Search Results (184)

Diabetes mellitus remains a major global health burden, and many patients do not achieve durable glycemic control despite modern pharmacotherapy. This narrative review synthesizes evidence on plant-derived strategies that may complement standard care, focusing on two clinically aligned domains: glucose-lowering medicinal plants and plant-based sugar substitutes that reduce dietary glycemic load. We summarize key mechanistic pathways, including inhibition of α-amylase/α-glucosidase, reduced intestinal glucose entry and absorption kinetics, glucose-dependent insulinotropic effects, improved insulin signaling, suppression of hepatic gluconeogenesis, and microbiota-linked effects. We critically appraise human evidence for selected botanicals (cinnamon, fenugreek, mulberry, gymnema, gynura, rosehip, and Jerusalem artichoke) and plant sweeteners (stevia and monk fruit). Overall, clinical effects are modest and heterogeneous; the most reproducible signals are observed for mulberry leaf in blunting postprandial glucose excursions, and for cinnamon, fenugreek, and gymnema, where meta-analyses suggest modest improvements in glycemic markers. Stevia and monk fruit are best supported as glycemically neutral sucrose substitutes, while inulin-type fructans show small-to-moderate benefits with sustained intake, limited by gastrointestinal tolerability at higher doses. Key gaps include a shortage of long-term randomized trials using standardized preparations and durable endpoints such as glycated hemoglobin. Plant-derived interventions are therefore best positioned as adjuncts within individualized, evidence-based glycemic management. Full article

Orforglipron (LY3502970) is a novel, orally available, nonpeptide glucagon-like peptide-1 receptor agonist (GLP-1 RA) designed to replicate the efficacy of injectable GLP-1 RAs for glycemic control and weight reduction while improving convenience and adherence. Preclinical studies have demonstrated potent receptor engagement, favorable pharmacokinetics, and central nervous system activity. Phase 1–3 clinical trials have shown significant reductions in glycated hemoglobin (HbA1c), fasting and postprandial glucose, body weight, and cardiovascular risk biomarkers, with an acceptable safety profile. This comprehensive review integrates pharmacological, clinical, and mechanistic evidence, critically evaluates the data, identifies knowledge gaps, and outlines future directions for orforglipron in the treatment of type 2 diabetes and obesity. Full article

This study investigated the generation of α-glucosidase inhibitory peptides from whey protein fermented by the marine-derived probiotic Lacticaseibacillus casei DS31 (isolated from the intestinal microbiota of the large yellow croaker, Larimichthys crocea) and assessed their potential for practical glycemic management. Fermentation markedly increased inhibitory activity, with the freeze-dried crude supernatant exhibiting an IC50 of 2.115 mg/mL. Activity was further enriched through stepwise purification: ultrafiltration (<3 kDa) improved potency (IC50 = 1.206 mg/mL), and subsequent Sephadex (crosslinked dextran) G-15 gel filtration yielded a more active E fraction (IC50 = 1.145 mg/mL). LC–MS/MS characterized 19 peptides, and integrated in silico screening (PeptideRanker combined with molecular docking) highlighted GEPGPEGPAG as a leading candidate, showing a more favorable predicted binding energy (−82.50 kcal/mol) than the positive control acarbose (−69.31 kcal/mol). Docking analysis suggests that GEPGPEGPAG may inhibit α-glucosidase by forming a stable network of hydrogen bonds, salt bridges, and hydrophobic interactions within the catalytic pocket. Overall, DS31-fermented whey and its enriched fractions show promise as functional ingredients for postprandial glycemic control. Full article

