{
    "abstract": "Type 1 diabetes is a serious, chronic disorder with an increasing incidence among children and adolescents. Glycemic control in individuals with type 1 diabetes is better managed through a basal-bolus regimen with either regular human or rapid-acting insulin analogues administered as a bolus at mealtimes. Rapid-acting insulin analogues have been hypothesized to cause optimal glycemic control and less risk of hypoglycemic episodes compared to regular human insulins. However, this has never been systematically assessed in children and adolescents with type 1 diabetes. Therefore, this systematic review aims to assess the beneficial and harmful effects of regular human insulins versus rapid-acting insulin analogues in children and adolescents.\nThis is a protocol for a systematic review. A search in major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries will be performed by a search specialist. We will include published and unpublished randomized clinical trials comparing regular human insulins versus rapid-acting insulin analogues (lispro, aspart, or glulisine). Two review authors will independently extract data and conduct risk of bias assessments. Primary outcomes will be severe hypoglycemia, ketoacidosis, and serious adverse events. Secondary outcomes will be quality of life, HbA1c, and non-serious adverse events. Data will be analyzed using fixed-effect meta-analyses, random-effects meta-analyses, and Trial Sequential Analysis. Several subgroup analyses are planned. Risk of bias will be assessed with the Cochrane Risk of Bias tool-version 2, an eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE).\nThe beneficial and adverse effects of regular human insulins versus rapid-acting insulin analogues have not been systematically assessed in children and adolescents. There is a need for a comprehensive systematic review of the current evidence.\nPROSPERO: CRD42024508625.",
    "authors": [
        {
            "affiliation": "Centre for Clinical Intervention Research, Copenhagen Trial Unit, Capital Region of Denmark, Copenhagen, Denmark. johanne.juul.petersen@ctu.dk.\nFaculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark. johanne.juul.petersen@ctu.dk.",
            "firstname": "Johanne Juul",
            "initials": "JJ",
            "lastname": "Petersen"
        },
        {
            "affiliation": "Centre for Clinical Intervention Research, Copenhagen Trial Unit, Capital Region of Denmark, Copenhagen, Denmark.\nMental Health Centre Stolpegaard, Mental Health Services in the Capital Region of Denmark, Gentofte, Denmark.\nDepartment of Psychology, University of Copenhagen, Copenhagen, Denmark.",
            "firstname": "Sophie",
            "initials": "S",
            "lastname": "Juul"
        },
        {
            "affiliation": "Centre for Clinical Intervention Research, Copenhagen Trial Unit, Capital Region of Denmark, Copenhagen, Denmark.\nDepartment of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.",
            "firstname": "Caroline Barkholt",
            "initials": "CB",
            "lastname": "Kamp"
        },
        {
            "affiliation": "Centre for Clinical Intervention Research, Copenhagen Trial Unit, Capital Region of Denmark, Copenhagen, Denmark.\nDepartment of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.",
            "firstname": "Pascal",
            "initials": "P",
            "lastname": "Faltermeier"
        },
        {
            "affiliation": "Centre for Clinical Intervention Research, Copenhagen Trial Unit, Capital Region of Denmark, Copenhagen, Denmark.\nDepartment of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.\nDepartment of Cardiology and Endocrinology, Slagelse Hospital, Region of Zealand, Slagelse, Denmark.",
            "firstname": "Christina Dam Bjerregaard",
            "initials": "CDB",
            "lastname": "Sillassen"
        },
        {
            "affiliation": "Unit of Pediatrics, Hospital Vithas Almer\u00eda, Instituto Hispalense de Pediatr\u00eda, Almer\u00eda, Andalusia, Spain.\nDepartment of Nursing, Physiotherapy, and Medicine, Faculty of Health Sciences, University of Almer\u00eda, Almer\u00eda, Spain.",
            "firstname": "Tiago Jeronimo",
            "initials": "TJ",
            "lastname": "Dos Santos"
        },
        {
            "affiliation": "Centre for Clinical Intervention Research, Copenhagen Trial Unit, Capital Region of Denmark, Copenhagen, Denmark.\nDepartment of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.",
            "firstname": "Janus Christian",
            "initials": "JC",
            "lastname": "Jakobsen"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2025. The Author(s).",
    "doi": "10.1186/s13643-024-02729-4",
    "journal": "Systematic reviews",
    "keywords": [
        "Adolescents",
        "Children",
        "Meta-analysis",
        "Rapid-acting insulin analogues",
        "Regular human insulins",
        "Type 1 diabetes"
    ],
    "methods": null,
    "publication_date": "2025-01-07",
    "pubmed_id": "39763007\n34883188\n3391346\n11724421\n20723815\n34427600\n16530579\n23780460\n23941366\n36177823\n24685959\n34099516\n29523007\n36537531\n26158184\n36507640\n32591065\n16301090\n31666181\n22270400\n30639280\n27362975\n31873857\n30622653\n29623593\n31690574\n22711298\n27160381\n8815760\n28922704\n30373636\n29258565\n25138801\n8366922\n19445743\n3048052\n9400915\n25555855\n25554246\n1593914\n20171303\n28207928\n35352103\n29207961\n12111919\n12958120\n16345038\n11914310\n20920306\n25416419\n3802833\n3616287\n18083463\n18411040\n18824466\n18824467\n20042080\n20865104\n27519923\n18436948\n21185693\n14517128\n20920306\n18436948\n14517128",
    "results": null,
    "title": "Regular human insulins versus rapid-acting insulin analogues in children and adolescents with type 1 diabetes: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis.",
    "xml": "<Element 'PubmedArticle' at 0x78850331f290>"
}