New findings presented at EASD 2026 suggest that mild, lifelong reductions in insulin signaling may be associated with a more favorable metabolic profile, challenging the view that all forms of insulin resistance are detrimental to health.
A genetic study presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2026 in Milan has revealed that certain forms of genetically determined insulin resistance may not be associated with an increased risk of diabetes or other adverse health outcomes.
Researchers from the University of Exeter, UK, analyzed whole-genome sequencing data from 458,784 UK Biobank participants of genetically inferred European ancestry, identifying 524 carriers of rare, predicted damaging variants in the insulin receptor gene (INSR). These variants provided a model for investigating the long-term effects of partially reduced insulin receptor signaling.
Despite exhibiting mildly elevated insulin levels, carriers demonstrated a more favorable metabolic profile, including lower triglycerides, LDL cholesterol, liver enzymes, and waist-to-hip ratio, with reductions ranging from 0.16 to 0.34 standard deviations (all p<0.0001). HDL cholesterol was also higher (0.17 standard deviations; p<0.000034), while BMI did not differ significantly.
Importantly, no statistically significant increase in all-cause mortality, diabetes, cardiovascular disease, or malignancy was detected among carriers (all OR<1.02; p>0.4). The favorable metabolic profile was also observed in the independent All of Us Biobank, while analyses of a young-onset diabetes cohort and the Type 2 Diabetes Knowledge Portal found no enrichment for diabetes.
The researchers suggest that mild, lifelong reductions in insulin receptor signaling may have different metabolic effects from the insulin resistance typically associated with type 2 diabetes and cardiometabolic disease.
These findings challenge the assumption that all forms of insulin resistance are harmful and could help identify new biological pathways involved in metabolic health. However, further research is needed to understand the mechanisms involved and determine whether they have therapeutic implications.
Abstract details: Murray Leech J, Hawkes G, Hattersley A, Weedon MN, Brown RJ, Semple RK, Patel K. Human genetics reveals novel metabolic benefits of lifelong partial insulin resistance. Oral presentation 53. Presented at: 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD); September 28–October 2, 2026; Milan, Italy.
Disclosures: This article was created by the touchENDOCRINOLOGY team utilizing AI as an editorial tool (ChatGPT [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: Study challenges conventional thinking on insulin resistance. touchENDOCRINOLOGY. September 2026
Editor: Nicola Cartridge, Director of Content
touchOPHTHALMOLOGY coverage of EASD 2026: This content has been developed independently by Touch Medical Media for touchENDOCRINOLOGY. It is not affiliated with the EASD.
