Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 1063

Publication Record

Connections

COVID-19 Severity Is Tripled in the Diabetes Community: A Prospective Analysis of the Pandemic's Impact in Type 1 and Type 2 Diabetes.
Gregory JM, Slaughter JC, Duffus SH, Smith TJ, LeStourgeon LM, Jaser SS, McCoy AB, Luther JM, Giovannetti ER, Boeder S, Pettus JH, Moore DJ
(2021) Diabetes Care 44: 526-532
MeSH Terms: COVID-19, Comorbidity, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Electronic Health Records, Female, Hospitalization, Humans, Hypertension, Male, Middle Aged, Odds Ratio, Prospective Studies, Severity of Illness Index
Show Abstract · Added December 7, 2020
OBJECTIVE - To quantify and contextualize the risk for coronavirus disease 2019 (COVID-19)-related hospitalization and illness severity in type 1 diabetes.
RESEARCH DESIGN AND METHODS - We conducted a prospective cohort study to identify case subjects with COVID-19 across a regional health care network of 137 service locations. Using an electronic health record query, chart review, and patient contact, we identified clinical factors influencing illness severity.
RESULTS - We identified COVID-19 in 6,138, 40, and 273 patients without diabetes and with type 1 and type 2 diabetes, respectively. Compared with not having diabetes, people with type 1 diabetes had adjusted odds ratios of 3.90 (95% CI 1.75-8.69) for hospitalization and 3.35 (95% CI 1.53-7.33) for greater illness severity, which was similar to risk in type 2 diabetes. Among patients with type 1 diabetes, glycosylated hemoglobin (HbA), hypertension, race, recent diabetic ketoacidosis, health insurance status, and less diabetes technology use were significantly associated with illness severity.
CONCLUSIONS - Diabetes status, both type 1 and type 2, independently increases the adverse impacts of COVID-19. Potentially modifiable factors (e.g., HbA) had significant but modest impact compared with comparatively static factors (e.g., race and insurance) in type 1 diabetes, indicating an urgent and continued need to mitigate severe acute respiratory syndrome coronavirus 2 infection risk in this community.
© 2020 by the American Diabetes Association.
0 Communities
2 Members
0 Resources
14 MeSH Terms
T-B Lymphocyte Interactions Promote Type 1 Diabetes Independently of SLAM-Associated Protein.
Bonami RH, Nyhoff LE, McNitt DH, Hulbert C, Felton JL, Kendall PL, Thomas JW
(2020) J Immunol 205: 3263-3276
MeSH Terms: Animals, Autoantibodies, B-Lymphocytes, Cell Communication, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Mice, Mice, Inbred NOD, Mice, Transgenic, Signaling Lymphocytic Activation Molecule Associated Protein, Th1 Cells
Show Abstract · Added December 1, 2020
Signaling lymphocytic activation molecule-associated protein (SAP), a critical intracellular signaling molecule for T-B lymphocyte interactions, drives T follicular helper (Tfh) cell development in germinal centers (GCs). High-affinity islet autoantibodies predict type 1 diabetes (T1D) but do not cause β cell destruction. This paradox intimates Tfh cells as key pathologic effectors, consistent with an observed Tfh signature in T1D. To understand how fully developed Tfh (GC Tfh) contribute to different autoimmune processes, we investigated the role of SAP in T1D and autoantibody-mediated arthritis. Whereas spontaneous arthritis depended on in the autoantibody-mediated K/BxN model, organized insulitis and diabetes onset were unabated, despite a blocked anti-insulin vaccine response in -deficient NOD mice. GC Tfh and GC B cell development were blocked by loss of in K/BxN mice. In contrast, although GC B cell formation was markedly reduced in -deficient NOD mice, T cells with a GC Tfh phenotype were found at disease sites. CXCR3 CCR6 (Tfh1) subset bias was observed among GC Tfh cells infiltrating the pancreas of NOD mice, which was enhanced by loss of NOD T cells override requirement to undergo activation and proliferation in response to Ag presentation, demonstrating the potential for productive cognate T-B lymphocyte interactions in T1D-prone mice. We find that is essential when autoantibody-driven immune complexes promote inflammation but is not required for effective organ-specific autoimmune attack. Thus, Tfh induced in classic GC reactions are dispensable for T1D, but the autoimmune process in the NOD model retains pathogenic Tfh without .
Copyright © 2020 by The American Association of Immunologists, Inc.
