Vitamins C, E, and ß-Carotene and Risk of Type 2 Diabetes: A Systematic Review and Meta-Analysis.

A systematic review and meta-analysis was conducted to assess the relationship between the common dietary antioxidants vitamin C, vitamin E, and ß-carotene and type 2 diabetes (T2D) and related traits. MEDLINE, Embase, and the Cochrane Library were searched for relevant publications up until May 2023. Studies were eligible if they had a cohort, case-control, or randomized controlled trial (RCT) design and examined dietary intake, supplementation, or circulating levels of these antioxidants as exposure, and insulin resistance, ß-cell function, or T2D incidence as outcomes. Summary relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) were estimated using random-effects models. The certainty of the evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluations framework. Among 6190 screened records, 25 prospective observational studies and 15 RCTs were eligible. Inverse associations were found between dietary and circulating antioxidants and T2D (observational studies). The lowest risk was seen at intakes of 70 mg/d of vitamin C (RR: 0.76; CI: 0.61, 0.95), 12 mg/d of vitamin E (RR: 0.72; CI: 0.61, 0.86), and 4 mg/d of ß-carotene (RR: 0.78; CI: 0.65, 0.94). Supplementation with vitamin E (RR: 1.01; CI: 0.93, 1.10) or ß-carotene (RR: 0.98; CI: 0.90, 1.07) did not have a protective effect on T2D (RCTs), and data on vitamin C supplementation was limited. Regarding insulin resistance, higher dietary vitamin C (RR: 0.85; CI: 0.74, 0.98) and vitamin E supplementation (MD: -0.35; CI: -0.65, -0.06) were associated with a reduced risk. The certainty of evidence was high for the associations between T2D and dietary vitamin E and ß-carotene, and low to moderate for other associations. In conclusion, moderate intakes of vitamins C, E, and ß-carotene may lower risk of T2D by reducing insulin resistance. Lack of protection with supplementation in RCTs suggests that adequate rather than high intakes may play a role in T2D prevention. This systematic review and meta-analysis was registered in PROSPERO with registration number CRD42022343482.

Antioxidant Nutrients and Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes: A Swedish Case-Control Study and Mendelian Randomization Analysis.

Antioxidant vitamins C and E are inversely associated with type 1 diabetes (T1D). We investigated if antioxidants are also associated with latent autoimmune diabetes in adults (LADA), with low (LADAlow) and high (LADAhigh) autoantibody levels, type 2 diabetes (T2D), and estimates of beta cell function (HOMA-B) and insulin resistance (HOMA-IR). We used Swedish case-control data with incident cases of LADA (n = 584) and T2D (n = 1989) and matched population-based controls (n = 2276). Odds ratios (OR) and 95% confidence intervals (CI) were calculated per one standard deviation higher beta-carotene, vitamin C, vitamin E, selenium, and zinc intakes. Two-sample Mendelian randomization (MR) analyses assessed causality between genetically predicted circulating antioxidants and LADA, T1D, and T2D, using summary statistics from genome-wide association studies. Among the antioxidants, vitamins C and E were inversely associated with LADAhigh (OR 0.84, CI 0.73, 0.98 and OR 0.80, CI 0.69, 0.94 respectively), but not with LADAlow or T2D. Vitamin E was also associated with higher HOMA-B and lower HOMA-IR. MR analyses estimated an OR of 0.50 (CI 0.20, 1.25) for the effect of vitamin E on T1D, but did not support causal relationships between antioxidants and either LADA or T2D. In conclusion, vitamin E may have a protective effect on autoimmune diabetes, possibly through preserved beta cell function and less insulin resistance.

Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes: the EPIC-InterAct case-cohort study.

