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1. Association of Glycemia, Lipids, and Blood Pressure With Cognitive Performance in People With Type 2 Diabetes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

Author

Luchsinger, José A, Younes, Naji, Manly, Jennifer J, Barzilay, Joshua, Valencia, Willy, Larkin, Mary E, Falck-Ytter, Corinna, Krause-Steinrauf, Heidi, Pop-Busui, Rodica, Florez, Hermes, Seaquist, Elizabeth, Crandall, Jill P, McKee, Melissa Diane, Brown-Friday, Janet, Xhori, Entila, Ballentine-Cargill, Keisha, Duran, Sally, Lukin, Jennifer, Beringher, Stephanie, Gonzalez de la torre, Susana, Phillips, Lawrence, Burgess, Elizabeth, Olson, Darin, Rhee, Mary, Wilson, Peter, Raines, Tasha Stephanie, Costello, Julie, Gullett, Chona, Maher-Albertelli, Maxine, Morehead, Folayan, Mungara, Radhika, Person, Saranjit, Savoye, Louise, Sibymon, Mabil, Tanukonda, Sridhar, White, Carol Ann, Holloway, Leah, Adams, Cynthia, Ross, April, Balasubramanyam, Ashok, Gonzalez, Erica, Wright, Charlyne, Hollander, Priscilla, Roe, Erin, Uy, Analyn, Burt, Polly, Estrada, Lorie, Chionh, Kris, Ismail-Beigi, Faramarz, Sayyed Kassem, Laure, Sood, Ajay, Tiktin, Margaret, Cramer, Bethany, Iacoboni, Jacalyn, Kononets, Maria V, Kulow, Tanya, Newman, Cynthia, Stancil, Katherine A, Sanders, Cristina, Tucker, Lisa, Werner, Amanda, Krol, Adrienne, McPhee, Gloria, Patel, Christine, Colosimo, Linda, Goland, Robin, Pring, James, Kringas, Patricia, Tejada, Jessica, Hausheer, Camille, Schneier, Harvey, Gumpel, Kelly, Kirpitch, Amanda, Green, Jennifer B, AbouAssi, Hiba, Chatterjee, Ranee, Feinglos, Mark N, English Jones, Jennifer, Khan, Shubi A, Kimpel, Jeanne B, Zimmer, Ronna P, Furst, Mary, Satterwhite, Barbara M, Thacker, Connie R, Evans Kreider, Kathryn, Mather, Kieren J, Lteif, Amale, Hamilton, Tonya, Patel, Nick, Riera, Gabriela, Jackson, Marcia, Pirics, Vivian, Howard, Devin, Aguillar, Danielle, Hurt, Sloan, Bergenstal, Richard, Carlson, Anders, Martens, Thomas, and Johnson, Mary

Subjects
Biomedical and Clinical Sciences, Hypertension, Clinical Research, Clinical Trials and Supportive Activities, Diabetes, Cardiovascular, Behavioral and Social Science, Aged, Blood Pressure, Cognition, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Lipids, Middle Aged, GRADE Research Group, GRADE Research Group Investigators:, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveType 2 diabetes is a risk factor for cognitive impairment. We examined the relation of glycemia, lipids, blood pressure (BP), hypertension history, and statin use with cognition in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methodsCross-sectional analyses from GRADE at baseline examined the association of glycemia (hemoglobin A1c [HbA1c]), LDL, systolic BP (SBP) and diastolic BP (DBP), hypertension history, and statin use with cognition assessed by the Spanish English Verbal Learning Test, letter and animal fluency tests, and Digit Symbol Substitution Test (DSST).ResultsAmong 5,047 GRADE participants, 5,018 (99.4%) completed cognitive assessments. Their mean age was 56.7 ± 10.0 years, and 36.4% were women. Mean diabetes duration was 4.0 ± 2.7 years. HbA1c was not related to cognition. Higher LDL was related to modestly worse DSST scores, whereas statin use was related to modestly better DSST scores. SBP between 120 and 139 mmHg and DBP between 80 and 89 mmHg were related to modestly better DSST scores. Hypertension history was not related to cognition.ConclusionsIn people with type 2 diabetes of a mean duration of

Published
2021

2. Bidirectional Associations Between Mental Health Disorders and Chronic Diabetic Complications in Individuals With Type 1 or Type 2 Diabetes.

Author

Watanabe, Maya, Reynolds, Evan L., Banerjee, Mousumi, Charles, Morten, Mizokami-Stout, Kara, Albright, Dana, Ang, Lynn, Lee, Joyce M., Pop-Busui, Rodica, Feldman, Eva L., and Callaghan, Brian C.

Subjects
TYPE 1 diabetes, TYPE 2 diabetes, MENTAL illness, DIABETES complications, PROPORTIONAL hazards models
Abstract

OBJECTIVE: To determine bidirectional associations between the timing of chronic diabetes complications (CDCs) and mental health disorders (MHDs) in individuals with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: We used a nationally representative health care claims database to identify matched individuals with type 1 or 2 diabetes or without diabetes using a propensity score quasirandomization technique stratified by age (0–19, 20–39, 40–59, and ≥60 years). CDCs and MHDs were identified using ICD-9/10 codes. We fit Cox proportional hazards models with time-varying diagnoses of CDCs or MHDs to investigate their association with the hazard of developing MHDs or CDCs, respectively. RESULTS: From 2001 to 2018, a total of 553,552 individuals were included (44,735 with type 1 diabetes, 152,187 with type 2 diabetes, and 356,630 without diabetes). We found that having a CDC increased the hazard of developing an MHD (hazard ratio [HR] 1.9–2.9; P < 0.05, with higher HRs in older age strata), and having an MHD increased the hazard of developing a CDC (HR 1.4–2.5; P < 0.05, with the highest HR in age stratum 0–19 years). In those aged <60 years, individuals with type 1 diabetes were more likely to have CDCs, whereas individuals with type 2 diabetes were more likely to have MHDs. However, the relationship between CDCs and MHDs in either direction was not affected by diabetes type (P > 0.05 for interaction effects). CONCLUSIONS: We found a consistent bidirectional association between CDCs and MHDs across the life span, highlighting the important relationship between CDCs and MHDs. Prevention and treatment of either comorbidity may help reduce the risk of developing the other. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Neuropathic Pain With and Without Diabetic Peripheral Neuropathy in Type 1 Diabetes.

Author

Braffett, Barbara H., El ghormli, Laure, Albers, James W., Feldman, Eva L., Herman, William H., Gubitosi-Klug, Rose A., Martin, Catherine L., Orchard, Trevor J., White, Neil H., Lachin, John M., Perkins, Bruce A., and Pop-Busui, Rodica

Subjects
TYPE 1 diabetes, DIABETES complications, SYMPTOMS, DIABETIC neuropathies, NEURALGIA
Abstract

OBJECTIVE: Diabetic peripheral neuropathy (DPN) is common; however, the features and burden of neuropathic pain (NP) in type 1 diabetes (T1D) are poorly understood. We evaluated the incidence of first occurrence, annual prevalence, remission, and risk factors for NP during long-term follow-up of participants with T1D. RESEARCH DESIGN AND METHODS: The Michigan Neuropathy Screening Instrument (MNSI) was administered annually (1994–2020) for 1,324 participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study. NP with clinical signs of DPN (NP DPN+) was defined according to self-reported NP plus an examination score >2, while NP without clinical signs of DPN (NP DPN−) was defined according to self-reported NP and an examination score ≤2. RESULTS: At EDIC year 1, median age for participants was 36 years (interquartile range 30, 41), diabetes duration 13 years (10, 18), and HbA1c 7.9% (7.2, 8.9). At year 26 (median diabetes duration 39 years), cumulative incidence of NP was 57%, regardless of concomitant clinical signs of DPN (36% NP DPN+ vs. 46% NP DPN−). NP prevalence was 20% at 26 years (11% NP DPN+ and 9% NP DPN−), suggesting frequent remission. Annualized remission rates were similar regardless of pain medication use. In addition to HbA1c, female sex was associated with NP DPN−. CONCLUSIONS: NP incidence in T1D was high and frequently occurred in the absence of clinical signs of neuropathy, as assessed with the MNSI. Pain remission was not explained by pain medication use. Effective clinical strategies for identification and management are needed. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Efficacy and Safety of LX9211 for Relief of Diabetic Peripheral Neuropathic Pain (RELIEF-DPN 1): Results of a Double-Blind, Randomized, Placebo-Controlled, Proof-of-Concept Study.

Author

Pop-Busui, Rodica, Patel, Anand, Sang, Christine Nai-Mei, Banks, Phillip L., Pierce, Phillip F., Sun, Franklin, Granowitz, Craig, and Gopinathan, Suma

Subjects
*NEURALGIA, *ANALGESIA, *PROOF of concept, *DIABETIC neuropathies, *LEAST squares, *STATISTICAL significance
Abstract

OBJECTIVE: To evaluate the efficacy of LX9211 in reducing pain related to diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS: In this double-blind, multicenter, proof-of-concept trial, 319 individuals with diabetic peripheral neuropathic pain (DPNP) were randomized (1:1:1) to LX9211 10 mg (n = 106), LX9211 20 mg (n = 106), or matching placebo (n = 107), administered once daily for 6 weeks. DPNP was rated daily with an 11-point numerical rating scale. The primary end point was change from baseline to week 6 in the average daily pain score. The difference between each LX9211 group and placebo was evaluated with mixed-model repeated-measures analysis. RESULTS: For those on low-dose LX9211 the primary efficacy end point was achieved: −1.39 vs. −0.72 points for placebo, least squares mean (SE) difference −0.67 (0.249), 95% CI −1.16 to −0.18, P = 0.007; results for high-dose LX9211 demonstrated improvement in pain severity versus placebo (−1.27 vs. −0.72 points, respectively), but the between-group LS mean difference did not reach the prespecified statistical significance (−0.55 [0.254], 95% CI −1.06 to −0.05, P = 0.030). Treatment benefit was observed beginning at week 1 and maintained thereafter. Results for LX9211 also demonstrated improvement in several patient-reported secondary outcomes. Most common adverse events (AEs) were dizziness, nausea, and headache. More participants treated with LX9211 (20 mg, n = 28 [26.4%]; 10 mg, 17 [16.0%]) than placebo (3 [2.8%]) discontinued study drug prematurely due to AEs; serious AEs were uncommon (2 [1.9%], 0, and 1 [0.9%], respectively). CONCLUSIONS: These preliminary findings of improvement in DPNP with LX9211 support further investigation in larger trials. [ABSTRACT FROM AUTHOR]

Published
2024
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5. REPLACE-BG: A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Well-Controlled Type 1 Diabetes

Author

Aleppo, Grazia, Ruedy, Katrina J, Riddlesworth, Tonya D, Kruger, Davida F, Peters, Anne L, Hirsch, Irl, Bergenstal, Richard M, Toschi, Elena, Ahmann, Andrew J, Shah, Viral N, Rickels, Michael R, Bode, Bruce W, Philis-Tsimikas, Athena, Pop-Busui, Rodica, Rodriguez, Henry, Eyth, Emily, Bhargava, Anuj, Kollman, Craig, and Beck, Roy W

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Diabetes, Pediatric, Prevention, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Adult, Aged, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin, Humans, Insulin Infusion Systems, Male, Middle Aged, Socioeconomic Factors, Young Adult, REPLACE-BG Study Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveTo determine whether the use of continuous glucose monitoring (CGM) without confirmatory blood glucose monitoring (BGM) measurements is as safe and effective as using CGM adjunctive to BGM in adults with well-controlled type 1 diabetes (T1D).Research design and methodsA randomized noninferiority clinical trial was conducted at 14 sites in the T1D Exchange Clinic Network. Participants were ≥18 years of age (mean 44 ± 14 years), had T1D for ≥1 year (mean duration 24 ± 12 years), used an insulin pump, and had an HbA1c ≤9.0% (≤75 mmol/mL) (mean 7.0 ± 0.7% [53 ± 7.7 mmol/mol]); prestudy, 47% were CGM users. Participants were randomly assigned 2:1 to the CGM-only (n = 149) or CGM+BGM (n = 77) group. The primary outcome was time in range (70-180 mg/dL) over the 26-week trial, with a prespecified noninferiority limit of 7.5%.ResultsCGM use averaged 6.7 ± 0.5 and 6.8 ± 0.4 days/week in the CGM-only and CGM+BGM groups, respectively, over the 26-week trial. BGM tests per day (including the two required daily for CGM calibration) averaged 2.8 ± 0.9 and 5.4 ± 1.4 in the two groups, respectively (P < 0.001). Mean time in 70-180 mg/dL was 63 ± 13% at both baseline and 26 weeks in the CGM-only group and 65 ± 13% and 65 ± 11% in the CGM+BGM group (adjusted difference 0%; one-sided 95% CI -2%). No severe hypoglycemic events occurred in the CGM-only group, and one occurred in the CGM+BGM group.ConclusionsUse of CGM without regular use of confirmatory BGM is as safe and effective as using CGM with BGM in adults with well-controlled T1D at low risk for severe hypoglycemia.

