Background: Type 1 diabetes (T1D) is a disease closely linked to nutrition and modifications in various dietary components have been part of the effort to prevent or slow the progression of the disease even before the discovery of insulin. Summary: The scientific focus in the prevention or progression modification of T1D is mostly centered on four dietary compounds and their modifications – gluten and its omission, vitamin D supplementation, omega-3 fatty acids supplementation, and decreasing of the amount of ingested carbohydrates. The aim of this narrative review was to provide an overview of nutritional interventions studied in children either as preventive methods or as modifiers in the early stages of T1D from autoantibody positive individuals to persons with newly diagnosed T1D. Key Messages: Our review shows that dietary modifications in various dietary components might be useful but none of them seems to provide universal effects in T1D prevention or progression modification. More research is therefore needed with focus on promising modes of action of individual dietary components.

Type 1 diabetes (T1D) is an autoimmune disease that leads to absolute insulin deficiency and the need for lifelong insulin replacement. Despite the effort to elucidate them, the mechanisms that drive the immune destruction of the beta-cells are still largely unknown. Among the candidate suspects of T1D development, viral infections [1], gut bacteriome composition [2] but also dietary factors are often mentioned [3]. The dietary approaches and nutritional intake recommendations for people with T1D are part of the international clinical practice guidelines [4, 5]. Yet, T1D is a complex disease that passes several stages before the clinical onset and several dietary components may have a preventive role even before it develops. It is possible to divide the possible preventive strategies (including the dietary) according to the disease stage and the aims these mean to achieve [6] (Table 1). Dietary components may play a role either as triggers very early in the human life and be considered as the means of primary prevention. They can be also considered as the accelerators or enhancers of the autoimmune process later in life as a part of secondary prevention or even have a role in delaying the decline of beta-cell capacity in new onset T1D as a form of tertiary prevention.

Table 1.

Preventive strategies in T1D

T1D stageEligible personsCommon outcome measuresAims
Primary prevention Before the T1D stages Persons with increased risk of T1D development Development of ≥2 autoantibodies Prevention of the onset of autoimmunity 
Secondary prevention Stage 1, stage 2 Persons with ≥2 autoantibodies (i.e., at an early stage of T1D) Clinical diagnosis of T1D Delaying the onset of insulin dependence 
Tertiary prevention Stage 3 Persons with newly diagnosed T1D Residual beta-cell capacity (C-peptide preservation) Prolonging of the partial clinical remission period 
Complications prevention Long-standing diabetes (Stage 4) Persons with long-standing T1D T1D metabolic outcome measures Prevention of the complication development 
T1D stageEligible personsCommon outcome measuresAims
Primary prevention Before the T1D stages Persons with increased risk of T1D development Development of ≥2 autoantibodies Prevention of the onset of autoimmunity 
Secondary prevention Stage 1, stage 2 Persons with ≥2 autoantibodies (i.e., at an early stage of T1D) Clinical diagnosis of T1D Delaying the onset of insulin dependence 
Tertiary prevention Stage 3 Persons with newly diagnosed T1D Residual beta-cell capacity (C-peptide preservation) Prolonging of the partial clinical remission period 
Complications prevention Long-standing diabetes (Stage 4) Persons with long-standing T1D T1D metabolic outcome measures Prevention of the complication development 

The attention in diabetes pathogenesis and prevention shifts toward cell therapy and immunotherapy but diet should not be overlooked as it might represent a safe and inexpensive way of intervening in the disease progression. Any intervention available of slowing the autoimmunity even after the T1D onset is crucial as people with preserved C-peptide production tend to have better metabolic outcomes [7]. This remains of essence as the global targets for T1D are often unmet, especially in children and adolescents [8, 9]. A search for a therapeutic approach (dietary components included) that could prolong the endogenous insulin secretion or improve the glycemic outcomes is therefore ongoing with direct impact not only on the length [10] but also the quality of life [11].

Various dietary components offer wide range of mechanisms of action on different levels of T1D pathophysiology. Vitamin D has a profound capacity to influence most of the immune cell types [12] and altogether leads to setting up a tolerogenic milieu [13]. The possible effects of gluten range from the described effects on immune cells [14] across the supposed direct effects on beta-cells [15] on to gut microbiome composition shifts [16]. These may all play a role in the development and progression of T1D. Omega-3 fatty acids have direct anti-inflammatory effects that have been studied in several autoimmune disorders as reviewed by Poggioli et al. [17]. The amount of carbohydrate and/or the glycemic load directly affects glycemia [18] and can thus be hypothesized to decrease the stress of the beta-cells in the early phases of T1D [19]. Apart from macronutrients, another broad field of interest lies in the micronutrients intake early in life as reviewed elsewhere [20].The aim of this review was to offer an insight into the current knowledge on the aforementioned dietary components that could affect T1D development, rapidity of clinical onset and the length of the partial remission period.

Since one of the peaks of the development of autoimmunity in T1D comes within the first 2 years of the life of an individual [21], it is reasonable to suspect very early triggers concerning the infant or even the newborn or prenatal periods at least in some of the T1D cases. Dietary habits or interventions in pregnant women, infants, or toddlers have thus been studied in this respect. The subjects in primary prevention studies are usually genetically susceptible individuals and the endpoint is the development of multiple islet autoantibodies.

A registry-based study from Denmark showed that the risk of developing autoimmunity is higher in the offspring of the mothers with highest gluten intake during pregnancy as compared to the offspring of those with lowest gluten intake [22]. A similarly based mother-child Norwegian study (MoBa) did not observe such an association in the mothers but instead, the risk increased with higher gluten intake of the child [23]. As far as vitamin D or its metabolite 25-hydroxyvitamin D (25(OH)D) are concerned, there was no association between their intake nor serum levels in pregnancy and autoimmunity development in the offspring [24, 25]. Lack of the anti-inflammatory omega-3 fatty acids is also mentioned with regard to T1D, yet neither their lower dietary intake nor their decreased serum levels in pregnancy were associated with T1D development in children [24, 26].

The first extra-uterine nutrition of a child comes from breastmilk which, in addition to nutrients, contains also several immuno-active substances [27]. Population data from large registries show that never being breastfed is associated with higher risk of T1D development in children [28]. Yet, concerning the length of breastfeeding, several studies have shown no association of autoantibody occurrence nor T1D development [29‒31]. Another consideration might be about the use of formula and its type since formula use is widespread in the high-income countries where the incidence of T1D is the highest. To that end, the robust TRIGR study compared the use of hydrolyzed and conventional formula and their role in the development of T1D. Despite 11 years of follow-up, no difference in T1D development was found between the hydrolyzed formula- or conventional formula-fed infants [32].

