Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Lancet. 2012 Jun 16;379(9833):2243-51. doi: 10.1016/S0140-6736(12)60525-X. Epub 2012 Jun 9.

Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study.

Collaborators (257)

Bray GA, Chatellier A, Duncan C, Greenway FL, Levy E, Ryan DH, Polonsky KS, Tobian J, Ehrmann D, Matulik MJ, Clark B, Czech K, DeSandre C, Hilbrich R, McNabb W, Semenske AR, Goldstein BJ, Furlong K, Smith KA, Wildman W, Pepe C, Goldberg RB, Calles J, Ojito J, Castillo-Florez S, Florez HJ, Giannella A, Lara O, Veciana B, Haffner SM, Hazuda HP, Montez MG, Lorenzo C, Martinez A, Hamman RF, Testaverde L, Bouffard A, Dabelea D, Jenkins T, Lenz D, Perreault L, Price DW, Steinke SC, Horton ES, Poirier CS, Swift K, Caballero E, Jackson SD, Lambert L, Lawton KE, Ledbury S, Kahn SE, Montgomery BK, Fujimoto W, Knopp RH, Lipkin EW, Marr M, Murillo A, Trence D, Kitabchi AE, Murphy ME, Applegate WB, Bryer-Ash M, Dagogo-Jack S, Frieson SL, Lambeth H, Lichtermann LC, Otkaei H, Rutledge LM, Sherman AR, Smith CM, Soberman JE, Williams-Cleaves B, Metzger BE, Molitch ME, Johnson MK, Giles MM, Larsen D, Niznik C, Pen SC, Schinleber PA, Nathan DM, McKitrick C, Turgeon H, Abbott K, Anderson E, Bissett L, Cagliero E, D'Anna K, Delahanty L, Florez JC, Goldman V, Poulos A, Tseng B, Barrett-Connor E, Carrion-Petersen ML, Horne J, Leos D, Mudaliar S, Smith J, Vejvoda K, Pi-Sunyer F, Lee JE, Foo ST, Hagamen S, Marrero DG, Kelly SM, Ackermann RT, Fineberg ES, Hadden A, Jackson MA, Kirkman MS, Mather KJ, Roach PJ, Wheeler ML, Ratner RE, Aroda V, Shapiro S, Bavido-Arrage C, Gibbs P, Uwaifo G, Wiggins R, Saad MF, Watson K, Botrous M, Jinagouda S, Budget M, Conzues C, Magpuri P, Ngo K, Xapthalamous K, White NH, Das S, Santiago A, Brown AL, Wernimont C, Saudek CD, Golden SH, Whittington T, Clark JM, Greene A, Jiggetts D, Mosley H, Reusing J, Rubin RR, Stephens S, Utsey E, Schade DS, Adams KS, Hemphill C, Hyde P, Butler L, Canady JL, Colleran K, Gonzales Y, Hernandez-McGinnis DA, Katz P, King C, Crandall J, Brown JO, Adorno E, Duffy H, Martinez H, Pompi D, Shamoon H, Walker EA, Wylie-Rosett J, Orchard T, Jeffries S, Kramer M, Smith M, Wing RR, Kriska A, Pettigrew J, Semler L, Venditti E, Weinzierl V, Arakaki RF, Baker-Ladao NK, Isonaga MK, Bermudez NE, Mau MK, Knowler WC, Cooeyate N, Hoskin MA, Natewa C, Percy CA, Acton KJ, Andre VL, Begay S, Bucca BC, Cook S, Doughty MS, Glass J, Glass M, Hanson RL, Hassenpflug D, Ingraham LE, Kobus KM, Krakoff J, Manus C, McCabe C, Michaels S, Morgan T, Nelson JA, Roy RJ, Smart M, Tonemah DP, Wilson C, Fowler S, Brenneman T, Abebe S, Bamdad J, Barkalow M, Bethepu J, Bezabeh T, Callaghan J, Christophi C, Edelstein SL, Gao Y, Gooding R, Gottlieb A, Grover N, Hoffman H, Jablonski K, Katz R, Kolinjivadi P, Lachin JM, Ma Y, Reamer S, Sapozhnikova A, Sherif H, Temprosa M, Pan Q, Foulkes M, Butler N, Venditti EM, Kriska AM, Semler L, Weinzierl V, Marcovina S, Strylewicz G, Albers J, Prineas RJ, Alexander T, Campbell C, Hall S, Hensley S, Li Y, Mills M, Soliman E, Zhang Z, Fradkin J, Garfield S, Gregg E, Zhang P, Herman WH.

Author information

  • 1University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Abstract

BACKGROUND:

Our objective was to quantify and predict diabetes risk reduction during the Diabetes Prevention Program Outcomes Study (DPPOS) in participants who returned to normal glucose regulation at least once during the Diabetes Prevention Program (DPP) compared with those who consistently met criteria for prediabetes.

METHODS:

DPPOS is an ongoing observational study of participants from the DPP randomised trial. For this analysis, diabetes cumulative incidence in DPPOS was calculated for participants with normal glucose regulation or prediabetes status during DPP with and without stratification by previous randomised treatment group. Cox proportional hazards modelling and generalised linear mixed models were used to quantify the effect of previous (DPP) glycaemic status on risk of later (DPPOS) diabetes and normal glucose regulation status, respectively, per SD in change. Included in this analysis were 1990 participants of DPPOS who had been randomly assigned to treatment groups during DPP (736 intensive lifestyle intervention, 647 metformin, 607 placebo). These studies are registered at ClinicalTrials.gov, NCT00004992 (DPP) and NCT00038727 (DPPOS).

FINDINGS:

Diabetes risk during DPPOS was 56% lower for participants who had returned to normal glucose regulation versus those who consistently had prediabetes (hazard ratio [HR] 0·44, 95% CI 0·37-0·55, p<0·0001) and was unaffected by previous group assignment (interaction test for normal glucose regulation and lifestyle intervention, p=0·1722; normal glucose regulation and metformin, p=0·3304). Many, but not all, of the variables that increased diabetes risk were inversely associated with the chance of a participant reaching normal glucose regulation status in DPPOS. Specifically, previous achievement of normal glucose regulation (odds ratio [OR] 3·18, 95% CI 2·71-3·72, p<0·0001), increased β-cell function (OR 1·28; 95% CI 1·18-1·39, p<0·0001), and insulin sensitivity (OR 1·16, 95% CI 1·08-1·25, p<0·0001) were associated with normal glucose regulation in DPPOS, whereas the opposite was true for prediction of diabetes, with increased β-cell function (HR 0·80, 95% CI 0·71-0·89, p<0·0001) and insulin sensitivity (HR 0·83, 95% CI 0·74-0·94, p=0·0001) having a protective effect. Among participants who did not return to normal glucose regulation in DPP, those assigned to the intensive lifestyle intervention had a higher diabetes risk (HR 1·31, 95% CI 1·03-1·68, p=0·0304) and lower chance of normal glucose regulation (OR 0·59, 95% CI 0·42-0·82, p=0·0014) than did the placebo group in DPPOS.

INTERPRETATION:

We conclude that prediabetes is a high-risk state for diabetes, especially in patients who remain with prediabetes despite intensive lifestyle intervention. Reversion to normal glucose regulation, even if transient, is associated with a significantly reduced risk of future diabetes independent of previous treatment group.

FUNDING:

US National Institutes of Health.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Comment in

PMID:
22683134
[PubMed - indexed for MEDLINE]
PMCID:
PMC3555407
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk