Type 2 Diabetes Mellitus (T2DM) represents a major global health issue, with its incidence anticipated to increase markedly in the forthcoming decades. Efficient non-pharmacological therapies, especially dietary approaches, are essential for regulating glycemic control and facilitating weight reduction. Intermittent Fasting (IF) and Continuous Caloric Restriction (CCR) are two well researched methodologies, but their relative effectiveness and enduring advantages continue to be topics of active discussion. This review systematically assesses and contrasts the impacts of intermittent fasting (IF) and continuous calorie restriction (CCR) on glycemic regulation and weight reduction in persons with type 2 diabetes mellitus (T2DM), highlighting their short-term and long-term effects, safety profiles, and adherence rates. A thorough literature analysis was performed utilizing PubMed and Google Scholar, concentrating on papers published from 2000 to 2024. The review encompassed randomized controlled trials and observational studies that investigated the effects of intermittent fasting (IF) and continuous calorie restriction (CCR) on glycemic indicators (HbA1c, fasting glucose) and body weight. IF shown substantial short-term advantages, encompassing marked decreases in HbA1c levels, fasting glucose, and body weight. Mechanistic discoveries emphasized better insulin sensitivity, augmented fat metabolism, and autophagy as key aspects. In contrast, CCR was linked to enduring metabolic enhancements, including decreased visceral fat and improved insulin sensitivity. Nevertheless, both dietary approaches demonstrated constraints.

Since type 2 diabetic patients often develop resistance to metformin as the progresses of diabetes, and almost all type 1 diabetic patients need receive insulin injection for hyperglycemia control. It is important to explore novel strategies with different mechanisms for diabetes management. Glucose-induced osmotic diuresis, known as polyuria, is the first clinical symptom in severe type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM). Drinking green tea or black tea effectively mitigates diabetic symptoms including polyuria, polydipsia, polyphagia and hyperglycemia in db/db mice via regulating renal aquaporin 2 and urine transporter A1 (UT-A1), in favor renal water reabsorption. This unique mechanism of action of tea could be useful for the treatment of diabetes in humans. In this study, we found that drinking Large-leaf yellow tea (LYT) for 5 weeks effectively ameliorated polyuria, polydipsia, polyphagia, hyperglycemia and excessive body weight gain, as well as upregulated renal water reabsorption associated proteins, including protein kinase C-alpha (PKC-α), membrane PKC-α and glycosylated UT-A1 in db/db mice. Four-days experiment were also confirmed the rapidly response of these proteins in favor renal water reabsorption and the amelioration of diabetic symptoms by LYT. We also found that green tea drinking effectively mitigated symptoms of diabetes in a mouse model for T1DM via upregulating these proteins. Moreover, green tea drinking prevented hepatorenal damage caused by hyperglycemia as suggested by the reduced levels of aspartate aminotransferase and creatinine in serum and the enhanced antioxidant defense system in liver and kidney. These results suggest the possible application of tea or tea constitutes in the clinical treatment of severe T2DM and T1DM, and the kidney is the target organ.

Corona Virus Disease 2019 (COVID-19) and diabetes interact to influence disease severity, yet their combined immunological characteristics remain unclear. Here, we analyzed Tim-3+ T cells in patients with COVID-19, Type 1 Diabetes (T1D), or both conditions. COVID-19 reduced peripheral T cell subsets but increased Tim-3+ cells, while T1D and COVID-19 with T1D showed the opposite pattern. Patients with Type 2 Diabetes (T2D) exhibited no significant alterations. In human samples and mouse models, Tim-3+ T cells demonstrated impaired activation and cytokine production. RNA-seq analysis in mice and RT-PCR analysis in human samples together identified the dysregulation of the JAK-STAT pathway in Tim-3+ T cells. These findings highlight Tim-3-mediated JAK-STAT dysregulation in T-cells as a potential mechanism linking COVID-19 and T1D, offering insights for therapeutic targeting.

This review describes a prolonged research endeavour to test the twin cycle hypothesis that type 2 diabetes is caused by fat-induced dysfunction of the liver and pancreas, guided by the happenstance of clinical practice. Testing of the personal fat threshold hypothesis, that individuals exhibit different levels of tolerance to intra-organ fat accumulation, is also described. Both hypotheses predict that type 2 diabetes is potentially reversible by weight loss. The results of the Counterpoint study supported the twin cycle hypothesis, leading to a second study which determined that short-duration diabetes was more likely to remit following the 10-15 kg weight loss. It also confirmed that remission was durable over 6 months on an isoenergetic, normal diet. Subsequently, it was shown that weight loss caused an immediate decrease of pancreas fat only in people with type 2 diabetes and also that postprandial incretin spikes after bariatric surgery had no role in normalising fasting plasma glucose. DiRECT, a 2 year randomised controlled study, demonstrated clinical utility, observing functional beta cell capacity to return almost to normal over 12 months. A small group of participants regained weight and redeveloped type 2 diabetes, allowing observation that the underlying pathophysiological mechanisms during onset of diabetes were as postulated by the twin cycle hypothesis. Major clinical benefit was demonstrated after a further 3 year follow-up in routine care, halving the incidence of serious adverse effect compared with the standard treatment control group. In answer to the question of whether individuals have a personal fat threshold for tolerance of fat, stepwise weight loss in people with type 2 diabetes and BMI in the range 21-27 kg/m2 resulted in remission in 70%, with a wide range of fat thresholds. Type 2 diabetes can be regarded as a condition of homogenous aetiology in genetically heterogenous individuals.

Improving β-cell function can lead to remission in some patients with type 2 diabetes mellitus (T2DM). However, research on pharmacotherapy-induced remission in youth-onset T2DM remains scarce. Our study aimed to identify the clinical characteristics of pediatric patients who experience remission.

We retrospectively reviewed 88 pediatric patients with T2DM followed for at least 1 year at Seoul National University Bundang Hospital between 2013 and 2023. Remission was defined as a glycosylated hemoglobin (HbA1c) level less than 6.5% for at least 3 months after ceasing glucose-lowering pharmacotherapy.

Among 88 patients (60 males, 68.2%) diagnosed at an average age of 14.4±2.1 years, 19 patients (21.6%) achieved remission after a median duration of 1.4 years. The remission group had a larger proportion of males (89.5% vs. 62.3%, P=0.024) and a lower urinary albumin-to-creatinine ratio (ACR) at diagnosis (P=0.011). They also showed lower HbA1c levels at 1 year and more significant changes in HbA1c and body mass index (all P<0.05). Higher urinary ACR levels correlated with a longer duration to achieve remission (hazard ratio, 0.928; P=0.013). In three of the 19 remission patients (15.8%), recurrence occurred after a median of 1.5 years.

Among Korean youth with T2DM, 21.6% achieved remission after a median duration of 1.4 years. Those who experienced remission were predominantly male, had lower ACR at diagnosis, and had significant weight loss within the first year. Further investigation into the factors influencing remission and long-term outcomes is essential.

The Wnt signaling pathway is critically involved in orchestrating cellular functions such as proliferation, migration, survival, and cell fate determination during development. Given its pivotal role in cellular communication, aberrant Wnt signaling has been extensively linked to the pathogenesis of various diseases. This review offers an in-depth analysis of the Wnt pathway, detailing its signal transduction mechanisms and principal components. Furthermore, the complex network of interactions between Wnt cascades and other key signaling pathways, such as Notch, Hedgehog, TGF-β, FGF, and NF-κB, is explored. Genetic mutations affecting the Wnt pathway play a pivotal role in disease progression, with particular emphasis on Wnt signaling's involvement in cancer stem cell biology and the tumor microenvironment. Additionally, this review underscores the diverse mechanisms through which Wnt signaling contributes to diseases such as cardiovascular conditions, neurodegenerative disorders, metabolic syndromes, autoimmune diseases, and cancer. Finally, a comprehensive overview of the therapeutic progress targeting Wnt signaling was given, and the latest progress in disease treatment targeting key components of the Wnt signaling pathway was summarized in detail, including Wnt ligands/receptors, β-catenin destruction complexes, and β-catenin/TCF transcription complexes. The development of small molecule inhibitors, monoclonal antibodies, and combination therapy strategies was emphasized, while the current potential therapeutic challenges were summarized. This aims to enhance the current understanding of this key pathway.

