University of Pittsburgh

Statins for Young T1D Patients, Too?

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Type 1 diabetes patients younger than 40 may be candidates for statin use, as guidelines recommend after age 40, researchers suggested.

Under the American Heart Association/American College of Cardiology definition, the 10-year cardiovascular risk was about 5% for type 1 diabetes patients ages 30 to 39 and about 13% in those ages 40 to 44, Rachel G. Miller, MD, of the University of Pittsburgh, and colleagues found.

Adding coronary revascularization to that definition — which also included cardiovascular death or nonfatal stroke or myocardial infarction — brought the 10-year risk to nearly 7% for type 1 diabetes patients in their 30s, the group reported here at the American Diabetes Association meeting.

Although still a little shy of the 7.5% 10-year risk threshold recommended for statin treatment in the guidelines, the 20% of the cohort already on a statin before age 40 was excluded along with a number of events that happened before the start of follow-up.

“We conclude that young adults aged 30 to 39 years with 20 or less years’ type 1 diabetes duration are at sufficiently high atherosclerotic cardiovascular disease risk to merit statin therapy,” the group concluded in their poster presentation.

Both the AHA/ACC and the American Diabetes Association guidelinesrecommend statins after 40 for essentially all diabetes patients and support possible use for younger people with cardiovascular disease risk factors.

“We’ve been comfortable with the concept that anybody over the age of 40 with type 2 should be on a statin and by extrapolation anybody who has type 1 over the age of 40 should be recommended for statins,” commentedNaveed Sattar, MD, a metabolic medicine specialist at the University of Glasgow, Scotland.

“What we now need is good guidance: Who are these people under 40 with type 1 who should get a statin, and how do we recognize them?” he toldMedPage Today.

There isn’t enough data to develop a risk score for type 1 diabetes yet, he noted. Lifetime risk might be a better criterion in that population than the 10-year risks, which are heavily predicated upon age and which underpin current guidelines, Sattar noted.

“I think in the next 2 or 3 years either from national databases within Scandinavia or Scotland we’re going to have a type 1 diabetes risk score that might allow us to look at this question,” he suggested.

Comparisons with the general population in the surrounding county showed huge elevations in risk with type 1 diabetes even at these early ages, but absolute event numbers were small in Miller’s study.

Among the 517 people under age 45 without pre-existing atherosclerotic cardiovascular disease followed from 1996 to 2011 in the Pittsburgh Epidemiology of Diabetes Complications study (a prospective group of childhood-onset cases seen at a single center soon after diagnosis):

  • One event occurred in 20- to 29-year-olds
  • 18 accrued in those in their 30s
  • 22 occurred in participants in their early 40s

The fatal coronary artery event and nonfatal stroke or MI rates were 134 per 100,000 in the cohort ages 20 to 29, 502 per 100,000 people in their 30s, and 1,336 per 100,000 in the 40 to 44 age range.

Sattar cautioned against overinterpreting the “very crude analysis.”

Single-dose zoledronic acid improves BMD in frail older women

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A single infusion of zoledronic acid in frail older women with cognitive impairment and mobility issues improved both bone density and bone turnover for 2 years, according to research in JAMA Internal Medicine.

The 2-year, randomized, placebo-controlled, double blind study suggests that even the most vulnerable patients can respond well to a bisphosphonate for osteoporosis treatment, according to researchers.

“Trials of younger and healthier elderly suggest that the risk of a devastating hip fracture can be cut in half with such therapy, so it’s important to know if that’s also true, for instance, for seniors in nursing homes,” Susan Greenspan, MD, of the department of medicine at University of Pittsburgh, toldEndocrine Today.

Susan Greenspan

Greenspan and colleagues analyzed data from 181 women aged 65 years or older with osteoporosis, including patients with cognitive impairments and immobility who lived in nursing homes or assisted living facilities, as part of the ZEST study. Participants were enrolled and treated from December 2007 to March 2012. All patients received either 5 mg IV zoledronic acid or placebo, as well as a daily divided dose of vitamin D (800 IU/day) and 1,200 mg/day of elemental calcium. Researchers measured hip and spine bone mineral density, as well as adverse events, such as falls, at 12 and 24 months.

Mean BMD at the hip increased by 2.8% for the treatment group compared with a –0.5% loss for the placebo group at 12 months (P < .001); a 2.6% increase compared with a –1.5% loss was observed for the treatment and placebo groups, respectively, at 24 months (P < .001). The treatment group also had a greater increase in mean spine BMD at 12 months (3% vs. 1.1%; P = .01) and at 24 months (4.5% vs. 0.7%; P < .001). Results were maintained after adjustment for a baseline imbalance in frailty, diabetes and anticonvulsant use, and there were no significant differences between groups in the number of deaths, fractures or cardiac events, according to researchers.

The study marks the first randomized trial of a potent antiresorptive therapy with a group of frail older women. With research now suggesting the drug can be administered to this particular group safely and is well tolerated, a larger trial is needed to determine whether fracture reduction can also be achieved, according to researchers.

“This study has answered those questions and, thereby, sets the stage for the bigger trial, which we hope will be funded by NIH,” Greenspan said. – by Regina Schaffer

‘HAVEN’T MY NEURONS SEEN THIS BEFORE?’

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The world grows increasingly more chaotic year after year, and our brains are constantly bombarded with images. A new study from Center for the Neural Basis of Cognition (CNBC), a joint project between Carnegie Mellon University and the University of Pittsburgh, reveals how neurons in the part of the brain responsible for recognizing objects respond to being shown a barrage of images. The study is published online by Nature Neuroscience.

The CNBC researchers showed animal subjects a rapid succession of images, some that were new, and some that the subjects had seen more than 100 times. The researchers measured the electrical response of individual neurons in the inferotemporal cortex, an essential part of the visual system and the part of the brain responsible for object recognition.

In previous studies, researchers found that when subjects were shown a single, familiar image, their neurons responded less strongly than when they were shown an unfamiliar image. However, in the current study, the CNBC researchers found that when subjects were exposed to familiar and unfamiliar images in a rapid succession, their neurons — especially the inhibitory neurons — fired much more strongly and selectively to images the subject had seen many times before.

It was such a dramatic effect, it leapt out at us,” said Carl Olson, a professor at Carnegie Mellon. “You wouldn’t expect there to be such deep changes in the brain from simply making things familiar. We think this may be a mechanism the brain uses to track a rapidly changing visual environment.”

The researchers then ran a similar experiment in which they used themselves as subjects, recording their brain activity using EEG. They found that the humans’ brains responded similarly to the animal subjects’ brains when presented with familiar or unfamiliar images in rapid succession. In future studies, they hope to link these changes in the brain to improvements in perception and cognition.

For Spiders, It’s Cruel to Be Kind.

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It turns out nice guys do finish last, at least among arachnids. A 6-year study of a New World spider reveals that although colonies composed of docile individuals fare better in the short term, their passive behavior ultimately does them in. A species may need a mean personality to keep from going extinct, the results suggest.

Not all spiders earn their frightening reputations. Even within a single species, some individuals are much mellower than others. Take the social spider Anelosimus studiosus, a native of North and South American forests that builds collective webs that house 40 to 100 individuals. In 2005, ecologists discovered that not all A. studiosus had the same disposition. When two spiders shared a container overnight, docile animals remained beside each other the whole time, whereas aggressive ones attacked each other and then moved to opposite corners. Jonathan Pruitt, an ecologist at the University of Pittsburgh in Pennsylvania, wondered which personality was more successful in the wild.

To find out, Pruitt performed personality tests on dozens of A. studiosus spiders and then arranged them into 90 couples consisting of an aggressive pair, a docile pair, or an aggressive spider matched with a docile one. The arachnids’ personalities are heritable, so a docile pair produces almost exclusively docile offspring, aggressive mates mainly make aggressive offspring, and mixed pairs produce a combination of docile and aggressive babies. After 1 week in the lab, each of the pairs had created small webs, or nests, on chicken wire within separate containers.

Pruitt returned to the Tennessee woods where he originally collected the spiders and wired each of the 90 nests onto trees and shrubs. For the next 5 years, he removed other species of spiders from the territory surrounding half of the webs. These 45 webs served as a control to test the hypothesis that disposition matters when hungry, solitary spiders abound in nature. The colonies in these well-maintained territories faired roughly the same as one another between 2007 and 2012, no matter the personality of their founders.

In contrast, colonies in the areas that were open to invaders differed from one another over time as solitary spiders began to infest the webs. Colonies founded by aggressive spiders successfully fought the intruders off, but produced fewer offspring because of the continuous conflict. In contrast, the predominantly docile colonies ignored intruders and continued to reproduce. In 2009, the docile colonies were flourishing, and their offspring had begun three times as many new colonies on nearby trees and shrubs compared with offspring from aggressive communities. Yet by 2010, the docile spiders’ apparent advantage began to wane as invaders increasingly ate them and stole the insects snagged by the colonies’ webs. By 2012, not a thread remained from the webs established by docile pairs, and only a quarter of those started by mixed pairs were left. Meanwhile,three-quarters of the original 15 nests founded by aggressive pairs stood strong, the team reports today inEcology Letters.

In nature, A. studiosus colonies consist of a mix of docile and aggressive individuals. In short-term studies, Pruitt says, aggressive spiders appear to be troublemakers because they often brawl with members of their own group. However, this study showed their importance when it comes to defense. “Originally, I thought aggressive spiders exploited docile ones, but now I see that the aggressive ones catch most of the food and take care of the society,” he says. Without aggressive spiders to care for them, docile spiders would go extinct whenever other spiders abound. Pruitt speculates that docile behavior still exists because it is useful to the colony in small doses. Perhaps docile individuals provide better care to hatchlings, he says.

For these spiders, passivity represents an “evolutionary dead end” because it comes with quick payoffs but dooms the lineage over time, Pruitt says. Much of the evidence for dead-end strategies comes from mathematical models that predict extinction after a tipping point, but this study documents such a strategy in action and defines the conditions that lead to a lineage’s demise. “The tipping point occurs when invaders are abundant,” Pruitt says. “Without them, colonies founded by docile individuals would flourish, but with them, they succumb to extinction.” The results from this study suggest something about aggression in general, Pruitt adds. “Species without defense might be driven to extinction by enemies”.

“This is a great, robust study that takes the study of animal temperament—which is kind of narrow—and puts it into a broad evolutionary framework,” says James Traniello, a behavioral ecologist at Boston University. “The whole idea of evolutionary dead-end strategies is poorly understood,” he says. A number of studies, such as those on Darwin’s finches, document how species diversify in real time, Traniello says, “and here we have a study that shows what goes on at the opposite side, how lineages decline.”

Source: sciencemag.org