This review investigates dietary strategies aimed at enhancing insulin sensitivity and reducing the risk of type 2 diabetes (T2D), with a special focus on recent meta-analysis evidence supporting the use of probiotics and synbiotics. Dietary interventions, such as the Mediterranean, low-carbohydrate, high-fiber, and plant-based diets, have shown significant promise in modulating glucose metabolism through mechanisms involving insulin receptor activation, glucagon-like peptide 1 (GLP-1) receptor signaling, and peroxisome proliferator–activated receptors (PPARs) regulation. Additionally, probiotics and synbiotics have emerged as complementary approaches, enhancing gut microbiota composition and improving insulin sensitivity through reduced inflammation and oxidative stress. The integration of molecular insights, including the role of siRNA and miRNA in gene regulation, highlights the potential for personalized nutritional therapies. This review provides evidence-based recommendations for daily dietary practices and suggests future research directions targeting combined dietary and molecular interventions for T2D management.

Type 2 Diabetes Mellitus (T2DM) is a very serious global problem. In Indonesia, this disease attacks at the most productive age; consequently, it can reduce economic status and life expectancy. The pathogenesis of T2DM is very closely related to inflammation and macrophage accumulation. However, no anti-inflammatory agent has been proven to play a role in the management of T2DM. Butyrate is a short chain fatty acid produced from resistant starch fermentation in the intestinal lumen. It is able to bind to GPR41 and GPR43 receptors on monocytes, so that it can change the pattern of cytokine expression, activation, migration and cell differentiation. Hence, it is interesting to examine the anti-inflammation effect of butyrate and the effect on monocyte migration. A total of 37 subjects were examined in this study. They were divided into two groups, with and without butyrate treatment. We analyzed two pro-inflammatory cytokines (Tumor Necrosis Factor TNF-α and Interleukin IL-6) and one anti-inflammatory cytokine, IL 10. Monocytes were isolated in type 1 collagen gel for migration testing using the µ-slide chemotaxis IBIDI. Image analysis used ImageJ and Chemotaxis tool software. There was a significant difference in the TNFα/IL 10 ratio between healthy groups and T2DM. Butyrate also appears to suppress TNFα cytokine production and increase IL10 production. It also decreases the accumulation distance of monocyte migration in T2DM.

The substantial increase in the prevalence of non-communicable diseases in Indonesia might be driven by rapid socio-economic development through urbanization. Here, we carried out a longitudinal 1-year follow-up study to evaluate the effect of urbanization, an important determinant of health, on metabolic profiles of young Indonesian adults. University freshmen/women in Jakarta, aged 16–25 years, who either had recently migrated from rural areas or originated from urban settings were studied. Anthropometry, dietary intake, and physical activity, as well as fasting blood glucose and insulin, leptin, and adiponectin were measured at baseline and repeated at one year follow-up. At baseline, 106 urban and 83 rural subjects were recruited, of which 81 urban and 66 rural were followed up. At baseline, rural subjects had better adiposity profiles, whole-body insulin resistance, and adipokine levels compared to their urban counterparts. After 1-year, rural subjects experienced an almost twice higher increase in BMI than urban subjects (estimate (95%CI): 1.23 (0.94; 1.52) and 0.69 (0.43; 0.95) for rural and urban subjects, respectively, P_int < 0.01). Fat intake served as the major dietary component, which partially mediates the differences in BMI between urban and rural group at baseline. It also contributed to the changes in BMI over time for both groups, although it does not explain the enhanced gain of BMI in rural subjects. A significantly higher increase of leptin/adiponectin ratio was also seen in rural subjects after 1-year of living in an urban area. In conclusion, urbanization was associated with less favorable changes in adiposity and adipokine profiles in a population of young Indonesian adults.

Background: Obesity is increasingly recognized as a metabolic disorder driven by gut microbiota dysbiosis and chronic low-grade inflammation within adipose tissue. Emerging evidence highlights the gut–adipose tissue axis as a critical mediator of energy balance and metabolic regulation. Marine algae—rich in polysaccharides, polyphenols, and carotenoids—offer bioactive compounds that modulate gut microbial composition and generate beneficial metabolites termed “postbiotics.” Objective: This review aims to comprehensively summarize current advances in understanding how marine-algal-derived postbiotics influence the gut microbiota–adipose tissue axis and contribute to obesity prevention and management. Methods: A structured literature search was conducted across PubMed, Scopus, Web of Science, ScienceDirect, and SpringerLink for studies published between 2015 and October 2025. Eligible studies included in vitro, in vivo, and human trials examining the effects of marine-algal compounds on gut microbiota composition, short-chain fatty acid (SCFA) production, adipose inflammation, and metabolic outcomes. Results: Marine-algal polysaccharides (fucoidan, alginate, laminarin, carrageenan, and ulvan) act as fermentable fibers that enhance SCFA production and enrich beneficial taxa such as Akkermansia, Lactobacillus, and Bacteroides, while reducing endotoxin-producing bacteria. Polyphenols and carotenoids (fucoxanthin, phlorotannins, astaxanthin) directly target adipogenesis, oxidative stress, and adipose browning. Animal studies consistently demonstrate reduced body weight, improved insulin sensitivity, and decreased inflammation following algae supplementation. Human trials—though limited—confirm safety and show microbiota modulation with modest weight loss. Conclusions: Marine-algal-derived postbiotics represent a promising, natural, and sustainable strategy to target the gut microbiota–adipose tissue axis in obesity. They offer multi-targeted mechanisms through microbial and host pathways, supporting their integration into functional food and nutraceutical development. Further clinical research and regulatory standardization are warranted to translate these findings into evidence-based interventions.

Background/Objectives: There has been a prominent rise in the use of GLP-1 RAs recently, particularly semaglutide, for the treatment of T2DM with or without obesity. Subcutaneous injections of semaglutide have demonstrated beneficial effects on cardiovascular risk factors. However, several factors hinder the use of subcutaneous administration. Therefore, the oral route is preferred; yet, it remains unclear whether oral semaglutide provides cardiovascular protection comparable to its subcutaneous counterpart. Methods: A systematic review in line with the PRISMA guidelines was performed based on eight databases (Scopus, Proquest, Science Direct, PubMed, Google Scholar, EBSCOHost, Clinical Key, and The Cochrane Library) to identify clinical studies that assessed the effects of oral semaglutide on cardiovascular risk factors, especially blood pressure and lipid or cholesterol profile in T2DM patients. Inclusion criteria included studies that used oral semaglutide on top of a mainstay treatment for T2DM compared to the placebo control group, assessed cardiovascular risk factors, and were conducted prospectively or in an RCT design. Case reports, ongoing studies with incomplete results, reviews, animal studies, and retrospective studies were excluded. The Newcastle-Ottawa scale and Jadad scale were used to assess the risk of bias in the included studies. Data extracted from the selected studies included patient characteristics, study design, research methodology, intervention regimen, and cardiovascular risk factors: SBP, DBP, TC, HDL, LDL, and TG. Data were presented in a table format to compare and synthesize the results of each study. Results: Five clinical studies were selected (two were randomized trials and three were observational, prospective studies). All five studies reported a consistent trend in the reduction in SBP (ranging from −2.60 to −12.74 mmHg) after oral semaglutide treatment. However, its effect on DBP was found to be less consistent. Lipid profile results show the most consistent trend in total cholesterol reduction (−8.80 to −22.19 mg/dL). Four studies reported a favorable reduction in LDL cholesterol (−7.6 to −18.0 mg/dL) and triglycerides (−11.00 to −40.13 mg/dL). HDL cholesterol shows the least consistent findings where three studies reported an increasing trend, yet this was not statistically significant; one study reported a mild increase in HDL (+0.90 ± 0.12; p < 0.0001); and one study reported a slight reduction in HDL (55.6 ± 2.5 to 51.6 ± 2.2; p < 0.05). Conclusions: Once-daily oral semaglutide is a promising add-on therapy for the treatment of T2DM with or without obesity in reducing cardiovascular risk factors, potentially lowering cardiovascular-related mortality. Thus, once-daily oral semaglutide may offer cardiovascular benefits comparable to the subcutaneous form, with the advantage of improved adherence.

Precision nutrition has emerged as a promising strategy for the prevention of type 2 diabetes mellitus (T2DM) by targeting molecular pathways underlying insulin resistance and impaired glucose metabolism. Accumulating evidence indicates that dietary patterns, caloric intake, and specific nutrients can modulate gene expression and epigenetic mechanisms involved in insulin signaling, inflammation, and energy homeostasis. This narrative review synthesizes recent human and experimental studies (2025–2026) examining how dietary components influence transcriptional and epigenetic regulation of insulin signaling and glucose metabolism in the context of T2DM prevention. A total of 29 peer-reviewed studies were included, encompassing dietary patterns, macronutrient manipulation, micronutrient and bioactive supplementation, and gene–diet interactions. Very-low-calorie diets consistently induced coordinated modulation of key metabolic genes, including downregulation of glucose transporter type 4 (GLUT4) and upregulation of PDK4, CPT1, and AMPK, reflecting a metabolic shift toward enhanced fatty acid oxidation and improved insulin sensitivity. In contrast, high-fat and fructose-rich diets promoted proinflammatory gene expression and immune activation, contributing to insulin resistance. Plant-based and vegan dietary patterns were associated with reduced epigenetic aging and improved insulin sensitivity through DNA methylation changes. Targeted interventions, including vitamin D combined with probiotics, dietary fiber, nucleotides, and trace elements such as copper, further demonstrated favorable transcriptional and epigenetic effects linked to improved glycemic control. Collectively, these findings highlight diet-driven modulation of insulin signaling and glucose metabolism at the molecular level and support nutrigenomics-guided precision nutrition as a viable preventive approach for T2DM. Integrating genetic and epigenetic insights into dietary strategies may enable more personalized and effective interventions to curb the growing global burden of type 2 diabetes.