1 Communities
0 Members
0 Resources
11 MeSH Terms
Metabolomics reveals the impact of Type 2 diabetes on local muscle and vascular responses to ischemic stress.
Beckman JA, Hu JR, Huang S, Farber-Eger E, Wells QS, Wang TJ, Gerszten RE, Ferguson JF
(2020) Clin Sci (Lond) 134: 2369-2379
MeSH Terms: Brachial Artery, Case-Control Studies, Diabetes Mellitus, Type 2, Endothelium, Vascular, Extremities, Female, Humans, Ischemia, Male, Metabolome, Metabolomics, Middle Aged, Muscle, Skeletal, Phosphorylcholine, Regional Blood Flow, Signal Transduction, Vasodilation
Show Abstract · Added September 14, 2020
OBJECTIVE - Type 2 diabetes mellitus (T2DM) reduces exercise capacity, but the mechanisms are incompletely understood. We probed the impact of ischemic stress on skeletal muscle metabolite signatures and T2DM-related vascular dysfunction.
METHODS - we recruited 38 subjects (18 healthy, 20 T2DM), placed an antecubital intravenous catheter, and performed ipsilateral brachial artery reactivity testing. Blood samples for plasma metabolite profiling were obtained at baseline and immediately upon cuff release after 5 min of ischemia. Brachial artery diameter was measured at baseline and 1 min after cuff release.
RESULTS - as expected, flow-mediated vasodilation was attenuated in subjects with T2DM (P<0.01). We confirmed known T2DM-associated baseline differences in plasma metabolites, including homocysteine, dimethylguanidino valeric acid and β-alanine (all P<0.05). Ischemia-induced metabolite changes that differed between groups included 5-hydroxyindoleacetic acid (healthy: -27%; DM +14%), orotic acid (healthy: +5%; DM -7%), trimethylamine-N-oxide (healthy: -51%; DM +0.2%), and glyoxylic acid (healthy: +19%; DM -6%) (all P<0.05). Levels of serine, betaine, β-aminoisobutyric acid and anthranilic acid were associated with vessel diameter at baseline, but only in T2DM (all P<0.05). Metabolite responses to ischemia were significantly associated with vasodilation extent, but primarily observed in T2DM, and included enrichment in phospholipid metabolism (P<0.05).
CONCLUSIONS - our study highlights impairments in muscle and vascular signaling at rest and during ischemic stress in T2DM. While metabolites change in both healthy and T2DM subjects in response to ischemia, the relationship between muscle metabolism and vascular function is modified in T2DM, suggesting that dysregulated muscle metabolism in T2DM may have direct effects on vascular function.
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Microvascular disease confers additional risk to COVID-19 infection.
Bale BF, Doneen AL, Vigerust DJ
(2020) Med Hypotheses 144: 109999
MeSH Terms: Adult, Aging, COVID-19, Cardiovascular Diseases, Child, Diabetes Mellitus, Disease Susceptibility, Humans, Hydrogen Peroxide, Hypertension, Hypochlorous Acid, Immunity, Innate, Lung, Microcirculation, Microvessels, Neutrophils, Pandemics, Peroxidase, Risk Factors, United States
Show Abstract · Added June 25, 2020
The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin "COVID-19 Clinical Guidance for the CV Care Team", there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% ≥80 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention.
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Myt Transcription Factors Prevent Stress-Response Gene Overactivation to Enable Postnatal Pancreatic β Cell Proliferation, Function, and Survival.
Hu R, Walker E, Huang C, Xu Y, Weng C, Erickson GE, Coldren A, Yang X, Brissova M, Kaverina I, Balamurugan AN, Wright CVE, Li Y, Stein R, Gu G
(2020) Dev Cell 53: 390-405.e10
MeSH Terms: Activating Transcription Factor 4, Animals, Cell Proliferation, DNA-Binding Proteins, Diabetes Mellitus, Female, Heat-Shock Proteins, Humans, Insulin Secretion, Insulin-Secreting Cells, Male, Mice, Mice, Knockout, Stress, Physiological, Transcription Factors
Show Abstract · Added May 6, 2020
Although cellular stress response is important for maintaining function and survival, overactivation of late-stage stress effectors cause dysfunction and death. We show that the myelin transcription factors (TFs) Myt1 (Nzf2), Myt2 (Myt1l, Nztf1, and Png-1), and Myt3 (St18 and Nzf3) prevent such overactivation in islet β cells. Thus, we found that co-inactivating the Myt TFs in mouse pancreatic progenitors compromised postnatal β cell function, proliferation, and survival, preceded by upregulation of late-stage stress-response genes activating transcription factors (e.g., Atf4) and heat-shock proteins (Hsps). Myt1 binds putative enhancers of Atf4 and Hsps, whose overexpression largely recapitulated the Myt-mutant phenotypes. Moreover, Myt(MYT)-TF levels were upregulated in mouse and human β cells during metabolic stress-induced compensation but downregulated in dysfunctional type 2 diabetic (T2D) human β cells. Lastly, MYT knockdown caused stress-gene overactivation and death in human EndoC-βH1 cells. These findings suggest that Myt TFs are essential restrictors of stress-response overactivity.
