Author: "Daneman D" / Publication Year Range: Last 10 years - Searchworks@Jio Institute Digital Library Search Results

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48 results on '"Daneman D"'

1. Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes

Author: Marcovecchio, ML, Colombo, M, Dalton, RN, McKeigue, PM, Benitez-Aguirre, P, Cameron, FJ, Chiesa, ST, Couper, JJ, Craig, ME, Daneman, D, Davis, EA, Deanfield, JE, Donaghue, KC, Jones, TW, Mahmud, FH, Marshall, SM, Neil, A, Colhoun, HM, Dunger, DB, Marcovecchio, ML, Colombo, M, Dalton, RN, McKeigue, PM, Benitez-Aguirre, P, Cameron, FJ, Chiesa, ST, Couper, JJ, Craig, ME, Daneman, D, Davis, EA, Deanfield, JE, Donaghue, KC, Jones, TW, Mahmud, FH, Marshall, SM, Neil, A, Colhoun, HM, and Dunger, DB
Abstract: OBJECTIVES: To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D. METHODS: Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and > 3 mL/min/1.73m2 /year, respectively), and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource. RESULTS: In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10-7 ; -0.18 [-0.26, -0.11], P = 5.1 × 10-6 ; -0.12 [-0.20, -0.05], P = 1.6 × 10-3 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10-8 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10-6 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10-6 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10-4 ). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR. CONCLUSIONS: In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR.
Published: 2020

2. Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

Author: Knip M., Akerblom H. K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H. -M., Dupre J., Fraser W. D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J. P., Lawson M. L., Ludvigsson J., Madacsy L., Mahon J. L., Ormisson A., Palmer J. P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N. H., Virtanen S. M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S. P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D. W., Brown C., Craig M., Johnston A., Bere L. J., Clarson C. L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J. -P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D. K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H. J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E. A. C., Woo V., Boland A., Clark H. D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J. C., Sauro V., Tawagi G. F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M. J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M. -C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E. A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J. C., Dawson C., Joyce C., Newhook L. A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M. J., Penner M., Sankaran K., Hardy-Brown K., King N., White R. A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M. -A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H. -M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A. -L., Hamalainen A. -M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A. S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S. -L., Selvenius J., Siljander H., Haanpaa P. -L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A. -M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A. R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M. -L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M. -L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G. B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y. M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M. B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J. A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J. R., Chueca M., Cortazar A., Echarte G., Frutos T. G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M. T., Hawkins F. G., Hernandez R., Herranz L., Pallardo L. F., Deibarra L. S., Fernandez B. H., Luis J. L., Ortiz-Quintana L., Recarte P. P., Arnau D. R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A. -M., Konefal M. S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A. -K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A. -B., Lyden G. -B., Nilsson N. -O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T. O., Andersson A. -C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I. -B., Strigard E., Svensson B. -L., Aman J., Breivik G. -E., Detlofsson I. -L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M. E., Gilmour C., Klein M. B., Lain C., Salerno D., Smith M. E., Vats K., Pfaff D. J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., Pediatrics, Knip M., Akerblom H.K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H.-M., Dupre J., Fraser W.D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J.P., Lawson M.L., Ludvigsson J., Madacsy L., Mahon J.L., Ormisson A., Palmer J.P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N.H., Virtanen S.M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S.P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D.W., Brown C., Craig M., Johnston A., Bere L.J., Clarson C.L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J.-P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D.K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H.J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E.A.C., Woo V., Boland A., Clark H.D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J.C., Sauro V., Tawagi G.F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M.J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M.-C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E.A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J.C., Dawson C., Joyce C., Newhook L.A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M.J., Penner M., Sankaran K., Hardy-Brown K., King N., White R.A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M.-A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H.-M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A.-L., Hamalainen A.-M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A.S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S.-L., Selvenius J., Siljander H., Haanpaa P.-L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A.-M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A.R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M.-L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M.-L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G.B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y.M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M.B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J.A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J.R., Chueca M., Cortazar A., Echarte G., Frutos T.G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M.T., Hawkins F.G., Hernandez R., Herranz L., Pallardo L.F., Deibarra L.S., Fernandez B.H., Luis J.L., Ortiz-Quintana L., Recarte P.P., Arnau D.R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A.-M., Konefal M.S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A.-K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A.-B., Lyden G.-B., Nilsson N.-O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T.O., Andersson A.-C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I.-B., Strigard E., Svensson B.-L., Aman J., Breivik G.-E., Detlofsson I.-L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M.E., Gilmour C., Klein M.B., Lain C., Salerno D., Smith M.E., Vats K., Pfaff D.J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., University of Zurich, and Knip, Mikael
Subjects: Male, Risk, medicine.medical_specialty, Casein, Breastfeeding, 030209 endocrinology & metabolism, 610 Medicine & health, 2700 General Medicine, Endocrinology and Diabetes, Disease-Free Survival, law.invention, Follow-Up Studie, Nutrition Policy, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, SDG 3 - Good Health and Well-being, law, Internal medicine, Diabetes mellitus, medicine, Humans, Cumulative incidence, 030212 general & internal medicine, Child, Infant Nutritional Physiological Phenomena, Original Investigation, 2. Zero hunger, Type 1 diabetes, business.industry, Hazard ratio, Absolute risk reduction, Infant, Newborn, Caseins, General Medicine, ta3121, medicine.disease, Infant Formula, 3. Good health, Diabetes Mellitus, Type 1, Infant formula, 10036 Medical Clinic, Endokrinologi och diabetes, Female, business, Human, Follow-Up Studies
Abstract: IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [HD040364, HD042444, HD051997]; Canadian Institutes of Health Research; Commission of the European Communities [QLK1-2002-00372]; European Foundation for the Study of Diabates/JDRF/Novo Nordisk; Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]; Dutch Diabetes Research Foundation; Finnish Diabetes Research Foundation; JDRF
Published: 2018

3. Growth Hormone Supplementation and Psychosocial Functioning to Adult Height in Turner Syndrome: A Questionnaire Study of Participants in the Canadian Randomized Trial

Author: Rovet, Joanne F., Van Vliet, Guy, Curtis, J. A., Cummings, E., Salisbury, S. R., Szots, F., Khoury, K., Collu, R., Deal, C. L., Huot, C., Barnes, R. D., Guyda, H. J., Legault, L., Polychronakos, C., Rodd, C., Faught, K. A., Lawrence, S. E., Lawson, M. L., Alexander, D. S., Daneman, D., Bailey, J. D., Ehrlich, R. M., Perlman, K., Sochett, E., MacMillan, A. B., Holland, F. J., Vander Meulen, J. A., Clarson, C. L., and Jenner, M. R.F.
Subjects: 0301 basic medicine, Coping (psychology), Endocrinology, Diabetes and Metabolism, Turner syndrome, Self-concept, 030209 endocrinology & metabolism, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Psychosocial functioning, law.invention, Correlation, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Randomized controlled trial, law, Behavior problems, Medicine, Growth hormone, Original Research, lcsh:RC648-665, business.industry, medicine.disease, Social relation, self-concept, behavior problems, 030104 developmental biology, growth hormone, Social competence, psychosocial functioning, business, Psychosocial, Clinical psychology
Abstract: Despite the long-held belief that growth hormone supplementation provides psychosocial benefits to patients with Turner syndrome (TS), this assumption has never been rigorously tested in a randomized control trial. As a sub-study of the Canadian growth-hormone trial, parent-, and patient-completed standardized questionnaires were used to compare 70 girls with TS who received injections (GH group) and 61 similarly followed untreated TS controls (C) on multiple facets of psychosocial functioning. Questionnaires were given (i) at baseline (session 1, mean age = 10.4 y), (ii) before estrogen therapy for puberty induction (session 2, mean age = 13.0 y), (iii) after 1 year of estrogen therapy (session 3, mean age = 14.4 y), and (iv) when growth stopped (session 4, mean age = 16.3 y). Groups were compared for multiple facets of psychosocial function within social, behavioral, self-esteem, and academic domains. Results were also correlated with indices of adult height. We found no global (i.e., across-session) group differences on any scales or subscales of the four domains. In both GH and C groups, age-related improvements were seen for social problems, externalizing behavior problems, and school functioning and age-related declines for social competence and social relations. Both parents and patients claimed GH received less teasing than C but C had more friends than GH. Results from analyses conducted within individual sessions showed that while GH at early sessions claimed to be more popular, more socially engaged, better adapted, and to have higher self-esteem than C, C was reported to be less anxious, depressed, and withdrawn than GH at adult height. The correlation analyses revealed different effects of adult height and height gain on outcome for the two groups. In GH, both height parameters were correlated with multiple parent- and/or self-reported indices from the four psychosocial domains, whereas in C, only adult height and two indices (viz., total self-concept and school functioning), were correlated. The observed modest gains in psychosocial functioning for patients with TS treated with GH highlight the need for alternative approaches to assist them in coping with the challenges of their condition.
Published: 2019

4. Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation

Author: Chiesa, S.T. Charakida, M. McLoughlin, E. Nguyen, H.C. Georgiopoulos, G. Motran, L. Elia, Y. Loredana Marcovecchio, M. Dunger, D.B. Neil Dalton, R. Daneman, D. Sochett, E. Mahmud, F.H. Deanfield, J.E.
Abstract: Aims High-density lipoprotein (HDL) function may be altered in patients with chronic disease, transforming the particle from a beneficial vasoprotective molecule to a noxious pro-inflammatory equivalent. Adolescents with Type 1 diabetes often have elevated HDL, but its vasoprotective properties and relationship to endothelial function have not been assessed. Methods and results Seventy adolescents with Type 1 diabetes (age 10-17 years) and 30 age-matched healthy controls supplied urine samples for the measurement of early renal dysfunction (albumin:creatinine ratio; ACR), blood samples for the assessment of cardiovascular risk factors (lipid profiles, HDL functionality, glycaemic control, and inflammatory risk score), and had their conduit artery endothelial function tested using flow-mediated dilation (FMD). HDL-c levels (1.69 ± 0.41 vs. 1.44 ± 0.29mmol/L; P < 0.001), and glycated haemoglobin (HbA1c) (8.4 ± 1.2 vs. 5.4 ± 0.2%; P < 0.001) were increased in all patients compared with controls. However, increased inflammation and HDL dysfunction were evident only in patients who also had evidence of early renal dysfunction (mean ± standard deviation for high-ACR vs. low-ACR and healthy controls: inflammatory risk score 11.3 ± 2.5 vs. 9.5 ± 2.4 and 9.2 ± 2.4, P < 0.01; HDL-mediated nitric-oxide bioavailability 38.0 ± 8.9 vs. 33.3 ± 7.3 and 25.0 ± 7.7%, P < 0.001; HDL-mediated superoxide production 3.71 ± 3.57 vs. 2.11 ± 3.49 and 1.91 ± 2.47nmol O2 per 250 000 cells, P < 0.05). Endothelial function (FMD) was impaired only in those who had both a high inflammatory risk score and high levels of HDL-c (P < 0.05). Conclusion Increased levels of HDL-c commonly observed in individuals with Type 1 diabetes may be detrimental to endothelial function when accompanied by renal dysfunction and chronic inflammation. © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
Published: 2019

5. ACE inhibitors and statins in adolescents with T1DM

Author: Marcovecchio ML, Chiesa ST, Bond S, Daneman D, Dawson S, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dalton RN, Deanfield J, Dunger DB, and Study Group AdDIT
Published: 2018

6. Renal and Cardiovascular Risk According to Tertiles of Urinary Albumin-to-Creatinine Ratio: The Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT)

