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PLoS One. 2011;6(7):e21518. doi: 10.1371/journal.pone.0021518. Epub 2011 Jul 26.

TCF7L2 polymorphism, weight loss and proinsulin:insulin ratio in the diabetes prevention program.

Collaborators (424)

Bray GA, Culbert IW, Champagne CM, Eberhardt B, Greenway F, Guillory FG, Herbert AA, Jeffirs ML, Kennedy BM, Lovejoy JC, Morris LH, Melancon LE, Ryan D, Sanford DA, Smith KG, Smith LL, St Amant JA, Tulley RT, Vicknair PC, Williamson D, Zachwieja JJ, Polonsky KS, Tobian J, Ehrmann D, Matulik MJ, Clark B, Czech K, DeSandre C, Hilbrich R, McNabb W, Semenske AR, Caro JF, Watson PG, Goldstein BJ, Smith KA, Mendoza J, Liberoni R, Pepe C, Spandorfer J, Donahue RP, Goldberg RB, Prineas R, Rowe P, Calles J, Cassanova-Romero P, Florez HJ, Giannella A, Kirby L, Larreal C, McLymont V, Mendez J, Ojito J, Perry A, Saab P, Haffner SM, Montez MG, Lorenzo C, Martinez A, Hamman RF, Nash PV, Testaverde L, Anderson DR, Ballonoff LB, Bouffard A, Calonge BN, Delve L, Farago M, Hill JO, Hoyer SR, Jortberg BT, Lenz D, Miller M, Price DW, Regensteiner JG, Seagle H, Smith CM, Steinke SC, VanDorsten B, Horton ES, Lawton KE, Arky RA, Bryant M, Burke JP, Caballero E, Callaphan KM, Ganda OP, Franklin T, Jackson SD, Jacobsen AM, Kula LM, Kocal M, Malloy MA, Nicosia M, Oldmixon CF, Pan J, Quitingon M, Rubtchinsky S, Seely EW, Schweizer D, Simonson D, Smith F, Solomon CG, Warram J, Kahn SE, Montgomery BK, Fujimoto W, Knopp RH, Lipkin EW, Marr M, Trence D, Kitabchi AE, Murphy ME, Applegate WB, Bryer-Ash M, Frieson SL, Imseis R, Lambeth H, Lichtermann LC, Oktaei H, Rutledge LM, Sherman AR, Smith CM, Soberman JE, Williams-Cleaves B, Metzger BE, Johnson MK, Behrends C, Cook M, Fitzgibbon M, Giles MM, Heard D, Johnson CK, Larsen D, Lowe A, Lyman M, McPherson D, Molitch ME, Pitts T, Reinhart R, Roston S, Schinleber PA, Nathan DM, McKitrick C, Turgeon H, Abbott K, Anderson E, Bissett L, Cagliero E, Florez JC, Delahanty L, Goldman V, Poulos A, Olefsky JM, Carrion-Petersen ML, Barrett-Connor E, Edelman SV, Henry RR, Horne J, Janesch SS, Leos D, Mudaliar S, Polonsky W, Smith J, Vejvoda K, Pi-Sunyer FX, Lee JE, Allison DB, Aronoff NJ, Crandall JP, Foo ST, Pal C, Parkes K, Pena MB, Rooney ES, Van Wye GE, Viscovich KA, Marrero DG, Prince MJ, Kelly SM, Dotson YF, Fineberg ES, Guare JC, Hadden AM, Ignaut JM, Jackson ML, Kirkman MS, Mather KJ, Porter BD, Roach PJ, Rowland ND, Wheeler ML, Ratner RE, Youssef G, Shapiro S, Bavido-Arrage C, Boggs G, Bronsord M, Brown E, Cheatham WW, Cola S, Evans C, Gibbs P, Kellum T, Levatan C, Nair AK, Passaro M, Uwaifo G, Saad MF, Budget M, Jinagouda S, Akbar K, Conzues C, Magpuri P, Ngo K, Rassam A, Waters D, Xapthalamous K, Santiago JV, Dagogo-Jack S, White NH, Das S, Santiago A, Brown A, Fisher E, Hurt E, Jones T, Kerr M, Ryder L, Wernimont C, Saudek CD, Bradley V, Sullivan E, Whittington T, Abbas C, Brancati FL, Clark JM, Charleston JB, Freel J, Horak K, Jiggetts D, Johnson D, Joseph H, Loman K, Mosley H, Rubin RR, Samuels A, Stewart KJ, Williamson P, Schade DS, Adams KS, Johannes C, Atler LF, Boyle PJ, Burge MR, Canady JL, Chai L, Gonzales Y, Hernandez-McGinnis DA, Katz P, King C, Rassam A, Rubinchik S, Senter W, Waters D, Shamoon H, Brown JO, Adorno E, Cox L, Crandall J, Duffy H, Engel S, Friedler A, Howard-Century CJ, Kloiber S, Longchamp N, Martinez H, Pompi D, Scheindlin J, Violino E, Walker E, Wylie-Rosett J, Zimmerman E, Zonszein J, Orchard T, Wing RR, Koenning G, Kramer MK, Barr S, Boraz M, Clifford L, Culyba R, Frazier M, Gilligan R, Harrier S, Harris L, Jeffries S, Kriska A, Manjoo Q, Mullen M, Noel A, Otto A, Semler L, Smith CF, Smith M, Venditti E, Weinzierl V, Williams KV, Wilson T, Arakaki RF, Latimer RW, Baker-Ladao NK, Beddow R, Dias L, Inouye J, Mau MK, Mikami K, Mohideen P, Odom SK, Perry RU, Knowler WC, Cooeyate N, Hoskin MA, Percy CA, Acton KJ, Andre VL, Barber R, Begay S, Bennett PH, Benson MB, Bird EC, Broussard BA, Chavez M, Dacawyma T, Doughty MS, Duncan R, Edgerton C, Ghahate JM, Glass J, Glass M, Gohdes D, Grant W, Hanson RL, Horse E, Ingraham LE, Jackson M, Jay P, Kaskalla RS, Kessler D, Kobus KM, Krakoff J, Manus C, Michaels S, Morgan T, Nashboo Y, Nelson JA, Poirier S, Polczynski E, Reidy M, Roumain J, Rowse D, Sangster S, Sewenemewa J, Tonemah D, Wilson C, Yazzie M, Bain R, Fowler S, Brenneman T, Abebe S, Bamdad J, Callaghan J, Edelstein SL, Gao Y, Grimes KL, Grover N, Haffner L, Jones S, Jones TL, Katz R, Lachin JM, Mucik P, Orlosky R, Rochon J, Sapozhnikova A, Sherif H, Stimpson C, Temprosa M, Walker-Murray F, Marcovina S, Strylewicz G, Aldrich FA, O'Leary D, Stamm E, Rautaharju P, Prineas RJ, Alexander T, Campbell C, Hall S, Li Y, Mills M, Pemberton N, Rautaharju F, Zhang Z, Mayer-Davis E, Moran RR, Ganiats T, David K, Sarkin AJ, Eastman R, Fradkin J, Garfield S, Gregg E, Zhang P, Herman W, Florez JC, Altshuler D, de Bakker PI, Franks PW, Hanson RL, Jablonski K, Knowler WC, McAteer JB, Pollin TI, Shuldiner AR.

