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Article ; Online: Vascular Calcification and Osteoprotegrin in Chronic Kidney Disease.

Lenhard, M James / Maser, Raelene E

2017 Volume 46, Issue 1, Page(s) 37–38

MeSH term(s)	Biomarkers/blood ; Humans ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/therapy ; Osteoprotegerin/blood ; Renal Dialysis/adverse effects ; Vascular Calcification/blood ; Vascular Calcification/etiology
Chemical Substances	Biomarkers ; Osteoprotegerin
Language	English
Publishing date	2017-06-15
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	604540-6
ISSN	1421-9670 ; 0250-8095
ISSN (online)	1421-9670
ISSN	0250-8095
DOI	10.1159/000477381
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Article: Vascular Calcification and Osteoprotegrin in Chronic Kidney Disease

Lenhard, M. James / Maser, Raelene E.

American Journal of Nephrology

2017 Volume 46, Issue 1, Page(s) 37–38

Institution	Diabetes and Metabolic Research Center, Christiana Care Health System, and Department of Medical Laboratory Sciences, University of Delaware, Newark, and Diabetes and Metabolic Diseases Center, Christiana Care Health System, Wilmington, DE, USA
Language	English
Publishing date	2017-06-15
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Editorial
ZDB-ID	604540-6
ISSN	1421-9670 ; 0250-8095
ISSN (online)	1421-9670
ISSN	0250-8095
DOI	10.1159/000477381
Database	Karger publisher's database

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Article ; Online: Osteopontin and osteoprotegerin levels in type 2 diabetes and their association with cardiovascular autonomic function.

Maser, Raelene E / Lenhard, M James / Pohlig, Ryan T / Balagopal, P Babu

Journal of diabetes and its complications

2016 Volume 30, Issue 3, Page(s) 507–510

Abstract: ... breathing (i.e., mean circular resultant (MCR) and expiration/inspiration (E/I) ratio) was used to assess ... multiple linear regression analysis with MCR or E/I ratio as the dependent variable, OPN was independently ... 598, p<0.001; E/I model R2=0.594, p<0.001).: Conclusion: Our results suggest that OPN is associated ...

Abstract	Aims: Osteopontin (OPN) and osteoprotegerin (OPG) are bone metabolism biomarkers potentially associated with nerve function. We evaluated the association of cardiovascular autonomic nerve function, OPN, and OPG in 50 individuals with type 2 diabetes mellitus (T2DM). Methods: RR-variation during deep breathing (i.e., mean circular resultant (MCR) and expiration/inspiration (E/I) ratio) was used to assess parasympathetic nerve function. Participants' demographics, HbA1c, 25-hydroxyvitamin D (25(OH)D), BMI, HOMA-IR, calcium, parathyroid hormone, creatinine, OPN, and OPG were determined. Results: Using stepwise multiple linear regression analysis with MCR or E/I ratio as the dependent variable, OPN was independently associated with reduced autonomic function. A previous report showed a significant association of cardiovascular autonomic function with age, 25(OH)D insufficiency, and the interaction of age×25(OH)D insufficiency. Here we report a novel association for OPN and its interaction with age indicating that for those who are younger, elevated OPN levels are related to a greater loss of autonomic function (MCR model R2=0.598, p<0.001; E/I model R2=0.594, p<0.001). Conclusion: Our results suggest that OPN is associated with reduced parasympathetic function, particularly in younger individuals with T2DM. Further studies are needed to determine if OPN is neuroprotective, involved in the pathogenesis of autonomic dysfunction, or a bystander.
MeSH term(s)	Adult ; Autonomic Nervous System/physiopathology ; Biomarkers/blood ; Cardiovascular System/physiopathology ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Osteopontin/blood ; Osteoprotegerin/blood ; Respiration ; Young Adult
Chemical Substances	Biomarkers ; Osteoprotegerin ; SPP1 protein, human ; TNFRSF11B protein, human ; Osteopontin (106441-73-0)
Language	English
Publishing date	2016-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1105840-7
ISSN	1873-460X ; 1056-8727
ISSN (online)	1873-460X
ISSN	1056-8727
DOI	10.1016/j.jdiacomp.2015.12.012
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Article: Pre-heparin lipoprotein lipase mass as a potential mediator in the association between adiponectin and HDL-cholesterol in type 2 diabetes.

Maser, Raelene E / Lenhard, M James / Pohlig, Ryan T / Balagopal, P Babu

Journal of clinical & translational endocrinology

2016 Volume 7, Page(s) 7–11

Abstract: Aim: Lipoprotein lipase (LPL) is a major enzyme in lipid metabolism. Dyslipidemia, characterized by decreased high-density lipoprotein cholesterol (HDL-C), is prevalent in persons with type 2 diabetes mellitus (T2DM). The aim of this study was to ... ...