Author: Marcovecchio, ML, Chiesa, ST, Armitage, J, Daneman, D, Donaghue, KC, Jones, TW, Mahmud, FH, Marshall, SM, Neil, HAW, Dalton, RN, Deanfield, J, Dunger, DB, Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (Addit) Study Group, Gray, AM, Jones, Timothy W [0000-0002-7989-1998], Mahmud, Farid H [0000-0002-4988-8480], Dunger, David B [0000-0002-2566-9304], Apollo - University of Cambridge Repository, and Gray, A
Subjects: musculoskeletal diseases, Male, medicine.medical_specialty, Urinalysis, Adolescent, Endocrinology, Diabetes and Metabolism, Urinary system, 030209 endocrinology & metabolism, Blood Pressure, 030204 cardiovascular system & hematology, Kidney, Carotid Intima-Media Thickness, Diabetic nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Albuminuria, Humans, Cumulative incidence, Diabetic Nephropathies, skin and connective tissue diseases, Child, Advanced and Specialized Nursing, Type 1 diabetes, Creatinine, medicine.diagnostic_test, business.industry, medicine.disease, Diabetes Mellitus, Type 1, chemistry, Cardiovascular Diseases, Microalbuminuria, Female, business, Diabetic Angiopathies, Glomerular Filtration Rate
Abstract: OBJECTIVE Baseline data from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) indicated that tertiles of urinary albumin-to-creatinine ratios (ACRs) in the normal range at age 10–16 years are associated with risk markers for diabetic nephropathy (DN) and cardiovascular disease (CVD). We aimed to determine whether the top ACR tertile remained associated with DN and CVD risk over the 2–4-year AdDIT study. RESEARCH DESIGN AND METHODS One hundred fifty adolescents (mean age 14.1 years [SD 1.6]) with baseline ACR in the upper tertile (high-ACR group) recruited to the AdDIT trial, who remained untreated, and 396 (age 14.3 years [1.6]) with ACR in the middle and lower tertiles (low-ACR group), who completed the parallel AdDIT observational study, were evaluated prospectively with assessments of ACR and renal and CVD markers, combined with carotid intima-media thickness (cIMT) at baseline and end of study. RESULTS After a median follow-up of 3.9 years, the cumulative incidence of microalbuminuria was 16.3% in the high-ACR versus 5.5% in the low-ACR group (log-rank P < 0.001). Cox models showed independent contributions of the high-ACR group (hazard ratio 4.29 [95% CI 2.08–8.85]) and HbA1c (1.37 [1.10–1.72]) to microalbuminuria risk. cIMT change from baseline was significantly greater in the high- versus low-ACR group (mean difference 0.010 mm [0.079], P = 0.006). Changes in estimated glomerular filtration rate, systolic blood pressure, and hs-CRP were also significantly greater in the high-ACR group (P < 0.05). CONCLUSIONS ACR at the higher end of the normal range at the age of 10–16 years is associated with an increased risk of progression to microalbuminuria and future CVD risk, independently of HbA1c.
Published: 2018

7. The Adolescent Cardio-Renal Intervention Trial (AdDIT): retinal vascular geometry and renal function in adolescents with type 1 diabetes

Author: Benitez-Aguirre, PZ, Wong, TY, Craig, ME, Davis, EA, Cotterill, A, Couper, JJ, Cameron, FJ, Mahmud, FH, Jones, TW, Hodgson, LAB, Dalton, RN, Dunger, DB, Donaghue, KC, Marshall, S, Armitage, J, Bingley, P, Van’t Hoff, W, Daneman, D, Neil, A, Deanfield, J, Verge, C, Bergman, P, Rodda, C, Marcovecchio, ML, Chiesa, S, Acerini, C, Ackland, F, Anand, B, Barrett, T, Birrell, V, Campbell, F, Charakida, M, Cheetham, T, Cooper, C, Doughty, I, Dutta, A, Edge, J, Gray, A, Hamilton-Shield, J, Heywood, J, Leech, N, Mann, N, Parker, R, Rayman, G, Robinson, JM, Russell-Taylor, M, Sankar, V, Smith, A, Thalange, N, Wilson, M, Yaliwal, C, Clarson, C, Curtis, J, Sochett, E, Benitez-Aguirre, PZ, Wong, TY, Craig, ME, Davis, EA, Cotterill, A, Couper, JJ, Cameron, FJ, Mahmud, FH, Jones, TW, Hodgson, LAB, Dalton, RN, Dunger, DB, Donaghue, KC, Marshall, S, Armitage, J, Bingley, P, Van’t Hoff, W, Daneman, D, Neil, A, Deanfield, J, Verge, C, Bergman, P, Rodda, C, Marcovecchio, ML, Chiesa, S, Acerini, C, Ackland, F, Anand, B, Barrett, T, Birrell, V, Campbell, F, Charakida, M, Cheetham, T, Cooper, C, Doughty, I, Dutta, A, Edge, J, Gray, A, Hamilton-Shield, J, Heywood, J, Leech, N, Mann, N, Parker, R, Rayman, G, Robinson, JM, Russell-Taylor, M, Sankar, V, Smith, A, Thalange, N, Wilson, M, Yaliwal, C, Clarson, C, Curtis, J, and Sochett, E
Abstract: Aims/hypothesis: We examined the hypothesis that elevation in urinary albumin creatinine ratio (ACR) in adolescents with type 1 diabetes is associated with abnormal retinal vascular geometry (RVG) phenotypes. Methods: A cross-sectional study at baseline of the relationship between ACR within the normoalbuminuric range and RVG in 963 adolescents aged 14.4 ± 1.6 years with type 1 diabetes (median duration 6.5 years) screened for participation in AdDIT. A validated algorithm was used to categorise log10 ACR into tertiles: upper tertile ACR was defined as ‘high-risk’ for future albuminuria and the lower two tertiles were deemed ‘low-risk’. RVG analysis, using a semi-automated computer program, determined retinal vascular calibres (standard and extended zones) and tortuosity. RVG measures were analysed continuously and categorically (in quintiles: Q1–Q5) for associations with log10 ACR and ACR risk groups. Results: Greater log10 ACR was associated with narrower vessel calibres and greater tortuosity. The high-risk group was more likely to have extended zone vessel calibres in the lowest quintile (arteriolar Q1 vs Q2–Q5: OR 1.67 [95% CI 1.17, 2.38] and venular OR 1.39 [0.98, 1.99]) and tortuosity in the highest quintile (Q5 vs Q1–Q4: arteriolar OR 2.05 [1.44, 2.92] and venular OR 2.38 [1.67, 3.40]). The effects of retinal vascular calibres and tortuosity were additive such that the participants with the narrowest and most tortuous vessels were more likely to be in the high-risk group (OR 3.32 [1.84, 5.96]). These effects were independent of duration, blood pressure, BMI and blood glucose control. Conclusions/interpretation: Higher ACR in adolescents is associated with narrower and more tortuous retinal vessels. Therefore, RVG phenotypes may serve to identify populations at high risk of diabetes complications during adolescence and well before onset of clinical diabetes complications.
Published: 2018

8. Regional differences in milk and complementary feeding patterns in infants participating in an international nutritional type 1 diabetes prevention trial

Author: Nucci, A. M., Virtanen, S. M., Sorkio, S., Barlund, S., Cuthbertson, D., Uusitalo, U., Lawson, M. L., Salonen, M., Berseth, C. L., Ormisson, A., Lehtonen, E., Savilahti, E., Becker, D. J., Dupre, J., Krischer, J. P., Knip, M., Akerblom, H. K., Mandrup-Poulsen, T., Arjas, E., Laara, E., Lernmark, A., Schmidt, B., Hyytinen, M., Koski, K., Koski, M., Pajakkala, E., Shanker, L., Bradley, B., Dosch, H. -M., Fraser, W., Lawson, M., Mahon, J. L., Sermer, M., Taback, S. P., Becker, D., Franciscus, M., Nucci, A., Palmer, J., Pekkala, M., Catteau, J., Howard, N., Crock, P., Craig, M., Clarson, C. L., Bere, L., Thompson, D., Metzger, D., Kwan, J., Stephure, D. K., Pacaud, D., Ho, J., Schwarz, W., Girgis, R., Thompson, M., Catte, D., Daneman, D., Martin, M. -J., Morin, V., Frenette, L., Ferland, S., Sanderson, S., Heath, K., Huot, C., Gonthier, M., Thibeault, M., Legault, L., Laforte, D., Cummings, E. A., Scott, K., Bridger, T., Crummell, C., Newman, S., Houlden, R., Breen, A., Carson, G., Kelly, S., Sankaran, K., Penner, M., White, R. A., Hardy Brown, K., King, N., Popkin, J., Robson, L., Coles, K., Al Taji, E., Aldhoon, I., Mendlova, P., Vavrinec, J., Vosahlo, J., Brazdova, L., Venhacova, J., Venhacova, P., Cipra, A., Tomsikova, Z., Paterova, P., Gogelova, P., Einberg, U., Riikjarv, M. -A., Tillmann, V., Hirvasniemi, M., Kleemola, P., Parkkola, A., Suomalainen, H., Jarvenpaa, A. -L., Hamalainen, A. -M., Haavisto, H., Tenhola, S., Lautala, P., Salonen, P., Aspholm, S., Siljander, H., Holm, C., Ylitalo, S., Lounamaa, R., Nuuja, A., Talvitie, T., Lindstrom, K., Huopio, H., Pesola, J., Veijola, R., Tapanainen, P., Alar, A., Korpela, P., Kaar, M. -L., Mustila, T., Virransalo, R., Nykanen, P., Aschemeier, B., Danne, T., Kordonouri, O., Krikovszky, D., Madacsy, L., Khazrai, Y. M., Maddaloni, E., Pozzilli, P., Mannu, C., Songini, M., de Beaufort, C., Schierloh, U., Bruining, J., Basiak, A., Wasikowa, R., Ciechanowska, M., Deja, G., Jarosz-Chobot, P., Szadkowska, A., Cypryk, K., Zawodniak-Szalapska, M., Castano, L., Gonzalez Frutos, T., Oyarzabal, M., Serrano-Rios, M., Martinez-Larrad, M. T., Hawkins, F. G., Rodriguez Arnau, D., Ludvigsson, J., Smolinska Konefal, M., Hanas, R., Lindblad, B., Nilsson, N. -O., Fors, H., Nordwall, M., Lindh, A., Edenwall, H., Aman, J., Johansson, C., Gadient, M., Schoenle, E., Daftary, A., Klein, M. B., Gilmour, C., Malone, P., Tanner-Blasiar, M., White, N., Devaskar, U., Horowitz, H., Rogers, L., Colon, R., Frazer, T., Torres, J., Goland, R., Greenberg, E., Nelson, M., Schachner, H., Softness, B., Ilonen, J., Trucco, M., Nichol, L., Harkonen, T., Vaarala, O., and Luopajarvi, K.
Subjects: Canada, endocrine system diseases, infant feeding, breastfeeding, type 1 diabetes, breastfeeding duration, complementary feeding, infant formula, Infant, Article, United States, Diet, Nutrition Policy, Europe, Diabetes Mellitus, Type 1, Milk, Nutrition Assessment, Double-Blind Method, Surveys and Questionnaires, Animals, Humans, Infant Food, Prospective Studies, Infant Nutritional Physiological Phenomena
Abstract: Differences in breastfeeding, other milk feeding and complementary feeding patterns were evaluated in infants at increased genetic risk with and without maternal type 1 diabetes (T1D). The Trial to Reduce IDDM in the Genetically at Risk is an international nutritional primary prevention double-blinded randomized trial to test whether weaning to extensively hydrolyzed vs. intact cow's milk protein formula will decrease the development of T1D-associated autoantibodies and T1D. Infant diet was prospectively assessed at two visits and seven telephone interviews between birth and 8 months. Countries were grouped into seven regions: Australia, Canada, Northern Europe, Southern Europe, Central Europe I, Central Europe II and the United States. Newborn infants with a first-degree relative with T1D and increased human leukocyte antigen-conferred susceptibility to T1D were recruited. A lower proportion of infants born to mothers with than without T1D were breastfed until 6 months of age in all regions (range, 51% to 60% vs. 70% to 80%). Complementary feeding patterns differed more by region than by maternal T1D. In Northern Europe, a higher proportion of infants consumed vegetables and fruits daily compared with other regions. Consumption of meat was more frequent in all European regions, whereas cereal consumption was most frequent in Southern Europe, Canada and the United States. Maternal T1D status was associated with breastfeeding and other milk feeding patterns similarly across regions but was unrelated to the introduction of complementary foods. Infant feeding patterns differed significantly among regions and were largely inconsistent with current recommended guidelines.
Published: 2017

