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Item 8076 Advancing Career Development of Physician-Scientists Engaged in Diabetes Research: Insights into the National K12 DiabDocs Program(Oxford University Press, 2024-10-05) Dasani, Komal D.; Bishop, Franziska K.; Golden, Sherita H.; Laffel, Lori M.; Mirmira, Raghavendra G.; Steck, Andrea K.; Willi, Steven M.; Maahs, David M.; DiMeglio, Linda A.; Pediatrics, School of MedicineBackground: In July 2022 the NIH established a multi-center National K12 “Diabetes-Docs: Physician-Scientist Career Development Program” (DiabDocs) to support mentored research experiences and tailored career development training for cohorts of physician scientists focused on diabetes research. DiabDocs scholars are board-certified or board-eligible physicians with training in pediatric or adult endocrinology or in another area tied to diabetes research and care. The program addresses the shortage of physicians engaged in diabetes research and is open to scholars at any eligible institution in the United States. Methods: The DiabDocs program was implemented by two multi-center Program Directors (MPD), in collaboration with an Executive Leadership Committee (ELC) comprised of experienced basic science and clinical/translational physician-scientists. Additional faculty from 19 different institutions have engaged in advisory and reviewer roles. The program solicits Letters of Intent (LOIs) annually from interested candidates followed by invitations for full applications; a program retreat features educational workshops and diversity training; and a Study Section selects Scholars. Currently, the program is in its third recruitment cycle for additional scholars to start Summer 2024. Additional career development programming is available through a series of interactive webinars. The program also has a strong commitment to diversity, equity, and inclusion, including a “DiabDiversity” program to support in-person engagement in DiabDocs experiences by under-represented in medicine trainees. Results: After two successful recruitment cycles in 2022-2023 that reviewed 24 LOIs, 11 scholars were selected. The funded scholars (6 Adult and 5 Pediatric Endocrinologists) include 3 individuals self-identifying as underrepresented in medicine and 7 females. For the 2023 application cycle, 24 LOIs were received (11 from Adult and 9 from Pediatric Endocrinology, 2 in combined Pediatric/Adult Endocrinology, and 2 from other specialties). Conclusions: The DiabDocs program aims to identify, recruit, and support outstanding early career physician scientists. The program provides a national network with resources for protected research time, career development programs, and national mentorship to develop cohorts of skilled professionals contributing to the advancement of diabetes research.Item Barriers to Screening: An Analysis of Factors Impacting Screening for Type 1 Diabetes Prevention Trials(Oxford University Press, 2023-01-11) Kinney, Mara; You, Lu; Sims, Emily K.; Wherrett, Diane; Schatz, Desmond; Lord, Sandra; Krischer, Jeffrey; Russell, William E.; Gottlieb, Peter A.; Libman, Ingrid; Buckner, Jane; DiMeglio, Linda A.; Herold, Kevan C.; Steck, Andrea K.; Pediatrics, School of MedicineContext: Participants with stage 1 or 2 type 1 diabetes (T1D) qualify for prevention trials, but factors involved in screening for such trials are largely unknown. Objective: To identify factors associated with screening for T1D prevention trials. Methods: This study included TrialNet Pathway to Prevention participants who were eligible for a prevention trial: oral insulin (TN-07, TN-20), teplizumab (TN-10), abatacept (TN-18), and oral hydroxychloroquine (TN-22). Univariate and multivariate logistic regression models were used to examine participant, site, and study factors at the time of prevention trial accrual. Results: Screening rates for trials were: 50% for TN-07 (584 screened/1172 eligible), 9% for TN-10 (106/1249), 24% for TN-18 (313/1285), 17% for TN-20 (113/667), and 28% for TN-22 (371/1336). Younger age and male sex were associated with higher screening rates for prevention trials overall and for oral therapies. Participants with an offspring with T1D showed lower rates of screening for all trials and oral drug trials compared with participants with other first-degree relatives as probands. Site factors, including larger monitoring volume and US