Endocrinology, Diabetes, and Metabolism Commons^™

Peripheral Quantitative Computed Tomography Detects Differences At The Radius In Prepubertal Children With Cystic Fibrosis Compared To Healthy Controls, Catherine E. O'Brien, Gulnur Com, John L. Fowlkes, Xinyu Tang, Laura P. James

Barnstable Brown Diabetes Center Faculty Publications

Introduction

In 2015, 11.9% of people with cystic fibrosis (CF) in the United States had osteopenia, 5.1% osteoporosis, and 0.3% experienced a fracture. Screening for CF-related bone disease starts in childhood, and dual energy x-ray absorptiometry (DXA) is the recommended method. It is unknown whether peripheral quantitative computed tomography (pQCT) can detect deficits earlier than DXA. This study compared pQCT and DXA scans in a group of pre-pubertal children with CF and healthy controls.

Methods

This was a cross-sectional study of children at Tanner stage 1. A pQCT scan of the radius at proximal and distal sites was performed plus …

Diabetes Conflict Outstrips The Positive Impact Of Self-Efficacy On Youth Adherence And Glycemic Control In Type 1 Diabetes., Amy E. Noser, Lindsay Huffhines, Mark A. Clements, Susana R. Patton

Manuscripts, Articles, Book Chapters and Other Papers

Objective: To examine whether self-efficacy buffers the deleterious consequences of diabetes-specific family conflict on self-monitoring blood glucose (SMBG) and glycated hemoglobin (HbA1c) in youth with type 1 diabetes mellitus (T1DM).

Methods: A total of 129 youth with T1DM (aged 10-16 years) completed measures of diabetes-specific family conflict and self-efficacy for diabetes management, and their blood glucose meter data and HbA1c were extracted from the electronic medical record. We preformed moderation analyses to examine whether self-efficacy moderated the association that diabetes-specific family conflict had with SMBG and HbA1c. We used simple slopes analyses to probe significant interactions.

Results: Our results indicated …

Effect Of Oral Semaglutide Compared With Placebo And Subcutaneous Semaglutide On Glycemic Control In Patients With Type 2 Diabetes: A Randomized Clinical Trial., Melanie Davies, Thomas R. Pieber, Marie-Louise Hartoft-Nielsen, Oluf K.H. Hansen, Serge Jabbour, Julio Rosenstock

Department of Medicine Faculty Papers

Importance: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection.

Objectives: To compare the effects of oral semaglutide with placebo (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control in patients with type 2 diabetes.

Design, Setting, and Patients: Phase 2, randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up at 100 sites (hospital clinics, general practices, and clinical research centers) in 14 countries conducted between December 2013 and December 2014. Of 1106 participants assessed, 632 with type 2 diabetes and insufficient glycemic control using diet and …

Effects Of Once-Weekly Exenatide On Cardiovascular Outcomes In Type 2 Diabetes, Rury R Holman, M Angelyn Bethel, Robert J Mentz, Vivian P Thompson, Yuliya Lokhnygina, John B Buse, Juliana C Chan, Jasmine Choi, Stephanie M Gustavson, Nayyar Iqbal, Aldo P Maggioni, Steven P Marso, Peter Öhman, Neha J Pagidipati, Neil Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez

Faculty, Staff and Student Publications

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.

METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy.

RESULTS: …

The Interactive Effect Of Diabetes Family Conflict And Depression On Insulin Bolusing Behaviors For Youth., Genevieve Maliszewski, Susana R. Patton, L Kurt Midyett, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Adherence to type 1 diabetes management declines as children enter adolescence. For youth, psychosocial variables including mood and interpersonal relationships play a large role in diabetes maintenance. The current study assessed the unique and interactive roles diabetes family conflict and depression have on insulin bolusing behaviors for youth ages 10-16 years.

METHODS: Ninety-one youth-parent dyads completed a survey assessing family conflict and depression. Mean daily blood glucose levels, mealtime insulin bolus scores ( BOLUS), and glycated hemoglobin (HbA1c) were collected from the medical record as outcome variables.

RESULTS: Parent-reported diabetes-related family conflict and youths' endorsed depression both significantly predicted …

Long-Term Excess Risk Of Stroke In People With Type 2 Diabetes In Sweden According To Blood Pressure Level: A Population-Based Case-Control Study., C Hedén Ståhl, M Lind, A-M Svensson, M Kosiborod, S Gudbjörnsdottir, A Pivodic, Mark A. Clements, A Rosengren

Manuscripts, Articles, Book Chapters and Other Papers

AIMS: To estimate the risk of stroke in people with Type 2 diabetes with different blood pressure levels compared with the risk in the general population in Sweden.

