Omega-3 Fatty Acid Lipidomics in Diabetes Peripheral 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 (combinedquestionnaire and a clinical examination of the response to vibration perceptionexamination 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 pricksensation will be performed (as measures of small-fiber neuropathy) for DPNconfirmation (41-43).

5. Be willing and capable of providing a written consent form and willing and able tocooperate with the medical procedures for the study duration.

6. Women of childbearing potential must be willing to use appropriate contraceptionduring 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 totoxins).

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 theCKD-EPI equation].

4. Use of warfarin (Coumadin), clopidogrel (Plavix), dipyridamole (Persantine), heparinor other anticoagulants, probenecid (Benemid, Probalan), sulfinpyrazone (Anturane)or other uricosuric agents; Participants must agree to not use high-dose aspirinduring the course of the study. Daily low-dose aspirin treatment (not more than 81mg 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 cardiactransplantation).

8. History of drug or alcohol abuse within 5 years, or current weekly alcoholconsumption >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 thestudy.

12. Current therapy for malignant disease other than basal cell or squamous cell skincancer.

13. History of gastrointestinal bleeding or active gastric ulcer;

14. Screening laboratory abnormalities including AST (SGOT) and or ALT (SGPT) > 2.5 xthe 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 itunlikely for the participant to complete study.

18. Known hypersensitivity to salsalate or inactive ingredients. Patients who haveexperienced asthma, hives, or other allergic-type reactions to aspirin or otherNSAIDs are excluded from participation.

19. Use of lithium.

20. Absent one or both great toes.