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  • 1
    Online Resource
    Online Resource
    Islet autoantibodies as precision diagnostic tools to characterize heterogeneity in type 1 diabetes: a systematic review
    Springer Science and Business Media LLC ; 2024
    In:  Communications Medicine Vol. 4, No. 1 ( 2024-04-06)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2024-04-06)
    Abstract: Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies. Methods We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment. Results Here we show that 152 studies that met extraction criteria most commonly characterized heterogeneity before diagnosis (91/152). Autoantibody type/target was most frequently examined, followed by autoantibody number. Recurring themes included correlations of autoantibody number, type, and titers with progression, differing phenotypes based on order of autoantibody seroconversion, and interactions with age and genetics. Only 44% specifically described autoantibody assay standardization program participation. Conclusions Current evidence most strongly supports the application of autoantibody features to more precisely define T1D before diagnosis. Our findings support continued use of pre-clinical staging paradigms based on autoantibody number and suggest that additional autoantibody features, particularly in relation to age and genetic risk, could offer more precise stratification. To improve reproducibility and applicability of autoantibody-based precision medicine in T1D, we propose a methods checklist for islet autoantibody-based manuscripts which includes use of precision medicine MeSH terms and participation in autoantibody standardization workshops.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-024-00478-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
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  • 2
    Online Resource
    Online Resource
    Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-10-05)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-10-05)
    Abstract: 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 $$\ge$$ ≥ 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.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00357-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 3
    Online Resource
    Online Resource
    The use of precision diagnostics for monogenic diabetes: a systematic review and expert opinion
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-10-05)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-10-05)
    Abstract: Monogenic diabetes presents opportunities for precision medicine but is underdiagnosed. This review systematically assessed the evidence for (1) clinical criteria and (2) methods for genetic testing for monogenic diabetes, summarized resources for (3) considering a gene or (4) variant as causal for monogenic diabetes, provided expert recommendations for (5) reporting of results; and reviewed (6) next steps after monogenic diabetes diagnosis and (7) challenges in precision medicine field. Methods Pubmed and Embase databases were searched (1990-2022) using inclusion/exclusion criteria for studies that sequenced one or more monogenic diabetes genes in at least 100 probands (Question 1), evaluated a non-obsolete genetic testing method to diagnose monogenic diabetes (Question 2). The risk of bias was assessed using the revised QUADAS-2 tool. Existing guidelines were summarized for questions 3-5, and review of studies for questions 6-7, supplemented by expert recommendations. Results were summarized in tables and informed recommendations for clinical practice. Results There are 100, 32, 36, and 14 studies included for questions 1, 2, 6, and 7 respectively. On this basis, four recommendations for who to test and five on how to test for monogenic diabetes are provided. Existing guidelines for variant curation and gene-disease validity curation are summarized. Reporting by gene names is recommended as an alternative to the term MODY. Key steps after making a genetic diagnosis and major gaps in our current knowledge are highlighted. Conclusions We provide a synthesis of current evidence and expert opinion on how to use precision diagnostics to identify individuals with monogenic diabetes.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00369-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 4
    Online Resource
    Online Resource
    Precision subclassification of type 2 diabetes: a systematic review
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-10-05)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-10-05)
    Abstract: Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic review to determine whether strategies to subclassify type 2 diabetes were associated with high quality evidence, reproducible results and improved outcomes for patients. Methods We searched PubMed and Embase for publications that used ‘simple subclassification’ approaches using simple categorisation of clinical characteristics, or ‘complex subclassification’ approaches which used machine learning or ‘omics approaches in people with established type 2 diabetes. We excluded other diabetes subtypes and those predicting incident type 2 diabetes. We assessed quality, reproducibility and clinical relevance of extracted full-text articles and qualitatively synthesised a summary of subclassification approaches. Results Here we show data from 51 studies that demonstrate many simple stratification approaches, but none have been replicated and many are not associated with meaningful clinical outcomes. Complex stratification was reviewed in 62 studies and produced reproducible subtypes of type 2 diabetes that are associated with outcomes. Both approaches require a higher grade of evidence but support the premise that type 2 diabetes can be subclassified into clinically meaningful subtypes. Conclusion Critical next steps toward clinical implementation are to test whether subtypes exist in more diverse ancestries and whether tailoring interventions to subtypes will improve outcomes.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00360-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 5
    Online Resource
    Online Resource
    Author Correction: Genotype-stratified treatment for monogenic insulin resistance: a systematic review
    Springer Science and Business Media LLC ; 2024
    In:  Communications Medicine Vol. 4, No. 1 ( 2024-03-26)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2024-03-26)
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-024-00482-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
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  • 6
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    Online Resource
    Effective interventions in preventing gestational diabetes mellitus: A systematic review and meta-analysis
    Springer Science and Business Media LLC ; 2024
    In:  Communications Medicine Vol. 4, No. 1 ( 2024-04-20)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2024-04-20)
    Abstract: Lifestyle choices, metformin, and dietary supplements may prevent GDM, but the effect of intervention characteristics has not been identified. This review evaluated intervention characteristics to inform the implementation of GDM prevention interventions. Methods Ovid, MEDLINE/PubMed, and EMBASE databases were searched. The Template for Intervention Description and Replication (TIDieR) framework was used to examine intervention characteristics ( who, what, when, where, and how ). Subgroup analysis was performed by intervention characteristics. Results 116 studies involving 40,940 participants are included. Group-based physical activity interventions (RR 0.66; 95% CI 0.46, 0.95) reduce the incidence of GDM compared with individual or mixed (individual and group) delivery format (subgroup p -value = 0.04). Physical activity interventions delivered at healthcare facilities reduce the risk of GDM (RR 0.59; 95% CI 0.49, 0.72) compared with home-based interventions (subgroup p -value = 0.03). No other intervention characteristics impact the effectiveness of all other interventions. Conclusions Dietary, physical activity, diet plus physical activity, metformin, and myoinositol interventions reduce the incidence of GDM compared with control interventions. Group and healthcare facility-based physical activity interventions show better effectiveness in preventing GDM than individual and community-based interventions. Other intervention characteristics (e.g. utilization of e-health) don’t impact the effectiveness of lifestyle interventions, and thus, interventions may require consideration of the local context.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-024-00491-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
