FRI055 LYNC-LD: Prospective Multicenter Natural History Study Of Lipodystrophy Syndromes To Determine Prevalence, Incidence And Predictors Of Diabetes And Severe Hypertriglyceridemia, And Their Complications

Abstract

Abstract Disclosure: M.C. Foss de Freitas: Advisory Board Member; Self; PTC Therapeutics. D.S. Rosenberg: None. M. Celik Guler: None. M. Yosef: None. S. Khalatbari: None. R. Carman: None. A. DillGomes: None. M. Ashmus: None. C. Spino: None. B. Akinci: Advisory Board Member; Self; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals. Consulting Fee; Self; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals, AstraZeneca, Lilly USA, LLC, Merck & Co., Novartis Pharmaceuticals, Novo Nordisk, Boehringer Ingelheim, Sanofi, Servier. R.J. Brown: Grant Recipient; Self; Regeneron Pharmaceuticals. E.A. Oral: Consulting Fee; Self; Regeneron Pharmaceuticals, Aegerion Pharmaceuticals, Ionis Pharmaceuticals Inc., Third Rock Ventures, Rejuvenate Inc. Grant Recipient; Self; Regeneron Pharmaceuticals, Aegerion Pharmaceuticals, Ionis Pharmaceuticals Inc., Novo Nordisk, Rhythm pharmaceuticals, Fractyl Laboratories, GID Dynamics. Other; Self; Aegerion Pharmaceuticals. Background: Lipodystrophy syndromes are rare disorders characterized by selective deficiency of adipose tissue leading to insulin resistance, diabetes mellitus, dyslipidemia and hepatic steatosis. We are conducting a comprehensive, multicenter and international observational registry study to document the natural history and prevalence of lipodystrophy syndromes in the contemporary era. Methods: All participants clinically diagnosed with a lipodystrophy syndrome, excluding HIV-associated lipodystrophy, at the participating centers may be enrolled. Once enrolled, demographic information and detailed medical history are obtained by the study team and from the participant. Patients are followed with reevaluations every 12 months. Participant questionnaires include the Patient Health Questionnaire (PHQ-9), the generalized anxiety disorder 7-item scale (GAD-7), the RAND SF-36 quality of life questionnaire, and a brief pain inventory (BPI). Univariable and multivariable repeated measure analyses were performed. Results: 148 individuals were enrolled from March 2018 to March 2022 (data-cut) with baseline age: 42 ± 15 years, 82% female, and BMI: 27.6 ± 6.5 kg/m2. Familial partial lipodystrophy is the most prevalent diagnosis (n=93, 65%), followed by congenital generalized lipodystrophy (n=13, 9.1%). There was a high prevalence of diabetes mellitus (77%), hypertriglyceridemia (82%), and hepatic steatosis (69%). 25% had at least one pancreatitis episode reported, with first episode of pancreatitis reported at age 30 ± 13 years. Cirrhosis was observed in 10% of the participants, with age of onset 39 ± 13 years. We observed a high incidence of depression and anxiety (47 and 45%) from medical history evaluation. The pain severity score (PSS) calculated from the BPI was positively associated with depression (PHQ9; p<0.0001) and anxiety (GAD-7; p=0.0003) adjusted for follow-up time. Patients with mild/moderate pain (PSS ≤4) showed a significant positive association with several Quality of Life (QoL) scores, such as physical functioning, limitation to physical health, limitation with emotional problems, and lack of energy/fatigue, social functioning, and general health (p<0.001 for all associations). During follow-up, we observed a decrease in triglyceride levels (from 585 ± 802 at baseline to 480 ± 486 mg/dL at year 3 (n=28)), while HbA1c increased from 7.4 ± 1.9 at baseline to 8.2 ± 2.1 % at year 3 (n=28). We observed 6 (4%) deaths during the 4-year follow-up. Conclusion: Our data may help clinicians, scientists, and patients with medical evaluation and decision-making in the clinical environment and provide insight into natural history as regulators evaluate new drugs. Presentation: Friday, June 16, 2023