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Omega-3 polyunsaturated fatty acids (PUFAs) represent valuable dietary adjuncts for subjects with hypertriglyceridemia and at increased risk of cardiovascular disease, including subjects with type 1 diabetes (T1D). However, the exact role of omega-3 PUFAs in the regulation of glucose homeostasis and chronic complications in patients with diabetes remains uncertain. Herein, we report a 3-year follow-up of an athlete adolescent with T1D who started to use continuous glucose monitoring (CGM) two years after the diagnosis, and initiated omega-3 PUFA supplementation four years after the clinical onset of T1D. CGM metrics related to a 18-month period of omega-3 PUFA supplementation (50 mg/Kg/day of EPA and DHA) was compared to CGM metrics referring to a 18-month period prior to the nutrition intervention. Omega-3 PUFA supplementation resulted in a significant reduction of mean glucose and glucose variability, along with a significant increase in Time in range (TIR) 70-180 mg/dL. No significant changes were observed in daily insulin requirements between the two study periods. Future studies will be of assistance to better understand the exact impact of omega-3 PUFAs on the regulation of glucose homeostasis in patients with type 1 and its complications.

Nutrition is an essential part of therapy for type 1 diabetes and is constantly evolving, offering growing opportunities to prevent this disease, slow down its evolution, and mitigate it. An attempt was made to bring together the current state of knowledge. In the path from the preclinical phase of the disease to its clinical onset, there is a phase known as the "honeymoon period" or partial remission, where different possible dietary options for combatting this disease have been presented. The most commonly used dietary models were compared, and the most frequent co-existing pathologies, such as overweight, non-alcoholic fatty liver disease, dyslipidemia, celiac disease, and metabolic instability, were addressed from their nutritional and dietary perspectives to provide clinicians with an updated framework of knowledge and support researchers in further investigations into the topic. Finally, a glimpse into the possible interplay between nutrition and the gut microbiome, food security, and ultra-processed food is provided. It is hoped that clinicians treating people with type 1 diabetes will be provided with further opportunities for the daily management of their patients through personalized nutrition.

Introduction: Type 1 diabetes (T1D) risk involves genetic susceptibility but also epigenetics, environment, and behaviors. Appropriate metabolic control, especially quickly after the diagnosis, is crucial for the patient quality of life., Methods: This study aimed to produce a quantitative comparison of the behavior, nutrition habits, and gut microbiota composition between the onset and the 1-year follow-up in 35 children with T1D., Results and Discussion: At follow-up, with the metabolic control, many parameters improved significantly, with respect to the onset, such as glycated hemoglobin (-19%), body mass index (BMI), and also nutritional behaviors, such as normal calorie intake (+6%), carbohydrate intake (-12%), extra portion request (-4%), and meals distribution during the day. Moreover, glycated hemoglobin decrement correlated with both total and rapid absorption carbohydrate intake (Spearman's rho = 0.288, 95% CI 0.066-0.510, p = 0.013), showing as the nutritional behavior supported the insulin therapy efficiency. The next-generation sequencing (NGS) analysis of microbiota revealed abundance differences for Ruminococcus bromii and Prevotella copri (higher at onset, p < 0.001) and the genera Succinivibrio and Faecalibacterium (lower at onset, p < 0.001), as a consequence of nutritional behavior, but it was not the only changing driver. The qRT-PCR analysis showed significant variations, in particular for Bacteroidetes and Bifidobacterium spp. (+1.56 log gene copies/g stool at follow-up, p < 0.001). During the year, in 11% of the patients, severe clinical episodes occurred (hypoglycemic or ketoacidosis). The likelihood of a severe hypoglycemic episode was modulated when the Methanobrevibacter smithii amount increased (odds ratio 3.7, 95% CI 1.2-11.4, p = 0.026). Integrated evaluation, including nutritional behavior and microbiota composition, could be considered predictive of the metabolic control management for children cohort with a recent diagnosis of T1D., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Traversi, Scaioli, Rabbone, Carletto, Ferro, Franchitti, Carrera, Savastio, Cadario, Siliquini, Cerutti and Durazzo.)

After the discovery of insulin, nutrition has become central in the management of diabetes in order to limit glycemic rise after meals, optimize metabolic control, and prevent complications. Over the past one hundred years, international scientific societies have consecutively refined nutritional needs and optimized food intake for the treatment of diabetes. In particular, over the past century, nutrition applied with pumps for the administration of insulin and continuous glucose monitoring have allowed substantial advancement in the treatment of type 1 diabetes mellitus. The role of some substances, such as vitamin D and n -3 polyunsaturated fatty acids, have been proposed without univocal conclusions, individually or in combination, or in the diet, to improve the nutrition of type 1 and type 2 diabetes. This second condition, which is highly associated with overweight, should be prevented from childhood onwards. Personalized nutrition could bypass the problem, reaching a scientific conclusion on the individual subject. This article focuses on childhood and adolescent diabetes, aims to provide a narrative summary of nutrition over the past century, and promotes the concept of personalized nutrition to pediatricians and pediatric diabetologists as a possible tool for the treatment of type 1 diabetes and the prevention of type 2 diabetes.

Objectives: Vitamin D plays an immunoregulatory activity. The aim of this study was to assess the correlation between blood serum 25(OH)D levels and Th17 and Treg circulating subsets, mainly Treg/inducible costimulatory-positive (ICOS+), which seems to have a protective role in autoimmunity, in children with type 1 diabetes mellitus (T1D) and their healthy siblings (S). The secondary aim was to evaluate the impact of vitamin D supplementation on these subsets., Patients and Methods: 22 T1D and 33 S were enrolled. Glucose, hemoglobin A1c, 25 OH vitamin D (25[OH]D), T helper type 17 (Th17; CD4+CCR6+), regulatory T cells (Treg; CD4+CD25+Foxp3+), and Treg/ICOS+ cells were evaluated. According to human leukocyte antigen (HLA) haplotypes, subjects were classified as "at risk" (HLA+), "protective haplotypes" (HLA-; "nested controls"), and "undetermined" (HLAUND). T1D and S subjects were supplemented with cholecalciferol 1000 IU/die and evaluated after 6 months., Results: Vitamin D insufficiency (74.4%) and deficiency (43%) were frequent. S subjects with 25(OH)D levels <25 nmol/L had Th17, Treg (p < 0.01), and Treg/ICOS+ (P < 0.05) percentages higher than subjects with 25(OH)D >75 nmol/L. Treg/ICOS+ percentages (P < 0.05) were higher in HLA- S subjects compared to percentages observed in S with T1D. At baseline, in S subjects, a decreasing trend in Th17 and Treg/ICOS+ values (P < 0.05) from vitamin D deficiency to sufficiency was observed; 25(OH)D levels were negative predictors of Treg/ICOS+ (R2 = 0.301) and Th17 percentages (R2 = 0.138). After 6 months, supplemented S subjects showed higher 25(OH)D levels (P < 0.0001), and lower Th17 (P < 0.0001) and Treg/ICOS+ (P < 0.05) percentages than at baseline; supplemented T1D patients only had a decrease in Th17 levels (P < 0.05)., Conclusion: Serum 25(OH)D levels seem to affect Th17 and Treg cell subsets in S subjects, consistent with its immunomodulating role. HLA role should be investigated in a larger population., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: The incidence of type 1 diabetes has increased over the last decades. The pathological pathway is not yet clear, even if genetic and environmental risk factors are known. An early diagnosis can avoid ketoacidosis and its complications. This work aims to discuss the determinants of both ketoacidosis at the onset and access by hospital emergency departments without a suspected diagnosis., Methods: An observational bi-centric prospective study was conducted in Northern Italy, on a paediatric population including Italian and migrant patients at the diabetes onset. Seventy-four type 1 diabetes patients, both Italian and migrant, were included in the study. Anthropometric, socio-economic, behavioural, clinical data were collected, and microbiota analyses were performed using stool samples., Results: Regular physical activity is associated with lower ketoacidosis incidence at onset (OR 0.33 95% CI 0.12-0.95 p < 0.05), as is higher blood vitamin D level (OR 0.92 95% CI 0.85-0.99 p < 0.05). Moreover, a higher weaning age (OR 0.49 95% CI 0.27-0.89 p < 0.05), higher vitamin D level (OR 0.90 95% CI 0.83-0.98 p < 0.05) and a higher level of Akkermansia muciniphila (OR 0.46 95% CI 0.25-0.87 p < 0.05) are associated factors to lower frequency of type 1 diabetes onset without a suspected diagnosis. Diabetes migrant status is not a risk factor for severe type 1 diabetes onset; on the other hand, some protective factors are significantly more diffused among Italians, such as regular sport activity and non-critical vitamin D levels., Conclusion: Behavioural and nutritional data, such as microbiota bio-indicators, seem to be useful to identify an at-risk population to prevent ketoacidosis and its severe complications.

Type 1 diabetes (T1D) is a common autoimmune disease that is characterized by insufficient insulin production. The onset of T1D is the result of gene-environment interactions. Sociodemographic and behavioural factors may contribute to T1D, and the gut microbiota is proposed to be a driving factor of T1D. An integrated preventive strategy for T1D is not available at present. This case-control study attempted to estimate the exposure linked to T1D to identify significant risk factors for healthy children. Forty children with T1D and 56 healthy controls were included in this study. Anthropometric, socio-economic, nutritional, behavioural, and clinical data were collected. Faecal bacteria were investigated by molecular methods. The findings showed, in multivariable model, that the risk factors for T1D include higher Firmicutes levels (OR 7.30; IC 2.26-23.54) and higher carbohydrate intake (OR 1.03; IC 1.01-1.05), whereas having a greater amount of Bifidobacterium in the gut (OR 0.13; IC 0.05 - 0.34) was a protective factor for T1D. These findings may facilitate the development of preventive strategies for T1D, such as performing genetic screening, characterizing the gut microbiota, and managing nutritional and social factors.

Background: There are 1.2 million of immigrant children living in Italy. However, data on their nutritional habits are limited. The aim of this study was to assess the nutritional profile in a cohort of both Italian and immigrant children., Methods: The study included 86 children aged 5-15 consecutively enrolled from January 2016 to May 2017 within a larger epidemiological study on determinants of diabetes. Immigrant state was defined on the basis of the parent origin. Data on nutritional profile, frequency of food group consumption, and eating habits were collected using the 24-hour dietary recall method and a questionnaire. Anthropometric parameters were measured., Results: In the cohort of immigrant children there was a higher prevalence of both overweight (27.3 vs. 14.1%) and obesity (18.2 vs. 3.1%) subjects and a greater total calorie intake compared to Italian children, mainly due to excess simple carbohydrate intake. Immigrant children had a higher consumption of sweets, snacks, and drinks with added sugar. Moreover, unhealthy habits, such as eating alone and eating while watching TV, were more frequent among immigrant children., Conclusions: In this cohort, immigrant children had a higher prevalence of overweight/obesity possibly due to less healthy nutritional habits. Culturally-tailored nutritional interventions may help preventing the development of obesity-related diseases in this population.

Vitamin D and omega 3 fatty acid (ω-3) co-supplementation potentially improves type 1 diabetes (T1D) by attenuating autoimmunity and counteracting inflammation. This cohort study, preliminary to a randomized control trial (RCT), is aimed at evaluating, in a series of T1D children assuming Mediterranean diet and an intake of cholecalciferol of 1000U/day from T1D onset, if ω-3 co-supplementation preserves the residual endogen insulin secretion (REIS). Therefore, the cohort of 22 "new onsets" of 2017 received ω-3 (eicosapentenoic acid (EPA) plus docosahexaenoic acid (DHA), 60 mg/kg/day), and were compared retrospectively vs. the 37 "previous onsets" without ω-3 supplementation. Glicosilated hemoglobin (HbA1c%), the daily insulin demand (IU/Kg/day) and IDAA1c, a composite index (calculated as IU/Kg/day × 4 + HbA1c%), as surrogates of REIS, were evaluated at recruitment (T0) and 12 months later (T12). In the ω-3 supplemented group, dietary intakes were evaluated at T0 and T12. As an outcome, a decreased insulin demand ( p < 0.01), particularly as pre-meal boluses ( p < 0.01), and IDAA1c ( p < 0.05), were found in the ω-3 supplemented group, while HbA1c% was not significantly different. Diet analysis in the ω-3 supplemented group, at T12 vs. T0, highlighted that the intake of arachidonic acid (AA) decreased ( p < 0.01). At T0, the AA intake was inversely correlated with HbA1c% ( p < 0.05; r ;. 0.411). In conclusion, the results suggest that vitamin D plus ω-3 co-supplementation as well as AA reduction in the Mediterranean diet display benefits for T1D children at onset and deserve further investigation.