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  • 7
    Online Resource
    Online Resource
    Refining the diagnosis of gestational diabetes mellitus: a systematic review and meta-analysis
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-12-18)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-12-18)
    Abstract: Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. Methods Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m 2 ) with offspring macrosomia or large-for-gestational age (LGA). Results A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [ n  = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [ n  = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. Conclusions Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00393-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 8
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    Online Resource
    Precision gestational diabetes treatment: a systematic review and meta-analyses
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-10-05)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-10-05)
    Abstract: Gestational Diabetes Mellitus (GDM) affects approximately 1 in 7 pregnancies globally. It is associated with short- and long-term risks for both mother and baby. Therefore, optimizing treatment to effectively treat the condition has wide-ranging beneficial effects. However, despite the known heterogeneity in GDM, treatment guidelines and approaches are generally standardized. We hypothesized that a precision medicine approach could be a tool for risk-stratification of women to streamline successful GDM management. With the relatively short timeframe available to treat GDM, commencing effective therapy earlier, with more rapid normalization of hyperglycaemia, could have benefits for both mother and fetus. Methods We conducted two systematic reviews, to identify precision markers that may predict effective lifestyle and pharmacological interventions. Results There was a paucity of studies examining precision lifestyle-based interventions for GDM highlighting the pressing need for further research in this area. We found a number of precision markers identified from routine clinical measures that may enable earlier identification of those requiring escalation of pharmacological therapy (to metformin, sulphonylureas or insulin). This included previous history of GDM, Body Mass Index and blood glucose concentrations at diagnosis. Conclusions Clinical measurements at diagnosis could potentially be used as precision markers in the treatment of GDM. Whether there are other sensitive markers that could be identified using more complex individual-level data, such as omics, and if these can feasibly be implemented in clinical practice remains unknown. These will be important to consider in future studies.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00371-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 9
    Online Resource
    Online Resource
    Utility and precision evidence of technology in the treatment of type 1 diabetes: a systematic review
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-10-05)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-10-05)
    Abstract: The greatest change in the treatment of people living with type 1 diabetes in the last decade has been the explosion of technology assisting in all aspects of diabetes therapy, from glucose monitoring to insulin delivery and decision making. As such, the aim of our systematic review was to assess the utility of these technologies as well as identify any precision medicine-directed findings to personalize care. Methods Screening of 835 peer-reviewed articles was followed by systematic review of 70 of them (focusing on randomized trials and extension studies with ≥50 participants from the past 10 years). Results We find that novel technologies, ranging from continuous glucose monitoring systems, insulin pumps and decision support tools to the most advanced hybrid closed loop systems, improve important measures like HbA1c, time in range, and glycemic variability, while reducing hypoglycemia risk. Several studies included person-reported outcomes, allowing assessment of the burden or benefit of the technology in the lives of those with type 1 diabetes, demonstrating positive results or, at a minimum, no increase in self-care burden compared with standard care. Important limitations of the trials to date are their small size, the scarcity of pre-planned or powered analyses in sub-populations such as children, racial/ethnic minorities, people with advanced complications, and variations in baseline glycemic levels. In addition, confounders including education with device initiation, concomitant behavioral modifications, and frequent contact with the healthcare team are rarely described in enough detail to assess their impact. Conclusions Our review highlights the potential of technology in the treatment of people living with type 1 diabetes and provides suggestions for optimization of outcomes and areas of further study for precision medicine-directed technology use in type 1 diabetes.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00358-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 10
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    Online Resource
    Participant characteristics in the prevention of gestational diabetes as evidence for precision medicine: a systematic review and meta-analysis
    Springer Science and Business Media LLC ; 2023
    In:  Communications Medicine Vol. 3, No. 1 ( 2023-10-05)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-10-05)
    Abstract: Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with responses to interventions in gestational diabetes mellitus (GDM) prevention. Methods We searched MEDLINE, EMBASE, and Pubmed to identify lifestyle (diet, physical activity, or both), metformin, myoinositol/inositol and probiotics interventions of GDM prevention published up to May 24, 2022. Results From 10347 studies, 116 studies ( n  = 40940 women) are included. Physical activity results in greater GDM reduction in participants with a normal body mass index (BMI) at baseline compared to obese BMI (risk ratio, 95% confidence interval: 0.06 [0.03, 0.14] vs 0.68 [0.26, 1.60] ). Combined diet and physical activity interventions result in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) than those with PCOS (0.62 [0.47, 0.82] vs 1.12 [0.78–1.61] ) and in those without a history of GDM than those with unspecified GDM history (0.62 [0.47, 0.81] vs 0.85 [0.76, 0.95] ). Metformin interventions are more effective in participants with PCOS than those with unspecified status (0.38 [0.19, 0.74] vs 0.59 [0.25, 1.43] ), or when commenced preconception than during pregnancy (0.21 [0.11, 0.40] vs 1.15 [0.86–1.55] ). Parity, history of having a large-for-gestational-age infant or family history of diabetes have no effect on intervention responses. Conclusions GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results disaggregated by a priori defined participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00366-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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