METHODS: This prospective case-control study included 408 076 people with Type 2 diabetes, aged ≥ 18 years, and free of prior stroke, registered in the Swedish National Diabetes Register 1998-2011. Age- and sex-matched control subjects (n = 1 913 507) without stroke from the general population were included. Stroke diagnoses were retrieved using International Classification of Disease codes from the Swedish patient and death registers. Cox hazard ratios and 95% confidence intervals …

Evaluating Parents' Self-Efficacy For Diabetes Management In Pediatric Type 1 Diabetes., Amy E. Noser, Susana R. Patton, Jason Van Allen, Michael B. Nelson, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

Objective: To examine the factor structure and construct validity of the Maternal Self-Efficacy for Diabetes Management Scale (MSED) in 135 youth ( Mage  = 13.50  ±  1.83 years), with type 1 diabetes mellitus.

Method: The study used exploratory factor analysis (EFA) to examine the factor structure and correlations to examine relationships among MSED factors and select parent and child diabetes-related health behaviors and outcomes.

Results: EFA identified an 11-item three-factor solution (χ 2 (25, n  = 133)  = 40.22, p  < .03, RMSEA = 0.07, CFI = 0.98, TLI = 0.97), with factors corresponding to parents' perceived ability to manage their child's diabetes (MSED-M), problem-solve issues surrounding glycemic control (MSED-P), and teach their child about diabetes care (MSED-T). Correlational analyses revealed significant associations between the MSED-M and MSED-T and parent-reported optimism and youth's diabetes-specific self-efficacy. The MSED-T was also associated with glycated hemoglobin and self-monitoring blood glucose.

Conclusions: Results provide preliminary evidence for the reliability and validity of a three-factor solution of the MSED.

Reexamining The Hypoglycemia Fear Survey For Parents Of Young Children In A Sample Of Children Using Insulin Pumps., Susana R. Patton, Amy E. Noser, Mark A. Clements, Lawrence M. Dolan, Scott W. Powers

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We update the psychometric properties of the Hypoglycemia Fear Survey-Parents of Young Children (HFS-PYC), a 26-item measure of parents' hypoglycemia fear for young children using an insulin pump.

METHODS: We combined three similar datasets for the analyses. The data analyzed included parents' responses to the HFS-PYC and a demographic form. For a subset of children (n = 91), we also analyzed self-monitoring of blood glucose data. We used confirmatory factor analysis (CFA) to confirm the measure's original factor structure. Additional analyses examined reliability and validity of a revised HFS-PYC for parents of young children using pumps.

RESULTS: We analyzed …

Risk Of Glucose Intolerance And Gestational Diabetes Mellitus In Relation To Maternal Habitual Snoring During Early Pregnancy., Chunfang Qiu, Wayne Lawrence, Bizu Gelaye, Lee Stoner, Ihunnaya O Frederick, Daniel A Enquobahrie, Tanya K Sorensen, Michelle A Williams

Articles, Abstracts, and Reports

BACKGROUND: Obstructive sleep apnea (OSA) or habitual snoring is known to be associated with impaired glucose tolerance and type 2 diabetes among both men and non-pregnant women. We examined the association of habitual snoring during early pregnancy with risk of impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM).

METHODS: A cohort of 1,579 women was interviewed during early pregnancy. We collected information about snoring frequency during early pregnancy. Results from screening and diagnostic tests for IGT and GDM were abstracted from medical records. Multivariate logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% …

Predictors Of Loss To Follow-Up Among Children With Type 2 Diabetes., Ashley Shoemaker, Peiyao Cheng, Robin L. Gal, Craig Kollman, William V. Tamborlane, Georgeanna J. Klingensmith, Mark A. Clements, Tamara S. Hannon, Rubina Heptulla, Joane Less, Jamie Wood, Pediatric Diabetes Consortium

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND/AIMS: Youth with type 2 diabetes (T2D) have poor compliance with medical care. This study aimed to determine which demographic and clinical factors differ between youth with T2D who receive care in a pediatric diabetes center versus youth lost to follow-up for >18 months.

METHODS: Data were analyzed from 496 subjects in the Pe-diatric Diabetes Consortium registry. Enrollment variables were selected a priori and analyzed with univariable and multivariable logistic regression models.

RESULTS: After a median of 1.3 years from enrollment, 55% of patients were lost to follow-up. The final model included age, race/ethnicity, parent education, and estimated distance to …

Adherence To Insulin Pump Behaviors In Young Children With Type 1 Diabetes Mellitus., Susana R. Patton, Kimberly A. Driscoll, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Parents of young children are responsible for daily type 1 diabetes (T1DM) cares including insulin bolusing. For optimal insulin pump management, parents should enter a blood glucose result (SMBG) and a carbohydrate estimate (if food will be consumed) into the bolus advisor in their child's pump to assist in delivering the recommended insulin bolus. Previously, pump adherence behaviors were described in adolescents; we describe these behaviors in a sample of young children.

