Faculty Bibliography

BACKGROUND:Limited information is available on the influence of vitamin D on falls in older high-functioning black American women. Endocrine Society guidelines propose serum 25(OH)D levels over 30 ng/mL. OBJECTIVE:To determine if maintenance of serum 25(OH)D above 30 ng/mL protects against falls. DESIGN/METHODS:adjusted to maintain serum 25(OH)D above 30 ng/mL. The primary outcomes were the prevention of bone loss and the decline in physical performance. PATIENTS/METHODS:The target population was healthy black women older than 60 years with serum 25(OH)D between 8 and 26 ng/mL. The trial was 3 years in duration with a falls questionnaire administered every 3 months. A total of 260 women entered the study, and 184 completed the 3 years. Mean age was 68.2 years. SETTING/METHODS:Research center in an academic health center. MAIN OUTCOMES MEASURE/METHODS:Prevention of falls. INTERVENTION/METHODS:dose was adjusted to maintain serum 25(OH)D above 30 ng/mL in the active group using a double-dummy design. RESULTS:Baseline 25(OH)D was 22 ng/mL. Mean serum 25(OH)D reached 47 ng/mL in the active group compared with 21 ng/mL in the placebo group. There were 14.2% falls in the previous year recalled at baseline. During the study, 46% reported falling in the treatment group compared with 47% in the placebo group. There was no association of serum 25(OH)D or vitamin D dose with the risk of falling. CONCLUSIONS:There is no benefit of maintaining serum 25(OH)D above 30 ng/mL compared with the Institute of Medicine recommendation (20 ng/mL) in preventing falls in healthy older black American women.

OBJECTIVES/OBJECTIVE:To examine the effect of 25-hydroxyvitamin D (25(OH)D) levels recommended by Endocrine Society guidelines (>30 ng/mL) on cognition in healthy older African-American women over 3 years. DESIGN/METHODS:Randomized, double-blind, placebo-controlled clinical trial. SETTING/METHODS:Bone Mineral Research Center at New York University Winthrop Hospital. PARTICIPANTS/METHODS:Healthy postmenopausal African American women aged 65 and older (N=260; mean age 68.2 ± 4.9; 46% college education or higher). INTERVENTION/METHODS:Half of the women were randomized to receive vitamin D (adjusted to achieve a serum level > 30 ng/mL) with calcium (diet and supplement total of 1,200 mg), and half were randomized to receive placebo with calcium (1,200 mg). MEASUREMENTS/METHODS:Cognitive assessments every 6 months using the Mini-Mental State Examination (MMSE) to detect cognitive decline. Mean MMSE scores were calculated over time for both groups. Those with MMSE scores less than 21 at baseline were excluded. RESULTS:was 3,490 ± 1,465 IU per day, and average serum 25(OH)D at 3 years was 46.8 ± 1.2 ng/mL in the active group and 20.7 ± 1.1 ng/mL in the placebo group. Serum 25(OH)D concentration was maintained at greater than 30 ng/mL in 90% of the active group. Over the 3-year period, MMSE scores increased in both groups (p < .001), although change over time was not significantly different between the groups. No adverse events associated with vitamin D were observed. CONCLUSION/CONCLUSIONS:There was no difference in cognition over time between older African-American women with serum concentrations of 25(OH)D of 30 ng/mL and greater than those taking placebo. There is no evidence to support vitamin D intake greater than the recommended daily allowance in this population for preventing cognitive decline.

Black Americans have lower levels of serum 25(OH)D but superior bone health compared to white Americans. There is controversy over whether they should be screened for vitamin D deficiency and have higher vitamin D requirements than recommended by the Institute of Medicine (IOM). The purpose of this trial was to determine whether Vitamin D supplementation in elderly black women prevents bone loss. A total of 260 healthy black American women, 60 years of age and older were recruited to take part in a two-arm, double-dummy 3-year randomized controlled trial (RCT) of vitamin D₃ versus placebo. The study was conducted in an ambulatory clinical research center. Vitamin D₃ dose was adjusted to maintain serum 25(OH)D above 75 nmol/L. Bone mineral density (BMD) and serum were measured for parathyroid hormone (PTH), C-terminal crosslink telopeptide (CTX), and bone-specific alkaline phosphatase (BSAP) every 6 months. Baseline serum 25(OH)D₃ was 54.8 ± 16.8 nmol/L. There was no group × time interaction effect for any BMD measurement. For all BMD measurements, except for total body and spine, there was a statistically significant negative effect of time (p < 0.001). An equivalency analysis showed that the treatment group was equivalent to the control group. Serum PTH and BSAP declined, with a greater decline of PTH in the treatment group. The rate of bone loss with serum 25(OH)D above 75 nmol/L is comparable to the rate of loss with serum 25(OH)D at the Recommended Dietary Allowance (RDA) of 50 nmol/L. Black Americans should have the same exposure to vitamin D as white Americans. © 2018 American Society for Bone and Mineral Research.

BACKGROUND/OBJECTIVE:Lipocalin Prostaglandin D2 synthase (LPGDS) contributes to the production of PGD2, which has been associated with adipogenesis. In this study, we aimed to investigate the role of PGD2 on obesity through its DP1 and DP2 receptor signaling using intraperitoneal injection of their respective agonists and antagonists. METHODS:mice were divided into five groups: vehicle control (n=5), DP1 receptor agonist (n=5), DP1 receptor antagonist (n=5), DP2 receptor agonist (n=5), and DP2 receptor antagonist (n=5), and the study was carried out for 10 weeks. RESULTS:Despite being on high fat diet, mice receiving DP1 receptor agonist sustained a significant inhibition of weight gain throughout the study gaining only 11.4% body weight compared to the controls gaining 61% body weight. Interestingly, parallel to the body weight, the DP1 receptor agonist group showed a significant reduction in food intake throughout the study. Consistently, fasting leptin, insulin and bile acids levels were elevated in the DP1 receptor agonist group compared to controls. As expected, there was a significant reduction in fasting glucose level in DP1 receptor agonist group. At last, as a result of weight gain inhibition, DP1 receptor agonist also imparted cardiovascular benefits showing significant reduction in aortic wall thickness, intima, adventia and lumen size. CONCLUSION:Based on the obtained results, we believe DP1 receptor agonism inhibited diet induced weight gain possibly through controlling appetite which consequently imparted beneficial cardiometabolic effects. DP1 receptor agonism may represent a novel therapeutic target for the management of obesity.

RATIONALE/BACKGROUND:Vitamin D deficiency is associated with bone loss, poor muscle strength, falls and fracture. This information in older African Americans (AAs) is sparse. OBJECTIVE:The study of the relationship of Physical performance, Osteoporosis prevention with vitamin D in older African Americans (PODA) is a randomized, double-blind, placebo-controlled 3-year trial examining the effect of vitamin D on bone loss and physical performance in older AA women. METHODS:dose was determined by the baseline serum 25OHD level, and adjusted further to maintain serum 25OHD between 30 and 69ng/ml. Subjects with baseline 25OHD levels ≤8ng/ml or ≥26ng/ml were excluded. Objective measures of neuromuscular strength [Short Physical Performance Battery (SPPB), grip strength and 6-minute walking distance (6MWD)] and bone mineral density (BMD) were obtained. RESULTS:SPPB gait speed, grip strength and 6MWD showed a significant positive correlation with free 25OHD. 1pg/ml increase in free 25OHD predicted a 32% increase in the odds of having higher gait speed and a 1.42lb. increase in grip strength. No significant differences in BMI, BMD, muscle mass, grip strength, serum total 25OHD and free 25OHD were observed between groups. None of the measures of physical performance showed an association with baseline serum 25OHD. CONCLUSIONS:This is the first study to show an association between free 25OHD and physical performance. These findings indicate a positive relationship of free 25OHD with gait speed and grip strength in older AA women. Further studies are needed to understand the role of free 25OHD.

CONTEXT: The vitamin D metabolite ratio (VMR) (serum 24,25(OH)2 D3 /25(OH)D3 ) has been proposed as a biomarker of vitamin D sufficiency to replace serum 25(OH)D. OBJECTIVE: To examine the relationships of 24,25(OH)2 D3 and VMR to functional biomarkers of bone health following vitamin D supplementation. SETTING: An ambulatory research centre. DESIGN: Serum from a previous research study of dose response of PTH, calcium absorption and bone turnover to vitamin D supplementation was analysed for vitamin D metabolites (25(OH)D, 24,25(OH)2 D3 ). OUTCOME: The relationship of serum 24,25(OH)2 D3 and VMR to calcium absorption, PTH and bone turnover markers was examined. RESULTS: Although there were strong correlations of serum 25(OH)D with 24,25(OH)2 D3 and free 25(OH)D, its correlation with VMR was lower. After vitamin D supplementation, the change in 25(OH)D, 24,25(OH)2 D3 and VMR was associated with the change in calcium absorption, PTH and CTX. The correlation of the change in PTH with the change in metabolites was the lowest for VMR. Moreover, estimated dose response for standardized values of vitamin D metabolites showed a beta-coefficient for VMR that was significantly less in magnitude compared to other metabolites. CONCLUSION: Serum 24,25(OH)2 D3 is closely associated with the dose response of serum 25(OH)D to vitamin D supplementation. However, the VMR does not appear to be equivalent to either of these metabolites in its response to increasing vitamin D intake or its association with PTH. It is unlikely that VMR will replace 25(OH)D as a biomarker for vitamin D sufficiency.

BACKGROUND:Glucagon-like peptide-1 (GLP-1) level was significantly increased post Vertical Sleeve Gastrectomy (VSG), an effect believed to contribute to its beneficial cardiometabolic effects. OBJECTIVE:To validate the beneficial GLP-1 mediated cardiometabolic effects post VSG using GLP-1 antagonist (exendin 9-39) in Zucker diabetic fatty rats. METHODS:Animals were divided into three (n = 5) groups: (i) sham, (ii) VSG, and (iii) VSG received exendin 9-39 (GLP-1 receptor antagonist). The study was performed over 12 weeks and parameters were measured 12 weeks post-surgery. RESULTS AND DISCUSSION/CONCLUSIONS:As expected, fasting blood glucose and insulin levels were improved post VSG due to enhanced GLP-1 secretion. However, both fasting glucose and insulin levels were impaired in the presence of GLP-1 antagonist. Baseline total cholesterol level pre-surgery was 100±1 mg/dl which remained unchanged in the VSG group but significantly increased to 140±8 mg/dl in the presence of antagonist. Interestingly, post-surgery there was a nearly 70% reduction in triglyceride level in the VSG group compared to sham which was overcome in the presence of antagonist. Myographic studies using aortic rings showed no significant change between groups. Additionally, blood pressure and heart rate also remained unchanged in all groups. Serum bile acid and L-PGDS levels increased post VSG but significantly decreased in the presence of antagonist, suggesting a strong association with GLP-1 and a novel mechanism of action. CONCLUSION/CONCLUSIONS:Enhanced GLP-1 secretion post VSG imparted beneficial cardiometabolic effects on blood glucose, insulin, total cholesterol, triglyceride, bile acids and L-PGDS levels which were abated in the presence of GLP-1 antagonist.

BACKGROUND:Vertical sleeve gastrectomy (VSG) ameliorates metabolic complications in obese and diabetic patients through unknown mechanisms. OBJECTIVE:synthase (L-PGDS) in glucose regulation in response to VSG using L-PGDS knock-out (KO), knock-in (KI), and C57BL/6 (wild type) mice. SETTING/METHODS:Winthrop University Hospital Research Institute. METHODS:Animals were divided into 6 groups: L-PGDS KO sham/VSG (n = 5), L-PGDS KI sham/VSG (n = 5), and C57BL/6 (wild type) sham/VSG (n = 5). Related parameters were measured in fasting animals after 10 weeks. RESULTS:Our intraperitoneal glucose tolerance tests and homeostatic model assessment insulin resistance results showed significant glycemic improvement 10 weeks post-VSG in both C57BL/6 and KI groups compared with the sham group. In contrast, the KO group developed glucose intolerance and insulin resistance similar to or greater than the sham group 10 weeks post-VSG. Interestingly, weight gain was insignificant 10 weeks post-VSG in all the groups and even trended higher in the KO group compared with sham. Peptide YY levels in the KO group post-VSG were slightly increased but significantly less than other groups. Similarly, the KO group showed significantly less leptin sensitivity in response to VSG compared with the KI group. Total cholesterol level remained unchanged in all groups irrespective of sham or surgery but interestingly, the KO group had significantly higher cholesterol levels. In parallel, adipocyte size was also found to be significantly increased in the KO group post-VSG compared with the sham group. CONCLUSION/CONCLUSIONS:Our findings propose that L-PGDS plays an important role in the beneficial metabolic effects observed after VSG.