Published
2017

7. Comparative Effects of Randomized Second-line Therapy for Type 2 Diabetes on a Composite Outcome Incorporating Glycemic Control, Body Weight, and Hypoglycemia: An Analysis of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)

Author

Kirkman, M. Sue, Tripputi, Mark, Krause-Steinrauf, Heidi, Bebu, Ionut, AbouAssi, Hiba, Burch, Henry, Duran-Valdez, Elizabeth, Florez, Hermes, Garvey, W. Timothy, Hsia, Daniel S., Salam, Maamoun, Pop-Busui, Rodica, Crandall, J.P., McKee, M.D., Behringer-Massera, S., Brown-Friday, J., Xhori, E., Ballentine-Cargill, K., Duran, S., and Estrella, H.

Subjects
TYPE 2 diabetes, GLYCEMIC control, HYPOGLYCEMIA, BODY weight, COMPARATIVE method, INSULIN pumps, ORAL medication
Abstract

OBJECTIVE: In Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) (5,047 participants, mean follow-up 5.0 years), differences in glycemic control were demonstrated over time among four randomized therapies added to metformin. Weight gain and hypoglycemia are also important outcomes for people with type 2 diabetes. We compared the effects of the four randomized GRADE medications on a composite outcome incorporating glycemic deterioration, weight gain, and hypoglycemia. RESEARCH DESIGN AND METHODS: The composite outcome was time to first occurrence of any of the following: HbA1c >7.5%, confirmed; ≥5% weight gain; or severe or recurrent nonsevere hypoglycemia. Secondary analyses included examination of individual components of the composite outcome, subgroup effects and potential mediators, and treatment satisfaction. Cumulative incidence was estimated with the Kaplan-Meier estimator. Cox proportional hazards models were used to assess pairwise group differences in risk of an outcome. RESULTS: Risk of reaching the composite outcome (events per 100 participants per treatment year [PTYs]) was lowest with liraglutide (19 per 100 PTYs) followed by sitagliptin (26 per 100 PTYs), glargine (29 per 100 PTYs), and glimepiride (40 per 100 PTYs); all pairwise comparisons were statistically significant. The order was the same for risk of weight gain and hypoglycemia, but risk of glycemic deterioration was lowest with glargine, followed by liraglutide, glimepiride, and sitagliptin. No significant heterogeneity in risk of composite outcome was detected across prespecified covariates. Participants who reached the composite outcome had modestly but significantly lower treatment satisfaction. CONCLUSIONS: Among participants treated with common second-line drug classes for type 2 diabetes, the liraglutide group had the lowest and glimepiride the highest risk of reaching a composite outcome encompassing glycemic deterioration, weight gain, and hypoglycemia. These findings may inform decision-making regarding type 2 diabetes therapy. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Mortality in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

Author

Banerji, Mary Ann, Buse, John B., Younes, Naji, Krause-Steinrauf, Heidi, Ghazi, Adline, Lee, Melissa, Park, Jean, Pop-Busui, Rodica, Underkofler, Chantal, Fortmann, Stephen P., Crandall, J.P., McKee, M.D., Behringer-Massera, S., Brown-Friday, J., Xhori, E., Ballentine-Cargill, K., Duran, S., Estrella, H., Gonzalez de la torre, S., and Lukin, J.

Subjects
COMPARATIVE method, DISEASE risk factors, MORTALITY, CAUSES of death, TYPE 2 diabetes
Abstract

OBJECTIVE: We report mortality outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) among people with type 2 diabetes diagnosed within 10 years and no recent history of cardiovascular events or cancer. RESEARCH DESIGN AND METHODS: Overall mortality rates and major causes of death were assessed over an average of 5 years of follow-up. Cause of death was adjudicated centrally by a committee masked to treatment assignment. We examined baseline covariates and the 10-year Framingham Risk Score for associations. RESULTS: Mortality rate was low (0.59 per 100 participant-years). Participants who died during follow-up were likely to be older, be male, have a history of hypertension, have a history of smoking, and have moderate albuminuria. The two most common underlying causes of death were "cardiovascular-cause" (a composite of underlying causes) (38.6%) and cancer (26.8%). There were no differences by treatment group. CONCLUSIONS: Among people with diabetes of relatively short duration, cause of death was varied. Attention to health risks beyond cardiovascular diseases is warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Psychosocial Care for People With Diabetic Neuropathy: Time for Action.

Author

Pouwer, Frans, Mizokami-Stout, Kara, Reeves, Neil D., Pop-Busui, Rodica, Tesfaye, Solomon, Boulton, Andrew J.M., and Vileikyte, Loretta

Abstract

Psychological factors and psychosocial care for individuals with diabetic neuropathy (DN), a common and burdensome complication of diabetes, are important but overlooked areas. In this article we focus on common clinical manifestations of DN, unremitting neuropathic pain, postural instability, and foot complications, and their psychosocial impact, including depression, anxiety, poor sleep quality, and specific problems such as fear of falling and fear of amputation. We also summarize the evidence regarding the negative impact of psychological factors such as depression on DN, self-care tasks, and future health outcomes. The clinical problem of underdetection and undertreatment of psychological problems is described, together with the value of using brief assessments of these in clinical care. We conclude by discussing trial evidence regarding the effectiveness of current pharmacological and nonpharmacological approaches and also future directions for developing and testing new psychological treatments for DN and its clinical manifestations. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19

Author

Alexi, Vasbinder, Elizabeth, Anderson, Husam, Shadid, Hanna, Berlin, Michael, Pan, Tariq U, Azam, Ibrahim, Khaleel, Kishan, Padalia, Chelsea, Meloche, Patrick, O'Hayer, Erinleigh, Michaud, Tonimarie, Catalan, Rafey, Feroze, Pennelope, Blakely, Christopher, Launius, Yiyuan, Huang, Lili, Zhao, Lynn, Ang, Monica, Mikhael, Kara, Mizokami-Stout, Subramaniam, Pennathur, Matthias, Kretzler, Sven H, Loosen, Athanasios, Chalkias, Frank, Tacke, Evangelos J, Giamarellos-Bourboulis, Jochen, Reiser, Jesper, Eugen-Olsen, Eva L, Feldman, Rodica, Pop-Busui, Salim S, Hayek, Kishan J, Padalia, Danny, Perry, Abbas, Bitar, Rayan, Kaakati, Beata, Samelko, Alex, Hlepas, Priya P, Patel, Xuexiang, Wang, Izzet, Altintas, Marius, Stauning, Morten, Baltzer Houlind, Mette B, Lindstrøm, Hejdi, Gamst-Jensen, Line Jee, Hartmann, Jan O, Nehlin, Thomas, Kallemose, Imran, Parvaiz, Christian, Rasmussen, Ove, Andersen, Jens, Tingleff, Maria-Evangelia, Adami, Nicky, Solomonidi, Maria, Tsilika, Maria, Saridaki, Vasileios, Lekakis, Tom, Luedde, Verena, Keitel, Eleni, Arnaoutoglou, Ioannis, Pantazopoulos, Eleni, Laou, Konstantina, Kolonia, Anargyros, Skoulakis, Pinkus, Tober-Lau, Raphael, Mohr, Florian, Kurth, Leif Erik, Sander, and Christoph, Jochum

Subjects
Inflammation, Male, Advanced and Specialized Nursing, SARS-CoV-2, Endocrinology, Diabetes and Metabolism, COVID-19, Middle Aged, Hospitalization, Hyperglycemia, Diabetes Mellitus, Internal Medicine, Humans, Female, Hospital Mortality, Pathophysiology/Complications, Biomarkers
Abstract

OBJECTIVE Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. RESEARCH DESIGN AND METHODS We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. RESULTS Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. CONCLUSIONS Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.

Published
2022

11. Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Author

Edward J. Boyko, Leila R. Zelnick, Barbara H. Braffett, Rodica Pop-Busui, Catherine C. Cowie, Gayle M. Lorenzi, Rose Gubitosi-Klug, Bernard Zinman, and Ian H. de Boer

Subjects
Blood Glucose, Glycated Hemoglobin, Advanced and Specialized Nursing, Diabetes Mellitus, Type 1, Risk Factors, Endocrinology, Diabetes and Metabolism, Internal Medicine, Humans, Extremities, Epidemiology/Health Services Research, Amputation, Surgical, Diabetic Foot
Abstract

OBJECTIVE Intensive glycemic control reduces the risk of kidney, retinal, and neurologic complications in type 1 diabetes (T1D), but whether it reduces the risk of lower-extremity complications is unknown. We examined whether former intensive versus conventional glycemic control among Diabetes Control and Complications Trial (DCCT) participants with T1D reduced the long-term risk of diabetic foot ulcers (DFUs) and lower-extremity amputations (LEAs) in the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) study. RESEARCH DESIGN AND METHODS DCCT participants (n = 1,441) completed 6.5 years on average of intensive versus conventional diabetes treatment, after which 1,408 were enrolled in EDIC and followed annually over 23 years for DFU and LEA occurrences by physical examination. Multivariable Cox proportional hazard regression models estimated associations of DCCT treatment assignment and time-updated exposures with DFU or LEA. RESULTS Intensive versus conventional glycemic control was associated with a significant risk reduction for all DFUs (hazard ratio 0.77 [95% CI 0.60, 0.97]) and a similar magnitude but nonsignificant risk reduction for first-recorded DFUs (0.78 [0.59, 1.03]) and first LEAs (0.70 [0.36, 1.36]). In adjusted Cox models, clinical neuropathy, lower sural nerve conduction velocity, and cardiovascular autonomic neuropathy were associated with higher DFU risk; estimated glomerular filtration rate CONCLUSIONS Early intensive glycemic control decreases long-term DFU risk, the most important antecedent in the causal pathway to LEA.

Published
2022

12. “The Times They Are A-Changin’” at Diabetes Care

Author

Kahn, Steven E., primary, Anderson, Cheryl A.M., additional, Buse, John B., additional, Selvin, Elizabeth, additional, Angell, Sonia Y., additional, Aroda, Vanita R., additional, Castle, Jessica R., additional, Cheng, Alice Y.Y., additional, Danne, Thomas, additional, Echouffo-Tcheugui, Justin B., additional, Florez, Jose C., additional, Gadgil, Meghana D., additional, Gastaldelli, Amalia, additional, Green, Jennifer B., additional, Jastreboff, Ania M., additional, Kanaya, Alka M., additional, Kandula, Namratha R., additional, Kovesdy, Csaba P., additional, Laiteerapong, Neda, additional, Nadeau, Kristen J., additional, Pop-Busui, Rodica, additional, Powe, Camille E., additional, Rebholz, Casey M., additional, Rickels, Michael R., additional, Sattar, Naveed, additional, Shaw, Jonathan E., additional, Sims, Emily K., additional, Utzschneider, Kristina M., additional, Vella, Adrian, additional, and Zhang, Cuilin, additional

Published
2022
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13. 'The Times They Are A-Changin'' at Diabetes Care

Author

Steven E. Kahn, Cheryl A.M. Anderson, John B. Buse, Elizabeth Selvin, Sonia Y. Angell, Vanita R. Aroda, Jessica R. Castle, Alice Y.Y. Cheng, Thomas Danne, Justin B. Echouffo-Tcheugui, Jose C. Florez, Meghana D. Gadgil, Amalia Gastaldelli, Jennifer B. Green, Ania M. Jastreboff, Alka M. Kanaya, Namratha R. Kandula, Csaba P. Kovesdy, Neda Laiteerapong, Kristen J. Nadeau, Rodica Pop-Busui, Camille E. Powe, Casey M. Rebholz, Michael R. Rickels, Naveed Sattar, Jonathan E. Shaw, Emily K. Sims, Kristina M. Utzschneider, Adrian Vella, and Cuilin Zhang

Subjects
Advanced and Specialized Nursing, Endocrinology, Diabetes and Metabolism, Internal Medicine
Published
2022

14. The Effect of Discontinuing Continuous Glucose Monitoring in Adults With Type 2 Diabetes Treated With Basal Insulin

Author

William Biggs, Ian Orozco, Georgia Davis, Katrina J. Ruedy, Roy W. Beck, Janet B. McGill, Anuj Bhargava, Davida F. Kruger, Grazia Aleppo, William H. Polonsky, Quang T Nguyen, Laura A. Young, David Price, John B. Buse, Shichun Bao, Ryan Bailey, Peter Calhoun, Guillermo E. Umpierrez, Rodica Pop-Busui, Athena Philis-Tsimikas, K. Jean Lucas, Thomas W. Martens, Richard M. Bergenstal, and Anne L. Peters

Subjects
Advanced and Specialized Nursing, Blood glucose monitoring, medicine.medical_specialty, Randomization, endocrine system diseases, medicine.diagnostic_test, business.industry, Continuous glucose monitoring, Endocrinology, Diabetes and Metabolism, Basal insulin, nutritional and metabolic diseases, Type 2 diabetes, medicine.disease, Gastroenterology, Basal (medicine), Emerging Technologies: Data Systems and Devices, Multicenter trial, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, business
Abstract

OBJECTIVE To explore the effect of discontinuing continuous glucose monitoring (CGM) after 8 months of CGM use in adults with type 2 diabetes treated with basal without bolus insulin. RESEARCH DESIGN AND METHODS This multicenter trial had an initial randomization to either real-time CGM or blood glucose monitoring (BGM) for 8 months followed by 6 months in which the BGM group continued to use BGM (n = 57) and the CGM group was randomly reassigned either to continue CGM (n = 53) or discontinue CGM with resumption of BGM for glucose monitoring (n = 53). RESULTS In the group that discontinued CGM, mean time in range (TIR) 70–180 mg/dL, which improved from 38% before initiating CGM to 62% after 8 months of CGM, decreased after discontinuing CGM to 50% at 14 months (mean change from 8 to 14 months −12% [95% CI −21% to −3%], P = 0.01). In the group that continued CGM use, little change was found in TIR from 8 to 14 months (baseline 44%, 8 months 56%, 14 months 57%, mean change from 8 to 14 months 1% [95% CI −11% to 12%], P = 0.89). Comparing the two groups at 14 months, the adjusted treatment group difference in mean TIR was −6% (95% CI −16% to 4%, P = 0.20). CONCLUSIONS In adults with type 2 diabetes treated with basal insulin who had been using real-time CGM for 8 months, discontinuing CGM resulted in a loss of about one-half of the initial gain in TIR that had been achieved during CGM use.

Published
2021

16. Association of Glycemia, Lipids, and Blood Pressure With Cognitive Performance in People With Type 2 Diabetes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)

Author

Elizabeth R. Seaquist, Heidi Krause-Steinrauf, José A. Luchsinger, Mary E. Larkin, Corinna Falck-Ytter, Jennifer J. Manly, Joshua I. Barzilay, Naji Younes, Hermes Florez, Rodica Pop-Busui, and Willy Marcos Valencia

Subjects
Research design, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Trials and Supportive Activities, Blood Pressure, Type 2 diabetes, Cardiovascular, Verbal learning, Medical and Health Sciences, Endocrinology & Metabolism, Cognition, [GRADE Research Group Investigators], Clinical Research, Diabetes mellitus, Internal medicine, Behavioral and Social Science, Diabetes Mellitus, Internal Medicine, medicine, Humans, Epidemiology/Health Services Research, Risk factor, Aged, Advanced and Specialized Nursing, business.industry, Diabetes, Middle Aged, GRADE Research Group, medicine.disease, Lipids, Cross-Sectional Studies, Blood pressure, Diabetes Mellitus, Type 2, Hypertension, Digit symbol substitution test, Female, business, Type 2
Abstract

OBJECTIVE Type 2 diabetes is a risk factor for cognitive impairment. We examined the relation of glycemia, lipids, blood pressure (BP), hypertension history, and statin use with cognition in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). RESEARCH DESIGN AND METHODS Cross-sectional analyses from GRADE at baseline examined the association of glycemia (hemoglobin A1c [HbA1c]), LDL, systolic BP (SBP) and diastolic BP (DBP), hypertension history, and statin use with cognition assessed by the Spanish English Verbal Learning Test, letter and animal fluency tests, and Digit Symbol Substitution Test (DSST). RESULTS Among 5,047 GRADE participants, 5,018 (99.4%) completed cognitive assessments. Their mean age was 56.7 ± 10.0 years, and 36.4% were women. Mean diabetes duration was 4.0 ± 2.7 years. HbA1c was not related to cognition. Higher LDL was related to modestly worse DSST scores, whereas statin use was related to modestly better DSST scores. SBP between 120 and 139 mmHg and DBP between 80 and 89 mmHg were related to modestly better DSST scores. Hypertension history was not related to cognition. CONCLUSIONS In people with type 2 diabetes of a mean duration of

Published
2021

18. Intensive Risk Factor Management and Cardiovascular Autonomic Neuropathy in Type 2 Diabetes: The ACCORD Trial

Author

Maria Sambataro, Joanna Mitri, Rodica Pop-Busui, Hertzel C. Gerstein, Hetal Shah, Luisa Sambado, Alessandro Doria, Vivian Fonseca, Xiuqin Sun, Carlos Bueno Junior, and Yaling Tang

Subjects
Advanced and Specialized Nursing, Research design, medicine.medical_specialty, Randomization, business.industry, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Odds ratio, medicine.disease, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Heart rate variability, business, Dyslipidemia, Glycemic
Abstract

OBJECTIVE The effects of preventive interventions on cardiovascular autonomic neuropathy (CAN) remain unclear. We examined the effect of intensively treating traditional risk factors for CAN, including hyperglycemia, hypertension, and dyslipidemia, in individuals with type 2 diabetes (T2D) and high cardiovascular risk participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS CAN was defined as heart rate variability indices below the fifth percentile of the normal distribution. Of 10,251 ACCORD participants, 71% (n = 7,275) had a CAN evaluation at study entry and at least once after randomization. The effects of intensive interventions on CAN were analyzed among these subjects through generalized linear mixed models. RESULTS As compared with standard intervention, intensive glucose treatment reduced CAN risk by 16% (odds ratio [OR] 0.84, 95% CI 0.75–0.94, P = 0.003)—an effect driven by individuals without cardiovascular disease (CVD) at baseline (OR 0.73, 95% CI 0.63–0.85, P < 0.0001) rather than those with CVD (OR 1.10, 95% CI 0.91–1.34, P = 0.34) (Pinteraction = 0.001). Intensive blood pressure (BP) intervention decreased CAN risk by 25% (OR 0.75, 95% CI 0.63–0.89, P = 0.001), especially in patients ≥65 years old (OR 0.66, 95% CI 0.49–0.88, P = 0.005) (Pinteraction = 0.05). Fenofibrate did not have a significant effect on CAN (OR 0.91, 95% CI 0.78–1.07, P = 0.26). CONCLUSIONS These data confirm a beneficial effect of intensive glycemic therapy and demonstrate, for the first time, a similar benefit of intensive BP control on CAN in T2D. A negative CVD history identifies T2D patients who especially benefit from intensive glycemic control for CAN prevention.

Published
2020

19. An Observational Study of the Equivalence of Age and Duration of Diabetes to Glycemic Control Relative to the Risk of Complications in the Combined Cohorts of the DCCT/EDIC Study

Author

Ionut Bebu, Pearl G. Lee, Barbara H. Braffett, David S. Schade, William I. Sivitz, William H. Herman, Gayle M. Lorenzi, Victoria R. Trapani, Rodica Pop-Busui, John M. Lachin, Amisha Wallia, and John I. Malone

Subjects
Adult, Blood Glucose, Male, Risk, Research design, medicine.medical_specialty, Pediatrics, Time Factors, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Glycemic Control, Cohort Studies, Diabetes Complications, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Diabetes mellitus, Epidemiology, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Age of Onset, Epidemiology/Health Services Research, Child, Glycemic, Glycated Hemoglobin, Advanced and Specialized Nursing, Type 1 diabetes, business.industry, Proportional hazards model, Age Factors, nutritional and metabolic diseases, Middle Aged, medicine.disease, Diabetes Mellitus, Type 1, Child, Preschool, Cohort, Female, Observational study, business
Abstract

OBJECTIVE This epidemiological analysis of the pooled Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort describes the equivalence of a 1-percentage point increase in HbA1c (such as from 7% to 8%) and years of additional age or duration of type 1 diabetes (T1D) relative to the risk of complications. RESEARCH DESIGN AND METHODS Separate Cox proportional hazards models determined the number of additional years of age and/or duration of T1D that would result in the same increase in risk of microvascular (retinopathy, nephropathy, and neuropathy) and cardiovascular complications and mortality as a 1-percentage point increase in HbA1c. RESULTS The risk of any cardiovascular disease associated with a 1-percentage point increase in HbA1c was equivalent to the risk associated with 4.3 (95% CI 2.7–5.9) additional years of age or 5.6 (95% CI 2.7–6.5) additional years’ duration of T1D. The risk of estimated glomerular filtration rate CONCLUSIONS Our results help evaluate the impact of glycemia on advanced complications in a way that may be more interpretable to health care providers and individuals with T1D.

Published
2020

20. The Contemporary Prevalence of Diabetic Neuropathy in Type 1 Diabetes: Findings From the T1D Exchange

Author

Nicole C. Foster, Elena Toschi, Viral N. Shah, Zoey Li, Kara Mizokami-Stout, Grazia Aleppo, Lynn Ang, Janet B. McGill, Richard E. Pratley, and Rodica Pop-Busui

Subjects
Advanced and Specialized Nursing, Research design, Type 1 diabetes, medicine.medical_specialty, Diabetic neuropathy, Diabetic ketoacidosis, business.industry, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Peripheral neuropathy, chemistry, Interquartile range, Diabetes mellitus, Internal medicine, Internal Medicine, Medicine, 030212 general & internal medicine, Glycated hemoglobin, business
Abstract

OBJECTIVE To evaluate the contemporary prevalence of diabetic peripheral neuropathy (DPN) in participants with type 1 diabetes in the T1D Exchange Clinic Registry throughout the U.S. RESEARCH DESIGN AND METHODS DPN was assessed with the Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) in adults with ≥5 years of type 1 diabetes duration. A score of ≥4 defined DPN. Associations of demographic, clinical, and laboratory factors with DPN were assessed. RESULTS Among 5,936 T1D Exchange participants (mean ± SD age 39 ± 18 years, median type 1 diabetes duration 18 years [interquartile range 11, 31], 55% female, 88% non-Hispanic white, mean glycated hemoglobin [HbA1c] 8.1 ± 1.6% [65.3 ± 17.5 mmol/mol]), DPN prevalence was 11%. Compared with those without DPN, DPN participants were older, had higher HbA1c, had longer duration of diabetes, were more likely to be female, and were less likely to have a college education and private insurance (all P < 0.001). DPN participants also were more likely to have cardiovascular disease (CVD) (P < 0.001), worse CVD risk factors of smoking (P = 0.008), hypertriglyceridemia (P = 0.002), higher BMI (P = 0.009), retinopathy (P = 0.004), reduced estimated glomerular filtration rate (P = 0.02), and Charcot neuroarthropathy (P = 0.002). There were no differences in insulin pump or continuous glucose monitor use, although DPN participants were more likely to have had severe hypoglycemia (P = 0.04) and/or diabetic ketoacidosis (P < 0.001) in the past 3 months. CONCLUSIONS The prevalence of DPN in this national cohort with type 1 diabetes is lower than in prior published reports but is reflective of current clinical care practices. These data also highlight that nonglycemic risk factors, such as CVD risk factors, severe hypoglycemia, diabetic ketoacidosis, and lower socioeconomic status, may also play a role in DPN development.

