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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

2017; Elsevier BV; Volume: 71; Issue: 1 Linguagem: Inglês

10.1053/j.ajkd.2017.07.015

1523-6838

Petter Bjornstad, Edward Nehus, Laure El ghormli, Fida Bacha, Ingrid Libman, Siripoom McKay, Steven M. Willi, Lori M. Laffel, Silva Arslanian, Kristen J. Nadeau, Siripoom McKay, Morey W. Haymond, Brian Anderson, C. Bush, Sheila Gunn, H. Holden, Stephanie M. Jones, George Jeha, S. McGirk, Shanthie Thamotharan, Leona Cuttler, E. Abrams, Terri Casey, W. Dahms, Carolyn E. Ievers‐Landis, Beth A. Kaminski, Michaela B. Koontz, Sarah A. MacLeish, Paul McGuigan, Sumana Narasimhan, Mitchell E. Geffner, V. Barraza, Nancy Chang, Bernard Conrad, Daina Dreimane, S. Estrada, Lynda K. Fisher, Evelyne Fleury‐Milfort, S. Hernández, B. Hollen, F. Kaufman, Ernest H. Law, V. Mansilla, Debra L. Miller, Cynthia Muñoz, R. Ortiz, A. Ward, K. Wexler, Yidong Xu, Patrice Yasuda, Lorraine Levitt Katz, Robert J. Berkowitz, S. Boyd, B. Johnson, J. Kaplan, C. Keating, C. A. Lassiter, Terri H. Lipman, G. McGinley, Heather McKnight, B. Schwartzman, Steven M. Willi, Silva Arslanian, Fida Bacha, Simon R. Foster, Bryan Galvin, Tamara S. Hannon, Andrea M. Kriska, Ingrid Libman, Marsha D. Marcus, Kristin E. Porter, Thomas J. Songer, Elizabeth M. Venditti, Robin Goland, Dympna Gallagher, P. Kringas, Natasha Leibel, Daniel P. K. Ng, M. Ovalles, Daniel S. Seidman, Lori M. Laffel, Ann Goebel-Fabbri, Michael Hall, Linda W. Higgins, Joyce Keady, M. Malloy, Kerry Milaszewski, Lisa Rasbach, David M. Nathan, A. Angelescu, L. Bissett, C. Ciccarelli, Linda M. Delahanty, Veronica Goldman, Olivier J. Hardy, Mary Larkin, Lynne L. Levitsky, R. McEachern, D. Norman, Dennis Chimezie Nwosu, S. Park‐Bennett, D. Richards, Nicole Sherry, Barbara Steiner, Sherida E. Tollefsen, Stefanie Carnes, D. Dempsher, D. Flomo, Timothy J. Whelan, B. Wolff, Ruth S. Weinstock, D. Bowerman, S. Bristol, Jane Bulger, J. Hartsig, Roberto Izquierdo, J. Kearns, R. Saletsky, Paula M. Trief, Philip Zeitler, N. Abramson, A. Bradhurst, N. Celona‐Jacobs, Janine Higgins, Megan M. Kelsey, Georgeanna J. Klingensmith, Kristen J. Nadeau, T. Witten, Kenneth C. Copeland, E. Boss, R Brown, J. Chadwick, Laura Chalmers, Steven D. Chernausek, A. Hebensperger, C. Macha, Rebecca A. Newgent, A. Nordyke, Darin E. Olson, T. Poulsen, Linda Pratt, J. Preske, J. Schanuel, S. Sternlof, Jane Lynch, Nancy Amodei, Rose Ann Barajas, C. Cody, Davis Hale, Javier Hernández, Christopher Ibarra, Elisa Morales, S. Rivera, G. Rupert, A. Wauters, N. White, Alejandra Arbeláez, D. Flomo, J. Jones, T. Jones, Michelle Sadler, Minna Tanner, A. Timpson, R. Joel Welch, Sonia Caprio, Margaret Grey, Cindy Guandalini, S. Lavietes, Paulina Rose, A. Syme, William V. Tamborlane, Kathryn Hirst, Sharon L. Edelstein, P. Feit, Nisha Grover, Cheng Long, Laura Pyle, Barbara Linder, Santica M. Marcovina, Jessica Harting, John Shepherd, Bin Fan, L. Marquez, M. Sherman, J S Brody, Michele Nichols, Elizabeth J. Mayer‐Davis, Y. Liu, João Lindemberg Bandeira Lima, Samuel S. Gidding, J. Puccella, Erin P. Ricketts, Ronald P. Danis, Amitha Domalpally, Ailsa Goulding, Sean Neill, Pamela Vargo, Denise E. Wilfley, D. Aldrich‐Rasche, Kierra A. Franklin, C. Massmann, Diane M. O’Brien, Judith K. Patterson, Tiffany L. Tibbs, David Van Buren, Mark R. Palmert, R. Ratner, D. Dremaine, Janet Silverstein,

Pancreatic function and diabetes

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. 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. Observational prospective cohort study. 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. 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. 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. 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. Longer follow-up is needed to capture the transition from hyperfiltration to rapid glomerular filtration rate decline in youth-onset T2DM. Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM.