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1. Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine

Author

Tobias, Deirdre K, Merino, Jordi, Ahmad, Abrar, Aiken, Catherine, Benham, Jamie L, Bodhini, Dhanasekaran, Clark, Amy L, Colclough, Kevin, Corcoy, Rosa, Cromer, Sara J, Duan, Daisy, Felton, Jamie L, Francis, Ellen C, Gillard, Pieter, Gingras, Véronique, Gaillard, Romy, Haider, Eram, Hughes, Alice, Ikle, Jennifer M, Jacobsen, Laura M, Kahkoska, Anna R, Kettunen, Jarno LT, Kreienkamp, Raymond J, Lim, Lee-Ling, Männistö, Jonna ME, Massey, Robert, Mclennan, Niamh-Maire, Miller, Rachel G, Morieri, Mario Luca, Most, Jasper, Naylor, Rochelle N, Ozkan, Bige, Patel, Kashyap Amratlal, Pilla, Scott J, Prystupa, Katsiaryna, Raghavan, Sridharan, Rooney, Mary R, Schön, Martin, Semnani-Azad, Zhila, Sevilla-Gonzalez, Magdalena, Svalastoga, Pernille, Takele, Wubet Worku, Tam, Claudia Ha-ting, Thuesen, Anne Cathrine B, Tosur, Mustafa, Wallace, Amelia S, Wang, Caroline C, Wong, Jessie J, Yamamoto, Jennifer M, Young, Katherine, Amouyal, Chloé, Andersen, Mette K, Bonham, Maxine P, Chen, Mingling, Cheng, Feifei, Chikowore, Tinashe, Chivers, Sian C, Clemmensen, Christoffer, Dabelea, Dana, Dawed, Adem Y, Deutsch, Aaron J, Dickens, Laura T, DiMeglio, Linda A, Dudenhöffer-Pfeifer, Monika, Evans-Molina, Carmella, Fernández-Balsells, María Mercè, Fitipaldi, Hugo, Fitzpatrick, Stephanie L, Gitelman, Stephen E, Goodarzi, Mark O, Grieger, Jessica A, Guasch-Ferré, Marta, Habibi, Nahal, Hansen, Torben, Huang, Chuiguo, Harris-Kawano, Arianna, Ismail, Heba M, Hoag, Benjamin, Johnson, Randi K, Jones, Angus G, Koivula, Robert W, Leong, Aaron, Leung, Gloria KW, Libman, Ingrid M, Liu, Kai, Long, S Alice, Lowe, William L, Morton, Robert W, Motala, Ayesha A, Onengut-Gumuscu, Suna, Pankow, James S, Pathirana, Maleesa, Pazmino, Sofia, Perez, Dianna, Petrie, John R, Powe, Camille E, Quinteros, Alejandra, Jain, Rashmi, Ray, Debashree, and Ried-Larsen, Mathias

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Health Services, Diabetes, Clinical Research, Pediatric, Metabolic and endocrine, Good Health and Well Being, Humans, Precision Medicine, Consensus, Diabetes Mellitus, Evidence-Based Medicine, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

Published
2023

10. Urinary Plasmin(ogen) as a Prognostic Factor for Hypertension

Author

Ray, Evan C, Miller, Rachel G, Demko, John E, Costacou, Tina, Kinlough, Carol L, Demko, Casey L, Unruh, Mark L, Orchard, Trevor J, and Kleyman, Thomas R

Subjects
Epidemiology, Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Cardiovascular, Clinical Research, Kidney Disease, Hypertension, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, albumin, ENaC, diabetes, hypertension, plasmin, Biomedical and clinical sciences, Health sciences
Abstract

