News from the latest research

VITAMIN D and MUSCLE STRENGTH in Adults

Vitamin D has been shown to offer no improvements in muscle strength for adults, according to a Norwegian study recently published in the Journal of Clinical Endocrinology and Metabolism.

The paper’s lead author, Kirsten V. Knutsen, of the University of Oslo, wrote that while vitamin D has multiple biological effects, “some of which appear to impact muscular functioning,” the effect of vitamin D on muscle strength in adults has not been established. The researchers also noted that vitamin D deficiency is “prevalent worldwide,” and in Norway especially, common among immigrants from Africa, the Middle East, and Asian countries.

The scientists evaluated 251 healthy adult males and females aged 18 to 50 years with a “non-Western immigrant background” in a randomized, doubleblind, placebo-controlled trial. Participants were given daily supplementation of 25µg (1000 IU) vitamin D3, 10µg (400 IU) vitamin D3, or placebo over the course of 16 weeks. Th ey measured for primary outcomes of the differences in participants’ jump heights between preand post-intervention. Th ey also measured for secondary outcomes the differences in hand-grip strength and chair-rising tests, in which participants were instructed to rise from a sitting position and to sit down again five times without using the chair arms, as fast as possible.

Theresults showed that percentage in jump height did not differ between those receiving vitamin D supplementation and those receiving the placebo. There were no significant effects of the intervention of vitamin D3 on either the primary or secondary outcomes.

The authors concluded, “Daily supplementation with 25 or 10µg vitamin D3 for 16 weeks did not improve muscle strength or power measured by the jump test, handgrip test, or chair-rising test in this population with low baseline vitamin D status.”

Primary Hyperparathyroidism GOES UNDIAGNOSED

People who have primary hyperparathyroidism (PHPT) often go undiagnosed, even though lab results indicating hypercalcemia could signal a problem and be an early warning sign of PHPT, according to a paper published in the December issue of the journal Surgery.

Allan Siperstein, MD, of the Cleveland Clinic’s Endocrine Surgery Department, and his team noted that when PHPT is recognized, “a review of the medical record reveals elevated calcium and/or parathyroid hormone (PTH) values have been present for longer periods of time.” Therefore, they set out to examine electronic medical records (EMR) and “gain insight into the incidence of undiagnosed and unrecognized PHPT.”

The researchers examined the EMR of 2.7 million patients and found that 54,198 (2%) had hypercalcemia (>10.5 mg/ dL). They then took a two-year sample of 7,269 hypercalcemic patients and discovered that only 33% had PTH levels checked. When stratified by calcium level, PTH was checked in 31% of those with calcium values between 10.6 and 11, and increased to 52% when calcium values were greater than 12. Overall, At least 43% of patients with elevated calcium were likely to have primary hyperparathyroidism with just over half of these confirmed by elevated PTH values and the remaining estimated to have PTH by chart review.

They concluded that unlike elevated blood sugars or cholesterol, typically prompting evaluation and treatment, elevated calcium values are often not evaluated. There is clearly opportunity for early recognition and treatment for patients with hyperparathyroidism.

BARIATRIC SURGERY Improves Sexual Functioning in Obese Women

Women who underwent bariatric surgery for obesity experienced an improvement in overall sexual functioning, a study published in the November 4 issue ofJAMA Surgery shows.

Scientists, led by David B. Sarwer, PhD, of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, assessed a prospective cohort study of 106 women who had weightloss surgery — 85 of whom underwent Rouxen-Y gastric bypass, and 21 of whom underwent laparoscopic adjustable gastric banding. One year after surgery, the women had lost a mean of 32.7% of initial body weight and 33.5% of initial body weight at postoperative year two.

Two years after surgery, the women reported “significant improvements in overall sexual functioning and specific domains of sexual functioning: arousal, lubrication, desires, and satisfaction” based on the Female Sexual Function Index — a 19-item questionnaire that assesses six domains of sexual functioning. The women also showed improvements in sex hormone levels when assessed by blood samples, as well as significant improvements “in most domains of quality of life.”

The authors concluded that “these results suggest that improvements in sexual health may be added to the list of benefits associated with large weight losses seen with bariatric surgery. Future studies should investigate if these changes endure over longer periods of time, and they should investigate changes in sexual functioning in men who undergo bariatric surgery.”

MIDRANGE TESTOSTERONE LEVELS Better for Older Men

Optimal androgen levels — meaning they are neither low nor high — in older men are associated with lower mortality, according to a study recently published in theJournal of Clinical Endocrinology and Metabolism.

Researchers led by Bu Beng Yeap, MBBS, FRACP, PhD, of the University of Western Australia, have shown that older men who have high levels of testosterone (T) may be prone to just as many health concerns and even a higher mortality risk.

The body metabolizes T into dihydrotestosterone (DHT), and the authors noted that a previous study showed an association between low DHT levels and risk of ischemic heart disease (IHD). They also looked at estradiol levels (E2), as “the association of DHT or E2 levels with ill health in aging men is controversial.”

The population-based cohort study analyzed the mortality rate in a group of 3,690 community-dwelling men between the ages of 70 to 89 in Perth, Western Australia. Participants’ testosterone and DHT levels were measured between 2001 and 2004. Researchers analyzed the group’s survival rate as of December 2010.

