Epidemiology Commons^™

Effects Of Genetic Variants Previously Associated With Fasting Glucose And Insulin In The Diabetes Prevention Program, Jose C. Florez, Kathleen A. Jablonski, Jarred B. Mcateer, Paul W. Franks, Clinton C. Mason, Kieren J. Mather, Edward Horton, Ronald Goldberg, Dana Dabelea, Steven E. Kahn, Richard F. Arakaki, Alan R. Shuldiner, William C. Knowler

Epidemiology Faculty Publications

Common genetic variants have been recently associated with fasting glucose and insulin levels in white populations. Whether these associations replicate in pre-diabetes is not known. We extended these findings to the Diabetes Prevention Program, a clinical trial in which participants at high risk for diabetes were randomized to placebo, lifestyle modification or metformin for diabetes prevention. We genotyped previously reported polymorphisms (or their proxies) in/near G6PC2, MTNR1B, GCK, DGKB, GCKR, ADCY5, MADD, CRY2, ADRA2A,FADS1, PROX1, SLC2A2, GLIS3, C2CD4B, IGF1, and IRS1 in 3,548 Diabetes …

Genetic Modulation Of Lipid Profiles Following Lifestyle Modification Or Metformin Treatment: The Diabetes Prevention Program, Toni I. Pollin, Tamara Isakova, Kathleen A. Jablonski, Paul I.W. De Bakker, Andrew Taylor, Jarred B. Mcateer, Qing Pan, Edward Horton, Linda M. Delahanty, David Altshuler, Alan R. Shuldiner, Ronald Goldberg, Jose C. Florez, George A. Bray

Epidemiology Faculty Publications

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, …

Fall In C-Peptide During First 2 Years From Diagnosis: Evidence Of At Least Two Distinct Phases From Composite Type 1 Diabetes Trialnet Data., Carla J. Greenbaum, Craig A. Beam, David Boulware, Stephen E. Gitelman, Peter A. Gottlieb, Kevan C. Herold, John M. Lachin, Paula L. Mcgee, Jerry P. Palmer, Mark D. Pescovitz, Heidi Krause-Steinrauf, Jay S. Skyler, Jay M. Sosenko

Epidemiology Faculty Publications

Interpretation of clinical trials to alter the decline in β-cell function after diagnosis of type 1 diabetes depends on a robust understanding of the natural history of disease. Combining data from the Type 1 Diabetes TrialNet studies, we describe the natural history of β-cell function from shortly after diagnosis through 2 years post study randomization, assess the degree of variability between patients, and investigate factors that may be related to C-peptide preservation or loss. We found that 93% of individuals have detectable C-peptide 2 years from diagnosis. In 11% of subjects, there was no significant fall from baseline by 2 …

Selective Impact Of Hiv Disease Progression On The Innate Immune System In The Human Female Reproductive Tract., Timothy Lahey, Mimi Ghosh, John V. Fahey, Zheng Sheng, Lucy R. Mukura, Yan Song, Susan Cu-Uvin, Kenneth H. Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira

Epidemiology Faculty Publications

Background

We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.

Methods

CVL from 57 HIV-infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/µl, 200–500 cells/µl, or <200 cells/µl of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti-gp160 HIV IgG antibodies were measured by ELISA and Luminex.

Results

CVL exhibited broad anti-HIV activity against multiple laboratory-adapted and transmitted/founder (T/F) viruses, with anti-HIV activity ranging from 0 to 100% …

Characteristics Of Children With Type 1 Diabetes And Persistent Suboptimal Glycemic Control., Hyuntae Kim, Angelo Elmi, Celia L. Henderson, Fran R. Cogen, Paul B. Kaplowitz

Epidemiology Faculty Publications

Objective: This study aims to determine the relationship between the duration of persistent poor glycemic control in type 1 diabetes mellitus (T1DM) children and the likelihood of subsequent improvement.

Methods: A retrospective cohort study was conducted on T1DM patients aged 6-18 years, followed for at least six visits at Children’s National Medical Center (Washington, DC) with at least one hemoglobin A1c (HbA1c) ≥10% after the first year since the initial visit (n=151). Medical records of patients with subsequently improved glycemic control were reviewed (n=39).

