Preprint paired analysis suggests VSG may improve metabolic and renal markers in youth with T2D and obesity
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Key Takeaway
Interpret preliminary VSG findings in youth with T2D and obesity cautiously due to small sample size.
This is a preprint paired analysis examining vertical sleeve gastrectomy (VSG) in youth with type 2 diabetes and obesity, using data from the IMPROMVE-T2D cohort and Teen-LABS study. The analysis followed 5 youth for 12 months, comparing pre-operative and post-operative states, with an independent cohort of 64 youth for additional context. The scope includes assessment of weight loss, insulin sensitivity, metabolic parameters, renal outcomes, and various molecular pathways.
The authors report improvements across multiple domains. These include weight loss, insulin sensitivity, and metabolic parameters, along with reductions in renal hyperfiltration, total kidney volume, mesangial matrix area, and microalbuminuria. At the molecular level, they observed repression of glycolysis, gluconeogenesis, and tricarboxylic acid cycle genes; upregulation of AMP-activated protein kinase and forkhead box O3; decreased ribosomal phosphorylated S6K; attenuation of mTORC1 activity; diminished JAK/STAT pathway activation in proximal tubule; and lower circulating ligands. No effect sizes, p-values, or confidence intervals were reported for these outcomes.
As a preprint, this work has not undergone peer review. The analysis is observational and based on a very small paired sample of 5 youth, limiting statistical power and generalizability. The authors do not report safety data, adverse events, or practice relevance. Funding sources include the University of Washington with the American Diabetes Association, University of Michigan with Chan Zuckerberg Initiative, and Breakthrough T1D.
Given the preliminary nature and small sample size, these findings should be interpreted cautiously. They suggest potential metabolic and renal benefits of VSG in this population but do not establish causality or long-term outcomes. Clinicians should await peer-reviewed publication and larger controlled studies before drawing clinical conclusions.
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View Original Abstract ↓
BACKGROUNDYouth with type 2 diabetes (T2D) and severe obesity face high risk of diabetic kidney disease, which metabolic bariatric surgery (MBS) can mitigate. This study explores structural and molecular changes in kidneys after vertical sleeve gastrectomy (VSG), a form of MBS.METHODSWe performed paired analyses, including metabolic profiling, kidney volume assessment, histological evaluation, and single-cell RNA sequencing (scRNA-seq), on kidney biopsies from 5 youth with T2D and obesity pre- and 12 months post-VSG in the IMPROVE-T2D (Impact of Metabolic surgery on Pancreatic, Renal and cardiOVascular hEalth in youth with T2D) cohort. Circulating proteomics with kidney transcriptomics were linked using data from an independent cohort of youth with obesity, with or without T2D, undergoing MBS in Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS, n = 64).RESULTSAfter VSG, participants lost weight and had improvements in insulin sensitivity and metabolic parameters. Kidney changes included reduced renal hyperfiltration, total kidney volume, mesangial matrix area, and microalbuminuria. scRNA-seq in proximal tubule (PT) and thick ascending limb cells indicated repression of glycolysis, gluconeogenesis, and tricarboxylic acid (TCA) cycle genes, with upregulation of AMP-activated protein kinase (AMPK) and forkhead box O3 (FOXO3). Decreased metabolic signaling aligned with reduced ribosomal phosphorylated S6K (pS6K), suggesting attenuated mTORC1 activity. Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation in PT was diminished, correlating with lower circulating ligands from Teen-LABS proteomic data.CONCLUSIONMBS/VSG prompts kidney molecular adaptations, providing potential targets for nonsurgical interventions against obesity- and diabetes-associated kidney disease.FUNDINGUniversity of Washington with the American Diabetes Association, University of Michigan with Chan Zuckerberg Initiative, and Breakthrough T1D.
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