METHODS: Pump data covering between 14-30 consecutive days were obtained for 116 children. Assessed adherence to essential pump adherence behaviors (eg, SMBG, carbohydrate entry, and insulin use) …

Considering Decision-Making And Sexuality In Menstrual Suppression Of Teens And Young Adults With Intellectual Disabilities., Kruti Acharya, John D. Lantos

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Effect Of Vitamins C And E On Endothelial Function In Type 1 Diabetes Mellitus, Rachel-Marie Cazeau, Hong Huang, John A. Bauer, Robert P. Hoffman

Pediatrics Faculty Publications

Background/Objectives. Endothelial dysfunction due to hyperglycemia-induced oxidative damage is an important predictor of future cardiovascular risk in patients with type 1 diabetes mellitus (T1DM) and is present in adolescent T1DM. We hypothesized that combined treatment with the antioxidant vitamins C and E might improve endothelial function (EF) and other biochemical risk factors in adolescents with T1DM. Subjects/Methods. Open-label antioxidant supplementation was given for six weeks with endpoint measurements collected at baseline and study completion. Endpoints measured included EF and plasma measurements of biochemical endothelial risk. Results. Two males and 7 females were studied. Mean age was 12.9 ± 0.9 yrs; …

Obesity Early In Adulthood Increases Risk But Does Not Affect Outcomes Of Hepatocellular Carcinoma, Manal M. Hassan, Reham Abdel-Wahab, Ahmed Kaseb, Ahmed Shalaby, Alexandria Phan, Hashem El-Serag, Ernest Hawk, Jeff Morris, Kanwal Pratap Singh Raghav, Ju-Seog Lee, Jean-Nicolas Vauthey, Gehan Bortus, Harrys Torres, Christopher Amos, Robert Wolff, Donghui Li

Dartmouth Scholarship

Despite the significant association between obesity and several cancers, it has been difficult to establish an association between obesity and hepatocellular carcinoma (HCC). Patients with HCC often have ascites, making it a challenge to accurately determine body mass index (BMI), and many factors contribute to the development of HCC. We performed a case–control study to investigate whether obesity early in adulthood affects risk, age of onset, or outcomes of patients with HCC.

Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism In High Fat Diet-Induced Obesity, R. Grace Walton, Beibei Zhu, Resat Unal, Michael Spencer, Manjula Sunkara, Andrew J. Morris, Richard Charnigo, Wendy S. Katz, Alan Daugherty, Deborah A. Howatt, Philip A. Kern, Brian S. Finlin

Barnstable Brown Diabetes Center Faculty Publications

Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization …

The Impact Of Salsalate Treatment On Serum Levels Of Advanced Glycation End Products In Type 2 Diabetes., Joshua I Barzilay, Kathleen A. Jablonski, Vivian Fonseca, Steven E Shoelson, Allison B Goldfine, Christopher Strauch, Vincent M Monnier, Tinsal-T2d Research Consortium.

GW Biostatistics Center

OBJECTIVE Salsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and fructoselysine …

Genetic Risk Of Progression To Type 2 Diabetes And Response To Intensive Lifestyle Or Metformin In Prediabetic Women With And Without A History Of Gestational Diabetes Mellitus., Shannon D Sullivan, Kathleen A. Jablonski, Jose C Florez, Dana Dabelea, Paul W Franks, Sam Dagogo-Jack, Catherine Kim, William C Knowler, Costas A Christophi, Robert Ratner, Diabetes Prevention Program Research Group.

GW Biostatistics Center

OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births.

RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM.

RESULTS β-Cell function was …

Targeting Inflammation Using Salsalate In Patients With Type 2 Diabetes: Effects On Flow-Mediated Dilation (Tinsal-Fmd)., Allison B Goldfine, J Stewart Buck, Cyrus Desouza, Vivian Fonseca, Yii-Der Ida Chen, Steven E Shoelson, Kathleen A. Jablonski, Mark A Creager, The Tinsal-Fmd Team

GW Biostatistics Center

OBJECTIVE: To test whether inhibiting inflammation with salsalate improves endothelial function in patients with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: We conducted an ancillary study to the National Institutes of Health-sponsored, multicenter, randomized, double-masked, placebo-controlled trial evaluating the safety and efficacy of salsalate in targeting inflammation to improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD) of the brachial artery were assessed at baseline and 3 and 6 months following randomization to either salsalate 3.5 g/day or placebo. The primary end point was change in FMD at 6 months.

