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In a 1-year randomized, double-blind study of 5 mg intravenous zoledronic acid versus 5 mg oral risedronate for both prevention and treatment of glucocorticoid-induced osteoporosis, zoledronic acid was superior to risedronate in increasing lumbar spine bone mineral density, but there were more adverse events in patients given zoledronic acid as a result of transient symptoms during the first 3 days after infusion. (Lancet [April 11, 2009] 373 (9671):1253)
A genetic risk score (GRS) calculated on the basis of 10 polymorphisms in 9 loci, was found to confer increasing risk of type 2 diabetes with each quintile of GRS, especially in individuals with BMI > 30 kg/m2, and a positive family history of diabetes, but addition of the GRS to a model of conventional risk factors improved discrimination by only 1%, in a study of 2809 patients with type 2 diabetes and 3501 healthy controls, (Ann Intern Med [April 21, 2009] 150 (8):541)
Mice lacking the intestinal lipid synthesis enzyme acyl CoA:monoacylglycerol acyltransferase-2 and fed a high-fat diet were protected against developing obesity, glucose intolerance, hypercholesterolemia, and fatty livers, suggesting that inhibition of this enzyme may be a useful treatment strategy for obesity and other metabolic diseases associated with excessive fat intake. (Nat Med [published online March 15, 2009])
A 1-year randomized trial among 194 obese participants of lifestyle versus sibutramine therapy found similar reductions in depression among these therapies, but a worsening of mood in 13.9% of all patients. (Obesity [May 2009] 17 (5):1009)
Night eating was found to be 2.5 and 2.8 times more common in obese men and women compared to normal weight controls and associated with binge eating and sleep-related problems, according to a study of 21,741 Swedish twins aged 20–47 years old. (Obesity [May 2009] 17 (5):1050)
Oxytocin was found to be a direct anabolic regulator of bone mass, based on complementary genetic and pharmacologic approaches, pointing to possible implications for osteoporosis therapy. (Proc Natl Acad Sci USA [April 28, 2009] 106 (17):7149)
Pyrvinium pamoate and harmol hydrochloride, two non-ligand inhibitors of androgen receptor activity, were found to be likely therapeutic candidates for such diseases as hirsutism, benign prostatic hypertrophy, and prostate cancer. (Proc Natl Acad Sci USA [April 28, 2009] 106 (17):7233)
Aspirin usage of 325 mg every other day was linked to a lower risk of diabetes, according to a 22-year longitudinal study of 22,071 healthy male physicians. (Am J Med [April 2009] 122 (4):374)
Examination of 70,781 men and women aged 66 years or older with stages I through III breast cancer found that those with breast cancer and diabetes are at increased risk of chemotherapy-related toxicities and have higher all-cause mortality than those who just had cancer alone. (J Clin Oncol [May 1, 2009] 27 (13):2170)
Rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism, according to a clinical trial of 17,802 healthy men and women who received either a 20 mg daily dose of the drug or placebo. (N Engl J Med [April 30, 2009] 360 (18):1851)
A 10-year prospective analysis among 4883 men and women 65 years or older revealed that even later in life, combined lifestyle factors—including physical activity level, dietary habits, smoking habits, alcohol use, and adiposity measures—are associated with a lowered incidence of new-onset diabetes mellitus. (Arch Intern Med [April 27, 2009] 169 (8):798)
Combined with lifestyle modification, voglibose, an 
-glucosidase inhibitor, reduced the development of type 2 diabetes in high-risk Japanese individuals with impaired glucose tolerance.