IntroductionPlasmin and its precursor, plasminogen, are detectable in urine from patients with glomerular disease. Urinary plasmin(ogen) levels correlate with blood pressure (BP) and may contribute to renal Na+ retention by activating the epithelial Na+ channel (ENaC). In a longitudinal nested-cohort study, we asked whether urinary plasmin(ogen) levels predict subsequent increase in BP, incident hypertension, or mortality in subjects with type I diabetes, who often develop proteinuria.MethodsThe Pittsburgh Epidemiology of Diabetes Complications (EDC) study followed up type I diabetic subjects for 25 years. Urine specimens from 70 subjects with a spectrum of baseline urinary albumin levels were examined. Outcomes included increased BP after 2 years (≥1 SD over baseline systolic or diastolic BP, examined via logistic regression), 25-year incident hypertension (≥140/90 mm Hg or initiating BP-lowering medications), and all-cause or cardiovascular mortality, examined using Cox regression.ResultsSubjects experiencing a 2-year increase in BP had higher baseline urinary plasmin(ogen)/creatinine levels (uPl/Cr) than other subjects (P = 0.04); the difference in baseline urinary albumin/creatinine levels (uAlb/Cr) was similar (P = 0.07). Baseline uPl/Cr was associated with increased 25-year hypertension incidence (hazard ratio = 2.05, P = 0.001), all-cause mortality (HR = 2.05, P = 0.01) and cardiovascular mortality (HR = 3.30, P = 0.005), although not independent of uAlb/Cr.ConclusionThis is the first long-term prospective study addressing clinical outcomes associated with increased urinary plasmin(ogen). Findings are consistent with a role for plasmin(ogen) in promoting increased BP, but also demonstrate the difficulty in distinguishing effects due to plasmin(ogen) from those of albuminuria.