AIMS/HYPOTHESIS: Islet autoimmunity may progress to adult-onset diabetes. We investigated whether circulating odd-chain fatty acids (OCFA) 15:0 and 17:0, which are inversely associated with type 2 diabetes, interact with autoantibodies against GAD65 (GAD65Ab) on the incidence of adult-onset diabetes. METHODS: We used the European EPIC-InterAct case-cohort study including 11,124 incident adult-onset diabetes cases and a subcohort of 14,866 randomly selected individuals. Adjusted Prentice-weighted Cox regression estimated HRs and 95% CIs of diabetes in relation to 1 SD lower plasma phospholipid 15:0 and/or 17:0 concentrations or their main contributor, dairy intake, among GAD65Ab-negative and -positive individuals. Interactions between tertiles of OCFA and GAD65Ab status were estimated by proportion attributable to interaction (AP). RESULTS: Low concentrations of OCFA, particularly 17:0, were associated with a higher incidence of adult-onset diabetes in both GAD65Ab-negative (HR 1.55 [95% CI 1.48, 1.64]) and GAD65Ab-positive (HR 1.69 [95% CI 1.34, 2.13]) individuals. The combination of low 17:0 and high GAD65Ab positivity vs high 17:0 and GAD65Ab negativity conferred an HR of 7.51 (95% CI 4.83, 11.69), with evidence of additive interaction (AP 0.25 [95% CI 0.05, 0.45]). Low dairy intake was not associated with diabetes incidence in either GAD65Ab-negative (HR 0.98 [95% CI 0.94, 1.02]) or GAD65Ab-positive individuals (HR 0.97 [95% CI 0.79, 1.18]). CONCLUSIONS/INTERPRETATION: Low plasma phospholipid 17:0 concentrations may promote the progression from GAD65Ab positivity to adult-onset diabetes.

Parental smoking, type 1 diabetes, and islet autoantibody positivity in the offspring: A systematic review and meta-analysis.

AIMS: Our aim was to synthesize current evidence on the association between parental smoking and incidence of type 1 diabetes and islet autoantibody positivity (IA) in the offspring by conducting a systematic review and meta-analysis. METHODS: We searched Medline, Embase, and Cochrane Library until January 21, 2021, for human studies with parental tobacco use as exposure, type 1 diabetes or IA as outcome, and hazard, risk, or odds ratios as effect estimates. Summary relative risks (RR) and 95% confidence intervals (CI) were estimated with random-effects models. Heterogeneity was quantified with the I2  statistic, bias with the ROBINS-I tool, and the certainty of evidence with the GRADE tool. RESULTS: We identified 535 records of which 23 were eligible including 25 927 cases of type 1 diabetes. Maternal smoking during pregnancy was associated with a reduced risk of type 1 diabetes (n = 22, RR 0.78, CI 0.71-0.86, I2 =69%). Including only studies with low to moderate risk of bias indicated similar results with less heterogeneity (n = 14, RR 0.73, CI 0.68-0.79, I2  = 44%). The certainty of evidence was graded as high. There was no clear association between type 1 diabetes and neither maternal (n = 6, RR 0.95, CI 0.78-1.14, I2  = 0%) nor paternal (n = 6, RR 0.90, 0.70-1.17, I2  = 68%) smoking during childhood. Furthermore, the association between maternal smoking during pregnancy and IA was weak (n = 4, RR 0.86, CI 0.44-1.65, I2  = 71%). CONCLUSIONS: Maternal smoking during pregnancy may reduce the risk of type 1 diabetes in the offspring. Further studies are needed to elucidate potential mechanisms underlying this association. REGISTRATION: Prospero CRD42021236717.

Dietary factors and risk of islet autoimmunity and type 1 diabetes: a systematic review and meta-analysis.

