Omega-3 supplements for improving peripheral nerve health in type-1 diabetes

INTERVENTION: Arm 1 (Treatment 1): trigylceride long‐chain omega‐3 oral supplement, twice daily oral capsule, for six months Adherence to treatment will be monitored by the analysis of systemic fatty acid profiles at the end of the study, and counting of the return of unused capsules at follow‐up visits by an independent researcher. CONDITION: Type‐1 diabetes PRIMARY OUTCOME: Central Corneal Nerve Fibre Length (CNFL) (measured in mm/mm2 using a Heidelberg Rostock Tomographer III with corneal module, quantified using a fully‐automated method (ACCMetrics)) SECONDARY OUTCOME: Central Corneal Nerve Branch Density (CNBD) (measured in mm/mm2 using a Heidelberg Rostock Tomographer III with corneal module, quantified using a fully‐automated method (ACCMetrics)) Central Corneal Nerve Fibre Density (CNFD) (measured in mm/mm2 using a Heidelberg Rostock Tomographer III with corneal module, quantified using a fully‐automated method (ACCMetrics)) Central corneal dendritic cell count (CDC) (measured in mm/mm2 using a Heidelberg Rostock Tomographer III with corneal module) Central corneal thresholds to a cold air stimulus (measured in mBar using a non‐contact corneal aesthesiometer) Central corneal thresholds to a room‐temperature air stimulus (measured in mBar using a non‐contact corneal aesthesiometer) Change in health state (as measured using the EQ‐5D‐5L questionnaire). Cutaneous silent period testing: lower limb (measuring silent period onset latency and duration) using an electromyographic (EMG) device (Dantec Keypoint G4 Workstation) Cutaneous silent period testing: upper limb (measuring silent period onset latency and duration), using an electromyographic (EMG) device (Dantec Keypoint G4 Workstation) Dry eye symptoms (measured using the validated Ocular Surface Disease Index (OSDI) questionnaire) Michigan Diabetic Neuropathy Score (MDNS) (measured through clinical examination) Nerve excitability composite profile (measured with QTRAC software using TROND protocol) Peripheral Corneal Nerve Branch Density (CNBD) (measured in mm/mm2 using a Heidelberg Rostock Tomographer III with corneal module, quantified using a fully‐automated method (ACCMetrics)) Peripheral Corneal Nerve Fibre Density (CNFD) (measured in mm/mm2 using a Heidelberg Rostock Tomographer III with corneal module, quantified using a fully‐automated method (ACCMetrics)) Peripheral corneal dendritic cell count (CDC) (measured in mm/mm2 using a Heidelberg Rostock Tomographer III with corneal module) Peripheral Corneal Nerve Fibre Length (CNFL) (measured in mm/mm2 using a Heidelberg Rostock Tomographer III with corneal module, quantified using a fully‐automated method (ACCMetrics)) Peripheral corneal thresholds to a cold air stimulus (measured in mBar using a non‐contact corneal aesthesiometer) Peripheral corneal thresholds to a room‐temperature air stimulus (measured in mBar using a non‐contact corneal aesthesiometer) Quantitative sensory testing (measuring cold detection thresholds at the foot), using a NerveCheck Master, pending instrumentation availability Quantitative sensory testing (measuring cold detection thresholds at the hand), using a NerveCheck Master, pending instrumentation availability Quantitative sensory testing (measuring heat detection thresholds at the foot), using a NerveCheck Master, pending instrumentation availability Quantitative sensory testing (measuring heat detection thresholds at the hand), using a NerveCheck Master, pending instrumentation availability Quantitative sensory testing (measuring vibration detection thresholds at the foot), using a NerveCheck Master, pending instrumentation availability Quantitative sensory testing (measuring vibration detection thresholds at the hand), using the NerveCheck Master, pending instrumentation availability Quantitative sudomotor axonal reflex testing (QSART), measured in sweat volume in nL using the QSWEAT system. Routine nerve conduction studies (NCS) – peroneal motor nerve (measured using Dantec Keypoint G4 Workstation) Routine nerve conduction studies (NCS) – tibial motor nerve (measured using Dantec Keypoint G4 Workstation) Routine nerve conduction studies (NCS) – median motor nerve (measured using Dantec Keypoint G4 Workstation) Routine nerve conduction studies (NCS) – median sensory nerve (measured using Dantec Keypoint G4 Workstation) Routine nerve conduction studies (NCS) – sural sensory nerve (measured using Dantec Keypoint G4 Workstation) Routine nerve conduction studies (NCS) – ulnar sensory nerve (measured using Dantec Keypoint G4 Workstation) Safety outcome: Change in best corrected visual acuity (BCVA) measured using a standard eye chart Safety outcome: Change in intraocular pressure (IOP) measured using a Goldmann tonometer Safety outcome: Diabetic retinopathy graded using the Wisconsin Scale grading system Safety outcome: Incidence of adverse events (AEs). Common AEs, such as gastrointestinal discomfort (e.g., loose stools, constipation, heartburn, nausea, bloating) and rare AEs, such as minor bleeding (e.g., nose bleeds) will be assessed as the number of participants reporting AEs at each follow‐up visit. Safety outcome: Standard blood pathology (fasting glucose, lipid profiles, FBC, ESR, CRP, Vitamin B‐12, Folate, TSH, UEC, HbA1C, liver function, electrolytes) Tear osmolarity: electrolyte concentration of the tears (measured in mOsm/L using the TearLab system (TearLab Corporation Pty Ltd) Tear stability: standard clinical measure of TBUT using sodium fluorescein dye. INCLUSION CRITERIA: Provision of written informed consent to participate Confirmed diagnosis of type‐1 diabetes for at least five years Ability to understand and follow study instructions, and intent to complete all study visits