Published
2018

20. Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine

Author

Tobias, Deirdre K., Merino, Jordi, Ahmad, Abrar, Aiken, Catherine, Benham, Jamie L., Bodhini, Dhanasekaran, Clark, Amy L., Colclough, Kevin, Corcoy, Rosa, Cromer, Sara J., Duan, Daisy, Felton, Jamie L., Francis, Ellen C., Gillard, Pieter, Gingras, Véronique, Gaillard, Romy, Haider, Eram, Hughes, Alice, Ikle, Jennifer M., Jacobsen, Laura M., Kahkoska, Anna R., Kettunen, Jarno L.T., Kreienkamp, Raymond J., Lim, Lee Ling, Männistö, Jonna M.E., Massey, Robert, Mclennan, Niamh Maire, Miller, Rachel G., Morieri, Mario Luca, Most, Jasper, Naylor, Rochelle N., Ozkan, Bige, Patel, Kashyap Amratlal, Pilla, Scott J., Prystupa, Katsiaryna, Raghavan, Sridharan, Rooney, Mary R., Schön, Martin, Semnani-Azad, Zhila, Sevilla-Gonzalez, Magdalena, Svalastoga, Pernille, Takele, Wubet Worku, Tam, Claudia Ha ting, Thuesen, Anne Cathrine B., Tosur, Mustafa, Wallace, Amelia S., Wang, Caroline C., Wong, Jessie J., Yamamoto, Jennifer M., Young, Katherine, Amouyal, Chloé, Andersen, Mette K., Bonham, Maxine P., Chen, Mingling, Cheng, Feifei, Chikowore, Tinashe, Chivers, Sian C., Clemmensen, Christoffer, Dabelea, Dana, Dawed, Adem Y., Deutsch, Aaron J., Dickens, Laura T., DiMeglio, Linda A., Dudenhöffer-Pfeifer, Monika, Evans-Molina, Carmella, Fernández-Balsells, María Mercè, Fitipaldi, Hugo, Fitzpatrick, Stephanie L., Gitelman, Stephen E., Goodarzi, Mark O., Grieger, Jessica A., Guasch-Ferré, Marta, Habibi, Nahal, Hansen, Torben, Huang, Chuiguo, Harris-Kawano, Arianna, Ismail, Heba M., Hoag, Benjamin, Johnson, Randi K., Jones, Angus G., Koivula, Robert W., Leong, Aaron, Leung, Gloria K.W., Libman, Ingrid M., Liu, Kai, Long, S. Alice, Lowe, William L., Morton, Robert W., Motala, Ayesha A., Onengut-Gumuscu, Suna, Pankow, James S., Pathirana, Maleesa, Pazmino, Sofia, Perez, Dianna, Petrie, John R., Powe, Camille E., Quinteros, Alejandra, Jain, Rashmi, Ray, Debashree, Ried-Larsen, Mathias, Saeed, Zeb, Santhakumar, Vanessa, Kanbour, Sarah, Sarkar, Sudipa, Monaco, Gabriela S.F., Scholtens, Denise M., Selvin, Elizabeth, Sheu, Wayne Huey Herng, Speake, Cate, Stanislawski, Maggie A., Steenackers, Nele, Steck, Andrea K., Stefan, Norbert, Støy, Julie, Taylor, Rachael, Tye, Sok Cin, Ukke, Gebresilasea Gendisha, Urazbayeva, Marzhan, Van der Schueren, Bart, Vatier, Camille, Wentworth, John M., Hannah, Wesley, White, Sara L., Yu, Gechang, Zhang, Yingchai, Zhou, Shao J., Beltrand, Jacques, Polak, Michel, Aukrust, Ingvild, de Franco, Elisa, Flanagan, Sarah E., Maloney, Kristin A., McGovern, Andrew, Molnes, Janne, Nakabuye, Mariam, Njølstad, Pål Rasmus, Pomares-Millan, Hugo, Provenzano, Michele, Saint-Martin, Cécile, Zhang, Cuilin, Zhu, Yeyi, Auh, Sungyoung, de Souza, Russell, Fawcett, Andrea J., Gruber, Chandra, Mekonnen, Eskedar Getie, Mixter, Emily, Sherifali, Diana, Eckel, Robert H., Nolan, John J., Philipson, Louis H., Brown, Rebecca J., Billings, Liana K., Boyle, Kristen, Costacou, Tina, Dennis, John M., Florez, Jose C., Gloyn, Anna L., Gomez, Maria F., Gottlieb, Peter A., Greeley, Siri Atma W., Griffin, Kurt, Hattersley, Andrew T., Hirsch, Irl B., Hivert, Marie France, Hood, Korey K., Josefson, Jami L., Kwak, Soo Heon, Laffel, Lori M., Lim, Siew S., Loos, Ruth J.F., Ma, Ronald C.W., Mathieu, Chantal, Mathioudakis, Nestoras, Meigs, James B., Misra, Shivani, Mohan, Viswanathan, Murphy, Rinki, Oram, Richard, Owen, Katharine R., Ozanne, Susan E., Pearson, Ewan R., Perng, Wei, Pollin, Toni I., Pop-Busui, Rodica, Pratley, Richard E., Redman, Leanne M., Redondo, Maria J., Reynolds, Rebecca M., Semple, Robert K., Sherr, Jennifer L., Sims, Emily K., Sweeting, Arianne, Tuomi, Tiinamaija, Udler, Miriam S., Vesco, Kimberly K., Vilsbøll, Tina, Wagner, Robert, Rich, Stephen