Objective: Two cases of Type 1 Diabetes (T1D) in pediatric subjects treated with supplementation with high dose vitamin D and omega 3 are reported. A similar pattern of remission of the disease was observed, resulting in restoration and subsequent persistence of optimal metabolic control, one and two years after T1D onset. Minimal basal insulin administration (0.1 IU/kg/die) in a single evening injection was required. The immunomodulatory and anti-inflammatory properties of the supplements were likely contributing to the observed effect. Similarities in genotyping and autoantibody patterns in these two cases could be of assistance to identify which subjects with T1D could benefit from this supplemental therapy. High dose vitamin D and omega 3 could be of assistance in childhood T1D therapy, to prolong preservation of endogenous insulin secretion in the absence of side effects. We do not know how long the state of remission can last, but these initial results are promising and represented a significant benefit for the two pediatric subjects treated. Larger controlled studies will determine the long-term effect of this proposed supplementation and its possible cost-benefits, including reduction of hypoglycemic episodes and complications.

In Type 1 Diabetes (T1D) in children, close to the onset the requirements of insulin are often reduced. This represents a transient recovery of endogenous insulin secretion named "honeymoon" because transient and followed by a progressive decline in C-peptide secretion. This case report describes the effect of administration of high dose vitamin D and Ω-3 fatty acids on T1D progression in a 8-year-old child. At today after one year and a half from the onset of T1D, the subject shows a near-normal blood glucose with the administration of 1.5-2 UI of insulin once a day. Thus this report may be of assistance to design additional studies to determine and validate the effect of administration of vitamin D and Ω-3 fatty acids on the progression of T1D.

Aims: To investigate on the relationship between severity of ketoacidosis, an important risk factor for C-peptide preservation, and long-term microvascular complications in childhood-onset type 1 diabetes mellitus (T1DM)., Methods: 230 childhood-onset diabetic patients (177 pre-pubertal), aged 7.0±3.8years followed for at least 15years after their diagnosis, were enrolled. Clinical and laboratory data at diagnosis, and C-peptide levels in a subset of patients, were compared with the severity of retinopathy and nephropathy, after a mean of 19.6±3.8years of disease. Digital retinal photographs were taken in all patients, and centrally graded. Repeated measurements of HbA1c and microalbuminuria for the whole duration of diabetes were collected in over half of the cases., Results: Out of 230 patients, those with the lowest age at diagnosis had the most severe DKA and clinical conditions (p<0.05), and lower C-peptide levels (p<0.0001) at diagnosis. There was a significant relationship between pH and clinical severity (r=-0.783, p<0.0001), and between pH and C-peptide levels (r=0.278, p<0.05). The severity of ketoacidosis had no relationship with subsequent lifetime HbA1c values and long-term microvascular complications. In logistic regression analysis, the only variables that independently influenced severity of retinopathy were lifetime HbA1c (B=0.838, p<0.001), duration of disease (B=0.208, p<0.005) and age at diagnosis (B=0.116, p<0.05)., Conclusions: The degree of metabolic derangement at diagnosis is not associated with retinopathy and nephropathy in childhood-onset T1DM. Age at diagnosis seems to be an important variable to be considered when evaluating the long-term effects of residual beta-cell function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: To assess whether vitamin D levels at birth were associated with risk of having type 1 diabetes up to 10 years of age and the potential modifier effect of ethnic group., Methods: The Piedmont Diabetes Registry and the Newborn Screening Regional data were linked to identify cases (n = 67 incident children aged ≤10 years at diabetes onset, 2002-2012) and up to five controls (n = 236) matched for birthday and ethnic group. Cards with neonatal blood spot were used and 25-hydroxyvitamin D(3) assessed with tandem mass spectroscopy., Results: In conditional logistic regression, OR for unit increment of log vitamin D was 0.78 (95 % CI 0.56-1.10). Vitamin D was significantly lower in migrant than in Italian control newborn babies (p < 0.0001), and interaction between vitamin D and migrant status was statistically significant (p = 0.04). Compared to migrant newborns babies with vitamin D ≥ 2.14 ng/ml, migrants with lower levels had an OR of 14.02 (1.76-111.70), whereas no association was evident in Italians., Conclusions: Our case-control study within the Piedmont Diabetes Registry showed no association between vitamin D levels at birth and risk of having type 1 diabetes up to 10 years of age, apart from the subgroup of migrant babies, which might have clinical implications if confirmed.