site vs international site, were associated with higher prevention trial screening rates. Conclusions: Clear differences exist between participants who screen for prevention trials and those who do not screen and between the research sites involved in prevention trial screening. Participant age, sex, and relationship to proband are significantly associated with prevention trial screening in addition to key site factors. Identifying these factors can facilitate strategic recruitment planning to support rapid and successful enrollment into prevention trials.Item Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes(Springer, 2024-09) Phillip, Moshe; Achenbach, Peter; Addala, Ananta; Albanese-O'Neill, Anastasia; Battelino, Tadej; Bell, Kirstine J.; Besser, Rachel E. J.; Bonifacio, Ezio; Colhoun, Helen M.; Couper, Jennifer J.; Craig, Maria E.; Danne, Thomas; de Beaufort, Carine; Dovc, Klemen; Driscoll, Kimberly A.; Dutta, Sanjoy; Ebekozien, Osagie; Elding Larsson, Helena; Feiten, Daniel J.; Frohnert, Brigitte I.; Gabbay, Robert A.; Gallagher, Mary P.; Greenbaum, Carla J.; Griffin, Kurt J.; Hagopian, William; Haller, Michael J.; Hendrieckx, Christel; Hendriks, Emile; Holt, Richard I. G.; Hughes, Lucille; Ismail, Heba M.; Jacobsen, Laura M.; Johnson, Suzanne B.; Kolb, Leslie E.; Kordonouri, Olga; Lange, Karin; Lash, Robert W.; Lernmark, Åke; Libman, Ingrid; Lundgren, Markus; Maahs, David M.; Marcovecchio, M. Loredana; Mathieu, Chantal; Miller, Kellee M.; O'Donnell, Holly K.; Oron, Tal; Patil, Shivajirao P.; Pop-Busui, Rodica; Rewers, Marian J.; Rich, Stephen S.; Schatz, Desmond A.; Schulman-Rosenbaum, Rifka; Simmons, Kimber M.; Sims, Emily K.; Skyler, Jay S.; Smith, Laura B.; Speake, Cate; Steck, Andrea K.; Thomas, Nicholas P. B.; Tonyushkina, Ksenia N.; Veijola, Riitta; Wentworth, John M.; Wherrett, Diane K.; Wood, Jamie R.; Ziegler, Anette-Gabriele; DiMeglio, Linda A.; Pediatrics, School of MedicineGiven the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.Item Correction to: Consensus guidance for monitoring individuals with islet autoantibody‑positive pre‑stage 3 type 1 diabetes(Springer, 2024) Phillip, Moshe; Achenbach, Peter; Addala, Ananta; Albanese-O'Neill, Anastasia; Battelino, Tadej; Bell, Kirstine J.; Besser, Rachel E. J.; Bonifacio, Ezio; Colhoun, Helen M.; Couper, Jennifer J.; Craig, Maria E.; Danne, Thomas; de Beaufort, Carine; Dovc, Klemen; Driscoll, Kimberly A.; Dutta, Sanjoy; Ebekozien, Osagie; Elding Larsson, Helena; Feiten, Daniel J.; Frohnert, Brigitte I.; Gabbay, Robert A.; Gallagher, Mary P.; Greenbaum, Carla J.; Griffin, Kurt J.; Hagopian, William; Haller, Michael J.; Hendrieckx, Christel; Hendriks, Emile; Holt, Richard I. G.; Hughes, Lucille; Ismail, Heba M.; Jacobsen, Laura M.; Johnson, Suzanne B.; Kolb, Leslie E.; Kordonouri, Olga; Lange, Karin; Lash, Robert W.; Lernmark, Åke; Libman, Ingrid; Lundgren, Markus; Maahs, David M.; Marcovecchio, M. Loredana; Mathieu, Chantal; Miller, Kellee M.; O'Donnell, Holly K.; Oron, Tal; Patil, Shivajirao P.; Pop-Busui, Rodica; Rewers, Marian J.; Rich, Stephen S.; Schatz, Desmond A.; Schulman-Rosenbaum, Rifka; Simmons, Kimber M.; Sims, Emily K.; Skyler, Jay S.; Smith, Laura B.; Speake, Cate; Steck, Andrea K.; Thomas, Nicholas P. B.; Tonyushkina, Ksenia N.; Veijola, Riitta; Wentworth, John M.; Wherrett, Diane K.; Wood, Jamie R.; Ziegler, Anette-Gabriele; DiMeglio, Linda A.; Pediatrics, School of MedicineItem Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review(Springer Nature, 2023-10-05) Felton, Jamie L.; Griffin, Kurt J.; Oram, Richard A.; Speake, Cate; Long, S. Alice; Onengut-Gumuscu, Suna; Rich, Stephen S.; Monaco, Gabriela S. F.; Evans-Molina, Carmella; DiMeglio, Linda A.; Ismail, Heba M.; Steck, Andrea K.; Dabelea, Dana; Johnson, Randi K.; Urazbayeva, Marzhan; Gitelman, Stephen; Wentworth, John M.; Redondo, Maria J.; Sims, Emily K.; Pediatrics, School of MedicineBackground: Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification. Methods: To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument. Results: We identify and summarize 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss at disease onset. Seventeen interventions, mostly immunotherapies, show benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employ precision analyses to assess features linked to treatment response. Age, beta cell function measures, and immune phenotypes are most frequently