Abstract
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 A1c 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 (≥140 mL/min/1.73 m2) when referenced to healthy adolescents (NHANES 1999-2002) and albumin-creatinine ratio ≥ 30 μg/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 A1c 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 65-74 |
| Number of pages | 10 |
| Journal | American Journal of Kidney Diseases |
| Volume | 71 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2018 |
Keywords
- Type 2 diabetes mellitus (T2DM)
- adolescents
- albumin-creatinine ratio (ACR)
- children
- creatinine
- cystatin C
- diabetic kidney disease (DKD)
- disease progression
- estimated glomerular filtration rate (eGFR)
- hyperfiltration
- increased albumin excretion
- insulin sensitivity
- kidney function
- youth-onset T2DM
ASJC Scopus subject areas
- Nephrology
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Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes : An Observational Analysis of Data From the TODAY Clinical Trial. / Bjornstad, Petter; Nehus, Edward; El ghormli, Laure; Bacha, Fida; Libman, Ingrid M.; McKay, Siripoom; Willi, Steven M.; Laffel, Lori; Arslanian, Silva; Nadeau, Kristen J.; McKay, S.; Haymond, M.; Anderson, B.; Bush, C.; Gunn, S.; Holden, H.; Jones, S. M.; Jeha, G.; McGirk, S.; Thamotharan, S.; Cuttler, L.; Abrams, E.; Casey, T.; Dahms, W.; Ievers-Landis, C.; Kaminski, B.; Koontz, M.; MacLeish, S.; McGuigan, P.; Narasimhan, S.; Geffner, M.; Barraza, V.; Chang, N.; Conrad, B.; Dreimane, D.; Estrada, S.; Fisher, L.; Fleury-Milfort, E.; Hernandez, S.; Hollen, B.; Kaufman, F.; Law, E.; Mansilla, V.; Miller, D.; Muñoz, C.; Ortiz, R.; Ward, A.; Wexler, K.; Xu, Y. K.; Yasuda, P.; Levitt Katz, L.; Berkowitz, R.; Boyd, S.; Johnson, B.; Kaplan, J.; Keating, C.; Lassiter, C.; Lipman, T.; McGinley, G.; McKnight, H.; Schwartzman, B.; Bacha, F.; Foster, S.; Galvin, B.; Hannon, T.; Kriska, A.; Libman, I.; Marcus, M.; Porter, K.; Songer, T.; Venditti, E.; Goland, R.; Gallagher, D.; Kringas, P.; Leibel, N.; Ng, D.; Ovalles, M.; Seidman, D.; Laffel, L.; Goebel-Fabbri, A.; Hall, M.; Higgins, L.; Keady, J.; Malloy, M.; Milaszewski, K.; Rasbach, L.; Nathan, D. M.; Angelescu, A.; Bissett, L.; Ciccarelli, C.; Delahanty, L.; Goldman, V.; Hardy, O.; Larkin, M.; Levitsky, L.; McEachern, R.; Norman, D.; Nwosu, D.; Park-Bennett, S.; Richards, D.; Sherry, N.; Steiner, B.; Tollefsen, S.; Carnes, S.; Dempsher, D.; Flomo, D.; Whelan, T.; Wolff, B.; Weinstock, R.; Bowerman, D.; Bristol, S.; Bulger, J.; Hartsig, J.; Izquierdo, R.; Kearns, J.; Saletsky, R.; Trief, P.; Zeitler, P.; Abramson, N.; Bradhurst, A.; Celona-Jacobs, N.; Higgins, J.; Kelsey, M.; Klingensmith, G.; Nadeau, K.; Witten, T.; Copeland, K.; Boss, E.; Brown, R.; Chadwick, J.; Chalmers, L.; Chernausek, S.; Hebensperger, A.; Macha, C.; Newgent, R.; Nordyke, A.; Olson, D.; Poulsen, T.; Pratt, L.; Preske, J.; Schanuel, J.; Sternlof, S.; Lynch, J.; Amodei, N.; Barajas, R.; Cody, C.; Hale, D.; Hernandez, J.; Ibarra, C.; Morales, E.; Rivera, S.; Rupert, G.; Wauters, A.; White, N.; Arbeláez, A.; Flomo, D.; Jones, J.; Jones, T.; Sadler, M.; Tanner, M.; Timpson, A.; Welch, R.; Caprio, S.; Grey, M.; Guandalini, C.; Lavietes, S.; Rose, P.; Syme, A.; Tamborlane, W.; Hirst, K.; Edelstein, S.; Feit, P.; Grover, N.; Long, C.; Pyle, L.; Linder, B.; Marcovina, S. M.; Harting, J.; Shepherd, J.; Fan, B.; Marquez, L.; Sherman, M.; Wang, J.; Nichols, M.; Mayer-Davis, E.; Liu, Y.; Lima, J.; Gidding, S.; Puccella, J.; Ricketts, E.; Danis, R.; Domalpally, A.; Goulding, A.; Neill, S.; Vargo, P.; Wilfley, D.; Aldrich-Rasche, D.; Franklin, K.; Massmann, C.; O'Brien, D.; Patterson, J.; Tibbs, T.; Van Buren, D.; Palmert, M.; Ratner, R.; Dremaine, D.; Silverstein, J.
