Unraveling the natural history of lipodystrophy syndromes: insights from the prospective LD-Lync study

Lipodystrophy syndromes represent a diverse group of rare disorders characterized by deficiency and abnormal distribution of adipose tissue that may be generalized (GL) or partial (PL), leading to significant metabolic abnormalities.

To elucidate the natural history of critical comorbidities of lipodystrophy.

Ongoing, prospective, multicenter, registry study (LD Lync; NCT03087253). This analysis reports 266 patients with lipodystrophy enrolled until October 11, 2023.

The median age was 39 years ([28-54], range: 6-76 years; male/female: 50/216). Hypertriglyceridemia (n = 202, 75.9%) was the most common comorbidity, followed by diabetes (n = 190, 72.0%), hepatic steatosis (n = 182, 68.4%), and hypertension (n = 130, 48.8%). Pancreatitis was detected in 21.8% of patients (n = 58), and cirrhosis in 7.1% of patients (n = 19). The median age at diagnosis was significantly earlier in patients with GL compared to those with PL for both diabetes (16 [14-32] years in GL vs 35 [25-50] years in PL) and hypertriglyceridemia (20 [15-26] years in GL vs 30 [22-49] years in PL) (P < .0001). Seven (2.6%) patients died during follow-up. Multiple medications were used to treat metabolic disease. Eighty-one (30.4%) patients received at least one dose of metreleptin during clinical studies or commercially during follow-up.

Our findings confirm that patients with lipodystrophy face a significant risk of comorbidities, with an earlier onset of diabetes, hypertriglyceridemia, and hepatic steatosis in those with GL compared to PL. This registry will serve as a crucial resource for gaining insights into the burden of disease in lipodystrophy.