Association of Baseline Characteristics With Insulin Sensitivity and β-Cell Function in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort
Authors: Rasouli Neda , Younes Naji , Utzschneider Kristina M. , Inzucchi Silvio E. , Balasubramanyam Ashok , Cherrington Andrea L. , Ismail-Beigi Faramarz , Cohen Robert M. , Olson Darin E. , DeFronzo Ralph A. , Herman William H. , Lachin John M. , Kahn Steven E. ,   GRADE Research Group, Crandall Jill P. , McKee Melissa Diane , Brown-Friday Janet , Xhori Entila , Ballentine-Cargill Keisha , Duran Sally , Lukin Jennifer , Beringher Stephanie , de la torre Susana Gonzalez , Phillips Lawrence , Burgess Elizabeth , Olson Darin , Rhee Mary , Wilson Peter , Raines Tasha Stephanie , Costello Julie , Gullett Chona , Maher-Albertelli Maxine , Morehead Folayan , Mungara Radhika , Person Saranjit , Savoye Louise , Sibymon Mabil , Tanukonda Sridhar , Ann White Carol , Holloway Leah , Adams Cynthia , Ross April , Balasubramanyam Ashok , Gonzalez Erica , Wright Charlyne , Hollander Priscilla , Roe Erin , Uy Analyn , Burt Polly , Estrada Lorie , Chionh Kris , Ismail-Beigi Faramarz , Falck-Ytter Corinna , Kassem Laure Sayyed , Sood Ajay , Tiktin Margaret , Cramer Bethany , Iacoboni Jacalyn , Kononets Maria V. , Kulow Tanya , Newman Cynthia , Stancil Katherine A. , Sanders Cristina , Tucker Lisa , Werner Amanda , Krol Adrienne , McPhee Gloria , Patel Christine , Colosimo Linda , Goland Robin , Pring James , Kringas Patricia , Tejada Jessica , Hausheer Camille , Schneier Harvey , Gumpel Kelly , Kirpitch Amanda , Green Jennifer B. , AbouAssi Hiba , Chatterjee Ranee , Feinglos Mark N. , Jones Jennifer English , Khan Shubi A. , Kimpel Jeanne B. , Zimmer Ronna P. , Furst Mary , Satterwhite Barbara M. , Thacker Connie R. , Kreider Kathryn Evans , Mather Kieren J. , Lteif Amale , Hamilton Tonya , Patel Nick , Riera Gabriela , Jackson Marcia , Pirics Vivian , Howard Devin , Aguillar Danielle , Hurt Sloan , Bergenstal Richard , Carlson Anders , Martens Thomas , Johnson Mary , Hill Renae , Hyatt Jamie , Jensen Connie , Madden Marcia , Martin Dianna , Willis Holly , Konerza Wanda , Passi Rebecca , Kleeberger Kathleen , Fortmann Stephen , Herson Michael , Mularski Karen , Glauber Harry , Prihoda James , Ash Britt , Carlson Christina , Ramey Phyllis Anne , Schield Emily , Torgrimson-Ojerio Britta , Arnold Kathy , Kauffman Bryan , Panos Elease , Sahnow Samantha , Bays Kristi , Cook Jennifer , Gluth Jennifer , Sasaki Debra , Schell Katrina , Criscola Jennifer , Friason Camille , Jones Suzi , Nazarov Sergey , Barzilay Joshua , Rassouli Negah , Puttnam Rachel , Curtis Michelle , Stokes Kia , Hollis Bonita , Sanders-Jones Cynthia , Nelson Roslin , El-Haqq Zakiah , Kolli Abby , Tran Tu , Wexler Deborah , Larkin Mary , Meigs James , Dushkin Amy , Rocchio Gianna , Chambers Brittany , Yepes Mike , Steiner Barbara , Dulin Hilary , Cayford Melody , DeManbey Andrea , Gurry Lindsey , Hillard Mallory , Martin Kimberly , Stevens Christine , Thangthaeng Nopporn , Kochis Raquel , Raymond Elyse , Ripley Valerie , Park Jean , Aroda Vanita , Ghazi Adline , Loveland Amy , Hurtado Maria , Kuhn Alexander , Mofor Florence , Florez Hermes J. , Valencia Willy Marcos , Marks Jennifer , Oropesa-Gonzalez Lisset , Riccio Veliz Ana K. , Nieto-Martinez Ramfis , Gutt Miriam , Ahmann Andrew , Aby-Daniel