This trial evaluated the effects of insulin aspart (IAsp) and insulin detemir and metformin on islet function in newly diagnosed type 2 diabetes mellitus (T2DM). A total of 96 T2DM patients were randomised into the control group (insulin detemir + metformin treatment) and the study group (insulin detemir + metformin + IAsp treatment), with 48 cases each. The study compared clinical outcomes, as well as changes in fasting plasma glucose (FPG), 2-hour postprandial blood glucose (PBG), glycated haemoglobin (HbA1c), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-β, quality of life, and sleep quality scores before and after treatment. Compared to the control group, the study group showed a higher total effective treatment rate, lower levels of FPG, 2-hour PBG, HbA1c, FINS, HOMA-IR, and sleep quality scores, while demonstrating higher HOMA-β and quality of life scores (all p < 0.05). Insulin detemir + metformin + IAsp was effective in treating T2DM, significantly enhancing insulin function and blood glucose levels, quality of life, and sleep quality. This combination therapy, though not commonly utilised in newly diagnosed T2DM patients, offers a novel therapeutic approach in clinical practice.

Prediabetes poses a significant risk of developing diabetes and it's complications. Africa faces specific challenges, hindering early recognition and management of prediabetes. We aimed to understand unique, ethnicity specific aspects of the burden, pathogenesis and management of prediabetes in Africa.

The rate of progression from prediabetes to diabetes is higher in African, compared to European populations. Prediabetes in Africans is driven mainly by hyperinsulinemia and reduced hepatic clearance causing obesity and insulin resistance, rather than impaired insulin sensitivity. High risk, difficult to reach individuals in lower socioeconomic strata, benefited from community versus facility-based screening. Intensive lifestyle changes with low calorie or low fat-high fiber diet provide longer lasting effect versus drug monotherapy. Using structured community-based screening, early detection of prediabetes is achievable, requiring dedicated stakeholder engagement. Further research into the etiology and sequencing of pathogenetic anomalies and preventive strategies in African populations is needed.

Background and Objectives: Elevated blood sugar poses an increasingly significant challenge to healthcare systems worldwide. We aimed to assess the efficacy of the SGLT-2i class in achieving metabolic control in patients with T2DM within a real-world standard-of-care regimen. Material and Methods: A prospective analysis was conducted over 6 months including individuals receiving care in an outpatient department, with baseline assessments and follow-ups at 3 and 6 months. Results: A total of 280 patients were assessed, with a mean age of 63.69 ± 9.16, 53.9% of which were males, with a mean DM duration of 9.06 ± 5.64 years, and a DM duration varying from 6 months to 24 years. Discussion: Real-world evidence bridges the gap between guidelines and practice. It emphasizes the need to overcome clinical inertia in order to optimize patient outcomes and contributes to the body of evidence supporting the efficacy of fixed-dose SGLT-2i combinations in managing T2DM and associated comorbidities. Conclusions: We demonstrate the significant clinical and therapeutic impact of SGLT-2i in T2DM patients in a real-world setting. This class of medication not only positively influences glycemic and weight control but also reduces CV risk factors and visceral adiposity.

The aim was to assess the clinical and radiographic peri-implant status among type-2 diabetic and non-diabetic individuals with major depressive disorders (MDD). Participants were divided into four groups; Group-1: patients with type-2 diabetes; Group-2: patients with MDD; Group-3: patients with type-2 diabetes and MDD; Group-4: healthy controls. Demographic data was collected, and medical history including most recent hemoglobin A1c (HbA1c) levels were retrieved from healthcare records. Peri-implant modified plaque and gingival indices (MPI and mGI) and peri-implant probing depth (PPD) were recorded; and crestal bone loss (CBL) was measured. Sample-size was estimated using data from a pilot investigation. Statistical analysis was performed using one way-analysis of variance and Bonferroni Post-hoc adjustment tests. P-vales below 0.05 were considered statistically significant. Thirty, 30, 30 and 30 individuals were included in groups 1, 2, 3 and 4. Mean HbA1c levels were higher in groups 1, 2 and 3 compared with Group-4 (P < 0.05). Thirty-seven, 40, 43 and 36 implants were present in groups 1, 2, 3 and 4, respectively. In groups 1, 2, 3 and 4, the implants were in function for a mean duration of 4.7 ± 2.4, 4.9 ± 1.8, 5.05 ± 1.7 and 10.6 ± 2.2 years, respectively. The mPI, mGI, PPD and CBL were significantly higher in groups 1, 2 and 3 than individuals in Group-4 (P < 0.05). There was significant correlation between peri-implant PD and HbA1c levels among individuals in Group-1 (P < 0.05). Peri-implant soft tissue and osseous statuses are compromised among patients with type-2 DM, and MDD regardless of whether these conditions occur individually or in combination. Clinical relevance: Peri-implant soft tissue and osseous statuses are compromised among patients with type-2 DM, and MDD regardless of whether these conditions occur individually or in combination.