RESULTS: A total …

Invited Commentary On: Orthotopic Heart Transplantation In Patients With Metabolic Risk Factors, Nicholas C. Cavarocchi, Paul Mather

Department of Surgery Faculty Papers

This is invited commentary to the following article:

Kilic, A., Conte, J. V., Shah, A. S., & Yuh, D. D. (2012). Orthotopic heart transplantation in patients with metabolic risk factors. Annals of Thoracic Surgery, 93(3), 718-724.

Basal Insulin Requirements On Continuous Subcutaneous Insulin Infusion During The First 12 Months After Diagnosis Of Type 1 Diabetes Mellitus., Neesha Ramchandani, Mary Kristine Ellis, Shobhit Jain, Sonal Bhandari, Henry Anhalt, Noel K. Maclaren, Svetlana Ten

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: While the endogenous first-phase insulin response has disappeared by the time of diagnosis of type 1 diabetes mellitus (T1DM), anecdotal evidence suggests that these patients can continue to have a second-phase insulin response during the first 12 months after diagnosis. We hypothesized that patients who are started on continuous subcutaneous insulin infusion (CSII) at the time of diagnosis of T1DM would have a lower basal insulin requirement than the 40-60% usually expected.

METHODS: We analyzed 38 patients with T1DM, age 9.9 +/- 6.4 years, 71% male, who were started on CSII within the first month of diagnosis.

RESULTS: Average …

Enhanced Estrogen-Induced Proliferation In Obese Rat Endometrium, Qian Zhang, Qi Shen, Joseph Celestino, Michael R Milam, Shannon N Westin, Robin A Lacour, Larissa A Meyer, Gregory L Shipley, Peter J A Davies, Lei Deng, Adrienne S Mccampbell, Russell R Broaddus, Karen H Lu

Faculty, Staff and Student Publications

OBJECTIVE: We tested the hypothesis that the proliferative estrogen effect on the endometrium is enhanced in obese vs lean animals.

STUDY DESIGN: Using Zucker fa/fa obese rats and lean control, we examined endometrial cell proliferation and the expression patterns of certain estrogen-regulated proproliferative and antiproliferative genes after short-term treatment with estradiol.

RESULTS: No significant morphologic/histologic difference was seen between the obese rats and the lean rats. Estrogen-induced proproliferative genes cyclin A and c-Myc messenger RNA expression were significantly higher in the endometrium of obese rats compared with those of the lean control. Expression of the antiproliferative gene p27Kip1 was suppressed …

Osteoarthritis Associated With Estrogen Deficiency., Jorge A Roman-Blas, Santos Castañeda, Raquel Largo, Gabriel Herrero-Beaumont

Jefferson Institute of Molecular Medicine Papers and Presentations

Osteoarthritis (OA) affects all articular tissues and finally leads to joint failure. Although articular tissues have long been considered unresponsive to estrogens or their deficiency, there is now increasing evidence that estrogens influence the activity of joint tissues through complex molecular pathways that act at multiple levels. Indeed, we are only just beginning to understand the effects of estrogen deficiency on articular tissues during OA development and progression, as well as on the association between OA and osteoporosis. Estrogen replacement therapy and current selective estrogen receptor modulators have mixed effectiveness in preserving and/or restoring joint tissue in OA. Thus, a …

Genes In Glucose Metabolism And Association With Spina Bifida, Christina M Davidson, Hope Northrup, Terri M King, Jack M Fletcher, Irene Townsend, Gayle H Tyerman, Kit Sing Au

Faculty, Staff and Student Publications

The authors test single nucleotide polymorphisms (SNPs) in coding sequences of 12 candidate genes involved in glucose metabolism and obesity for associations with spina bifida. Genotyping was performed on 507 children with spina bifida and their parents plus anonymous control DNAs from Hispanic and Caucasian individuals. The transmission disequilibrium test was performed to test for genetic associations between transmission of alleles and spina bifida in the offspring (P < .05). A statistically significant association between Lys481 of HK1 (G allele), Arg109Lys of LEPR (G allele), and Pro196 of GLUT1 (A allele) was found ( P = .019, .039, and .040, respectively). Three SNPs on 3 genes involved with glucose metabolism and obesity may be associated with increased susceptibility to spina bifida.

Reduction In The Incidence Of Type 2 Diabetes With Lifestyle Intervention Or Metformin., William C. Knowler, Elizabeth Barrett-Connor, Sarah E. Fowler, Richard F. Hamman, John M. Lachin, Elizabeth A. Walker, David M. Nathan, P. G. Watson, J. T. Mendoza, K. A. Smith, J. Caro, B. Goldstein, C. Lark, L. Menefee, L. Murphy, C. Pepe, J. M. Spandorfer

Department of Medicine Faculty Papers

BACKGROUND: Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.

METHODS: We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least …