In: American Journal of Kidney Diseases, Vol. 71, No. 1, 01.2018, p. 65-74.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes
T2 - An Observational Analysis of Data From the TODAY Clinical Trial
AU - Bjornstad, Petter
AU - Nehus, Edward
AU - El ghormli, Laure
AU - Bacha, Fida
AU - Libman, Ingrid M.
AU - McKay, Siripoom
AU - Willi, Steven M.
AU - Laffel, Lori
AU - Arslanian, Silva
AU - Nadeau, Kristen J.
AU - McKay, S.
AU - Haymond, M.
AU - Anderson, B.
AU - Bush, C.
AU - Gunn, S.
AU - Holden, H.
AU - Jones, S. M.
AU - Jeha, G.
AU - McGirk, S.
AU - Thamotharan, S.
AU - Cuttler, L.
AU - Abrams, E.
AU - Casey, T.
AU - Dahms, W.
AU - Ievers-Landis, C.
AU - Kaminski, B.
AU - Koontz, M.
AU - MacLeish, S.
AU - McGuigan, P.
AU - Narasimhan, S.
AU - Geffner, M.
AU - Barraza, V.
AU - Chang, N.
AU - Conrad, B.
AU - Dreimane, D.
AU - Estrada, S.
AU - Fisher, L.
AU - Fleury-Milfort, E.
AU - Hernandez, S.
AU - Hollen, B.
AU - Kaufman, F.
AU - Law, E.
AU - Mansilla, V.
AU - Miller, D.
AU - Muñoz, C.
AU - Ortiz, R.
AU - Ward, A.
AU - Wexler, K.
AU - Xu, Y. K.
AU - Yasuda, P.
AU - Levitt Katz, L.
AU - Berkowitz, R.
AU - Boyd, S.
AU - Johnson, B.
AU - Kaplan, J.
AU - Keating, C.
AU - Lassiter, C.
AU - Lipman, T.
AU - McGinley, G.
AU - McKnight, H.
AU - Schwartzman, B.
AU - Bacha, F.
AU - Foster, S.
AU - Galvin, B.
AU - Hannon, T.
AU - Kriska, A.
AU - Libman, I.
AU - Marcus, M.
AU - Porter, K.
AU - Songer, T.
AU - Venditti, E.
AU - Goland, R.
AU - Gallagher, D.
AU - Kringas, P.
AU - Leibel, N.
AU - Ng, D.
AU - Ovalles, M.
AU - Seidman, D.
AU - Laffel, L.
AU - Goebel-Fabbri, A.
AU - Hall, M.
AU - Higgins, L.
AU - Keady, J.
AU - Malloy, M.
AU - Milaszewski, K.
AU - Rasbach, L.
AU - Nathan, D. M.
AU - Angelescu, A.
AU - Bissett, L.
AU - Ciccarelli, C.
AU - Delahanty, L.
AU - Goldman, V.
AU - Hardy, O.
AU - Larkin, M.
AU - Levitsky, L.
AU - McEachern, R.
AU - Norman, D.
AU - Nwosu, D.
AU - Park-Bennett, S.
AU - Richards, D.
AU - Sherry, N.
AU - Steiner, B.
AU - Tollefsen, S.
AU - Carnes, S.
AU - Dempsher, D.
AU - Flomo, D.
AU - Whelan, T.
AU - Wolff, B.
AU - Weinstock, R.
AU - Bowerman, D.
AU - Bristol, S.
AU - Bulger, J.
AU - Hartsig, J.
AU - Izquierdo, R.
AU - Kearns, J.
AU - Saletsky, R.
AU - Trief, P.
AU - Zeitler, P.
AU - Abramson, N.
AU - Bradhurst, A.
AU - Celona-Jacobs, N.
AU - Higgins, J.
AU - Kelsey, M.
AU - Klingensmith, G.
AU - Nadeau, K.
AU - Witten, T.
AU - Copeland, K.
AU - Boss, E.
AU - Brown, R.
AU - Chadwick, J.
AU - Chalmers, L.
AU - Chernausek, S.
AU - Hebensperger, A.
AU - Macha, C.
AU - Newgent, R.
AU - Nordyke, A.
AU - Olson, D.
AU - Poulsen, T.
AU - Pratt, L.
AU - Preske, J.
AU - Schanuel, J.
AU - Sternlof, S.
AU - Lynch, J.