BACKGROUND: Numerous dietary components have been linked to the development of islet autoimmunity (IA) and type 1 diabetes (T1D); however, no associations are firmly established. This systematic review and meta-analysis aimed to synthesize current knowledge on diet and incidence of IA and T1D. METHODS: Literature search was performed in Medline, Embase, and Cochrane Library, from inception until October 2020. Eligible studies had IA or T1D as outcome; any dietary exposure; case-control, cohort, or randomized controlled trial design; and hazard, risk, or odds ratios as measures of association. Summary relative risks (RR) and 95% confidence intervals (CI) were estimated with random-effects models. Certainty of evidence was assessed with GRADE. PROSPERO registration number: CRD42020212505. FINDINGS: Among 5935 identified records, 96 were eligible, and pooled estimates could be produced for 26 dietary factors. Evidence with moderate/high certainty indicated lower risk of T1D in relation to longer (≥6-12 vs <6-12 months, RR: 0⋅39, CI: 0⋅26-0⋅58, I2=43%) and exclusive (≥2-3 vs <2-3 months, RR: 0⋅68, CI: 0⋅58-0⋅80, I2=0%) breastfeeding, later introduction to gluten (3-6 vs <3-5 months, RR: 0⋅36, CI: 0⋅17-0⋅75, I2=0%), cow's milk (≥2-3 vs <2-3 months, RR: 0⋅69, CI: 0⋅59-0⋅81, I2=0%), and fruit (4-6 vs <4-5 months, RR: 0⋅47, CI: 0⋅25-0⋅86, I2=0%). Higher childhood intake of cow's milk was associated with increased risk of both IA (per 2-3 portions/day, RR: 1⋅25, CI: 1⋅06-1⋅47, I2=0%) and T1D (≥2-3 vs <2-3 glasses/day, RR: 1⋅81, CI: 1⋅12-2⋅91, I2=31%). For the remaining dietary factors investigated, there was no association, or the evidence was of low certainty. INTERPRETATION: This study suggests that breastfeeding and late introduction of gluten, fruit, and cow's milk may reduce the risk of T1D, whereas high childhood cow's milk intake may increase it. FUNDING: Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare (FORTE), Novo Nordisk Foundation, and Swedish Diabetes Foundation.

Latent class growth modelling for the evaluation of intervention outcomes: example from a physical activity intervention.

Intervention studies often assume that changes in an outcome are homogenous across the population, however this assumption might not always hold. This article describes how latent class growth modelling (LCGM) can be performed in intervention studies, using an empirical example, and discusses the challenges and potential implications of this method. The analysis included 110 young adults with mobility disability that had participated in a parallel randomized controlled trial and received either a mobile app program (n = 55) or a supervised health program (n = 55) for 12 weeks. The primary outcome was accelerometer measured moderate to vigorous physical activity (MVPA) levels in min/day assessed at baseline, 6 weeks, 12 weeks, and 1-year post intervention. The mean change of MVPA from baseline to 1-year was estimated using paired t-test. LCGM was performed to determine the trajectories of MVPA. Logistic regression models were used to identify potential predictors of trajectories. There was no significant difference between baseline and 1-year MVPA levels (4.8 min/day, 95% CI: -1.4, 10.9). Four MVPA trajectories, 'Normal/Decrease', 'Normal/Increase', 'Normal/Rapid increase', and 'High/Increase', were identified through LCGM. Individuals with younger age and higher baseline MVPA were more likely to have increasing trajectories of MVPA. LCGM uncovered hidden trajectories of physical activity that were not represented by the average pattern. This approach could provide significant insights when included in intervention studies. For higher accuracy it is recommended to include larger sample sizes.

Association of changes in cardiorespiratory fitness with health-related quality of life in young adults with mobility disability: secondary analysis of a randomized controlled trial of mobile app versus supervised training.

BACKGROUND: Young adults with mobility disability report lower health-related quality of life (HRQoL) than their able-bodied peers. This study aims to examine potential differences between the effects of mobile app versus supervised training and the association of cardiorespiratory fitness change with HRQoL in young adults with mobility disability. METHODS: This is a secondary analysis of a parallel randomized controlled trial of a mobile app (n = 55) and a supervised health program (n = 55) that was provided for 12 weeks to 110 adults (18-45 years) with self-perceived mobility disability. Recruitment took place at rehabilitation centers in Stockholm, Sweden. Cardiorespiratory fitness was estimated from the results of a submaximal cycle ergometer test and HRQoL was assessed with the SF-36 questionnaire. Follow up was at 6 weeks, 12 weeks, and 1-year and all examinations were performed by blinded investigators. Between group differences of changes in HRQoL at follow up were estimated in intention-to-treat analysis using linear regression models. Crude and adjusted mixed-effects models estimated the associations between cardiorespiratory fitness change and HRQoL. Stratified analysis by intervention group was also performed. RESULTS: In total, 40/55 from the mobile app group and 49/55 from the supervised training group were included in the intention to treat analysis. No significant differences were observed between the effects of the two interventions on HRQoL. In both crude and adjusted models, cardiorespiratory fitness change was associated with the general health (adjusted ß = 1.30, 95% CI: 0.48, 2.13) and emotional role functioning (adjusted ß = 1.18, 95% CI: 0.11, 2.25) domains of SF-36. After stratification, the associations with general health (adjusted ß = 1.88, 95% CI: 0.87, 2.90) and emotional role functioning (adjusted ß = 1.37, 95% CI: 0.18, 2.57) were present only in the supervised group. CONCLUSION: This study found positive associations between cardiorespiratory fitness change and HRQoL in young adults with mobility disability who received supervised training. The effects of mobile app versus supervised training on HRQoL remain unclear. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) registry ISRCTN22387524 ; Prospectively registered on February 4th, 2018.