Published
2020

21. Continuous Glucose Monitoring in Adults With Type 1 Diabetes With 35 Years Duration From the DCCT/EDIC Study

Author

Gubitosi-Klug, Rose A., primary, Braffett, Barbara H., additional, Bebu, Ionut, additional, Johnson, Mary L., additional, Farrell, Kaleigh, additional, Kenny, David, additional, Trapani, Victoria R., additional, Meadema-Mayer, Lynne, additional, Soliman, Elsayed Z., additional, Pop-Busui, Rodica, additional, Lachin, John M., additional, Bergenstal, Richard M., additional, and Tamborlane, William V., additional

Published
2022
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22. Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes According to Baseline HbA1c and Insulin Use: An Analysis From the FIDELIO-DKD Study

Author

Rossing, Peter, primary, Burgess, Ellen, additional, Agarwal, Rajiv, additional, Anker, Stefan D., additional, Filippatos, Gerasimos, additional, Pitt, Bertram, additional, Ruilope, Luis M., additional, Gillard, Pieter, additional, MacIsaac, Richard J., additional, Wainstein, Julio, additional, Joseph, Amer, additional, Brinker, Meike, additional, Roessig, Lothar, additional, Scott, Charlie, additional, Bakris, George L., additional, Vallejos, Augusto, additional, MacIsaac, Richard, additional, Schernthaner, Guntram, additional, Canziani, Maria Eugenia F., additional, Temelkova-Kurktschiev, Theodora, additional, Tobe, Sheldon, additional, González, Fernando, additional, Liu, Zhi-Hong, additional, Ángelo, Andrés, additional, Bonfanti, Cadena, additional, Francisco Jaramillo, Carlos, additional, Prazny, Martin, additional, Rossing, Peter, additional, Strand, Jorma, additional, Marre, Michel, additional, Schmieder, Roland, additional, Wanner, Christoph, additional, Sarafidis, Pantelis A., additional, Chan, Juliana, additional, Rosivall, László, additional, Eustace, Joseph, additional, Grossman, Ehud, additional, Yagil, Yoram, additional, Remuzzi, Giuseppe, additional, Koya, Daisuke, additional, Wada, Takashi, additional, Madero Rovalo, Magdalena, additional, Gansevoort, Ron, additional, Kooy, Adriaan, additional, Finnes, Trine, additional, De Leon, Froilan, additional, Gumprecht, Janusz, additional, Teixeira e Costa, Fernando, additional, Dreval, Alexander, additional, Vathsala, Anantharaman, additional, Amod, Aslam, additional, Gon Kim, Sin, additional, Wan Lee, Byung, additional, Pascual Santos, Julio, additional, Tengmark, Bengt-Olov, additional, Burnier, Michel, additional, Lee, Chien-Te, additional, Yamwong, Sukit, additional, Sari, Ramazan, additional, McCafferty, Kieran, additional, Mankovsky, Borys, additional, Adler, Sharon, additional, Fried, Linda, additional, Toto, Robert, additional, Williams, Mark, additional, Quang Khanh, Tran, additional, Aizenberg, Diego, additional, Bartolacci, Inés, additional, Besada, Diego, additional, Bittar, Julio, additional, Chahin, Mariano, additional, Elbert, Alicia, additional, Gelersztein, Elizabeth, additional, Liberman, Alberto, additional, Maffei, Laura, additional, Pérez Manghi, Federico, additional, Sanabria, Hugo, additional, Viñes, Gloria, additional, Wassermann, Alfredo, additional, Abhayaratna, Walter, additional, Acharya, Shamasunder, additional, Ekinci, Elif, additional, Lee, Darren, additional, Mann Mah, Peak, additional, Nelson, Craig, additional, Packham, David, additional, Pape, Alexia, additional, Roger, Simon, additional, Stephenson, Hugo, additional, Suranyi, Michael, additional, Wittert, Gary, additional, Vale, Elizabeth, additional, Clodi, Martin, additional, Ebenbichler, Christoph, additional, Fliesser-Görzer, Evelyn, additional, Hanusch, Ursula, additional, Krebs, Michael, additional, Lhotta, Karl, additional, Ludvik, Bernhard, additional, Mayer, Gert, additional, Neudorfer, Peter, additional, Paulweber, Bernhard, additional, Prager, Rudolf, additional, Preiß, Wolfgang, additional, Prischl, Friedrich, additional, Schernthaner, Gerit-Holger, additional, Sourij, Harald, additional, Wiesholzer, Martin, additional, Doubel, Peter, additional, Engelen, Wendy, additional, Hougardy, Jean-Michel, additional, Krzesinski, Jean-Marie, additional, Maes, Bart, additional, Speeckaert, Marijn, additional, Stas, Koen, additional, van Gaal, Luc, additional, Vanbelleghem, Hilde, additional, Antunes, Daniela, additional, Botelho, Roberto, additional, Brito, Claudia, additional, Canani, Luis, additional, Eugenia Canziani, Maria, additional, Cerqueira, Maria, additional, de Paula, Rogerio, additional, Eliaschewitz, Freddy, additional, Eduardo Figueiredo, Carlos, additional, Forti, Adriana, additional, Hissa, Miguel, additional, Leite Jr, Maurilo, additional, Lima, Emerson, additional, Noronha, Irene, additional, Paolino, Bruno, additional, Paschoalin, Nathalia, additional, Paschoalin, Raphael, additional, Pecoits Filho, Roberto, additional, Pereira, Marcio, additional, Portes, Evandro, additional, Precoma, Dalton, additional, Rea, Rosangela, additional, Riella, Miguel, additional, Eduardo Salles, Joao, additional, Vasconcellos, Eduardo, additional, Vencio, Sergio, additional, Apostolova, Emiliya, additional, Boshnyashka, Radostina, additional, Farah, Ghassan, additional, Georgiev, Dimitar, additional, Gushterova, Valentina, additional, Klyuchkova, Neli, additional, Lucheva, Mariya, additional, Manova, Petya, additional, Minkova, Dotska, additional, Nonchev, Boyan, additional, Pichmanova, Mariyana, additional, Prakova, Zhulieta, additional, Rangelov, Rangel, additional, Rashkov, Rosen, additional, Stanchev, Pavel, additional, Stoyanovska-Elencheva, Bilyana, additional, Tagarev, Zhivko, additional, Temelkova-Kurktschieva, Theodora, additional, Vasileva, Svetla, additional, Yoncheva-Mihaylova, Mariana, additional, Barre, Paul, additional, Carlson, Brian, additional, Conway, James, additional, Cournoyer, Serge, additional, Dumas, Richard, additional, Fikry, Sameh, additional, Goluch, Richard, additional, Hamet, Pavel, additional, Hart, Randolph, additional, Henein, Sam, additional, Liutkus, Joanne, additional, Madore, Francois, additional, Martinho, Valdemar, additional, Mazza, Giuseppe, additional, McFarlane, Philip, additional, O'Keefe, Dennis, additional, Peterson, Sean, additional, Schwartz, Daniel, additional, Shu, Daniel, additional, Steele, Andrew, additional, Tellier, Guy, additional, Tennankore, Karthik, additional, Tsoukas, George, additional, Tytus, Richard, additional, Vitou, Louise, additional, Walsh, Michael, additional, Weisnagel, Stanley, additional, Wilderman, Igor, additional, Yale, Jean-Francois, additional, Cobos, Jorge, additional, Godoy, Juan, additional, Lobos, Sergio, additional, Carlos Palma, Juan, additional, Carlos Prieto, Juan, additional, Reyes, Eliana, additional, Romero, Carmen, additional, Saavedra, Victor, additional, Vega, Mario, additional, Bu, Ruifang, additional, Cai, Hanqing, additional, Chen, Nan, additional, Chen, Qinkai, additional, Chen, Dejun, additional, Cheng, Jinluo, additional, Dong, Youping, additional, Dong, Junwu, additional, Guan, Tianjun, additional, Hao, Chuanming, additional, Huang, Wen, additional, Jiang, Fangfang, additional, Lei, Minxiang, additional, Li, Ling, additional, Li, Zhonghe, additional, Li, Xuemei, additional, Li, Jingmei, additional, Li, Yan, additional, Liang, Xinling, additional, Liang, Bo, additional, Liu, Fang, additional, Liu, Yinghong, additional, Liu, Yuantao, additional, Liu, Zhihong, additional, Long, Gang, additional, Lu, Guoyuan, additional, Lu, Weiping, additional, Lu, Yibing, additional, Luo, Ping, additional, Ma, Jianhua, additional, Mo, Zhaohui, additional, Niu, Jianying, additional, Peng, Ai, additional, Shen, Jiansong, additional, Shen, Feixia, additional, Shi, Bingyin, additional, Su, Qing, additional, Sun, Zhuxing, additional, Tang, Shuifu, additional, Tong, Nanwei, additional, Wang, Hao, additional, Wang, Xinjun, additional, Wang, Lihua, additional, Wang, Guixia, additional, Wang, Jianqin, additional, Wang, Yangang, additional, Wang, Li, additional, Wei, Jiali, additional, Wu, Tianfeng, additional, Wu, Chaoqing, additional, Xing, Changying, additional, Xiong, Fei, additional, Xu, Xudong, additional, Xu, Ning, additional, Yan, Tiekun, additional, Yang, Jinkui, additional, Yin, Aiping, additional, Zeng, Longyi, additional, Zhang, Hao, additional, Zhang, Yanlin, additional, Zhang, Ying, additional, Zhao, Wenjing, additional, Zhao, Zhiquan, additional, Zheng, Hongguang, additional, Zhong, Ling, additional, Zhu, Dalong, additional, Zhuang, Yongze, additional, Arango, Clara, additional, Barrera, Sandra, additional, Beltrán López, Nelly, additional, Benitez, Diego, additional, Blanco, Guillermo, additional, Cadena, Andrés, additional, Coronel, Julian, additional, Cure, Carlos, additional, Durán, Carlos, additional, González, Alexander, additional, Guzmán, Gustavo, additional, Hernández, Eric, additional, Ibarra, Jaime, additional, Jaramillo, Carlos, additional, Jaramillo, Nicolás, additional, Kattah, William, additional, Molina, Dora, additional, Sánchez, Gregorio, additional, Terront, Mónica, additional, Trujillo, Freddy, additional, Urina, Miguel, additional, Vargas, Ruben, additional, Villegas, Iván, additional, Yupanqui, Hernán, additional, Alferi, Dino, additional, Brada, Michal, additional, Brezina, Jiri, additional, Bucek, Petr, additional, Edelsberger, Tomas, additional, Gulakova, Drahomira, additional, Hasalova Zapletalova, Jitka, additional, Hola, Olga, additional, Hornova, Lucie, additional, Houdova, Jana, additional, Hrmova, Helena, additional, Karasek, David, additional, Kopecka, Sarka, additional, Kovar, Richard, additional, Krcova, Eva, additional, Kuchar, Jiri, additional, Kutejova, Vlasta, additional, Lubanda, Hana, additional, Matyasek, Ivo, additional, Mokrejsova, Magdalena, additional, Okenka, Libor, additional, Pumprla, Jiri, additional, Tomanek, Pavel, additional, Bech, Jesper, additional, Faber, Jens, additional, Gislason, Gunnar, additional, Hangaard, Jørgen, additional, Jaroslaw Pacyk, Grzegorz, additional, Juhl, Claus, additional, Krarup, Thure, additional, Lindhardt, Morten, additional, Madsbad, Sten, additional, Nielsen, Joan, additional, Pedersen-Bjergaard, Ulrik, additional, Poulsen, Per, additional, Rasmussen, Ole, additional, Schousboe, Karoline, additional, Honkasalo, Mikko, additional, Humaloja, Kari, additional, Kananen, Kristiina, additional, Kantola, Ilkka, additional, Koistinen, Arvo, additional, Korsoff, Pirkko, additional, Lahtela, Jorma, additional, Nieminen, Sakari, additional, Nieminen, Tuomo, additional, Sadeharju, Karita, additional, Sulosaari, Sakari, additional, Cariou, Bertrand, additional, Chantrel, François, additional, Clavel, Sylvaine, additional, Combe, Christian, additional, Fauvel, Jean-Pierre, additional, Gallouj, Karim, additional, Gouet, Didier, additional, Guerci, Bruno, additional, Guerrot, Dominique, additional, Hourmant, Maryvonne, additional, Klein, Alexandre, additional, Mariat, Christophe, additional, Mesbah, Rafik, additional, Le