Plant-based fermented foods are increasingly promoted for glycemic control, yet their mechanisms and clinical impact remain incompletely defined. This narrative review synthesizes mechanistic, preclinical, and human data for key matrices—kimchi and other fermented vegetables, tempeh/miso/natto, and related legume ferments, kombucha and fermented teas, plant-based kefir, and cereal/pulse sourdoughs. Across these systems, microbial β-glucosidases, esterases, tannases, and phenolic-acid decarboxylases remodel polyphenols toward more bioaccessible aglycones and phenolic acids, while lactic and acetic fermentations generate organic acids, exopolysaccharides, bacterial cellulose, γ-polyglutamic acid, γ-aminobutyric acid, and bioactive peptides. We map these postbiotic signatures onto proximal mechanisms—α-amylase/α-glucosidase inhibition, viscosity-driven slowing of starch digestion, gastric emptying and incretin signaling, intestinal-barrier reinforcement, and microbiota-dependent short-chain–fatty-acid and bile-acid pathways—and their downstream effects on AMPK/Nrf2 signaling and the gut–liver axis. Animal models consistently show improved glucose tolerance, insulin sensitivity, and hepatic steatosis under fermented vs. non-fermented diets. In humans, however, glycemic effects are modest and highly context-dependent: The most robust signal is early postprandial attenuation with γ-PGA-rich natto, strongly acidified or low-glycemic sourdough breads, and selected kombucha formulations, particularly in individuals with impaired glucose regulation. We identify major sources of heterogeneity (starters, process parameters, substrates, background diet) and safety considerations (sodium, ethanol, gastrointestinal symptoms) and propose minimum reporting standards and trial designs integrating metabolomics, microbiome, and host-omics. Overall, plant-based ferments appear best positioned as adjuncts within cardiometabolic dietary patterns and as candidates for “purpose-built” postbiotic products targeting early glycemic excursions and broader metabolic risk. Full article

Background: Metabolic syndrome, a clinical condition defined by central obesity, impaired glucose regulation, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol across the lifespan, is now a major public health issue typically managed with lifestyle, behavioral, and dietary recommendations. However, “one-size-fits-all” recommendations often yield modest, heterogeneous responses and poor long-term adherence, creating a clinical need for more targeted and implementable preventive and therapeutic strategies. Objective: To synthesize evidence on how the gut microbiome can inform precision nutrition and exercise approaches for metabolic syndrome prevention and management, and to evaluate readiness for clinical translation. Key findings: The gut microbiome may influence cardiometabolic risk through microbe-derived metabolites and pathways involving short-chain fatty acids, bile acid signaling, gut barrier integrity, and low-grade systemic inflammation. Diet quality (e.g., Mediterranean-style patterns, higher fermentable fiber, or lower ultra-processed food intake) consistently relates to more favorable microbial functions, and intervention studies show that high-fiber/prebiotic strategies can improve glycemic control alongside microbiome shifts. Physical exercise can also modulate microbial diversity and metabolic outputs, although effects are typically subtle and may depend on baseline adiposity and sustained adherence. Emerging “microbiome-informed” personalization, especially algorithms predicting postprandial glycemic responses, has improved short-term glycemic outcomes compared with standard advice in controlled trials. Targeted microbiome-directed approaches (e.g., Akkermansia muciniphila-based supplementation and fecal microbiota transplantation) provide proof-of-concept signals, but durability and scalability remain key limitations. Conclusions: Microbiome-informed personalization is a promising next step beyond generic guidelines, with potential to improve adherence and durable metabolic outcomes. Clinical implementation will require standardized measurement, rigorous external validation on clinically meaningful endpoints, interpretable decision support, and equity-focused evaluation across diverse populations. Full article

Carbohydrates have been the center of type 1 diabetes dietary management. Emerging evidence highlights the important effects of fat and protein in postprandial hyperglycemia, suggesting that an increase in daily fat and protein intake, combined with appropriate insulin dose adjustments, might lead to better glycemic control. It is well studied that meals containing fat or protein lead to late postprandial hyperglycemia. Studies that researched the use of these macronutrients observed the need for extended or dual wave boluses to achieve euglycemia and that no consistent improvement in HbA1c or time in range was related to higher protein or fat intake. Optimizing glycemic control in pediatric T1D requires strategies beyond carbohydrate counting. While balanced macronutrient distribution remains the main solid factor in stable glycemic profiles, more studies regarding the variety of macronutrients’ formulation in optimizing glycemic control are needed. Full article

