Omega-3 and Vitamin D Supplements in Childhood T1D

Omega 3 Long Chain Polyunsaturated Fatty Acids, Enriched Mediterranean Diet and Vitamin D Supplementation in Childhood Type 1 Diabetes: One Year Case-cohort Study

The study was conducted in 64 patients with T1D of which 26 had the onset in 2017, and 38 in 2016, 2015 and 2014. All received vitamin D 1000 IU /day since disease's onset. Moreover in the 2017 group omega-3 were supplemented, starting within 3 and 6 months from the disease's outbreak, and those were considered cases; the other 38 were enrolled as controls. Four cases and one control dropped out. Finally in 59/64 were compared data of glycosylated hemoglobin percentage (HbA1c%), average insulin daily requirement (IU/Kg/day), and IDAA1c [Insulin Daily dose Adjusted for HbA1c, a surrogate index of residual endogen insulin secretion, calculated as insulin daily dose (IU/Kg/24 h) x 4 + HbA1c%] at recruitment (T0), and 3 (T3), 6 (T6), 12 (T12) months after. T0 in cases was at the start of supplementation of omega-3, and consequently 3, 6 and 12 months after; in controls were found data in clinical records of outpatient beginning from the 3rd month and 3-6-12 months thereafter. Then 22 cases and 37 controls were compared.

Was assessed the comparability of cases and controls at baseline for gender, age, body weight, HbA1c% and device for insulin therapy. The preparation of omega-3 administered was a highly purified fish oil to avoid pollutants, containing a mixture of omega-3 long chain fatty acids standardized for contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in a 2: 1 ratio, in capsules or in liquid form. The liquid preparation was used in the case of difficulties in swallowing capsules or concomitant celiac disease because it was certified as gluten-free (Ener Zone Omega 3 RX® Equipe Enervit). The preparations contained antioxidants to preserve omega-3 LCFA, tocopherol (1 mg in 1 g of omega-3 LCFA), palmitate, and rosemary extract. EPA and DHA were administered at 50-60 mg/kg/day for 12 months. The investigation of Arachidonic Acid (AA)/EPA ratios was performed in cases on recruitment (T0), and repeated after 3 (T3), 6 (T6), and 12 months (T12). Cholecalciferol supplementation was fixed at 1000 IU/day (25 mcg/day), both in cases and controls. Vitamin D level was determined as 25(OH)D level at the clinical onset of T1D, at T0, T3, T6, and T12 in cases, and at clinical onset of controls.

A cohort study was performed in 2017, in all T1D patients 1-18 years old with onset in the years 2014-2017. Supplementation with omega3 was proposed to all subjects with onset in 2017. Patients with onset in 2014-2015-2016 were enrolled only as control subjects. The work was performed on retrospectively collected data in medical records for patients with start of the disease in 2014-2016. Patients enrolled since 2017 have been studied prospectively.

Of eligible subjects, 26/64 started an intervention program with Ω-3 (CASES). The intervention consisted in supplementation with highly purified Ω-3, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a dose of 50-60 mg/kg/day for 12 months

Others 38/64 subjects joined to the study as data contributors, and were entered as controls (CONTR).

Supplementation with Ω-3, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a dose of 50-60 mg/kg/day for 12 months, currently underway or completed after 12 months of omega-3 administration, in 22/64 T1D children

The Daily Insulin Needs (IU/Kg/day), and the Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/day) respectively represent the average total (sum of boluses and basal) and average pre-meal (sum of pre-meal boluses) insulin doses administered in one day to each patient. They have been calculated over a week, and were expressed in International Units / Kg of weight, higher values mean a worse outcome.

percentage of glycated hemoglobin measured through the high-performance liquid chromatography (HPLC).

The IDAA1c (insulin daily dose adjusted for glycosylated hemoglobin percentage) was calculated as HbA1c percentage + average daily insulin dose (IU/kg/24 h) x 4. A score <9 meet definition of partial remission and Residual Endogenic Insulin Secretion (REIS). IDAA1c represents a surrogate index of insulin secretion and of metabolic control. In a scale from 5 to 12, higher score mean a worse outcome (e.g. <5.5 is expected in a normal individual, <9 in an individual in partial remission. See reference).

Inclusion Criteria: All T1D patients aged 1-18 years whose disease onset had been in 2017, 2016, 2015, 2014 affering to the Pediatric Diabetology of AOU Novara (Italy) written consents of parents without assumption of omega 3 supplementation before 2017 Exclusion Criteria: renal cysts sarcoidosis histoplasmosis hyperparathyroidis lymphoma tuberculosis Patients treated with drugs that could affect immunity or glucose metabolism, including corticosteroids, ciclosporin and tacrolimus

the IPD and any additional supporting information will become available and for ten years, including the start and end dates or period of availability. This may be provided starting to date when data are published or otherwise made available.

Cadario F, Savastio S, Ricotti R, Rizzo AM, Carrera D, Maiuri L, Ricordi C. Administration of vitamin D and high dose of omega 3 to sustain remission of type 1 diabetes. Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):512-515. doi: 10.26355/eurrev_201801_14203.

Baidal DA, Ricordi C, Garcia-Contreras M, Sonnino A, Fabbri A. Combination high-dose omega-3 fatty acids and high-dose cholecalciferol in new onset type 1 diabetes: a potential role in preservation of beta-cell mass. Eur Rev Med Pharmacol Sci. 2016 Jul;20(15):3313-8.