Background: Vitamin D status during pregnancy is related to neonatal vitamin D status. Vitamin D deficiency has been associated with an increased risk of rickets in children and osteomalacia in adults. Aim of this study was to investigate 25OHD levels in maternal serum and in neonatal blood spots in native and migrant populations living in Novara (North Italy, 45°N latitude)., Methods and Findings: We carried out a cross sectional study from April 1st 2012 to March 30th 2013, in a tertiary Care Center. Maternal blood samples after delivery and newborns' blood spots were analyzed for 25OHD levels in 533 pairs. Maternal country of origin, skin phototype, vitamin D dietary intake and supplementation during pregnancy were recorded. Multivariate regression analysis, showed a link between neonatal and maternal 25OHD levels (R-square:0.664). Severely deficient 25OHD values (<25 nmol/L) were found in 38% of Italian and in 76.2% of migrant's newborns (p <0.0001), and in 18% of Italian and 48,4% of migrant mothers (p <0.0001) while 25OHD deficiency (≥25 and <50 nmol/L) was shown in 40.1% of Italian and 21.7% of migrant's newborns (p <0.0001), and in 43.6% of Italian and 41.3% of migrant mothers (p <0.0001). Italian newborns and mothers had higher 25OHD levels (34.4±19.2 and 44.9±21.2 nmol/L) than migrants (17.7±13.7 and 29.7±16.5 nmol/L; p<0.0001). A linear decrease of 25OHD levels was found with increasing skin pigmentation (phototype I 42.1 ±18.2 vs phototype VI 17.9±10.1 nmol/l; p<0.0001). Vitamin D supplementation resulted in higher 25OHD values both in mothers and in their newborns (p<0.0001)., Conclusions: Vitamin D insufficiency in pregnancy and in newborns is frequent especially among migrants. A prevention program in Piedmont should urgently be considered and people identified as being at risk should be closely monitored. Vitamin D supplementation should be taken into account when considering a preventative health care policy.

Aim: We aim to investigate vitamin D (25OHD) levels in children with or without type 1 diabetes (T1D) according to latitude and skin color., Methods: We compared 25OHD levels in children with T1D living in Piedmont, of Caucasian or Moroccan origin, with healthy control subjects matched for age and ethnicity. Data of resident children in Morocco, with and without T1D, were used for comparison., Results: Caucasian (21.4±1.5 vs. 24.0±0.5 ng/mL, P<0.05) and Moroccan children with T1D (12.0±2.6 vs. 17.1±1.7 ng/mL, P<0.05) living in Piedmont had lower 25OHD levels than their counterparts without diabetes. Moroccan children living in Morocco with and without T1D had similar 25OHD levels. Vitamin D deficiency was associated with T1D in Caucasian and Moroccan children living in Piedmont (OR: 1.720, CI95% 1.034-2.860, P<0.03), CONCLUSION: Lower vitamin D levels were associated with T1D in Piedmont. Further studies are necessary to explain a possible relationship between vitamin D and T1D.

Context and Objective: Ghrelin secretion is altered at the onset and after the start of insulin therapy in children with type 1 diabetes. Contemporary regulation of acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (OBST) remains undefined in this disease. It is unknown as to whether they could be good predictors of changes in glucose and metabolic control., Design, Setting, and Subjects: This was a longitudinal study conducted in a tertiary care center. AG, UAG, and OBST were measured at baseline and after 2 years of follow-up in 51 children and adolescents with a history of type 1 diabetes extending beyond 1 year. A total of 33 healthy matched subjects were used as controls., Results: Age-, puberty-, and body mass index-adjusted UAG levels were lower (P < .005) and OBST levels were higher (P < .009) in children with type 1 diabetes, with respect to controls. AG levels were similar to controls, but all ratios of the three peptides are altered in diabetic patients. OBST (P < .05) was negatively correlated with C-peptide (P < .05) and insulin antibodies (P < .008) at the onset of diabetes. In diabetic patients, baseline AG and UAG levels were negatively correlated with insulin dosage in the short and long term (P < .001). AG, but not OBST, was positively correlated with C-peptide levels 2 years after diagnosis (P < .05). Overall, the peptides were not predictive of glucose and metabolic control., Conclusions: UAG, AG, OBST, and their ratios are differently regulated in children with type 1 diabetes, suggesting a role in the metabolic balance of the disease, with insulin a likely regulator of AG and UAG. The peptides do not appear to be good long-term predictors of glucose control, with further investigations needed to explain whether OBST could be a precocious predictor of islet dysfunction.