S., Franks, Paul W., Tobias, Deirdre K., Merino, Jordi, Ahmad, Abrar, Aiken, Catherine, Benham, Jamie L., Bodhini, Dhanasekaran, Clark, Amy L., Colclough, Kevin, Corcoy, Rosa, Cromer, Sara J., Duan, Daisy, Felton, Jamie L., Francis, Ellen C., Gillard, Pieter, Gingras, Véronique, Gaillard, Romy, Haider, Eram, Hughes, Alice, Ikle, Jennifer M., Jacobsen, Laura M., Kahkoska, Anna R., Kettunen, Jarno L.T., Kreienkamp, Raymond J., Lim, Lee Ling, Männistö, Jonna M.E., Massey, Robert, Mclennan, Niamh Maire, Miller, Rachel G., Morieri, Mario Luca, Most, Jasper, Naylor, Rochelle N., Ozkan, Bige, Patel, Kashyap Amratlal, Pilla, Scott J., Prystupa, Katsiaryna, Raghavan, Sridharan, Rooney, Mary R., Schön, Martin, Semnani-Azad, Zhila, Sevilla-Gonzalez, Magdalena, Svalastoga, Pernille, Takele, Wubet Worku, Tam, Claudia Ha ting, Thuesen, Anne Cathrine B., Tosur, Mustafa, Wallace, Amelia S., Wang, Caroline C., Wong, Jessie J., Yamamoto, Jennifer M., Young, Katherine, Amouyal, Chloé, Andersen, Mette K., Bonham, Maxine P., Chen, Mingling, Cheng, Feifei, Chikowore, Tinashe, Chivers, Sian C., Clemmensen, Christoffer, Dabelea, Dana, Dawed, Adem Y., Deutsch, Aaron J., Dickens, Laura T., DiMeglio, Linda A., Dudenhöffer-Pfeifer, Monika, Evans-Molina, Carmella, Fernández-Balsells, María Mercè, Fitipaldi, Hugo, Fitzpatrick, Stephanie L., Gitelman, Stephen E., Goodarzi, Mark O., Grieger, Jessica A., Guasch-Ferré, Marta, Habibi, Nahal, Hansen, Torben, Huang, Chuiguo, Harris-Kawano, Arianna, Ismail, Heba M., Hoag, Benjamin, Johnson, Randi K., Jones, Angus G., Koivula, Robert W., Leong, Aaron, Leung, Gloria K.W., Libman, Ingrid M., Liu, Kai, Long, S. Alice, Lowe, William L., Morton, Robert W., Motala, Ayesha A., Onengut-Gumuscu, Suna, Pankow, James S., Pathirana, Maleesa, Pazmino, Sofia, Perez, Dianna, Petrie, John R., Powe, Camille E., Quinteros, Alejandra, Jain, Rashmi, Ray, Debashree, Ried-Larsen, Mathias, Saeed, Zeb, Santhakumar, Vanessa, Kanbour, Sarah, Sarkar, Sudipa, Monaco, Gabriela S.F., Scholtens, Denise M., Selvin, Elizabeth, Sheu, Wayne Huey Herng, Speake, Cate, Stanislawski, Maggie A., Steenackers, Nele, Steck, Andrea K., Stefan, Norbert, Støy, Julie, Taylor, Rachael, Tye, Sok Cin, Ukke, Gebresilasea Gendisha, Urazbayeva, Marzhan, Van der Schueren, Bart, Vatier, Camille, Wentworth, John M., Hannah, Wesley, White, Sara L., Yu, Gechang, Zhang, Yingchai, Zhou, Shao J., Beltrand, Jacques, Polak, Michel, Aukrust, Ingvild, de Franco, Elisa, Flanagan, Sarah E., Maloney, Kristin A., McGovern, Andrew, Molnes, Janne, Nakabuye, Mariam, Njølstad, Pål Rasmus, Pomares-Millan, Hugo, Provenzano, Michele, Saint-Martin, Cécile, Zhang, Cuilin, Zhu, Yeyi, Auh, Sungyoung, de Souza, Russell, Fawcett, Andrea J., Gruber, Chandra, Mekonnen, Eskedar Getie, Mixter, Emily, Sherifali, Diana, Eckel, Robert H., Nolan, John J., Philipson, Louis H., Brown, Rebecca J., Billings, Liana K., Boyle, Kristen, Costacou, Tina, Dennis, John M., Florez, Jose C., Gloyn, Anna L., Gomez, Maria F., Gottlieb, Peter A., Greeley, Siri Atma W., Griffin, Kurt, Hattersley, Andrew T., Hirsch, Irl B., Hivert, Marie France, Hood, Korey K., Josefson, Jami L., Kwak, Soo Heon, Laffel, Lori M., Lim, Siew S., Loos, Ruth J.F., Ma, Ronald C.W., Mathieu, Chantal, Mathioudakis, Nestoras, Meigs, James B., Misra, Shivani, Mohan, Viswanathan, Murphy, Rinki, Oram, Richard, Owen, Katharine R., Ozanne, Susan E., Pearson, Ewan R., Perng, Wei, Pollin, Toni I., Pop-Busui, Rodica, Pratley, Richard E., Redman, Leanne M., Redondo, Maria J., Reynolds, Rebecca M., Semple, Robert K., Sherr, Jennifer L., Sims, Emily K., Sweeting, Arianne, Tuomi, Tiinamaija, Udler, Miriam S., Vesco, Kimberly K., Vilsbøll, Tina, Wagner, Robert, Rich, Stephen S., and Franks, Paul W.

