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  • 1
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    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)
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00366-x
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 3096949-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    Impact of individual and environmental factors on dietary or lifestyle interventions to prevent type 2 diabetes development: 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)
    Kurzfassung: The variability in the effectiveness of type 2 diabetes (T2D) preventive interventions highlights the potential to identify the factors that determine treatment responses and those that would benefit the most from a given intervention. We conducted a systematic review to synthesize the evidence to support whether sociodemographic, clinical, behavioral, and molecular factors modify the efficacy of dietary or lifestyle interventions to prevent T2D. Methods We searched MEDLINE, Embase, and Cochrane databases for studies reporting on the effect of a lifestyle, dietary pattern, or dietary supplement interventions on the incidence of T2D and reporting the results stratified by any effect modifier. We extracted relevant statistical findings and qualitatively synthesized the evidence for each modifier based on the direction of findings reported in available studies. We used the Diabetes Canada Clinical Practice Scale to assess the certainty of the evidence for a given effect modifier. Results The 81 publications that met our criteria for inclusion are from 33 unique trials. The evidence is low to very low to attribute variability in intervention effectiveness to individual characteristics such as age, sex, BMI, race/ethnicity, socioeconomic status, baseline behavioral factors, or genetic predisposition. Conclusions We report evidence, albeit low certainty, that those with poorer health status, particularly those with prediabetes at baseline, tend to benefit more from T2D prevention strategies compared to healthier counterparts. Our synthesis highlights the need for purposefully designed clinical trials to inform whether individual factors influence the success of T2D prevention strategies.
    Materialart: Online-Ressource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00363-0
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 3096949-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    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)
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00357-y
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 3096949-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    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)
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00369-8
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 3096949-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: 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)
    Kurzfassung: A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy. Methods We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review. Results Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes. Conclusions Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.
    Materialart: Online-Ressource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00359-w
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 3096949-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    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)
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00358-x
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 3096949-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    Genotype-stratified treatment for monogenic insulin resistance: 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)
    Kurzfassung: Monogenic insulin resistance (IR) includes lipodystrophy and disorders of insulin signalling. We sought to assess the effects of interventions in monogenic IR, stratified by genetic aetiology. Methods Systematic review using PubMed, MEDLINE and Embase (1 January 1987 to 23 June 2021). Studies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. Individual data were extracted and duplicates were removed. Outcomes were analysed for each gene and intervention, and in aggregate for partial, generalised and all lipodystrophy. Results 10 non-randomised experimental studies, 8 case series, and 23 case reports meet inclusion criteria, all rated as having moderate or serious risk of bias. Metreleptin use is associated with the lowering of triglycerides and haemoglobin A1c (HbA1c) in all lipodystrophy ( n  = 111), partial ( n  = 71) and generalised lipodystrophy ( n  = 41), and in LMNA , PPARG , AGPAT2 or BSCL2 subgroups ( n  = 72,13,21 and 21 respectively). Body Mass Index (BMI) is lowered in partial and generalised lipodystrophy, and in LMNA or BSCL2 , but not PPARG or AGPAT2 subgroups. Thiazolidinediones are associated with improved HbA1c and triglycerides in all lipodystrophy ( n  = 13), improved HbA1c in PPARG ( n  = 5), and improved triglycerides in LMNA ( n  = 7). In INSR -related IR, rhIGF-1, alone or with IGFBP3, is associated with improved HbA1c ( n  = 17). The small size or absence of other genotype-treatment combinations preclude firm conclusions. Conclusions The evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to improve metabolic markers in lipodystrophy, and rhIGF-1 appears to lower HbA1c in INSR-related IR. For other interventions, there is insufficient evidence to assess efficacy and risks in aggregated lipodystrophy or genetic subgroups.
    Materialart: Online-Ressource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00368-9
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 3096949-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
    Springer Science and Business Media LLC ; 2023
    In:  Nature Medicine
    Details
    In: Nature Medicine, Springer Science and Business Media LLC
    Materialart: Online-Ressource
    ISSN: 1078-8956 , 1546-170X
    URL: Article
    DOI: 10.1038/s41591-023-02502-5
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 1484517-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    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)
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00360-3
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 3096949-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    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)
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-023-00371-0
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 3096949-9
    Standort Signatur Einschränkungen Verfügbarkeit
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