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  • 1
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    Oropharyngeal Skeletal Disease Accompanying High Bone Mass and Novel LRP5 Mutation
    Wiley ; 2005
    In:  Journal of Bone and Mineral Research Vol. 20, No. 5 ( 2005-05), p. 878-885
    Details
    In: Journal of Bone and Mineral Research, Wiley, Vol. 20, No. 5 ( 2005-05), p. 878-885
    Abstract: Gain‐of‐function mutation in the gene encoding LRP5 causes high bone mass. A 59‐year‐old woman carrying a novel LRP5 missense mutation, Arg154Met , manifested skeletal disease affecting her oropharynx as well as dense bones, showing that exuberant LRP5 effects are not always benign. Introduction: Gain‐of‐function mutation ( Gly171Val ) of LDL receptor‐related protein 5 (LRP5) was discovered in 2002 in two American kindreds with high bone mass and benign phenotypes. In 2003, however, skeletal disease was reported for individuals from the Americas and Europe carrying any of six novel LRP5 missense mutations affecting the same LRP5 protein domain. Furthermore, in 2004, we described a patient with neurologic complications from dense bones and extensive oropharyngeal exostoses caused by the Gly171Val defect. Materials and Methods: A 59‐year‐old woman was referred for dense bones. Three years before, mandibular buccal and lingual exostoses (osseous “tori”) were removed because of infections from food trapping between the teeth and exostoses. Maxillary buccal and palatal exostoses were asymptomatic. Radiographic skeletal survey showed marked thickening of the skull base and diaphyses of long bones (endosteal hyperostosis). BMD Z scores assessed by DXA were +8.5 and +8.7 in the total hip and L 1 ‐L 4 spine (both ∼195% average control), respectively. LRP5 mutation analysis was carried out for the LRP5 domain known to cause high bone mass. Results: Biochemical evaluation excluded most secondary causes of dense bones, and male‐to‐male transmission in her family indicated autosomal dominant inheritance. PCR amplification and sequencing of LRP5 exons 2‐4 and adjacent splice sites revealed heterozygosity for a new LRP5 missense mutation, Arg154Met . Conclusions: LRP5 Arg154Met is a novel defect that changes the same first “β‐propeller” module as the eight previously reported LRP5 gain‐of‐function missense mutations. Arg154Met alters a region important for LRP5 antagonism by dickkopf (Dkk). Therefore, our patient's extensive oropharyngeal exostoses and endosteal hyperostosis likely reflect increased Wnt signaling and show that exuberant LRP5 effects are not always benign.
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    URL: Article
    DOI: 10.1359/JBMR.041223
    RVK:
    XA 52230
    Language: English
    Publisher: Wiley
    Publication Date: 2005
    detail.hit.zdb_id: 2008867-X
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  • 2
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    Personalized cytomic assessment of vascular health: Evaluation of the vascular health profile in diabetes mellitus : Personalized Cytomic Assessment of Vascular Health
    Wiley ; 2013
    In:  Cytometry Part B: Clinical Cytometry Vol. 84B, No. 4 ( 2013-07), p. 255-266
    Details
    In: Cytometry Part B: Clinical Cytometry, Wiley, Vol. 84B, No. 4 ( 2013-07), p. 255-266
    Type of Medium: Online Resource
    ISSN: 1552-4949
    URL: Issue
    URL: Article
    DOI: 10.1002/cyto.b.v84b.4
    DOI: 10.1002/cyto.b.21095
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 2180651-2
    SSG: 12
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  • 3
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    Cognitive Impairment in Older Adults with Type 1 Diabetes: Longitudinal data from the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) Study
    Wiley ; 2022
    In:  Alzheimer's & Dementia Vol. 18, No. S7 ( 2022-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S7 ( 2022-12)
