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Adipose Tissue_Appetite_and Obesity

MON-694 - Distinct Clinical Features of Acquired and Genetic Lipodystrophy Syndromes: Results from the LD-Lync Study

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Ozge Besci, MD: No financial relationships to disclose
Yasmin K. Aly, MD: No financial relationships to disclose
Frances D. Rodriguez-Ramos, BS: No financial relationships to disclose
Elif A. Oral, MD: No relevant disclosure to display


Background:
Lipodystrophy syndromes (LD), characterized by partial or generalized loss of adipose tissue and severe metabolic complications, may be congenital or acquired. Comprehensive longitudinal data comparing acquired and genetic LD subtypes remains limited. We aimed to characterize the natural history of acquired LD and identify key differences compared with genetic LD.

Methods:
A multicenter, prospective, observational study (LD-Lync, NCT03087253, data cut June 2025) was conducted. Annual assessments included medical history, questionnaires, laboratory data, anthropometrics, and clinical outcomes. Baseline characteristics and outcomes were compared between acquired and genetic LD using Chi-square or Fisher’s exact test for categorical and Wilcoxon Two-Sample Test for continuous variables.

Results:
Among 335 participants (80% female, 39 (28–54) years) enrolled, acquired LD (n=48) and genetic LD (n=287), including congenital generalized and familial partial LD (CGL/FPLD), had similar ages at baseline and LD onset. Overlapping autoimmune and inflammatory conditions were common in acquired LD, including rheumatologic/connective tissue disease (n=10), dermatologic disorders (n=23), gastrointestinal disease (n=10), immune deficiency (n=6), and exposure to cancer-related treatments (n=7), with a previous malignancy diagnosis also frequently observed (n=12). Patients with acquired LD had a lower median baseline BMI compared with genetic LD (22.4 vs 25.5 kg/m², p=0.020). Metabolic complications were significantly more prevalent in genetic LD, including hypertriglyceridemia (81.4% vs 58.3%, p=0.001), fatty liver disease (70.8% vs 50.0%, p=0.017), acanthosis nigricans (51.7% vs 29.2%, p=0.009), polycystic ovary syndrome (41.9% vs 17.1%, p=0.016), sleep apnea (26.0% vs 12.5%, p=0.028), and claudication (32.5% vs 14.6%, p=0.020). In contrast, cancer was significantly more frequent in acquired LD (25.0% vs 5.3%, p< 0.001) and occurred at a younger age (32 (14-48) vs 48 (42-49) years, p=0.020). In subpopulation analysis, cancer was more common in acquired partial LD than in FPLD (20.7% vs 6.2%, p=0.030), with a trend toward younger age at diagnosis (39 (20–48) vs 48.5 (43–52) years, p=0.074). Other metabolic complications (i.e., diabetes, cardiovascular problems, pancreatitis) and mortality were similar between groups.

Conclusion:
Genetic LD is associated with a higher burden of metabolic complications, whereas acquired LD shows a strong association with malignancy and immune-mediated conditions. Some of these differences may be partly explained by the distinct distribution of partial versus generalized LD in genetic and acquired forms. However, together, these findings highlight the need for subtype-specific clinical management strategies, with particular emphasis on cancer surveillance and immunologic evaluation in patients with acquired LD.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*