Diabetes and Metabolic Research Center

Newark, DE, United States

Diabetes and Metabolic Research Center

Newark, DE, United States

Time filter

Source Type

Maser R.E.,University of Delaware | Maser R.E.,Diabetes and Metabolic Research Center | Lenhard M.J.,Diabetes and Metabolic Research Center | Lenhard M.J.,Diabetes and Metabolic Diseases Center | And 2 more authors.
Diabetes, Obesity and Metabolism | Year: 2013

Aim: The renin-angiotensin-aldosterone system (RAAS) and autonomic nervous system regulate the cardiovascular system. Blockade of the RAAS may slow the progression of end-organ damage. Direct renin inhibition offers a means for blocking the RAAS. The objective of this study was to examine the effect of direct renin inhibition on cardiovascular autonomic function. Methods: In this double-blind, placebo-controlled trial, 60 individuals with diabetes were randomly assigned to 300mg of aliskiren or placebo once daily for 6weeks. The primary end point was a change in tests of cardiovascular autonomic function. Autonomic function was assessed by power spectral analysis and RR-variation during deep breathing [i.e. mean circular resultant (MCR), expiration/inspiration (E/I) ratio]. The MCR and E/I ratio assess parasympathetic function. Secondary measures included change in biochemical parameters [e.g. plasma renin activity, leptin and interleukin-6]. Change in cardiovascular autonomic function and blood analytes were analysed by a mixed effects model for repeated measures. Results: Baseline characteristics were similar between treatment groups. In response to aliskiren compared with placebo, blood pressure was reduced as well as plasma renin activity [from 2.4±3.8 (mean±standard deviation) to 0.5±0.4μg/l/h, p<0.001]. There was a significant interaction (aliskiren×visit) for MCR (p=0.003) and E/I ratio (p=0.003) indicating improvement in MCR and E/I ratio for those on aliskiren. MCR means, baseline vs. follow-up, were 41.8±19.7 vs. 50.8±26.1 (aliskiren) and 38.2±23.6 vs. 37.5±24.1 (placebo). Conclusions: Parasympathetic function (i.e. MCR and E/I ratio) was enhanced by downregulation of the RAAS. © 2012 Blackwell Publishing Ltd.


Maser R.E.,University of Delaware | Maser R.E.,Diabetes and Metabolic Research Center | James Lenhard M.,Diabetes and Metabolic Research Center | James Lenhard M.,Diabetes and Metabolic Diseases Center | And 3 more authors.
Surgery for Obesity and Related Diseases | Year: 2013

Background: Osteocalcin (OC), a protein synthesized by osteoblasts, is a marker of bone turnover with undercarboxylated OC (ucOC) being involved in glucose homeostasis. Although laparoscopic Roux-en-Y gastric bypass (LRYGB)-induced weight loss likely alters bone turnover, data on markers of bone turnover remain less clear. The aim of this study was to examine the effect of surgically induced weight loss on OC and ucOC. Methods: A total of 32 individuals with a body mass index 50.2±10.2 kg/m2 underwent LRYGB. Osteocalcin, ucOC, other blood analytes (e.g., vitamin D, leptin, total and high-molecular-weight adiponectin), and homeostasis model assessment for insulin resistance were measured before and after weight loss. The effect of an acute nutrient load on OC parameters after a mixed meal tolerance test also was assessed. Results: Six months after surgery, there was an increase in OC (17.8±7.4 [mean±SD] [baseline] versus 31.5±9.8 ng/mL [follow-up]; P<.001) and ucOC (7.3±6.2 versus 18.5±8.9 ng/mL; P<.001). Although adiponectin increased, only the magnitude of change in OC and leptin was correlated (r =-.43; P =.017). After weight loss, an acute nutrient load reduced OC (31.5±9.8 [0-hour] versus 29.6±8.2 [2-hour] ng/mL; P =.024), whereas ucOC was higher (18.8±9.3 [0-hour] versus 21.1±8.6 [2-hour] ng/mL; P<.001). Conclusion: Surgically induced weight loss was associated with increases in OC and ucOC. Underlying mechanisms are unclear, but change in OC may be related to change in leptin. After a nutrient load, the increase in ucOC suggests a potential role as a short-term compensatory regulator of glucose homeostasis. © 2013 American Society for Metabolic and Bariatric Surgery. All rights reserved.


Maser R.E.,University of Delaware | Maser R.E.,Diabetes and Metabolic Research Center | Lenhard M.J.,Diabetes and Metabolic Research Center | Lenhard M.J.,Diabetes and Metabolic Diseases Center | Kolm P.,Christiana Care Outcomes Research
Journal of Diabetes and its Complications | Year: 2014

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 30-35 weeks gestation and 2-3 months 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 2-3 months 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. © 2014 Elsevier Inc.


PubMed | University of Delaware, Christiana Care Outcomes Research and Diabetes and Metabolic Research Center
Type: Journal Article | Journal: Journal of diabetes and its complications | Year: 2014

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.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.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).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.