    Abstract: Adults with type 1 diabetes (T1D) are at increased risk for cognitive impairment, accelerated brain aging, and Alzheimer’s disease and related dementias (ADRD). However, longitudinal data on cognitive aging, cognitive impairment and ADRD in adults with T1D are still scarce. The aim of this study was to characterize cognitive impairment in a longitudinal sample of older adults with T1D. Method We analyzed data collected as part of the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) Study (Pratley et al., JAMA, 2020; 323(23):2397‐2406), in which 22 endocrinology practices in the United States participated. Participants with T1D ≥ 60 years of age who completed the NIH Toolbox Cognition Battery at two time points (baseline and one year follow up) were included in this study (n = 171). Cognitive impairment was classified using recommendations from Holdnack et al, 2017 (Holdnack et al., Arch Clin Neuropsychol, 2017; 32(5):574‐584). Result At baseline, 50% of the participants (N = 86/171) met criteria for cognitive impairment. Of those, 56% (N = 48/86) were still classified as having cognitive impairment a year later (28% of the total sample, N = 48/171). Conversely, 44% (N = 38/86) of the participants classified with impairment at baseline reverted to no impairment by a year. Of those classified as having normal cognition during the baseline assessment, 20% converted to impaired at the follow up (N = 17/85), while 80% (N = 68/85) remained normal. Conclusion These data indicate that caution is warranted when assessing cognition in older adults with T1D, as a large percentage of those identified as having cognitive impairment at baseline reverted to normal after a year. Serial cognitive assessment is suggested. Longitudinal research with more diverse samples of older adults with T1D is needed to better understand the clinical utility of the NIH toolbox cognition battery and other neuropsychological assessments in older individuals with T1D.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v18.S7
    DOI: 10.1002/alz.066626
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2201940-6
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  • 4
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    Different β‐cell secretory phenotype in non‐obese compared to obese early type 2 diabetes
    Wiley ; 2020
    In:  Diabetes/Metabolism Research and Reviews Vol. 36, No. 5 ( 2020-07)
    Details
    In: Diabetes/Metabolism Research and Reviews, Wiley, Vol. 36, No. 5 ( 2020-07)
    Abstract: Type 2 diabetes (T2D) is characterized by impaired tissue sensitivity to insulin action (ie, insulin resistance) and impaired β‐cell insulin secretion. Because obesity contributes importantly to the development of insulin resistance, we sought to determine whether insulin secretory defects would predominate in non‐obese compared to obese T2D. Methods We measured β‐cell function and secretory capacity using the glucose‐potentiated arginine test in T2D subjects early in the disease course classified as non‐obese (BMI 〈 30; n = 12) or obese (BMI ≥30 kg/m 2 ; n = 28) and additionally compared responses from non‐obese T2D with a non‐diabetic control group (n = 12). Results The acute insulin response to glucose potentiation of arginine‐induced insulin release was less in non‐obese T2D than in controls and associated with impaired β‐cell sensitivity to glucose (PG 50 ). Proinsulin secretory ratios were increased in non‐obese T2D when compared to obese T2D. Obese T2D subjects had reduced insulin sensitivity (M/I) while non‐obese T2D subjects had insulin sensitivity that was comparable to controls. Conclusions In non‐obese T2D, insulin secretory defects predominate with impaired β‐cell sensitivity to glucose and proinsulin processing in the absence of insulin resistance. Future studies should consider whether different β‐cell secretory phenotypes and tissue sensitivity to insulin explain the varying responsiveness to T2D interventions.
    Type of Medium: Online Resource
    ISSN: 1520-7552 , 1520-7560
    URL: Issue
    URL: Article
    DOI: 10.1002/dmrr.v36.5
    DOI: 10.1002/dmrr.3295
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2001565-3
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  • 5
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    Acute Hyperinsulinemia Alters Bone Turnover in Women and Men With Type 1 Diabetes
    Wiley ; 2020
    In:  JBMR Plus Vol. 4, No. 9 ( 2020-09)
    Details
    In: JBMR Plus, Wiley, Vol. 4, No. 9 ( 2020-09)