tested. However, analyses are typically not prespecified, with inconsistent methods of reporting, and tend to report positive findings. Conclusions: While the quality of prevention and intervention trials is overall high, the low quality of precision analyses makes it difficult to draw meaningful conclusions that inform clinical practice. To facilitate precision medicine approaches to T1D prevention, considerations for future precision studies include the incorporation of uniform outcome measures, reproducible biomarkers, and prespecified, fully powered precision analyses into future trial design.Item HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 Haplotype Protects Autoantibody-Positive Relatives From Type 1 Diabetes Throughout the Stages of Disease Progression(American Diabetes Association, 2016-04) Pugliese, Alberto; Boulware, David; Yu, Liping; Babu, Sunanda; Steck, Andrea K.; Becker, Dorothy; Rodriguez, Henry; DiMeglio, Linda; Evans-Molina, Carmella; Harrison, Leonard C.; Schatz, Desmond; Palmer, Jerry P.; Greenbaum, Carla; Eisenbarth, George S.; Sosenko, Jay M.; Medicine, School of MedicineThe HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is linked to protection from the development of type 1 diabetes (T1D). However, it is not known at which stages in the natural history of T1D development this haplotype affords protection. We examined a cohort of 3,358 autoantibody-positive relatives of T1D patients in the Pathway to Prevention (PTP) Study of the Type 1 Diabetes TrialNet. The PTP study examines risk factors for T1D and disease progression in relatives. HLA typing revealed that 155 relatives carried this protective haplotype. A comparison with 60 autoantibody-negative relatives suggested protection from autoantibody development. Moreover, the relatives with DRB1*15:01-DQA1*01:02-DQB1*06:02 less frequently expressed autoantibodies associated with higher T1D risk, were less likely to have multiple autoantibodies at baseline, and rarely converted from single to multiple autoantibody positivity on follow-up. These relatives also had lower frequencies of metabolic abnormalities at baseline and exhibited no overall metabolic worsening on follow-up. Ultimately, they had a very low 5-year cumulative incidence of T1D. In conclusion, the protective influence of DRB1*15:01-DQA1*01:02-DQB1*06:02 spans from autoantibody development through all stages of progression, and relatives with this allele only rarely develop T1D.Item The Influence of Type 2 Diabetes–Associated Factors on Type 1 Diabetes(American Diabetes Association, 2019-08-01) Redondo, Maria J.; Evans-Molina, Carmella; Steck, Andrea K.; Atkinson, Mark A.; Sosenko, Jay; Pediatrics, School of MedicineCurrent efforts to prevent progression from islet autoimmunity to type 1 diabetes largely focus on immunomodulatory approaches. However, emerging data suggest that the development of diabetes in islet autoantibody–positive individuals may also involve factors such as obesity and genetic variants associated with type 2 diabetes, and the influence of these factors increases with age at diagnosis. Although these factors have been linked with metabolic outcomes, particularly through their impact on β-cell function and insulin sensitivity, growing evidence suggests that they might also interact with the immune system to amplify the autoimmune response. The presence of factors shared by both forms of diabetes contributes to disease heterogeneity and thus has important implications. Characteristics that are typically considered to be nonimmune should be incorporated into predictive algorithms that seek to identify at-risk individuals and into the designs of trials for disease prevention. The heterogeneity of diabetes also poses a challenge in diagnostic classification. Finally, after clinically diagnosing type 1 diabetes, addressing nonimmune elements may help to prevent further deterioration of β-cell function and thus improve clinical outcomes. This Perspectives in Care article highlights the role of type 2 diabetes–associated genetic factors (e.g., gene variants at transcription factor 7-like 2 [TCF7L2]) and obesity (via insulin resistance, inflammation, β-cell stress, or all three) in the pathogenesis of type 1 diabetes and their impacts on age at diagnosis. Recognizing that type 1 diabetes might result from the sum of effects from islet autoimmunity and type 2 diabetes–associated factors, their