Tang J.,Kogod Center on Aging |
Pei Y.,Guangdong Medical College |
Zhou G.,Guangdong Medical College
Experimental Gerontology | Year: 2013
Diabetes mellitus is a metabolic disorder that is characterized by high blood glucose because of the insulin-resistance and insulin-deficiency in Type 2, while the insulin deficiency due to destruction of islet cells in the pancreas in Type 1. The development of Type 2 diabetes is caused by a combination of lifestyle and genetic factors. Aging patients with diabetes are at increased risk of developing cognitive and memory dysfunctions, which is one of the significant symptoms of Alzheimer disease (AD). Also, over 2/3 of AD patients were clinically indentified with impairment of glucose. Cognitive dysfunction would be associated with poor self-care ability in diabetes patients. This review will briefly summarize the current knowledge of the pathogenesis of these two diseases and highlight similarities in their pathophysiologies. Furthermore, we will shortly discuss recent progress in the insulin-targeted strategy, aiming to explore the inner linkage between these two diseases in aging populations. © 2013 Elsevier Inc.
Giannella L.,Cesare Magati Hospital |
Beraldi R.,Kogod Center on Aging |
Giulini S.,University of Modena and Reggio Emilia |
Cerami L.B.,Cesare Magati Hospital |
And 2 more authors.
International Journal of Gynecology and Obstetrics | Year: 2012
Objective: To evaluate the diagnostic accuracy of measuring cervical length (CL) in combination with cervical and plasma nitric oxide metabolite (NOx) levels to identify women undergoing preterm labor (PTL) who will deliver preterm. Methods: A hospital-based prospective cohort study of 730 women undergoing spontaneous PTL between 24 and 33 weeks + 6 days of pregnancy was conducted. Measurement of cervical and plasma NOx levels and ultrasonographic assessment of CL were performed to find the best model to predict preterm delivery (PTD). Optimal cut-off values were calculated by receiver operating characteristic (ROC) curve analysis. Logistic regression analysis and rank correlation tests were also performed. Results: CL of 15 mm or less, cervical NOx levels greater than 87.6 μmol/L, and plasma NOx levels greater than 123 μmol/L (P < 0.0001) were the only factors significantly associated with PTD within 7 days of sampling. This combined model provided high diagnostic accuracy (sensitivity 80.0%; specificity 99.2%). Both cervical and plasma NOx levels were negatively correlated with CL (r = - 0.453, P < 0.0001 and r = - 0.362, P < 0.0001, respectively). Conclusion: Combined measurement of CL and levels of cervical and plasma NOx could help identify women undergoing symptomatic PTL who are at increased risk of PTD. © 2011 International Federation of Gynecology and Obstetrics.
Davidge-Pitts C.,Endocrine Research Unit |
Escande C.J.,Kogod Center on Aging |
Conover C.A.,Endocrine Research Unit
Journal of Endocrinology | Year: 2014
Fat distribution differs between individuals, and those with visceral fat predominance develop metabolic profiles that increase the risk of adverse cardiovascular events. This is due, in part, to the proinflammatory state associated with visceral obesity as well as depot-specific adipogenesis. The IGF system is important in adipose tissue development and metabolic function. Pregnancy-associated plasma protein A (PAPPA) is a novel zinc metalloproteinase that regulates local IGF availability. The first aim of this study was to characterize PAPPA mRNA and protein expression in primary cultures of human preadipocytes isolated from omental, mesenteric, and subcutaneous depots. PAPPA expression was significantly increased in omental preadipocytes compared with mesenteric and subcutaneous preadipocytes. The second aim of this study was to investigate the factors regulating PAPPA expression, focusing on proinflammatory cytokines and resveratrol that have been shown to have negative and positive effects, respectively, on metabolism and diet-induced obesity. Treatment of cultured primary human preadipocytes with tumor necrosis factor a and interleukin 1b led to significant increases in PAPPA expression. Activated pathways mediating cytokine-induced PAPPA expression include the nuclear factor kB pathway and the MAPK family, particularly c-Jun NH2-terminal kinase and p38 MAPK. Resveratrol, a polyphenolic compound with beneficial cardiometabolic effects, significantly downregulated PAPPA expression under basal and stimulated conditions. Effects of resveratrol on PAPPA appeared to be mediated through pathways independent of silent mating type information regulation 2 homolog 1 (SIRT1) and AMP kinase activation. Depot-specific PAPPA expression in human preadipocytes may contribute to a depot-specific function. © 2014 Society for Endocrinology.
