A Novel Method of Management of High Output Chyle Leak Following Neck Dissection: Indocyanine Green Fluorescence-guided Robotic Transthoracic Thoracic Duct Ligation: A Case Series.

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycaemia and is associated with multiple systemic complications. Chronic hyperglycaemia and related metabolic disturbances can impair bone remodelling and compromise bone quality and microarchitecture, increasing skeletal vulnerability. The effects of different antidiabetic treatment combinations on diabetes-associated skeletal alterations remain insufficiently characterized. We investigated the effects of canagliflozin alone and in combination with metformin and fenugreek seed extract on glycaemic control and skeletal alterations in a high-fat diet (HFD)-streptozotocin (STZ)-induced diabetic rat model. Diabetes was induced in female Wistar rats using a HFD followed by STZ (35 mg/kg, intraperitoneally), and animals were treated orally for 12 weeks with canagliflozin (10 or 20 mg/kg), fenugreek seed extract (400 mg/kg), canagliflozin (10 mg/kg) plus metformin (200 mg/kg), or canagliflozin (10 mg/kg) plus metformin (200 mg/kg) and fenugreek seed extract (400 mg/kg). At the end of the treatment period, glycaemic and skeletal parameters were assessed, including serum insulin, HbA1c, serum TRAP activity, urinary calcium excretion, femoral trabecular microarchitecture and histological changes. Diabetic rats exhibited marked hyperglycaemia and deterioration of femoral trabecular microarchitecture, with reductions in bone volume fraction, trabecular thickness, trabecular number and connectivity density (Conn. D) and increases in trabecular separation and structural model index (SMI). Treatment with canagliflozin, fenugreek seed extract and combination regimens attenuated these diabetes-associated alterations. At week 12, the canagliflozin-metformin-fenugreek combination reduced fasting blood glucose by approximately 57.8% and HbA1c by approximately 47.4% compared with diabetic controls and was associated with improved trabecular microarchitectural parameters. Serum TRAP activity and urinary calcium excretion were also reduced by approximately 26.1% and 31.4%, respectively. Histological findings were consistent with the micro-computed tomography (micro-CT) observations. Overall, canagliflozin-based combination treatments were associated with improved metabolic control and attenuation of femoral trabecular deterioration in this experimental model, supporting further investigation of their skeletal effects and underlying mechanisms.