Type 2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance, progressive β-cell dysfunction, and persistent hyperglycemia. While GLP-1 receptor agonists have revolutionized the management of T2D by improving glycemic control and reducing body weight, their insulinotropic effects increase the workload on pancreatic β-cells, which may hasten β-cell decline in certain individuals. Peptide YY (PYY), a gut-derived hormone secreted alongside glucagon-like peptide-1 (GLP-1) from L-cells, presents a unique and complementary therapeutic approach. In contrast to GLP-1, PYY does not directly induce insulin release but confers metabolic advantages by suppressing appetite through Y2 receptor pathways, enhancing insulin sensitivity via peripheral Y1/Y4 receptors, and slowing gastric emptying to minimize postprandial glucose surges. Notably, recent research suggests PYY supports the preservation and restoration of pancreatic islets by improving their structure and function without increasing the secretory demand. PYY levels are substantially increased after bariatric surgery, where it plays a pivotal role in weight-loss-independent improvements in glycemic regulation and islet hormone dynamics. These attributes position PYY as a strong candidate for use in combination with GLP-1 analogs, especially in individuals with advanced β-cell impairment or those who respond inadequately to GLP-1 monotherapy. This review discusses PYY’s physiological functions, mechanistic actions, and therapeutic opportunities in T2D, highlighting its potential as a valuable adjunct or alternative in gut-hormone-oriented treatment strategies. Full article

Gestational diabetes mellitus (GDM) is a heterogeneous disorder that compromises maternal and offspring health. Conventional medical nutrition therapy focuses on nutrient composition and caloric targets but largely omits timing and individualized biology. This narrative review synthesizes mechanistic, epidemiologic and interventional evidence linking circadian biology and meal timing (chrononutrition) to maternal glycemic control. Observational cohorts associate late eating and breakfast skipping with worse glycemia, while pilot interventions and CGM-based studies indicate that front-loading carbohydrates, restricting evening carbohydrate, extending overnight fasting (≈10–12 h), and simple within-meal sequencing can reduce postprandial excursions and increase time-in-range. We propose a pragmatic, tiered clinical pathway in which routine second-trimester triage (50 g glucose challenge test and ultrasound abdominal subcutaneous fat thickness) identifies higher-risk women for short-term CGM phenotyping and prioritized chrononutrition counseling. Integrating phenotype-matched timing interventions with dietetic support and digital decision tools allows rapid, individualized adjustments informed by real-time glucose patterns and patient chronotype. In principle, this tiered strategy could improve daily glycemic profiles, reduce the need for pharmacotherapy, and translate into better neonatal outcomes if supported by larger randomized trials. Chrononutrition therefore offers a promising extension of standard care: simple, low-cost adjustments to “when” food is eaten, supported by digital tools, could allow nutrition therapy for GDM to become more precise, more responsive, and ultimately more effective for both mother and child. Key priorities include validating bedside and chrono-omic stratifiers, testing scalable delivery platforms, and ensuring equitable access to personalized chrononutrition in pregnancy. Full article

Background/Objectives: Plants and fruits of Physalis philadelphica Lam. Solanacea are commonly used in traditional medicine to improve some illnesses such as diabetes, in North and Central American countries. The aim was to evaluate the effects of aqueous maceration (He-M) and ultrasound-assisted (He-US) extracts of P. philadelphica husk on hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress in obese rats. Methods: The effects of husk extracts on carbohydrate and lipid absorption were evaluated using oral starch and lipid tolerance tests in healthy male Wistar rats. Obesity was then induced using a high-fructose and saturated fat diet, followed by 16 weeks of extract administration. Results: He-US significantly reduced the postprandial glycemic spike, while both extracts lowered serum triglyceride levels (~50%) following lipid loading, compared with the negative control. In obese rats, both extracts reduced body weight gain (~10%) and lowered fasting glucose levels (22% for He-M and 15% for He-US), compared with the obese control. He-US also reduced insulin levels (~32%), insulin resistance (~53%), and free fatty acids (~52%), while He-M improved hepatic steatosis and reduced liver triglycerides (~26%). Both extracts reduced hepatic nitrite levels, although only He-M significantly decreased lipid peroxidation (~32%). Additionally, both treatments enhanced hepatic antioxidant enzyme activity. Conclusions: Husk extracts exerted beneficial effects on hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress markers in obese rats. Full article

Background/Objectives: Optimal postprandial glycemic control is crucial to maintain time in range (TIR:3.9–10.0 mmol/L, 70–180 mg/dL) and time in tight range (TITR:3.9–7.8 mmol/L, 70–140 mg/dL), both important to reduce microvascular complications in type 1 diabetes mellitus (T1DM). However, insulin dosing based on carbohydrate counting fails to compensate for delayed hyperglycemia from protein and fat. This study evaluated two advanced insulin dosing algorithms designed to improve postprandial control in adolescents with T1DM. Methods: In this randomized, prospective, double-blind, crossover trial, 58 adolescents with T1DM (median age 15.5 years) were enrolled, all using continuous subcutaneous insulin infusion and a continuous glucose monitoring system in non-automated mode. For two consecutive days, participants consumed standardized mixed meals for breakfast (50 g of carbohydrates, 200 kcal from protein and fat) and received an extended bolus delivered for four hours, based on the Pankowska Equation (PE, i.e., Fat-Protein Units × Insulin-to-Carbohydrate Ratio (ICR)) and the Sieradzki Equation (SE, i.e., 30% × Carbohydrate Units × ICR). Postprandial glucose was monitored for five hours using a glucometer and Continuous Glucose Monitoring (CGM). The primary outcome was the capillary blood glucose level at predefined time points. The secondary outcomes were the frequency of hypoglycemia and glycemic variability parameters. Results: Both methods kept postprandial glucose within the recommended TIR. The SE method provided longer TITR (82.51% vs. 70.49%, p = 0.6281) and fewer hypoglycemic episodes at 180 and 300 min. Glucose levels at 60 min, were higher after PE (136 ± 35.2 mg/dL vs. 124 ± 32.2 mg/dL, p = 0.016). Conclusions: Both algorithms provided effective postprandial control after a mixed meal, but SE achieved a longer TITR and fewer late hypoglycemic events. Full article

Background: Dietary polyphenols, particularly flavonoids, have been associated with improved glycemic control and reduced risk of type 2 diabetes. Raspberry leaf (RL) is a rich but underexplored source of such bioactives, including ellagitannins, flavonoids, and phenolic acids. While raspberry fruit has received some attention in nutritional science, the metabolic effects of raspberry leaf—especially its influence on postprandial glucose and insulin responses—remain largely unstudied. Objective: This study is the first to investigate the acute effects of RL tea consumption on postprandial blood glucose and insulin levels in healthy individuals following intake of common dietary carbohydrates (sucrose and glucose). Methods: In a randomized crossover study, 22 healthy adults (12 males, 10 females) consumed 50 g of glucose or sucrose with or without 10 g of RL tea in four separate sessions. Blood glucose and insulin levels were measured at fasting and at 15, 30, 60, 90, and 120 min post-ingestion. A total of 37 polyphenolic compounds were identified in the RL infusion using LC–MS, following a 5-minute hot water extraction. The contents of ellagitannins, flavonoids, and phenolic acids were 38 mg, 7 mg, and 4 mg per 10 g of RL, respectively, contributing to a total polyphenol content of 50 mg per 10 g. Results: When RL tea was consumed with sucrose, postprandial blood glucose levels were significantly reduced at 15 and 30 min by 1.19 ± 0.88 mmol/L (25.59% reduction, p = 0.001) and 2.03 ± 1.05 mmol/L (43.57% reduction, p = 0.0004), respectively. Insulin concentrations were also significantly lower at 15 min (113.90 ± 59.58 pmol/L, p = 0.019), 30 min (161.76 ± 91.96 pmol/L, p = 0.0008), and 60 min (139.44 ± 75.96 pmol/L, p = 0.025). No significant differences were observed with glucose ingestion. Conclusions: This study provides the first clinical evidence that RL tea can blunt early postprandial glycemic and insulinemic responses to sucrose in healthy individuals. The data suggest that these effects are likely mediated by relatively low levels of polyphenols—particularly ellagic acid—through inhibition of carbohydrate-digesting enzymes such as α-glucosidase and β-fructofuranosidase. These findings support the potential of RL tea as a simple, dietary approach to modulate glucose metabolism and warrant further investigation in populations at risk for metabolic disorders. Full article

Background/Objectives: Arabinoxylan (AX) has shown potential benefits in glycemic control; however, findings remain inconclusive. This systematic review and meta-analysis aimed to assess the impact of AX intake on glycemic control in preclinical and clinical studies. Methods: A database search was conducted in PubMed, Embase, Cochrane Library, and CINAHL. A total of 133 studies were included for systematic review and extracted data from 46 clinical studies and 25 preclinical studies were further analyzed for meta-analysis. Results: The AX consumption improved overall postprandial glycemic control in clinical studies, as evidenced by reductions in glucose iAUC (SMD: −0.41; 95% CI: [−0.57, −0.25]), insulin iAUC (SMD: −0.28; 95% CI: [−0.44, −0.12]), glucose iPeak (SMD: −0.52; 95% CI: [−0.80, −0.25]), and insulin iPeak (SMD: −0.24; 95% CI: [−0.41, −0.06]) compared to the control. For chronic glycemic control, fasting glucose (Hedges’ g: −1.18; 95% CI: [−1.56, −0.80]), insulin (Hedges’ g: −1.07; 95% CI: [−1.92, −0.23]), HbA1c (Hedges’ g: −2.93; 95% CI: [−5.48, −0.38]), and HOMA-IR (Hedges’ g: −2.44; 95% CI: [−3.66, −1.22]) reduced in preclinical studies, while improvements were limited to fasting glucose (MD: −0.10; 95% CI: [−0.16, −0.03]) in clinical studies. Subgroup analyses revealed that AX exerted a greater glycemic-lowering effect in metabolically impaired animals and individuals compared to healthy counterparts. Furthermore, extracted AX was found to be more effective than intrinsic AX in optimizing glycemic control. Conclusions: The consumption of AX improves glycemic control, particularly in metabolically impaired animals and human participants. Moreover, the benefit appears more pronounced with extract AX interventions. Full article

Moringa oleifera leaf (MOL) and their extracts have been demonstrated to possess hypoglycemic effects in a variety of species, but they are still unknown in dogs. This study examined the effects of Moringa oleifera leaf peptide (MOLP) on α-amylase and α-glucosidase activities. Furthermore, we assessed the impact of MOLP on the estimated glycemic index (eGI) of snacks in vitro and the postprandial glycemic response in dogs. The findings indicated that MOLP exhibited significant inhibitory activities against α-amylase (IC₅₀ = 2.29 ± 0.10 mg/mL) and α-glucosidase (IC₅₀ = 2.80 ± 0.04 mg/mL). Moreover, the MOLP-containing snacks exhibited a lower rate of starch hydrolysis during in vitro digestion, leading to a notable reduction in the eGI when compared to white bread (WB) and control snacks. Incorporating MOLP into snacks causes smoother alterations in postprandial blood glucose, significantly reducing glucose peak, time to peak, and glycemic index (GI). Our findings indicate that MOLP exhibits hypoglycemic potential, offering a scientific foundation for the future development of functional foods aimed at managing diabetes in dogs. Full article