Food groups and risk of type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies.

The aim of this systematic review and meta-analysis was to synthesize the knowledge about the relation between intake of 12 major food groups and risk of type 2 diabetes (T2D). We conducted a systematic search in PubMed, Embase, Medline (Ovid), Cochrane Central, and Google Scholar for prospective studies investigating the association between whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages (SSB) on risk of T2D. Summary relative risks were estimated using a random effects model by contrasting categories, and for linear and non-linear dose-response relationships. Six out of the 12 food-groups showed a significant relation with risk of T2D, three of them a decrease of risk with increasing consumption (whole grains, fruits, and dairy), and three an increase of risk with increasing consumption (red meat, processed meat, and SSB) in the linear dose-response meta-analysis. There was evidence of a non-linear relationship between fruits, vegetables, processed meat, whole grains, and SSB and T2D risk. Optimal consumption of risk-decreasing foods resulted in a 42% reduction, and consumption of risk-increasing foods was associated with a threefold T2D risk, compared to non-consumption. The meta-evidence was graded "low" for legumes and nuts; "moderate" for refined grains, vegetables, fruit, eggs, dairy, and fish; and "high" for processed meat, red meat, whole grains, and SSB. Among the investigated food groups, selecting specific optimal intakes can lead to a considerable change in risk of T2D.

Food groups and risk of all-cause mortality: a systematic review and meta-analysis of prospective studies.

Background: Suboptimal diet is one of the most important factors in preventing early death and disability worldwide.Objective: The aim of this meta-analysis was to synthesize the knowledge about the relation between intake of 12 major food groups, including whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages, with risk of all-cause mortality.Design: We conducted a systematic search in PubMed, Embase, and Google Scholar for prospective studies investigating the association between these 12 food groups and risk of all-cause mortality. Summary RRs and 95% CIs were estimated with the use of a random effects model for high-intake compared with low-intake categories, as well as for linear and nonlinear relations. Moreover, the risk reduction potential of foods was calculated by multiplying the RR by optimal intake values (serving category with the strongest association) for risk-reducing foods or risk-increasing foods, respectively.Results: With increasing intake (for each daily serving) of whole grains (RR: 0.92; 95% CI: 0.89, 0.95), vegetables (RR: 0.96; 95% CI: 0.95, 0.98), fruits (RR: 0.94; 95% CI: 0.92, 0.97), nuts (RR: 0.76; 95% CI: 0.69, 0.84), and fish (RR: 0.93; 95% CI: 0.88, 0.98), the risk of all-cause mortality decreased; higher intake of red meat (RR: 1.10; 95% CI: 1.04, 1.18) and processed meat (RR: 1.23; 95% CI: 1.12, 1.36) was associated with an increased risk of all-cause mortality in a linear dose-response meta-analysis. A clear indication of nonlinearity was seen for the relations between vegetables, fruits, nuts, and dairy and all-cause mortality. Optimal consumption of risk-decreasing foods results in a 56% reduction of all-cause mortality, whereas consumption of risk-increasing foods is associated with a 2-fold increased risk of all-cause mortality.Conclusion: Selecting specific optimal intakes of the investigated food groups can lead to a considerable change in the risk of premature death.