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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.