Browsing by Subject "Pre-diabetes"

Now showing 1 - 3 of 3
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    Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review
    (Springer Nature, 2023-10-05) Felton, Jamie L.; Griffin, Kurt J.; Oram, Richard A.; Speake, Cate; Long, S. Alice; Onengut-Gumuscu, Suna; Rich, Stephen S.; Monaco, Gabriela S. F.; Evans-Molina, Carmella; DiMeglio, Linda A.; Ismail, Heba M.; Steck, Andrea K.; Dabelea, Dana; Johnson, Randi K.; Urazbayeva, Marzhan; Gitelman, Stephen; Wentworth, John M.; Redondo, Maria J.; Sims, Emily K.; Pediatrics, School of Medicine
    Background: Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification. Methods: To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument. Results: We identify and summarize 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss at disease onset. Seventeen interventions, mostly immunotherapies, show benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employ precision analyses to assess features linked to treatment response. Age, beta cell function measures, and immune phenotypes are most frequently tested. However, analyses are typically not prespecified, with inconsistent methods of reporting, and tend to report positive findings. Conclusions: While the quality of prevention and intervention trials is overall high, the low quality of precision analyses makes it difficult to draw meaningful conclusions that inform clinical practice. To facilitate precision medicine approaches to T1D prevention, considerations for future precision studies include the incorporation of uniform outcome measures, reproducible biomarkers, and prespecified, fully powered precision analyses into future trial design.
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    Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study
    (Springer International Publishing, 2014-02) Marrero, D.; Pan, Q.; Barrett-Connor, E.; de Groot, Mary; Zhang, P.; Percy, C.; Florez, H.; Ackermann, R.; Montez, M.; Rubin, R. R.; DPPOS Research Group; Department of Medicine, IU School of Medicine
    Purpose The purpose of this study is to assess if diagnosis of type 2 diabetes affected health-related quality of life (HRQoL) among participants in the Diabetes Prevention Program/Diabetes Prevention Program Outcome Study and changes with treatment or diabetes duration. Methods 3,210 participants with pre-diabetes were randomized to metformin (MET), intensive lifestyle intervention (ILS), or placebo (PLB). HRQoL was assessed using the SF-36 including: (1) 8 SF-36 subscales; (2) the physical component (PCS) and mental component summary (MCS) scores; and (3) the SF-6D. The sample was categorized by diabetes free versus diagnosed. For diagnosed subgroup, mean scores in the diabetes-free period, at 6 months, 2, 4 and 6 years post-diagnosis, were compared. Results PCS and SF-6D scores declined in all participants in all treatment arms (P <.001). MCS scores did not change significantly in any treatment arm regardless of diagnosis. ILS participants reported a greater decrease in PCS scores at 6 months post-diagnosis (P <.001) and a more rapid decline immediately post-diagnosis in SF-6D scores (P = .003) than the MET or PLB arms. ILS participants reported a significant decrease in the social functioning subscale at 6 months (P <.001) and two years (P <.001) post-diagnosis. Conclusions Participants reported a decline in measures of overall health state (SF-6D) and overall physical HRQoL, whether or not they were diagnosed with diabetes during the study. There was no change in overall mental HRQoL. Participants in the ILS arm with diabetes reported a more significant decline in some HRQoL measures than those in the MET and PLB arms that developed diabetes.
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    Islet Autoimmunity in Adults With Impaired Glucose Tolerance and Recently Diagnosed, Treatment Naïve Type 2 Diabetes in the Restoring Insulin SEcretion (RISE) Study
    (Frontiers Media, 2021-04-26) Brooks-Worrell, Barbara M.; Tjaden, Ashley H.; Edelstein, Sharon L.; Palomino, Brenda; Utzschneider, Kristina M.; Arslanian, Silva; Mather, Kieren J.; Buchanan, Thomas A.; Nadeau, Kristen J.; Atkinson, Karen; Barengolts, Elena; Kahn, Steven E.; Palmer, Jerry P.; RISE Consortium; Medicine, School of Medicine
    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.