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

THE IMPACT OF METABOLIC STATUS ON PAIN AND CENTRAL SENSITIZATION IN WOMEN WITH LIPEDEMA: A CROSS-SECTIONAL OBSERVATIONAL STUDY

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.

Study Overview

• Status: Recruiting
• Conditions: Pain; Central Sensitization; Lipedema; HOMA-IR

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 59

Contacts and Locations

• Study Contact: Name: Fatma B Akdağ; Phone Number: +90 537 452 96 60; Email: fatma.betul820@gmail.com
• Study Contact Backup: Name: Yeliz Özdemir; Phone Number: +90 536 846 94 97; Email: yelizbahar1@gmail.com

Study Locations

• Turkey (Türkiye)
  • Pendik
    • Istanbul, Pendik, Turkey (Türkiye), 34890
      • Recruiting
      • Marmara University Faculty of Medicine Pendik Training and Research Hospital
      • Contact: Secretary General Secretary; Phone Number: +90 2166254545; Email: fatma.betul820@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 18 years or older with a diagnosis of lipedema who have undergone laboratory testing in which metabolic markers were evaluated within the past three months.

Description

Inclusion Criteria:

• Being female and aged 18 years or older
• Having chronic pain persisting for at least 3 months
• Having sufficient cognitive ability to understand and respond to the assessment scales used in the study
• Voluntarily agreeing to participate in the study and providing written informed consent

Exclusion Criteria:

• Presence of a history of malignancy, active infection, inflammatory rheumatic disease, or severe systemic disease
• History of known neurological disorders (e.g., stroke, multiple sclerosis, epilepsy)
• Diagnosis of severe psychiatric disorders (e.g., psychotic disorders, bipolar disorder)
• Pregnancy or breastfeeding
• Presence of cognitive impairment or communication difficulties that could affect the study results
• Diagnosed diabetes mellitus
• Active thyroid disease (uncontrolled hypothyroidism or hyperthyroidism)
• Cushing's syndrome or other significant endocrine disorders
• Use of antidiabetic medications
• Use of lipid-lowering therapy (e.g., statins, fibrates)
• Systemic glucocorticoid use within the past 3 months
• Use of medications that may significantly affect central pain mechanisms (e.g., high-dose opioids, antipsychotic drugs)
• History of major surgery or invasive treatment for pain within the past 3 months

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Female patients diagnosed with lipedema; Patients aged 18 years and older who are followed with a diagnosis of lipedema and who have undergone laboratory testing in which metabolic markers were evaluated within the last three months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central Sensitization Inventory (CSI)	The Central Sensitization Inventory is a self-report screening tool developed to assess the presence and severity of symptoms associated with central sensitization. The inventory evaluates symptoms reflecting sensitization in central nervous system pain-processing mechanisms, including widespread pain, fatigue, sleep disturbances, and cognitive complaints. The CSI consists of 25 items, each scored on a scale from 0 to 4, with a total score ranging from 0 to 100. A total score of 40 or higher is considered to be associated with a high likelihood of central sensitization.	At baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Rating Scale (NRS)	The Numeric Rating Scale (NRS) is used to measure and monitor pain intensity. A score of "0" represents no pain, while "10" indicates the worst pain imaginable. Patients are asked to rate their pain on a scale from 0 to 10. Due to its simplicity and ease of understanding, this scale is frequently used in clinical research.	At baseline
Fatigue Severity Scale (FSS)	The Fatigue Severity Scale is a self-report measure used to evaluate the impact of fatigue on daily life and functional activities. The scale consists of 9 items, each scored on a scale from 1 to 7. Higher average scores indicate greater fatigue severity.	At baseline
Neuropathic Pain Diagnostic Questionnaire (DN4)	The DN4 questionnaire was developed to assess the presence of neuropathic pain. It consists of 10 items derived from symptom-based questions and clinical examination findings. The total score ranges from 0 to 10, and a score of 4 or higher is considered indicative of neuropathic pain.	At baseline
Short Form-12 (SF-12)	The Short Form-12 is a questionnaire used to assess general health status and health-related quality of life. It consists of 12 items. Scores range from 0 to 100, with higher scores indicating better quality of life.	At baseline
Jenkins Sleep Scale (JSS)	The Jenkins Sleep Scale is a self-report measure consisting of four items that evaluates the frequency of sleep problems experienced over the past month. Higher scores indicate a greater frequency of sleep disturbance symptoms, such as difficulty falling asleep, nocturnal awakenings, and early morning awakening.	At baseline
Lower Extremity Functional Scale (LEFS)	The Lower Extremity Functional Scale is a self-report measure consisting of 20 items that evaluates lower extremity functional status during activities of daily living. Lower total scores indicate greater functional limitation, whereas higher scores reflect better lower extremity function.	At baseline
International Physical Activity Questionnaire (IPAQ)	The International Physical Activity Questionnaire is a measure consisting of seven items that assess the time spent walking, performing moderate-intensity and vigorous-intensity activities, and sitting. The total score is calculated by considering the duration (minutes) and frequency (days) of walking, moderate-intensity activity, and vigorous-intensity activity. Energy expenditure for these activities is expressed in MET-minutes. Standard MET values have been established for each activity: sitting 1.5 MET, walking 3.3 MET, moderate-intensity physical activity 4 MET, and vigorous-intensity physical activity 8 MET. Using these values, daily and weekly physical activity levels can be calculated.	At baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOMA-IR (Homeostatic Model Assessment of Insulin Resistance)	HOMA-IR is an index widely used to assess insulin resistance and is calculated using fasting glucose and fasting insulin levels. In this study, HOMA-IR will be calculated using the following formula: HOMA-IR = [Fasting insulin (µIU/mL) × Fasting glucose (mg/dL)] / 405. Although there is no universally accepted single cut-off value for HOMA-IR, studies conducted in adult populations commonly interpret HOMA-IR values as follows: <1.0 indicates normal insulin sensitivity, 1.0-1.9 borderline insulin resistance, and ≥2.0 suggestive of insulin resistance; particularly HOMA-IR ≥2.5 is frequently used as a threshold indicating insulin resistance. In this study, HOMA-IR will be evaluated both as a continuous variable and categorized according to these commonly used reference values in the literature.	At baseline
Triglyceride/HDL Cholesterol (TG/HDL) Ratio	The TG/HDL ratio is a metabolic indicator obtained by dividing the serum triglyceride level by the high-density lipoprotein cholesterol (HDL) level and is associated with atherogenic dyslipidemia and insulin resistance. In this study, the TG/HDL ratio will be calculated using the formula TG (mg/dL) / HDL (mg/dL). Although there is no universally accepted cut-off value for the TG/HDL ratio, studies conducted in adult populations commonly classify values as follows: <2.0 normal, 2.0-3.0 borderline, and ≥3.0 indicative of increased metabolic risk; particularly TG/HDL ≥3.5 is frequently considered associated with insulin resistance and increased cardiometabolic risk. In this study, the TG/HDL ratio will be categorized according to these commonly used reference values in the literature.	At baseline
Waist-to-Hip Ratio	The waist-to-hip ratio is calculated by dividing waist circumference by hip circumference and is used to assess abdominal fat distribution. In women, a value of ≥0.85 is considered indicative of central obesity and increased cardiometabolic risk.	At baseline

Collaborators and Investigators

• Sponsor: Marmara University

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Pain; Triglyceride; HOMA-IR; Lipedema; Fasting Blood Glucose; Fasting Insulin
• Additional Relevant MeSH Terms: Neurologic Manifestations; Connective Tissue Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Pain; Lipedema
• Other Study ID Numbers: 09.2026.26-0134

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No