To assess burden and clinical features of type 1 diabetes in migrant with respect to Italian children. Prevalent children with type 1 diabetes were identified through a multicenter study, including 46 pediatric outpatients diabetic clinics. A nested case-control study was also performed, comparing features at diabetes onset and after 1 year of insulin treatment in 84 migrants and 75 Italian children with onset in 2011, matched for age and sex. Out of 7,812 children cared for by pediatric diabetologists, 761 (10%) were migrant and 548 of them were born in Italy. Age at diagnosis was lower in migrants born in Italy (5.1 years, interquartile range (IQR) 2.2-7.7) than in those born in their original countries (7.8 years, IQR 5.3-10.3) and in Italians (9.8 years, IQR 5.9-13.0, p < 0.001). At diabetes onset, migrants had lower frequencies of positivities of markers of β-cell autoimmunity (96 vs. 99.5%, p < 0.01), higher values of weight loss (11 vs. 7%, p < 0.01), HbA1c (70 vs. 58 mmol/mol, p < 0.001), and insulin requirement (0.70 ± 0.03 vs. 0.63 ± 0.10 UI/kg/die, p = 0.05) and lower levels of 25-OH vitamin D3 (15.0 ± 2.8 vs. 20.8 ± 1.3, p = 0.03). Moreover, they experienced higher frequencies of hospitalizations during the first year of disease (19.2 vs. 2.7%, p < 0.001). Burden of type 1 diabetes in migrant children is increasing in Italy, with younger age at onset and different clinical features than in Italian children. Higher hospitalization rates and poorer glycemic control over the first year underline that approach to diabetes care in migrants needs to be improved.

Aim: To evaluate if nutritional intakes and lipid profile fulfill international guidelines and recommendations before and after a structured dietician training to a Mediterranean- style diet in an Italian pediatric population with Type 1 diabetes., Methods: A 6-month prospective cohort study. Baseline and after-intervention nutritional intakes, lipid profile, glycated hemoglobin (HbA(1c)), and clinical parameters of 96 children and adolescents with Type 1 diabetes were assessed. A comparative computerized system which was approved and validated by the Italian Diabetologist Association was used to define the amounts of nutrients., Results: At baseline mean daily dietary intakes of carbohydrates, proteins, and lipids were respectively (mean ± SEM) 51.8 ± 0.5, 15.9 ± 0.2, 33.8 ± 0.6%, with a contribution of cholesterol of 248.7 ± 12.5 mg/day. Fiber assumption was 18.0 ± 0.4 g/day. The 64.5% and 29.1% (p<0.0001) of subjects had at least one lipid parameter higher than 75(th) and 95(th) percentiles, respectively, of selected cut points (American Diabetes Association guidelines for total and LDL-cholesterol and American Academy of Pediatrics standards for HDL-cholesterol and triglycerides). Six months after the dietician intervention, dietary lipids and cholesterol decreased (p<0.0001) while fibers (p<0.0001) increased. LDL-cholesterol, non-HDL-cholesterol, and total cholesterol:HDL-cholesterol ratios significantly decreased (p<0.001) with a reduction of rate of subjects with at least one pathological lipid parameter (p<0.01) independently by weight and glucose control., Conclusions: Italian pediatric subjects with Type 1 diabetes present a balanced diet with exception of lipids intake and a suboptimal lipid profile. A structured dietician training to a Mediterranean-style diet improves the quality of nutrient intakes being followed by a reduction of LDL-cholesterol, non- HDL-cholesterol, and total cholesterol:HDL-cholesterol ratios.