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Background: Lipedema is a poorly known disorder of painful subcutaneous adipose tissue (SAT) likely affecting millions of women worldwide. Stage 1 lipedema has smooth skin with increased underlying fat, Stage 2 has indentations and nodules, and Stage 3 has large extrusions of skin and SAT. Women with lipedema have more SAT below the waist. As this gynoid fat is known to be cardioprotective, we aimed to determine if health declined with increasing stage and extent of lipedema SAT. Methods and Findings: Chart review from June 2012 to February 2013 at a tertiary academic center. Fifty women and one man were included in consecutive order. Fat was assessed in 29 areas for lipomas, size of the depot, and presence of lipedema fat. Pain was assessed by a numerical pain scale. Average age of patients was 50 ± 13 y; average body mass index was 38 ± 12 kg/m2. Median age of development of lipedema was 20 y. Pain occurred daily in 89.7%. None of the patients with Stage 1 lipedema had diabetes, hypertension or dyslipidemia. The amount of lipedema fat differed significantly between Stages of lipedema (p=0.003), with Stage 3 having significantly more. There was no difference in fat depot size or number of lipomas amongst Stages. Only one of 51 patients had type 2 diabetes. There was an increase in shortness of breath, palpitations, urination, and numbness in Stage 3. Conclusions: Lipedema fat can develop in any SAT location and increases in association with increasing signs and symptoms of systemic illness.