9. Oxidative Stress and Cardiovascular Risk in Type 1 Diabetes Mellitus: Insights From the DCCT/EDIC Study

Author: Tang, W.H. Wilson, primary, McGee, Paula, additional, Lachin, John M., additional, Li, Daniel Y., additional, Hoogwerf, Byron, additional, Hazen, Stanley L., additional, Nathan, D.M., additional, Zinman, B., additional, Crofford, O., additional, Genuth, S., additional, Brown‐Friday, J., additional, Crandall, J., additional, Engel, H., additional, Engel, S., additional, Martinez, H., additional, Phillips, M., additional, Reid, M., additional, Shamoon, H., additional, Sheindlin, J., additional, Gubitosi‐Klug, R., additional, Mayer, L., additional, Pendegast, S., additional, Zegarra, H., additional, Miller, D., additional, Singerman, L., additional, Smith‐Brewer, S., additional, Novak, M., additional, Quin, J., additional, Genuth, Saul, additional, Palmert, M., additional, Brown, E., additional, McConnell, J., additional, Pugsley, P., additional, Crawford, P., additional, Dahms, W., additional, Gregory, N.S., additional, Lackaye, M.E., additional, Kiss, S., additional, Chan, R., additional, Orlin, A., additional, Rubin, M., additional, Brillon, D., additional, Reppucci, V., additional, Lee, T., additional, Heinemann, M., additional, Chang, S., additional, Levy, B., additional, Jovanovic, L., additional, Richardson, M., additional, Bosco, B., additional, Dwoskin, A., additional, Hanna, R., additional, Barron, S., additional, Campbell, R., additional, Bhan, A., additional, Kruger, D., additional, Jones, J.K., additional, Edwards, P.A., additional, Carey, J.D., additional, Angus, E., additional, Thomas, A., additional, Galprin, A., additional, McLellan, M., additional, Whitehouse, F., additional, Bergenstal, R., additional, Johnson, M., additional, Gunyou, K., additional, Thomas, L., additional, Laechelt, J., additional, Hollander, P., additional, Spencer, M., additional, Kendall, D., additional, Cuddihy, R., additional, Callahan, P., additional, List, S., additional, Gott, J., additional, Rude, N., additional, Olson, B., additional, Franz, M., additional, Castle, G., additional, Birk, R., additional, Nelson, J., additional, Freking, D., additional, Gill, L., additional, Mestrezat, W., additional, Etzwiler, D., additional, Morgan, K., additional, Aiello, L.P., additional, Golden, E., additional, Arrigg, P., additional, Asuquo, V., additional, Beaser, R., additional, Bestourous, L., additional, Cavallerano, J., additional, Cavicchi, R., additional, Ganda, O., additional, Hamdy, O., additional, Kirby, R., additional, Murtha, T., additional, Schlossman, D, additional, Shah, S., additional, Sharuk, G., additional, Silva, P., additional, Silver, P., additional, Stockman, M., additional, Sun, J., additional, Weimann, E., additional, Wolpert, H., additional, Aiello, L.M., additional, Jacobson, A., additional, Rand, L., additional, Rosenzwieg, J., additional, Larkin, M.E., additional, Christofi, M., additional, Folino, K., additional, Godine, J., additional, Lou, P., additional, Stevens, C., additional, Anderson, E., additional, Bode, H., additional, Brink, S., additional, Cornish, C., additional, Cros, D., additional, Delahanty, L., additional, eManbey, ., additional, Haggan, C., additional, Lynch, J., additional, McKitrick, C., additional, Norman, D., additional, Moore, D., additional, Ong, M., additional, Taylor, C., additional, Zimbler, D., additional, Crowell, S., additional, Fritz, S., additional, Hansen, K., additional, Gauthier‐Kelly, C., additional, Service, F.J., additional, Ziegler, G., additional, Barkmeier, A., additional, Schmidt, L., additional, French, B., additional, Woodwick, R., additional, Rizza, R., additional, Schwenk, W.F., additional, Haymond, M., additional, Pach, J., additional, Mortenson, J., additional, Zimmerman, B., additional, Lucas, A., additional, Colligan, R., additional, Luttrell, L., additional, Lopes‐Virella, M., additional, Caulder, S., additional, Pittman, C., additional, Patel, N., additional, Lee, K., additional, Nutaitis, M., additional, Fernandes, J., additional, Hermayer, K., additional, Kwon, S., additional, Blevins, A, additional, Parker, J., additional, Colwell, J., additional, Lee, D., additional, Soule, J., additional, Lindsey, P., additional, Bracey, M., additional, Farr, A., additional, Elsing, S., additional, Thompson, T., additional, Selby, J., additional, Lyons, T., additional, Yacoub‐Wasef, S., additional, Szpiech, M., additional, Wood, D., additional, Mayfield, R., additional, Molitch, M., additional, Adelman, D., additional, Colson, S., additional, Jampol, L., additional, Lyon, A., additional, Gill, M., additional, Strugula, Z., additional, Kaminski, L., additional, Mirza, R., additional, Simjanoski, E., additional, Ryan, D., additional, Johnson, C., additional, Wallia, A., additional, Ajroud‐Driss, S., additional, Astelford, P., additional, Leloudes, N., additional, Degillio, A., additional, Schaefer, B., additional, Mudaliar, S., additional, Lorenzi, G, additional, Goldbaum, M., additional, Jones, K., additional, Prince, M., additional, Swenson, M., additional, Grant, I., additional, Reed, R., additional, Lyon, R., additional, Kolterman, O., additional, Giotta, M., additional, Clark, T., additional, Friedenberg, G., additional, Sivitz, W.I., additional, Vittetoe, B., additional, Kramer, J., additional, Bayless, M., additional, Zeitler, R., additional, Schrott, H., additional, Olson, N., additional, Snetselaar, L., additional, Hoffman, R., additional, MacIndoe, J., additional, Weingeist, T., additional, Fountain, C., additional, Miller, R., additional, Johnsonbaugh, S., additional, Patronas, M., additional, Carney, M., additional, Mendley, S., additional, Salemi, P., additional, Liss, R., additional, Hebdon, M., additional, Counts, D., additional, Donner, T., additional, Gordon, J., additional, Hemady, R., additional, Kowarski, A., additional, Ostrowski, D., additional, Steidl, S., additional, Jones, B., additional, Herman, W.H., additional, Martin, C.L., additional, Pop‐Busui, R., additional, Greene, D.A., additional, Stevens, M.J., additional, Burkhart, N., additional, Sandford, T., additional, Floyd, J., additional, Bantle, J., additional, Flaherty, N., additional, Terry, J., additional, Koozekanani, D., additional, Montezuma, S., additional, Wimmergren, N., additional, Rogness, B., additional, Mech, M., additional, Strand, T., additional, Olson, J., additional, McKenzie, L., additional, Kwong, C., additional, Goetz, F., additional, Warhol, R., additional, Hainsworth, D., additional, Goldstein, D., additional, Hitt, S., additional, Giangiacomo, J., additional, Schade, D.S, additional, Canady, J.L., additional, Burge, M.R., additional, Das, A., additional, Avery, R.B., additional, Ketai, L.H., additional, Chapin, J.E., additional, Schluter, M.L., additional, Rich, J., additional, Johannes, C., additional, Hornbeck, D., additional, Schutta, M., additional, Bourne, P.A., additional, Brucker, A., additional, Braunstein, S., additional, Schwartz, S., additional, Maschak‐Carey, B.J., additional, Baker, L., additional, Orchard, T., additional, Cimino, L., additional, Songer, T., additional, Doft, B., additional, Olson, S., additional, Becker, D., additional, Rubinstein, D., additional, Bergren, R.L., additional, Fruit, J., additional, Hyre, R., additional, Palmer, C., additional, Silvers, N., additional, Lobes, L., additional, Rath, P. Paczan, additional, Conrad, P.W., additional, Yalamanchi, S., additional, Wesche, J., additional, Bratkowksi, M., additional, Arslanian, S., additional, Rinkoff, J., additional, Warnicki, J., additional, Curtin, D., additional, Steinberg, D., additional, Vagstad, G., additional, Harris, R., additional, Steranchak, L., additional, Arch, J., additional, Kelly, K., additional, Ostrosaka, P., additional, Guiliani, M., additional, Good, M., additional, Williams, T., additional, Olsen, K., additional, Campbell, A., additional, Shipe, C., additional, Conwit, R., additional, Finegold, D., additional, Zaucha, M., additional, Drash, A., additional, Morrison, A., additional, Malone, J.I., additional, Bernal, M.L., additional, Pavan, P.R., additional, Grove, N., additional, Tanaka, E.A., additional, McMillan, D., additional, Vaccaro‐Kish, J., additional, Babbione, L., additional, Solc, H., additional, DeClue, T.J., additional, Dagogo‐Jack, S., additional, Wigley, C., additional, Ricks, H., additional, Kitabchi, A., additional, Chaum, E., additional, Murphy, M.B., additional, Moser, S., additional, Meyer, D., additional, Iannacone, A., additional, Yoser, S., additional, Bryer‐Ash, M., additional, Schussler, S., additional, Lambeth, H., additional, Raskin, P., additional, Strowig, S., additional, Basco, M., additional, Cercone, S., additional, Barnie, A., additional, Devenyi, R., additional, Mandelcorn, M., additional, Brent, M., additional, Rogers, S., additional, Gordon, A., additional, Bakshi, N., additional, Perkins, B., additional, Tuason, L., additional, Perdikaris, F., additional, Ehrlich, R., additional, Daneman, D., additional, Perlman, K., additional, Ferguson, S, additional, Palmer, J., additional, Fahlstrom, R., additional, de Boer, I.H., additional, Kinyoun, J., additional, Van Ottingham, L., additional, Catton, S., additional, Ginsberg, J., additional, McDonald, C., additional, Harth, J., additional, Driscoll, M., additional, Sheidow, T., additional, Mahon, J., additional, Canny, C., additional, Nicolle, D., additional, Colby, P., additional, Dupre, J., additional, Hramiak, I., additional, Rodger, N.W., additional, Jenner, M., additional, Smith, T., additional, Brown, W., additional, May, M., additional, Lipps Hagan, J., additional, Agarwal, A., additional, Adkins, T., additional, Lorenz, R., additional, Feman, S., additional, Survant, L., additional, White, N.H., additional, Levandoski, L., additional, Grand, G., additional, Thomas, M., additional, Joseph, D., additional, Blinder, K., additional, Shah, G., additional, Burgess, D., additional, Boniuk, I., additional, Santiago, J., additional, Tamborlane, W., additional, Gatcomb, P., additional, Stoessel, K., additional, Ramos, P., additional, Fong, K., additional, Ossorio, P., additional, Ahern, J., additional, Meadema‐Mayer, L., additional, Beck, C., additional, Farrell, K., additional, Quin, J, additional, Gaston, P., additional, Trail, R., additional, Lachin, J., additional, Backlund, J., additional, Bebu, I., additional, Braffett, B., additional, Diminick, L., additional, Gao, X., additional, Hsu, W., additional, Klumpp, K., additional, Pan, H., additional, Trapani, V., additional, Cleary, P., additional, McGee, P., additional, Sun, W., additional, Villavicencio, S., additional, Anderson, K., additional, Dews, L., additional, Younes, Naji, additional, Rutledge, B., additional, Chan, K., additional, Rosenberg, D., additional, Petty, B., additional, Determan, A., additional, Kenny, D., additional, Williams, C., additional, Cowie, C., additional, Siebert, C., additional, Steffes, M., additional, Arends, V., additional, Bucksa, J., additional, Nowicki, M., additional, Chavers, B., additional, O'Leary, D., additional, Polak, J., additional, Harrington, A., additional, Funk, L., additional, Crow, R, additional, Gloeb, B., additional, Thomas, S., additional, O'Donnell, C., additional, Soliman, E.Z., additional, Zhang, Z.M., additional, Li, Y., additional, Campbell, C., additional, Keasler, L., additional, Hensley, S., additional, Hu, J., additional, Barr, M., additional, Taylor, T., additional, Prineas, R., additional, Feldman, E.L., additional, Albers, J.W., additional, Low, P., additional, Sommer, C., additional, Nickander, K., additional, Speigelberg, T., additional, Pfiefer, M., additional, Schumer, M., additional, Moran, M., additional, Farquhar, J., additional, Ryan, C., additional, Sandstrom, D., additional, Geckle, M., additional, Cupelli, E., additional, Thoma, F., additional, Burzuk, B., additional, Woodfill, T., additional, Danis, R., additional, Blodi, B., additional, Lawrence, D., additional, Wabers, H., additional, Gangaputra, S., additional, Neill, S., additional, Burger, M., additional, Dingledine, J., additional, Gama, V., additional, Sussman, R., additional, Davis, M., additional, Hubbard, L., additional, Budoff, M., additional, Darabian, S., additional, Rezaeian, P., additional, Wong, N., additional, Fox, M., additional, Oudiz, R., additional, Kim, L, additional, Detrano, R., additional, Cruickshanks, K., additional, Dalton, D., additional, Bainbridge, K., additional, Lima, J., additional, Bluemke, D., additional, Turkbey, E., additional, der Geest, ., additional, Liu, C., additional, Malayeri, A., additional, Jain, A., additional, Miao, C., additional, Chahal, H., additional, Jarboe, R., additional, Monnier, V., additional, Sell, D., additional, Strauch, C., additional, Hazen, S., additional, Pratt, A., additional, Tang, W., additional, Brunzell, J., additional, Purnell, J., additional, Natarajan, R., additional, Miao, F., additional, Zhang, L., additional, Chen, Z., additional, Paterson, A., additional, Boright, A., additional, Bull, S., additional, Sun, L., additional, Scherer, S., additional, Lyons, T.J., additional, Jenkins, A., additional, Klein, R., additional, Virella, G., additional, Jaffa, A., additional, Carter, R., additional, Stoner, J., additional, Garvey, W.T., additional, Lackland, D., additional, Brabham, M., additional, McGee, D., additional, Zheng, D., additional, Mayfield, R.K., additional, Maynard, J., additional, Wessells, H., additional, Sarma, A, additional, Dunn, R., additional, Holt, S., additional, Hotaling, J., additional, Kim, C., additional, Clemens, Q., additional, Brown, J., additional, and McVary, K., additional
Published: 2018
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10. Impact of neighbourhood-level inequity on paediatric diabetes care

Author: Clarke, A. B. M., primary, Daneman, D., additional, Curtis, J. R., additional, and Mahmud, F. H., additional
Published: 2017
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11. Resources and population served: a description of the Ontario Paediatric Diabetes Network

Author: Shulman, R., primary, Miller, F. A., additional, Stukel, T. A., additional, Daneman, D., additional, and Guttmann, A., additional
Published: 2016
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12. EXPLORING MYOCARDIAL FUNCTION IN ADOLESCENT TYPE 1 DIABETES

Author: Bradley, T.J., primary, Slorach, C., additional, Cherney, D.Z., additional, Daneman, D., additional, Deda, L., additional, Dunger, D.B., additional, Elia, Y., additional, Har, R., additional, Hui, W., additional, Mahmud, F.H., additional, Moineddin, R., additional, Sochett, E., additional, and Mertens, L., additional
Published: 2014
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13. THE EFFECT OF ALBUMIN:CREATININE RATIO ON STANDARD ECHOCARDIOGRAPHIC PARAMETERS IN ADOLESCENT TYPE 1 DIABETES

Author: Bradley, T.J., primary, Slorach, C., additional, Cherney, D.Z., additional, Daneman, D., additional, Deda, L., additional, Dunger, D.B., additional, Elia, Y., additional, Har, R., additional, Hui, W., additional, Mahmud, F.H., additional, Moineddin, R., additional, Mertens, L., additional, and Sochett, E., additional
Published: 2014
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14. Socioeconomic representativeness of Australian, Canadian and British cohorts from the paediatric diabetes AdDIT study: comparisons to regional and national data.

Author: Mahmud FH, Clarke ABM, Elia Y, Curtis J, Benitez-Aguirre P, Cameron FJ, Chiesa ST, Clarson C, Couper JJ, Craig ME, Dalton RN, Daneman D, Davis EA, Deanfield JE, Donaghue KC, Jones TW, Marshall SM, Neil A, and Marcovecchio ML
Subjects: Adolescent, Humans, Australia epidemiology, Canada epidemiology, Clinical Trials as Topic, Cross-Sectional Studies, Retrospective Studies, Socioeconomic Factors, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 1 therapy
Abstract: Background: Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations., Methods: Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK). Representativeness was assessed by comparing the AdDIT cohort's distribution of deprivation quintiles with that of the local paediatric type 1 diabetes population (regional), and the broader type 1 diabetes population for which the trial's intervention was targeted (national)., Results: Recruited study cohorts from each country had higher proportions of participants with higher SES, and significant underrepresentation of lower SES, in relation to their national references. The socioeconomic make-up in Australia mirrored that of the regional population (p = 0.99). For Canada, the 2nd least deprived (p = 0.001) and the most deprived quintiles (p < 0.001) were over- and under-represented relative to the regional reference, while the UK featured higher regional and national SES bias with over-representation and under-representation from the least-deprived and most-deprived quintiles (p < 0.0001)., Conclusions: Significant national differences in trial participation of low SES participants were observed, highlighting limitations in access to clinical research and the importance of reporting sociodemographic representation in diabetes clinical trials., Trial Registration: NCT01581476. Registered on 20 April 2012., (© 2023. The Author(s).)
Published: 2023
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15. The Ongoing Transmutation of Type 1 Diabetes: Disparities in Care and Outcomes.

Author: Shulman R, Nakhla M, and Daneman D
Subjects: Humans, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 1 therapy, Healthcare Disparities
Published: 2021
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16. INSPIRED but Tired: How Medical Faculty's Job Demands and Resources Lead to Engagement, Work-Life Conflict, and Burnout.

Author: Lee RS, Son Hing LS, Gnanakumaran V, Weiss SK, Lero DS, Hausdorf PA, and Daneman D
Abstract: Background: Past research shows that physicians experience high ill-being (i.e., work-life conflict, stress, burnout) but also high well-being (i.e., job satisfaction, engagement)., Objective: To shed light on how medical faculty's experiences of their job demands and job resources might differentially affect their ill-being and their well-being with special attention to the role that the work-life interface plays in these processes., Methods: Qualitative thematic analysis was used to analyze interviews from 30 medical faculty (19 women, 11 men, average tenure 13.36 years) at a top research hospital in Canada., Findings: Medical faculty's experiences of work-life conflict were severe. Faculty's job demands had coalescing (i.e., interactive) effects on their stress, work-life conflict, and exhaustion. Although supportive job resources (e.g., coworker support) helped to mitigate the negative effects of job demands, stimulating job resources (e.g., challenging work) contributed to greater work-life conflict, stress, and exhaustion. Thus, for these medical faculty job resources play a dual-role for work-life conflict. Moreover, although faculty experienced high emotional exhaustion, they did not experience the other components of burnout (i.e., reduced self-efficacy, and depersonalization). Some faculty engaged in cognitive reappraisal strategies to mitigate their experiences of work-life conflict and its harmful consequences., Conclusion: This study suggests that the precise nature and effects of job demands and job resources may be more complex than current research suggests. Hospital leadership should work to lessen unnecessary job demands, increase supportive job resources, recognize all aspects of job performance, and, given faculty's high levels of work engagement, encourage a climate that fosters work-life balance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Son Hing, Gnanakumaran, Weiss, Lero, Hausdorf and Daneman.)
Published: 2021
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17. Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes.

Author: Chiesa ST, Marcovecchio ML, Benitez-Aguirre P, Cameron FJ, Craig ME, Couper JJ, Davis EA, Dalton RN, Daneman D, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dunger DB, and Deanfield JE
Subjects: Adolescent, Albuminuria urine, C-Reactive Protein metabolism, Creatinine analysis, Diabetes Mellitus, Type 1 blood, Double-Blind Method, Drug Therapy, Combination, Endothelium, Vascular physiopathology, Female, Glycated Hemoglobin metabolism, Humans, Lipids blood, Male, Pulse Wave Analysis, Vascular Stiffness physiology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Diabetes Mellitus, Type 1 physiopathology, Endothelium, Vascular drug effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Vascular Stiffness drug effects
Abstract: An increased albumin-creatinine ratio within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period and investigated the effect of ACE (angiotensin-converting enzyme) inhibitors and statins in high-risk adolescents. Endothelial function (flow-mediated dilation and reactive hyperemia index) and arterial stiffness (carotid-femoral pulse wave velocity) were assessed in 158 high-risk participants recruited to a randomized, double-blind placebo-controlled 2×2 factorial trial (randomized, placebo-controlled trial) of ACE inhibitors and/or statins in adolescents with type 1 diabetes (AdDIT [Adolescent Type 1 Diabetes cardio-renal Intervention Trial]). Identical measures were also assessed in 215 lower-risk individuals recruited to a parallel observational study. In the randomized, placebo-controlled trial, high-risk patients randomized to ACE inhibitors had improved flow-mediated dilation after 2 to 4 years of follow-up (mean [95% CI]: 6.6% [6.0-7.2] versus 5.3% [4.7-5.9]; P =0.005), whereas no effect was observed following statin use (6.2% [5.5-6.8] versus 5.8% [5.1-6.4]; P =0.358). In the observational study, patients classed as high-risk based on albumin-creatinine ratio showed evidence of endothelial dysfunction at the end of follow-up (flow-mediated dilation=4.8% [3.8-5.9] versus 6.3% [5.8-6.7] for high-risk versus low-risk groups; P =0.015). Neither reactive hyperemia index nor pulse wave velocity were affected by either treatment ( P >0.05 for both), but both were found to increase over the duration of follow-up (0.07 [0.03-0.12]; P =0.001 and 0.5 m/s [0.4-0.6]; P <0.001 for reactive hyperemia index and pulse wave velocity, respectively). ACE inhibitors improve endothelial function in high-risk adolescents as they transition through puberty. The longer-term protective effects of this intervention at this early age remain to be determined. Registration- URL: https://www.clinicaltrials.gov; Unique identifier NCT01581476.
Published: 2020
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18. Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes.

Author: Marcovecchio ML, Colombo M, Dalton RN, McKeigue PM, Benitez-Aguirre P, Cameron FJ, Chiesa ST, Couper JJ, Craig ME, Daneman D, Davis EA, Deanfield JE, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil A, Colhoun HM, and Dunger DB
Subjects: Adolescent, Adult, Age Factors, Biomarkers blood, Child, Cohort Studies, Cystatin C blood, Diabetic Nephropathies diagnosis, Fibroblast Growth Factor-23, Fibroblast Growth Factors blood, Glomerular Filtration Rate, Humans, Middle Aged, Osteopontin blood, Trefoil Factor-3 blood, Young Adult, beta 2-Microglobulin blood, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 complications, Diabetic Nephropathies blood, Diabetic Nephropathies etiology
Abstract: Objectives: To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D., Methods: Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and > 3 mL/min/1.73m 2 /year, respectively), and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource., Results: In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10 -7 ; -0.18 [-0.26, -0.11], P = 5.1 × 10 -6 ; -0.12 [-0.20, -0.05], P = 1.6 × 10 -3 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10 -8 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10 -6 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10 -6 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10 -4 ). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR., Conclusions: In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR., (© 2020 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)
Published: 2020
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19. Disconnections between medical education and medical practice: A neglected dilemma.

Author: Benatar S and Daneman D
Subjects: Humans, Delivery of Health Care organization & administration, Education, Medical organization & administration
Abstract: Medical practice has changed profoundly over the past 60 years. Many changes have also been made in medical education, often with a view to countering adverse aspects of highly specialised, commercialised and bureaucratised modern medical practice. Regardless of the state of the world today and of the variety of changes that may occur in the years ahead, excellence in the application of bedside skills and technological advances, accompanied by excellence in humanistic aspects of caring for patients as people, will remain preeminent goals at the heart of medical practice. Powerful social forces that negatively influence practice cannot be counteracted through changes in medical education alone and need to be addressed directly within health systems. Shifting healthcare towards a valued social service is arguably essential for improving both public and individual health through more widespread universal access to high quality and effectively integrated health care.
Published: 2020
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20. Medication Adherence During Adjunct Therapy With Statins and ACE Inhibitors in Adolescents With Type 1 Diabetes.

