The gut microbiota plays a fundamental role in human nutrition and metabolism and may have direct implications for type 2 diabetes and associated preconditions. An improved understanding of relations between human gut microbiota and glucose metabolism could lead to novel opportunities for type 2 diabetes prevention, but human observational studies reporting on such findings have not been extensively reviewed. Here, we review the literature on associations between gut microbiota and markers and stages of glucose dysregulation and insulin resistance in healthy adults and in adults with metabolic disease and risk factors. We present the current evidence for identified key bacteria and their potential roles in glucose metabolism independent of overweight, obesity, and metabolic drugs. We provide support for SCFAs mediating such effects and discuss the role of diet, as well as metabolites derived from diet and gut microbiota interactions. From 5983 initially identified PubMed records, 45 original studies were eligible and reviewed. α Diversity and 45 bacterial taxa were associated with selected outcomes. Six taxa were most frequently associated with glucose metabolism: Akkermansia muciniphila, Bifidobacterium longum, Clostridium leptum group, Faecalibacterium prausnitzii, and Faecalibacterium (inversely associated) and Dorea (directly associated). For Dorea and A. muciniphila, associations were independent of metabolic drugs and body measures. For A. muciniphila and F. prausnitzii, limited evidence supported SCFA mediation of potential effects on glucose metabolism. We conclude that observational studies applying metagenomics sequencing to identify species-level relations are warranted, as are studies accounting for confounding factors and investigating SCFA and postprandial glucose metabolism. Such advances in the field will, together with mechanistic and prospective studies and investigations into diet–gut microbiota interactions, have the potential to bring critical insight into roles of gut microbiota and microbial metabolites in human glucose metabolism and to contribute toward the development of novel prevention strategies for type 2 diabetes, including precision nutrition.

OBJECTIVE To consider the effects of whole-grain processing, specifically milling, on glycemic control in free-living adults with type 2 diabetes. RESEARCH DESIGN AND METHODS Participants of this crossover trial were randomized to two interventions of 2 weeks, separated by washout. They were advised to replace the grain foods they normally consumed with intervention foods. Intervention foods were nutrient-matched whole-grain products of wheat, oats, and brown rice that differed in their degree of processing. No other lifestyle advice was given. Continuous glucose monitoring systems were worn. Other cardiometabolic risk factors and alkylresorcinols (a biomarker of whole-grain intake) were measured pre- and postintervention. RESULTS Thirty-one adults with type 2 diabetes (63 ± 13 years old, BMI 32.4 ± 7 kg/m², HbA_1c 7.5 ± 3.4% [59 ± 14 mmol/mol]) commenced the trial; 28 (90%) completed both interventions. The increase in alkylresorcinols did not differ between interventions, and there was no difference in reported energy intake. Postprandial responses were 9% (95% CI 3–15) lower following breakfast and 6% (1–10) lower following all meals of less-processed whole grains when compared with finely milled grains. Day-long glycemic variability also was reduced when measured by 24-h SD (−0.16 mmol/L [95% CI −0.25 to −0.06]) and mean amplitude of glycemic excursion (−0.36 [95% CI −0.65 to −0.08]). Mean change in body weight differed by 0.81 kg (95% CI 0.62–1.05) between interventions, increasing during the finely milled intervention and decreasing during the less-processed whole-grain intervention. This was not a mediating factor for the glycemic variables considered. CONCLUSIONS Consuming less-processed whole-grain foods over 2 weeks improved measures of glycemia in free-living adults with type 2 diabetes compared with an equivalent amount of whole-grain foods that were finely milled. Dietary advice should promote the consumption of minimally processed whole grains.

Background: Accurate assessment of self-reported appetite under free-living conditions is warranted to conduct large-scale intervention studies measuring appetite at a feasible cost. However, the performance of visual analogue scales (VASs) for this purpose has not been widely examined. Method: This randomized crossover trial was conducted to evaluate VASs in free-living vs. clinic-based settings and to assess appetite response following hypocaloric whole-grain rye and refined wheat diets. Twenty-nine healthy adults with overweight or obesity continuously answered VAS questions about their perceived appetite from morning to evening. Results: No differences in whole-day VAS scores (primary outcome) between clinic-based and free-living settings were observed, whereas measures of total area under the curve (tAUC) showed increased fullness in clinic-based interventions of 7% (p < 0.008) for whole-day responses and 13% (p < 0.03) following a snack. Appetite responses for a whole day did not differ between diets whereas rye-based dinners induced 12% (p < 0.016) higher fullness and reduced hunger by 17% (p < 0.02) irrespective of setting. A reduction in hunger of 15% (p < 0.05) was also observed following rye-based vs. wheat-based lunches. Conclusion: The results suggest that the VAS is valid for evaluation of appetite responses between diets under free-living conditions. No difference in self-reported appetite over the whole day was found after whole-grain rye vs. refined wheat-based diets, but there were some suggested differences at certain postprandial periods, in individuals with overweight or obesity.

