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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. Source


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. Source


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. Source


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. Source


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. Source

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