{
  "abstract": "Increased fasting insulin reflects insulin resistance and is as a precursor to type 2 diabetes and a risk factor for kidney, heart and liver diseases and mortality. Cluster-specific fasting insulin polygenic scores (PS) characterize insulin resistance mechanisms based on insulin-related genetic associations with metabolic traits, and they have not been evaluated for liver outcomes. We calculated seven previously developed FI cluster-specific PS, including non-diabetogenic (Preserved Insulin Secretion, Elevated Insulin Secretion, Proinsulin) and diabetogenic clusters (Adiposity-driven Hyperinsulinemia, Visceral Adiposity, Lipodystrophy, Liver/Lipid) in 12,631 participants of the Hispanic Community Healthy Study/Study of Latinos (HCHS/SOL), and tested their association with type 2 diabetes, cardiovascular, kidney and liver outcomes. We also tested the association of FI clusters with indices of insulin homeostasis in additional 1,316 Hispanic individuals. Among HCHS/SOL participants (mean age 46 years, 59% women, 20% with diabetes), we validated associations of FI cluster-specific PS and the 19 traits used to generate clusters. The Lipodystrophy cluster was associated with type 2 diabetes (p-value =3.5 x 10-5). In addition, the Adiposity-driven Hyperinsulinemia cluster was associated with the hepatic steatosis index (p-value = 2.2 x1017) and the fatty liver index (p-value = 1.7 x1014), while the Liver/Lipid cluster with liver fibrosis (p-value = 1.5 x104) and lower kidney function (p-value = 5.2 x 10-5). The non-diabetogenic Elevated Insulin Secretion cluster-specific PS was associated with the disposition index (p = 0.0015). These results support insulin resistance mechanisms implicated in type 2 diabetes, liver and kidney outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "The University of North Carolina at Chapel Hill"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "K. M. Reynolds"
    },
    {
      "name": "J. Lash"
    },
    {
      "name": "A. Morris"
    },
    {
      "name": "M. L. Daviglus"
    },
    {
      "name": "L. C. Gallo"
    },
    {
      "name": "K. D. Taylor"
    },
    {
      "name": "J. Cai"
    },
    {
      "name": "J. Cui"
    },
    {
      "name": "H. Mattix-Kramer"
    },
    {
      "name": "Y.-D. I. Chen"
    },
    {
      "name": "D. Sotres-Alvarez"
    },
    {
      "name": "J. I. I. Rotter"
    },
    {
      "name": "M. O. Goodarzi"
    },
    {
      "affs": [
        0
      ],
      "name": "N. Franceschini"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0x6p56b32fn98.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.03.26367229",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.11.03.26367229v1.full",
  "id": "0x6p56b32fn98",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.11.03.26367229v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "endocrinology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.11.03.26367229v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0x6p56b32fn98.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T00:21:02Z",
      "native_id": "10.64898/2026.11.03.26367229",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.11.03.26367229v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:endocrinology",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Insulin genetic clusters and clinical outcomes in Hispanics/Latinos",
  "title_text": "Insulin genetic clusters and clinical outcomes in Hispanics/Latinos",
  "type": "preprint",
  "updated_at": "2026-11-07T00:20:51Z",
  "url": "https://research.draconitic.com/paper/0x6p56b32fn98",
  "venue": "medRxiv",
  "versions": []
}