(Lancet [published online April 22, 2009])
A randomized controlled trial of 1123 participants with type 2 diabetes and no symptoms of coronary artery disease found that cardiac event rates were low in this patient group and were not significantly reduced by MRI screening for myocardial ischemia. (JAMA [April 15, 2009] 301 (15):1547)
According to a retrospective cohort study of 7820 patients hospitalized with acute myocardial infarction and hyperglycemic on admission, spontaneous development of hypoglycemia was linked to increased mortality whereas iatrogenic hypoglycemia after insulin therapy was not. (JAMA [April 15, 2009] 301 (15):1556)
A prospective phase I/II study of 23 patients with newly diagnosed type 1 diabetes mellitus, aged 13–31 years, who underwent autologous nonmyeloablative hematopoietic stem cell transplantation found that these patients had increased C-peptide levels and that most achieved insulin independence with good glycemic control. (JAMA [April 15, 2009] 301 (15):1573)
A study of 69 metformin-treated patients with type 2 diabetes who were randomly treated for 1 year with exenatide or insulin glargine found that exenatide significantly improved β-cell function compared to insulin glargine. Once treatment with either drug was stopped however, β-cell function and glycemic control returned to pretreatment values, suggesting that ongoing treatment with either of these drugs is necessary. (Diabetes Care [May 2009] 32 (5):762)
Subjects diagnosed with type 1 diabetes through the Diabetes Prevention Trial-Type 1 had few symptoms, normal A1C, rare ketosis, and evidence for insulin production at the time of diagnosis, suggesting that intermittent screening and follow-up of islet autoantibody-positive subjects may allow for early diagnosis and that sole screening of A1C may not be adequate. (Diabetes Care [May 2009] 32 (5):769)
Examination of 652 women with type 1 diabetes revealed that female sexual dysfunction was common, with depression being the major predictor for this disorder. (Diabetes Care [May 2009] 32 (5):780)
Metabolic profiling of obese versus lean humans and examination of rats fed on high-fat, high-fat with supplemented branched-chain amino acid (BCAA), or standard cow, revealed that BCAA contributes to the development of obesity-associated insulin resistance. (Cell Metab [April 8, 2009] 9:311)[CrossRef]
Two new studies indicated that bisphosphonates may not raise the risk of esophageal cancer. (N Engl J Med [April 23, 2009] 360 (17):1789)
A prospective observational study of 4006 men and women showed that daily nitrate use was associated with increased bone mineral density at the hip and spine of both groups. (Osteoporos Int [May 2009] 20:737)[CrossRef]
Brown Adipose Tissue Found in Adults
Three recent studies in The New England Journal of Medicine confirmed the presence of energy-burning brown adipose tissue in adults, paving the way for exploiting this fat in weight control.
Once thought only to exist in small mammals and newborns, and then to completely dwindle upon human adulthood, brown fat differs from white fat in its appearance and function. For one, the presence of more mitochondria lends to its brown color. Also, these cells contain multiple lipid droplets as opposed to the one fat lipid droplet seen in regular fat. Whereas white fat primarily stores fat, brown fat helps to regulate body temperature by non-shivering thermogenesis.
Mounting evidence over the years suggests brown fat’s presence in adults. Brown fat depots appeared in adult patients with catecholamine-secreting tumors such as pheochromocytomas and paragangliomas. Furthermore, radiologists reported the presence of increased "noise" in their 18F-fluorodeoxyglucose positron-emission tomographic and computed tomographic (PET/CT) scans in the neck, chest, and abdomen—all areas where brown fat lurks in infants—during the winter months that would dampen when the patients were placed in warmer environments.
Exploiting the latter phenomena, all three NEJM articles prospected for brown fat. Wouter van Marken Lichtenbelt, Ph.D., of the University of Masstricht in The Netherlands, and his group, compared PET/CT scans in 24 men, who were either lean or obese, during exposure to cold temperature and room temperature conditions. They found that the leaner men had increased amounts of more active brown adipose tissue than those who were obese, and that this activity disappeared in individuals at room temperature.
Similarly, C. Ronald Kahn, M.D., of Harvard Medical School in Boston, and his colleagues pored over PET/CT scans of nearly 2000 patients and found that more women than men had positive scans showing active brown fat—7.5% vs. 3.1% or a ratio of 2:1—and that the amount declined with age.
The third group, led by Sven Enerbäck, M.D., Ph.D., at the University of Göteborg, Sweden, used PET/CT scans to pinpoint brown adipose tissue deposits in subjects exposed to cold, and confirmed the tissue’s identity by looking at brown adipose tissue-specific genes such as uncoupling protein 1.
Researchers and clinicians remain cautiously optimistic about this finding. "It’s interesting as an indication that this tissue is still present and chemically active in adult humans," said Rudolph Leibel, M.D., co-director of the Naomi Berrie Diabetes Center at Columbia University. "Whether this tissue will be exploitable as a therapeutic device will need to be readdressed," he said, adding that previously, investigators had reported that overfed rats had increased activity of brown adipose tissue, linking this fat not only to temperature regulation, but to calorie burning. The pharmaceutical industry tried to activate thermogenesis through β-agonists in humans, but limited efficacy and elevations in blood pressure led to abandonment of this approach to obesity treatment.
