Type 2 diabetes is a common complex metabolic disorder. Currently, more than 380 million people live with type 2 diabetes globally, and this number is expected to increase to more than 550 million by 2030.¹ Recently, studies^2-5 have indicated a role of gut microbiome in type 2 diabetes. Differences in gut microbiome composition with type 2 diabetes status may comprise pathways on how dietary and other environmental factors affect development of insulin resistance and type 2 diabetes. Several studies^2-4 have indicated that, compared with healthy participants, patients with type 2 diabetes have a lower overall α diversity of gut microbiome composition. More specifically, lower abundance of certain butyrate-producing bacteria, such as class Clostridia and genus Faecalibacterium, have been observed in patients with type 2 diabetes.^2-5 For example, Larsen et al³ reported a lower abundance of Clostridia in patients with type 2 diabetes, and Qin et al⁵ observed that patients with type 2 diabetes had lower abundance of Faecalibacterium. In addition, some nonbutyrate bacteria, such as Haemophilus parainfluenzae, have also been reported to be associated with type 2 diabetes.⁵ However, these associations were not very strong, and most of these specific bacteria have not been reproduced in other cohorts.⁶ Furthermore, these previous studies^2-6 had several limitations. They were limited in sample sizes, ranging from 20³ to 784² participants. Larger samples with more statistical power may be required to detect true associations. Moreover, in most of these previous observational studies,^2-5 key confounders, such as lifestyle and socioeconomic status, that are known to be determinants of gut microbiome and type 2 diabetes⁷ were not controlled for. Finally, because almost all these previous studies^2-5 were conducted in patient populations or case-control settings, it is unclear whether associations are also relevant on a population level and whether type 2 diabetes–associated bacteria are associated to key subclinical parameters, such as insulin resistance and fasting glucose, among groups without diabetes. Examining associations for gut microbiome and such subclinical parameters will help investigators infer potential pathways behind gut microbiome and type 2 diabetes risk. Acquiring and updating this knowledge are particularly relevant, considering the increasing recognition that gut microbiome may play an important role in the development of type 2 diabetes and could be a promising target for prevention and treatment of type 2 diabetes. Therefore, we aimed to investigate the associations between gut microbiome composition with insulin resistance and type 2 diabetes in 2 large population-based cohorts, using a microbiome-wide approach and taking into account various sociodemographic and lifestyle factors.

OBJECTIVE: We examined the relationship between ultra-processed food (UPF) intake and type 2 diabetes (T2D) risk among 3 large U.S. cohorts, conducted a meta-analysis of prospective cohort studies, and assessed meta-evidence quality. RESEARCH DESIGN AND METHODS: We included 71,871 women from the Nurses’ Health Study, 87,918 women from the Nurses’ Health Study II, and 38,847 men from the Health Professional Follow-Up Study. Diet was assessed using food frequency questionnaires and UPF was categorized per the NOVA classification. Associations of total and subgroups of UPF with T2D were assessed using Cox proportional hazards models. We subsequently conducted a meta-analysis of prospective cohort studies on total UPF and T2D risk, and assessed meta-evidence quality using the NutriGrade scoring system. RESULTS: Among the U.S. cohorts (5,187,678 person-years; n = 19,503 T2D cases), the hazard ratio for T2D comparing extreme quintiles of total UPF intake (percentage of grams per day) was 1.46 (95% CI 1.39–1.54). Among subgroups, refined breads; sauces, spreads, and condiments; artificially and sugar-sweetened beverages; animal-based products; and ready-to-eat mixed dishes were associated with higher T2D risk. Cereals; dark and whole-grain breads; packaged sweet and savory snacks; fruit-based products; and yogurt and dairy-based desserts were associated with lower T2D risk. In the meta-analysis (n = 415,554 participants; n = 21,932 T2D cases), each 10% increment in total UPF was associated with a 12% (95% CI 10%–13%) higher risk. Per NutriGrade, high-quality evidence supports this relationship. CONCLUSIONS: High-quality meta-evidence shows that total UPF consumption is associated with higher T2D risk. However, some UPF subgroups were associated with lower risk in the U.S. cohorts.

