Effects of Fish Oil ± Salsalate on the Omega-3 Index and the Circulating Lipidome of Omega-3 Polyunsaturated Fatty Acid Metabolites in Patients with Type 2 Diabetes and Diabetic Neuropathy

Inclusion Criteria: 1. T2D according to American Diabetes Association (ADA) criteria (38). 2. Age ≥ 18 yr. 3. HbA1c \< 9.5%. 4. Presence of DPN based on Michigan Neuropathy Screening Instrument (combined questionnaire and a clinical examination of the response to vibration perception examination using a 128 Hz tuning fork and ankle reflexes), a validated, sensitive, and specific instrument for the diagnosis of DPN as reported (39,40). Pin prick sensation will be performed (as measures of small-fiber neuropathy) for DPN confirmation (41-43). 5. Be willing and capable of providing a written consent form and willing and able to cooperate with the medical procedures for the study duration. 6. Women of childbearing potential must be willing to use appropriate contraception during the entire trial.

Exclusion Criteria: 1. History of any other causes of neuropathy (e.g. other neurological disorders, medications-induced, occupational history, active hepatitis C infection, exposure to toxins). 2. History of persistent macroalbuminuria \[random urine microalbumin creatinine ratio (ACR) up to 300 mg/gm\]is acceptable if calculated GFR is \>60 (16). 3. Serum creatinine \>1.4 for women and \>1.5 for men or eGFR \<60 \[calculated using the CKD-EPI equation\]. 4. Use of warfarin (Coumadin), clopidogrel (Plavix), dipyridamole (Persantine), heparin or other anticoagulants, probenecid (Benemid, Probalan), sulfinpyrazone (Anturane) or other uricosuric agents; Participants must agree to not use high-dose aspirin during the course of the study. Daily low-dose aspirin treatment (not more than 81 mg per day) may be continued if currently prescribed. 5. Uncontrolled hypertension 6. Triglyceride \> 400 mg/100ml. 7. History of previous organ transplantation (kidney, pancreas, liver, lung or cardiac transplantation). 8. History of drug or alcohol abuse within 5 years, or current weekly alcohol consumption \>10 units/week. 9. Pregnancy or lactation or desire to become pregnant in the next 12 months 10. Requiring long-term glucocorticoid therapy or chronic immunosuppressive therapy: inhaled steroid use for management of asthma is not an absolute exclusion. . 11. Participation in an experimental medication trial within 3 months of starting the study. 12. Current therapy for malignant disease other than basal cell or squamous cell skin cancer. 13. History of gastrointestinal bleeding or active gastric ulcer; 14. Screening laboratory abnormalities including AST (SGOT) and or ALT (SGPT) \> 2.5 x the upper limit of normal (ULN), total bilirubin \> 1.5 x ULN, platelets \< 100,000; 15. History of taking fish oil supplements in the 6 months prior to the screening visit. 16. History of fish or shellfish allergy. 17. Presence of any condition that in the opinion of the investigators would make it unlikely for the participant to complete study. 18. Known hypersensitivity to salsalate or inactive ingredients. Patients who have experienced asthma, hives, or other allergic-type reactions to aspirin or other NSAIDs are excluded from participation. 19. Use of lithium. 20. Absent one or both great toes.