AU - Amodei, N.
AU - Barajas, R.
AU - Cody, C.
AU - Hale, D.
AU - Hernandez, J.
AU - Ibarra, C.
AU - Morales, E.
AU - Rivera, S.
AU - Rupert, G.
AU - Wauters, A.
AU - White, N.
AU - Arbeláez, A.
AU - Flomo, D.
AU - Jones, J.
AU - Jones, T.
AU - Sadler, M.
AU - Tanner, M.
AU - Timpson, A.
AU - Welch, R.
AU - Caprio, S.
AU - Grey, M.
AU - Guandalini, C.
AU - Lavietes, S.
AU - Rose, P.
AU - Syme, A.
AU - Tamborlane, W.
AU - Hirst, K.
AU - Edelstein, S.
AU - Feit, P.
AU - Grover, N.
AU - Long, C.
AU - Pyle, L.
AU - Linder, B.
AU - Marcovina, S. M.
AU - Harting, J.
AU - Shepherd, J.
AU - Fan, B.
AU - Marquez, L.
AU - Sherman, M.
AU - Wang, J.
AU - Nichols, M.
AU - Mayer-Davis, E.
AU - Liu, Y.
AU - Lima, J.
AU - Gidding, S.
AU - Puccella, J.
AU - Ricketts, E.
AU - Danis, R.
AU - Domalpally, A.
AU - Goulding, A.
AU - Neill, S.
AU - Vargo, P.
AU - Wilfley, D.
AU - Aldrich-Rasche, D.
AU - Franklin, K.
AU - Massmann, C.
AU - O'Brien, D.
AU - Patterson, J.
AU - Tibbs, T.
AU - Van Buren, D.
AU - Palmert, M.
AU - Ratner, R.
AU - Dremaine, D.
AU - Silverstein, J.
N1 - Funding Information: Support: This work was completed with funding from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/National Institutes of Health grant numbers T32-DK063687 , U01-DK61212 , U01-DK61230 , U01-DK61239 , U01-DK61242 , and U01-DK61254 ; the National Center for Research Resources (NCRR) General Clinical Research Centers Program grant numbers M01-RR00036 (Washington University School of Medicine), M01-RR00043-45 (Children’s Hospital Los Angeles), M01-RR00069 (University of Colorado Denver), M01-RR00084 (Children’s Hospital of Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125 (Yale University), and M01-RR14467 (University of Oklahoma Health Sciences Center); and from the NCRR Clinical and Translational Science Awards grant numbers UL1-RR024134 (Children’s Hospital of Philadelphia), UL1-RR024139 (Yale University), UL1-RR024153 (Children’s Hospital of Pittsburgh), UL1-RR024989 (Case Western Reserve University), UL1-RR024992 (Washington University in St Louis), UL1-RR025758 (Massachusetts General Hospital), and UL1-RR025780 (University of Colorado Denver). NIDDK had no role in study design; collection, analysis, and interpretation of data; and writing the report. Drug and supplies donations in support of the study’s efforts were received from Becton, Dickinson and Company; Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; LifeScan, Inc; Pfizer; Sanofi Aventis. None of these companies had any role in any aspect of the study. Funding Information: We gratefully acknowledge the participation and guidance of the American Indian partners associated with the clinical center located at the University of Oklahoma Health Sciences Center, including members of the Absentee Shawnee Tribe, Cherokee Nation, Chickasaw Nation, Choctaw Nation of Oklahoma, and Oklahoma City Area Indian Health Service. Publisher Copyright: © 2017 National Kidney Foundation, Inc.
PY - 2018/1
Y1 - 2018/1
N2 - 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 A1c 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 (≥140 mL/min/1.73 m2) when referenced to healthy adolescents (NHANES 1999-2002) and albumin-creatinine ratio ≥ 30 μg/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 A1c 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.
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 A1c 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 (≥140 mL/min/1.73 m2) when referenced to healthy adolescents (NHANES 1999-2002) and albumin-creatinine ratio ≥ 30 μg/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 A1c 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.
KW - Type 2 diabetes mellitus (T2DM)
KW - adolescents
KW - albumin-creatinine ratio (ACR)
KW - children
KW - creatinine
KW - cystatin C
KW - diabetic kidney disease (DKD)
KW - disease progression
KW - estimated glomerular filtration rate (eGFR)
KW - hyperfiltration
KW - increased albumin excretion
KW - insulin sensitivity
KW - kidney function
KW - youth-onset T2DM
UR - http://www.scopus.com/inward/record.url?scp=85034050494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034050494&partnerID=8YFLogxK
U2 - 10.1053/j.ajkd.2017.07.015
DO - 10.1053/j.ajkd.2017.07.015
M3 - Article
C2 - 29157731
AN - SCOPUS:85034050494
VL - 71
SP - 65
EP - 74
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 1
ER -