Clasen B.F.,University of Aarhus |
Poulsen M.M.,Aarhus University Hospital |
Escande C.,Kogod Center on Aging |
Escande C.,Institute Pasteur |
And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014
Context: Growth hormone (GH) secretion is reduced in obesity, despite normal serum insulin-like growthfactor I (IGF-1) levels, but the association between obesity and the GH signaling is unknown. Furthermore, SIRT1, an nicotinamide adenine dinucleotide-dependent protein deacetylase, reduces hepatic IGF-1 production in mice via blunting of GH-induced STAT5 signaling. Objective: To study GH signaling in muscle and fat in obese subjects and the interaction with concomitant administration of the putative SIRT1 activator resveratrol, and to assess the effects of inhibiting or knocking down SIRT1 on GH regulated genes in vitro. Design and Participants: Twenty-four obese males were examined in a randomized, double blinded, parallel-group study with resveratrol or placebo treatment for 5 weeks followed by a GH bolus. Muscle and fat biopsies were collected before and after GH. Body composition was assessed by DEXA and MRI. Main Outcome Measure: (1) Effect of body composition and age on GH-stimulated STAT5b phosphorylation and IGF-1, SOCS2, and CISH mRNA in muscle and fat. (2) The impact of resveratrol treatment on GH activity. (3) Impact of inhibiting or knocking down SIRT1 on effects of GH in vitro. Results: Significant GH-induced STAT5b phosphorylation in muscle and fat in obese subjects was recorded together with increased CISH and SOCS2 mRNA. GH-induced STAT5b phosphorylation in muscle correlated positively with age [r = 0.53, p<0.01], but not with body composition. Resveratrol administration had no impact on body composition, serum IGF-1, or GH signaling in vivo, and SIRT1 knock down or inhibition did not affect GH signaling in vitro. Conclusion: (1) GH induced STAT5b phosphorylation is detectable in muscle and fat in adult males with simple obesity, but is not determined by body composition. (2) Resveratrol supplementation does not impact circulating IGF-1 levels or GH signaling inhumanmuscle and fat. (3) Our data speak against a major impact of SIRT1on GH action in human subjects. Copyright © 2014 by the Endocrine Society.
Takahashi P.Y.,Kogod Center on Aging
Advances in skin & wound care | Year: 2011
Older adults frequently experience pressure ulcers (PrUs) and suffer the risks of the ulceration. Risk factors for PrUs remain unclear in a community population. The objective of this study was to determine the risk factors for future pressure ulceration in a community sample. This was a retrospective cohort study. All patients older than 60 years in a primary care panel in Olmsted County, Minnesota, on January 1, 2005, were enrolled (n = 12,650). METHODS AND OUTCOMES: The primary outcome was a new diagnosis of pressure ulceration within 40 months of index date. The predictor risk variables included demographic and comorbid health risk factors. The data were analyzed using univariable and multivariable logistic regression. The authors created a final model based on multivariable risk factors. Of 12,650 patients, 366 patients developed an incident PrU (2.9%). In the final model, age, male sex, and long-term-care facility admission were significant factors. Prior pressure ulceration with an odds ratio of 5.60 (95% confidence interval, 3.86-8.14) was the largest risk factor. Diabetes, falls, cataracts, renal insufficiency, and peripheral vascular disease were also associated with PrU development. PrU development involves important risk factors of prior PrU development and long-term-care facility placement as the 2 largest risk factors. Both factors are easily determined by history. Increasing age and comorbid medical conditions also impact PrU development as important risk factors for PrU development.