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  • 1
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    94-OR: CGM Metrics, HbA1c, and Retinopathy Are Differentially Associated by Disease Duration in Long-Duration Type 1 Diabetes
    American Diabetes Association ; 2022
    In:  Diabetes Vol. 71, No. Supplement_1 ( 2022-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Continuous glucose monitor (CGM) -derived metrics provide measures of glycemic variability that are not captured with the use of HbA1c alone. However, they have not been evaluated in long-duration type 1 diabetes (T1D) subjects, in whom the greater risk of glycemic excursions and comorbidities highlight the need for other glycemic markers apart from HbA1c. Among the Joslin “Medalists” with T1D≥50 years, a single consecutive 14-day block of CGM data was remotely obtained from a subset of CGM users (n=64) after a period of routine activities. Using linear regression, mean historical HbA1c associated with mean glucose (β= 17.54, p & lt;0.0001) , glucose management indicator (GMI; β= 0.42, p & lt;0.0001) , and time above range (TAR) & gt;250 mg/dL (β= 3.31, p=0.0003) ; and inversely with time in range (TIR) 70-180 mg/dL (β= -8.08, p=0.0003) and time below range (TBR) & lt;70 mg/dL (β= -2.11, p=0.0006) . While no associations were found between CGM metrics and complications in the overall subset, tertile analysis by T1D duration (tertile 1, 51-61 years; tertile 2, 62-69 years; tertile 3, 70-85 years) revealed that T1D duration modified the effect of CGM metrics on proliferative retinopathy (PDR) even after adjusting for HbA1c (p for interaction & lt;0.05) . In subjects with the longest T1D duration (tertile 3) , PDR associated with mean glucose (β= 26.92, p=0.02) , GMI (β= 0.64, p=0.02) , and TAR (β= 6.81, p=0.03) ; and inversely with TIR (β= -12.57, p=0.04) . Tertile analysis of HbA1c and complications in the overall Medalist cohort (n=952) showed that HbA1c associated with PDR in tertile 1 (p=0.03) . Our results suggest that while HbA1c and CGM metrics are closely linked in long-duration T1D subjects, they may provide differential contributions to the temporal onset of microvascular complications, independent of each other. Additionally, as development to PDR has been demonstrated to stabilize in Medalists with the longest T1D duration, favorable values of CGM metrics may contribute to this protection. Disclosure M.Yu: None. T.Boumenna: None. J.Gauthier: None. R.Tham: None. W.Fickweiler: None. J.Sun: Consultant; American Diabetes Association, American Medical Association, Research Support; Adaptive Sensory Technology, Boehringer Ingelheim International GmbH, Genentech, Inc., Jaeb Center for Health Research, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Optovue, Incorporated, Physical Sciences, Inc, Roche Pharmaceuticals. H.Shah: None. G.L.King: Advisory Panel; Medtronic, Research Support; Janssen Pharmaceuticals, Inc. Funding American Diabetes Association (9-18-CVD1-005) ; Mary K. Iacocca Family Foundation, Thomas Beatson Jr. Foundation, National Eye Institute (R01EY026080-01)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-94-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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  • 2
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    188-OR: Inflammatory and Insulinemic Dietary Patterns Associate with Nephropathy in Type 1 Diabetes (T1D)
    American Diabetes Association ; 2021
    In:  Diabetes Vol. 70, No. Supplement_1 ( 2021-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 70, No. Supplement_1 ( 2021-06-01)
    Abstract: Diabetic nephropathy (DN) causes much morbidity and mortality in T1D, necessitating better mechanistic insights for improved prevention and therapy. In addition to hyperglycemia, DN pathogenesis may involve inflammation or insulin resistance, and diets modulating these pathways may impact DN risk. In this cross-sectional study, we examined associations of inflammatory and insulinemic potentials of whole diets with DN in a subset of the Joslin 50-year Medalist Study, comprising 570 individuals with T1D & gt;50 years and food frequency questionnaire data. Empirical dietary inflammatory pattern (EDIP) and empirical index for hyperinsulinemia (EDIH) scores were separately derived as weighted sums of foods and beverages previously shown to be predictive of circulating inflammatory biomarkers or C-peptide levels, respectively. In multivariable-adjusted logistic regression models, including age, sex, BMI, exercise, lipids, HbA1c, and hypertension as covariates, 1 S.D. increments in EDIP and EDIH associated with 0.46 (95% CI 0.26-0.84, p=0.01) and 0.31 (95% CI 0.15-0.68, p=0.003) reduced odds of being protected against DN (167 events, CKD-EPI eGFR & lt; 60 ml/min/1.73 m2), respectively. Both scores inversely correlated with continuous eGFR (p=0.03 and 0.0003, respectively). Neither index associated with HbA1c, retinopathy severity, neuropathy or cardiovascular diseases. Both scores positively correlated (p & lt;0.05) with C-reactive protein, which correlated to HbA1c but did not offset the effects of EDIP or EDIH on DN. These findings show that dietary patterns with higher inflammatory and insulinemic potentials are associated with DN in T1D, independent of glycemic control, inflammation or hypertension, suggesting the involvement of a metabolic and renal-selective pathway underlying DN pathogenesis. Future studies will focus on whether consumption of diets with low EDIP and EDIH can protect against DN onset and progression, and the potential pathways through which they do this. Disclosure H. Shah: None. A. Adam: None. T. Boumenna: None. M. Yu: None. J. Li: None. F. Hu: None. F. K. Tabung: None. G. L. King: Consultant; Self; Agios, Inc., Medtronic, Other Relationship; Self; Janssen Pharmaceuticals, Inc.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db21-188-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
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  • 3
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    573-P: Continuous Glucose Monitoring Measures Impact Cognitive Function in Long-Duration Type 1 Diabetes
    American Diabetes Association ; 2022
    In:  Diabetes Vol. 71, No. Supplement_1 ( 2022-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: As people with type 1 diabetes (T1D) live longer, they are increasingly presented with greater health risks tied to aging-related cognitive decline. We previously reported that participants of the Joslin 50-year Medalist Study (“Medalists”) , with T1D ≥50 years, have impaired cognitive function compared to controls without diabetes, and similar to those with type 2 diabetes. While glycemic control has been shown to impact cognitive function, the impact of day-to-day continuous glucose monitoring (CGM) measures is unclear. CGM provides measures of glycemic variability uncaptured by HbA1c alone. A 2-week block of CGM data was procured from a subset of Medalists (n=64) who also had undergone a cognitive battery testing psychomotor function (Grooved Pegboard) , verbal learning and memory (RAVLT- immediate and delayed recall) , working memory (Wechsler) and executive function (WASI) . In a cross-sectional study, log-transformed CGM metrics were tested for associations with cognitive domains in linear regression models adjusted for duration of diabetes, education status and sex. Better psychomotor function was associated with a higher time in range 70 - 180 mg/dL (p=0.04) , and with lower: glucose coefficient of variation (p=0.02) , time above range (TAR) & gt;180 -250 mg/dL (p=0.01) , TAR & gt; 250 mg/dL (p=0.07) , mean glucose (p=0.07) and glucose management indicator (p=0.07) . Better delayed recall associated with lower time below range & lt; 70 mg/dL (p=0.02) and better immediate recall with lower TAR & gt; 180 -250 mg/dl (p=0.08) . Lower HbA1c previously associated with better executive function in the Medalists, but not with other cognitive domains. This CGM study shows that glucose variability and hyperglycemia impact psychomotor function, while hypoglycemia impacts verbal learning and memory. Thus, better day-to-day glucose management in conjunction with long-term HbA1c control, are potentially important to prevent cognitive decline in aging populations with long-duration T1D. Disclosure H.Shah: None. M.Yu: None. T.Boumenna: None. J.Gauthier: None. R.Tham: None. A.Adam: None. G.L.King: Advisory Panel; Medtronic, Research Support; Janssen Pharmaceuticals, Inc. Funding Beatson Foundation
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-573-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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  • 4
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    42-OR: Association of Vitreous Retinol Binding Protein 3 with Inflammatory Cytokines and Progression of Diabetic Retinopathy in Type 1 and Type 2 Diabetes
    American Diabetes Association ; 2022
