PMID- 29157731 OWN - NLM STAT- MEDLINE DCOM- 20190812 LR - 20221207 IS - 1523-6838 (Electronic) IS - 0272-6386 (Print) IS - 0272-6386 (Linking) VI - 71 IP - 1 DP - 2018 Jan TI - Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial. PG - 65-74 LID - S0272-6386(17)30893-4 [pii] LID - 10.1053/j.ajkd.2017.07.015 [doi] AB - BACKGROUND: Diabetic kidney disease is a major cause of premature mortality in type 2 diabetes mellitus (T2DM). Worsening insulin sensitivity independent of glycemic control may contribute to the development of diabetic kidney disease. We investigated the longitudinal association of insulin sensitivity with hyperfiltration and increased albumin excretion in adolescents with T2DM. STUDY DESIGN: Observational prospective cohort study. SETTING & PARTICIPANTS: 532 TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) participants aged 12 to 17 years with T2DM duration less than 2 years at baseline. The TODAY Study was a multicenter randomized clinical trial that examined the efficacy of 3 treatment regimens (metformin monotherapy, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention program) to achieve durable glycemic control. PREDICTORS: Natural log-transformed estimated insulin sensitivity (reciprocal of fasting insulin), hemoglobin A(1c) concentration, age, race-ethnicity, treatment group, body mass index, loss of glycemic control, and hypertension. OUTCOMES: Hyperfiltration was defined as 99th percentile or higher of estimated glomerular filtration rate (>/=140mL/min/1.73m(2)) when referenced to healthy adolescents (NHANES 1999-2002) and albumin-creatinine ratio >/= 30mug/mg at 3 consecutive annual visits. RESULTS: Hyperfiltration was observed in 7.0% of participants at baseline and in 13.3% by 5 years, with a cumulative incidence of 5.0% over 5 years. The prevalence of increased albumin excretion was 6% at baseline and 18% by 5 years, with a cumulative incidence of 13.4%. There was an 8% increase in risk for hyperfiltration per 10% lower estimated insulin sensitivity in unadjusted and adjusted models (P=0.01). Increased albumin excretion was associated with hemoglobin A(1c) concentration, but not estimated insulin sensitivity. LIMITATIONS: Longer follow-up is needed to capture the transition from hyperfiltration to rapid glomerular filtration rate decline in youth-onset T2DM. CONCLUSIONS: Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM. CI - Copyright (c) 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. FAU - Bjornstad, Petter AU - Bjornstad P AD - University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO. FAU - Nehus, Edward AU - Nehus E AD - Cincinnati Children's Hospital Medical Center, Cincinnati, OH. FAU - El Ghormli, Laure AU - El Ghormli L AD - George Washington University Biostatistics Center, Rockville, MD. Electronic address: elghorml@bsc.gwu.edu. FAU - Bacha, Fida AU - Bacha F AD - Texas Children's Hospital, Baylor College of Medicine, Houston, TX. FAU - Libman, Ingrid M AU - Libman IM AD - Children's Hospital University of Pittsburgh Medical Center, Pittsburgh, PA. FAU - McKay, Siripoom AU - McKay S AD - Baylor College of Medicine, Houston, TX. FAU - Willi, Steven M AU - Willi SM AD - Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. FAU - Laffel, Lori AU - Laffel L AD - Joslin Diabetes Center, Boston, MA. FAU - Arslanian, Silva AU - Arslanian S AD - Children's Hospital University of Pittsburgh Medical Center, Pittsburgh, PA. FAU - Nadeau, Kristen J AU - Nadeau KJ AD - University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO. CN - TODAY Study Group LA - eng GR - UL1 RR024153/RR/NCRR NIH HHS/United States GR - UL1 RR025780/RR/NCRR NIH HHS/United States GR - M01 RR000069/RR/NCRR NIH HHS/United States GR - M01 RR000036/RR/NCRR NIH HHS/United States GR - U01 DK061242/DK/NIDDK NIH HHS/United States GR - UL1 RR024992/RR/NCRR NIH HHS/United States GR - P30 DK036836/DK/NIDDK NIH HHS/United States GR - U01 DK061212/DK/NIDDK NIH HHS/United States GR - M01 RR001066/RR/NCRR NIH HHS/United States GR - M01 RR014467/RR/NCRR NIH HHS/United States GR - U01 DK061230/DK/NIDDK NIH HHS/United States GR - M01 RR000043/RR/NCRR NIH HHS/United States GR - UL1 RR025758/RR/NCRR NIH HHS/United States GR - M01 RR000084/RR/NCRR NIH HHS/United States GR - UL1 TR002345/TR/NCATS NIH HHS/United States GR - U01 DK061254/DK/NIDDK NIH HHS/United States GR - T32 DK063687/DK/NIDDK NIH HHS/United States GR - UL1 RR024139/RR/NCRR NIH HHS/United States GR - UL1 RR024989/RR/NCRR NIH HHS/United States GR - M01 RR000125/RR/NCRR NIH HHS/United States GR - U01 DK061239/DK/NIDDK NIH HHS/United States GR - UL1 RR024134/RR/NCRR NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, N.I.H., Extramural DEP - 20171120 PL - United States TA - Am J Kidney Dis JT - American journal of kidney diseases : the official journal of the National Kidney Foundation JID - 8110075 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin A) EIN - Am J Kidney Dis. 2019 Apr;73(4):580. PMID: 30773238 MH - Adolescent MH - Blood Glucose/metabolism MH - Diabetes Mellitus, Type 2/*blood/complications/epidemiology MH - Diabetic Nephropathies/*blood/epidemiology/etiology MH - Disease Progression MH - Follow-Up Studies MH - Glomerular Filtration Rate MH - Glycated Hemoglobin/metabolism MH - Humans MH - Insulin Resistance/*physiology MH - Morbidity/trends MH - *Nutrition Surveys MH - Prospective Studies MH - Risk Factors MH - Survival Rate/trends MH - Time Factors MH - United States PMC - PMC5744896 MID - NIHMS921803 OTO - NOTNLM OT - Type 2 diabetes mellitus (T2DM) OT - adolescents OT - albumin-creatinine ratio (ACR) OT - children OT - creatinine OT - cystatin C OT - diabetic kidney disease (DKD) OT - disease progression OT - estimated glomerular filtration rate (eGFR) OT - hyperfiltration OT - increased albumin excretion OT - insulin sensitivity OT - kidney function OT - youth-onset T2DM FIR - McKay, S IR - McKay S FIR - Haymond, M IR - Haymond M FIR - Anderson, B IR - Anderson B FIR - Bush, C IR - Bush C FIR - Gunn, S IR - Gunn S FIR - Holden, H IR - Holden H FIR - Jones, S M IR - Jones SM FIR - Jeha, G IR - Jeha G FIR - McGirk, S IR - McGirk S FIR - Thamotharan, S IR - Thamotharan S FIR - Cuttler, L IR - Cuttler L FIR - Abrams, E IR - Abrams E FIR - Casey, T IR - Casey T FIR - Dahms, W IR - Dahms W FIR - Ievers-Landis, C IR - Ievers-Landis C FIR - Kaminski, B IR - Kaminski B FIR - Koontz, M IR - Koontz M FIR - MacLeish, S IR - MacLeish S FIR - McGuigan, P IR - McGuigan P FIR - Narasimhan, S IR - Narasimhan S FIR - Geffner, M IR - Geffner M FIR - Barraza, V IR - Barraza V FIR - Chang, N IR - Chang N FIR - Conrad, B IR - Conrad B FIR - Dreimane, D IR - Dreimane D FIR - Estrada, S IR - Estrada S FIR - Fisher, L IR - Fisher L FIR - Fleury-Milfort, E IR - Fleury-Milfort E FIR - Hernandez, S IR - Hernandez S FIR - Hollen, B IR - Hollen B FIR - Kaufman, F IR - Kaufman F FIR - Law, E IR - Law E FIR - Mansilla, V IR - Mansilla V FIR - Miller, D IR - Miller D FIR - Munoz, C IR - Munoz C FIR - Ortiz, R IR - Ortiz R FIR - Ward, A IR - Ward A FIR - Wexler, K IR - Wexler K FIR - Xu, Y K IR - Xu YK FIR - Yasuda, P IR - Yasuda P FIR - Levitt Katz, L IR - Levitt Katz L FIR - Berkowitz, R IR - Berkowitz R FIR - Boyd, S IR - Boyd S FIR - Johnson, B IR - Johnson B FIR - Kaplan, J IR - Kaplan J FIR - Keating, C IR - Keating C FIR - Lassiter, C IR - Lassiter C FIR - Lipman, T IR - Lipman T FIR - McGinley, G IR - McGinley G FIR - McKnight, H IR - McKnight H FIR - Schwartzman, B IR - Schwartzman B FIR - Willi, S IR - Willi S FIR - Arslanian, S IR - Arslanian S FIR - Bacha, F IR - Bacha F FIR - Foster, S IR - Foster S FIR - Galvin, B IR - Galvin B FIR - Hannon, T IR - Hannon T FIR - Kriska, A IR - Kriska A FIR - Libman, I IR - Libman I FIR - Marcus, M IR - Marcus M FIR - Porter, K IR - Porter K FIR - Songer, T IR - Songer T FIR - Venditti, E IR - Venditti E FIR - Goland, R IR - Goland R FIR - Gallagher, D IR - Gallagher D FIR - Kringas, P IR - Kringas P FIR - Leibel, N IR - Leibel N FIR - Ng, D IR - Ng D FIR - Ovalles, M IR - Ovalles M FIR - Seidman, D IR - Seidman D FIR - Laffel, L IR - Laffel L FIR - Goebel-Fabbri, A IR - Goebel-Fabbri A FIR - Hall, M IR - Hall M FIR - Higgins, L IR - Higgins L FIR - Keady, J IR - Keady J FIR - Malloy, M IR - Malloy M FIR - Milaszewski, K IR - Milaszewski K FIR - Rasbach, L IR - Rasbach L FIR - Nathan, D M IR - Nathan DM FIR - Angelescu, A IR - Angelescu A FIR - Bissett, L IR - Bissett L FIR - Ciccarelli, C IR - Ciccarelli C FIR - Delahanty, L IR - Delahanty L FIR - Goldman, V IR - Goldman V FIR - Hardy, O IR - Hardy O FIR - Larkin, M IR - Larkin M FIR - Levitsky, L IR - Levitsky L FIR - McEachern, R IR - McEachern R FIR - Norman, D IR - Norman D FIR - Nwosu, D IR - Nwosu D FIR - Park-Bennett, S IR - Park-Bennett S FIR - Richards, D IR - Richards D FIR - Sherry, N IR - Sherry N FIR - Steiner, B IR - Steiner B FIR - Tollefsen, S IR - Tollefsen S FIR - Carnes, S IR - Carnes S FIR - Dempsher, D IR - Dempsher D FIR - Flomo, D IR - Flomo D FIR - Whelan, T IR - Whelan T FIR - Wolff, B IR - Wolff B FIR - Weinstock, R IR - Weinstock R FIR - Bowerman, D IR - Bowerman D FIR - Bristol, S IR - Bristol S FIR - Bulger, J IR - Bulger J FIR - Hartsig, J IR - Hartsig J FIR - Izquierdo, R IR - Izquierdo R FIR - Kearns, J IR - Kearns J FIR - Saletsky, R IR - Saletsky R FIR - Trief, P IR - Trief P FIR - Zeitler, P IR - Zeitler P FIR - Abramson, N IR - Abramson N FIR - Bradhurst, A IR - Bradhurst A FIR - Celona-Jacobs, N IR - Celona-Jacobs N FIR - Higgins, J IR - Higgins J FIR - Kelsey, M IR - Kelsey M FIR - Klingensmith, G IR - Klingensmith G FIR - Nadeau, K IR - Nadeau K FIR - Witten, T IR - Witten T FIR - Copeland, K IR - Copeland K FIR - Boss, E IR - Boss E FIR - Brown, R IR - Brown R FIR - Chadwick, J IR - Chadwick J FIR - Chalmers, L IR - Chalmers L FIR - Chernausek, S IR - Chernausek S FIR - Hebensperger, A IR - Hebensperger A FIR - Macha, C IR - Macha C FIR - Newgent, R IR - Newgent R FIR - Nordyke, A IR - Nordyke A FIR - Olson, D IR - Olson D FIR - Poulsen, T IR - Poulsen T FIR - Pratt, L IR - Pratt L FIR - Preske, J IR - Preske J FIR - Schanuel, J IR - Schanuel J FIR - Sternlof, S IR - Sternlof S FIR - Lynch, J IR - Lynch J FIR - Amodei, N IR - Amodei N FIR - Barajas, R IR - Barajas R FIR - Cody, C IR - Cody C FIR - Hale, D IR - Hale D FIR - Hernandez, J IR - Hernandez J FIR - Ibarra, C IR - Ibarra C FIR - Morales, E IR - Morales E FIR - Rivera, S IR - Rivera S FIR - Rupert, G IR - Rupert G FIR - Wauters, A IR - Wauters A FIR - White, N IR - White N FIR - Arbelaez, A IR - Arbelaez A FIR - Flomo, D IR - Flomo D FIR - Jones, J IR - Jones J FIR - Jones, T IR - Jones T FIR - Sadler, M IR - Sadler M FIR - Tanner, M IR - Tanner M FIR - Timpson, A IR - Timpson A FIR - Welch, R IR - Welch R FIR - Caprio, S IR - Caprio S FIR - Grey, M IR - Grey M FIR - Guandalini, C IR - Guandalini C FIR - Lavietes, S IR - Lavietes S FIR - Rose, P IR - Rose P FIR - Syme, A IR - Syme A FIR - Tamborlane, W IR - Tamborlane W FIR - Hirst, K IR - Hirst K FIR - Edelstein, S IR - Edelstein S FIR - Feit, P IR - Feit P FIR - Grover, N IR - Grover N FIR - Long, C IR - Long C FIR - Pyle, L IR - Pyle L FIR - Linder, B IR - Linder B FIR - Marcovina, S M IR - Marcovina SM FIR - Harting, J IR - Harting J FIR - Shepherd, J IR - Shepherd J FIR - Fan, B IR - Fan B FIR - Marquez, L IR - Marquez L FIR - Sherman, M IR - Sherman M FIR - Wang, J IR - Wang J FIR - Nichols, M IR - Nichols M FIR - Mayer-Davis, E IR - Mayer-Davis E FIR - Liu, Y IR - Liu Y FIR - Lima, J IR - Lima J FIR - Gidding, S IR - Gidding S FIR - Puccella, J IR - Puccella J FIR - Ricketts, E IR - Ricketts E FIR - Danis, R IR - Danis R FIR - Domalpally, A IR - Domalpally A FIR - Goulding, A IR - Goulding A FIR - Neill, S IR - Neill S FIR - Vargo, P IR - Vargo P FIR - Wilfley, D IR - Wilfley D FIR - Aldrich-Rasche, D IR - Aldrich-Rasche D FIR - Franklin, K IR - Franklin K FIR - Massmann, C IR - Massmann C FIR - O'Brien, D IR - O'Brien D FIR - Patterson, J IR - Patterson J FIR - Tibbs, T IR - Tibbs T FIR - Van Buren, D IR - Van Buren D FIR - Palmert, M IR - Palmert M FIR - Ratner, R IR - Ratner R FIR - Dremaine, D IR - Dremaine D FIR - Silverstein, J IR - Silverstein J EDAT- 2017/11/22 06:00 MHDA- 2019/08/14 06:00 PMCR- 2019/01/01 CRDT- 2017/11/22 06:00 PHST- 2017/02/16 00:00 [received] PHST- 2017/07/25 00:00 [accepted] PHST- 2017/11/22 06:00 [pubmed] PHST- 2019/08/14 06:00 [medline] PHST- 2017/11/22 06:00 [entrez] PHST- 2019/01/01 00:00 [pmc-release] AID - S0272-6386(17)30893-4 [pii] AID - 10.1053/j.ajkd.2017.07.015 [doi] PST - ppublish SO - Am J Kidney Dis. 2018 Jan;71(1):65-74. doi: 10.1053/j.ajkd.2017.07.015. Epub 2017 Nov 20.