Author: Niechciał E, Acerini CL, Chiesa ST, Stevens T, Dalton RN, Daneman D, Deanfield JE, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dunger DB, and Marcovecchio ML
Subjects: Adolescent, Angiotensin-Converting Enzyme Inhibitors adverse effects, Australia epidemiology, Canada epidemiology, Chemotherapy, Adjuvant, Child, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 1 metabolism, Diabetic Angiopathies prevention & control, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Insulin therapeutic use, Male, United Kingdom epidemiology, Angiotensin-Converting Enzyme Inhibitors administration & dosage, Cardiovascular Diseases prevention & control, Diabetes Mellitus, Type 1 drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Medication Adherence statistics & numerical data
Abstract: Objective: Suboptimal adherence to insulin treatment is a main issue in adolescents with type 1 diabetes. However, to date, there are no available data on adherence to adjunct noninsulin medications in this population. Our aim was to assess adherence to ACE inhibitors and statins and explore potential determinants in adolescents with type 1 diabetes., Research Design and Methods: There were 443 adolescents with type 1 diabetes recruited into the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) and exposed to treatment with two oral drugs-an ACE inhibitor and a statin-as well as combinations of both or placebo for 2-4 years. Adherence was assessed every 3 months with the Medication Event Monitoring System (MEMS) and pill count., Results: Median adherence during the trial was 80.2% (interquartile range 63.6-91.8) based on MEMS and 85.7% (72.4-92.9) for pill count. Adherence based on MEMS and pill count dropped from 92.9% and 96.3%, respectively, at the first visit to 76.3% and 79.0% at the end of the trial. The percentage of study participants with adherence ≥75% declined from 84% to 53%. A good correlation was found between adherence based on MEMS and pill count ( r = 0.82, P < 0.001). Factors associated with adherence were age, glycemic control, and country., Conclusions: We report an overall good adherence to ACE inhibitors and statins during a clinical trial, although there was a clear decline in adherence over time. Older age and suboptimal glycemic control at baseline predicted lower adherence during the trial, and, predictably, reduced adherence was more prevalent in subjects who subsequently dropped out., (© 2020 by the American Diabetes Association.)
Published: 2020
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21. Dynamic Tensions Following New Pedagogy in Undergraduate Medical Education.

Author: Daneman D and Benatar S
Subjects: Canada, Education, Medical, Undergraduate methods, Humans, United States, Curriculum trends, Education, Medical, Undergraduate trends, Teaching trends
Abstract: The authors draw on their many decades of combined experience with medical students, observing their maturation into practice in widely differing contexts, to reaffirm some of the essential goals of medical education. They briefly review curricular changes in medical education over the past 100 years, then focus on the dynamic tension in undergraduate medical education (UME) resulting from new pedagogy. Specifically, these tensions arise from the differing trajectories and directions of the 3 traditional pillars of academic medicine: clinical excellence, state-of-the-art education, and cutting-edge research. The authors highlight the role of generalism as an essential foundation of UME, as well as the dilemma of a shrinking cadre of medical students choosing a generalist career path. To address challenges stemming from pedagogical changes, the authors offer 4 observations. First, a more condensed approach to faculty development may be to ensure that bringing teachers up to speed on the new curriculum is not excessively burdensome. Second would be a more gradual introduction of the proposed changes. Third, some discussion about medical education pedagogy and curricular development ought to have a place in UME to prepare the next generation of physicians for ongoing changes in accreditation and in approaches to education. Finally, more appropriate funding of medical education would alleviate some of the burden and anxiety by acknowledging its nonmaterial value.
Published: 2019
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22. Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation.

Author: Chiesa ST, Charakida M, McLoughlin E, Nguyen HC, Georgiopoulos G, Motran L, Elia Y, Marcovecchio ML, Dunger DB, Dalton RN, Daneman D, Sochett E, Mahmud FH, and Deanfield JE
Subjects: Adolescent, Biomarkers blood, Case-Control Studies, Child, Chronic Disease, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 complications, Female, Humans, Hyperlipidemias blood, Hyperlipidemias physiopathology, Inflammation blood, Inflammation physiopathology, Male, Renal Insufficiency blood, Renal Insufficiency etiology, Renal Insufficiency physiopathology, Diabetes Mellitus, Type 1 physiopathology, Endothelium, Vascular physiopathology, Hyperlipidemias etiology, Inflammation etiology, Lipoproteins, HDL blood
Abstract: Aims: High-density lipoprotein (HDL) function may be altered in patients with chronic disease, transforming the particle from a beneficial vasoprotective molecule to a noxious pro-inflammatory equivalent. Adolescents with Type 1 diabetes often have elevated HDL, but its vasoprotective properties and relationship to endothelial function have not been assessed., Methods and Results: Seventy adolescents with Type 1 diabetes (age 10-17 years) and 30 age-matched healthy controls supplied urine samples for the measurement of early renal dysfunction (albumin:creatinine ratio; ACR), blood samples for the assessment of cardiovascular risk factors (lipid profiles, HDL functionality, glycaemic control, and inflammatory risk score), and had their conduit artery endothelial function tested using flow-mediated dilation (FMD). HDL-c levels (1.69 ± 0.41 vs. 1.44 ± 0.29mmol/L; P < 0.001), and glycated haemoglobin (HbA1c) (8.4 ± 1.2 vs. 5.4 ± 0.2%; P < 0.001) were increased in all patients compared with controls. However, increased inflammation and HDL dysfunction were evident only in patients who also had evidence of early renal dysfunction (mean ± standard deviation for high-ACR vs. low-ACR and healthy controls: inflammatory risk score 11.3 ± 2.5 vs. 9.5 ± 2.4 and 9.2 ± 2.4, P < 0.01; HDL-mediated nitric-oxide bioavailability 38.0 ± 8.9 vs. 33.3 ± 7.3 and 25.0 ± 7.7%, P < 0.001; HDL-mediated superoxide production 3.71 ± 3.57 vs. 2.11 ± 3.49 and 1.91 ± 2.47nmol O2 per 250 000 cells, P < 0.05). Endothelial function (FMD) was impaired only in those who had both a high inflammatory risk score and high levels of HDL-c (P < 0.05)., Conclusion: Increased levels of HDL-c commonly observed in individuals with Type 1 diabetes may be detrimental to endothelial function when accompanied by renal dysfunction and chronic inflammation., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Published: 2019
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23. A newborn with a massive goiter.

Author: Ivanisevic I, Daneman D, and Zdravkovic VM
Published: 2019
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24. A new strategy for vascular complications in young people with type 1 diabetes mellitus.

Author: Marcovecchio ML, Dalton RN, Daneman D, Deanfield J, Jones TW, Neil HAW, and Dunger DB
Subjects: Adolescent, Age Factors, Child, Child, Preschool, Diabetes Mellitus, Type 1 drug therapy, Female, Follow-Up Studies, Humans, Insulin therapeutic use, Male, Severity of Illness Index, Blood Glucose analysis, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 diagnosis, Glycemic Index
Abstract: Diabetes vascular complications, including cardiovascular disease, diabetic nephropathy and retinopathy, have a negative effect on the long-term prognosis of young people with type 1 diabetes mellitus (T1DM). Poor glycaemic control and consequent increased HbA 1c levels are major risk factors for the development of vascular complications. HbA 1c levels are the main focus of current management strategies; however, the recommended target is rarely achieved in adolescents. Thus, a clear need exists for improved biomarkers to identify high-risk young people early and to develop new intervention strategies. Evidence is accumulating that early increases in urinary albumin excretion could be predictive of adolescents with T1DM who are at an increased risk of developing vascular complications, independent of HbA 1c levels. These findings present an opportunity to move towards the personalized care of adolescents with T1DM, which takes into consideration changes in albumin excretion and other risk factors in addition to HbA 1c levels.
Published: 2019
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25. Fostering Transformative Learning in a Social Pediatrics Research Summer Studentship.

Author: Talarico S, Zubairi M, Daneman D, Punnett A, and Martimianakis MAT
Subjects: Adult, Female, Humans, Male, Ontario, Young Adult, Curriculum, Education, Medical, Undergraduate organization & administration, Healthcare Disparities, Pediatrics education, Students, Medical psychology
Abstract: Problem: Teaching future doctors the skills necessary to address health disparities is a challenge for medical educators. In response, the authors developed and implemented the Social Pediatrics Research Summer Studentship (SPReSS) program for medical students at the University of Toronto., Approach: The curriculum incorporated research and clinical placements into a formal seminar series. Participating students were required to complete a research project and to write a reflection describing a situation that challenged their thinking. The authors and curriculum developers applied transformative learning principles not only to facilitate critical reflection and learning in the students but also as an innovative approach to program development and evaluation. The authors conducted a thematic analysis of the reflections of 23 students participating in the program in June and July 2013, 2014, and 2015 to evaluate the SPReSS program., Outcomes: The analysis revealed students' empathic responses to marginalized patients, and these responses acted as triggers for critical reflection. Students described feeling empowered to act as advocates and wrote that these feelings were reinforced through faculty members' role modeling. According to their reflections, students found the program both challenging and rewarding, particularly the integration of the clinical and research experiences which made broader sociopolitical phenomena introduced through assigned readings and seminar discussions concrete., Next Steps: The authors are exploring models, including a fourth-year selective or multiyear longitudinal experience, to support more students. They also hope to involve more community partners and to evaluate long-term outcomes of participants.
Published: 2019
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26. Renal and Cardiovascular Risk According to Tertiles of Urinary Albumin-to-Creatinine Ratio: The Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT).

Author: Marcovecchio ML, Chiesa ST, Armitage J, Daneman D, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dalton RN, Deanfield J, and Dunger DB
Subjects: Adolescent, Albuminuria epidemiology, Albuminuria urine, Blood Pressure physiology, Cardiovascular Diseases urine, Carotid Intima-Media Thickness, Child, Creatinine blood, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 epidemiology, Diabetic Angiopathies etiology, Diabetic Angiopathies urine, Diabetic Nephropathies epidemiology, Diabetic Nephropathies physiopathology, Diabetic Nephropathies urine, Female, Glomerular Filtration Rate physiology, Humans, Kidney physiopathology, Male, Risk Factors, Urinalysis, Albuminuria complications, Cardiovascular Diseases etiology, Creatinine urine, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 urine, Diabetic Nephropathies etiology
Abstract: Objective: Baseline data from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) indicated that tertiles of urinary albumin-to-creatinine ratios (ACRs) in the normal range at age 10-16 years are associated with risk markers for diabetic nephropathy (DN) and cardiovascular disease (CVD). We aimed to determine whether the top ACR tertile remained associated with DN and CVD risk over the 2-4-year AdDIT study., Research Design and Methods: One hundred fifty adolescents (mean age 14.1 years [SD 1.6]) with baseline ACR in the upper tertile (high-ACR group) recruited to the AdDIT trial, who remained untreated, and 396 (age 14.3 years [1.6]) with ACR in the middle and lower tertiles (low-ACR group), who completed the parallel AdDIT observational study, were evaluated prospectively with assessments of ACR and renal and CVD markers, combined with carotid intima-media thickness (cIMT) at baseline and end of study., Results: After a median follow-up of 3.9 years, the cumulative incidence of microalbuminuria was 16.3% in the high-ACR versus 5.5% in the low-ACR group (log-rank P < 0.001). Cox models showed independent contributions of the high-ACR group (hazard ratio 4.29 [95% CI 2.08-8.85]) and HbA 1c (1.37 [1.10-1.72]) to microalbuminuria risk. cIMT change from baseline was significantly greater in the high- versus low-ACR group (mean difference 0.010 mm [0.079], P = 0.006). Changes in estimated glomerular filtration rate, systolic blood pressure, and hs-CRP were also significantly greater in the high-ACR group ( P < 0.05)., Conclusions: ACR at the higher end of the normal range at the age of 10-16 years is associated with an increased risk of progression to microalbuminuria and future CVD risk, independently of HbA 1c ., (© 2018 by the American Diabetes Association.)
Published: 2018
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27. Social Determinants of Health Are Associated with Markers of Renal Injury in Adolescents with Type 1 Diabetes.