    Abstract: Type 1 diabetes (T1D) increases fracture risk across the lifespan. The low bone turnover associated with T1D is thought to be related to glycemic control, but it is unclear whether peripheral hyperinsulinemia due to dependence on exogenous insulin has an independent effect on suppressing bone turnover. The purpose of this study was to test the bone turnover marker (BTM) response to acute hyperinsulinemia. Fifty‐eight adults aged 18 to 65 years with T1D over 2 years were enrolled at seven T1D Exchange Clinic Network sites. Participants had T1D diagnosis between age 6 months to 45 years. Participants were stratified based on their residual endogenous insulin secretion measured as peak C‐peptide response to a mixed meal tolerance test. BTMs (CTX, P1NP, sclerostin [SCL], osteonectin [ON] , alkaline phosphatase [ALP], osteocalcin [OCN] , osteoprotegerin [OPG], osteopontin [OPN] , and IGF‐1) were assessed before and at the end of a 2‐hour hyperinsulinemic‐euglycemic clamp (HEC). Baseline ON ( r = −0.30, p = .022) and OCN ( r = −0.41, p = .002) were negatively correlated with age at T1D diagnosis, but baseline BTMs were not associated with HbA1c. During the HEC, P1NP decreased significantly (−14.5 ± 44.3%; p = .020) from baseline. OCN, ON, and IGF‐1 all significantly increased (16.0 ± 13.1%, 29.7 ± 31.7%, 34.1 ± 71.2%, respectively; all p   〈  .001) during the clamp. The increase in SCL was not significant (7.3 ± 32.9%, p = .098), but the decrease in CTX (−12.4 ± 48.9, p = .058) neared significance. ALP and OPG were not changed from baseline ( p = .23 and p = .77, respectively). Baseline ON and SCL were higher in men, but OPG was higher in women (all p  ≤ .029). SCL was the only BTM that changed differently in women than men. There were no differences in baseline BTMs or change in BTMs between C‐peptide groups. Exogenous hyperinsulinemia acutely alters bone turnover, suggesting a need to determine whether strategies to promote healthy remodeling may protect bone quality in T1D. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
    Type of Medium: Online Resource
    ISSN: 2473-4039 , 2473-4039
    URL: Issue
    URL: Article
    DOI: 10.1002/jbm4.v4.9
    DOI: 10.1002/jbm4.10389
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2905710-3
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  • 6
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    A randomized dose‐response trial of aerobic exercise and health‐related quality of life in colon cancer survivors
    Wiley ; 2018
    In:  Psycho-Oncology Vol. 27, No. 4 ( 2018-04), p. 1221-1228
    Details
    In: Psycho-Oncology, Wiley, Vol. 27, No. 4 ( 2018-04), p. 1221-1228
    Abstract: To examine the dose‐response effects of aerobic exercise on health‐related quality of life (HRQoL) among colon cancer survivors. Methods Thirty‐nine stage I to III colon cancer survivors were randomized to 1 of 3 groups: usual‐care control, 150 min·wk −1 of aerobic exercise (low‐dose) and 300 min·wk −1 of aerobic exercise (high‐dose) for 6 months. HRQoL outcomes included the Short Form (SF)‐36 physical and mental component summary, Functional Assessment of Cancer Therapy‐Colorectal, Pittsburgh Sleep Quality Index, Fear of Cancer Recurrence Inventory, Fatigue Symptom Inventory, and North Central Cancer Treatment Group bowel function questionnaire, assessed at baseline and post intervention. The primary hypothesis was that exercise would improve HRQoL outcomes in a dose‐response fashion, such that high‐dose aerobic exercise would yield the largest improvements in HRQoL outcomes. Results Over 6 months, the low‐dose group completed 141 ± 10 min·wk −1 of aerobic exercise, and the high‐dose group completed 247 ± 11 min·wk −1 of aerobic exercise. Over 6 months, exercise improved the physical component summary score of the SF‐36 ( P trend  = 0.002), the Functional Assessment of Cancer Therapy‐Colorectal ( P trend  = 0.025), the Pittsburgh Sleep Quality Index ( P trend  = 0.049), and the Fatigue Symptom Inventory ( P trend  = 0.045) in a dose‐response fashion. Between‐group standardized mean difference effects sizes for the above‐described findings were small to moderate in magnitude (0.35–0.75). No dose‐response effects were observed for the mental component summary score of the SF‐36, the Fear of Cancer Recurrence Inventory, or bowel function. Conclusion Higher doses of aerobic exercise, up to 300 min·wk −1 , improve multiple HRQoL outcomes among stage I to III colon cancer survivors. These findings provide evidence that aerobic exercise may provide multiple health benefits for colon cancer survivors.
    Type of Medium: Online Resource
    ISSN: 1057-9249 , 1099-1611
    URL: Issue
    URL: Article
    DOI: 10.1002/pon.v27.4
    DOI: 10.1002/pon.4655
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1495115-0
    SSG: 5,2
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  • 7
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    Dual‐hormone artificial pancreas for management of type 1 diabetes: Recent progress and future directions
    Wiley ; 2021
    In:  Artificial Organs Vol. 45, No. 9 ( 2021-09), p. 968-986
    Details
    In: Artificial Organs, Wiley, Vol. 45, No. 9 ( 2021-09), p. 968-986
    Abstract: Over the last few years, technological advances have led to tremendous improvement in the management of type 1 diabetes (T1D). Artificial pancreas systems have been shown to improve glucose control compared with conventional insulin pump therapy. However, clinically significant hypoglycemic and hyperglycemic episodes still occur with the artificial pancreas. Postprandial glucose excursions and exercise‐induced hypoglycemia represent major hurdles in improving glucose control and glucose variability in many patients with T1D. In this regard, dual‐hormone artificial pancreas systems delivering other hormones in addition to insulin (glucagon or amylin) may better reproduce the physiology of the endocrine pancreas and have been suggested as an alternative tool to overcome these limitations in clinical practice. In addition, novel ultra‐rapid‐acting insulin analogs with a more physiological time–action profile are currently under investigation for use in artificial pancreas devices, aiming to address the unmet need for further improvements in postprandial glucose control. This review article aims to discuss the current progress and future outlook in the development of novel ultra‐rapid insulin analogs and dual‐hormone closed‐loop systems, which offer the next steps to fully closing the loop in the artificial pancreas.
    Type of Medium: Online Resource
    ISSN: 0160-564X , 1525-1594
    URL: Issue
    URL: Article
    DOI: 10.1111/aor.v45.9
    DOI: 10.1111/aor.14023
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2003825-2
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  • 8
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    Dyslipidaemia and statin use in individuals aged 10 to 〈40 years in the T1D Exchange clinic registry
    Wiley ; 2019
    In:  Diabetes, Obesity and Metabolism Vol. 21, No. 1 ( 2019-01), p. 170-172
    Details
    In: Diabetes, Obesity and Metabolism, Wiley, Vol. 21, No. 1 ( 2019-01), p. 170-172
    Abstract: For individuals aged 10 to 〈 40 years with type 1 diabetes and dyslipidaemia, US national guidelines recommend consideration of statin therapy based on age, low‐density lipoprotein cholesterol (LDL‐C) level and other cardiovascular risk factors. We evaluated dyslipidaemia prevalence, statin therapy use, and associations between not meeting target LDL‐C [ 〈 100 mg/dL ( 〈 5.55 mmol/L)] and other cardiovascular disease (CVD) risk factors in individuals aged 10 to 〈 40 years in the T1D Exchange clinic registry. In 7223 participants, statin use was 2% in 10 to 〈 18 year olds, 4% in 18 to 〈 25 year olds, and 21% in 25 to 〈 40 year olds. Individuals not on statin therapy with LDL‐C above target were more likely to have ≥1 additional CVD risk factor(s) than those with LDL‐C in the target range for all age groups (all P 〈 0.01). While most individuals not on statin therapy had LDL‐C in the target range, those who did not were more likely to have ≥1 additional CVD risk factor(s), and therefore longitudinal study of lipid levels and statin use is needed to see if treatment of dyslipidaemia to target LDL‐C levels may lower the risk of future CVD in individuals aged 10 to 〈 40 years with type 1 diabetes.
