The Impact of Metabolic Status on Pain and Central Sensitization in Women With Lipedema: A Cross-Sectional Observational Study

Overview

The aim of this study is to evaluate the effect of metabolic markers (HOMA-IR, triglyceride/HDL ratio, HbA1c, waist and hip circumference measurements, BMI, etc.) on pain and central sensitization in patients diagnosed with lipedema. The primary objective is to investigate the association between metabolic markers and central sensitization. The secondary objective is to assess the relationship between metabolic markers and pain intensity, pain phenotype, and functional status.

Lipedema is a chronic disorder observed in women, characterized by symmetrical accumulation of adipose tissue in the lower extremities, easy bruising, and marked tenderness or pain. In lipedema, pain is often spontaneous, increases with pressure, and does not always correlate with the amount of adipose tissue. This suggests that lipedema-related pain cannot be explained solely by peripheral mechanical factors. Previous studies in patients with lipedema have demonstrated reduced pressure pain thresholds, bilateral and symmetrical hyperalgesia, and increased pain sensitivity extending beyond the areas of local adipose tissue involvement. These findings suggest that alterations in central pain processing mechanisms may occur in lipedema and that central sensitization may play a role. However, systematic studies specifically evaluating central sensitization in lipedema remain limited. Although lipedema has long been considered a "metabolically protected" condition, recent studies have reported that insulin resistance, dyslipidemia, and components of metabolic syndrome are more frequently observed, particularly in lipedema cases accompanied by obesity. HOMA-IR, which is used to evaluate insulin resistance; the triglyceride/HDL ratio (TG/HDL), a marker of atherogenic dyslipidemia; and HbA1c, reflecting long-term glycemic load, are closely associated with chronic inflammation and metabolic dysfunction. In the chronic pain literature, metabolic dysfunction has been shown to play an important role in the development of central sensitization and nociplastic pain, with obesity, insulin resistance, and dyslipidemia being associated with central pain amplification. However, to the best of our knowledge, no studies in lipedema have simultaneously evaluated the relationship between metabolic parameters, pain phenotype, and central sensitization. The aim of this study is to evaluate the effects of metabolic markers (HOMA-IR, triglyceride/HDL ratio, HbA1c, waist and hip circumference measurements, BMI, etc.) on pain and central sensitization in patients diagnosed with lipedema. The primary objective is to investigate the association between metabolic markers and central sensitization. The secondary objective is to assess the relationship between metabolic markers and pain intensity, pain phenotype, and functional status.