Author: Cummings LAM, Clarke A, Sochett E, Daneman D, Cherney DZ, Reich HN, Scholey JW, Dunger DB, and Mahmud FH
Subjects: Acute Kidney Injury diagnosis, Adolescent, Biomarkers metabolism, Creatinine blood, Female, Glomerular Filtration Rate, Humans, Inflammation Mediators metabolism, Logistic Models, Male, Serum Albumin, Human metabolism, Social Marginalization, Acute Kidney Injury etiology, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 psychology, Social Determinants of Health
Abstract: Objective: To examine the relationship between the social determinants of health and markers of early renal injury in adolescent patients with type 1 diabetes (T1D)., Study Design: Renal outcomes included estimated glomerular filtration rate (eGFR) and albumin-creatinine excretion ratio (ACR). Differences in urinary and serum inflammatory markers also were assessed in relation to social determinants of health. Regression analysis was used to evaluate the association between the Ontario Marginalization Index (ON-Marg) as a measure of the social determinants of health, patient characteristics, ACR, eGFR, and renal filtration status (hyperfiltration vs normofiltration)., Results: Participants with T1D (n = 199) with a mean age of 14.4 ± 1.7 years and diabetes duration of 7.2 ± 3.1 years were studied. Mean eGFR was 122.0 ± 19.4 mL/min/1.73 m 2 . Increasing marginalization was positively associated with eGFR (P < .0001) but not with ACR (P = .605). Greater marginalization was associated with greater median levels of urinary interleukin (IL)-2, IL-12 (p40), macrophage-derived chemokine, monocyte chemoattractant protein-3, and tumor necrosis factor-β and serum IL-2. ON-Marg was significantly associated with eGFR after we controlled for age, sex, body mass index z score, ethnicity, serum glucose, and hemoglobin A1c in linear regression. A similar association between hyperfiltration and ON-Marg score was observed in multivariable logistic regression., Conclusion: Increasing marginalization is significantly associated with both eGFR and hyperfiltration in adolescents with T1D and is associated with significant changes in urinary inflammatory biomarkers. These findings highlight a potentially important interaction between social and biological determinants of health in adolescents with T1D., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2018
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28. Hyperfiltration, urinary albumin excretion, and ambulatory blood pressure in adolescents with Type 1 diabetes mellitus.

Author: Lovshin JA, Škrtić M, Bjornstad P, Moineddin R, Daneman D, Dunger D, Reich HN, Mahmud F, Scholey J, Cherney DZI, and Sochett E
Subjects: Adolescent, Age Factors, Albuminuria diagnosis, Albuminuria physiopathology, Biomarkers, Blood Pressure Monitoring, Ambulatory, Cardiovascular Diseases diagnosis, Cardiovascular Diseases physiopathology, Child, Circadian Rhythm, Creatinine blood, Cystatin C blood, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 physiopathology, Diabetic Nephropathies diagnosis, Diabetic Nephropathies physiopathology, Female, Follow-Up Studies, Glycated Hemoglobin metabolism, Humans, Lipoproteins, LDL blood, Male, Prognosis, Risk Factors, Time Factors, Albuminuria etiology, Blood Pressure, Cardiovascular Diseases etiology, Diabetes Mellitus, Type 1 complications, Diabetic Nephropathies etiology, Glomerular Filtration Rate, Kidney physiopathology
Abstract: Adolescents with Type 1 diabetes mellitus (T1DM) are at risk for hyperfiltration and elevated urinary albumin-to-creatinine ratio (ACR), which are early indicators of diabetic nephropathy. Adolescents with T1DM also develop early changes in blood pressure, cardiovascular structure, and function. Our aims were to define the relationships between hyperfiltration, ACR, and 24-h ambulatory blood pressure over time in adolescents with T1DM. Normotensive, normoalbuminuric adolescents ( n = 98) with T1DM underwent baseline and 2-yr 24-h ambulatory blood pressure monitoring, glomerular filtration rate (eGFR) estimated by cystatin C (Larsson equation) , and ACR measurements. Linear regression models adjusted for diabetes duration, sex, and HbA1c were used to determine associations. Hyperfiltration (eGFR ≥ 133 ml/min) was present in 31% at baseline and 21% at 2-yr follow-up. Hyperfiltration was associated with greater odds of rapid GFR decline (>3 ml·min -1 ·yr -1 ) [OR: 5.33, 95%; CI: 1.87-15.17; P = 0.002] over 2 yr. Natural log of ACR at baseline was associated with greater odds of hyperfiltration (OR: 1.71, 95% CI: 1.00-2.92; P = 0.049) and 2-yr follow-up (OR: 2.14, 95%; CI: 1.09-4.19; P = 0.03). One SD increase in eGFR, but not ln ACR, at 2-yr follow-up conferred greater odds of nighttime nondipping pattern (OR: 1.96, 95% CI: 1.06-3.63; P = 0.03). Hyperfiltration was prevalent at baseline and at 2-yr follow-up, predicted rapid decline in GFR, and was related to ACR. Elevated GFR at 2-yr follow-up was associated with nighttime nondipping pattern. More work is needed to better understand early relationships between renal hemodynamic and systemic hemodynamic changes in adolescents with T1DM to reduce future cardiorenal complications.
Published: 2018
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29. ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes.

Author: Marcovecchio ML, Chiesa ST, Bond S, Daneman D, Dawson S, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dalton RN, Deanfield J, and Dunger DB
Subjects: Adolescent, Albuminuria etiology, Angiotensin-Converting Enzyme Inhibitors adverse effects, Area Under Curve, Child, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 urine, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Lipids blood, Male, Medication Adherence, Albuminuria prevention & control, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Creatinine urine, Diabetes Mellitus, Type 1 drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
Abstract: Background: Among adolescents with type 1 diabetes, rapid increases in albumin excretion during puberty precede the development of microalbuminuria and macroalbuminuria, long-term risk factors for renal and cardiovascular disease. We hypothesized that adolescents with high levels of albumin excretion might benefit from angiotensin-converting-enzyme (ACE) inhibitors and statins, drugs that have not been fully evaluated in adolescents., Methods: We screened 4407 adolescents with type 1 diabetes between the ages of 10 and 16 years of age and identified 1287 with values in the upper third of the albumin-to-creatinine ratios; 443 were randomly assigned in a placebo-controlled trial of an ACE inhibitor and a statin with the use of a 2-by-2 factorial design minimizing differences in baseline characteristics such as age, sex, and duration of diabetes. The primary outcome for both interventions was the change in albumin excretion, assessed according to the albumin-to-creatinine ratio calculated from three early-morning urine samples obtained every 6 months over 2 to 4 years, and expressed as the area under the curve. Key secondary outcomes included the development of microalbuminuria, progression of retinopathy, changes in the glomerular filtration rate, lipid levels, and measures of cardiovascular risk (carotid intima-media thickness and levels of high-sensitivity C-reactive protein and asymmetric dimethylarginine)., Results: The primary outcome was not affected by ACE inhibitor therapy, statin therapy, or the combination of the two. The use of an ACE inhibitor was associated with a lower incidence of microalbuminuria than the use of placebo; in the context of negative findings for the primary outcome and statistical analysis plan, this lower incidence was not considered significant (hazard ratio, 0.57; 95% confidence interval, 0.35 to 0.94). Statin use resulted in significant reductions in total, low-density lipoprotein, and non-high-density lipoprotein cholesterol levels, in triglyceride levels, and in the ratio of apolipoprotein B to apolipoprotein A1, whereas neither drug had significant effects on carotid intima-media thickness, other cardiovascular markers, the glomerular filtration rate, or progression of retinopathy. Overall adherence to the drug regimen was 75%, and serious adverse events were similar across the groups., Conclusions: The use of an ACE inhibitor and a statin did not change the albumin-to-creatinine ratio over time. (Funded by the Juvenile Diabetes Research Foundation and others; AdDIT ClinicalTrials.gov number, NCT01581476 .).
Published: 2017
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30. I am green with envy......

Author: Daneman D
Published: 2017
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31. Insulin pump use and discontinuation in children and teens: a population-based cohort study in Ontario, Canada.

Author: Shulman R, Stukel TA, Miller FA, Newman A, Daneman D, and Guttmann A
Subjects: Adolescent, Child, Child, Preschool, Cohort Studies, Diabetes Mellitus, Type 1 blood, Female, Humans, Male, Ontario epidemiology, Social Class, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 1 epidemiology, Insulin administration & dosage, Insulin Infusion Systems statistics & numerical data, Withholding Treatment statistics & numerical data
Abstract: Objective: To describe insulin pump use by youth since introduction of universal funding in Ontario, Canada and to explore the relationship between pump use and pediatric diabetes center characteristics and the relationship between discontinuation and center and patient characteristics., Research Design and Methods: Observational, population-based cohort study of youth with type 1 diabetes (<19 yr) who received pump funding from 2006 to 2013 (n = 3700). We linked 2012 survey data from 33 pediatric diabetes centers to health administrative databases. We tested the relationship between center-level pump uptake and center characteristics (center type, physician model, and availability of 24-h support) using an adjusted negative binomial model; we studied center- and patient-level factors (socioeconomic status and baseline glycemic control) associated with discontinuation using a Cox proportional hazards model with generalized estimating equations., Results: Pump users were more likely to be in the highest income quintile than non-pump users (29.6 vs. 19.1%, p < 0.0001). In 2012, mean percent pump use was 38.0% with variability across centers. There was no association between uptake and center characteristics. Discontinuation was low (0.42/100 person-yr) and was associated with being followed at a small community center [hazard ratio (HR): 2.24 (1.05-4.76)] and being more deprived [HR: 2.36 (1.14-1.48)]. Older age was associated with a lower rate of discontinuation [HR: 0.31 (0.14-0.66)]., Conclusions: Rates of pump use have increased since 2006 and discontinuation is rare. Large variation in uptake across centers was not explained by the factors we examined but may reflect variation in patient populations or practice patterns, and should be further explored., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2017
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32. The relationship between urinary renin-angiotensin system markers, renal function, and blood pressure in adolescents with type 1 diabetes.

Author: Burns KD, Lytvyn Y, Mahmud FH, Daneman D, Deda L, Dunger DB, Deanfield J, Dalton RN, Elia Y, Har R, Van JA, Bradley TJ, Slorach C, Hui W, Xiao F, Zimpelmann J, Mertens L, Moineddin R, Reich HN, Sochett E, Scholey JW, and Cherney DZ
Subjects: Adolescent, Albuminuria metabolism, Angiotensinogen urine, Biomarkers metabolism, Creatinine urine, Diabetes Mellitus, Type 1 metabolism, Female, Glomerular Filtration Rate physiology, Humans, Kidney metabolism, Male, Peptidyl-Dipeptidase A urine, Blood Pressure physiology, Diabetes Mellitus, Type 1 physiopathology, Kidney physiopathology, Renin-Angiotensin System physiology
Abstract: The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess 1 ) levels of urinary RAAS components and 2 ) the association between RAAS components and HbA1c, the urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and blood pressure (BP) in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). Urinary angiotensinogen and angtionsin-converting enzyme (ACE) 2 levels, activity of ACE and ACE2, BP, HbA1c, ACR, and eGFR were measured in 65 HC and 194 T1D from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). Urinary levels of all RAAS components were higher in T1D vs. HC ( P < 0.0001). Higher HbA1c was associated with higher urinary angiotensinogen, ACE2, and higher activity of ACE and ACE2 ( P < 0.0001, P = 0.0003, P = 0.003, and P = 0.007 respectively) in T1D. Higher ACR (within the normal range) was associated with higher urinary angiotensinogen ( P < 0.0001) and ACE activity ( P = 0.007), but not with urinary ACE2 activity or ACE2 levels. These observations were absent in HC. Urinary RAAS components were not associated with BP or eGFR in T1D or HC. Otherwise healthy adolescents with T1D exhibit higher levels of urinary RAAS components compared with HC. While levels of all urinary RAAS components correlate with HbA1c in T1D, only urinary angiotensinogen and ACE activity correlate with ACR, suggesting that these factors reflect an intermediary pathogenic link between hyperglycemia and albuminuria within the normal range., (Copyright © 2017 the American Physiological Society.)
Published: 2017
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33. Pediatric Insulin Pump Therapy: Reflecting on the First 10 Years of a Universal Funding Program in Ontario.

Author: Shulman R, Miller FA, Stukel TA, Daneman D, and Guttmann A
Subjects: Adolescent, Child, Child, Preschool, Diabetes Mellitus, Type 1 complications, Diabetic Ketoacidosis epidemiology, Healthcare Disparities, Humans, Insulin administration & dosage, Insulin Infusion Systems statistics & numerical data, Ontario, Diabetes Mellitus, Type 1 drug therapy, Insulin Infusion Systems adverse effects, Insulin Infusion Systems economics
Abstract: We evaluated the universal funding program for pediatric insulin pumps in Ontario by examining the dynamics underlying patterns of pump use and adverse events using population-based health administrative data available at the Institute for Clinical Evaluative Sciences (ICES), supplemented by other data. We found that (1) pump use has increased steadily since 2006 with variation across centres and disparity in use by socioeconomic status; (2) pump discontinuation is uncommon; (3) physicians value pump therapy in numerous ways that provide important insights into patterns of uptake; and (4) the safety profile of pump therapy is, in general, very good; however, individuals of lower socioeconomic status are at an increased risk of acute diabetes complications, most frequently diabetic ketoacidosis. This comprehensive mixed-methods evaluation reveals the need to understand and intervene to reduce social disparities in the use and adverse outcomes of technologies used for diabetes management.
Published: 2017
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34. Social Determinants of Health Are Associated with Modifiable Risk Factors for Cardiovascular Disease and Vascular Function in Pediatric Type 1 Diabetes.

Author: Inman M, Daneman D, Curtis J, Sochett E, Clarke A, Dunger DB, Deanfield J, and Mahmud FH
Subjects: Adolescent, Female, Humans, Male, Pulse Wave Analysis, Risk Factors, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 physiopathology, Diabetic Angiopathies epidemiology, Diabetic Angiopathies etiology, Diabetic Cardiomyopathies epidemiology, Diabetic Cardiomyopathies etiology, Social Determinants of Health, Vascular Stiffness
Abstract: Objective: To evaluate the relationship between social determinants of health (SDH) and cardiovascular disease (CVD) risk factors as well as a measure of arterial stiffness in adolescents with type 1 diabetes (T1D)., Study Design: SDH were measured with the validated Ontario Marginalization Index, derived from deidentified postal code data and stratified by quintile (first = least deprived; fifth = most deprived). SDH dimensions included material deprivation; ethnic concentration; and measures of dependency and residential instability. Metabolic control (hemoglobin A1c), cardiovascular risk metrics, and pulse wave velocity, as a measure of arterial stiffness, were related to SDH. Data were evaluated from a cohort of Canadian adolescents within the Adolescent Diabetes Cardiorenal Intervention Trial, a T1D clinical trial, Results: A total of 704 participants were evaluated, and significant differences in hemoglobin A1c were evident at the extremes of material deprivation (8.4% vs 9.1% for least vs most deprived, P < .01). CVD risk factors were analyzed in 199 participants, with the most deprived reporting significantly less exercise (P = .004) and increased rates of smoking (P = .008). Increased material deprivation was associated with fewer metrics of "ideal" cardiovascular health attained. Arterial stiffness, as measured by pulse wave velocity, was associated positively with age, body mass index z score, and material deprivation., Conclusion: Increased material deprivation was associated with poorer glycemic control. Modifiable, lifestyle-related risk factors for CVD and early arterial wall change are associated with SDH and represent a target for clinical intervention to reduce future CVD burden in adolescents with T1D., (Copyright © 2016 Elsevier Inc. All rights reserved.)
Published: 2016
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35. Pediatric Reference Values and Z Score Equations for Left Ventricular Systolic Strain Measured by Two-Dimensional Speckle-Tracking Echocardiography.

Author: Dallaire F, Slorach C, Bradley T, Hui W, Sarkola T, Friedberg MK, Jaeggi E, Dragulescu A, Mahmud FH, Daneman D, and Mertens L
Subjects: Adolescent, Cardiology standards, Child, Child, Preschool, Echocardiography methods, Echocardiography statistics & numerical data, Elastic Modulus physiology, Elasticity Imaging Techniques methods, Elasticity Imaging Techniques statistics & numerical data, Female, Humans, Image Interpretation, Computer-Assisted methods, Infant, Male, Ontario epidemiology, Radiography standards, Reference Values, Reproducibility of Results, Sensitivity and Specificity, Stress, Mechanical, Aging physiology, Echocardiography standards, Elasticity Imaging Techniques standards, Heart Ventricles diagnostic imaging, Image Interpretation, Computer-Assisted standards, Pediatrics standards, Ventricular Function, Left physiology
Abstract: Background: In pediatric echocardiography, myocardial strain measurements are likely influenced by cardiac size and growth in healthy children. The application of this technique in clinical practice has been hampered by the lack of good normal reference values for the pediatric population. The aim of this study was to determine reference values and Z score equations for left ventricular systolic circumferential and longitudinal strain in a healthy pediatric population., Methods: Two hundred thirty-three healthy subjects 1 to 18 years of age were prospectively recruited. Left ventricular systolic longitudinal and circumferential strain measurements were recorded using two-dimensional speckle-tracking. Normalization for body size was performed using parametric nonlinear regression modeling. Several analyses were performed to detect potential residual associations with body size, residual heteroscedasticity, or departure from an adequate Z score distribution., Results: There were weak but statistically significant nonlinear associations between body size and most strain values. Body surface area was superior to adjust for body size compared with age, height, and weight. Most strain values displayed a second-order polynomial relationship with body surface area. Z score equations were computed with adequate normal distributions and without residual associations in relation to BSA for most strain parameters., Conclusions: There was a weak but significant influence of body size on most left ventricular circumferential and longitudinal systolic strain parameters used in pediatric echocardiography. Z scores are presented for strain measurements normalized to body surface area and adjusted for heteroscedasticity. The use of these normalized values may reduce the risk for misclassification caused by normal variation in myocardial strain values during growth., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)
Published: 2016
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36. Low socioeconomic status is associated with adverse events in children and teens on insulin pumps under a universal access program: a population-based cohort study.

Author: Shulman R, Stukel TA, Miller FA, Newman A, Daneman D, Wasserman JD, and Guttmann A
Abstract: Objective: To describe adverse events in pediatric insulin pump users since universal funding in Ontario and to explore the role of socioeconomic status and 24-hour support., Research Design and Methods: Population-based cohort study of youth (<19 years) with type 1 diabetes (n=3193) under a universal access program in Ontario, Canada, from 2006 to 2013. We linked 2012 survey data from 33 pediatric diabetes centers to health administrative databases. The relationship between patient and center-level characteristics and time to first diabetic ketoacidosis (DKA) admission or death was tested using a Cox proportional hazards model and the rate of diabetes-related emergency department visits and hospitalizations with a Poisson model, both using generalized estimating equations., Results: The rate of DKA was 5.28/100 person-years and mortality 0.033/100 person-years. Compared with the least deprived quintile, the risk of DKA or death for those in the most deprived quintile was significantly higher (HR 1.58, 95% CI 1.05 to 2.38) as was the rate of diabetes-related acute care use (RR 1.60, 95% CI 1.27 to 2.00). 24-hour support was not associated with these outcomes. Higher glycated hemoglobin, prior DKA, older age, and higher nursing patient load were associated with a higher risk of DKA or death., Conclusions: The safety profile of pump therapy in the context of universal funding is similar to other jurisdictions and unrelated to 24-hour support. Several factors including higher deprivation were associated with an increased risk of adverse events and could be used to inform the design of interventions aimed at preventing poor outcomes in high-risk individuals.
Published: 2016
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37. The state of child and youth well-being in Canada: Not even close to good enough!

Author: Daneman D, Stanwick R, and Williams RC
Published: 2016
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38. Association Between Plasma Uric Acid Levels and Cardiorenal Function in Adolescents With Type 1 Diabetes.

Author: Lytvyn Y, Mahmud FH, Daneman D, Deda L, Dunger DB, Deanfield J, Dalton RN, Elia Y, Har R, Bradley TJ, Slorach C, Hui W, Moineddin R, Reich HN, Scholey JW, Mertens L, Sochett E, and Cherney DZ
Subjects: Adolescent, Blood Pressure, Cardio-Renal Syndrome complications, Case-Control Studies, Child, Creatinine blood, Diabetes Mellitus, Type 1 complications, Endothelium physiopathology, Female, Glomerular Filtration Rate, Humans, Male, Pulse Wave Analysis, Serum Albumin metabolism, Vascular Stiffness, Cardio-Renal Syndrome blood, Cardiovascular System physiopathology, Diabetes Mellitus, Type 1 blood, Kidney physiopathology, Uric Acid blood
Abstract: Objective: The relationship between plasma uric acid (PUA) and renal and cardiovascular parameters in adolescents with type 1 diabetes (T1D) is not well understood. Our aims in this exploratory analysis were to study the association between PUA and estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), blood pressure, endothelial function, and arterial stiffness in T1D adolescents. These associations were also studied in healthy control (HC) subjects., Research Design and Methods: We studied 188 T1D subjects recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) and 65 HC subjects. Baseline PUA, eGFRcystatin C, ACR, blood pressure, flow-mediated dilation (FMD), and carotid-femoral pulse wave velocity (PWV) were measured., Results: PUA was lower in T1D vs. HC subjects (242 ± 55 vs. 306 ± 74 μmol/L, respectively; P < 0.0001). Higher PUA was inversely associated with eGFR in T1D subjects (r = -0.48, P < 0.0001) even after correction for baseline clinical demographic characteristics. PUA was not associated with ACR in T1D after adjustment for potential confounders such as eGFR. For cardiovascular parameters, PUA levels did not associate with systolic blood pressure, FMD, or PWV in T1D or HC subjects., Conclusions: Even within the physiological range, PUA levels were significantly lower in T1D adolescent patients compared with HC subjects. There was an inverse relationship between PUA and eGFR in T1D, likely reflecting an increase in clearance. There were no associations observed with ACR, blood pressure, arterial stiffness, or endothelial function. Thus, in contrast with adults, PUA may not yet be associated with cardiorenal abnormalities in adolescents with T1D., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
Published: 2016
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39. Assessing social determinants of health in a pediatric diabetes clinical research trial: Are recruited subjects representative of the larger clinical population?

Author: Inman M, Daneman D, Curtis J, Sochett E, Elia Y, Dunger DB, Deanfield J, and Mahmud FH
Subjects: Adolescent, Child, Cohort Studies, Female, Humans, Male, Pediatrics, Clinical Trials as Topic standards, Diabetes Mellitus prevention & control, Epidemiologic Research Design, Patient Selection, Social Determinants of Health
Abstract: Social determinants of health (SDH) impact clinical outcomes and are often poorly described in research trials. Using a validated tool, SDH dimensions were compared between adolescents enrolled and not enrolled into a large diabetes study. We observed that our study cohort reflected a SDH profile mirroring the eligible population., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
Published: 2016
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40. The urinary inflammatory profile in gluten free diet-adherent adolescents with type 1 diabetes and celiac disease.

