The Effect of Ethnicity in the Rate of Beta-Cell Functional Loss in the First 3 Years After Type 1 Diabetes Diagnosis
Authors: Tosur Mustafa , Cleves Mario A , Sosenko Jay M , Libman Ingrid , Baidal David A , Balasubramanyam Ashok , Redondo Maria J ,   Type 1 Diabetes TrialNet Study Group, Greenbaum C J , Anderson M , Antinozzi P , Atkinson M , Battaglia M , Becker D , Bingley P , Bosi E , Buckner J , Colman P , DiMeglio L , Gitelman S , Goland R , Gottlieb P , Herold K , Insel R , Kay T , Knip M , Krischer J , Lernmark A , Marks J B , Moran A , Palmer J , Peakman M , Philipson L , Pugliese A , Raskin P , Redondo M , Rodriguez H , Roep B , Russell W , Spain L , Schatz D A , Sosenko J , Wherrett D , Wilson D , Winter W , Ziegler A , Benoist C , Blum J , Bourcier K , Chase P , Clare-Salzler M , Clynes R , Eisenbarth G , Fathman C G , Grave G , Hering B , Kaufman F , Leschek E , Mahon J , Nanto-Salonen K , Nepom G , Orban T , Parkman R , Pescovitz M , Peyman J , Roncarolo M , Savage P , Simell O , Sherwin R , Siegelman M , Skyler J S , Steck A , Thomas J , Trucco M , Wagner J , Greenbaum Carla J , Bourcier Katarzyna , Insel Richard , Krischer Jeffrey P , Leschek Ellen , Rafkin Lisa , Spain Lisa , Cowie Catherine , Foulkes Mary , Krause-Steinrauf Heidi , Lachin John M , Malozowski Saul , Peyman John , Ridge John , Savage Peter , Skyler Jay S , Zafonte Stephanie J , Greenbaum Carla J , Kenyon Norma S , Rafkin Lisa , Santiago Irene , Sosenko Jay M , Skyler Jay S , Krischer Jeffrey P , Bundy Brian , Abbondondolo Michael , Adams Timothy , Amado Darlene , Asif Ilma , Boonstra Matthew , Bundy Brian , Burroughs Cristina , Cuthbertson David , Deemer Mary , Eberhard Christopher , Fiske Steve , Ford Julie , Garmeson Jennifer , Guillette Heather , Geyer Susan , Hays Brian , Henderson Courtney , Henry Martha , Heyman Kathleen , Hsiao Belinda , Karges Christina , Keaton Nichole , Kinderman Amanda , Law Pat , Leinbach Ashely , Linton Cristin , Liu Shu , Lloyd Jennifer , Malloy Jamie , Maddox Kristin , Martin Julie , Miller Jessica , Milliot Eric , Moore Margaret , Muller Sarah , Nguyen Thuy , O’Donnell Ryan , Oduah Vanessa , Pilger Jennifer , Roberts Amy , Sadler Kelly , Stavros Tina , Tamura Roy , Wood Keith , Xu Ping , Young Kenneth , Alies Persida , Badias Franz , Baker Aaron , Bassi Monica , Beam Craig , Boulware David , Bounmananh London , Bream Susan , Freeman Doug , Gough Jessica , Ginem Jinin , Granger Moriah , Kieffer Mary Holloway Michelle , Lane Page , Nallamshetty Lavanya , Parrimon Yazandra , Paulus Kate , Ramiro Joy , Ritzie AQesha Luvon , Sharma Archana , Shor Audrey , Song Xiaohong , Terry Amanda , Weinberger Jeanne , Wootten Margaret , Lachin John M , Foulkes Mary , Harding Pamela , Krause-Steinrauf Heidi , McDonough Susan , McGee Paula F , Hess Kimberly Owens , Phoebus Donna , Quinlan Scott , Raiden Erica , Greenbaum Carla J , Batts Emily , Buddy Chris , Kirpatrick Kristin , Ramey Mary , Shultz Ann , Webb Chris , Romesco Melita , Fradkin Judith , Leschek Ellen , Spain Lisa , Savage Peter , Blumberg Emily , Beck Gerald , Brillon David , Gubitosi-Klug Rose , Laffel Lori , Veatch Robert , Wallace Dennis , Braun Jonathan , Lernmark Ake , Lo Bernard , Mitchell Herman , Naji Ali , Nerup Jorn , Orchard Trevor , Steffes Michael , Tsiatis Anastasios , Zinman Bernard , Loechelt Brett , Baden Lindsey , Green Michael , Weinberg Adriana , Marcovina Santica , Palmer Jerry P , Weinberg Adriana , Yu Liping , Babu Sunanda , Winter William , Eisenbarth George S , Bingley Polly , Clynes Raphael , DiMeglio Linda , Eisenbarth George , Greenbaum Carla , Hays Brian , Krischer Jeffrey , Leschek Ellen , Marks Jennifer , Matheson Della , Rafkin Lisa , Rodriguez Henry , Skyler Jay , Sosenko Jay , Spain Lisa , Wilson Darrell , Redondo Maria J , Gomez David , Zheng Xiati , Pena Sandra , Pietropaolo Massimo , Greenbaum Carla , Batts Emily , Brown Tyler , Buckner Jane , Dove Angela , Hammond Marissa , Hefty Deborah , Klein Jani , Kuhns Kristen , Letlau McKenzie , Lord Sandra , McCulloch-Olson Marli , Miller Lisa , Nepom Gerald , Odegard Jared , Ramey Mary , Sachter Elaine , St. Marie Marissa , Stickney Kimberly , VanBuecken Dana , Vellek Ben , Webber Christine , Allen Laurie , Bollyk Jenna , Hilderman Nicole , Ismail Hebatullah , Lamola Steve , Sanda Srinath , Vendettuoli Heather , Tridgell David , Monzavi Roshanak , Bock Meredith , Fisher Lynda , Halvorson Mary , Jeandron Debra , Kim Mimi , Wood Jamie , Geffner Mitchell , Kaufman Francine , Parkman Robertson , Salazar Christine , Goland Robin , Clynes Raphael , Cook Steve , Freeby Matthew , Gallagher Mary Pat , Gandica Rachelle , Greenberg Ellen , Kurland Amy , Pollak Sarah , Wolk Amy , Chan Mary , Koplimae Linda , Levine Elizabeth , Smith Kelly , Trast Jeniece , DiMeglio Linda , Blum Janice , Evans-Molina Carmella , Hufferd Robin , Jagielo Bonnie , Kruse Christy , Patrick Vanessa , Rigby Mark , Spall Maria , Swinney Kim , Terrell Jennifer , Christner Lyla , Ford LeeAnn , Lynch Sheryl , Menendez Martha , Merrill Patricia , Pescovitz Mark , Rodriguez Henry , Alleyn Cielo , Baidal David , Fay Steve , Gaglia Jason , Resnick Brittany , Szubowicz Sarah , Weir Gordon , Benjamin Ronald , Conboy Debbie , deManbey Andrea , Jackson Richard , Jalahej Heyam , Orban Tihmar , Ricker Alyne , Wolfsdorf Joseph , Zhang Hui H , Wilson Darrell , Aye Tandy , Baker Bonita , Barahona Karen , Buckingham Bruce , Esrey Kerry , Esrey Trudy , Fathman Garry , Snyder Radhika , Aneja Beenu , Chatav Maya , Espinoza Oralia , Frank Eliana , Liu Jenny , Perry Jennifer , Pyle Rebecca , Rigby Alison , Riley Kristin , Soto Adriana , Gitelman Stephen , Adi Saleh , Anderson Mark , Berhel Ashley , Breen Kathy , Fraser Kathleen , Gerard-Gonzalez Andrea , Jossan Paula , Lustig Robert , Moassesfar Sara , Mugg Amy , Ng David , Prahalod Priya , Rangel-Lugo Martha , Sanda Srinath , Tarkoff Joshua , Torok Christine , Wesch Rebecca , Aslan Ivy , Buchanan Jeanne , Cordier Jennifer , Hamilton Celia , Hawkins Louise , Ho Thu , Jain Anjali , Ko Karen , Lee Theresa , Phelps Shelly , Rosenthal Stephen , Sahakitrungruang Taninee , Stehl Lorraine , Taylor Lisa , Wertz Marcia , Wong Jenise , Philipson Louis , Briars Rosemary , Devine Nancy , Littlejohn Elizabeth , Grant Tiffany , Gottlieb Peter , Klingensmith Georgeanna , Steck Andrea , Alkanani Aimon , Bautista Kimberly , Bedoy Ruth , Blau Aaron , Burke Betsy , Cory Laraine , Dang MyLinh , Fitzgerald-Miller Lisa , Fouts Alex , Gage Vicky , Garg Satish , Gesauldo Patricia , Gutin Raymond , Hayes Cory , Hoffman Michelle , Ketchum Kaitlin , Logsden-Sackett Nyla , Maahs David , Messer Laurel , Meyers Lisa , Michels Aaron , Peacock Stesha , Rewers Marian , Rodriguez Perla , Sepulbeda Flor , Sippl Rachel , Steck Andrea , Taki Iman , Tran Bao-Khan , Tran Tuan , Wadwa R Paul , Zeitler Philip , Barker Jennifer , Barry Sandra , Birks Laurie , Bomsburger Leah , Bookert Terra , Briggs Leah , Burdick Patricia , Cabrera Rosio , Chase Peter , Cobry Erin , Conley Amy , Cook Gabrielle , Daniels Joseph , DiDomenico Dominic , Eckert Jennifer , Ehler Angelica , Eisenbarth George , Fain Pamela , Fiallo-Scharer Rosanna , Frank Nicole , Goettle Hannah , Haarhues Michelle , Harris Sherrie , Horton Lauren , Hutton John , Jeffrrey Joy , Jenison Rachael , Jones Kelly , Kastelic Whitney , King Maria Amelia , Lehr Debbie , Lungaro Jenna , Mason Kendra , Maurer Heather , Nguyen Luy , Proto Allison , Realsen Jaime , Schmitt Kristina , Schwartz Mara , Skovgaard San , Smith Jennifer , Vanderwel Brandon , Voelmle Mary , Wagner Rebecca , Wallace Amy , Walravens Philip , Weiner Laurie , Westerhoff Becky , Westfall Emily , Widmer Katina , Wright Hali , Schatz Desmond , Abraham Annie , Atkinson Mark , Cintron Miriam , Clare-Salzler Michael , Ferguson Jessica , Haller Michael , Hosford Jennifer , Mancini Diane , Rohrs Hank , Silverstein Janet , Thomas Jamie , Winter William , Cole Gloria , Cook Roberta , Coy Ryan , Hicks Elena , Lewis Nancy , Marks Jennifer , Pugliese Alberto , Blaschke Carlos , Matheson Della , Pugliese Alberto , Sanders-Branca Natalia , Sosenko Jay , Arce Luz Arazo Ray , Cisneros Mario , Sabbag Samir , Moran Antoinette , Gibson Carrie , Fife Brian , Hering Bernhard , Kwong Christine , Leschyshyn Janice , Nathan Brandon , Pappenfus Beth , Street Anne , Boes Mary Ann , Eck Sarah Peterson , Finney Lois , Fischer Theresa Albright , Martin Andrea , Muzamhindo Chenai Jacqueline , Rhodes Missy , Smith Jennifer , Wagner John , Wood Bryan , Becker Dorothy , Delallo Kelli , Diaz Ana , Elnyczky Barbara , Libman Ingrid , Pasek Beata , Riley Karen , Trucco Massimo , Copemen Brian , Gwynn Diane , Toledo Frederico , Rodriguez Henry , Bollepalli Sureka , Diamond Frank , Eyth Emily , Henson Danielle , Lenz Anne , Shulman Dorothy , Raskin Phillip , Adhikari Soumya , Dickson Brian , Dunnigan Erin , Lingvay Ildiko , Pruneda Lourdes , Ramos-Roman Maria , Raskin Philip , Rhee Chanhaeng , Richard John , Siegelman Mark , Sturges Daytheon , Sumpter Kathryn , White Perrin , Alford Marilyn , Arthur Jamie , Aviles-Santa M Larissa , Cordova Erica , Davis Renee , Fernandez Stefani , Fordan Steve , Hardin Tauri , Jacobs Aris , Kaloyanova Polina , Lukacova-Zib Ivanna , Mirfakhraee Sasan , Mohan Alok , Noto Hiroshi , Smith Oralenda , Torres