Diabetes and Metabolic Diseases Center

Wilmington, DE, United States

Diabetes and Metabolic Diseases Center

Wilmington, DE, United States

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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 | Kolm P.,Christiana Care Outcomes Research | Modlesky C.M.,University of Delaware | Beck T.J.,Johns Hopkins University | Lenhard M.J.,Diabetes and Metabolic Diseases Center
Journal of Clinical Densitometry | Year: 2012

We investigated the association of age at onset of type 1 diabetes with areal bone mineral density (aBMD), estimates of bone strength, and outer diameter. Using dual-energy X-ray absorptiometry (DXA), aBMD, axial strength (cross-sectional area [CSA]), bending strength (section modulus [SM]), and outer diameter at the narrow neck, intertrochanter, and shaft of the proximal femur were determined for 60 adults. Analysis of covariance (ANCOVA) was used to determine if the DXA-based measures of bone were related to age at onset and if this relationship differed by gender. Age at onset, gender, and the interaction of age at onset by gender were included in the ANCOVA models along with current age, duration, height, lean soft tissue mass, and hemoglobin A1c as covariates. In the adjusted models with CSA, SM, or outer diameter as the dependent variable, age at onset (p< 0.01) and gender (p< 0.0001) were significant with no interaction. For shaft aBMD, there was a significant age at onset by gender interaction (p= 0.0285), where an earlier onset was associated with lower aBMD in the femoral shaft of females but not males. The findings suggest that an earlier onset of type 1 diabetes is associated with lower measures of bone strength and outer diameter. © 2012 The International Society for Clinical Densitometry.


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.


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 | 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.


Lenhard M.J.,Diabetes and Metabolic Diseases Center | Kinsley B.T.,University College Dublin | Kinsley B.T.,Materials Misericordiae University Hospital
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2014

Pregnancies affected by type 1 diabetes (T1D) carry a major risk for poor fetal, neonatal and maternal outcomes. Achieving normoglycemia while minimizing the risk of hypoglycemia is a major goal in the management of T1D as this can greatly reduce the risk of complications. However, maintaining optimal glucose levels is challenging because insulin requirements are not uniform throughout the course of the pregnancy. Over the past decade, there has been significant improvement in the methods for glucose monitoring and insulin administration, accompanied by an increase in the number of treatment options available to pregnant patients with T1D. Through study of the scientific literature and accumulated evidence, we review advances in the management of T1D in pregnancy and offer advice on how to achieve optimal care for the patient. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.


PubMed | Diabetes and Metabolic Diseases Center
Type: Journal Article | Journal: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians | Year: 2014

Pregnancies affected by type 1 diabetes (T1D) carry a major risk for poor fetal, neonatal and maternal outcomes. Achieving normoglycemia while minimizing the risk of hypoglycemia is a major goal in the management of T1D as this can greatly reduce the risk of complications. However, maintaining optimal glucose levels is challenging because insulin requirements are not uniform throughout the course of the pregnancy. Over the past decade, there has been significant improvement in the methods for glucose monitoring and insulin administration, accompanied by an increase in the number of treatment options available to pregnant patients with T1D. Through study of the scientific literature and accumulated evidence, we review advances in the management of T1D in pregnancy and offer advice on how to achieve optimal care for the patient.

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