interactions, or both affects disease prediction, prevention, diagnosis, and treatment.Item Proinsulin:C-peptide ratio trajectories over time in relatives at increased risk of progression to type 1 diabetes(Elsevier, 2021-02-19) Triolo, Taylor M.; Pyle, Laura; Seligova, Sona; Yu, Liping; Simmons, Kimber; Gottlieb, Peter; Evans-Molina, Carmella; Steck, Andrea K.; Medicine, School of MedicineObjective: Biomarkers are needed to characterize heterogeneity within populations at risk for type 1 diabetes. The ratio of proinsulin to C-peptide (PI:C ratio), has been proposed as a biomarker of beta cell dysfunction and is associated with progression to type 1 diabetes. However, relationships between PI:C ratios and autoantibody type and number have not been examined. We sought to characterize PI:C ratios in multiple islet autoantibody positive, single autoantibody positive and autoantibody negative relatives of individuals with type 1 diabetes. Methods: We measured PI:C ratios and autoantibodies with both electrochemiluminescence (ECL) assays (ECL-IAA, ECL-GADA and ECL-IA2A) and radiobinding (RBA) assays (mIAA, GADA, IA2A and ZnT8A) in 98 relatives of individuals with type 1 diabetes followed in the TrialNet Pathway to Prevention Study at the Barbara Davis Center for a mean of 7.4 ± 4.1 years. Of these subjects, eight progressed to T1D, 31 were multiple autoantibody (Ab) positive, 37 were single Ab positive and 22 were Ab negative (by RBA). Results: In cross-sectional analyses, there were no significant differences in PI:C ratios between type 1 diabetes and/or multiple Ab positive subjects (4.16 ± 4.06) compared to single Ab positive subjects (4.08 ± 4.34) and negative Ab subjects (3.72 ± 3.78) (p = 0.92) overall or after adjusting for age, sex and BMI. Higher PI:C ratios were associated with mIAA titers (p = 0.03) and showed an association with ECL-IA2A titers (p = 0.09), but not with ECL-IAA, GADA, ECL-GADA, IA2A nor ZnT8A titers. In mixed-effects longitudinal models, the trajectories of PI:C ratio over time were significantly different between the Ab negative and multiple Ab positive/type 1 diabetes groups, after adjusting for sex, age, and BMI (p = 0.04). Conclusions: PI:C ratio trajectories increase over time in subjects who have multiple Ab or develop type 1 diabetes and may be a helpful biomarker to further characterize and stratify risk of progression to type 1 diabetes over time.Item Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective(American Diabetes Association, 2022) Sims, Emily K.; Besser, Rachel E. J.; Dayan, Colin; Rasmussen, Cristy Geno; Greenbaum, Carla; Griffin, Kurt J.; Hagopian, William; Knip, Mikael; Long, Anna E.; Martin, Frank; Mathieu, Chantal; Rewers, Marian; Steck, Andrea K.; Wentworth, John M.; Rich, Stephen S.; Kordonouri, Olga; Ziegler, Anette-Gabriele; Herold, Kevan C.; NIDDK Type 1 Diabetes TrialNet Study Group; Pediatrics, School of MedicineMost screening programs to identify individuals at risk for type 1 diabetes have targeted relatives of people living with the disease to improve yield and feasibility. However, ∼90% of those who develop type 1 diabetes do not have a family history. Recent successes in disease-modifying therapies to impact the course of early-stage disease have ignited the consideration of the need for and feasibility of population screening to identify those at increased risk. Existing population screening programs rely on genetic or autoantibody screening, and these have yielded significant information about disease progression and approaches for timing for screening in clinical practice. At the March 2021 Type 1 Diabetes TrialNet Steering Committee meeting, a session was held in which ongoing efforts for screening in the general population were discussed. This report reviews the background of these efforts and the details of those programs. Additionally, we present hurdles that need to be addressed for successful implementation of population screening and provide initial recommendations for individuals with positive screens so that standardized guidelines for monitoring and follow-up can be established.Item Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine(Springer Nature, 2023) 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., Jr.; 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.; Pediatrics, School of MedicinePrecision 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.