Background: Low-glycemic index (GI) carbohydrates like isomaltulose (ISO) are known to enhance incretin release and to improve postprandial glucose control at the following meal (an effect known as second meal effect, or SME), which is particularly beneficial for individuals with metabolic syndrome (MetS). This study aimed to assess the most effective preprandial interval of ISO- or saccharose (SUC) snacks (1 h vs. 3 h preload) to enhance prandial incretin responses to a subsequent meal. Methods: In a randomized crossover design, 15 participants with MetS completed four experimental conditions on four non-consecutive days, combining two preload types (ISO or SUC) and two preload timings (Intervention A: 3 h preload; Intervention B: 1 h preload). Specifically, the four conditions were (1) ISO + Intervention A, (2) SUC + Intervention A, (3) ISO + Intervention B, and (4) SUC + Intervention B. The order of conditions was randomized and separated by a 3–7-day washout period to minimize carryover effects. On each study day, participants consumed two mixed meal tests (MMT-1 and MMT-2) with a standardized preload (50 g ISO or SUC) administered either 3 h or 1 h prior to MMT-2. Blood samples were collected over 9 h at 15 predefined time points for analysis of glucose, insulin, C-peptide, and incretin hormones (GLP-1, GIP, and PYY). Results: The unique digestion profile of ISO resulted in a blunted glucose ascent rate (ΔG/Δt: 0.28 vs. 0.53 mmol/L/min for SUC, p < 0.01), paralleled by synonyms PYY elevation over 540 min monitoring, compared with SUC. ISO also led to higher and more sustained GLP-1 and PYY levels, while SUC induced a stronger GIP response. Notably, the timing of ISO consumption significantly influenced PYY secretion, with the 3 h preload showing enhanced PYY responses and a more favorable SME compared to the 1 h preload. Conclusions: ISO, particularly when consumed 3 h before a meal (vs. 1 h), offers significant advantages over SUC by elevating PYY levels, blunting the glucose ascent rate, and sustaining GLP-1 release. This synergy enhances the second meal effect, suggesting ISO’s potential for managing postprandial glycemic excursions in MetS. Full article

Background/Objectives: Postprandial hyperglycemia is a risk factor for diabetes and cardiovascular diseases, even in healthy individuals. Kanzaki mulberry leaf and water chestnut tea (MW tea), a blend of mulberry (Morus alba) leaves and water chestnut (Trapa japonica) leaves and husks, is rich in polyphenols and 1-deoxynojirimycin (DNJ) and may suppress postprandial glucose spikes, but evidence regarding its short-term daily intake is limited. This study aimed to evaluate the postprandial glycemic response and safety of two-week MW tea consumption using continuous glucose monitoring (CGM). Methods: We conducted a randomized, double-blind, placebo-controlled, two-period crossover trial involving 31 participants. Each intervention period lasted two weeks, separated by a one-week washout. Participants consumed either MW tea or a placebo before meals. Interstitial glucose levels were measured every 15 min using CGM. Postprandial glucose responses were recorded every 15 min for 180 min after a standardized meal on the first day of each period. The primary outcome was the coefficient of variation (CV) in glucose levels, calculated using data from the central 10 days of each intervention period. Safety was assessed using CGM-derived hypoglycemia metrics and blood test results. Results: The CV of glucose levels during the MW tea period was significantly lower than during the placebo period (mean difference: 0.02, p = 0.0006). A significant reduction in 1 h postprandial glucose area under the curve was also observed. No significant differences were found in hypoglycemia occurrence, liver/renal/inflammatory markers, or self-reported adverse symptoms. Notably, 1,5-anhydroglucitol (1,5-AG) levels significantly increased during MW tea intake, suggesting improved glycemic control. Conclusions: Short-term consumption of Kanzaki MW tea effectively suppressed postprandial glucose variability without safety concerns. These findings support MW tea as a promising natural supplement for glycemic management and the prevention of diabetes. Full article