Abstract	Aim: Lipoprotein lipase (LPL) is a major enzyme in lipid metabolism. Dyslipidemia, characterized by decreased high-density lipoprotein cholesterol (HDL-C), is prevalent in persons with type 2 diabetes mellitus (T2DM). The aim of this study was to determine whether pre-heparin LPL mass mediates the association between adiponectin and HDL-C in individuals with T2DM. Methods: Pre-heparin LPL mass was measured via an enzyme-linked immunosorbent assay, adiponectin by radioimmunoassay, and HDL-C was determined enzymatically. Participants' (n = 50) demographics, HbA1c, adiposity, homeostasis model assessment for insulin resistance (HOMA-IR), serum creatinine, and lipids were measured. Path analysis was utilized to test whether pre-heparin LPL mass is a mediator in the relationship between adiponectin and HDL-C. Results: All four criteria for mediation were satisfied in the path analysis. The indirect effect of adiponectin on HDL-C through pre-heparin LPL mass was significant, p = 0.001, whereas the direct effect of adiponectin on HDL-C was not significant, p = 0.074. These results remained consistent even after adjustments for age, gender, body mass index, HOMA-IR, and serum creatinine in the model. Conclusion: The findings in this study suggest that pre-heparin LPL mass may mediate the association between adiponectin and HDL-C in T2DM. This relationship for measures of HDL-C functionality requires future investigation.
Language	English
Publishing date	2016-12-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2834222-7
ISSN	2214-6237
ISSN	2214-6237
DOI	10.1016/j.jcte.2016.12.002
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Article ; Online: Autonomic modulation in gestational diabetes mellitus.

Maser, Raelene E / Lenhard, M James / Kolm, Paul

Journal of diabetes and its complications

2014 Volume 28, Issue 5, Page(s) 684–688

Abstract: Aims: The aim of this study was to evaluate the influence of gestational diabetes mellitus (GDM) and positional aortocaval compression on cardiovascular autonomic nervous system (ANS) function in late pregnancy.: Methods: Pregnant women with (n=31) ... ...

Abstract	Aims: The aim of this study was to evaluate the influence of gestational diabetes mellitus (GDM) and positional aortocaval compression on cardiovascular autonomic nervous system (ANS) function in late pregnancy. Methods: Pregnant women with (n=31) and without (n=12) GDM were evaluated at 30-35weeks gestation and 2-3months postpartum. Measures of ANS function included power spectral analysis (performed sitting) and RR-variation during deep breathing (performed supine). Time-related changes (late pregnancy versus 2-3months postpartum) for measurements of cardiovascular ANS function were analyzed using multivariate analysis of variance for repeated measures. Results: Baseline characteristics were similar for both groups. Comparing ANS measures for GDM+versus GDM- women during pregnancy and postpartum revealed no significant differences. Time related changes indicated that during late pregnancy total spectral power, low frequency (LF) power, high frequency (HF) power, and RR-variation during deep breathing were significantly reduced (p<0.001 for all). The LF/HF ratio, however, was not significantly affected during late pregnancy (p=0.678). Conclusions: Our results suggest decreased activity in both branches of the ANS during mid-third trimester pregnancy, but no significant change in sympathovagal balance. Aortocaval compression appears to affect ANS function whether tests were performed sitting or supine for GDM+and GDM- women.
MeSH term(s)	Adolescent ; Adult ; Autonomic Nervous System/physiopathology ; Cardiovascular System/physiopathology ; Diabetes, Gestational/physiopathology ; Female ; Follow-Up Studies ; Heart Rate/physiology ; Humans ; Postpartum Period/physiology ; Posture ; Pregnancy ; Pregnancy Trimester, Third ; Supine Position/physiology ; Young Adult
Language	English
Publishing date	2014-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1105840-7
ISSN	1873-460X ; 1056-8727
ISSN (online)	1873-460X
ISSN	1056-8727
DOI	10.1016/j.jdiacomp.2014.05.005
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Article: Vitamin D Insufficiency is Associated with Reduced Parasympathetic Nerve Fiber Function in Type 2 Diabetes.

Maser, Raelene E / Lenhard, M James / Pohlig, Ryan T

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

2014 Volume 21, Issue 2, Page(s) 174–181

Abstract: ... the association of cardiovascular autonomic function, 25-hydroxyvitamin D (25[OH]D) insufficiency (i.e., levels ... individuals with T2DM. Cardiovascular autonomic function (i.e., parasympathetic function) was assessed by RR ... variation during deep breathing (i.e., mean circular resultant [MCR] and expiration/inspiration [E/I] ratio ...

Abstract	Objective: Vitamin D insufficiency is prevalent in subjects with type 2 diabetes mellitus (T2DM) and is associated with peripheral neuropathy. However, there are little data regarding vitamin D status in patients with cardiovascular autonomic neuropathy. Our objective was to evaluate the association of cardiovascular autonomic function, 25-hydroxyvitamin D (25[OH]D) insufficiency (i.e., levels <30 ng/mL), and multiple metabolic parameters in subjects with T2DM. Methods: We examined 50 individuals with T2DM. Cardiovascular autonomic function (i.e., parasympathetic function) was assessed by RR-variation during deep breathing (i.e., mean circular resultant [MCR] and expiration/inspiration [E/I] ratio). Metabolic parameters included measures of adiposity, glycemic control, insulin resistance, calcium metabolism, and 25(OH)D. Results: Participants with 25(OH)D insufficiency (n = 26) were younger (66 ± 9 vs. 60 ± 10 years, P<.05), more insulin resistant, had a higher body mass index (BMI) and lower adiponectin levels. The MCR (39.5 ± 26.3 vs. 27.6 ± 17.2, P<.01) and E/I ratio (1.21 ± 0.17 vs. 1.15 ± 0.09, P<.01) were lower for those with 25(OH)D insufficiency after controlling for age. A stepwise selection procedure regressing MCR and E/I ratio on a number of metabolic parameters resulted in a model identifying age and 25(OH)D insufficiency as significant determinants for both measures. The interaction of age x 25(OH)D insufficiency was also included (MCR model, R2 = 0.491, P<.001; E/I ratio, R2 = 0.455, P<.001). Neither glycemic control nor other metabolic parameters were selected. Conclusion: Our results suggest that 25(OH)D insufficiency is associated with reduced parasympathetic function, with a stronger association in younger persons with T2DM. Studies are needed to determine if vitamin D supplementation into the sufficient range could prevent or delay the onset of cardiovascular autonomic dysfunction.
MeSH term(s)	Aged ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nerve Fibers/physiology ; Parasympathetic Nervous System/physiopathology ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Vitamin D Deficiency/physiopathology
Chemical Substances	Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H)
Language	English
Publishing date	2014-10-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1473503-9
ISSN	1530-891X
ISSN	1530-891X
DOI	10.4158/EP14332.OR
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Article ; Online: Screening for asymptomatic coronary artery disease in patients with type 2 diabetes.

Vinik, Aaron I / Maser, Raelene E

JAMA

2009 Volume 302, Issue 7, Page(s) 735–6; author reply 736–7

MeSH term(s)	Coronary Artery Disease/diagnostic imaging ; Coronary Artery Disease/etiology ; Diabetes Mellitus, Type 2/complications ; Diabetic Angiopathies/diagnostic imaging ; Diabetic Angiopathies/etiology ; Exercise Test ; Humans ; Myocardial Perfusion Imaging
Language	English
Publishing date	2009-08-19
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2009.1188
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Article ; Online: Effect of parathyroidectomy on osteopontin and undercarboxylated osteocalcin in patients with primary hyperparathyroidism.

Maser, Raelene E / Lenhard, M James / Pohlig, Ryan T / Balagopal, P Babu / Abdel-Misih, Raafat

Endocrine research

2017 Volume 43, Issue 1, Page(s) 21–28

Abstract: ... with inflammatory markers (e.g., interleukin-6 [IL-6], lipocalin-2), insulin resistance (i.e., homeostasis model ... assessment for insulin resistance [HOMA-IR]), adiposity (i.e., leptin, adiponectin), PTH, calcium, 25 ...