Diana , Joarder Farahnaz , Morimoto Victoria , Sprague Carol , Yamashita Daisuke , Cady Nancy , Kirchhoff Patricia , Rivera-Eschright Nadia , Adducci Joseph , Gomez Brianna Morales , Goncharova Alina , Hox Sophia H. , Petrovitch Helen , Matwichyna Michael , Jenkins Victoria , Bermudez Nina O. , Ishii Renée R. , Hsia Daniel S. , Cefalu William T. , Greenway Frank L. , Waguespack Celeste , King Erin , Haynes Natalie , Thomassie Amy , Bourgeois Brandi , Hazlett Claire , Henry Robert , Mudaliar Sunder , Boeder Schafer , Pettus Jeremy , Diaz Elsa , DeLue Catherine , Castro Erick , Hernandez Sylvia , Krakoff Jonathan , Curtis Jeffrey M. , Killean Tina , Joshevama Erica , Diaz Enrique , Martin Denelle , Karshner Tracey , Albu Jeanine , Pi-Sunyer F. Xavier , Frances Sylvaine , Maggio Carol , Ellis Emily , Bastawrose Joseph , Gong Xiuqun , Banerji Mary Ann , August Phyllis , Lorber Daniel , Brown Necole M. , Josephson Debra H. , Thomas Lorraine L. , Tsovian Mari , Cherian Ajini , Jacobson Marlo H. , Mishko Motria M. , Kirkman M. Sue , Bergamo Katherine , Buse John B. , Dostou Jean , Young Laura , Goley April , Kerr Jeffrey , Largay Joseph F. , Guarda Sonia , Cuffee Juanita , Culmer Dawn , Fraser Rachael , Almeida Hope , Coffer Samantha , Debnam Elizabeth , Kiker Lauren , Morton Sarah , Garvey Kim , Fuller Gai , Garvey W. Timothy , Cherrington Andrea , Golson Dana , Griffith Olivia , Catherine Mary Robertson , Agne April , McCullars Steve , Cohen Robert M. , Craig Jacqueline , Kersey Kimberly , Rogge M. Colleen , Wilson Carla , Burton Kathryn , Lipp Sonia , Mary Beth Vonder Meulen , Rasouli Neda , Schroeder Emily , Steiner Stephanie , Baker Chelsea , Underkofler Chantal , Douglass Sara , Sivitz William , Cline Erin , Knosp Laura , McConnell Jennifer , Lowe Tamara , Herman William H. , Pop-Busui Rodica , Tan Meng H. , Martin Catherine , Waltje Andrea , Goodhall Lynn , Eggleston Rebecca , Kuo Shihchen , Bule Stephanie , Kessler Nancy , LaSalle Elizabeth , Seaquist Elizabeth R. , Bantle Anne , Kumar Anjali , Redmon Bruce , Bantle John , Harindhanavudhi Tasma , Coe Mary , Mech Michael , Taddese Abdisa , Lesne Lesia , Smitha Shannon , Desouz Cyrus , Kuechenmeister Lisa , Shivaswamy Vijay , Morales Ana Laura , Rodriguez Maria Grace , Seipel Kris , Alfred Alissa , Eggert Jenna , Lord Grace , Taylor William , Tillson Renee , Schade David S. , Adolphe Allen , Burge Mark , Duran-Valdez Elizabeth , Martinez Janae , Hernandez McGinnis Doris , Pucchetti Benjamin , Scripsick Elizabeth , DeFronzo Ralph A. , Cersosimo Eugenio , Abdul-Ghani Muhammad , Triplitt Curtis , Verastiqui Hector , Garza Rosa Irene , Wright Kathryn , Puckett Curtiss , Raskin Philip , Rhee Chanhaeng , Abraham Soma , Jordan Lin Fan , Sao Serey , Morton Luisa , Smith Oralenda , Osornio Walker Laura , Schnurr-Breen Laura , Ayala Rosa , Kraymer Robert Brian , Sturgess Daytheon , Utzschneider Kristina M. , Kahn Steven E. , Alarcon-Casas Wright Lorena , Boyko Edward J. , Tsai Elaine C. , Trence Dace L. , Fattaleh Basma N. , Montgomery Brenda K. , Atkinson Karen M. , Concepcion Tessa , Kozedub Alexandra , Moak Cameron , Rhothisen Samantha , Elasy Tom A. , Martin Stephanie , Shackelford Laura , Goidel Rita , Hinkle Nina , Lipps Hogan Janie , Lovell Cynthia , Myers Janet , McGill Janet B. , Salam Maamoun , Kissel Sarah , Schweiger Toni , Recklein