Development of lipodystrophy severity score to assess disease burden

A newly developed 8-domain clinical tool showed high content validity, feasibility, and reliability in assessing disease burden in lipodystrophy patients.

This summary is based on the publication of Brown RJ, Akinci B, Yosef M, et al. - Lipodystrophy Severity Score to Assess Disease Burden in Lipodystrophy. J Clin Endocrinol Metab. 2025 Feb 19:dgaf103 [Online ahead of print]. doi: 10.1210/clinem/dgaf103.

Introduction and methods

Background

Lipodystrophy syndromes are a rare and heterogeneous group of disorders characterized by selective loss or absence of adipose tissue [1], which may lead to insulin resistance, dyslipidemia, severe metabolic disease, and organ-specific complications [2-5]. To assess the disease burden in lipodystrophy, clinicians often depend on basic laboratory measures, such as HbA1c and triglycerides. However, as lipodystrophy encompasses multisystem organ abnormalities, a comprehensive approach to measure and quantify the disease burden is required.

Aim of the study

The study aim was to develop a lipodystrophy severity score (LDS) to assess the disease burden in patients with lipodystrophy that can aid in monitoring disease progression and/or identifying treatment benefits.

Methods

A group of 8 disease experts developed an 8-domain LDS, in consultation with patient organizations. The domains were: diabetes/insulin resistance, microvascular complications of diabetes, lipids, cardiovascular, liver, kidney, reproductive, and other. An online application of the LDS is available at https://ldscoring.com.

Feasibility and content validity of the LDS were rated by 28 other treating physicians and 9 representatives from different patient organizations. Using hypothetical patient profiles, the LDS was compared with the Clinical Global Impression (CGI) severity score, each scored at 2 different time points. The intrapatient change in LDS between 2 visits was compared with the CGI improvement score (CIS). For external validation, the LDS was calculated in 2 study cohorts of lipodystrophy patients treated with metreleptin, a leptin analogue.

Main results

Feasibility, content validity, and reliability

• The overall feasibility index was 100% for both treating physicians and patient organization representatives.
• The overall content validity index was 96% for treating physicians and 88% for patient organization representatives.
• The overall intraclass correlation coefficient was 0.969 (95%CI: 0.933–0.992) at baseline and 0.960 (95%CI: 0.919–0.987) at follow-up visits, indicating high reliability.
• Similar results were found for domain-specific index values.

Comparisons with CGI score and CIS

• The mean total LDS showed a strong correlation with the mean total CGI score at baseline (Pearson’s r=0.858; P<0.001) and follow-up (Pearson’s r=0.872; P<0.001).
• The mean numeric change in total LDS from baseline to follow-up was also strongly related to the mean total CIS (Pearson’s r=0.951; P<0.001).

Performance of LDS in metreleptin-treated patient cohorts

• In the cohort of patients with generalized lipodystrophy (n=62), treatment with metreleptin for 12 months reduced the median total LDS from 46 (IQR: 29–59) at baseline to 26 (IQR: 18–37) at 12 months (P<0.001), with 54% of the patients showing an improvement in total LDS of ≥25% at 12 months.
• In the patient cohort with partial lipodystrophy (n=17), the median total LDS decreased from 65 (IQR: 52–75) to 61 (IQR: 44–68) after 12 months of metreleptin treatment (P=0.04), with 2 patients (12%) experiencing a ≥25% improvement in total LDS at 12 months.

Conclusion

This newly developed 8-domain LDS showed high content validity, feasibility, and reliability as a clinical tool for assessment of disease burden in lipodystrophy patients. According to the authors, “[t]he LDS can reflect the severity of diverse manifestations of lipodystrophy and monitor changes following interventions.”

Find this article online at J Clin Endocrinol Metab.

References

1. Hussain I, Garg A. Lipodystrophy syndromes. Endocrinol Metab Clin North Am. 2016;45(4):783-797.
2. Oral EA. Lipoatrophic diabetes and other related syndromes. Rev Endocr Metab Disord. 2003;4(1):61-77.
3. Akinci B, Meral R, Oral EA. Phenotypic and genetic characteristics of lipodystrophy: pathophysiology, metabolic abnormalities, and comorbidities. Curr Diab Rep. 2018;18(12):143.
4. Akinci B, Oral EA, Neidert A, et al. Comorbidities and survival in patients with lipodystrophy: An International Chart Review Study. J Clin Endocrinol Metab. 2019;104(11):5120-5135.
5. Lim K, Haider A, Adams C, Sleigh A, Savage DB. Lipodistrophy: a paradigm for understanding the consequences of “overloading” adipose tissue. Physiol Rev. 2021;101(3):907-993.