Genotype-stratified treatment for monogenic insulin resistance: a systematic review
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(Published version)
Date
2023
Authors
Semple, R.K.
Patel, K.A.
Auh, S.
Franks, P.W.
Rich, S.S.
Wagner, R.
Vilsbøll, T.
Vesco, K.K.
Udler, M.S.
Tuomi, T.
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Journal article
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Communications Medicine, 2023; 3(1):134-1-134-11
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Robert K. Semple, Kashyap A. Patel, Sungyoung Auh, ADA/EASD PMDI and Rebecca J. Brown
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Abstract
Background 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.
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Corrected by: Author Correction: Genotype-stratified treatment for monogenic insulin resistance: a systematic review, in Communications Medicine volume 4, Article number: 57 (2024). https://doi.org/10.1038/s43856-024-00482-2. The file Supplementary Data 3 was missing when this article was published. It has now been added and can be accessed via the Supplementary information section in the online version of the article. Citations to Supplementary Data 3 in the article remain unchanged.
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This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023, corrected publication 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/.