Abstract	Purpose: Surgical treatment for primary hyperparathyroidism (PHPT) improves bone metabolism. Osteocalcin (OC) and its undercarboxylated form (ucOC) are associated with bone and energy metabolism. Osteopontin (OPN), a multifunctional protein expressed in bone, is involved in resorption, along with β-carboxyl-terminal cross-linking telopeptide of type 1 collagen (β-CTX), and osteoprotegerin (OPG). Our aim was to investigate these biomarkers of bone metabolism in patients with PHPT. Methods: We examined 30 individuals with PHPT, in a clinical research facility, before and 1 month following parathyroidectomy. Circulating levels of OC, ucOC, OPN, β-CTX, and OPG were examined as bone biomarkers along with inflammatory markers (e.g., interleukin-6 [IL-6], lipocalin-2), insulin resistance (i.e., homeostasis model assessment for insulin resistance [HOMA-IR]), adiposity (i.e., leptin, adiponectin), PTH, calcium, 25-hydroxyvitamin D, creatinine, and demographics. Results: Participants (27 females/3 males) were 60 ± 9 (mean±SD) years old. There was a significant reduction of ucOC (7.9 ± 5.1 [median±SIQR] vs. 6.6 ± 3.7 ng/mL, p = 0.022) and OPN (75.4 ± 14.5 vs. 54.5 ± 9.2 ng/mL, p < 0.001) pre- versus post-parathyroidectomy. There were no univariate differences postoperatively for IL-6, HOMA-IR, leptin, or adiponectin. Regression analysis showed that postoperative levels of adiponectin, IL-6, and OPN were significantly associated with ucOC, while adjusting for PTH and albumin corrected calcium levels (model R Conclusion: The lower 1-month postoperative OPN and ucOC levels in PHPT seem to indicate reduced bone resorption. Decreased ucOC levels may also suggest lower energy demands postoperatively.
MeSH term(s)	Adiponectin/blood ; Aged ; Female ; Follow-Up Studies ; Humans ; Hyperparathyroidism, Primary/blood ; Hyperparathyroidism, Primary/surgery ; Insulin Resistance/physiology ; Interleukin-6/blood ; Leptin/blood ; Male ; Middle Aged ; Osteocalcin/blood ; Osteopontin/blood ; Osteoprotegerin/blood ; Parathyroidectomy
Chemical Substances	ADIPOQ protein, human ; Adiponectin ; IL6 protein, human ; Interleukin-6 ; Leptin ; Osteoprotegerin ; SPP1 protein, human ; TNFRSF11B protein, human ; Osteocalcin (104982-03-8) ; Osteopontin (106441-73-0)
Language	English
Publishing date	2017-09-22
Publishing country	England
Document type	Journal Article
ZDB-ID	605823-1
ISSN	1532-4206 ; 0743-5800
ISSN (online)	1532-4206
ISSN	0743-5800
DOI	10.1080/07435800.2017.1369432
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Article ; Online: Osteopontin and clusterin levels in type 2 diabetes mellitus: differential association with peripheral autonomic nerve function.

Maser, Raelene E / James Lenhard, M / Pohlig, Ryan T / Babu Balagopal, P

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2017 Volume 38, Issue 9, Page(s) 1645–1650

Abstract: ... of this study was to investigate the potential relationship of OPN and clusterin with sudomotor function (i.e ... feet. Demographics (e.g., age, gender, race, body mass index (BMI)), HbA1c, 25-hydroxyvitamin D ...

Abstract	Osteopontin (OPN) and clusterin are secreted glycoproteins potentially associated with nerve function. Sudomotor dysfunction is associated with the development of foot ulcerations. The purpose of this study was to investigate the potential relationship of OPN and clusterin with sudomotor function (i.e., autonomic nerves that control sweating) in participants with type 2 diabetes mellitus (T2DM). Sudomotor function was assessed using SUDOSCAN® which measures electrochemical skin conductance (ESC) of the hands and feet. Demographics (e.g., age, gender, race, body mass index (BMI)), HbA1c, 25-hydroxyvitamin D, creatinine, OPN, and clusterin were also determined for the participants. Fifty individuals with T2DM (age = 59±11 years; 23/27 male/female; 13 African Americans) participated in this study. Lower ESC for the hands and feet were observed in African Americans versus Caucasians/Asians (p < 0.05). No significant ESC differences were observed for good [HbA1c <7%] versus poor [HbA1c ≥7%] glycemic control. With regard to gender, ESC values were lower for the hands for females (p < 0.05). In linear regression with ESC for the hands or feet as the dependent variable, increased OPN levels, but not clusterin, were independently associated with reduced sudomotor function while adjusting for age, gender, race, BMI, and glycemic control (ESC hands model R
MeSH term(s)	Autonomic Nervous System/metabolism ; Autonomic Nervous System Diseases/blood ; Autonomic Nervous System Diseases/ethnology ; Clusterin/blood ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/ethnology ; Diabetic Neuropathies/blood ; Diabetic Neuropathies/ethnology ; Female ; Foot/physiopathology ; Galvanic Skin Response/physiology ; Glycated Hemoglobin/metabolism ; Hand/physiopathology ; Humans ; Linear Models ; Male ; Middle Aged ; Osteopontin/blood ; Sweating/physiology ; Vitamin D/analogs & derivatives ; Vitamin D/blood
Chemical Substances	CLU protein, human ; Clusterin ; Glycated Hemoglobin A ; SPP1 protein, human ; hemoglobin A1c protein, human ; Osteopontin (106441-73-0) ; Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H)
Language	English
Publishing date	2017-06-21
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-017-3019-1
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Article ; Online: Neuropathy: the crystal ball for cardiovascular disease?

Vinik, Aaron I / Maser, Raelene E / Ziegler, Dan

Diabetes care

2010 Volume 33, Issue 7, Page(s) 1688–1690

MeSH term(s)	Cardiovascular Diseases/epidemiology ; Diabetes Mellitus, Type 2/epidemiology ; Diabetic Neuropathies/epidemiology ; Humans ; Risk Factors
Language	English
Publishing date	2010-06-28
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc10-0745
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