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Background and Objectives: Diabetes mellitus type 2 (T2DM) is a chronic disease associated with fluid accumulation in the interstitial tissue. Manual lymphatic drainage (MLD) plays a role in reducing lymphoedema, like intermittent pneumatic compression (IPC). By the present pilot study, we aimed to evaluate the efficacy of a synergistic treatment with MLD and IPC in reducing lower limb lymphedema in T2DM patients. Materials and Methods: Adults with a clinical diagnosis of T2DM and lower limb lymphedema (stage II–IV) were recruited from July to December 2020. Study participants were randomized into two groups: experimental group, undergoing a 1-month rehabilitative program consisting of MLD and IPC (with a compression of 60 to 80 mmHg); control group, undergoing MLD and a sham IPC (with compression of <30 mmHg). The primary outcome was the lower limb lymphedema reduction, assessed by the circumferential method (CM). Secondary outcomes were: passive range of motion (pROM) of hip, knee, and ankle; quality of life; laboratory exams as fasting plasma glucose and HbA1c. At baseline (T0) and at the end of the 1-month rehabilitative treatment (T1), all the outcome measures were assessed, except for the Hb1Ac evaluated after three months. Results: Out of 66 T2DM patients recruited, only 30 respected the eligibility criteria and were randomly allocated into 2 groups: experimental group (n = 15; mean age: 54.2 ± 4.9 years) and control group (n = 15; mean age: 54.0 ± 5.5 years). At the intra-group analysis, the experimental group showed a statistically significant improvement of all outcome measures (p < 0.05). The between-group analysis showed a statistically significant improvement in pROM of the hip, knee, ankle, EQ-VAS, and EQ5D3L index at T1. Conclusions: A multimodal approach consisting of IPC and MLD showed to play a role in reducing lower limb lymphedema, with an increase of pROM and HRQoL. Since these are preliminary data, further studies are needed.

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