    In:  Diabetes Vol. 71, No. Supplement_1 ( 2022-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Although inflammatory cytokines and vascular endothelial growth factor (VEGF) have been proposed to underlie the progression of diabetic retinopathy (DR) , there remains an important need to identify biomarkers for early stages of DR. Findings from the Joslin Medalist Study, composed of individuals who have had insulin-dependent diabetes for 50 years or longer, showed that Retinol Binding Protein 3 (RBP3) was significantly higher both in retina and vitreous samples with no to mild DR compared to those with proliferative DR (PDR) . In this study, we examined vitreous and plasma samples from 2people with type 1 and type 2 diabetes from the Joslin Beetham Eye Institute and Medalist Study to evaluate the relationship between vitreous RBP3, inflammatory cytokines, and DR severity and progression. PDR was associated with lower levels of IL- (P=0.007) , IFN-γ (P=0.001) , and higher levels of IL-15 (P=0.01) and IL-6 (P=0.02) in vitreous. Vitreous VEGF was positively associated with increasing DR severity in surgical samples (P & lt;0.05) . Plasma VEGF was not associated with vitreous VEGF concentration. No significant relationships were found between inflammatory markers in the vitreous and plasma from the same individual. Increased vitreous RBP3 concentration was associated with less severe DR in all eyes (P & lt;0.0001) , post-mortem (P & lt;0.0001) and surgical samples from type 1 and type 2 diabetic patients (P=0.03) with diabetes duration of & lt;50 years (mean±SD 27±13 years) . Higher vitreous RBP3 concentration was associated with lower risk of PDR onset (P & lt;0.0001) . Lower vitreous TNF-α, TNF-β, and VEGF were associated with increased vitreous RBP3 concentration (P & lt;0.05, all) . These findings suggest that inflammatory cytokines and risk of DR worsening may be decreased by RBP3, supporting its potential use as biomarker for severity and progression of DR. Disclosure W.Fickweiler: None. J.D.Cavallerano: None. L.P.Aiello: Consultant; KalVista Pharmaceuticals, Inc., Novo Nordisk, Stock/Shareholder; KalVista Pharmaceuticals, Inc. J.Sun: Consultant; American Diabetes Association, American Medical Association, Research Support; Adaptive Sensory Technology, Boehringer Ingelheim International GmbH, Genentech, Inc., Jaeb Center for Health Research, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Optovue, Incorporated, Physical Sciences, Inc, Roche Pharmaceuticals. G.L.King: Advisory Panel; Medtronic, Research Support; Janssen Pharmaceuticals, Inc. H.Park: None. K.Park: None. M.G.Mitzner: None. D.B.Robinson: None. T.Chokshi: None. T.Boumenna: None. J.Gauthier: None. I.Wu: None. Funding American Diabetes Association (7-21-PDF-022) ; National Eye Institute (R01EYE26080-01) , the National Institute of Diabetes and Digestive and Kidney Diseases and National Institutes of Health (DP3-DK-094333-01) ; JDRF (17-2013-310) ; the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-42-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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  • 5
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    MIND Diet and Cognitive Function in Puerto Rican Older Adults
    Oxford University Press (OUP) ; 2022
    In:  The Journals of Gerontology: Series A Vol. 77, No. 3 ( 2022-03-03), p. 605-613
    Details
    In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 77, No. 3 ( 2022-03-03), p. 605-613
    Abstract: Healthy diets have been associated with better cognitive function. Socioeconomic factors including education, poverty, and job complexity may modify the relationship between diet and cognition. Methods We used adjusted linear mixed models to examine the association between long-term adherence to the Mediterranean-Dietary Approaches to Stop Hypertension - Intervention for Neurodegenerative Delay (MIND) diet and cognitive function over 8 years of follow-up in Puerto Rican adults residing in the Boston, MA area (aged 45–75 years at baseline). We also examined whether the MIND diet—cognition association was confounded or modified by socioeconomic measures. Results In both cross-sectional and longitudinal analyses the highest, versus lowest, MIND quintile was associated with better cognition function (β = 0.093; 95% CI: 0.035, 0.152; p trend = .0019), but not with cognitive trajectory over 8 years. Education & lt;=8th grade (β = −0.339; 95% CI: 0.394, −0.286; p & lt; .0001) and income-to-poverty ratio & lt;120% (β = −0.049; 95% CI: −0.092, −0.007; p = .024) were significantly associated with lower cognitive function, while higher job complexity (β = 0.008; 95% CI: 0.006, 0.011; p & lt; .0001) was associated with better cognition function. These variables acted as confounders, but not effect modifiers of the MIND-diet—cognitive function relationship. Conclusion Adherence to the MIND diet was associated with better cognitive function at baseline and over 8 years of follow-up; however, MIND diet was not associated with 8-year cognitive trajectory. More studies are needed to better understand whether the MIND diet is protective against long-term cognitive decline.
