Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY

Arslanian, Silva; ghormli, Laure El; Bacha, Fida; Caprio, Sonia; Goland, Robin; Haymond, Morey W.; Levitsky, Lynne L.; Nadeau, Kristen J.; White, Neil H.; Willi, Steven M.

doi:10.2337/dc16-0455

Cited by 37 publications

(39 citation statements)

References 44 publications

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“…Adiponectin is known to be a biomarker of insulin sensitivity in youth, as well as in adults. In TODAY, adiponectin concentrations were predictive of glycemic efficacy on the randomized treatment prior to failure, consistent with adult data . Lower increment in HMW adiponectin levels in non‐Hispanic Blacks compared with the other racial groups seemed to explain the racial differences observed in TODAY with higher failure rates in non‐Hispanic Black youth .…”

Section: Discussionsupporting

confidence: 70%

“…There were no differences in the response to insulin in relation to age, sex, race, BMI, or duration of diabetes. This is in contrast to our previous reports of sex and race differences in response to oral hypoglycemic agents in TODAY participants . These findings are also somewhat different than in adult studies.…”

Section: Discussionmentioning

confidence: 99%

“…Demographic data were collected at randomization, as were blood samples for HbA1c, total and high molecular weight (HMW) adiponectin, inflammatory markers, and fasting lipids . Race‐ethnicity was determined by self‐report and participants were categorized as non‐Hispanic Black, non‐Hispanic White, Hispanic, or “Other” (including Asian, American Indian, and Alaska Native).…”

Section: Methodsmentioning

confidence: 99%

“…HbA1c, C‐peptide, and insulin were measured as previously reported . Total adiponectin concentrations were measured using latex beads based assay reagents on a Modular P Chemistry analyzer (Roche Hitachi, Inc., Indianapolis, IN) and HMW adiponectin was measured using ELISA (R&D Systems, Inc., Minneapolis, MN) . Inflammatory markers, including high sensitivity C reactive protein (hs‐CRP), homocysteine, plasminogen activator inhibitor‐1(PAI‐1), and interleukin‐6 (IL‐6), were determined using standard methods…”

Section: Methodsmentioning

confidence: 99%

“…The TODAY cohort provides a unique opportunity to examine the effects of insulin therapy in youth with type 2 diabetes. Our previous evaluation of risk factors for glycemic failure in TODAY indicated that higher failure rates were associated with β‐cell dysfunction, higher HbA1c at randomization, and African‐American race . In addition, the change in total and high molecular weight adiponectin concentrations over the first 6 months post randomization in TODAY was predictive of the responsiveness to oral diabetes therapy …”

Section: Introductionmentioning

confidence: 99%

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Predictors of response to insulin therapy in youth with poorly‐controlled type 2 diabetes in the TODAY trial

et al. 2019

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Objective To understand the factors associated with glycemic control after starting insulin in youth with type 2 diabetes following glycemic failure (persistent HbA1c ≥8%) with metformin alone, metformin + rosiglitazone or metformin + lifestyle in the TODAY study. Methods Change in HbA1c after add‐on insulin therapy and the factors predictive of glycemic response were evaluated. At 1‐year postinsulin initiation, 253 youth had a mean of 3.9 ± 1.0 visits since the time of insulin initiation. Participants were divided into three groups according to glycemic control: consistent decrease in HbA1c by ≥0.5%, change <0.5%, or consistent increase in HbA1c ≥0.5%, at 75% or more of the visits. Results Within 1‐year postinsulin initiation, 33.2% of participants had a consistent HbA1c decrease of ≥0.5%, 46.2% changed HbA1c <0.5%, and 20.6% had an increase ≥0.5%. At randomization into TODAY and at time of insulin initiation, the three glycemia groups were similar in age, sex, race‐ethnicity, pubertal stage, BMI z‐score, diabetes duration, and insulin secretion indices. Consistent HbA1c improvement was associated with higher insulin sensitivity (1/fasting insulin) at randomization and at time of failure, higher adiponectin at randomization, and was not associated with indices of β‐cell function. Conclusions Response to add‐on insulin was highly variable among youth in TODAY. Greater insulin sensitivity and higher adiponectin concentrations at randomization were associated with improved glycemic control after initiation of insulin. Due to limited information on adherence to insulin injections, the roles of adherence to the prescribed insulin regimen or psychosocial factors are unknown.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predictors of response to insulin therapy in youth with poorly‐controlled type 2 diabetes in the TODAY trial

et al. 2019

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Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes

Lu,

Wolfs,

El ghormli

et al. 2024

JAMA Netw Open

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ImportanceYouth-onset type 2 diabetes (T2D) has a more aggressive phenotype than adult-onset T2D, including rapid loss of glycemic control and increased complication risk.ObjectiveTo identify associations of growth hormone mediators with glycemic failure, beta cell function, and insulin sensitivity in youth-onset T2D.Design, Setting, and ParticipantsThis post hoc secondary analysis of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomized clinical trial, which enrolled participants from July 2004 to February 2009, included 398 participants from 15 university-affiliated medical centers with available plasma samples from baseline and 36 months. Participants were youths aged 10 to 17 years with a duration of T2D of less than 2 years who were randomized to metformin, metformin plus lifestyle intervention, or metformin plus rosiglitazone. Participants were followed up for a mean (SD) of 3.9 (1.5) years during the trial, ending in 2011. Statistical analysis was performed from August 2022 to November 2023.ExposurePlasma insulin-like growth factor-1 (IGF-1), growth hormone receptor (GHR), and insulin-like growth factor binding protein 1 (IGFBP-1).Main Outcomes and MeasuresMain outcomes were (1) loss of glycemic control during the TODAY study, defined as hemoglobin A1c (HbA1c) level of 8% or more for 6 months or inability to wean from insulin therapy, and (2) baseline and 36-month measures of glycemia (fasting glucose, HbA1c), insulin sensitivity (1/fasting C-peptide), high-molecular-weight adiponectin, and beta cell function (C-peptide index, C-peptide oral disposition index).ResultsThis analysis included 398 participants (mean [SD] age, 13.9 [2.0] years; 248 girls [62%]; 166 Hispanic participants [42%]; 134 non-Hispanic Black participants [34%], and 84 non-Hispanic White participants [21%]). A greater increase in IGF-1 level between baseline and 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995 [95% CI, 0.991-0.997]; P &lt; .001) and higher C-peptide index per 100-ng/mL increase in IGF-1 (β [SE], 0.015 [0.003]; P &lt; .001). A greater increase in log2 GHR level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.75 [95% CI, 1.05-2.99]; P = .04) and lower C-peptide index (β [SE], −0.02 [0.006]; P &lt; .001). A greater increase in log2 IGFBP-1 level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.37 [95% CI, 1.09-1.74]; P = .007) and higher high-molecular-weight adiponectin (β [SE], 431 [156]; P = .007).Conclusions and RelevanceThis study suggests that changes in plasma growth hormone mediators are associated with loss of glycemic control in youth-onset T2D, with IGF-1 associated with lower risk and GHR and IGFBP-1 associated with increased risk.Trial RegistrationClinicalTrials.gov Identifier: NCT00081328

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Biomarkers of Insulin Resistance

Cox-York

Pereira

2019

Contemporary Endocrinology

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Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY

Cited by 37 publications

References 44 publications

Predictors of response to insulin therapy in youth with poorly‐controlled type 2 diabetes in the TODAY trial

Predictors of response to insulin therapy in youth with poorly‐controlled type 2 diabetes in the TODAY trial

Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes

Biomarkers of Insulin Resistance

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