Carol , Tamborlane William , Gatcomb Patricia , Camp Anne , Gulanski Barbara , Inzucchi Silvio , Pham Kim , Alguard Michele , Lessard Katarzyna , Perez Magalys , Magenheimer Elizabeth , Montoza Abmaridel , Nathan David M. , Nathan David M. , Lachin John , Buse John B. , Kahn Steven E. , Krause-Steinrauf Heidi , Larkin Mary , Tiktin Margaret , Wexler Deborah , Burch Henry B. , Linder Barbara , Bremer Andrew , Lachin John , Krause-Steinrauf Heidi , Younes Naji , Backman Michael , Bebu Ionut , Buys C.J. , Fagan Murphy Anna , Gao Yuping , Gramzinski Michaela , Hall Stephanie , Legowski Elizabeth , Arey Alyssa , Bethepu Joel , Lund Claire , Mangat Dhaliwal Pam , McGee Paula , Mesimer Emily , Ngo Lisa , Steffes Michael , Seegmiller Jesse , Saenger Amy , Arends Valerie , Gabrielson Deanna , Conner Todd , Warren Stuart , Day Jolene , Scrymgeour Alexandra , Soliman Elsayed Z. , Zhang Zhu-Ming , Campbell Charles , Hu Julie , Keasler Lisa , Hensley Susan , Li Yabing , Herman William , Martin Catherine , Waltje Andrea , Kuo Shihchen , Mihalcea Rada , Perez-Rosas Veronica , Prosser Lisa , Resnicow Kenneth , Ye Wen , Shao Hui , Zhang Ping , Luchsinger Jose , Sanchez Danurys , Burch Henry B. , Bremer Andrew , Linder Barbara , Fradkin Judith , Groessl Erik , Chong Helen , Hillery Naomi , Abdouch Ivan , Brantley Paula , Broyles Frances E. , Canaris Gay , Copeland Paul , Craine Jeri J. , Fein Warren L. , Lee Melissa S. , Meiners Rebecca , Meiners Vaughn , O’Neal Hollis , Park James E. , Sledge Edward , Steppel-Resnick Jeanne , Turchin Alexander , Brooks-Worrell Barbara , Hampe Christiane S. , Newgard Christopher B. , Palmer Jerry P. , Shojaie Ali , Higgins John , Fischer Lawrence , Golden Sherita , Gonzalez Jeffery , Naik Aanand , Walker Elizabeth , Doner Lotenberg Lynne , Gallivan Joanne M. , Lim Joanne , Tuncer Diane M. , Behringer-Massera Stephanie 
Published: December 2020

OBJECTIVE
We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA1c) and the associations with selected phenotypic characteristics.

RESEARCH DESIGN AND METHODS
This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosed &lt;10 years earlier and were on metformin monotherapy. Insulin sensitivity and β-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS
The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m2, HbA1c 7.5 ± 0.5%, and type 2 diabetes duration 4.0 ± 2.8 years. Women had higher DI than men but similar insulin sensitivity. DI was the highest in Black/African Americans, followed by American Indians/Alaska Natives, Asians, and Whites in descending order. Compared with Whites, American Indians/Alaska Natives had significantly higher HbA1c, but Black/African Americans and Asians had lower HbA1c. However, when adjusted for glucose levels, Black/African Americans had higher HbA1c than Whites. Insulin sensitivity correlated inversely with BMI, waist-to-hip ratio, triglyceride-to-HDL-cholesterol ratio (TG/HDL-C), and the presence of metabolic syndrome, whereas DI was associated directly with age and inversely with BMI, HbA1c, and TG/HDL-C.

CONCLUSIONS
In the GRADE cohort, β-cell function differed by sex and race and was associated with the concurrent level of HbA1c. HbA1c also differed among the races, but not by sex. Age, BMI, and TG/HDL-C were associated with multiple measures of β-cell function and insulin sensitivity.