to the program," said George Bray, M.D., chief of the division of clinical obesity and metabolism at the Pennington Biomedical Research Center in Baton Rouge, Louisiana, and one of the coauthors of the study article.
In the article, researchers from the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) study found similar weight loss after 6 months and 2 years among participants assigned to four heart-healthy diets that differed in their proportions of three major nutrients—fats, proteins, and carbohydrates. The group assigned 811 overweight and obese adults to one of four diets that ranged in fat content and percentages of energy derived from these macronutrients: a low-fat, average protein diet (20% fat, 15% protein, 65% carbohydrate); a low-fat, high protein diet (20% fat, 25% protein, 55% carbohydrate); a high-fat, average protein diet (40% fat, 15% protein, 45% carbohydrate); and a high-fat, high-protein diet (40% fat, 25% protein, 35% carbohydrate).
The team gave the participants personalized calorie goals, ranging from 1,200 to 2,400 calories a day and required them to participate in moderate exercises of 90 minutes per week such that the overall caloric intake was lower than their daily energy requirement. Additionally, participants recorded their food intake in a diary or an online tool and attended group and individual instructional sessions for 2 years.
On average, participants shed 13 pounds at 6 months and maintained a 9-pound loss at 2 years. They also whittled their waistlines by 1 to 3 inches by the end of the study. Across all four diets craving, fullness, hunger, and diet satisfaction were all similar. Additionally, 14%-15% of the participants had a reduction of at least 10% of their initial body weight, which previous studies have shown to help lower risk factors for heart disease and other medical conditions.
As the largest diet comparison study performed to date, diet specialists hail the study as seminal to the field.
"This study shows that doctors and their patients should spend more time on the amount of food consumed and less attention to the macronutrient composition," said Gary Foster, Ph.D., Director of the Center for Obesity Research and Education at Temple University in Philadelphia, Pennsylvania. "Essentially, whatever you’re eating, eat a little less of it instead of going through the mental gymnastics of counting fats and carbs."
Others in the field point out that this study indicates a diet can be custom-made for the patient to better their chances for long-term success.
"To improve adherence in individual patients, clinicians can learn to match up patients with an appropriate strategy based on lifestyle, medical history, and specific food preferences," said Michael Dansinger, M.D., Principal Investigator of the Tufts Popular Diet Trial, and weight loss and nutrition advisor for the primetime TV weight loss series "The Biggest Loser," adding that his previously published study also found that adherence level, rather than diet type, was the key determinant of weight loss and health benefits.
He suggested that the best approach would be to get patients to commit to a dieting plan and make sure that they have numerous external supports such as doctors, personal trainers, dieticians, friends, and family. (N Engl J Med [February 26, 2009] 360:859)[CrossRef]
Thyroid Cancer Linked to Two Common Gene Variants
Researchers have narrowed in on two common gene variants—on chromosomes 9 and 14—that show an increased susceptibility for thyroid cancer, paving the way for future genetic testing screens for this disease.
"The risk of thyroid cancer has a greater genetic component than the risk of any other cancer, and the effect has been shown to extend beyond the nuclear family," said Julius Gudmundsson at deCODE Genetics in Reykjavík, Iceland, and co-authors in their recent online article in Nature Genetics.
The team conducted a genome-wide association study on an Icelandic study population of 192 thyroid cancer cases and approximately 37,000 controls, followed by a replication study of two case-control groups of European descent (342 cases and 348 controls in the United States, and 90 cases and 1,343 controls in Spain). The first study identified nine single nucleotide polymorphisms (SNPs), which were then genotyped in an additional 241 thyroid cancer cases and resulted in the two SNP candidates, located on 9q22.33 and 14q13.3.
Their research shows that close to 4% of individuals of European descent are homozygous for both high risk alleles, which increases their risk of thyroid cancer by nearly 6-fold compared with noncarriers. The incidence of thyroid cancer is 4.9 and 14.1 per 100,000 in the U.S. for males and females of European ancestry, respectively. Iceland has a similar incidence rate, at 4.6 and 12.1 per 100,000 for males and females, respectively.
Biologically, the locations of each of these SNPs are of interest to thryoidologists as each fall close to two genes that are involved in thyroid development—the chromosome 9 SNP is close to FOXE1 and the chromosome 14 SNP is near NKX2-1. Both variants contribute to a heightened risk of papillary and follicular thyroid cancer, two of the most common forms of thyroid cancer. Furthermore, both SNPs are associated with a decrease in serum levels of thyroid stimulating hormone, potentially causing less thyroid differentiation and more susceptibility to malignancy. Additionally, the chromosome 9 SNP is linked to increased levels of free triiodothyronine and decreased levels of free thyroxine.
Kári Stefánsson, M.D., president and CEO of deCODE and one of the paper’s coauthors, indicated that genetic tests for these candidate genes could be made available to the public within weeks.
Dr. Stefánsson claimed that the tests hold some value.
"We want people to be aware of the risk of disease but not at the risk of scaring them," he said. "We want to make people aware of their risk of disease because we hope it helps to motivate them to change their behavior such as eating better."
However, most thyroidologists and geneticists question whether the public will fully understand the clinical implications of these tests.
"This is not quite ready for clinical prime time—yet. More research needs to be done to bring clinical context to genomic content," said Charis Eng, M.D., Ph.D., chairperson of the Genomic Medicine Institute and Director of the Center for Personalized Genetic Healthcare at the Cleveland Clinic in Ohio, adding that the public and caregivers need to be educated on the broad topic of variant-related risks for disease, and in this context, exactly what is their chance for developing thyroid cancer. The population lifetime risk of thyroid cancer is generally at 1% or less, with higher rates for females than males, she said, explaining that even if a person was found to carry these variants, the six-fold increased risk for thyroid cancer would just raise the lifetime risk from <1% to <6%. (Nat Gen [published ahead of print February 6, 2009])
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Endocrine Practice |
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TopEndocrine DiscoveryEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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Adult Treatment Panel III (ATP III) guidelines are relatively cost-effective and would have a large public health impact if implemented fully in the United States, according to an assessment of their cost-effectiveness and public health impact. Alternate strategies may be preferred, however, depending on the cost of statins and how much society is willing to pay for better health outcomes. (Ann Intern Med [February 17, 2009]150 (4):243)
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Milestones in Endocrinology |
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TopEndocrine DiscoveryEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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In the Journal 25 Years Ago |
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TopEndocrine DiscoveryEndocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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"The present study indicates that both orbital cobalt irradiation combined with systemic methylprednisolone treatment and systemic methylprednisolone therapy alone are valuable methods of treatment for Graves’ ophthalmopathy, but the combined therapy proved to be more effective."
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Footnotes |
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