    Type of Medium: Online Resource
    ISSN: 1462-8902 , 1463-1326
    URL: Issue
    URL: Article
    DOI: 10.1111/dom.2019.21.issue-1
    DOI: 10.1111/dom.13475
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2004918-3
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  • 9
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    Changes in vitamin D binding protein and vitamin D concentrations associated with liver transplantation
    Wiley ; 2012
    In:  Liver International Vol. 32, No. 2 ( 2012-02), p. 287-296
    Details
    In: Liver International, Wiley, Vol. 32, No. 2 ( 2012-02), p. 287-296
    Abstract: Vitamin D deficiency is associated with fractures, infections and death. Liver disease impairs vitamin D and vitamin D binding protein ( DBP ) metabolism. Aims We aimed to determine the impact of liver transplantation on vitamin D , particularly on DBP and free vitamin D concentrations. Methods Serum 25( OH )D, 1,25( OH ) 2 D and DBP concentrations were measured in 202 adults before liver transplantation and 3 months later in 155. Free vitamin D concentrations were estimated from these values. Risk factors for 25( OH )D deficiency ( 〈 20 ng/ml) and low 1,25( OH ) 2 D ( 〈 20 pg/ml) were examined with logistic regression, and changes in concentrations following transplantation with linear regression. Results Pretransplant, 84% were 25( OH )D deficient, 13% had 25( OH )D concentrations 〈 2.5 ng/ml, and 77% had low 1,25( OH ) 2 D. Model for end‐stage liver disease score ≥20 ( P   〈  0.005) and hypoalbuminemia ( P   〈  0.005) were associated with low 25( OH )D and 1,25( OH ) 2 D concentrations. Following transplantation, 25( OH )D concentrations increased a median of 17.8 ng/ml ( P   〈  0.001). Albumin increased from a median of 2.7 to 3.8 g/dl ( P   〈  0.001) and DBP from 8.6 to 23.8 mg/dl ( P   〈  0.001). Changes in total 25( OH )D were positively and independently associated with changes in DBP ( P   〈  0.05) and albumin ( P   〈  0.001). Free 25( OH )D concentrations rose from 6.0 to 9.7 pg/ml ( P   〈  0.001). In contrast, total 1,25( OH ) 2  Dconcentrations rose only by 4.3 pg/ml ( P   〈  0.001) and free 1,25( OH ) 2   D concentrations declined ( P   〈  0.001). Conclusions Serum total and free 25( OH )D and DBP concentrations rose substantially following transplantation, while 1,25( OH ) 2 D concentrations showed modest changes and free 1,25( OH ) 2 D decreased. Studies of the effects of vitamin D status on diverse transplant complications are needed.
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    URL: Article
    DOI: 10.1111/liv.2011.32.issue-2
    DOI: 10.1111/j.1478-3231.2011.02638.x
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 2124684-1
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  • 10
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    Selective association of electrocardiographic abnormalities with insulin sensitivity and beta‐cell function in type 2 diabetes mellitus: a cross‐sectional analysis
    Wiley ; 2016
    In:  Diabetes/Metabolism Research and Reviews Vol. 32, No. 7 ( 2016-10), p. 736-744
    Details
    In: Diabetes/Metabolism Research and Reviews, Wiley, Vol. 32, No. 7 ( 2016-10), p. 736-744
    Abstract: We investigated the association of electrocardiographic (ECG) abnormalities with markers of insulin resistance and pancreatic beta‐cell dysfunction in a cross‐sectional study of type 2 diabetes patients. Methods Electrocardiographic criteria were evaluated in the Penn Diabetes Heart Study participants ( n  = 1671; 64% male; 61% Caucasian), including a sub‐sample ( n  = 710) that underwent oral glucose tolerance testing. The Matsuda Insulin Sensitivity Index and homeostasis model assessment of insulin resistance (HOMA‐IR) estimated insulin sensitivity; Insulinogenic Index and homeostasis model assessment of beta‐cell function assessed beta‐cell function. Multivariable regression modelling was used to analyse associations of ECG changes with these indices. Results In unadjusted analyses, subjects in the highest quartile of Matsuda index had the lowest prevalence of Q‐waves (6.3% versus 15.3%, p  = 0.005). In adjusted models, an inverse association was seen between Q‐waves and log Matsuda index [one standard deviation increase; OR = 0.59 (95% CI 0.43‐0.87 p = 0.001)]. In the full Penn Diabetes Heart Study, there was a direct association between Q‐waves and HOMA‐IR [one standard deviation increase; OR = 1.43 (95% CI 1.13–1.81, p  = 0.003)]. In adjusted models, left ventricular hypertrophy also was inversely associated with Matsuda index and directly with HOMA‐IR. Higher Insulinogenic Index scores were associated with a lower prevalence of nonspecific ST changes [OR = 0.78 (95% CI 0.62–0.98, p  = 0.032)]. Conclusions In type 2 diabetic patients, both oral glucose tolerance testing‐derived and HOMA‐derived measures of insulin resistance were associated with pathologic Q‐waves and left ventricular hypertrophy on ECGs. Copyright © 2016 John Wiley & Sons, Ltd.
    Type of Medium: Online Resource
    ISSN: 1520-7552 , 1520-7560
    URL: Issue
    URL: Article
    DOI: 10.1002/dmrr.v32.7
    DOI: 10.1002/dmrr.2794
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2001565-3
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