Copyright © 2020 Elsevier Inc. All rights reserved.
3 Communities
2 Members
0 Resources
15 MeSH Terms
The Peripheral Peril: Injected Insulin Induces Insulin Insensitivity in Type 1 Diabetes.
Gregory JM, Cherrington AD, Moore DJ
(2020) Diabetes 69: 837-847
MeSH Terms: Animals, Diabetes Mellitus, Type 1, Gene Expression Regulation, Humans, Insulin, Insulin Resistance
Show Abstract · Added April 22, 2020
Insulin resistance is an underappreciated facet of type 1 diabetes that occurs with remarkable consistency and considerable magnitude. Although therapeutic innovations are continuing to normalize dysglycemia, a sizable body of data suggests a second metabolic abnormality-iatrogenic hyperinsulinemia-principally drives insulin resistance and its consequences in this population and has not been addressed. We review this evidence to show that injecting insulin into the peripheral circulation bypasses first-pass hepatic insulin clearance, which leads to the unintended metabolic consequence of whole-body insulin resistance. We propose restructuring insulin therapy to restore the physiological insulin balance between the hepatic portal and peripheral circulations and thereby avoid the complications of life-long insulin resistance. As technology rapidly advances and our ability to ensure euglycemia improves, iatrogenic insulin resistance will become the final barrier to overcome to restore normal physiology, health, and life in type 1 diabetes.
© 2020 by the American Diabetes Association.
0 Communities
2 Members
0 Resources
6 MeSH Terms
Coregulator Sin3a Promotes Postnatal Murine β-Cell Fitness by Regulating Genes in Ca Homeostasis, Cell Survival, Vesicle Biosynthesis, Glucose Metabolism, and Stress Response.
Yang X, Graff SM, Heiser CN, Ho KH, Chen B, Simmons AJ, Southard-Smith AN, David G, Jacobson DA, Kaverina I, Wright CVE, Lau KS, Gu G
(2020) Diabetes 69: 1219-1231
MeSH Terms: Aging, Animals, Basic Helix-Loop-Helix Transcription Factors, Calcium, Cell Survival, Diabetes Mellitus, Female, Gene Expression Regulation, Developmental, Homeostasis, Insulin-Secreting Cells, Male, Mice, Mice, Knockout, Nerve Tissue Proteins, Repressor Proteins, Sin3 Histone Deacetylase and Corepressor Complex
Show Abstract · Added April 7, 2020
Swi-independent 3a and 3b (Sin3a and Sin3b) are paralogous transcriptional coregulators that direct cellular differentiation, survival, and function. Here, we report that mouse Sin3a and Sin3b are coproduced in most pancreatic cells during embryogenesis but become much more enriched in endocrine cells in adults, implying continued essential roles in mature endocrine cell function. Mice with loss of in endocrine progenitors were normal during early postnatal stages but gradually developed diabetes before weaning. These physiological defects were preceded by the compromised survival, insulin-vesicle packaging, insulin secretion, and nutrient-induced Ca influx of -deficient β-cells. RNA sequencing coupled with candidate chromatin immunoprecipitation assays revealed several genes that could be directly regulated by Sin3a in β-cells, which modulate Ca/ion transport, cell survival, vesicle/membrane trafficking, glucose metabolism, and stress responses. Finally, mice with loss of both and in multipotent embryonic pancreatic progenitors had significantly reduced islet cell mass at birth, caused by decreased endocrine progenitor production and increased β-cell death. These findings highlight the stage-specific requirements for the presumed "general" coregulators Sin3a and Sin3b in islet β-cells, with Sin3a being dispensable for differentiation but required for postnatal function and survival.
© 2020 by the American Diabetes Association.
2 Communities
2 Members
0 Resources
16 MeSH Terms
Repeatability and Reproducibility of Pancreas Volume Measurements Using MRI.