    Type of Medium: Online Resource
    ISSN: 1079-5006 , 1758-535X
    URL: Article
    DOI: 10.1093/gerona/glab261
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2043927-1
    SSG: 12
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  • 6
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    87-OR: Vitreous Retinol Binding Protein 3 Is Increased in Patients without Advanced Diabetic Retinopathy in Type 1 and Type 2 Diabetes
    American Diabetes Association ; 2021
    In:  Diabetes Vol. 70, No. Supplement_1 ( 2021-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 70, No. Supplement_1 ( 2021-06-01)
    Abstract: Retinol Binding Protein 3 (RBP3), a retinol transport protein secreted mainly by photoreceptors, may inhibit progression of diabetic retinopathy (DR) by decreasing glucose uptake and inflammation in the retina. In people with type 1 diabetes with duration of ≥50yrs (Joslin Medalist Study), & gt;40% of Medalists exhibited no to mild non-proliferative diabetic retinopathy (NPDR) and increased expression of RBP3 compared to those with severe DR. We examined 213 vitreous samples from a larger population of Medalists and patients with type 1 and type 2 diabetes with shorter diabetes duration (mean±SD 26.5±12.7 years) from the Joslin Beetham Eye Institute to determine whether vitreous RBP3 levels are correlated with DR severity and progression in a broad population with diabetes. RBP3 was increased in vitreous from people with no diabetes compared to subjects with type 1 and type 2 diabetes (p & lt;0.0001). Type of diabetes (type 1 vs. type 2, p=0.44) and A1c (p=0.68) were not associated with RBP3. In patients with both type 1 and 2 diabetes, vitreous RBP3 levels gradually decreased from the highest concentration in no to mild NPDR (15.7 nM) to the lowest concentrations in advanced DR (moderate-severe: 8.2 nM, p=0.01 vs. no-mild NPDR; active proliferative DR: 8.4 nM, p=0.0003 vs. no-mild NPDR; quiescent proliferative DR: 3.5 nM, p & lt;0.0001 vs. no-mild NPDR). RBP3 was higher in moderate-severe NPDR compared to quiescent PDR (p=0.03). RBP3 concentrations in surgical samples from living donors were lower than those from post-mortem Medalists (p & lt;0.01), but were associated with DR severity in both groups (p=0.03 and p & lt;0.0001, respectively). Increased RBP3 concentrations were associated with reduced risk of PDR development over time (n=34, p & lt;0.001). These findings indicate that elevated vitreous RBP3 is associated with decreased DR severity and decreased risk of PDR development, supporting the postulate that RBP3 is a protective factor and therapeutic target for the progression of DR. Disclosure W. Fickweiler: None. G. L. King: Consultant; Self; Agios, Inc., Medtronic, Other Relationship; Self; Janssen Pharmaceuticals, Inc. H. Park: None. K. Park: None. T. Boumenna: None. J. Gauthier: None. I. Wu: None. J. D. Cavallerano: None. L. P. Aiello: Consultant; Self; KalVista Pharmaceuticals, Novo Nordisk, Regeneron Pharmaceuticals Inc., Stock/Shareholder; Self; KalVista Pharmaceuticals. J. Sun: Other Relationship; Self; Novo Nordisk, Roche Pharma, Research Support; Self; Adaptive Sensory Technology, Boehringer Ingelheim Pharmaceuticals, Inc., KalVista Pharmaceuticals, Optovue, Roche Pharma. Funding National Eye Institute (R01EY026080-01); National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK094333-01); JDRF (17-2013-310); Beatson Foundation; Dianne Nunnally Hoppes Fund
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db21-87-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
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  • 7
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    Prospective study of flavonoid intake and risk of primary open‐angle glaucoma
    Wiley ; 2018
    In:  Acta Ophthalmologica Vol. 96, No. 6 ( 2018-09)
    Details
    In: Acta Ophthalmologica, Wiley, Vol. 96, No. 6 ( 2018-09)
    Abstract: To evaluate the association between flavonoid intake and incident primary open‐angle glaucoma ( POAG ). Methods We followed 65 516 women from the Nurses’ Health Study (from 1984) and 42 156 men from the Health Professionals Follow‐up Study (from 1986) biennially to 2012, who were 40+ years old, free of POAG , and reported eye examinations. Dietary flavonoid intake was assessed with validated repeated semi‐quantitative food frequency questionnaires. Incident POAG cases ( n  = 1575) were confirmed with medical record review. Cohort‐specific multivariable‐adjusted relative risks ( RR s) and 95% confidence intervals (CIs) were calculated and meta‐analysed. Results Total flavonoid intake was not associated with risk of POAG development [ RR for highest (Q5: median ~645 mg/day) versus lowest quintile (Q1: ~130 mg/day) = 0.91 (95% CI = 0.77, 1.08); p for trend (p‐trend) = 0.19]; the flavonoid subclasses of flavones, flavanones, polymeric flavanols or anthocyanidins were also not associated (Q5 versus Q1 comparison p‐values ≥0.05 and p‐trend ≥0.09). Higher intakes of flavonols and monomeric flavanols were nominally associated with lower POAG risk, based on the Q5 versus Q1 comparisons or p‐trends. The Q5 versus Q1 comparison RR s were: for flavonols, 0.82 (95% CI = 0.69, 0.97; p‐trend = 0.05; ~28 versus ~8 mg/day), and for monomeric flavanols, 0.86 (95% CI = 0.72, 1.02; p‐trend=0.04; ~110 versus 10 mg/day). The food/beverage that contributed most to both the variation of flavonols and monomeric flavanols was tea; consuming ~2 cups/day was associated with 18% lower POAG risk ( RR =0.82; 95% CI = 0.68, 0.99; p‐trend = 0.02). Conclusion Total flavonoid intake was not associated with POAG risk. Greater intakes of flavonols and monomeric flavanols and of tea showed suggestive modest associations with lower risk; these results need confirmation.
    Type of Medium: Online Resource
    ISSN: 1755-375X , 1755-3768
    URL: Issue
    URL: Article
    DOI: 10.1111/aos.2018.96.issue-6
    DOI: 10.1111/aos.13705
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 8
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    Discordant 16S and 23S rRNA Gene Phylogenies for the Genus Helicobacter : Implications for Phylogenetic Inference and Systematics
    American Society for Microbiology ; 2005
    In:  Journal of Bacteriology Vol. 187, No. 17 ( 2005-09), p. 6106-6118
    Details
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 187, No. 17 ( 2005-09), p. 6106-6118
    Abstract: Analysis of 16S rRNA gene sequences has become the primary method for determining prokaryotic phylogeny. Phylogeny is currently the basis for prokaryotic systematics. Therefore, the validity of 16S rRNA gene-based phylogenetic analyses is of fundamental importance for prokaryotic systematics. Discrepancies between 16S rRNA gene analyses and DNA-DNA hybridization and phenotypic analyses have been noted in the genus Helicobacter . To clarify these discrepancies, we sequenced the 23S rRNA genes for 55 helicobacter strains representing 41 taxa ( 〉 2,700 bases per sequence). Phylogenetic-tree construction using neighbor-joining, parsimony, and maximum likelihood methods for 23S rRNA gene sequence data yielded stable trees which were consistent with other phenotypic and genotypic methods. The 16S rRNA gene sequence-derived trees were discordant with the 23S rRNA gene trees and other data. Discrepant 16S rRNA gene sequence data for the helicobacters are consistent with the horizontal transfer of 16S rRNA gene fragments and the creation of mosaic molecules with loss of phylogenetic information. These results suggest that taxonomic decisions must be supported by other phylogenetically informative macromolecules, such as the 23S rRNA gene, when 16S rRNA gene-derived phylogeny is discordant with other credible phenotypic and genotypic methods. This study found Wolinella succinogenes to branch with the unsheathed-flagellum cluster of helicobacters by 23S rRNA gene analyses and whole-genome comparisons. This study also found intervening sequences (IVSs) in the 23S rRNA genes of strains of 12 Helicobacter species. IVSs were found in helices 10, 25, and 45, as well as between helices 31′ and 27′. Simultaneous insertion of IVSs at three sites was found in H. mesocricetorum.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    URL: Article
    DOI: 10.1128/JB.187.17.6106-6118.2005
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2005
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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  • 9
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    Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma
    American Medical Association (AMA) ; 2019
    In:  JAMA Ophthalmology Vol. 137, No. 7 ( 2019-07-01), p. 756-
    Details
    In: JAMA Ophthalmology, American Medical Association (AMA), Vol. 137, No. 7 ( 2019-07-01), p. 756-
    Type of Medium: Online Resource
    ISSN: 2168-6165
    URL: Article
    DOI: 10.1001/jamaophthalmol.2019.0900
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2019
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  • 10
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    Real-World Experience on the Use of COVID-19 Vaccination in Multiple Sclerosis Patients Treated with Cladribine Tablets Participating in the ADVEVA® Patient Support Program within the Gulf and Latin American Regions
    Elsevier BV ; 2023
    In:  Multiple Sclerosis and Related Disorders Vol. 71 ( 2023-03), p. 104351-
    Details
    In: Multiple Sclerosis and Related Disorders, Elsevier BV, Vol. 71 ( 2023-03), p. 104351-
    Type of Medium: Online Resource
    ISSN: 2211-0348
    URL: Article
    DOI: 10.1016/j.msard.2022.104351
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2645330-7
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