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Withdrawal of medications leads to worsening of OGTT parameters in youth with impaired glucose tolerance or recently-diagnosed type 2 diabetes.

ABSTRACT: BACKGROUND:The RISE Pediatric Medication Study compared strategies for preserving ?-cell function, including a 9-month follow-up after treatment withdrawal to test treatment effect durability. OBJECTIVE:Evaluate OGTT measures of glucose and ?-cell response through 12 months of intervention and 9?months of medication washout. PARTICIPANTS:Youth (n = 91) aged 10 to 19?years with BMI ?85th percentile and impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes (T2D). METHODS:A multicenter randomized clinical trial comparing insulin glargine for 3?months followed by metformin for 9?months (G?Met) or metformin alone (Met) for 12 months. We report within-group changes from baseline to end of medication intervention (M12), baseline to 9?months post-medication withdrawal (M21), and end of medication (M12) to M21. OGTT C-peptide index [CPI] paired with 1/fasting insulin evaluated ?-cell response. RESULTS:At M12, both treatments were associated with stable fasting glucose (G?Met baseline 6.0?±?0.1 vs M12 5.9?±?0.2?mmol/L, P = .62; Met baseline 6.1?±?0.2 vs M12 6.0?±?0.2?mmol/L, P = .73) and 2-hour glucose (G?Met baseline 10.2?±?0.4 vs M12 9.3?±?0.5?mmol/L, P = .03; Met baseline 10.2?±?0.4 vs M12 10.6?±?0.6?mmol/L, P = .88). Following medication withdrawal, fasting glucose worsened (G?Met M21 8.6?±?1.8, P = .004; Met M21 7.8?±?0.7?mmol/L, P = .003), as did 2-hour glucose (G?Met M21 13.2?±?1.4, P = .002; Met M21 13.1?±?1.2?mmol/L, P = .006), associated with declines in ?-cell response. CONCLUSIONS:G?Met and Met were associated with stable glucose measures during 12 months of treatment in youth with IGT or recently diagnosed T2D. Glucose and ?-cell response worsened post-medication withdrawal, suggesting treatment must be long-term or alternative treatments pursued.

SUBMITTER: Hannon TS

PROVIDER: S-EPMC7642167 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Withdrawal of medications leads to worsening of OGTT parameters in youth with impaired glucose tolerance or recently-diagnosed type 2 diabetes.

Hannon Tamara S TS Edelstein Sharon L SL Arslanian Silva A SA Caprio Sonia S Zeitler Philip S PS Buchanan Thomas A TA Ehrmann David A DA Mather Kieren J KJ Tripputi Mark M Kahn Steven E SE Nadeau Kristen J KJ

Pediatric diabetes 20201013 8

<h4>Background</h4>The RISE Pediatric Medication Study compared strategies for preserving β-cell function, including a 9-month follow-up after treatment withdrawal to test treatment effect durability.<h4>Objective</h4>Evaluate OGTT measures of glucose and β-cell response through 12 months of intervention and 9 months of medication washout.<h4>Participants</h4>Youth (n = 91) aged 10 to 19 years with BMI ≥85th percentile and impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes (T ...[more]

PMID: 32985775

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Project description:The presence of islet autoantibodies and islet reactive T cells (T+) in adults with established type 2 diabetes (T2D) have been shown to identify those patients with more severe β-cell dysfunction. However, at what stage in the progression toward clinical T2D does islet autoimmunity emerge as an important component influencing β-cell dysfunction? In this ancillary study to the Restoring Insulin SEcretion (RISE) Study, we investigated the prevalence of and association with β-cell dysfunction of T+ and autoantibodies to the 65 kDa glutamic acid decarboxylase antigen (GADA) in obese pre-diabetes adults with impaired glucose tolerance (IGT) and recently diagnosed treatment naïve (Ndx) T2D. We further investigated the effect of 12 months of RISE interventions (metformin or liraglutide plus metformin, or with 3 months of insulin glargine followed by 9 months of metformin or placebo) on islet autoimmune reactivity. We observed GADA(+) in 1.6% of NdxT2D and 4.6% of IGT at baseline, and in 1.6% of NdxT2D and 5.3% of IGT at 12 months, but no significant associations between GADA(+) and β-cell function. T(+) was observed in 50% of NdxT2D and 60.4% of IGT at baseline, and in 68.4% of NdxT2D and 83.9% of IGT at 12 months. T(+) NdxT2D were observed to have significantly higher fasting glucose (p = 0.004), and 2 h glucose (p = 0.0032), but significantly lower steady state C-peptide (sscpep, p = 0.007) compared to T(-) NdxT2D. T(+) IGT participants demonstrated lower but not significant (p = 0.025) acute (first phase) C-peptide response to glucose (ACPRg) compared to T(-) IGT. With metformin treatment, T(+) participants were observed to have a significantly lower Hemoglobin A1c (HbA1c, p = 0.002) and fasting C-peptide (p = 0.002) compared to T(-), whereas T(+) treated with liraglutide + metformin had significantly lower sscpep (p = 0.010) compared to T(-) participants. In the placebo group, T(+) participants demonstrated significantly lower ACPRg (p = 0.001) compared to T(-) participants. In summary, T(+) were found in a large percentage of obese pre-diabetes adults with IGT and in recently diagnosed T2D. Moreover, T(+) were significantly correlated with treatment effects and β-cell dysfunction. Our results demonstrate that T(+) are an important component in T2D.

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Withdrawal of medications leads to worsening of OGTT parameters in youth with impaired glucose tolerance or recently-diagnosed type 2 diabetes.

Publications

Withdrawal of medications leads to worsening of OGTT parameters in youth with impaired glucose tolerance or recently-diagnosed type 2 diabetes.

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