Williams JM, Hilmes MA, Archer B, Dulaney A, Du L, Kang H, Russell WE, Powers AC, Moore DJ, Virostko J
(2020) Sci Rep 10: 4767
MeSH Terms: Adolescent, Adult, Child, Diabetes Mellitus, Type 1, Female, Humans, Magnetic Resonance Imaging, Male, Organ Size, Pancreas, Reproducibility of Results, Young Adult
Show Abstract · Added March 19, 2020
Reduced pancreas volume, as measured by non-contrast magnetic resonance imaging (MRI), is observed in individuals with newly-diagnosed type 1 diabetes (T1D) and declines over the first year after diagnosis. In this study, we determined the repeatability and inter-reader reproducibility of pancreas volume measurements by MRI. Test-retest scans in individuals with or without T1D (n = 16) had an intraclass correlation coefficient (ICC) of 0.985 (95% CI 0.961 to 0.995) for pancreas volume. Independent pancreas outlines by two board-certified radiologists (n = 30) yielded an ICC of 0.945 (95% CI 0.889 to 0.973). The mean Dice coefficient, a measurement of the degree of overlap between pancreas regions of interest between the two readers, was 0.77. Prandial state did not influence pancreatic measurements, as stomach volume did not correlate with pancreas volume. These data demonstrate that MRI measurements of pancreas volume between two readers are repeatable and reproducible with ICCs that correspond to excellent clinical significance (ICC > 0.9), are not related to changes in stomach volume, and could be a useful tool for clinical investigation of diabetes and other pancreas pathologies.
0 Communities
2 Members
0 Resources
12 MeSH Terms
A compendium of G-protein-coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure.
Ceddia RP, Collins S
(2020) Clin Sci (Lond) 134: 473-512
MeSH Terms: Adipocytes, Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Energy Metabolism, Humans, Lipolysis, Nucleotides, Cyclic, Receptors, G-Protein-Coupled, Signal Transduction
Show Abstract · Added March 26, 2020
With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand-receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein-coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
0 Communities
2 Members
0 Resources
10 MeSH Terms
Genome-wide meta-analysis associates GPSM1 with type 2 diabetes, a plausible gene involved in skeletal muscle function.
Ding Q, Tan ALM, Parra EJ, Cruz M, Sim X, Teo YY, Long J, Alsafar H, Petretto E, Tai ES, Chen H
(2020) J Hum Genet 65: 411-420
MeSH Terms: Animals, Asian Continental Ancestry Group, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Genome-Wide Association Study, Guanine Nucleotide Dissociation Inhibitors, Humans, Mice, Muscle, Skeletal, Polymorphism, Single Nucleotide
Show Abstract · Added March 3, 2020
Genome-wide association studies (GWASs) have identified many genetic variations associated with type 2 diabetes mellitus (T2DM) in Asians, but understanding the functional genetic variants that influence traits is often a complex process. In this study, fine mapping and other analytical strategies were performed to investigate the effects of G protein signaling modulator 1 (GPSM1) on insulin resistance in skeletal muscle. A total of 128 single-nucleotide polymorphisms (SNPs) within GPSM1 were analysed in 21,897 T2DM cases and 32,710 healthy controls from seven GWASs. The SNP rs28539249 in intron 9 of GPSM1 showed a nominally significant association with T2DM in Asians (OR = 1.07, 95% CI = 1.04-1.10, P < 10). The GPSM1 mRNA was increased in skeletal muscle and correlated with T2DM traits across obese mice model. An eQTL for the cis-acting regulation of GPSM1 expression in human skeletal muscle was identified for rs28539249, and the increased GPSM1 expression related with T2DM traits within GEO datasets. Another independent Asian cohort showed that rs28539249 is associated with the skeletal muscle expression of CACFD1, GTF3C5, SARDH, and FAM163B genes, which are functionally enriched for endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) pathways. Moreover, rs28539249 locus was predicted to disrupt regulatory regions in human skeletal muscle with enriched epigenetic marks and binding affinity for CTCF. Supershift EMSA assays followed luciferase assays demonstrated the CTCF specifically binding to rs28539249-C allele leading to decreased transcriptional activity. Thus, the post-GWAS annotation confirmed the Asian-specific association of genetic variant in GPSM1 with T2DM, suggesting a role for the variant in the regulation in skeletal muscle.
0 Communities
1 Members
0 Resources
11 MeSH Terms