Author: De Melo EN, Deda L, Har R, Reich HN, Scholey JW, Daneman D, Moineddin R, Motran L, Elia Y, Cherney DZ, Sochett EB, and Mahmud FH
Subjects: Adolescent, Blood Proteins analysis, Case-Control Studies, Celiac Disease blood, Celiac Disease complications, Child, Cytokines analysis, Cytokines blood, Cytokines urine, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 complications, Female, Humans, Inflammation blood, Male, Proteome analysis, Celiac Disease diet therapy, Celiac Disease urine, Diabetes Mellitus, Type 1 diet therapy, Diabetes Mellitus, Type 1 urine, Diet, Gluten-Free, Inflammation urine, Patient Compliance statistics & numerical data
Abstract: Aims: Our objective was to characterize urinary cytokine/chemokine excretion in adolescents with type 1 diabetes (T1D) and celiac disease (CD) adhering to gluten free diet (GFD) compared to matched T1D patients and healthy control (HC) group from an existing cohort., Methods: Eighteen T1D+CD+GFD patients aged 10-16years were identified and matched 2:1 for age, sex, diabetes duration and glycated hemoglobin to 36 T1D subjects and 36 HC. T1D+CD+GFD patients were adherent with a GFD. Urine and serum levels of cytokines/chemokines as well as baseline clinical and laboratory variables were assessed., Results: T1D+CD+GFD patients exhibited lower levels of urinary IL-1B, IL-4, IL-5 (p<0.05) and IFN-γ, IL-8 and G-CSF levels (p<0.07) compared with T1D patients. Urinary biomarker levels between T1D+CD+GFD and HC were mostly similar. In contrast, urinary FGF-2, Flt-3, IL-1B, IL-1RA, IL-4, IL-5, IL-9, IL-10, IL-12p40, IL-15, MIP-1β, and TNF-β (p<0.05) were higher in T1D patients compared to HC. Similar levels of inflammatory markers were seen in the serum for all 3 groups., Conclusions: T1D+CD+GFD patients demonstrated decreased urinary inflammatory cytokine/chemokines compared to T1D and some similar to HC, which is suggestive of a potential modulatory role of treated CD on urinary markers., (Copyright © 2015 Elsevier Inc. All rights reserved.)
Published: 2016
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41. Prolactin Levels During Long-Term Risperidone Treatment in Children and Adolescents: a reanalysis of data.

Author: Findling RL and Daneman D
Subjects: Adolescent, Antipsychotic Agents administration & dosage, Child, Data Interpretation, Statistical, Female, Humans, Male, Risperidone administration & dosage, Antipsychotic Agents adverse effects, Attention Deficit and Disruptive Behavior Disorders drug therapy, Genital Diseases, Female chemically induced, Gynecomastia chemically induced, Menstruation Disturbances chemically induced, Prolactin drug effects, Risperidone adverse effects
Published: 2016
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42. Valuing technology: A qualitative interview study with physicians about insulin pump therapy for children with type 1 diabetes.

Author: Shulman R, Miller FA, Daneman D, and Guttmann A
Subjects: Biomedical Technology, Child, Health Policy, Humans, Interviews as Topic, Ontario, Pediatrics, Qualitative Research, Diabetes Mellitus, Type 1 drug therapy, Insulin Infusion Systems, Physicians psychology
Abstract: Insulin pumps for children with type 1 diabetes have been broadly adopted despite equivocal evidence about comparative effectiveness. To understand why and inform policy related to public funding for new technologies, we explored how physicians interpret the value of pumps. We conducted open-ended, semi-structured interviews with 16 physicians from a pediatric diabetes network in Ontario, Canada, and analyzed the data using interpretive description. Respondents recognized that pumps fell short of expectations because they required hard work, as well as family and school support. Yet, pumps were valued for their status as new technologies and as a promising step in developing future technology. In addition, they were valued for their role within a therapeutic relationship, given the context of chronic childhood disease. These findings identify the types of beliefs that influence the adoption and diffusion of technologies. Some beliefs bear on hopes for new technology that may inappropriately hasten adoption, creating excess cost with little benefit. On the other hand, some beliefs identify potential benefits that are not captured in effectiveness studies, but may warrant consideration in resource allocation decisions. Still others suggest the need for remediation, such as those bearing on disparity in pump use by socioeconomic status. Understanding how technologies are valued can help stakeholders decide how to address such beliefs and expectations in funding decisions and implementation protocols., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
Published: 2016
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43. Preventing Diabetic Ketoacidosis.

Author: Jefferies CA, Nakhla M, Derraik JG, Gunn AJ, Daneman D, and Cutfield WS
Subjects: Adolescent, Age Factors, Child, Child, Preschool, Diabetic Ketoacidosis complications, Female, Humans, Infant, Male, Risk Factors, Sex Factors, Diabetes Mellitus, Type 1 complications, Diabetic Ketoacidosis etiology, Diabetic Ketoacidosis prevention & control
Abstract: Diabetic ketoacidosis (DKA) is a major cause of morbidity and mortality in children with type 1 diabetes mellitus (T1DM). This article examines the factors associated with DKA in children with T1DM, both at first presentation and in recurrent cases. The challenge for future research is to find effective ways to improve primary care physician and general community awareness of T1DM to reduce DKA at presentation and develop practical, cost-effective programs to reduce recurrent DKA., (Copyright © 2015 Elsevier Inc. All rights reserved.)
Published: 2015
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44. Pediatric Diabetes and Endocrinology.

Author: Palmert MR and Daneman D
Subjects: Humans, Diabetes Mellitus, Endocrinology, Pediatrics
Published: 2015
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45. Eating Disorders in Girls and Women With Type 1 Diabetes: A Longitudinal Study of Prevalence, Onset, Remission, and Recurrence.

Author: Colton PA, Olmsted MP, Daneman D, Farquhar JC, Wong H, Muskat S, and Rodin GM
Subjects: Adolescent, Age of Onset, Child, Diabetes Mellitus, Type 1 epidemiology, Feeding Behavior, Feeding and Eating Disorders epidemiology, Feeding and Eating Disorders therapy, Female, Humans, Longitudinal Studies, Ontario epidemiology, Prevalence, Recurrence, Young Adult, Diabetes Mellitus, Type 1 complications, Feeding and Eating Disorders complications
Abstract: Objective: Girls and women with type 1 diabetes are at increased risk for developing eating disorders (EDs), and these disorders are associated with serious diabetes-related medical complications. This study describes the longitudinal course of disturbed eating behavior (DEB) and EDs in a cohort with type 1 diabetes., Research Design and Methods: A total of 126 girls with type 1 diabetes receiving care for diabetes at The Hospital for Sick Children in Toronto participated in a series of seven interview-based assessments of ED behavior and psychopathology over a 14-year period, beginning in late childhood. Survival analysis was used., Results: Mean age was 11.8 ± 1.5 years at time 1 and 23.7 ± 2.1 years at time 7. At time 7, 32.4% (23/71) met the criteria for a current ED, and an additional 8.5% (6/71) had a subthreshold ED. Mean age at ED onset (full syndrome or below the threshold) was 22.6 years (95% CI 21.6-23.5), and the cumulative probability of onset was 60% by age 25 years. The average time between onset of ED and subsequent ED remission was 4.3 years (95% CI 3.1-5.5), and the cumulative probability of remission was 79% by 6 years after onset. The average time between remission of ED and subsequent recurrence was 6.5 years (95% CI 4.4-8.6), and the cumulative probability of recurrence was 53% by 6 years after remission., Conclusions: In this longitudinal study, EDs were common and persistent, and new onset of ED was documented well into adulthood. Further research regarding prevention and treatment for this vulnerable group is urgently needed., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
Published: 2015
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46. Child well-being in Canada: how can we improve on "average"?

Author: Hepburn CM and Daneman D
Subjects: Canada, Child, Humans, United Nations, Child Welfare statistics & numerical data, Developed Countries statistics & numerical data, Health Policy
Published: 2015
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47. The urinary cytokine/chemokine signature of renal hyperfiltration in adolescents with type 1 diabetes.

Author: Har RL, Reich HN, Scholey JW, Daneman D, Dunger DB, Moineddin R, Dalton RN, Motran L, Elia Y, Deda L, Ostrovsky M, Sochett EB, Mahmud FH, and Cherney DZ
Subjects: Adolescent, Albuminuria, Biomarkers blood, Biomarkers urine, Blood Glucose, Child, Creatinine urine, Cystatin C blood, Diabetic Nephropathies pathology, Female, Glucose Clamp Technique, Humans, Hyperglycemia pathology, Kidney, Kidney Function Tests, Male, Chemokines blood, Chemokines urine, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 urine, Glomerular Filtration Rate physiology
Abstract: Objective: Urinary cytokine/chemokine levels are elevated in adults with type 1 diabetes (T1D) exhibiting renal hyperfiltration. Whether this observation extends to adolescents with T1D remains unknown. Our first objective was to determine the relationship between hyperfiltration and urinary cytokines/chemokines in normotensive, normoalbuminuric adolescents with T1D using GFR(cystatin). Our second aim was to determine the relationship between urine and plasma levels of inflammatory biomarkers, to clarify the origin of these factors., Methods: Urine and serum cytokines/chemokines (Luminex platform) and GFR(cystatin) were measured in normofiltering (n = 111, T1D-N, GFR<135 ml/min/1.73 m(2)) and hyperfiltering (n = 31, T1D-H, GFR ≥ 135 ml/min/1.73 m(2)) adolescents with T1D (ages 10-16), and in age and sex matched healthy control subjects (HC, n = 59)., Results: We noted significant step-wise increases in urinary cytokine/chemokine excretion according to filtration status with highest levels in T1D-H, with parallel trends in serum analyte concentrations. After adjusting for serum glucose at the time of sampling, differences in urinary cytokine excretion were not statistically significant. Only serum IL-2 significantly differed between HC and T1D (p = 0.0076)., Conclusions: Hyperfiltration is associated with increased urinary cytokine/chemokine excretion in T1D adolescents, and parallel trends in serum cytokine concentration. The GFR-associated trends in cytokine excretion may be driven by the effects of ambient hyperglycemia. The relationship between hyperfiltration, glycemia, and variations in serum and urine cytokine expression and their impact on future renal and systemic vascular complications requires further study.
Published: 2014
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48. Early atherosclerosis relates to urinary albumin excretion and cardiovascular risk factors in adolescents with type 1 diabetes: Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT).

Author: Maftei O, Pena AS, Sullivan T, Jones TW, Donaghue KC, Cameron FJ, Davis E, Cotterill A, Craig ME, Gent R, Dalton N, Daneman D, Dunger D, Deanfield J, and Couper JJ
Subjects: Adolescent, Albuminuria epidemiology, Atherosclerosis etiology, Biomarkers metabolism, Blood Pressure physiology, Case-Control Studies, Child, Cholesterol, LDL blood, Cross-Sectional Studies, Endothelium, Vascular metabolism, Female, Humans, Male, Risk Factors, Atherosclerosis physiopathology, Cardiovascular Diseases etiology, Carotid Intima-Media Thickness, Diabetes Mellitus, Type 1 physiopathology
Abstract: Objective: The origins of cardiovascular and renal disease in type 1 diabetes begin during childhood. We aimed to evaluate carotid (cIMT) and aortic intima-media thickness (aIMT) and their relationship with cardiovascular risk factors and urinary albumin excretion in adolescents with type 1 diabetes in the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT)., Research Design and Methods: A total of 406 adolescents with type 1 diabetes, who were 14.1 ± 1.9 years old with type 1 diabetes duration of 6.7 ± 3.7 years, and 57 age-matched control subjects provided clinical and biochemical data and ultrasound measurements of vascular structure (cIMT and aIMT). Vascular endothelial and smooth muscle function was also measured in 123 of 406 with type 1 diabetes and all control subjects., Results: In type 1 diabetic subjects, mean/maximal aIMT (P < 0.006; <0.008), but not mean/maximal cIMT, was greater than in control subjects. Mean/maximal aIMT related to urinary albumin-to-creatinine ratio (multiple regression coefficient [SE], 0.013 [0.006], P = 0.03; 0.023 [0.007], P = 0.002), LDL cholesterol (0.019 [0.008], P = 0.02; 0.025 [0.011], P = 0.02), and age (0.010 [0.004], P = 0.004; 0.012 [0.005], P = 0.01), independent of other variables. Mean/maximal cIMT was greater in males (0.023 [0.006], P = 0.02; 0.029 [0.007], P < 0.0001), and mean cIMT related independently to systolic blood pressure (0.001 [0.001], P = 0.04). Vascular smooth muscle function related to aIMT and cIMT but not to urinary albumin excretion., Conclusions: aIMT may be a more sensitive marker of atherosclerosis than cIMT in type 1 diabetes during mid-adolescence. Higher urinary albumin excretion, even within the normal range, is associated with early atherosclerosis and should direct clinical attention to modifiable cardiovascular risk factors., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
Published: 2014
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