Meur, Yannick, additional, Monier, Arnaud, additional, Moranne, Olivier, additional, Serusclat, Pierre, additional, Vendrely, Benoit, additional, Verges, Bruno, additional, Zaoui, Philippe, additional, Axthelm, Christoph, additional, Bergmann, Andreas, additional, Birkenfeld, Andreas L., additional, Braun, Hermann, additional, Busch, Klaus, additional, Contzen, Christel, additional, Degenhardt, Stefan, additional, Derwahl, Karl, additional, Giebel, Thomas, additional, Hagenow, Andreas, additional, Haller, Hermann, additional, Hasslacher, Christoph, additional, Horacek, Thomas, additional, Jungmair, Wolfgang, additional, Kloos, Christof, additional, Koch, Thorsten, additional, Krüger, Thilo, additional, Mühlfeld, Anja, additional, Müller, Joachim, additional, Pfützner, Andreas, additional, Pistrosch, Frank, additional, Rose, Ludger, additional, Rump, Lars, additional, Schettler, Volker, additional, Schiefke, Ingolf, additional, Schlichthaar, Heike, additional, Schröppel, Bernd, additional, Schürholz, Thomas, additional, Sigal, Helena, additional, Stemler, Lutz, additional, Strack, Georg, additional, Täschner, Heidrun, additional, Toursarkissian, Nicole, additional, Tschöpe, Diethelm, additional, Ulmer, Achim, additional, van der Giet, Markus, additional, Winkelmann, Bernhard R., additional, Boletis, Ioannis, additional, Hatziagelaki, Erifili, additional, Ioannidis, Ioannis, additional, Kounadi, Theodora, additional, Makriniotou, Ioanna, additional, Papadopoulou, Dorothea, additional, Papagianni, Aikaterini, additional, Passadakis, Ploumis, additional, Stefanidis, Ioannis, additional, Pang Ip, Tai, additional, Lee, Paul, additional, Yan Andrea Luk, On, additional, Wang, Angela, additional, Yeung, Vincent, additional, Bajcsi, Dora, additional, Danos, Peter, additional, Harcsa, Eleonora, additional, Kazup, Szilvia, additional, Keltai, Katalin, additional, Kirschner, Robert, additional, Kiss, Julianna, additional, Kovacs, Laszlo, additional, Lamboy, Beata, additional, Literati-Nagy, Botond, additional, Mileder, Margit, additional, Nagy, Laszlo, additional, Noori, Ebrahim, additional, Nyirati, Gabor, additional, Petro, Gizella, additional, Schneider, Karoly, additional, Szocs, Albert, additional, Vasas, Szilard, additional, Wudi, Krisztina, additional, Zilahi, Zsolt, additional, Zsom, Marianna, additional, Eustace, Joe, additional, Holian, John, additional, Reddan, Donal, additional, O'Meara, Yvonne, additional, Abramof Ness, Rosane, additional, Adawi, Faiad, additional, Armaly, Zaher, additional, Atar, Shaul, additional, Ben Chetrit, Sydney, additional, Berar Yanay, Noa, additional, Chernin, Gil, additional, Darawsha, Mahmud, additional, Efrati, Shai, additional, Elias, Mazen, additional, Farber, Evgeny, additional, Glandt, Mariela, additional, Halabi, Majdi, additional, Khazim, Khaled, additional, Liberty, Idit, additional, Mosenzon, Ofri, additional, Nimer, Assy, additional, Schwartz, Doron, additional, Zukermann, Robert, additional, Ilieva Parvanova, Aneliya, additional, Avogaro, Angelo, additional, Giorgio Battaglia, Giovanni, additional, Tiziano Bevilacqua, Maurizio, additional, Bonora, Enzo, additional, Antonio Bossi, Carlo, additional, Calabrò, Paolo, additional, Luigi Cavalot, Franco, additional, Cimino, Roberto, additional, Gennaro Cozzolino, Mario, additional, David, Salvatore, additional, Emdin, Michele, additional, Fiaccadori, Enrico, additional, Fiorina, Paolo, additional, Bruno Giorda, Carlo, additional, Cristina Gregorini, Maria, additional, La Manna, Gaetano, additional, Carlo Maggi, Davide, additional, Manti, Roberta, additional, Meregalli, Giancarla, additional, Pani, Antonello, additional, Perico, Norberto, additional, Piatti, PierMarco, additional, Pisani, Antonio, additional, Ettore Pontiroli, Antonio, additional, Ponzani, Paola, additional, Santorelli, Gennaro, additional, Santoro, Domenico, additional, Scanziani, Renzo, additional, Teatini, Ugo, additional, Tonolo, Giancarlo, additional, Trevisan, Roberto, additional, Maria Veronelli, Anna, additional, Luciano Viviani, Giorgio, additional, Araki, Hideo, additional, Ebisui, Osamu, additional, Fujita, Naruhiro, additional, Furuya, Ryuichi, additional, Hamamoto, Yoshiyuki, additional, Hatazaki, Masahiro, additional, Hayashi, Terumasa, additional, Higashi, Takayuki, additional, Hirohata, Yoshihide, additional, Horinouchi, Shuji, additional, Inagaki, Masayuki, additional, Ishii, Masao, additional, Ishiko, Tamayo, additional, Jinnouchi, Hideaki, additional, Kanai, Hidetoshi, additional, Kanda, Daisuke, additional, Kanehara, Hideo, additional, Kashima, Masayuki, additional, Kato, Kiyoe, additional, Katsuki, Takeshi, additional, Kawamitsu, Katsunori, additional, Kawasaki, Satsuki, additional, Kikuchi, Fumi, additional, Kikuchi, Hidetoshi, additional, Kobayashi, Kunihisa, additional, Koide, Junko, additional, Kubota, Miyuki, additional, Kusano, Yoshiro, additional, Maeda, Hajime, additional, Matsubayashi, Sunao, additional, Matsumoto, Kazunari, additional, Matsuo, Yasuto, additional, Matsuoka, Naoki, additional, Miyaoka, Hiroaki, additional, Murao, Satoshi, additional, Nakayama, Mikihiro, additional, Nakazawa, Jun, additional, Nomiyama, Takashi, additional, Noritake, Masayuki, additional, Ogiwara, Takayuki, additional, Ohashi, Hiroshi, additional, Okamoto, Hideki, additional, Osonoi, Takeshi, additional, Sasaki, Nobuhiro, additional, Sekigami, Taiji, additional, Shibasaki, Taro, additional, Shibata, Hirotaka, additional, Shinoda, Junji, additional, Sobajima, Hiroshi, additional, Sugitatsu, Kazuya, additional, Sugiura, Toshiyuki, additional, Sugiyama, Toru, additional, Suzuki, Daisuke, additional, Suzuki, Hiroyuki, additional, Suzuki, Masaaki, additional, Takeda, Asami, additional, Tanaka, Asami, additional, Tanaka, Seiichi, additional, Tsunematsu, Izumi, additional, Ujihara, Makoto, additional, Yamada, Daishiro, additional, Yamada, Masayo, additional, Yamagata, Kazuo, additional, Yamakawa, Ken, additional, Yamakawa, Fumiko, additional, Yamasaki, Yoshimitsu, additional, Yambe, Yuko, additional, Yanagida, Taihei, additional, Yanai, Hidekatsu, additional, Yasuda, Tetsuyuki, additional, Kriauciuniene, Dovile, additional, Lasiene, Jurate, additional, Navickas, Antanas, additional, Radzeviciene, Lina, additional, Urbanaviciene, Egle, additional, Urbonas, Gediminas, additional, Velaviciene, Audrone, additional, Abd Ghani, Rohana, additional, Azizah Aziz, Nor, additional, Yuan Lee, Li, additional, Loong Loh, Chek, additional, Mohd Ali, Norhaliza, additional, Mohd Noor, Nurain, additional, Nur Fatnoon, Nik, additional, Ahmad, Nik, additional, Ratnasingam, Jeyakantha, additional, Hasnul Halimi Bin, Wan, additional, Hasan, Wan, additional, Mohd Izani, Wan, additional, Mohamed, Wan, additional, Avila Pardo, Sandro, additional, Bastidas Adrian, Miriam, additional, Chew Wong, Alfredo, additional, Escobedo de la Peña, Jorge, additional, Fanghänel Salmón, Guillermo, additional, González Gálvez, Guillermo, additional, Gutiérrez Ochoa, Ramiro, additional, Irizar Santana, Saúl, additional, Méndez Machado, Gustavo, additional, Nevarez Ruiz, Luis, additional, Ramos Ibarra, Denisse, additional, Ramos López, Gabriel, additional, Sauque Reyna, Leobardo, additional, Solache Ortiz, Gustavo, additional, Valdez Ortiz, Rafael, additional, Villagordoa Mesa, Juan, additional, Bakker, R.C., additional, Barendregt, J.N.M., additional, Boonstra, A.H., additional, Bos, Willem, additional, Brouwer, C.B., additional, van Buren, M., additional, Krekels, Marielle, additional, van Leendert, Ruud J.M., additional, Lieverse, Louis A.G., additional, Luik, P.T., additional, Lars Penne, E., additional, Smak Gregoor, Peter, additional, Vogt, Liffert, additional, Baker, John, additional, Crawford, Veronica, additional, Cutfield, Rick, additional, Dunn, Peter, additional, Krebs, Jeremy, additional, Nirmalaraj, Kingsley, additional, Scott, Russell, additional, Smuts, Nine, additional, Eriksen, Erik, additional, Høivik, Hans, additional, Karlsson, Thomas, additional, Scott Munk, Peter, additional, Radtke, Maria, additional, Risberg, Knut, additional, Rocke, Jan, additional, Solnør, Leidulv, additional, Stenehjem, Aud-Eldrid, additional, Tafjord, Anne-Beathe, additional, Pamugas, Glenda, additional, Panelo, Araceli, additional, Perez, Ronald, additional, Tanque, Maribel, additional, Tirador, Louie, additional, Villa, Michael, additional, Butrymowicz, Patrycja, additional, Ciechanowski, Kazimierz, additional, Cieslik, Grazyna, additional, Franek, Edward, additional, Hoffmann, Michal, additional, Krzykowska, Jolanta, additional, Kurnatowska, Ilona, additional, Landa, Katarzyna, additional, Madrzejewski, Adam, additional, Madziarska, Katarzyna, additional, Mazur, Stanislaw, additional, Napora, Piotr, additional, Nowicki, Michal, additional, Ocicka-Kozakiewicz, Anna, additional, Rewerska, Barbara, additional, Rusicka, Teresa, additional, Ruxer, Jan, additional, Skokowska, Ewa, additional, Stankiewicz, Andrzej, additional, Stompor, Tomasz, additional, Tiuryn-Petrulewicz, Agnieszka, additional, Wasilewska, Katarzyna, additional, Wierusz-Wysocka, Bogna, additional, Wnetrzak-Michalska, Renata, additional, Almeida, Edgar, additional, Ballesteros, Rosa, additional, Barreto, Carlos, additional, Beirao, Idalina, additional, Birne, Rita, additional, Esteves, Cesar, additional, Guia, Jose, additional, Heitor, Susana, additional, Marques, Olinda, additional, Melo, Pedro, additional, Nolasco, Fernando, additional, Pereira, Amalia, additional, Roque, Cristina, additional, Rosario, Francisco, additional, Silva, Gil, additional, Silva, Ana, additional, Vila Lobos, Ana, additional, Cortes-Maisonet, Gregorio, additional, Roman-Miranda, Amaury, additional, Albota, Adrian, additional, Bala, Cornelia, additional, Barbonta, Hortensia, additional, Caceaune, Elena, additional, Catrinoui, Doina, additional, Constantin, Ciprian, additional, Dumitrescu, Adriana, additional, Mindrescu, Nicoleta, additional, Mistode, Cristina, additional, Negrisanu, Gabriela, additional, Onaca, Adriana, additional, Paveliu, Silvia, additional, Pintilei, Ella, additional, Pop, Lavinia, additional, Popa, Amorin, additional, Popescu, Alexandrina, additional, Radulian, Gabriela, additional, Szilagyi, Iosif, additional, Turcu, Liana, additional, Vacaru, Georgeta, additional, Vlad, Adrian, additional, Antsiferov, Mikhail, additional, Arkhipov, Mikhail, additional, Babkin, Andrey, additional, Barbarash, Olga, additional, Baranov, Vitaliy, additional, Chernyavskaya, Elena, additional, Demko, Arkadiy, additional, Edin, Anton, additional, Ermakova, Polina, additional, Fadeev, Valentin, additional, Galyavich, Albert, additional, Gaysina, Leyla, additional, Gordeev, Ivan, additional, Ipatko, Irina, additional, Kalashnikova, Marina, additional, Khalimov, Yuriy, additional, Klimontov, Vadim, additional, Kobalava, Zhanna, additional, Kosmacheva, Elena, additional, Koziolova, Natalya, additional, Kvitkova Sergey