Author information

  • 1The Biostatistics Center, The George Washington University, Rockville, Maryland, United States of America. dppmail@bsc.gwu.edu

Abstract

AIMS:

TCF7L2 variants have been associated with type 2 diabetes, body mass index (BMI), and deficits in proinsulin processing and insulin secretion. Here we sought to test whether these effects were apparent in high-risk individuals and modify treatment responses.

METHODS:

We examined the potential role of the TCF7L2 rs7903146 variant in predicting resistance to weight loss or a lack of improvement of proinsulin processing during 2.5-years of follow-up participants (N = 2,994) from the Diabetes Prevention Program (DPP), a randomized controlled trial designed to prevent or delay diabetes in high-risk adults.

RESULTS:

We observed no difference in the degree of weight loss by rs7903146 genotypes. However, the T allele (conferring higher risk of diabetes) at rs7903146 was associated with higher fasting proinsulin at baseline (P<0.001), higher baseline proinsulin:insulin ratio (p<0.0001) and increased proinsulin:insulin ratio over a median of 2.5 years of follow-up (P = 0.003). Effects were comparable across treatment arms.

CONCLUSIONS:

The combination of a lack of impact of the TCF7L2 genotypes on the ability to lose weight, but the presence of a consistent effect on the proinsulin:insulin ratio over the course of DPP, suggests that high-risk genotype carriers at this locus can successfully lose weight to counter diabetes risk despite persistent deficits in insulin production.

PMID:
21814547
[PubMed - indexed for MEDLINE]
PMCID:
PMC3144193
Free PMC Article

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