Type 1 Diabetes Mellitus
Conditions
Keywords
omega3, T1D remission period, honeymoon period, AA/EPA ratio
Brief summary
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.
Detailed description
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.
Interventions
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
DRUGVitamin D supplementation
Cholecalciferol 1000 IU/die
Sponsors
University of Eastern Piedmont
Azienda Ospedaliero Universitaria Maggiore della Carita
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Insulin Need (IU/Kg/Day) and Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/Day) at 12 Months | 12 months | 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. |
| HbA1c Percentage | 12 months | percentage of glycated hemoglobin measured through the high-performance liquid chromatography (HPLC). |
| Number of Participants With Insulin Demand Adjusted for HbA1c %(IDAA1c) <9 | 12 months | 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). |
Participant flow
Recruitment details
The recruitment started 03/17/2017 with the enrollment of the first patient, and ended on 06/08/2019 with the end of the omega-3 supplementation period of the last enrolled patient. All participants were introduced since the beginning of T1D to tailored insulin therapy, to Mediterranean diet (according to a standardized item detailed in reference), and received 1000 IU/day of vitamin D supplementation.
Participants by arm
| Arm | Count |
|---|---|
| CASES The T1D onsets were eligible subjects, of which 26/64 new onsets 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 60 mg/kg/day for 12 months. The supplementation with omega 3 started within 3th and 6th months of T1D clinical onset and lasted one year.
They had been introduced to the Mediterranean diet according to a standardized item and received 1000 IU/day of vitamin D supplementation since the beginning of T1D | 26 |
| CONTROLS The Previous T1D onsets, 38/64 subjects joined to the study as controls (CONTROLS). They received vitamin D supplementation 1000 IU/day and Mediterranean diet according to a standardized item since the onset of T1D, without omega 3; retrospectively their available data from 3th and 6th months of overt disease for the following year, were compared | 38 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 0 |
Baseline characteristics
| Characteristic | CASES | CONTROLS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 26 Participants | 38 Participants | 64 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.7 years STANDARD_DEVIATION 4.6 | 8.8 years STANDARD_DEVIATION 3.6 | 8.75 years STANDARD_DEVIATION 4 |
| Race/Ethnicity, Customized Albania | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Italian | 20 Participants | 33 Participants | 53 Participants |
| Race/Ethnicity, Customized North Africa | 4 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Pakistan | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Italy | 26 participants | 38 participants | 64 participants |
| Sex: Female, Male Female | 14 Participants | 20 Participants | 34 Participants |
| Sex: Female, Male Male | 12 Participants | 18 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 37 |
| other Total, other adverse events | 1 / 26 | 0 / 38 |
| serious Total, serious adverse events | 0 / 22 | 0 / 37 |
Outcome results
Primary
Daily Insulin Need (IU/Kg/Day) and Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/Day) at 12 Months
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.
Time frame: 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CASES New T1D Onsets 2017 | Daily Insulin Need (IU/Kg/Day) and Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/Day) at 12 Months | Daily insulin need | 0.49 IU/Kg/day | Standard Deviation 0.2 |
| CASES New T1D Onsets 2017 | Daily Insulin Need (IU/Kg/Day) and Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/Day) at 12 Months | Daily Insulin Pre-meal Demand | 0.22 IU/Kg/day | Standard Deviation 0.1 |
| CONTROLS Previous T1D Onsets | Daily Insulin Need (IU/Kg/Day) and Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/Day) at 12 Months | Daily insulin need | 0.63 IU/Kg/day | Standard Deviation 0.1 |
| CONTROLS Previous T1D Onsets | Daily Insulin Need (IU/Kg/Day) and Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/Day) at 12 Months | Daily Insulin Pre-meal Demand | 0.34 IU/Kg/day | Standard Deviation 0.1 |
p-value: <0.05Wilcoxon (Mann-Whitney)
p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
HbA1c Percentage
percentage of glycated hemoglobin measured through the high-performance liquid chromatography (HPLC).
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CASES New T1D Onsets 2017 | HbA1c Percentage | 7.4 percentage of HbA1c | Standard Deviation 1 |
| CONTROLS Previous T1D Onsets | HbA1c Percentage | 7.8 percentage of HbA1c | Standard Deviation 1 |
p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
Number of Participants With Insulin Demand Adjusted for HbA1c %(IDAA1c) <9
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).
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CASES New T1D Onsets 2017 | Number of Participants With Insulin Demand Adjusted for HbA1c %(IDAA1c) <9 | 12 Participants |
| CONTROLS Previous T1D Onsets | Number of Participants With Insulin Demand Adjusted for HbA1c %(IDAA1c) <9 | 7 Participants |
p-value: <0.05Chi-squared