Levashov, Lyudmila, additional, Libis, Roman, additional, Marasaev, Vyacheslav, additional, Malykh, Natalia, additional, Martynenko, Vladimir, additional, Malyutina, Sofya, additional, Merai, Imad, additional, Mkrtumyan, Ashot, additional, Nechaeva, Galina, additional, Petunina, Nina, additional, Palyutin, Shamil, additional, Pimenov, Leonid, additional, Rechkova, Elena, additional, Rodionova, Tatyana, additional, Rymar, Oksana, additional, Sardinov, Ruslan, additional, Semenova, Olga, additional, Sherenkov, Alexander, additional, Solovev, Oleg, additional, Smolyarchuk, Elena, additional, Strongin, Leonid, additional, Ukhanova, Olga, additional, Verlan, Nadezhda, additional, Vorokhobina, Natalya, additional, Yakhontov, Davyd, additional, Yakushin, Sergey, additional, Zakharova, Elena, additional, Zalevskaya, Alsu, additional, Zanozina, Olga, additional, Zhdanova, Elena, additional, Zhukova, Larisa, additional, Zykova, Tatyana, additional, Fang Sum, Chee, additional, Muhummad Suhail, Sufi, additional, San Tan, Ru, additional, Wong, Edmund, additional, Babikova, Jana, additional, Buganova, Ingrid, additional, Dzupina, Andrej, additional, Ochodnicka, Zuzana, additional, Sosovec, Dalibor, additional, Spodniakova, Denisa, additional, Ahmed, Fayzal, additional, Bhana, Sindeep, additional, Distiller, Larry, additional, Jansen van Rensburg, Dirkie, additional, Joshi, Mukesh, additional, Joshi, Shaifali, additional, Lakha, Deepak, additional, Mitha, Essack, additional, Podgorski, Gracjan, additional, Ranjith, Naresh, additional, Rayner, Brian, additional, Rheeder, Paul, additional, Sarvan, Mohamed, additional, Seeber, Mary, additional, Siebert, Heidi, additional, Tayob, Mohammed, additional, Trokis, Julien, additional, Urbach, Dorothea, additional, van Zyl, Louis, additional, Choi, Bum-Soon, additional, Gi Choi, Moon, additional, Chung, ChoonHee, additional, Hwang, YouCheol, additional, Kim, ChongHwa, additional, Kim, InJoo, additional, Kim, JaeHyeon, additional, Kim, SinGon, additional, Kim, SungGyun, additional, Hee Kim, Tae, additional, Lee, WooJe, additional, Lee, ByungWan, additional, Wook Lee, Kang, additional, Oh, Kook-Hwan, additional, Eun Oh, Ji, additional, Kyu Oh, Yun, additional, Oh, Dong-Jin, additional, Park, Junbeom, additional, Joon Shin, Seok, additional, Sung, Su-Ah, additional, Myung Yu, Jae, additional, Agraz, Irene, additional, Javier Ampudia, Francisco, additional, Bouarich, Hanane, additional, Calero, Francesca, additional, Castro, Cristina, additional, Cigarrán Guldris, Secundino, additional, Cruzado Garrit, Josep, additional, de Álvaro, Fernando, additional, Galcerán, Josep, additional, González Albarrán, Olga, additional, Hernández Jaras, Julio, additional, Ibernón, Meritxell, additional, Martínez Deben, Francisco, additional, Dolores Martínez Esteban, Ma, additional, María Pascual Izuel, José, additional, Martins, Judith, additional, Mediavilla, Juan, additional, Michán, Alfredo, additional, Poch, Esteban, additional, Polaina Rusillo, Manuel, additional, Sánchez Juan, Carlos, additional, Santamaría Olmo, Rafael, additional, Julián, José, additional, de la Morena, Segura, additional, Soto, Alfonso, additional, Troya, Maribel, additional, Bruchfeld, Annette, additional, Curiac, Dan, additional, Eliasson, Ken, additional, Frank, Malin, additional, Guron, Gregor, additional, Hellberg, Olof, additional, Hellgren, Margareta, additional, Larnefeldt, Hans, additional, Lindholm, Carl-Johan, additional, Löndahl, Magnus, additional, Rein-Hedin, Erik, additional, Soveri, Inga, additional, Spaak, Jonas, additional, Ackermann, Daniel, additional, Bilz, Stefan, additional, Forster, Christian, additional, Kalbermatter, Stefan, additional, Kistler, Andreas, additional, Pechére-Bertschi, Antoinette, additional, Schultes, Bernd, additional, Chang, Chiz-Tzung, additional, Hung, Cheng-Chieh, additional, Jiang, Ju-Ying, additional, Lin, Shuei-Liong, additional, Tarng, Der-Cherng, additional, Tu, Shih-Te, additional, Wu, Mai-Szu, additional, Wu, Ming-Ju, additional, Deerochanawong, Chaicharn, additional, Kitiyakara, Chagriya, additional, Ophascharoensuk, Vuddhidej, additional, Pongchaiyakul, Chatlert, additional, Satirapoj, Bancha, additional, Eren, Necmi, additional, Gul, Ibrahim, additional, Gulel, Okan, additional, Kocyigit, Ismail, additional, Kumbasar, Abdulbaki, additional, Sahin, Idris, additional, Sayin, Burak, additional, Tavli, Talat, additional, Ustundag, Sedat, additional, Yenicerioglu, Yavuz, additional, Bondarets, Iryna, additional, Botsyurko, Volodymyr, additional, Chernikova, Viktoriia, additional, Donets, Oleksandra, additional, Fushtey, Ivan, additional, Grachova, Mariia, additional, Isayeva, Anna, additional, Kogut, Dmytro, additional, Komisarenko, Julia, additional, Kravchun, Nonna, additional, Malyar, Kateryna, additional, Martynyuk, Liliya, additional, Maslyanko, Vitaliy, additional, Myshanych, Halyna, additional, Pererva, Larysa, additional, Pertseva, Nataliia, additional, Serhiyenko, Oleksandr, additional, Smirnov, Ivan, additional, Sokolova, Liubov, additional, Stryzhak, Vasyl, additional, Vlasenko, Maryna, additional, AbouSaleh, Ahmad, additional, Barratt, Jonathan, additional, Dang, Cuong, additional, Kahal, Hassan, additional, Kirk, Adam, additional, Kilvert, Anne, additional, Phi Kon, Sui, additional, Patel, Dipesh, additional, Rice, Sam, additional, Vijayaraman, Arutchelvam, additional, Wong, Yuk-ki, additional, Gibson, Martin, additional, Wahba, Mona, additional, Zaidi, Reza, additional, Acosta, Idalia, additional, Adams, Atoya, additional, Ajani, Dilawar, additional, Ali, Slamat, additional, Alicic, Radica, additional, Al-Karadsheh, Amer, additional, Alla, Sreedhara, additional, Allison, D., additional, Andrawis, Nabil, additional, Arif, Ahmed, additional, Awad, Ahmed, additional, Azizad, Masoud, additional, Bahrami, Michael, additional, Bansal, Shweta, additional, Barag, Steven, additional, Barakzoy, Ahmad, additional, Barney, Mark, additional, Barzilay, Joshua, additional, Bashir, Khalid, additional, Bautista, Jose, additional, Beddhu, Srinivasan, additional, Belo, Diogo, additional, Benjamin, Sabrina, additional, Berenji, Ramin, additional, Bhargava, Anuj, additional, Birriel, Jose, additional, Brietzke, Stephen, additional, Brosius, Frank, additional, Brusco, Osvaldo, additional, Burgner, Anna, additional, Busch, Robert, additional, Canadas, Rafael, additional, Caramori, Maria, additional, Cardona, Jose, additional, Case, Christopher, additional, Cruz, Humberto, additional, Dandillaya, Ramprasad, additional, Dawoud, Dalia, additional, Din, Zia, additional, Dixon, Bradley, additional, Doshi, Ankur, additional, Drakakis, James, additional, El Shahawy, Mahfouz, additional, El-Meanawy, Ashraf, additional, El-Shahawy, Mohammed, additional, Evans, John, additional, Fadda, George, additional, Farooq, Umar, additional, Fernando, Roland, additional, Fink, Raymond, additional, First, Brian, additional, Fitz-Patrick, David, additional, Flack, John, additional, Fluck, Patrick, additional, Fogelfeld, Leon, additional, Fonseca, Vivian, additional, Frias, Juan, additional, Galphin, Claude, additional, Garcia-Mayol, Luis, additional, Goldstein, Gary, additional, Gonzalez, Edgar, additional, Gonzalez-Abreu, Francisco, additional, Gore, Ashwini, additional, Grant, David, additional, Habwe, Violet, additional, Hamilton, Maxine, additional, Hammoud, Jamal, additional, Handelsman, Stuart, additional, Hartman, Israel, additional, Heigerick, Glenn, additional, Henry, Andrew, additional, Hernandez, German, additional, Hernandez-Cassis, Carlos, additional, Herrera, Carlos, additional, Hertel, Joachim, additional, Huang, Wenyu, additional, Iglesias, Rogelio, additional, Iranmanesh, Ali, additional, Jackson, Timothy, additional, Jain, Mahendra, additional, Jamerson, Kenneth, additional, Johnson, Karen, additional, Judd, Eric, additional, Kaplan, Joshua, additional, Kayali, Zeid, additional, Khan, Bobby, additional, Khan, Muhammad, additional, Kharait, Sourabh, additional, Sue Kirkman, M., additional, Kopyt, Nelson, additional, Kotzker, Wayne, additional, Kovesdy, Csaba, additional, Kreit, Camil, additional, Krishna, Arvind, additional, Kronfli, Saeed, additional, Lee, Keung, additional, LeJeune, Derek, additional, Lemus, Brenda, additional, Leon-Forero, Carlos, additional, Linfert, Douglas, additional, Lora, Henry, additional, Lurie, Alexander, additional, Maddukuri, Geetha, additional, Magno, Alexander, additional, Maletz, Louis, additional, Mandayam, Sreedhar, additional, Markell, Mariana, additional, Mayfield, Ronald, additional, Mbogua, Caroline, additional, McMullen, Dierdre, additional, Meisner, Carl, additional, Minton, Stephen, additional, Mocherla, Bharat, additional, Mohandas, Rajesh, additional, Montero, Manuel, additional, Moustafa, Moustafa, additional, Nadkarni, Salil, additional, Nakhle, Samer, additional, Navarro, Jesus, additional, Neyra, Nilda, additional, Nica, Romanita, additional, Nicol, Philip, additional, Norwood, Paul, additional, Numrungroad, Visal, additional, O'Donovan, Richard, additional, Odugbesan, A., additional, Paoli-Bruno, Jorge, additional, Parikh, Samir, additional, Patel, Rakesh, additional, Peixoto, Aldo, additional, Pergola, Pablo, additional, Perlman, Alan, additional, Pettis, Karlton, additional, Pisoni, Roberto, additional, Ponduchi, Mirela, additional, Posada, Jorge, additional, Prabhakar, Sharma, additional, Radhakrishnan, Jai, additional, Rahman, Mahboob, additional, Raina, Rupesh, additional, Rastogi, Anjay, additional, Reisin, Efrain, additional, Rendell, Marc, additional, Robertson, David, additional, Rocco, Michael, additional, Romeu, Hugo, additional, Rosas, Sylvia, additional, Rosenfeld, Jack, additional, Ross, Dennis, additional, Rothman, Jeffrey, additional, Rudolph, Lance, additional, Ruhullah, Yusuf, additional, Ruoff, Gary, additional, Ryu, Jeffrey, additional, Sahani, Mandeep, additional, Sam, Ramin, additional, Samuels, Garfield, additional, Sanchez, William, additional, Santos, Vladimir, additional, Satko, Scott, additional, Saxena, Sanjeev, additional, Scott, David, additional, Seco, Gilberto, additional, Seek, Melvin, additional, Serota, Harvey, additional, Shafi, Tariq, additional, Shahid, Nauman, additional, Shanik, Michael, additional, Sharma, Santosh, additional, Sinha, Arjun, additional, Smelser, James, additional, Smith, Mark, additional, Soe, Kyaw, additional, Solomon, Richard, additional, Soroka, Eugene, additional, Soufer, Joseph, additional, Spinowitz, Bruce, additional, Spry, Leslie, additional, Suarez, Rosa, additional, Subramanian, Bala, additional, Szerlip, Harold, additional, Tamirisa, Aparna, additional, Thomson, Stephen, additional, Tran, Tuan-Huy, additional, Treger, Richard, additional, Trullenque, Gretel, additional, Turk, Thomas, additional, Umpierrez, Guillermo, additional, Urbach, Daniel, additional, Valdes, Martin, additional, Valika, Shujauddin, additional, Vega, Damaris, additional, Weissman, Peter, additional, Whaley-Connell, Adam, additional, Winston, Jonathan, additional, Wise, Jonathan, additional, Wynne, Alan, additional, Zeig, Steven, additional, Chu, Phuong, additional, Van Hoang, Lam, additional, Khanh, Tran, additional, Thi Phi Nga, Nguyen, additional, Nguyen Son, Pham, additional, and Phuong Tran, Lan, additional