The weaning and the introduction of other foods create another possible window of opportunity for autoimmunity triggers. The timing of introduction of the cow’s milk does not seem to affect the development of autoimmunity or T1D [29‒31]. Yet, studying the introduction of solid foods including gluten yielded some, albeit conflicting results. The increased risk of autoimmunity development if gluten introduced before the age of 3 months was observed in the German BABYDIET study [33, 34] whereas the international TEDDY study identified increasing risk with later introduction of gluten [31]. In the international DAISY study, the risk was increased if gluten was introduced before the fourth or after the seventh month of age [35]. To add to the confusion, no association of the timing of gluten introduction was observed in a study by Ludvigsson [36]. An intervention study with 150 at risk children comparing control (6 months) and late (12 months) introduction of gluten concluded there was no difference in the autoimmunity development nor T1D occurrence [37, 38].

The risk stemming from the amount of ingested gluten is similarly conflicted with the DIPP study observing a considerably higher risk of T1D with higher intake of gluten (adjusted HR 3.4 per 10 g increase in gluten intake per day) [39] as did the above-mentioned Norwegian registry MoBa study (adjusted HR 1.5 per 10 g increase in gluten intake per day) [40] while in the DAISY study, no significant association was observed [41].

Concerning vitamin D, the TEDDY study has found association between higher plasma (25(OH)D) and lower risk of the development of autoantibodies but the effect size was very small (OR 0.93 per 5 nmol increase in (25(OH)D)) [42]. Furthermore, other previously mentioned and similarly designed studies (DAISY, DIPP) found no such association between vitamin D intake nor plasma 25(OH)D levels making vitamin D deficiency an unlikely trigger of T1D [43, 44].

Both DAISY and DIPP studies showed association between either the intake or serum levels of some of the omega-3 fatty acids and lower risk of autoimmunity development [45, 46]. A nested case-control study within the DIPP cohort also weakly associated the decreased risk with higher serum levels of linolenic acid which may be connected to lower milk meat fat intake and instead to higher intake of vegetable fats [47]. These associations are yet to be confirmed by prospective studies. The studies focusing on dietary components in primary prevention of T1D are summarized in Table 2.

Table 2.

Overview of literature on dietary components in primary prevention of T1D

InterventionReferencesMain objectiveStudy designStudy populationResultsComments and limitations
Breastfeeding/Infant formula Frederiksen et al. [29] (2013) Association of breastfeeding/solid foods introduction with the development of T1D Observational study (DAISY cohort) 1,835 children with high-risk HLA alleles or one affected first-cv (FDR) Duration of exclusive/any breastfeeding was not associated with the development of T1D Exposure to solid foods before 4 months or after 6 months of age is associated with the development of T1D 
Lund-Blix et al. [28] (2017) Association of breastfeeding with the development of T1D Population-based cohort study 155,392 children from Norwegian and Danish birth registries No breastfeeding was associated with higher risk of developing T1D No association with the duration of full/any breastfeeding 
Hakola et al. [30] (2018) Association of breastfeeding/solid foods introduction with IA development Observational study (DIPP cohort) 5,915 newborns with high-risk HLA alleles Duration of exclusive/any breastfeeding was not associated with the development of IA or T1D Early introduction of solid foods was associated with the IA development up to the age of 3 years, no association with cow’s milk introduction 
Uusitalo et al. [31] (2018) Association of breastfeeding/solid foods introduction with IA development Observational study (TEDDY cohort) 7,563 newborns with high-risk HLA alleles Duration of exclusive/any breastfeeding was not associated with the development of IA or T1D No association with the timing of introduction of solid foods, later introduction of gluten was associated with higher risk of IA development 
Knip et al. [32] (2018) Comparison between extensively hydrolyzed and conventional formula Randomized controlled trial (TRIGR) 2,159 children with one affected FDR and HLA susceptibility No difference in T1D development between hydrolyzed and conventional formula fed infants  
Gluten Ziegler et al. [33] (2003) Association of the gluten introduction with IA development Observational study (BABYDIAB cohort) 1,610 children with at least one affected parent Introduction of gluten before the age of 3 months increased the risk of IA development Introduction of gluten after the age of 6 months does not increase the risk of IA development 
Norris et al. [35] (2003) Association of the gluten introduction with IA development Observational study (DAISY cohort) 1,183 newborns with high-risk HLA or one affected FDR Introduction of gluten before the age of 4 months and after the age of 7 months increased the risk of IA development  
Ludvigsson [36] (2003) Association of the gluten introduction with IA development Observational study 210 newborns of mothers with atopic disease No association between the timing of gluten introduction and the risk of IA development No association with the timing of introduction of cow’s milk and IA development 
 Beyerlein et al. [38] (2014) Association of the gluten introduction with IA development Randomized controlled trial (BABYDIET cohort) 150 children with one affected parent and HLA susceptibility No difference in IA development between the groups that introduced gluten either at 6 or 12 months  
Uusitalo et al. [31] (2018) Association of the gluten introduction with IA development Observational study (TEDDY cohort) 7,563 newborns with high-risk HLA alleles Later introduction of gluten was associated with higher risk of IA development Lower risk if gluten introduced before 4 months, higher if after 9 months 
Vitamin D Simpson et al. [43] (2011) Associations of vitamin D intake and plasma 25(OH)D levels and the risk of IA or T1D development Observational study (DAISY cohort) 2,644 newborns with high-risk HLA or one affected FDR No association between vitamin D intake nor plasma 25(OH)D levels and IA or T1D development  
Norris et al. [42] (2018) Associations of plasma 25(OH)D and the risk of IA development Observational study (TEDDY cohort) 8,676 children with high-risk HLA alleles Higher plasma 25(OH)D levels were associated with lower risk of IA development The decrease in IA development risk was very low (OR 0.93 per 5 nmol/L) 
Makinen et al. [44] (2016) Associations of umbilical cord 25(OH)D level and the risk of IA development Observational study (DIPP cohort) 764 newborns with high-risk HLA alleles The 25(OH)D levels at birth were not associated with IA or T1D development  
Omega 3 fatty acids Virtanen et al. [47] (2010) Associations of serum fatty acid levels and the development of IA Nested case-control study 108 children with developed IA and 216 autoantibody negative controls The serum levels of myristic, pentadecanoic and palmitoleic acid isomers 16:1 n-7 and 16:1 n-9 were positively associated with the risk of developing IA The serum level of linoleic acid was inversely associated with IA development 
Norris et al. [46] (2007) Associations of serum omega-3 fatty acids intake and the risk of IA development Observational study (DAISY cohort) 1,770 newborns with high-risk HLA or one affected FDR Omega-3 fatty acid intake was inversely associated with IA development Omega-3 fatty acid content on erythrocyte membranes was also inversely associated with IA development 
Niinisto et al. [45] (2017) Associations of serum fatty acids levels and the risk of IA development Observational study (DIPP cohort) 7,782 children with high-risk HLA alleles Higher levels of pentadecanoic, palmitic, palmitoleic and docosahexaenoic acids were associated with decreased IA development risk Higher Arachidonic: Docosahexaenoic and n-6:n-3 ratios were associated with higher risk of IA development 
InterventionReferencesMain objectiveStudy designStudy populationResultsComments and limitations
Breastfeeding/Infant formula Frederiksen et al. [29] (2013) Association of breastfeeding/solid foods introduction with the development of T1D Observational study (DAISY cohort) 1,835 children with high-risk HLA alleles or one affected first-cv (FDR) Duration of exclusive/any breastfeeding was not associated with the development of T1D Exposure to solid foods before 4 months or after 6 months of age is associated with the development of T1D 
Lund-Blix et al. [28] (2017) Association of breastfeeding with the development of T1D Population-based cohort study 155,392 children from Norwegian and Danish birth registries No breastfeeding was associated with higher risk of developing T1D No association with the duration of full/any breastfeeding 
Hakola et al. [30] (2018) Association of breastfeeding/solid foods introduction with IA development Observational study (DIPP cohort) 5,915 newborns with high-risk HLA alleles Duration of exclusive/any breastfeeding was not associated with the development of IA or T1D Early introduction of solid foods was associated with the IA development up to the age of 3 years, no association with cow’s milk introduction 
Uusitalo et al. [31] (2018) Association of breastfeeding/solid foods introduction with IA development Observational study (TEDDY cohort) 7,563 newborns with high-risk HLA alleles Duration of exclusive/any breastfeeding was not associated with the development of IA or T1D No association with the timing of introduction of solid foods, later introduction of gluten was associated with higher risk of IA development 
Knip et al. [32] (2018) Comparison between extensively hydrolyzed and conventional formula Randomized controlled trial (TRIGR) 2,159 children with one affected FDR and HLA susceptibility No difference in T1D development between hydrolyzed and conventional formula fed infants  
Gluten Ziegler et al. [33] (2003) Association of the gluten introduction with IA development Observational study (BABYDIAB cohort) 1,610 children with at least one affected parent Introduction of gluten before the age of 3 months increased the risk of IA development Introduction of gluten after the age of 6 months does not increase the risk of IA development 
Norris et al. [35] (2003) Association of the gluten introduction with IA development Observational study (DAISY cohort) 1,183 newborns with high-risk HLA or one affected FDR Introduction of gluten before the age of 4 months and after the age of 7 months increased the risk of IA development  
Ludvigsson [36] (2003) Association of the gluten introduction with IA development Observational study 210 newborns of mothers with atopic disease No association between the timing of gluten introduction and the risk of IA development No association with the timing of introduction of cow’s milk and IA development 
 Beyerlein et al. [38] (2014) Association of the gluten introduction with IA development Randomized controlled trial (BABYDIET cohort) 150 children with one affected parent and HLA susceptibility No difference in IA development between the groups that introduced gluten either at 6 or 12 months  
Uusitalo et al. [31] (2018) Association of the gluten introduction with IA development Observational study (TEDDY cohort) 7,563 newborns with high-risk HLA alleles Later introduction of gluten was associated with higher risk of IA development Lower risk if gluten introduced before 4 months, higher if after 9 months 
Vitamin D Simpson et al. [43] (2011) Associations of vitamin D intake and plasma 25(OH)D levels and the risk of IA or T1D development Observational study (DAISY cohort) 2,644 newborns with high-risk HLA or one affected FDR No association between vitamin D intake nor plasma 25(OH)D levels and IA or T1D development  
Norris et al. [42] (2018) Associations of plasma 25(OH)D and the risk of IA development Observational study (TEDDY cohort) 8,676 children with high-risk HLA alleles Higher plasma 25(OH)D levels were associated with lower risk of IA development The decrease in IA development risk was very low (OR 0.93 per 5 nmol/L) 
Makinen et al. [44] (2016) Associations of umbilical cord 25(OH)D level and the risk of IA development Observational study (DIPP cohort) 764 newborns with high-risk HLA alleles The 25(OH)D levels at birth were not associated with IA or T1D development  
Omega 3 fatty acids Virtanen et al. [47] (2010) Associations of serum fatty acid levels and the development of IA Nested case-control study 108 children with developed IA and 216 autoantibody negative controls The serum levels of myristic, pentadecanoic and palmitoleic acid isomers 16:1 n-7 and 16:1 n-9 were positively associated with the risk of developing IA The serum level of linoleic acid was inversely associated with IA development 
Norris et al. [46] (2007) Associations of serum omega-3 fatty acids intake and the risk of IA development Observational study (DAISY cohort) 1,770 newborns with high-risk HLA or one affected FDR Omega-3 fatty acid intake was inversely associated with IA development Omega-3 fatty acid content on erythrocyte membranes was also inversely associated with IA development 
Niinisto et al. [45] (2017) Associations of serum fatty acids levels and the risk of IA development Observational study (DIPP cohort) 7,782 children with high-risk HLA alleles Higher levels of pentadecanoic, palmitic, palmitoleic and docosahexaenoic acids were associated with decreased IA development risk Higher Arachidonic: Docosahexaenoic and n-6:n-3 ratios were associated with higher risk of IA development 