Abhimanyu Garg, M.D., internal medicine professor at the Center for Human Nutrition in The University of Texas Southwestern Medical Center at Dallas, concurred: "Whether the lack of it or reduced activity of brown adipose tissue will be one of the factors causing obesity remains to be seen." He further pointed out that thyroid hormone and adrenergic agents stimulate this tissue. Dr. Garg suggested that a thyroid hormone analogue or adrenergic receptor stimulating agent may be developed that acts solely on brown fat and not on other tissues. (N Engl J Med [April 9, 2009]360 (15):1500; N Engl J Med [April 9, 2009] 360(15):1509; N Engl J Med [April 9, 2009] 360(15):1518)
Medicare Linked to Improved Cardiovascular and Diabetes Outcomes
More Americans may be in control of their cardiovascular disease and diabetes, but racial, ethnic, and socioeconomic differences continue to persist, calling to question the idea of universal or expanded health care coverage for adults before they can receive Medicare coverage.
Racial and ethnic minorities and less educated adults are more likely to be uninsured or underinsured, making it less likely that they receive basic clinical services for these conditions. Essentially these groups may end up playing a waiting game in which they address their health issues once they reach age 65 and are eligible for Medicare. While this may work for some, for others it may be too late.
A recent study published in the Annals of Internal Medicine used data from the 1999–2006 National Health and Nutrition Examination Survey to measure changes in disease control over time as well as the possible association of improved control with near-universal Medicare coverage after age 65. Using a serial cross-sectional study design, the authors focused on people who reported having diabetes, hypertension, coronary heart disease, or stroke. The authors defined disease control in the following fashion: hemoglobin A1C levels <7% among patients with diabetes; average blood pressure <140/90 mm Hg among those with hypertension; and total cholesterol levels <5.2 mmol/L (200 mg/dL) among those with diabetes, coronary heart disease, or stroke.
Over these 8 years, the authors found that disease control measures improved overall from 10% to 21%. However, improvements in disease control were not associated with discernable reductions in racial, ethnic, or socioeconomic differences in blood pressure or glycemic control. An 8% difference was seen in hypertension control rates between white and African American adults, and a 15% difference in diabetes control rates was observed between high school graduates and nongraduates. Gaps in glycemic control actually widened between white and Hispanic adults.
"The tide is rising and appears to be lifting all boats, but there are still many racial and ethnic minorities and adults of lower socioeconomic status being left behind," said J. Michael McWilliams, M.D., Ph.D., assistant professor at the Department of Health Care Policy of Harvard, and the study’s lead author.
The numbers improved when McWilliams’ group analyzed the health disparities by age, specifically before and after 65 years of age. Before age 65, African American patients had a 7.0 mm Hg higher systolic blood pressure than white patients. But after this cut-off age, this difference was only 2.8 mm Hg. Similarly, the mean difference in hemoglobin A1C levels between non-high school graduates and graduates was 0.6% before age 65 and 0.1% after age 65.
"This implies that while current quality improvement may not be reducing disparities, we might expect universal coverage to do so," said Dr. McWilliams. "Health disparities have existed for far too long in this country, and addressing uninsurance is likely to be a key part of the solution."
In an accompanying editorial in the same journal, Ashwini R. Seghal, M.D., Director of the Center for Reducing Health Disparities, at Case Western Reserve University, Cleveland, Ohio, indicated a call to action must be taken to expand health care coverage, especially now that this is back on the current Administration’s political agenda.
"As physicians and researchers, we have described insurance-related health disparities and studied their mechanisms. Too seldom have we implemented interventions designed specifically to reduce disparities," he wrote. "A comprehensive universal health care intervention is desirable, feasible, and necessary."
Harold Pollack, Ph.D., Chair of the Center for Health Administration Studies at the University of Chicago, echoed the same sentiment. "The health reform debate often turns out to be a health financing debate. For instance, how do we finance medical services? One of the issues that’s actually lost is would we be healthier if we covered everyone?" (Ann Intern Med [April 21, 2009]150 (8):505)
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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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"Peak calcitonin after pentagastrin stimulation remains the best diagnostic marker for medullary thyroid cancer. However, CEA may be a better prognostic indicator, as it discriminated more efficiently between patients with and without metastases."
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