All-cause mortality in people with type 2 diabetes and lipodystrophy-like metabolic phenotype
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Journal of the Endocrine Society
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,255
Funders: Abbott Laboratories, Amylin Pharmaceuticals, AstraZeneca, GlaxoSmithKline, Sanofi, King Pharmaceuticals, Schering-Plough, Merck KGaA, Omron Healthcare, European Commission, Bayer HealthCare, Ministero della Salute, Ministero dell’Istruzione, dell’Università e della Ricerca, Università degli Studi di Padova, Novo Nordisk, Sapienza Università di Roma, Innovative Medicines Initiative, Centers for Disease Control and Prevention, National Institute on Aging, National Heart, Lung, and Blood Institute, National Eye Institute, National Institute of Diabetes and Digestive and Kidney Diseases, Novartis Portugal, Niilo Helanderin Säätiö, NextGenerationEU
Awards: G1033601615, G1534766142, G1771691406, G1955785366, G2150788371, G217652925, G2247514905, G2748055689, G3186661918, G3667269547, G401067667, G4887349202, G4931486092, G552090665, G5830467628, G604937562, G67324039, G692906228, G7683729920, G77894727, G781655334, G8233719108, European Health Data and Evidence Network
OpenAlex ID: W7222947051