FDR, first-degree relatives; HLA, human leukocyte antigen; IA, islet autoimmunity; T1D, type 1 diabetes.

The progression from autoantibody positivity toward clinical diagnosis of T1D usually spans a period of several years [48] during which a child encounters a variety of possible environmental accelerators of the autoimmune process making this period an attractive target for various interventions. The subjects for the studies aimed at secondary prevention are multiple-autoantibody positive individuals without or with dysglycemia (stage 1 or stage 2 T1D) and the usual endpoint is the clinical diagnosis of T1D (stage 3). The studies performed so far lacked sufficient power which might change in the future with the advent of T1D autoantibody screening.

Again, the role of gluten was studied in this setting albeit in studies with a limited number of participants. In the Italian cross-over study with gluten-free diet (GFD) by Pastore et al. [49] 17 multiple antibody positive children did not decrease their autoantibody titer levels during the GFD but their insulin resistance increased after the reintroduction of gluten, possibly due to the intake of different types of carbohydrates during the diets. A rather small study from Germany included 7 multiple antibody positive children who kept GFD for 12 months and compared their development of T1D to 30 children on a regular diet. No significant differences were observed between the groups, although, interestingly, no child in the GFD group developed T1D during the intervention [50].

Lower levels of serum 25(OH)D did not seem to increase the risk of progression toward T1D in any of the large cohort studies in which this has been examined (DAISY, BABYDIET) [43, 51]. Similarly, no association was observed between omega-3 fatty acids serum levels and the progression rate toward T1D [52].

The DAISY study also showed that increased sugar intake and higher glycemic index are associated with increased risk of progression toward T1D in antibody positive individuals, especially in those carrying high-risk HLA genotypes [53]. One of the proposed mechanisms is an increased stress for beta-cell endoplasmic reticulum which might propel cell destruction and via neo-antigen formation fuel further progression. Surprisingly, no studies assessing the role of decreasing carbohydrate load or glycemic index in order to stall or slow down the progression toward stage 3 T1D are currently available. Table 3 summarizes the dietary components examined in secondary prevention of T1D.

Table 3.

Overview of literature on dietary components in secondary prevention of T1D

InterventionReferencesMain objectiveStudy designStudy populationResultsComments and limitations
Gluten Pastore et al. [49] (2003) Role of gluten/gluten-free diet (GFD) in T1D progression Single-arm crossover trial 17 multiple autoantibody positive subjects with affected first degree relatives (FDR) No difference in autoantibody titers after 6 months of GFD Insulin resistance decreased during the GFD period and increased after the reintroduction of gluten 
Füchtenbusch et al. [50] (2004) Role of gluten/gluten-free diet (GFD) in T1D progression Prospective controlled trial 7 multiple autoantibody positive subjects with affected FDR on GFD/30 multiple autoantibody positive controls with affected FDR No difference in autoantibody titers after 12 months of GFD No difference in the cumulative risk of T1D development between the groups 
Vitamin D Simpson et al. [43] (2011) Association between vitamin D intake and plasma 25(OH)D levels and progression to T1D Observational study (DAISY cohort) 198 IA-positive children No association between vitamin D intake nor plasma 25(OH)D levels and progression to T1D  
Raab et al. [51] (2014) Prevalence of vitamin D deficiency and its association with the progression to T1D Cross-sectional study 108 multiple IA-positive children/406 IA-negative children/244 children with newly diagnosed T1D Cumulative incidence of T1D did not differ between children with vitamin D deficiency and those with sufficient vitamin D levels Children with multiple IA had lower plasma 25(OH)D levels and higher prevalence of vitamin D deficiency than IA-negative children 
Omega-3 fatty acids Miller et al. [52] (2011) Association of omega-3 fatty acid intake and the progression to T1D Observational study (DAISY cohort) 157 IA-positive children Omega-3 fatty acid intake was not associated with the progression to T1D Erythrocyte membrane omega-3 fatty acid levels were not associated with progression to T1D either 
Carbohydrate intake Lamb et al. [53] (2015) Association of sugar intake and the progression of T1D Observational study (DAISY cohort) 142 IA-positive children Total intake of sugars was significantly associated with the progression to T1D in IA-positive children The association was the highest in children with high-risk HLA genotype 
InterventionReferencesMain objectiveStudy designStudy populationResultsComments and limitations
Gluten Pastore et al. [49] (2003) Role of gluten/gluten-free diet (GFD) in T1D progression Single-arm crossover trial 17 multiple autoantibody positive subjects with affected first degree relatives (FDR) No difference in autoantibody titers after 6 months of GFD Insulin resistance decreased during the GFD period and increased after the reintroduction of gluten 
Füchtenbusch et al. [50] (2004) Role of gluten/gluten-free diet (GFD) in T1D progression Prospective controlled trial 7 multiple autoantibody positive subjects with affected FDR on GFD/30 multiple autoantibody positive controls with affected FDR No difference in autoantibody titers after 12 months of GFD No difference in the cumulative risk of T1D development between the groups 
Vitamin D Simpson et al. [43] (2011) Association between vitamin D intake and plasma 25(OH)D levels and progression to T1D Observational study (DAISY cohort) 198 IA-positive children No association between vitamin D intake nor plasma 25(OH)D levels and progression to T1D  
Raab et al. [51] (2014) Prevalence of vitamin D deficiency and its association with the progression to T1D Cross-sectional study 108 multiple IA-positive children/406 IA-negative children/244 children with newly diagnosed T1D Cumulative incidence of T1D did not differ between children with vitamin D deficiency and those with sufficient vitamin D levels Children with multiple IA had lower plasma 25(OH)D levels and higher prevalence of vitamin D deficiency than IA-negative children 
Omega-3 fatty acids Miller et al. [52] (2011) Association of omega-3 fatty acid intake and the progression to T1D Observational study (DAISY cohort) 157 IA-positive children Omega-3 fatty acid intake was not associated with the progression to T1D Erythrocyte membrane omega-3 fatty acid levels were not associated with progression to T1D either 
Carbohydrate intake Lamb et al. [53] (2015) Association of sugar intake and the progression of T1D Observational study (DAISY cohort) 142 IA-positive children Total intake of sugars was significantly associated with the progression to T1D in IA-positive children The association was the highest in children with high-risk HLA genotype 

FDR, first-degree relatives; GFD, gluten-free diet; HLA, human leukocyte antigen; IA, islet autoimmunity; T1D, type 1 diabetes.

The enrollment of subjects to clinical trials for the tertiary prevention of T1D is considerably easier with a large pool of newly diagnosed persons with T1D being available. On the other hand, interventions at this point occur late in the natural course of T1D and are unlikely to have massive immediate impact. The outcomes for these studies are mostly aimed at C-peptide preservation, partial clinical remission period prolongation and/or better control of T1D.

Several studies aimed to investigate the role of GFD shortly after the onset of T1D. First, Svensson et al. [54] compared 15 children with diabetes (CwD) who initiated GFD after T1D onset to historical cohorts and found a prolonged partial remission period (assessed by insulin dose adjusted HbA1c, IDAA1c) and lower HbA1c at 12 months. In another, larger and more methodically sound study, a more pronounced partial remission, lower HbA1c and lower decrease of C-peptide throughout the first year after T1D onset were found in 20 CwD on GFD compared to 19 CwD on control diet [55]. A similarly designed study reached similar conclusions with lower HbA1c and a tendency to higher IDAA1c [56], yet remained underpowered due to recruitment difficulties which were mentioned in all of the studies. Furthermore, due to the lack of randomization, these studies were prone to selection bias and thus not able to confirm causality of their findings.

The possible effects of vitamin D in recently diagnosed subjects were studied in several randomized controlled trials (RCTs). While Gabbay et al. [57] have seen higher levels of stimulated C-peptide in the vitamin D3 receiving group, no effects on stimulated C-peptide or area under the curve of C-peptide were observed in similarly powered trials [58‒60]. No effects on HbA1c or IDAA1c were observed in any of the trials. A more recent RCT showed borderline yet insignificant differences between the vitamin D3 and placebo groups in stimulated C-peptide, HbA1c and IDAA1c [61]. Omega-3 fatty acids intake as a means of retaining endogenous secretion was assessed only in combination with vitamin D3 supplementation in a cohort study which found lower insulin dose and IDAA1c in supplemented CwD against historical cohort [62]. In an observational study, long-chain omega-3 fatty acids were positively associated with preserved beta-cell function [63], while in the same study, higher vitamin D at baseline was associated with lower beta-cell function at 2 years after onset.

In the abovementioned observational study of nutritional intake at the onset of T1D and further, carbohydrate intake did not associate with beta-cell preservation [63]. Several cases showing uncommonly prolonged complete remission of T1D after the initiation of low-carbohydrate diet (LCD) after onset were nonetheless described [64, 65]. A summary of dietary components trials in tertiary prevention of T1D is available in Table 4.

Table 4.

