All-cause mortality in people with type 2 diabetes and lipodystrophy-like metabolic phenotype

Abstract

Aim: We wanted to investigate whether the lipodystrophy (LD)-like phenotype increases mortality in type 2 diabetes. To this end we first developed and confirmed the triglyceride/BMI ratio (TBR index) as an inexpensive and widely available marker of the LD-like metabolic phenotype. The TBR index was then tested for association with all-cause mortality in patients with type 2 diabetes.

Research design and methods: Associations between TBR and mortality were assessed by Cox in 3 type 2 diabetes cohorts (n = 2137, n = 960, and n = 5060). A 20-SNP genotype risk score (GRS), associated with LD-like phenotype was investigated to identify the molecular basis of TBR variability.

Main finding: In all cohorts, the highest TBR decile showed features of LD-like phenotype, including atherogenic dyslipidemia, lower BMI, worse glycemic control, insulin resistance, elevated gamma-glutamyl transferase, and hypoadiponectinemia. In the meta-analysis, decile 10 had higher mortality risk (HR = 1.46, P < .0001). Finally, in a subset of 1 of the 3 cohorts, the LD-like GRS was significantly associated with TBR.

Conclusion: The TBR is a novel, inexpensive and easily available marker that identifies a subgroup of type 2 diabetes patients with a LD-like phenotype, partly explained by genetic factors. Our findings help disentangle the heterogeneity of death risk in diabetes, refine diagnostic and follow-up algorithms and enable specific treatments for improving long-term outcomes in LD-like individuals.

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Cite

BibTeX RIS

BibTeX

@article{paola2026allcause,
  title = {{All-cause mortality in people with type 2 diabetes and lipodystrophy-like metabolic phenotype}},
  author = {Rosa Di Paola and Claudia Menzaghi and Mario Mastroianno and Monia Garofolo and Lucia Salvemini and Daniela Lucchesi and Salvatore De Cosmo and Giuseppe Penno and Philippe Froguel and Alessandro Doria and Vincenzo Trischitta},
  journal = {Journal of the Endocrine Society},
  year = {2026},
  month = oct,
  doi = {10.1210/jendso/bvag238},
  url = {https://europepmc.org/article/PMC/PMC13720639},
  note = {CC BY-NC-ND},
}

RIS

TY  - JOUR
TI  - All-cause mortality in people with type 2 diabetes and lipodystrophy-like metabolic phenotype
AU  - Rosa Di Paola
AU  - Claudia Menzaghi
AU  - Mario Mastroianno
AU  - Monia Garofolo
AU  - Lucia Salvemini
AU  - Daniela Lucchesi
AU  - Salvatore De Cosmo
AU  - Giuseppe Penno
AU  - Philippe Froguel
AU  - Alessandro Doria
AU  - Vincenzo Trischitta
PY  - 2026
DA  - 2026/10/19
JO  - Journal of the Endocrine Society
DO  - 10.1210/jendso/bvag238
UR  - https://europepmc.org/article/PMC/PMC13720639
AB  - Aim: We wanted to investigate whether the lipodystrophy (LD)-like phenotype increases mortality in type 2 diabetes. To this end we first developed and confirmed the triglyceride/BMI ratio (TBR index) as an inexpensive and widely available marker of the LD-like metabolic phenotype. The TBR index was then tested for association with all-cause mortality in patients with type 2 diabetes.  Research design and methods: Associations between TBR and mortality were assessed by Cox in 3 type 2 diabetes cohorts (n = 2137, n = 960, and n = 5060). A 20-SNP genotype risk score (GRS), associated with LD-like phenotype was investigated to identify the molecular basis of TBR variability.  Main finding: In all cohorts, the highest TBR decile showed features of LD-like phenotype, including atherogenic dyslipidemia, lower BMI, worse glycemic control, insulin resistance, elevated gamma-glutamyl transferase, and hypoadiponectinemia. In the meta-analysis, decile 10 had higher mortality risk (HR = 1.46, P < .0001). Finally, in a subset of 1 of the 3 cohorts, the LD-like GRS was significantly associated with TBR.  Conclusion: The TBR is a novel, inexpensive and easily available marker that identifies a subgroup of type 2 diabetes patients with a LD-like phenotype, partly explained by genetic factors. Our findings help disentangle the heterogeneity of death risk in diabetes, refine diagnostic and follow-up algorithms and enable specific treatments for improving long-term outcomes in LD-like individuals.
SN  - 2472-1972
ER  -

Abstract

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