Kidney stones are a prevalent disorder that is linked to a range of metabolic variables. The cardiometabolic index (CMI) is a newly developed combined measure used to evaluate the state of cardiometabolic health. Nevertheless, the association between CMI and kidney stone remains little investigated.

In this study, cross-sectional analysis was done on NHANES data from 2007 to 2018. The association between the prevalence of kidney stones and the CMI was investigated using a logistic regression analysis. To look into the nonlinear link between them, we used restricted cubic spline (RCS) analysis. The study was made more reliable and accurate by using sensitivity analysis and subgroup analysis to look for factors that may have contributed to the different results.

A significant association was seen between increased CMI and the prevalence of kidney stones (OR = 1.19, 95% CI: 1.06-1.32). The RCS analysis revealed crucial CMI values that exhibited a robust association within a certain range. Subgroup studies revealed that this link was particularly prominent among those below the age of 50, females, obese, CKD and diabetes patients. The dependability of the study's conclusions was further established using sensitivity analysis.

This study established a notable association between CMI and a higher prevalence of kidney stones, emphasizing the significance of CMI as a comprehensive measure for evaluating metabolic risk. Furthermore, it suggests that monitoring CMI levels could be beneficial in identifying populations with a high prevalence of kidney stones.

High-intensity interval training (HIIT) has potential health benefits in the treatment of many chronic diseases. However, the efficacy of HIIT in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. This systematic review and meta-analysis aimed to assess the impact of HIIT on intrahepatic lipids (IHLs) , liver enzymes, and metabolic profiles in individuals with MASLD. All randomized-controlled trials (RCT) that evaluated and compared the effects of HIIT on clinical parameters in patients with MASLD were searched using the PubMed, EMBASE, WOS, and Cochrane databases. Data analysis and integration were performed using RevMan 5.3 (Cochrane Collaboration, Copenhagen, Denmark) and Stata version 18 software (StataCorp LLC, College Station, Texas, USA), and outcomes were assessed using the standardized mean difference (SMD). Our results showed that compared with other types of exercise or no exercise, HIIT could reduce the levels of IHL [SMD: -0.56%, 95% confidence interval (CI): -0.99 to -0.13, P = 0.01], BMI (SMD: -0.31, 95% CI: -0.62 to -0.01, P = 0.04), alanine aminotransferase (ALT) (SMD: -0.61, 95% CI: -0.95 to -0.26, P = 0.0006), and aspartate aminotransaminase (AST) (SMD: -0.43, 95% CI: -0.81 to -0.05, P = 0.03) in patients with MASLD. In addition, subgroup analyses showed that HIIT had a positive impact on clinical indicators in patients with MASLD with an intervention duration of less than equal to 8 weeks. This study supports the idea that HIIT can significantly reduce IHL, BMI, ALT, and AST levels, and further studies are needed to assess the long-term adherence and treatment effects of HIIT.

Increases in the prevalence of type 2 diabetes (T2D) pose significant challenges to its prediction and prevention.

We aimed to evaluate whether cumulative exposure to a high triglyceride to high-density lipoprotein-cholesterol (TG/HDL-C) ratio is associated with increased T2D risk in young adults.

We collected South Korean National Health Insurance Service data between 2009 and 2012 from 1,840,251 young adults without T2D aged 20 to 39 years who underwent 4 consecutive annual health checkups. Participants were classified into 5 groups based on exposure to a high TG/HDL-C ratio, defined as the highest TG/HDL-C ratio quartile. T2D risk was evaluated using a multivariate Cox proportional hazard model.

During the 6.53-year follow-up period, 40,286 participants (2.2%) developed T2D. The cumulative incidence of T2D increased with higher TG/HDL-C exposure scores. The adjusted hazard ratios of TG/HDL-C ratio exposure scores for T2D were 1.584 (95% CI, 1.488-1.686), 2.101 (95% CI, 1.980-2.228), 2.942 (95% CI, 2.787-3.106), and 4.962 (95% CI, 4.718-5.219) for groups with scores of 1 to 4, respectively, compared with those with a score of 0. Further subgroup analyses stratified by age, sex, and statin use revealed no significant differences in risk of T2D.

Cumulative exposure to high TG/HDL-C ratio was associated with increased risk of T2D in young Korean adults, suggesting its importance in prediction and prevention. Subgroup analysis revealed no significant differences in age, sex, or statin use. Further research is required to explore the underlying mechanisms and develop effective interventions.

Background Diabetes distress (DD) is a significant barrier to effective diabetes management, impacting self-care behaviors and glycemic control. While most studies utilize glycated hemoglobin (HbA1c) as a standard marker for glycemic regulation, cost constraints often limit its availability. This study explores the shift from HbA1c to random blood sugar (RBS) as an alternative measure and assesses the impact of individualized interventions on DD and glycemic outcomes in individuals with uncontrolled type 2 diabetes mellitus (T2DM). Methods A quasi-experimental study was conducted on 180 participants aged 18-65 years, divided into an experimental group (n=82) receiving structured psychological and lifestyle counseling and a control group (n=98) receiving standard care. DD and RBS levels were recorded at baseline and after three months of the intervention. Statistical analyses included Pearson's correlation, student's t-test, and Wilcoxon signed-rank tests to evaluate changes in distress levels and glycemic control. Results Post-intervention, the experimental group showed a significant reduction in DD (t = 15.26, p < 0.001, Cohen's d = 1.685) and RBS (mean reduction = 10.68%), confirming the effectiveness of the structured interventions. The control group exhibited an unexpected increase in DD (t = -8.75, p < 0.001, Cohen's d = -0.960), whereas RBS remained largely unchanged (1.29% increase). A significant correlation (p = 0.000) between DD reduction and RBS improvement was observed. Conclusions Individualized interventions significantly reduced diabetes distress and improved glycemic outcomes, demonstrating that RBS may serve as a cost-effective alternative to HbA1c. Future research should focus on directly comparing RBS and HbA1c levels and evaluating the long-term sustainability of the intervention benefits across different age groups.

Introduction The triglyceride glucose (TyG) index and modified TyG-indices have been suggested as a reliable indication of insulin resistance. The present study aimed to investigate the predictive utility of TyG index and modified TyG indices (TyG-waist circumference, TyG-body mass index, TyG-waist-to-hip ratio, and TyG-waist-to-height ratio) for assessing glycemic control in type 2 diabetes mellitus (T2DM). Methods The present hospital-based cross-sectional study recruited 383 T2DM patients. On the basis of HbA1c levels, patients were grouped into poor glycemic control (n=168) and good glycemic control (n=215). Baseline and biochemical parameters including TyG and modified TyG indices were compared between the groups. We used a Spearman correlation analysis to look for an association between TyG and TyG-related indices and glycemic control. We conducted receiver operating characteristic curve analysis to evaluate the predictive capability of TyG-index and modified TyG indices in assessing poor glycemic control in T2DM. Results T2DM with poor glycemic control had significantly elevated TyG and modified TyG indices when compared to those with good glycemic control. The TyG index and modified TyG indices showed a strong correlation with glycemic control in individuals with T2DM. The TyG index exhibited greater predictive capacity for poor glycemic control as compared to the modified TyG indices. Conclusion Patients with T2DM who are treated in clinical settings with limited resources may benefit from using the TyG index to evaluate their glycemic control.

Triglyceride glucose-body mass (TyG-BMI) index, sedentary behavior (SB) and physical activity (PA) are independently associated with all-cause mortality and myocardial infarction (MI). However, it remains unclear whether TyG-BMI index and the combination of SB and PA exhibit joint effects on all-cause mortality and MI.

Among 502 356 participants from the UK Biobank, 297 761 eligible participants were selected. The Cox proportional hazards model and the restricted cubic spline regression model were used to assess the associations of TyG-BMI with all-cause mortality and MI. To conduct stratified analysis, participants were classified into four groups by SB (<6 h/d and ≥ 6 h/d) and moderate to vigorous physical activity (MVPA) (<150 min/wk and ≥ 150 min/wk). Additionally, the multiplicative interaction was assessed between TyG-BMI and SB & MVPA. Furthermore, to estimate their joint associations, participants were conjointly classified into twelve new groups by TyG-BMI (tertiles) and SB & MVPA (four groups).