Abstract

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

Published
2023

26. Leisure Sedentary Behavior Levels and Meeting Program Goals in a Community Lifestyle Intervention for Diabetes Prevention.

Author

Rockette-Wagner, Bonny, Miller, Rachel G., Eaglehouse, Yvonne L., Arena, Vincent C., Kramer, M. Kaye, and Kriska, Andrea M.

Subjects
SEDENTARY behavior, DIABETES prevention, EXERCISE therapy, PHYSICAL activity, PHYSIOLOGICAL aspects of physical fitness
Abstract

Background: The importance of leisure sedentary behavior (LSB) change in diabetes prevention efforts is not well known. This study examines the relationships between changes in self-reported LSB and the primary intervention goals (weight and moderateintensity to vigorous-intensity physical activity [MVPA]) during a community-based translation of the Diabetes Prevention Program (the Group Lifestyle Balance Program). Methods: A total of 322 adults at risk for type 2 diabetes were recruited from 3 community centers, a worksite, and military site. Community and worksite participants were randomized to immediate or delayed-delivery (control) intervention. All military site participants (n = 99) received immediate intervention. Logistic and linear generalized estimating equations were used to determine associations between LSB changes and weight-related outcomes and MVPA. Results: Results were obtained for 259 (80.4%) participants. The LSB decreased after 6 and 12 months (mean [95% confidence interval]: -25.7 [-38.6 to -12.8] and -16.1 [-28.2 to -3.9] min/d; both P < .05). Each 20-minute reduction in LSB was associated with a 5% increase in odds of meeting the weight-loss goal (6 mo: odds ratio = 1.05 [1.002 to 1.102]; P = .042; adjusted model including MVPA), but LSB was not related to changes in reported MVPA minutes or MVPA goal achievement. Conclusion: Within the context of existing lifestyle intervention programs, reducing sedentary behavior has the potential to contribute to weight loss separately from reported MVPA improvement. [ABSTRACT FROM AUTHOR]

Published
2021
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41. Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes

Author

Mychaleckyj, Josyf C., primary, Valo, Erkka, additional, Ichimura, Takaharu, additional, Ahluwalia, Tarunveer S., additional, Dina, Christian, additional, Miller, Rachel G., additional, Shabalin, Ivan G., additional, Gyorgy, Beata, additional, Cao, JingJing, additional, Onengut-Gumuscu, Suna, additional, Satake, Eiichiro, additional, Smiles, Adam M., additional, Haukka, Jani K., additional, Tregouet, David-Alexandre, additional, Costacou, Tina, additional, O’Neil, Kristina, additional, Paterson, Andrew D., additional, Forsblom, Carol, additional, Keenan, Hillary A., additional, Pezzolesi, Marcus G., additional, Pragnell, Marlon, additional, Galecki, Andrzej, additional, Rich, Stephen S., additional, Sandholm, Niina, additional, Klein, Ronald, additional, Klein, Barbara E., additional, Susztak, Katalin, additional, Orchard, Trevor J., additional, Korstanje, Ron, additional, King, George L., additional, Hadjadj, Samy, additional, Rossing, Peter, additional, Bonventre, Joseph V., additional, Groop, Per-Henrik, additional, Warram, James H., additional, and Krolewski, Andrzej S., additional

Published
2021
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44. Circulating Free Fatty Acid and Phospholipid Signature Predicts Early Rapid Kidney Function Decline in Patients With Type 1 Diabetes

Author

Afshinnia, Farsad, primary, Rajendiran, Thekkelnaycke M., primary, He, Chenchen, primary, Byun, Jaeman, primary, Montemayor, Daniel, primary, Darshi, Manjula, primary, Tumova, Jana, primary, Kim, Jiwan, primary, Limonte, Christine P, primary, Miller, Rachel G., primary, Costacou, Tina, primary, Orchard, Trevor J., primary, Ahluwalia, Tarunveer S., primary, Rossing, Peter, primary, Snell-Bergeon, Janet K, primary, Boer, Ian H. de, primary, Natarajan, Loki, primary, Michailidis, George, primary, Sharma, Kumar, primary, and Pennathur, Subramaniam, primary

Published
2021
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45. Impact of Maintenance Session Attendance and Early Weight Loss Goal Achievement on Weight Loss Success in a Community-Based Diabetes Prevention Program Intervention

Author

Napoleone, Jenna M., primary, Miller, Rachel G., additional, Devaraj, Susan M., additional, Rockette-Wagner, Bonny, additional, Arena, Vincent C., additional, Venditti, Elizabeth M., additional, Kramer, Kaye, additional, Strotmeyer, Elsa S., additional, and Kriska, Andrea M., additional

Published
2021
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