To accommodate “nonlinear associations,” the men’s hormone levels were analyzed as quartiles. Men in the second and third quartiles (midrange levels — 9.8 to 15.8 nmol/L) had lower all-cause mortality than their counterparts in the first and fourth quartiles. “Levels of T, calculated free T, and DHT corresponding to values within the third quartile were consistently associated with the lowest risk of dying of any cause.”

“In conclusion,” the authors wrote, “optimal circulating total T is a robust biomarker for survival in aging men. However, higher DHT levels are associated with reduced IHD mortality, consistent with a possible cardioprotective influence of androgen exposure,” although they noted that further research is needed.

COUP-TFII Plays Role in Inflammation, Endometrial Diseases

Chicken ovalbumin upstream promotertranscription factor II (COUP-TFII) plays a role in controlling the expression of inflammatory cytokines, a study recently published in Molecular Endocrinology has shown.

What’s more, COUPTFII — an orphan nuclear receptor involved in cell-fate specification, organogenesis, angiogenesis, and metabolism — regulates a subset of genes in endometrial stroma cell decidualization, such as those involved in cell adhesion, angiogenesis, and inflammation.

This discovery by a group of investigators led by Drs. F. DeMayo, S. Tsai, (Baylor College of Medicine) S. Young (University of North Carolina), B. Lessey (Greenville Health System), and J. Jeong (Michigan State University) may provide a key insight into COUP-TFII’s role in embryo implantation and endometrial diseases such as endometriosis, a disease that affects about 6% – 10% of women and occurs in 40% – 50% of infertile women. The most common — and debilitating — symptom is chronic pelvic pain.

The scientists collected human endometrial samples of full-thickness endometrium from 23 regularly cycling women with no history of endometriosis between the ages of 18 and 50 who were undergoing a hysterectomy. These samples were collected at the time of surgery in order to examine COUP-TFII in the endometrium throughout the menstrual cycle. They then obtained biopsies from another 47 regularly cycling women aged 18 to 50 “to compare COUPTFII expression patterns of euptopic endometrium between with and without endometriosis.” Moreover, they collected biopsies during the secretory phase of the menstrual cycle from nine patients diagnosed with endometriosis to compare differential expression of COUP-TFII between eutopic and ectopic endometrium of same patient.

DeMayo and team then “interrogated” the COUPTFII by using a “small interfering RNA-mediated loss of function approach” in primary endometrial stromal cells they collected and found that COUPTFII had a “selective effect on gene expression.”

The researchers demonstrated that “COUP-TFII is spatially and temporally expressed in endometrial stroma cells during the menstrual cycle in women. Furthermore, COUP-TFII was found to be reduced in stroma cells of ectopic lesions in endometriosis patients. Cistromic and transcriptomic analyses demonstrated that COUP-TFII regulates processes critical for human endometrial stroma cell decidualization in vitro. Specifically, COUP-TFII is responsible for the down regulation of inflammatory genes during decidualization. This may contribute to the function of decidual stroma cells in pregnancy and the pathology observed in endometriosis.”

GHRELIN SUPPRESION After RYGB Surgery

Obese patients with type 2 diabetes (T2D) who undergo Roux-en-Y gastric bypass (RYGB) surgery may develop a return to normal regulation of acylated ghrelin (AG), which leads to improved glucose control, according to a study recently published in the International Journal of Obesity.

AG is a gluco-regulatory/appetite hormone, and Sangeeta R. Kashyap, MD, at the Cleveland Clinic, and her team wanted to investigate whether the hormone had any effect on glucose metabolism and body composition after RYGB. The authors wrote, “Acylated ghrelin appears to be more important in appetite regulation, as it has potent effects on hypothalamic food initiation centers and adipogenesis. In addition, total/ acylated ghrelin reduces glucosestimulated insulin secretion and attenuates glucose uptake. Thus, given the improvement in body fat and glycemic control following bariatric surgery, it seems reasonable to expect that bariatric surgery could suppress acylated ghrelin in obese individuals with type 2 diabetes.” However, until now, there had been no data on the effects of bariatric surgeries on acylated ghrelin in people with type 2 diabetes.

The researchers evaluated 53 obese, “poorly controlled” patients with T2D in the Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial, a prospective, randomized control study. The participants either received intensive medical therapy (IMT), a combination of IMT and RYGB surgery, or IMT and sleeve gastrectomy (SG), then “a mixed-meal tolerance test at baseline, 12, and 24 months (m), for evaluation of AG suppression (post-prandial minus fasting) and beta-cell function (oral disposition index; glucose-stimulated insulin secretion x Matsuda index).”

RYGB and SG produced “comparable” reduced body fat in the patients at one year and two years, but IMT had no effect. The scientists seemed to have expected the results of IMT, as they wrote that long-term compliance to IMT is often poor and usually leads to additional pharmacological treatment. Beta-cell function improved in the RYGB patients and was better at two years than patients who received IMT. At two years, the bariatric surgeries lowered post-prandial AG more than IMT, and AG suppression was better following RYGB at two years than IMT or SG. “At 24m,” the researchers wrote, “AG suppression was associated with increased post-prandial GLP-1 (r=0.32, P<0.02) and decreased android fat (r=0.38; P<0.006).” Kashyap and her team concluded the “enhanced AG suppression persists for up to two years after RYGB,” which results in reduced body fat and improved insulin secretion, and the findings may explain why patients who undergo RYGB surgery experience improved glucose control.

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