Evidence for associations between long-term protein intake with mortality is not consistent. We aimed to examine associations of dietary protein from different sources with all-cause and cause-specific mortality. We followed 7786 participants from three sub-cohorts of the Rotterdam Study, a population-based cohort in the Netherlands. Dietary data were collected using food-frequency questionnaires at baseline (1989–1993, 2000–2001, 2006–2008). Deaths were followed until 2018. Associations were examined using Cox regression. Additionally, we performed a highest versus lowest meta-analysis and a dose–response meta-analysis to summarize results from the Rotterdam Study and previous prospective cohorts. During a median follow-up of 13.0 years, 3589 deaths were documented in the Rotterdam Study. In this cohort, after multivariable adjustment, higher total protein intake was associated with higher all-cause mortality [e.g. highest versus lowest quartile of total protein intake as percentage of energy (Q4 versus Q1), HR = 1.12 (1.01, 1.25)]; mainly explained by higher animal protein intake and CVD mortality [Q4 versus Q1, CVD mortality: 1.28 (1.03, 1.60)]. The association of animal protein intake and CVD was mainly contributed to by protein from meat and dairy. Total plant protein intake was not associated with all-cause or cause-specific mortality, mainly explained by null associations for protein from grains and potatoes; but higher intake of protein from legumes, nuts, vegetables, and fruits was associated with lower risk of all-cause and cause-specific mortality. Findings for total and animal protein intake were corroborated in a meta-analysis of eleven prospective cohort studies including the Rotterdam Study (total 64,306 deaths among 350,452 participants): higher total protein intake was associated with higher all-cause mortality [pooled RR for highest versus lowest quantile 1.05 (1.01, 1.10)]; and for dose–response per 5 energy percent (E%) increment, 1.02 (1.004, 1.04); again mainly driven by an association between animal protein and CVD mortality [highest versus lowest, 1.09 (1.01, 1.18); per 5 E% increment, 1.05 (1.02, 1.09)]. Furthermore, in the meta-analysis a higher plant protein intake was associated with lower all-cause and CVD mortality [e.g. for all-cause mortality, highest versus lowest, 0.93 (0.87, 0.99); per 5 E% increment, 0.87 (0.78, 0.98), for CVD mortality, highest versus lowest 0.86 (0.73, 1.00)]. Evidence from prospective cohort studies to date suggests that total protein intake is positively associated with all-cause mortality, mainly driven by a harmful association of animal protein with CVD mortality. Plant protein intake is inversely associated with all-cause and CVD mortality. Our findings support current dietary recommendations to increase intake of plant protein in place of animal protein.Clinical trial registry number and website NTR6831, https://www.trialregister.nl/trial/6645

OBJECTIVE: We evaluated the associations between changes in plant-based diets and subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We prospectively followed 76,530 women in the Nurses’ Health Study (NHS) (1986–2012), 81,569 women in NHS II (1991–2017), and 34,468 men in the Health Professionals Follow-up Study (1986–2016). Adherence to plant-based diets was assessed every 4 years with the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs). We pooled results of the three cohorts using meta-analysis. RESULTS: We documented 12,627 cases of type 2 diabetes during 2,955,350 person-years of follow-up. After adjustment for initial BMI and initial and 4-year changes in alcohol intake, smoking, physical activity, and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest decrease (>10%) in PDI and hPDI over 4 years had a 12–23% higher diabetes risk in the subsequent 4 years (pooled HR, PDI 1.12 [95% CI 1.05, 1.20], hPDI 1.23 [1.16, 1.31]). Each 10% increment in PDI and hPDI over 4 years was associated with a 7–9% lower risk (PDI 0.93 [0.91, 0.95], hPDI 0.91 [0.87, 0.95]). Changes in uPDI were not associated with diabetes risk. Weight changes accounted for 6.0–35.6% of the associations between changes in PDI and hPDI and diabetes risk. CONCLUSIONS: Improving adherence to overall and healthful plant-based diets was associated with a lower risk of type 2 diabetes, whereas decreased adherence to such diets was associated with a higher risk.

Background: Artificially sweetened beverages (ASB) are consumed globally, but their impact on overall health remains uncertain. We summarized published associations between ASB intake with all-cause and cause-specific mortality. Methods: We searched Medline, Embase, Web of Science, and Cochrane CENTRAL databases until August 2023. Random effect meta-analysis was conducted to calculate pooled risk ratios (RRs) and 95% confidence intervals (95%CIs) for highest versus lowest categories of ASB consumption in relation to all-cause and cause-specific mortality. Linear and non-linear dose-response analyses were also performed. Results: Our systematic review and meta-analysis included 11 prospective cohort studies. During a median/mean follow-up period of 7.0 to 28.9 years, 235,609 deaths occurred among 2,196,503 participants. Intake of ASB was associated with higher risk of all-cause and CVD mortality with pooled RRs (95%CIs) of highest vs. lowest intake categories of 1.13 (1.06, 1.21) (I² = 66.3%) for all-cause mortality and 1.26 (1.10, 1.44) (I² = 52.0%) for CVD mortality. Dose-response analysis revealed a non-linear association of ASB with all-cause mortality (p_{non−linearity} = 0.01), but a linear positive association with CVD mortality (p_{non−linearity} = 0.54). No significant association was observed for ASB intake and cancer mortality. Moreover, a secondary meta-analysis demonstrated that replacing 1 serving/day of sugary sweetened beverages (SSB) with ASB was associated with 4–6% lower risk of all-cause and CVD mortality. Per NutriGrade, the evidence quality for associations between ASB intake with all-cause and CVD mortality was moderate. Conclusions: Higher intake of ASB was associated with higher risk of all-cause and CVD mortality, albeit a lower risk than for SSB. Systematic review registration: PROSPERO registration no. CRD42022365701.