Nenita , Wherrett Diane , Balmer Diana , Eisel Lesley , Kovalakovska Roze , Mehan Mala , Sultan Farah , Ahenkorah Brenda , Cevallos Jose , Razack Natasha , Mary Ricci Jo , Rhode Angela , Srikandarajah Mithula , Steger Rachel , Russell William E , Black Margo , Brendle Faith , Brown Anne , Moore Daniel , Pittel Eric , Robertson Alyssa , Shannon April , Thomas James W , Herold Kevan , Feldman Laurie , Sherwin Robert , Tamborlane William , Weinzimer Stuart , Toppari Jorma , Kallio Tiina , Kärkkäinen Maarit , Mäntymäki Elina , Niininen Tiina , Nurmi Birgitta , Rajala Petro , Romo Minna , Suomenrinne Sointu , Näntö-Salonen Kirsti , Simell Olli , Simell Tuula , Bosi Emanuele , Battaglia Manuela , Bianconi Eleonora , Bonfanti Riccardo , Grogan Pauline , Laurenzi Andrea , Martinenghi Sabina , Meschi Franco , Pastore Matteo , Falqui Luca , Muscato Maria Teresa , Viscardi Matteo , Bingley Polly , Castleden Harriet , Farthing Nicola , Loud Sam , Matthews Claire , McGhee Jennifer , Morgan Ann , Pollitt Joanna , Elliot-Jones Rebecca , Wheaton Carole , Knip Mikael , Siljander Heli , Suomalainen Heli , Colman Peter , Healy Felicity , Mesfin Shelley , Redl Leanne , Wentworth John , Willis Jinny , Farley Maree , Harrison Leonard , Perry Christine , Williams Fiona 
Published: June 2020

Abstract

Objective
We set forth to compare ethnicities for metabolic and immunological characteristics at the clinical diagnosis of type 1 diabetes (T1D) and assess the effect of ethnicity on beta-cell functional loss within 3 years after clinical diagnosis.

Research Methods and Design
We studied participants in TrialNet New Onset Intervention Trials (n = 624, median age = 14.4 years, 58% male, 8.7% Hispanic) and followed them prospectively for 3 years. Mixed meal tolerance tests (MMTT) were performed within 6 months following clinical diagnosis and repeated semiannually. Unless otherwise indicated, analyses were adjusted for age, sex, BMI Z-score, and diabetes duration.

Results
At T1D clinical diagnosis, Hispanics, compared with non-Hispanic whites (NHW), had a higher frequency of diabetic ketoacidosis (DKA) (44.7% vs 25.3%, OR = 2.36, P = 0.01), lower fasting glucose (97 vs 109 mg/dL, P = 0.02) and higher fasting C-peptide (1.23 vs 0.94 ng/mL, P = 0.02) on the first MMTT, and higher frequency of ZnT8 autoantibody positivity (n = 201, 94.1% vs 64%, OR = 7.98, P = 0.05). After exclusion of participants in experimental arms of positive clinical trials, C-peptide area under the curve (AUC) trajectories during the first 3 years after clinical diagnosis were not significantly different between Hispanics and NHW after adjusting for age, sex, BMI-z score, and DKA (n = 413, P = 0.14).

Conclusion
Despite differences in the metabolic and immunological characteristics at clinical diagnosis of T1D between Hispanics and NHW, C-peptide trajectories did not differ significantly in the first 3 years following clinical diagnosis after adjustment for body mass index and other confounders. These findings may inform the design of observational studies and intervention trials in T1D.