High intake of whole grains has consistently been associated with reduced risk of obesity, coronary artery disease, and type 2 diabetes. Dietary interventions have shown beneficial metabolic effects of whole grains, but the metabolic response varies with different types of cereals. We evaluate the metabolic effects of substituting refined wheat with wholegrain rye foods within a complex diet, examining the day-long postprandial response of glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), ghrelin, glucose, and inflammatory biomarkers in individuals with overweight and obesity. Twenty-nine healthy adults with body mass index of 32 ± 9 kg/m² were randomly assigned to 3 intervention days, separated by 1-wk washout. Participants adhered to a hypocaloric diet rich in wholegrain rye for 1 intervention and refined wheat for the second intervention and were randomly assigned to either diet for the third intervention with continuous blood sampling. No differences in GIP, GLP-1, or ghrelin levels were found between the diets when measured throughout the whole intervention day. GIP total area under the curve after the rye-based lunch was 31% (P < 0.05) lower compared with the wheat-based lunch, and ghrelin concentrations were 29% (P < 0.05) lower after the rye-based dinner. Baseline Homeostatic Model Assessment for Insulin Resistance-adjusted model showed 61% (P = 0.015) lower whole-day GLP-1 and 40% (P = 0.03) lower GIP after the rye-based diet. Day-long glucose incremental area under the curve was 30% (P < 0.001) lower after the rye-based diet, and glycemic variability was measured as SD reduced (-0.13 mmol/L, P = 0.04). The rye-based diet compared with refined wheat induced higher glycoprotein N-acetylation A, as measured by z-scores (0.36, P = 0.014). Overall, no day-long differences in gut hormone levels were observed, but the wholegrain rye-based compared with refined wheat-based dinner showed lower postprandial ghrelin concentrations. The rye-based diet improved day-long glycemic control in individuals with overweight and obesity. Observations of diet-induced inflammation after whole-grain rye intake warrant further investigation. This study was registered at Clinical Trials Registry of clinicaltrials.gov (NCT05004584): https://clinicaltrials.gov/study/NCT05004584?locStr=Gothenburg,%20Sweden&country=Sweden&state=V%C3%A4stra%20G%C3%B6taland%20County&city=Gothenburg&distance=50&term=appetite&aggFilters=status:com&rank=1.

Aims: Recent observational data indicate higher ultra-processed food intakes are associated with a broad range of adverse health outcomes. Experimental studies on why this might be are lacking. We have considered the effects of wholegrain processing on measures of appetite in free-living adults with type 2 diabetes. Materials and methods: Participants were randomised to two interventions of two-weeks duration, separated by washout. Interventions were nutrient-matched wholegrain foods that differed by the amount of processing. Self-reported hunger and satiety were indicated on visual analogue scales before or after meals for four days at baseline and the end of each intervention. Metabolite markers of appetite were measured pre and post intervention in fasting plasma. Results: 31 adults (63 ± 13 years old, BMI 32.4 ± 7, HbA1c 7.5 ± 3.4% (59 ± 14 mmol mol⁻¹)) commenced the trial, 28 (90%) completed both interventions. Wholegrain consumption, as measured by alkylresorcinols, was balanced between interventions. Self-reported pre-meal hunger was consistently lower at breakfast (MD, mean difference 0.49/10 95% CI 0.03 to 0.94), lunch (MD 0.67/10 95% CI 0.09 to 1.25), and dinner (MD −0.71/10 95% CI 0.19 to 1.23) during the intervention of less processed whole grains when compared with pre-intervention measures, however this did not result in a difference between interventions. Change in metabolite markers of appetite did not differ between interventions. Conclusions: A significant difference in hunger or satiety between less and more processed whole grains over intervention periods of two weeks was not detected within the current trial. Further experimental studies are needed to consider the potential effects of food processing on physiological processes such as appetite to provide mechanistic understanding behind observations of highly processed food intakes and adverse health outcomes.

Background/Objectives Maternal obesity and gestational diabetes mellitus (GDM) are increasingly common metabolic conditions during pregnancy, potentially affecting offspring metabolic development and adiposity across childhood. We investigated longitudinal adiposity and anthropometric development in preschool children born to women with normal weight, obesity, or GDM, and explored associations between maternal metabolic markers during pregnancy and offspring adiposity outcomes. Subjects/Methods The Pregnancy Obesity Nutrition Child Health (PONCH) cohort is a longitudinal mother–child study including offspring of women with normal weight (NW), obesity (OB), or GDM during pregnancy. Repeated anthropometric measurements and body composition assessments by air-displacement plethysmography were obtained annually between ages 2 and 6 years in 178 children (NW, n = 80; OB, n = 57; GDM, n = 41). Longitudinal differences between maternal groups were evaluated using mixed-effects models. Results Children in the OB group exhibited higher adiposity throughout preschool age compared with the NW group, including BMI (16.9 vs 16.2kg/m², p < 0.001), body fat percentage (28.0% vs 24.9%, p < 0.001), and fat mass (5.22 vs 4.35kg, p < 0.001). Differences became more pronounced with age and were generally greater in boys, whereas adiposity profiles remained similar between the GDM and NW groups. Maternal adiposity-related markers showed progressively stronger associations with offspring adiposity across childhood, including fat mass in 6-year-old boys (r = 0.60, p < 0.001) and girls (r = 0.40, p = 0.04). Maternal glycaemic markers showed limited associations, primarily observed at 2 years of age in girls, whereas associations at later ages were sparse and inconsistent. Conclusions Offspring of women with obesity exhibited progressively greater adiposity throughout preschool age compared with offspring of women with normal weight and GDM. These findings suggest that maternal obesity may represent a more sustained determinant of offspring adiposity development during early childhood and support early preventive strategies. Continued longitudinal follow-up will be important to determine whether these differences persist into later childhood and adolescence.