Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial

TODAY Study Group

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)65-74
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume71
Issue number1
DOIs
StatePublished - Jan 1 2018

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Diabetic Nephropathies
Type 2 Diabetes Mellitus
Insulin Resistance
Clinical Trials
Albumins
Metformin
rosiglitazone
Therapeutics
Glomerular Filtration Rate
Hemoglobins
Premature Mortality
Nutrition Surveys
Incidence
Hyperglycemia
Observational Studies
Life Style
Fasting
Creatinine
Body Mass Index
Cohort Studies

Keywords

  • 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
  • Type 2 diabetes mellitus (T2DM)
  • youth-onset T2DM

ASJC Scopus subject areas

  • Nephrology

Cite this

@article{a3510acdc2a24ea6ac34bd44a8f2e5b0,
title = "Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial",
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.",
keywords = "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, Type 2 diabetes mellitus (T2DM), youth-onset T2DM",
author = "{TODAY Study Group} and Petter Bjornstad and Edward Nehus and {El ghormli}, Laure and Fida Bacha and Libman, {Ingrid M.} and Siripoom McKay and Willi, {Steven M.} and Lori Laffel and Silva Arslanian and Nadeau, {Kristen J.} and S. McKay and M. Haymond and B. Anderson and C. Bush and S. Gunn and H. Holden and Jones, {S. M.} and G. Jeha and S. McGirk and S. Thamotharan and L. Cuttler and E. Abrams and T. Casey and W. Dahms and C. Ievers-Landis and B. Kaminski and M. Koontz and S. MacLeish and P. McGuigan and S. Narasimhan and M. Geffner and V. Barraza and N. Chang and B. Conrad and D. Dreimane and S. Estrada and L. Fisher and E. Fleury-Milfort and S. Hernandez and B. Hollen and F. Kaufman and E. Law and V. Mansilla and D. Miller and C. Mu{\~n}oz and R. Ortiz and A. Ward and K. Wexler and Xu, {Y. K.} and Joao Lima",
year = "2018",
month = "1",
day = "1",
doi = "10.1053/j.ajkd.2017.07.015",
language = "English (US)",
volume = "71",
pages = "65--74",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "1",

}

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 - TODAY Study Group

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 - Lima, Joao

PY - 2018/1/1

Y1 - 2018/1/1

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 - 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 - Type 2 diabetes mellitus (T2DM)

KW - youth-onset T2DM

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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

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