Overview of literature on dietary components in tertiary prevention of T1D

InterventionReferencesMain objectiveStudy designStudy populationResultsComments and limitations
Gluten Svensson et al. [54] (2016) Preservation of C-peptide through gluten-free diet (GFD) Cohort study with historical controls 15 new onset CwD on GFD/historical controls No difference in stimulated C-peptide between the groups Prolonged partial remission period and lower HbA1c at 12 months in the GFD group 
Neuman et al. [55] (2020) Preservation of C-peptide through GFD Prospective controlled trial 20 new onset CwD on GFD/19 new onset controls Lower loss of stimulated C-peptide in the GFD group More pronounced partial remission period and lower HbA1c at 12 months in the GFD group 
Söderström et al. [56] (2022) Preservation of C-peptide through GFD Prospective controlled trial 14 new onset CwD on GFD/9 new onset controls No difference in stimulated C-peptide between the groups No difference in partial remission, lower HbA1c at 6 months in the GFD group 
Vitamin D Pitocco et al [59] (2006) Preservation of C-peptide through vitamin D3 substitution Randomized controlled trial 34 PwD with new onset randomized to vitamin D3 group/33 to nicotinamide group No difference in stimulated C-peptide between the groups Lower insulin dose in the vitamin D3 group, no difference in HbA1c 
Walter et al. [58] (2010) Preservation of C-peptide through vitamin D3 substitution Randomized controlled trial 22 PwD with new onset randomized to vitamin D3 group/18 to placebo No difference in stimulated C-peptide between the groups No difference in HbA1c nor insulin dose 
Bizzarri et al. [60] (2010) Preservation of C-peptide through vitamin D3 substitution Randomized controlled trial 15 PwD with new onset randomized to vitamin D3 group/12 to placebo No difference in stimulated C-peptide between the groups No difference in HbA1c nor insulin dose 
Gabbay et al [57] (2012) Preservation of C-peptide through vitamin D3 substitution Randomized controlled trial 19 people with new onset T1D (PwD) randomized vitamin D3 group/19 to placebo Vitamin D3 group retained more stimulated C-peptide at 12 and 18 months No difference in HbA1c nor insulin dose 
Omega-3 fatty acids Mayer-Davis et al. [63] (2013) Association of nutrition and preservation of C-peptide Observational study (SEARCH cohort) 1,316 youth with T1D Docosahexaenoic acid eicosapentaenoic acid intake was associated with higher C-peptide retention Vitamin D intake was inversely associated with C-peptide retention 
 Cadario et al. [62] (2019) Partial remission prolongation through omega-3 fatty acids and vitamin D3 substitution Cohort study with historical controls 22 new onset PwD receiving omega-3 fatty acid and vitamin D3 substitution/37 historical controls More pronounced partial remission in the intervention group Lower insulin dose in the intervention group, no difference in HbA1c at 12 months 
Carbohydrate intake Mayer-Davis et al. [63] (2013) Association of nutrition and preservation of C-peptide Observational study (SEARCH cohort) 1,316 youth with T1D No association between carbohydrate intake and C-peptide retention  
InterventionReferencesMain objectiveStudy designStudy populationResultsComments and limitations
Gluten Svensson et al. [54] (2016) Preservation of C-peptide through gluten-free diet (GFD) Cohort study with historical controls 15 new onset CwD on GFD/historical controls No difference in stimulated C-peptide between the groups Prolonged partial remission period and lower HbA1c at 12 months in the GFD group 
Neuman et al. [55] (2020) Preservation of C-peptide through GFD Prospective controlled trial 20 new onset CwD on GFD/19 new onset controls Lower loss of stimulated C-peptide in the GFD group More pronounced partial remission period and lower HbA1c at 12 months in the GFD group 
Söderström et al. [56] (2022) Preservation of C-peptide through GFD Prospective controlled trial 14 new onset CwD on GFD/9 new onset controls No difference in stimulated C-peptide between the groups No difference in partial remission, lower HbA1c at 6 months in the GFD group 
Vitamin D Pitocco et al [59] (2006) Preservation of C-peptide through vitamin D3 substitution Randomized controlled trial 34 PwD with new onset randomized to vitamin D3 group/33 to nicotinamide group No difference in stimulated C-peptide between the groups Lower insulin dose in the vitamin D3 group, no difference in HbA1c 
Walter et al. [58] (2010) Preservation of C-peptide through vitamin D3 substitution Randomized controlled trial 22 PwD with new onset randomized to vitamin D3 group/18 to placebo No difference in stimulated C-peptide between the groups No difference in HbA1c nor insulin dose 
Bizzarri et al. [60] (2010) Preservation of C-peptide through vitamin D3 substitution Randomized controlled trial 15 PwD with new onset randomized to vitamin D3 group/12 to placebo No difference in stimulated C-peptide between the groups No difference in HbA1c nor insulin dose 
Gabbay et al [57] (2012) Preservation of C-peptide through vitamin D3 substitution Randomized controlled trial 19 people with new onset T1D (PwD) randomized vitamin D3 group/19 to placebo Vitamin D3 group retained more stimulated C-peptide at 12 and 18 months No difference in HbA1c nor insulin dose 
Omega-3 fatty acids Mayer-Davis et al. [63] (2013) Association of nutrition and preservation of C-peptide Observational study (SEARCH cohort) 1,316 youth with T1D Docosahexaenoic acid eicosapentaenoic acid intake was associated with higher C-peptide retention Vitamin D intake was inversely associated with C-peptide retention 
 Cadario et al. [62] (2019) Partial remission prolongation through omega-3 fatty acids and vitamin D3 substitution Cohort study with historical controls 22 new onset PwD receiving omega-3 fatty acid and vitamin D3 substitution/37 historical controls More pronounced partial remission in the intervention group Lower insulin dose in the intervention group, no difference in HbA1c at 12 months 
Carbohydrate intake Mayer-Davis et al. [63] (2013) Association of nutrition and preservation of C-peptide Observational study (SEARCH cohort) 1,316 youth with T1D No association between carbohydrate intake and C-peptide retention  

CwD, children with diabetes; GFD, gluten-free diet; T1D, type 1 diabetes; PwD, people with type 1 diabetes.

Dietary components may play a role in many stages of T1D. From the development of autoantibodies, diet has been employed to prevent, postpone or stall the progression of the disease. However, despite identifying several promising compounds, the results of the studies have so far been mostly indecisive and conflicting. This may be due to the fact that various dietary compounds target different parts of T1D pathogenesis. While gluten or omega-3 fatty acids may play a role very early and may influence the risk of autoantibody development, it does not seem likely that these would consistently decrease the velocity of progression toward T1D. Conversely, carbohydrate intake or glycemic load does not seem to affect the risk of autoantibody development but may play a role around the onset of T1D as it could decrease the beta-cell stress. Results of the studies concerning the role of vitamin D are rather conflicting and do not allow for firm conclusions. Despite some progress in the field of diabetes prevention, there are still many gaps in our knowledge. To fill these, high-quality research is needed. Therein comes the advantage of dietary modulations as these are often considered safe and are considerably cheaper than cell therapy or immunotherapy. The way forward lies in focusing on the promising associations of various dietary compound and exploring these further, a task that could be achieved with the help of population wide screening programs that would identify children with early stages of T1D suitable to these trials.

The authors declare no conflict of interests.

Author’s research is supported by Czech Ministry of Health AZV grant NU21-01-00085.

