Decoding inflammation to target hybrid diabetes phenotypes
5 affiliations
- 1International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Sciences, Università di Milano
- 2Translational Medicine Department, Sidra Medicine
- 3Division of Endocrinology, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco
- 4Department of Biomedical and Clinical Sciences, Università di Milano and Pio Albergo Trivulzio Hospital
- 5Nephrology Division, Boston Children’s Hospital and Transplantation Research Center, Brigham and Women’s Hospital, Harvard Medical School
Abstract
With the escalating global epidemic of overweight and obesity worldwide, metabolic abnormalities (i.e., central obesity, insulin resistance, dyslipidemia and hypertension) are raising in patients with type 1 diabetes (T1D). On the other hand, data are emerging on the detection of autoimmune markers in obese individuals previously diagnosed with type 2 diabetes (T2D). These overlapping immune-metabolic features, characterizing hybrid phenotypes of diabetes such as double diabetes (DD) and latent autoimmune diabetes in adults (LADA), add a new layer of complexity in the diabetes spectrum and increase the risk of diabetes-related complications and mortality. Low-grade chronic inflammation is thought to play a pivotal role in the pathogenesis of DD and LADA and may represent a major driver in β-cell dysfunction and metabolic dysregulation. However, the literature on the topic is still limited, as well as the availability of specific therapeutic clinical approaches. This review aims to summarize current evidence on inflammatory and immune-metabolic biomarkers for early detection and identification of DD and LADA as compared to other types of diabetes. Novel diagnostic strategies, including genomics, miRNomics, metabolomics and microbiomics analysis, together with therapeutic options targeting metabolic and inflammatory pathways will be also explored. Challenges, including disease heterogeneity will be discussed alongside future directions, emphasizing the need for personalized medicine and longitudinal studies to shed more light on this overlooked hybrid phenotypes of diabetes.
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BibTeX
@article{rossi2026decoding,
title = {{Decoding inflammation to target hybrid diabetes phenotypes}},
author = {Giada Rossi and Annalisa Terranegra and Maria Elena Lunati and Ida Pastore and Lorenzo Pozzi Canova and Loredana Bucciarelli and Vincenzo Cimino and Cristian Loretelli and Moufida Ben Nasr and Paolo Fiorina and Francesca D’Addio},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1922969},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1922969/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Decoding inflammation to target hybrid diabetes phenotypes
AU - Giada Rossi
AU - Annalisa Terranegra
AU - Maria Elena Lunati
AU - Ida Pastore
AU - Lorenzo Pozzi Canova
AU - Loredana Bucciarelli
AU - Vincenzo Cimino
AU - Cristian Loretelli
AU - Moufida Ben Nasr
AU - Paolo Fiorina
AU - Francesca D’Addio
PY - 2026
DA - 2026/10/15
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1922969
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1922969/full
AB - With the escalating global epidemic of overweight and obesity worldwide, metabolic abnormalities (i.e., central obesity, insulin resistance, dyslipidemia and hypertension) are raising in patients with type 1 diabetes (T1D). On the other hand, data are emerging on the detection of autoimmune markers in obese individuals previously diagnosed with type 2 diabetes (T2D). These overlapping immune-metabolic features, characterizing hybrid phenotypes of diabetes such as double diabetes (DD) and latent autoimmune diabetes in adults (LADA), add a new layer of complexity in the diabetes spectrum and increase the risk of diabetes-related complications and mortality. Low-grade chronic inflammation is thought to play a pivotal role in the pathogenesis of DD and LADA and may represent a major driver in β-cell dysfunction and metabolic dysregulation. However, the literature on the topic is still limited, as well as the availability of specific therapeutic clinical approaches. This review aims to summarize current evidence on inflammatory and immune-metabolic biomarkers for early detection and identification of DD and LADA as compared to other types of diabetes. Novel diagnostic strategies, including genomics, miRNomics, metabolomics and microbiomics analysis, together with therapeutic options targeting metabolic and inflammatory pathways will be also explored. Challenges, including disease heterogeneity will be discussed alongside future directions, emphasizing the need for personalized medicine and longitudinal studies to shed more light on this overlooked hybrid phenotypes of diabetes.
SN - 1664-2392
ER -