Predictors of Psychosocial Burden and Pain in Lipodystrophy Syndromes

Background: Lipodystrophy (LD) syndromes comprise diverse rare disorders resulting from the deficiency of adipose tissue, leading to ectopic accumulation of excess lipids and metabolic comorbidities such as diabetes and dyslipidemia. We recently reported the presence of psychosocial difficulties and chronic pain in LD syndromes. We now investigate predictors of psychosocial aspects of LD using our prospective registry study LD Lync: Clinical Trials.gov # NCT03087253. Methods: LD Lync study is a multicenter prospective study that currently has 267 patients clinically diagnosed with LD syndrome, excluding HIV-associated cases. Participants' demographic information is obtained at baseline, and the study team completes a detailed medical history, physical examination, and anthropometric measurements at baseline and annual follow-up visits. Participants also complete questionnaires at each visit, including the Patient Health Questionnaire (PHQ9) depression module, Generalized Anxiety Disorder 7-Item Scale (GAD7), RAND SF-36 Quality of Life Questionnaire, Brief Pain Inventory (BPI), Michigan Body Map, Quality of Life questionnaire, and Modified Binge Eating Scale (Modified-BES 13). Univariable and multivariable analysis models (adjusted for gender and age) are used to understand the association between LD subtypes (including congenital generalized, familial partial, acquired generalized, and acquired partial lipodystrophy) health complications, and questionnaire results. Results: In univariable analyses, higher PHQ9 scores were associated with LD complications such as pancreatitis (p=0.0017), fatty liver disease (p<0.0001), and cardiac disease (p=0.0241), and with presence of physical dysfunction (p<0.0001), fatigue (p<0.0001), or chronic pain (in 3 or more regions, p=0.0059), role limitations (p<0.0001), and impaired social functioning (p<0.0001). In multivariable analyses, higher PHQ9 scores were associated with higher anxiety as measured by GAD7 scores (p<0.0001), emotional distress (p=0.0025), increased fatigue severity (p<0.0001), and chronic depression (p=0.014). In the multivariable model for GAD7 scores, increased PHQ9 scores (p<0.0001) and emotional distress (p<0.0001) were important predictors. Neither lipodystrophy subtype nor baseline serum leptin concentration predicted PHQ9, pain interference scores, or the presence of multiregional pain. Conclusion: Our analyses represent the most comprehensive evaluation of the psychosocial burden of LD to date. In patients with LD, there is a significant association between the presence of metabolic comorbidities with psychosocial burden and pain. Further research is required to understand the mechanisms of these relationships.