Results: Patients aged 12-18 years, females, and Medicaid patients were twice as likely to be in …

Demographics And Survival Of Aids Cases With Cancer, Washington, Dc, 1996-2006, Heather A. Young, Eric Engels, Anne-Marie Sufian-Kargbo, Alicia Vargas, Kathleen Rogers, Tiffany West, Amanda D. Castel

Epidemiology Faculty Publications

Background

Washington, DC (DC) has one of the highest HIV/AIDS rates in the U.S and cancer is the second leading cause of death among DC residents. This study sought to examine the demographic characteristics and survival of persons with AIDS defining cancers (ADCs) compared to those with non-AIDS defining cancers (NADCs) between the early HAART era (1996-2001) and the late HAART era (2002-2006) in DC.

Methods

Cases reported from 1996-2006 to the DC Cancer Registry and the AIDS Surveillance Registry were linked using a probabilistic matching algorithm. Cases were included if the cancer occurred from 4 months to 60 months …

High And Persistent Hiv Seroincidence In Men Who Have Sex With Men Across 47 U.S. Cities, Marta-Louise Ackers, Alan E. Greenberg, Carol Y. Lin, Bradford N. Bartholow, Adrian Hirsch Goodman, Michael Longhi, Marc Gurwith

Epidemiology Faculty Publications

Objective

To provide HIV seroincidence data among men who have sex with men (MSM) in the United States and to identify predictive factors for seroconversion.

Methods

From 1998–2002, 4684 high-risk MSM, age 18–60 years, participated in a randomized, placebo-controlled HIV vaccine efficacy trial at 56 U.S. clinical trial sites. Demographics, behavioral data, and HIV status were assessed at baseline and 6 month intervals. Since no overall vaccine efficacy was detected, data were combined from both trial arms to calculate HIV incidence based on person-years (py) of follow-up. Predictors of seroconversion, adjusted hazards ratio (aHR), were evaluated using a Cox proportional …

Progestogens To Prevent Preterm Birth In Twin Pregnancies: An Individual Participant Data Meta-Analysis Of Randomized Trials., Ewoud Schuit, Sarah Stock, Rolf H.H. Groenwold, Kimberly Maurel, C. Andrew Combs, Thomas Garite, Catherine Y. Spong, Elizabeth A. Thom, Dwight J. Rouse, Steve N. Caritis, George Saade, Julia M. Zachary, Jane E. Norman, Line Rode, Katharina Klein, Ann Tabor, Elcin Cetingoz, John C. Morrison, Everett F. Magann, Christian M. Briery, Vicente Serra, Alfredo Perales, Juan Meseguer, Anwar Nassar, Arianne C. Lim, Karel G.M. Moons, Anneke Kwee, Ben W.J. Mol

Epidemiology Faculty Publications

Background

Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death.

Methods/design

We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The …

Does Secondary Inflammatory Breast Cancer Represent Post-Surgical Metastatic Disease?, Salman Hashmi, Ladan Zolfaghari, Paul H. Levine

Epidemiology Faculty Publications

The phenomenon of accelerated tumor growth following surgery has been observed repeatedly and merits further study. Inflammatory breast carcinoma (IBC) is widely recognized as an extremely aggressive malignancy characterized by micrometastasis at the time of diagnosis, with one interesting subgroup defined as secondary IBC where pathologically identifiable IBC appears after surgical treatment of a primary non-inflammatory breast cancer. One possible mechanism can be related to the stimulation of dormant micrometastasis through local angiogenesis occurring as part of posttraumatic healing. In this report, we review cases of secondary IBC and others where localized trauma was followed by the appearance of IBC …

Alternate Estrogen Receptors Promote Invasion Of Inflammatory Breast Cancer Cells Via Non-Genomic Signaling, Kazufumi Ohshiro, Arnold M. Schwartz, Paul H. Levine, Rakesh Kumar

Epidemiology Faculty Publications

Although Inflammatory Breast Cancer (IBC) is a rare and an aggressive type of locally advanced breast cancer with a generally worst prognosis, little work has been done in identifying the status of non-genomic signaling in the invasiveness of IBC. The present study was performed to explore the status of non-genomic signaling as affected by various estrogenic and anti-estrogenic agents in IBC cell lines SUM149 and SUM190. We have identified the presence of estrogen receptor α (ERα) variant, ERα36 in SUM149 and SUM190 cells. This variant as well as ERβ was present in a substantial concentration in IBC cells. The treatment …