Published
2022
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23. Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19

Author

Vasbinder, Alexi, primary, Anderson, Elizabeth, additional, Shadid, Husam, additional, Berlin, Hanna, additional, Pan, Michael, additional, Azam, Tariq U., additional, Khaleel, Ibrahim, additional, Padalia, Kishan, additional, Meloche, Chelsea, additional, O’Hayer, Patrick, additional, Michaud, Erinleigh, additional, Catalan, Tonimarie, additional, Feroze, Rafey, additional, Blakely, Pennelope, additional, Launius, Christopher, additional, Huang, Yiyuan, additional, Zhao, Lili, additional, Ang, Lynn, additional, Mikhael, Monica, additional, Mizokami-Stout, Kara, additional, Pennathur, Subramaniam, additional, Kretzler, Matthias, additional, Loosen, Sven H., additional, Chalkias, Athanasios, additional, Tacke, Frank, additional, Giamarellos-Bourboulis, Evangelos J., additional, Reiser, Jochen, additional, Eugen-Olsen, Jesper, additional, Feldman, Eva L., additional, Pop-Busui, Rodica, additional, and Hayek, Salim S., additional

Published
2022
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24. Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Author

Boyko, Edward J., primary, Zelnick, Leila R., additional, Braffett, Barbara H., additional, Pop-Busui, Rodica, additional, Cowie, Catherine C., additional, Lorenzi, Gayle M., additional, Gubitosi-Klug, Rose, additional, Zinman, Bernard, additional, and de Boer, Ian H., additional

Published
2022
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25. Beliefs Around Hypoglycemia and Their Impacts on Hypoglycemia Outcomes in Individuals with Type 1 Diabetes and High Risks for Hypoglycemia Despite Using Advanced Diabetes Technologies

Author

Lin, Yu Kuei, primary, Richardson, Caroline R., additional, Dobrin, Iulia, additional, DeJonckheere, Melissa J., additional, Mizokami-Stout, Kara, additional, Fetters, Michael D., additional, Aikens, James E., additional, Fisher, Simon J., additional, Ye, Wen, additional, and Pop-Busui, Rodica, additional

Published
2022
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27. Preventing Early Renal Loss in Diabetes (PERL) Study: A Randomized Double-Blinded Trial of Allopurinol—Rationale, Design, and Baseline Data

Author

Amisha Wallia, Irl B. Hirsch, Afshin Parsa, Alessandro Doria, J. Sonya Haw, Catherine Spino, Bruce A. Perkins, Amy B. Karger, Peter Rossing, Katherine R. Tuttle, Andrzej T. Galecki, Ruth S. Weinstock, Rodica Pop-Busui, Sylvia E. Rosas, Guillermo E. Umpierrez, Ronald J. Sigal, David M. Maahs, Ildiko Lingvay, Janet B. McGill, Maryam Afkarian, Jill P. Crandall, Mark E. Molitch, Ronnie Aronson, Peter A. Senior, Allison B. Goldfine, Sarit Polsky, Michael Mauer, Maria Luiza Caramori, David Z.I. Cherney, Chun Yi Wu, Ian H. de Boer, Marlon Pragnell, and Tom Elliott

Subjects
Male, medicine.medical_specialty, Allopurinol, Endocrinology, Diabetes and Metabolism, Urology, Renal function, Blood Pressure, 030209 endocrinology & metabolism, Placebo, Renin-Angiotensin System, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Risk Factors, Multicenter trial, Diabetes mellitus, Internal Medicine, medicine, Albuminuria, Humans, Diabetic Nephropathies, 030212 general & internal medicine, Aged, Advanced and Specialized Nursing, Type 1 diabetes, Emerging Therapies: Drugs and Regimens, business.industry, Middle Aged, medicine.disease, Uric Acid, Diabetes Mellitus, Type 1, Blood pressure, Disease Progression, Female, medicine.symptom, business, Glomerular Filtration Rate, medicine.drug
Abstract

OBJECTIVE Higher serum uric acid (SUA) is associated with diabetic kidney disease (DKD). Preventing Early Renal Loss in Diabetes (PERL) evaluates whether lowering SUA with allopurinol slows glomerular filtration rate (GFR) loss in people with type 1 diabetes (T1D) and mild to moderate DKD. We present the PERL rationale, design, and baseline characteristics. RESEARCH DESIGN AND METHODS This double-blind, placebo-controlled, multicenter trial randomized 530 participants with T1D, estimated GFR (eGFR) of 40–99.9 mL/min/1.73 m2, SUA ≥4.5 m/dL, and micro- to macroalbuminuric DKD or normoalbuminuria with declining kidney function (NDKF) (defined as historical eGFR decline ≥3 mL/min/1.73 m2/year) to allopurinol or placebo. The primary outcome is baseline-adjusted iohexol GFR (iGFR) after 3 years of treatment plus a 2-month washout period. RESULTS Participants are 66% male and 84% white. At baseline, median age was 52 years and diabetes duration was 35 years, 93% of participants had hypertension, and 90% were treated with renin-angiotensin system inhibitors (median blood pressure 127/71 mmHg). Median HbA1c was 8%, SUA 5.9 mg/dL, iGFR 68 mL/min/1.73 m2, and historical eGFR slope −3.5 mL/min/1.73 m2/year. Compared with participants with albuminuria (n = 419), those with NDKF (n = 94) were significantly older (56 vs. 52 years), had lower HbA1c (7.7 vs. 8.1%) and SUA (5.4 vs. 6.0 mg/dL), and had higher eGFR (82 vs. 74 mL/min/1.73 m2) and historical eGFR loss (−4.7 vs. −2.5 mL/min/1.73 m2/year). These differences persisted when comparing groups with similar rates of historical eGFR loss. CONCLUSIONS PERL will determine the effect of allopurinol on mild to moderate DKD in T1D, with or without albuminuria. Participants with normoalbuminuria and rapid GFR loss manifested many DKD risk factors of those with albuminuria, but with less severity.

Published
2019

28. Risk Factors for Kidney Disease in Type 1 Diabetes

Author

William V. Tamborlane, Catherine C. Cowie, John M. Lachin, Mark E. Molitch, Andrew D. Paterson, Bruce A. Perkins, Gayle M. Lorenzi, Ian H. de Boer, Ionut Bebu, Trevor J. Orchard, William H. Herman, Neil H. White, and Rodica Pop-Busui

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, Time Factors, Adolescent, Endocrinology, Diabetes and Metabolism, Renal function, 030209 endocrinology & metabolism, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Albuminuria, Humans, Diabetic Nephropathies, 030212 general & internal medicine, Epidemiology/Health Services Research, Randomized Controlled Trials as Topic, Glycemic, Advanced and Specialized Nursing, Type 1 diabetes, business.industry, Proportional hazards model, Hazard ratio, medicine.disease, Diabetes Mellitus, Type 1, Hyperglycemia, Female, Kidney Diseases, Microalbuminuria, business, Follow-Up Studies, Glomerular Filtration Rate, Kidney disease
Abstract

OBJECTIVE In type 1 diabetes (T1D), the course of microalbuminuria is unpredictable and timing of glomerular filtration rate (GFR) loss is uncertain. Thus, there is a need to identify the risk factors associated with the development of more advanced stages of kidney disease through large, long-term systematic analysis. RESEARCH DESIGN AND METHODS Multivariable Cox proportional hazards models assessed the association of baseline and time-dependent glycemic and nonglycemic risk factors for incident macroalbuminuria and reduced estimated GFR (eGFR; defined as RESULTS Higher mean HbA1c (hazard ratio [HR] 1.969 per 1% higher level [95% CI 1.671–2.319]) and male sex (HR 2.767 [95% CI 1.951–3.923]) were the most significant factors independently associated with incident macroalbuminuria, whereas higher mean triglycerides, higher pulse, higher systolic blood pressure (BP), longer diabetes duration, higher current HbA1c, and lower mean weight had lower magnitude associations. For incident reduced eGFR, higher mean HbA1c (HR 1.952 per 1% higher level [95% CI 1.714–2.223]) followed by higher mean triglycerides, older age, and higher systolic BP were the most significant factors. CONCLUSIONS Although several risk factors associated with macroalbuminuria and reduced eGFR were identified, higher mean glycemic exposure was the strongest determinant of kidney disease among the modifiable risk factors. These findings may inform targeted clinical strategies for the frequency of screening, prevention, and treatment of kidney disease in T1D.

Published
2019

29. Corneal Confocal Microscopy Predicts the Development of Diabetic Neuropathy: A Longitudinal Diagnostic Multinational Consortium Study

Author

Perkins, Bruce A., primary, Lovblom, Leif Erik, additional, Lewis, Evan J.H., additional, Bril, Vera, additional, Ferdousi, Maryam, additional, Orszag, Andrej, additional, Edwards, Katie, additional, Pritchard, Nicola, additional, Russell, Anthony, additional, Dehghani, Cirous, additional, Pacaud, Danièle, additional, Romanchuk, Kenneth, additional, Mah, Jean K., additional, Jeziorska, Maria, additional, Marshall, Andrew, additional, Shtein, Roni M., additional, Pop-Busui, Rodica, additional, Lentz, Stephen I., additional, Tavakoli, Mitra, additional, Boulton, Andrew J.M., additional, Efron, Nathan, additional, and Malik, Rayaz A., additional

Published
2021
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30. Neuropathy and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study

Author

Martin, Catherine L., Albers, James W., and Pop-Busui, Rodica

Subjects
Diabetes therapy, Type 1 diabetes -- Research -- Development and progression, Health
Abstract

OBJECTIVE To describe the development and progression of neuropathy and related findings among patients with type 1 diabetes who participated in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions [...]

Published
2014
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32. Identification of factors associated with sural nerve regeneration and degeneration in diabetic neuropathy

Author

Hur, Junguk, Sullivan, Kelli A., Callaghan, Brian C., Pop-Busui, Rodica, and Feldman, Eva L.

Subjects
Cholesterol -- Physiological aspects, Diabetic neuropathies -- Risk factors -- Physiological aspects, Health
Abstract

OBJECTIVE--Patients with diabetic neuropathy (DN) demonstrate variable degrees of nerve regeneration and degeneration. Our aim was to identify risk factors associated with sural nerve degeneration in patients with DN. RESEARCH [...]

Published
2013
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33. Peripheral neuropathy in adolescents and young adults with type 1 and type 2 diabetes from the SEARCH for diabetes in youth follow-up cohort: a pilot study

Author

Jaiswal, Mamta, Lauer, Abigail, Martin, Catherine L., Bell, Ronny A., Divers, Jasmin, Dabelea, Dana, Pettitt, David J., Saydah, Sharon, Pihoker, Catherine, Standiford, Debra A., Rodriguez, Beatrz L., Pop-Busui, Rodica, and Feldman, Eva L.

Subjects
Cholesterol -- Analysis, Teenagers -- Analysis, Youth -- Analysis, Type 2 diabetes -- Research -- Analysis, Health, American Diabetes Association
Abstract

OBJECTIVE--To estimate the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in a pilot study among youth participating in the SEARCH for Diabetes in Youth study. RESEARCH DESIGN [...]

Published
2013
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34. Risk Factors for Longitudinal Resting Heart Rate and Its Associations With Cardiovascular Outcomes in the DCCT/EDIC Study

Author

Rodica Pop-Busui, Andrew D. Paterson, Barbara H. Braffett, Amy B. Karger, Rose Gubitosi-Klug, Elsayed Z. Soliman, Trevor J. Orchard, Annette Barnie, Sareh Keshavarzi, Samuel Dagogo-Jack, and Gayle M. Lorenzi

Subjects
Research design, Adult, Male, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Disease, Diabetes Therapy, Cardiovascular System, 03 medical and health sciences, 0302 clinical medicine, Heart Rate, Risk Factors, Internal medicine, Diabetes mellitus, Heart rate, Epidemiology, Internal Medicine, Medicine, Humans, 030212 general & internal medicine, Advanced and Specialized Nursing, Type 1 diabetes, Proportional hazards model, business.industry, medicine.disease, Diabetes Mellitus, Type 1, Cardiology, business, Follow-Up Studies
Abstract

OBJECTIVE Individuals with diabetes have higher resting heart rate compared with those without, which may be predictive of long-term cardiovascular disease (CVD) risk. Using data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study, we evaluated whether the beneficial effect of intensive versus conventional diabetes therapy on heart rate persisted, the factors mediating the differences in heart rate between treatment groups, and the effects of heart rate on future CVD risk. RESEARCH DESIGN AND METHODS Longitudinal changes in heart rate, from annual electrocardiograms over 22 years of EDIC follow-up, were evaluated in 1,402 participants with type 1 diabetes. Linear mixed models were used to assess the effect of DCCT treatment group on mean heart rate over time, and Cox proportional hazards models were used to estimate the effect of heart rate on CVD risk during DCCT/EDIC. RESULTS At DCCT closeout, 52% of participants were male and mean ± SD age was 33 ± 7 years, diabetes duration 12 ± 5 years, and HbA1c 7.4 ± 1.2% (intensive) and 9.1 ± 1.6% (conventional). Through EDIC, participants in the intensive group had significantly lower heart rate in comparison with the conventional group. While significant group differences in heart rate were fully attenuated by DCCT/EDIC mean HbA1c, higher heart rate predicted CVD and major adverse cardiovascular events independent of other risk factors. CONCLUSIONS After 22 years of follow-up, former intensive versus conventional therapy remained significantly associated with lower heart rate, consistent with the long-term beneficial effects of intensive therapy on CVD. DCCT treatment group effects on heart rate were explained by differences in DCCT/EDIC mean HbA1c.

Published
2020

35. Risk Factors for the Presence and Progression of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes: ADDITION-Denmark

Author

Jesper Fleischer, Marit E. Jørgensen, Morten Charles, Rodica Pop-Busui, Henning Andersen, Torsten Lauritzen, Signe T Andersen, Daniel R. Witte, and Troels S. Jensen

Subjects
Male, Research design, Denmark, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Logistic regression, Diabetic Angiopathies/epidemiology, 0302 clinical medicine, Diabetic Neuropathies, Heart Rate, Risk Factors, Prevalence, Autonomic Nervous System Diseases/epidemiology, Diabetic Neuropathies/epidemiology, food and beverages, Middle Aged, Cardiovascular Diseases, Disease Progression, Cardiology, Female, Heart Rate/physiology, Cart, medicine.medical_specialty, 030209 endocrinology & metabolism, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Autonomic reflex, Humans, Obesity, Aged, Advanced and Specialized Nursing, business.industry, Cardiovascular Diseases/epidemiology, Diabetes Mellitus, Type 2/complications, fungi, Hypertriglyceridemia, medicine.disease, Denmark/epidemiology, Autonomic Nervous System Diseases, Diabetes Mellitus, Type 2, Obesity/complications, business, Diabetic Angiopathies, Follow-Up Studies
Abstract

OBJECTIVE To examine the course of cardiovascular autonomic neuropathy (CAN) and related cardiometabolic risk factors in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS CAN and cardiometabolic risk factors were assessed in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) at 6-year (n = 777) and 13-year (n = 443) follow-up examinations. Cardiovascular autonomic reflex tests (CARTs)—that is, lying to standing, deep breathing, and the Valsalva maneuver—and 2-min resting heart rate variability (HRV) indices were obtained as the main measures of CAN. Risk factors related to CAN status, as determined by CARTs, were studied by using multivariate logistic regressions. The effects of risk factors on continuous CARTs and HRV indices, and their changes over time, were estimated in linear mixed models. RESULTS A progressive yet heterogeneous course of CAN occurred between the 6- and 13-year follow-ups. Higher HbA1c, weight, BMI, and triglycerides were associated with prevalent CAN. No significant effect of risk factors on CARTs was found when they were analyzed as continuous variables. CART indices decreased over time, and a trend of decreasing HRV indices was seen. Higher HbA1c and BMI were associated with lower HRV index values, but these differences diminished over time. CONCLUSIONS These data confirm that hyperglycemia, obesity, and hypertriglyceridemia are negatively related to indices of CAN, although these effects diminish over time. The observed heterogeneous course of CAN may challenge the present clinical approach of categorically classifying CARTs to diagnose CAN and the notion of CAN being irreversible.

Published
2018

36. Therapeutic Lifestyle Changes Improve HDL Function by Inhibiting Myeloperoxidase-Mediated Oxidation in Patients With Metabolic Syndrome

Author

Anna V. Mathew, Lei Li, Rodica Pop-Busui, Jaeman Byun, Mamta Jaiswal, Subramaniam Pennathur, Yanhong Guo, George Michailidis, and Y. Eugene Chen

Subjects
Male, Proteomics, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, Pilot Projects, 030204 cardiovascular system & hematology, Diet, Mediterranean, medicine.disease_cause, Mice, chemistry.chemical_compound, 0302 clinical medicine, skin and connective tissue diseases, Cells, Cultured, Metabolic Syndrome, e-Letters: Comments and Responses, biology, Middle Aged, Exercise Therapy, 3. Good health, Myeloperoxidase, lipids (amino acids, peptides, and proteins), Female, Therapeutic Lifestyle Changes, Lipoproteins, HDL, Oxidation-Reduction, Adult, Cardiovascular and Metabolic Risk, medicine.medical_specialty, Adolescent, Diet therapy, Proinflammatory cytokine, Young Adult, 03 medical and health sciences, Patient Education as Topic, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Animals, Humans, Life Style, Aged, Caloric Restriction, Peroxidase, Advanced and Specialized Nursing, Cholesterol, business.industry, Cholesterol, HDL, nutritional and metabolic diseases, Biological Transport, medicine.disease, Oxidative Stress, 030104 developmental biology, Endocrinology, chemistry, biology.protein, sense organs, Metabolic syndrome, business, Risk Reduction Behavior, Oxidative stress, Diet Therapy
Abstract

OBJECTIVE Phagocyte-derived myeloperoxidase (MPO) and proinflammatory HDL are associated with metabolic syndrome (MetS) and increased cardiovascular disease risk. Therapeutic lifestyle changes (TLCs), such as a Mediterranean diet and exercise, decrease this risk. However, the link among TLCs, HDL, and MPO-mediated oxidative stress remains unclear. RESEARCH DESIGN AND METHODS In this study, we characterized changes in cholesterol efflux capacity (CEC), a metric of HDL function; MPO-mediated oxidation; and the HDL proteomic profile in 25 patients with MetS who underwent 12 weeks of TLCs. RESULTS After 12 weeks, before significant changes to HDL levels, most MetS components improved as a result of the TLCs. CEC was significantly increased, and HDL MPO oxidation products, 3-chlorotyrosine and 3-nitrotyrosine, were decreased with TLCs. The changes in CEC were inversely related to the unit changes in 3-chlorotyrosine after we controlled for changes in the other MetS components. TLCs did not remodel the HDL proteome. CONCLUSIONS In summary, TLCs improved HDL function by inhibiting MPO-mediated oxidative stress even before appreciable changes in HDL levels.

Published
2018

40. Intensive Risk Factor Management and Cardiovascular Autonomic Neuropathy in Type 2 Diabetes: The ACCORD Trial.

Author

Tang, Yaling, Shah, Hetal, Bueno Junior, Carlos Roberto, Sun, Xiuqin, Mitri, Joanna, Sambataro, Maria, Sambado, Luisa, Gerstein, Hertzel C., Fonseca, Vivian, Doria, Alessandro, Pop-Busui, Rodica, and Busui, Rodica Pop

Subjects
TYPE 2 diabetes, CARDIOVASCULAR diseases risk factors, DYSLIPIDEMIA, HEART beat, GLYCEMIC control, MOTOR vehicle driving, CARDIOVASCULAR disease prevention, BLOOD pressure, RESEARCH, RESEARCH methodology, CARDIOVASCULAR diseases, BLOOD sugar, MEDICAL cooperation, EVALUATION research, FENOFIBRATE, COMPARATIVE studies, RESEARCH funding, DISEASE complications
Abstract

Objective: The effects of preventive interventions on cardiovascular autonomic neuropathy (CAN) remain unclear. We examined the effect of intensively treating traditional risk factors for CAN, including hyperglycemia, hypertension, and dyslipidemia, in individuals with type 2 diabetes (T2D) and high cardiovascular risk participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.Research Design and Methods: CAN was defined as heart rate variability indices below the fifth percentile of the normal distribution. Of 10,251 ACCORD participants, 71% (n = 7,275) had a CAN evaluation at study entry and at least once after randomization. The effects of intensive interventions on CAN were analyzed among these subjects through generalized linear mixed models.Results: As compared with standard intervention, intensive glucose treatment reduced CAN risk by 16% (odds ratio [OR] 0.84, 95% CI 0.75-0.94, P = 0.003)-an effect driven by individuals without cardiovascular disease (CVD) at baseline (OR 0.73, 95% CI 0.63-0.85, P < 0.0001) rather than those with CVD (OR 1.10, 95% CI 0.91-1.34, P = 0.34) (Pinteraction = 0.001). Intensive blood pressure (BP) intervention decreased CAN risk by 25% (OR 0.75, 95% CI 0.63-0.89, P = 0.001), especially in patients ≥65 years old (OR 0.66, 95% CI 0.49-0.88, P = 0.005) (Pinteraction = 0.05). Fenofibrate did not have a significant effect on CAN (OR 0.91, 95% CI 0.78-1.07, P = 0.26).Conclusions: These data confirm a beneficial effect of intensive glycemic therapy and demonstrate, for the first time, a similar benefit of intensive BP control on CAN in T2D. A negative CVD history identifies T2D patients who especially benefit from intensive glycemic control for CAN prevention. [ABSTRACT FROM AUTHOR]

Published
2021
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44. An Observational Study of the Equivalence of Age and Duration of Diabetes to Glycemic Control Relative to the Risk of Complications in the Combined Cohorts of the DCCT/EDIC Study

Author

Bebu, Ionut, primary, Braffett, Barbara H., additional, Schade, David, additional, Sivitz, William, additional, Malone, John I., additional, Pop-Busui, Rodica, additional, Lorenzi, Gayle M., additional, Lee, Pearl, additional, Trapani, Victoria R., additional, Wallia, Amisha, additional, Herman, William H., additional, and Lachin, John M., additional

Published
2020
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45. The Prevalence and Determinants of Cognitive Deficits and Traditional Diabetic Complications in the Severely Obese

Author

Callaghan, Brian C., primary, Reynolds, Evan L., additional, Banerjee, Mousumi, additional, Chant, Ericka, additional, Villegas-Umana, Emily, additional, Gardner, Thomas W., additional, Votruba, Kristen, additional, Giordani, Bruno, additional, Pop-Busui, Rodica, additional, Pennathur, Subramaniam, additional, and Feldman, Eva L., additional

Published
2020
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