V.N. wrote the manuscript. L.P., S.P., and Z.S. provided insight into the interventions in early stages of T1D and revised the manuscript critically. All authors contributed to the discussion, reviewed and edited the manuscript, and approved the final version to be published.

1.
Hyoty
H
.
Viruses in type 1 diabetes
.
Pediatr Diabetes
.
2016
;
17
(
Suppl 22
):
56
64
.
2.
Knip
M
,
Honkanen
J
.
Modulation of type 1 diabetes risk by the intestinal microbiome
.
Curr Diab Rep
.
2017
;
17
(
11
):
105
.
3.
Antvorskov
JC
,
Josefsen
K
,
Engkilde
K
,
Funda
DP
,
Buschard
K
.
Dietary gluten and the development of type 1 diabetes
.
Diabetologia
.
2014
;
57
(
9
):
1770
80
.
4.
Holt
RIG
,
DeVries
JH
,
Hess-Fischl
A
,
Hirsch
IB
,
Kirkman
MS
,
Klupa
T
, et al
.
The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
.
Diabetologia
.
2021
;
64
(
12
):
2609
52
.
5.
Annan
SF
,
Higgins
LA
,
Jelleryd
E
,
Hannon
T
,
Rose
S
,
Salis
S
, et al
.
ISPAD clinical practice consensus guidelines 2022: nutritional management in children and adolescents with diabetes
.
Pediatr Diabetes
.
2022
;
23
(
8
):
1297
321
.
6.
Chiarelli
F
,
Giannini
C
,
Primavera
M
.
Prediction and prevention of type 1 diabetes in children
.
Clin Pediatr Endocrinol
.
2019
;
28
(
3
):
43
57
.
7.
Taylor
PN
,
Collins
KS
,
Lam
A
,
Karpen
SR
,
Greeno
B
,
Walker
F
, et al
.
C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis
.
Lancet Diabetes Endocrinol
.
2023
;
11
(
12
):
915
25
.
8.
Miller
KM
,
Beck
RW
,
Foster
NC
,
Maahs
DM
.
HbA1c levels in type 1 diabetes from early childhood to older adults: a deeper dive into the influence of technology and socioeconomic status on HbA1c in the T1D exchange clinic registry findings
.
Diabetes Technol Ther
.
2020
;
22
(
9
):
645
50
.
9.
Foster
NC
,
Beck
RW
,
Miller
KM
,
Clements
MA
,
Rickels
MR
,
DiMeglio
LA
, et al
.
State of type 1 diabetes management and outcomes from the T1D exchange in 2016–2018
.
Diabetes Technol Ther
.
2019
;
21
(
2
):
66
72
.
10.
Orchard
TJ
.
Cardiovascular disease in type 1 diabetes: a continuing challenge
.
Lancet Diabetes Endocrinol
.
2021
;
9
(
9
):
548
9
.
11.
Herman
WH
,
Braffett
BH
,
Kuo
S
,
Lee
JM
,
Brandle
M
,
Jacobson
AM
, et al
.
What are the clinical, quality-of-life, and cost consequences of 30 years of excellent vs. poor glycemic control in type 1 diabetes
.
J Diabetes Complications
.
2018
;
32
(
10
):
911
5
.
12.
Martens
PJ
,
Gysemans
C
,
Verstuyf
A
,
Mathieu
AC
.
Vitamin D’s effect on immune function
.
Nutrients
.
2020
;
12
(
5
):
1248
.
13.
Prietl
B
,
Treiber
G
,
Pieber
TR
,
Amrein
K
.
Vitamin D and immune function
.
Nutrients
.
2013
;
5
(
7
):
2502
21
.
14.
Palova-Jelinkova
L
,
Danova
K
,
Drasarova
H
,
Dvorak
M
,
Funda
DP
,
Fundova
P
, et al
.
Pepsin digest of wheat gliadin fraction increases production of IL-1β via TLR4/MyD88/TRIF/MAPK/NF-κB signaling pathway and an NLRP3 inflammasome activation
.
PLoS One
.
2013
;
8
(
4
):
e62426
.
15.
Dall
M
,
Calloe
K
,
Haupt-Jorgensen
M
,
Larsen
J
,
Schmitt
N
,
Josefsen
K
, et al
.
Gliadin fragments and a specific gliadin 33-mer peptide close KATP channels and induce insulin secretion in INS-1E cells and rat islets of langerhans
.
PLoS One
.
2013
;
8
(
6
):
e66474
.
16.
Neuman
V
,
Pruhova
S
,
Kulich
M
,
Kolouskova
S
,
Vosahlo
J
,
Romanova
M
, et al
.
Changes in the gut bacteriome upon gluten-free diet intervention do not mediate beta cell preservation
.
Diabetologia
.
2023
;
66
(
1
):
241
6
.
17.
Poggioli
R
,
Hirani
K
,
Jogani
VG
,
Ricordi
C
.
Modulation of inflammation and immunity by omega-3 fatty acids: a possible role for prevention and to halt disease progression in autoimmune, viral, and age-related disorders
.
Eur Rev Med Pharmacol Sci
.
2023
;
27
(
15
):
7380
400
.
18.
Schmidt
S
,
Christensen
MB
,
Serifovski
N
,
Damm-Frydenberg
C
,
Jensen
JEB
,
Fløyel
T
, et al
.
Low versus high carbohydrate diet in type 1 diabetes: a 12-week randomized open-label crossover study
.
Diabetes Obes Metab
.
2019
;
21
(
7
):
1680
8
.
19.
Shah
SC
,
Malone
JI
,
Simpson
NE
.
A randomized trial of intensive insulin therapy in newly diagnosed insulin-dependent diabetes mellitus
.
N Engl J Med
.
1989
;
320
(
9
):
550
4
.
20.
Maguolo
A
,
Gabbianelli
R
,
Maffeis
C
.
Micronutrients in early life and offspring metabolic health programming: a promising target for preventing non-communicable diseases
.
Eur J Clin Nutr
.
2023
;
77
(
12
):
1105
12
.
21.
Knip
M
,
Korhonen
S
,
Kulmala
P
,
Veijola
R
,
Reunanen
A
,
Raitakari
OT
, et al
.
Prediction of type 1 diabetes in the general population
.
Diabetes Care
.
2010
;
33
(
6
):
1206
12
.
22.
Antvorskov
JC
,
Halldorsson
TI
,
Josefsen
K
,
Svensson
J
,
Granstrom
C
,
Roep
BO
, et al
.
Association between maternal gluten intake and type 1 diabetes in offspring: national prospective cohort study in Denmark
.
BMJ
.
2018
;
362
:
k3547
.
23.
Lund-Blix
NA
,
Tapia
G
,
Marild
K
,
Brantsaeter
AL
,
Eggesbø
M
,
Mandal
S
, et al
.
Maternal fibre and gluten intake during pregnancy and risk of childhood celiac disease: the MoBa study
.
Sci Rep
.
2020
;
10
(
1
):
16439
.
24.
Silvis
K
,
Aronsson
CA
,
Liu
X
,
Uusitalo
U
,
Yang
J
,
Tamura
R
, et al
.
Maternal dietary supplement use and development of islet autoimmunity in the offspring: TEDDY study
.
Pediatr Diabetes
.
2019
;
20
(
1
):
86
92
.
25.
Miettinen
ME
,
Reinert
L
,
Kinnunen
L
,
Harjutsalo
V
,
Koskela
P
,
Surcel
HM
, et al
.
Serum 25-hydroxyvitamin D level during early pregnancy and type 1 diabetes risk in the offspring
.
Diabetologia
.
2012
;
55
(
5
):
1291
4
.
26.
Sørensen
IM
,
Joner
G
,
Jenum
PA
,
Eskild
A
,
Stene
LC
.
Serum long chain n-3 fatty acids (EPA and DHA) in the pregnant mother are independent of risk of type 1 diabetes in the offspring
.
Diabetes Metab Res Rev
.
2012
;
28
(
5
):
431
8
.
27.
Andreas
NJ
,
Kampmann
B
,
Mehring Le-Doare
K
.
Human breast milk: a review on its composition and bioactivity
.
Early Hum Dev
.
2015
;
91
(
11
):
629
35
.
28.
Lund-Blix
NA
,
Dydensborg Sander
S
,
Størdal
K
,
Nybo Andersen
AM
,
Rønningen
KS
,
Joner
G
, et al
.
Infant feeding and risk of type 1 diabetes in two large scandinavian birth cohorts
.
Diabetes Care
.
2017
;
40
(
7
):
920
7
.
29.
Frederiksen
B
,
Kroehl
M
,
Lamb
MM
,
Seifert
J
,
Barriga
K
,
Eisenbarth
GS
, et al
.
Infant exposures and development of type 1 diabetes mellitus: the Diabetes Autoimmunity Study in the Young (DAISY)
.
JAMA Pediatr
.
2013
;
167
(
9
):
808
15
.
30.
Hakola
L
,
Takkinen
HM
,
Niinisto
S
,
Ahonen
S
,
Nevalainen
J
,
Veijola
R
, et al
.
Infant feeding in relation to the risk of advanced islet autoimmunity and type 1 diabetes in children with increased genetic susceptibility: a cohort study
.
Am J Epidemiol
.
2018
;
187
(
1
):
34
44
.
31.
Uusitalo
U
,
Lee
HS
,
Andren Aronsson
C
,
Vehik
K
,
Yang
J
,
Hummel
S
, et al
.
Early infant diet and islet autoimmunity in the TEDDY study
.
Diabetes Care
.
2018
;
41
(
3
):
522
30
.
32.
Writing Group for the TRIGR Study Group
;
Knip
M
,
Akerblom
HK
,
Al Taji
E
,
Becker
D
,
Bruining
J
, et al
.
Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes: the TRIGR randomized clinical trial
.
JAMA
.
2018
;
319
(
1
):
38
48
.
33.
Ziegler
AG
,
Schmid
S
,
Huber
D
,
Hummel
M
,
Bonifacio
E
.
Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies
.
JAMA
.
2003
;
290
(
13
):
1721
8
.
34.
Chmiel
R
,
Beyerlein
A
,
Knopff
A
,
Hummel
S
,
Ziegler
AG
,
Winkler
C
.
Early infant feeding and risk of developing islet autoimmunity and type 1 diabetes
.
Acta Diabetol
.
2015
;
52
(
3
):
621
4
.
35.
Norris
JM
,
Barriga
K
,
Klingensmith
G
,
Hoffman
M
,
Eisenbarth
GS
,
Erlich
HA
, et al
.
Timing of initial cereal exposure in infancy and risk of islet autoimmunity
.
JAMA
.
2003
;
290
(
13
):
1713
20
.
36.
Ludvigsson
J
.
Cow-milk-free diet during last trimester of pregnancy does not influence diabetes-related autoantibodies in nondiabetic children
.
Ann N Y Acad Sci
.
2003
;
1005
:
275
8
.
37.
Hummel
S
,
Pfluger
M
,
Hummel
M
,
Bonifacio
E
,
Ziegler
AG
.
Primary dietary intervention study to reduce the risk of islet autoimmunity in children at increased risk for type 1 diabetes: the BABYDIET study
.
Diabetes Care
.
2011
;
34
(
6
):
1301
5
.
38.
Beyerlein
A
,
Chmiel
R
,
Hummel
S
,
Winkler
C
,
Bonifacio
E
,
Ziegler
AG
.
Timing of gluten introduction and islet autoimmunity in young children: updated results from the BABYDIET study
.
Diabetes Care
.
2014
;
37
(
9
):
e194
5
.
39.
Hakola
L
,
Miettinen
ME
,
Syrjala
E
,
Akerlund
M
,
Takkinen
HM
,
Korhonen
TE
, et al
.
Association of cereal, gluten, and dietary fiber intake with islet autoimmunity and type 1 diabetes
.
JAMA Pediatr
.
2019
;
173
(
10
):
953
60
.
40.
Lund-Blix
NA
,
Tapia
G
,
Marild
K
,
Brantsaeter
AL
,
Njølstad
PR
,
Joner
G
, et al
.
Maternal and child gluten intake and association with type 1 diabetes: the Norwegian Mother and Child Cohort Study
.
PLoS Med
.
2020
;
17
(
3
):
e1003032
.
41.
Lund-Blix
NA
,
Dong
F
,
Marild
K
,
Seifert
J
,
Baron
AE
,
Waugh
KC
, et al
.
Gluten intake and risk of islet autoimmunity and progression to type 1 diabetes in children at increased risk of the disease: the diabetes autoimmunity study in the young (DAISY)
.
Diabetes Care
.
2019
;
42
(
5
):
789
96
.
42.
Norris
JM
,
Lee
HS
,
Frederiksen
B
,
Erlund
I
,
Uusitalo
U
,
Yang
J
, et al
.
Plasma 25-hydroxyvitamin D concentration and risk of islet autoimmunity
.
Diabetes
.
2018
;
67
(
1
):
146
54
.
43.
Simpson
M
,
Brady
H
,
Yin
X
,
Seifert
J
,
Barriga
K
,
Hoffman
M
, et al
.
No association of vitamin D intake or 25-hydroxyvitamin D levels in childhood with risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY)
.
Diabetologia
.
2011
;
54
(
11
):
2779
88
.
44.
Makinen
M
,
Mykkanen
J
,
Koskinen
M
,
Simell
V
,
Veijola
R
,
Hyoty
H
, et al
.
Serum 25-hydroxyvitamin D concentrations in children progressing to autoimmunity and clinical type 1 diabetes
.
J Clin Endocrinol Metab
.
2016
;
101
(
2
):
723
9
.
45.
Niinisto
S
,
Takkinen
HM
,
Erlund
I
,
Ahonen
S
,
Toppari
J
,
Ilonen
J
, et al
.
Fatty acid status in infancy is associated with the risk of type 1 diabetes-associated autoimmunity
.
Diabetologia
.
2017
;
60
(
7
):
1223
33
.
46.
Norris
JM
,
Yin
X
,
Lamb
MM
,
Barriga
K
,
Seifert
J
,
Hoffman
M
, et al
.
Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes
.
JAMA
.
2007
;
298
(
12
):
1420
8
.
47.
Virtanen
SM
,
Niinisto
S
,
Nevalainen
J
,
Salminen
I
,
Takkinen
HM
,
Kaaria
S
, et al
.
Serum fatty acids and risk of advanced beta-cell autoimmunity: a nested case-control study among children with HLA-conferred susceptibility to type I diabetes
.
Eur J Clin Nutr
.
2010
;
64
(
8
):
792
9
.
48.
Ziegler
AG
,
Rewers
M
,
Simell
O
,
Simell
T
,
Lempainen
J
,
Steck
A
, et al
.
Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children
.
JAMA
.
2013
;
309
(
23
):
2473
9
.
49.
Pastore
MR
,
Bazzigaluppi
E
,
Belloni
C
,
Arcovio
C
,
Bonifacio
E
,
Bosi
E
.
Six months of gluten-free diet do not influence autoantibody titers, but improve insulin secretion in subjects at high risk for type 1 diabetes
.
J Clin Endocrinol Metab
.
2003
;
88
(
1
):
162
5
.
50.
Fuchtenbusch
M
,
Ziegler
AG
,
Hummel
M
.
Elimination of dietary gluten and development of type 1 diabetes in high risk subjects
.
Rev Diabet Stud
.
2004
;
1
(
1
):
39
41
.
51.
Raab
J
,
Giannopoulou
EZ
,
Schneider
S
,
Warncke
K
,
Krasmann
M
,
Winkler
C
, et al
.
Prevalence of vitamin D deficiency in pre-type 1 diabetes and its association with disease progression
.
Diabetologia
.
2014
;
57
(
5
):
902
8
.
52.
Miller
MR
,
Yin
X
,
Seifert
J
,
Clare-Salzler
M
,
Eisenbarth
GS
,
Rewers
M
, et al
.
Erythrocyte membrane omega-3 fatty acid levels and omega-3 fatty acid intake are not associated with conversion to type 1 diabetes in children with islet autoimmunity: the Diabetes Autoimmunity Study in the Young (DAISY)
.
Pediatr Diabetes
.
2011
;
12
(
8
):
669
75
.
53.
Lamb
MM
,
Frederiksen
B
,
Seifert
JA
,
Kroehl
M
,
Rewers
M
,
Norris
JM
.
Sugar intake is associated with progression from islet autoimmunity to type 1 diabetes: the Diabetes Autoimmunity Study in the Young
.
Diabetologia
.
2015
;
58
(
9
):
2027
34
.
54.
Svensson
J
,
Sildorf
SM
,
Pipper
CB
,
Kyvsgaard
JN
,
Bøjstrup
J
,
Pociot
FM
, et al
.
Potential beneficial effects of a gluten-free diet in newly diagnosed children with type 1 diabetes: a pilot study
.
Springerplus
.
2016
;
5
(
1
):
994
.
55.
Neuman
V
,
Pruhova
S
,
Kulich
M
,
Kolouskova
S
,
Vosahlo
J
,
Romanova
M
, et al
.
Gluten-free diet in children with recent-onset type 1 diabetes: a 12-month intervention trial
.
Diabetes Obes Metab
.
2020
;
22
(
5
):
866
72
.
56.
Soderstrom
H
,
Cervin
M
,
Dereke
J
,
Hillman
M
,
Tiberg
I
,
Norstrom
F
, et al
.
Does a gluten-free diet lead to better glycemic control in children with type 1 diabetes? Results from a feasibility study and recommendations for future trials
.
Contemp Clin Trials Commun
.
2022
;
26
:
100893
.
57.
Gabbay
MA
,
Sato
MN
,
Finazzo
C
,
Duarte
AJ
,
Dib
SA
.
Effect of cholecalciferol as adjunctive therapy with insulin on protective immunologic profile and decline of residual β-cell function in new-onset type 1 diabetes mellitus
.
Arch Pediatr Adolesc Med
.
2012
;
166
(
7
):
601
7
.
58.
Walter
M
,
Kaupper
T
,
Adler
K
,
Foersch
J
,
Bonifacio
E
,
Ziegler
AG
.
No effect of the 1alpha,25-dihydroxyvitamin D3 on beta-cell residual function and insulin requirement in adults with new-onset type 1 diabetes
.
Diabetes Care
.
2010
;
33
(
7
):
1443
8
.
59.
Pitocco
D
,
Crino
A
,
Di Stasio
E
,
Manfrini
S
,
Guglielmi
C
,
Spera
S
, et al
.
The effects of calcitriol and nicotinamide on residual pancreatic beta-cell function in patients with recent-onset Type 1 diabetes (IMDIAB XI)
.
Diabet Med
.
2006
;
23
(
8
):
920
3
.
60.
Bizzarri
C
,
Pitocco
D
,
Napoli
N
,
Di Stasio
E
,
Maggi
D
,
Manfrini
S
, et al
.
No protective effect of calcitriol on beta-cell function in recent-onset type 1 diabetes: the IMDIAB XIII trial
.
Diabetes Care
.
2010
;
33
(
9
):
1962
3
.
61.
Nwosu
BU
,
Parajuli
S
,
Jasmin
G
,
Fleshman
J
,
Sharma
RB
,
Alonso
LC
, et al
.
Ergocalciferol in new-onset type 1 diabetes: a randomized controlled trial
.
J Endocr Soc
.
2022
;
6
(
1
):
bvab179
.
62.
Cadario
F
,
Pozzi
E
,
Rizzollo
S
,
Stracuzzi
M
,
Beux
S
,
Giorgis
A
, et al
.
Vitamin D and omega-3 supplementations in mediterranean diet during the 1st year of overt type 1 diabetes: a cohort study
.
Nutrients
.
2019
;
11
(
9
):
2158
.
63.
Mayer-Davis
EJ
,
Dabelea
D
,
Crandell
JL
,
Crume
T
,
D’Agostino
RB
Jr
,
Dolan
L
, et al
.
Nutritional factors and preservation of C-peptide in youth with recently diagnosed type 1 diabetes: SEARCH Nutrition Ancillary Study
.
Diabetes Care
.
2013
;
36
(
7
):
1842
50
.
64.
Bouillet
B
,
Rouland
A
,
Petit
JM
,
Verges
B
.
A low-carbohydrate high-fat diet initiated promptly after diagnosis provides clinical remission in three patients with type 1 diabetes
.
Diabetes Metab
.
2020
;
46
(
6
):
511
3
.
65.
Thewjitcharoen
Y
,
Wanothayaroj
E
,
Jaita
H
,
Nakasatien
S
,
Butadej
S
,
Khurana
I
, et al
.
Prolonged honeymoon period in a Thai patient with adult-onset type 1 diabetes mellitus
.
Case Rep Endocrinol
.
2021
;
2021
:
3511281
.