Maser R.E.,University of Delaware | Maser R.E.,Diabetes and Metabolic Research Center | Lenhard M.J.,Diabetes and Metabolic Research Center | Lenhard M.J.,Diabetes and Metabolic Diseases Center | Pohlig R.T.,University of Delaware
Endocrine Practice | Year: 2015

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.


Maser R.E.,University of Delaware | Maser R.E.,Diabetes and Metabolic Research Center | Lenhard M.J.,Diabetes and Metabolic Research Center | Lenhard M.J.,Diabetes and Metabolic Diseases Center | And 2 more authors.
Endocrine Practice | Year: 2015

Objective: Coronary artery calcification (CAC) is a prominent feature of atherosclerosis and is associated with cardiovascular events. In vitro studies have suggested that osteoprotegerin (OPG) and osteocalcin (OC) exert anticalcification potential in the vessel wall. The objective of this study was to investigate the association of CAC and serum bone biomarkers in persons with type 2 diabetes. Methods: We examined 50 individuals with type 2 diabetes. CAC imaging was performed by multidetector computed tomography. CAC scores ≥10, expressed in Agatston units, were considered abnormal. OC, undercarboxylated OC (ucOC), and OPG levels were determined by enzyme-linked immunosorbent assay. Results: Abnormal CAC scores were found for 64% of the study cohort. OPG levels were significantly elevated (5.5 ± 2.0 pmol/L vs. 4.2 ± 1.7 pmol/L; P = .026) for those with abnormal CAC scores. No univariate differences were found for OC or ucOC. Logistic regression analyses revealed that an increase in serum OPG level was significantly associated with an increase in CAC score (odds ratio, 3.324; 95% confidence interval, 1.321 to 8.359; P = .011). Longer duration of diabetes was a significant covariate (P = .026), whereas nonsignificant covariates in the final model were age, gender, systolic blood pressure, body mass index, insulin resistance determined by the homeostasis model assessment for insulin resistance, leptin, adiponectin, and glycemic control. The Nagelkerke R2 for the model was 0.66. Neither OC nor ucOC were significantly associated with elevated CAC scores. Conclusion: Our results suggest that OPG is a more useful serum biomarker than OC or ucOC for identifying those at increased risk of arterial calcification in type 2 diabetes. Copyright © 2015 AACE.


Maser R.E.,University of Delaware | Lenhard M.J.,Diabetes and Metabolic Research Center | Pohlig R.T.,University of Delaware | Balagopal P.B.,Biomedical Research and Analysis Laboratory
Journal of Diabetes and its Complications | Year: 2015

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. © 2015 Elsevier Inc.


Maser R.E.,University of Delaware | Maser R.E.,Diabetes and Metabolic Research Center | Lenhard M.J.,Diabetes and Metabolic Research Center | Lenhard M.J.,Diabetes and Metabolic Diseases Center | And 3 more authors.
Surgery for Obesity and Related Diseases | Year: 2013

Background: Obesity is associated with autonomic imbalance. With respect to cardiovascular autonomic dysfunction, this is characterized by reduced heart rate variability (HRV). Our objective was to determine the effect of surgically induced weight loss on cardiovascular autonomic nerve fiber function in subjects with severe obesity and examine whether an association with reduced insulin resistance exists. The setting was a hospital and private practice in the United States. Methods: A total of 32 morbidly obese patients (body mass index 51 ± 11 kg/m2) underwent laparoscopic Roux-en-Y gastric bypass. Measures of HRV (e.g., power spectral analysis, RR variation during deep breathing) were used to evaluate autonomic function before and 6 months after surgery. The homeostasis model assessment of insulin resistance index (HOMA-IR) was used to assess insulin resistance. Results: At 6 months after bariatric surgery, the patients had lost 58% excess body mass index with improvement in the HOMA-IR (3.0 ± 1.4 versus 1.1 ±.7; P <.001). Measures of RR variation during deep breathing and total spectral power, low frequency (LF) power (influenced by sympathetic and parasympathetic activity), and high frequency (HF) power (parasympathetic activity) increased with weight loss. The LF/HF ratio was lower (1.5 ± 1.5 versus.9 ±.7, P <.05) with a reduction in weight. Spectral analysis of HRV combined with spectral analysis of respiratory activity generated the respiration frequency area (RFA) and low frequency area. The RFA was increased, and the LFA/RFA ratio was reduced with weight loss. HOMA-IR and HRV did not correlate. Conclusion: Surgically induced weight loss has a favorable effect on autonomic function, but it does not appear to be directly attributable to reduced insulin resistance. © 2013 American Society for Metabolic and Bariatric Surgery.


PubMed | University of Delaware, Biomedical Research & Analysis Laboratory and Diabetes and Metabolic Research Center
Type: Journal Article | Journal: Journal of diabetes and its complications | Year: 2016

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).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.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 age25(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).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.


PubMed | University of Delaware and Diabetes and Metabolic Research Center
Type: Journal Article | Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists | Year: 2015

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.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.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.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.

Loading Diabetes and Metabolic Research Center collaborators
Loading Diabetes and Metabolic Research Center collaborators