During a median follow-up of 13.8 and 13.6 years, 21 335 deaths and 9 116 MI were observed, respectively. The dose-response relationship of TyG-BMI with all-cause mortality was U-shaped with a cut-off point at 225.09, whereas the relationship with MI was positive nonlinear with a cut-off point at 266.87. A synergistic effect on all-cause mortality was observed between TyG-BMI tertile 1 and ≥ 6 h/d SB & <150 min/wk MVPA (P for interaction < 0.001). When MVPA ≥ 150 min/wk combined with SB either <6 h/d or not, TyG-BMI tertile 2 showed no significant association with all-cause mortality risk, with HRs(95%CIs) of 0.98 (0.93-1.03) for <6 h/d SB and 1.00 (0.94-1.07) for ≥ 6 h/d SB. When one of the two healthy behaviors was present (i.e., either <6 h/d SB with <150 min/wk MVPA, or ≥ 150 min/wk MVPA with ≥ 6 h/d SB), its combination with TyG-BMI tertile 1 showed no significant association with MI risk, with HRs(95%CIs) of 1.07(0.95-1.20) and 1.09(0.94-1.25), respectively.

TyG-BMI index and the combination of SB and PA were independently and jointly associated with risks of all-cause mortality and MI. Our findings highlight the importance of improving insulin resistance to reduce all-cause mortality risk, particularly in individuals with long-term SB and insufficient PA, who are more susceptible to the adverse effects of TyG-BMI index. In long-term sedentary individuals, meeting PA guidelines (≥ 150 min/wk of MVPA) effectively mitigated risks of all-cause mortality and MI associated with TyG-BMI index.

The Atherogenic Index of Plasma (AIP) was originally developed primarily as a marker for assessing atherosclerosis. Consequently, this study investigates the potential association between AIP and type 2 diabetic complications through a cross-sectional design.

The National Metabolic Management Center(MMC) serves as a comprehensive platform dedicated to the establishment of standardized protocols for the diagnosis, treatment, and long-term follow-up of metabolic diseases. Following the relevant inclusion and exclusion criteria, a total of 3,094 patients were enrolled for subsequent analysis. In this study, logistic regression, restricted cubic splines, and subgroup analyses were employed to evaluate the association between the AIP and four major complications of type 2 diabetes, namely, type 2 diabetes with carotid atherosclerosis (DA), diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN).

The logistic regression results demonstrate that in the fully adjusted model, each SD increase in AIP correlates with an elevated risk of type 2 diabetic kidney disease (DKD), with the risk of kidney damage intensifying alongside higher AIP groupings. The RCS analysis and subgroup analyses similarly revealed a dose-response relationship between AIP levels and the risk of DKD. Furthermore, the AIP was not found to be statistically significantly associated with DA, DR,and DPN.

The AIP may serve as a valuable predictive indicator for evaluating kidney damage in patients with type 2 diabetes, and regular screening of AIP in this population could provide significant benefits in the prevention of DKD.

SLC7A11, often called xCT, belongs to the SLC family of transporters, which mediates the cellular influx of cystine and the efflux of glutamate. These transport processes are crucial for synthesizing GSH, enhancing the cell's ability to mitigate oxidative stress (OS). Emerging studies highlight the pivotal role of OS in triggering and exacerbating various metabolic and endocrine disorders, underlining the critical importance of regulating SLC7A11 expression levels. This study reviews the diverse roles of SLC7A11 in endocrine and metabolic diseases, examining its relationship with the metabolism of three key nutrients: proteins and amino acids, carbohydrates, and lipids. Additionally, the involvement of SLC7A11 in the onset and development of various common endocrine and metabolic disorders is analyzed. Additionally, it provides an overview of the current clinical and experimental use of SLC7A11 inhibitors and agonists. This review aims to offer insightful perspectives into the involvement of SLC7A11 in endocrine and metabolic pathologies and to foster the development of innovative therapeutic strategies that target SLC7A11.

Pancreatic islet β-cells express the Cpt1a gene, which encodes the enzyme carnitine palmitoyltransferase 1A (CPT1A), an enzyme that facilitates entry of long-chain fatty acids into the mitochondria. Because fatty acids are required for glucose-stimulated insulin secretion, we tested the hypothesis that CPT1A is essential to support islet β-cell function and mass. In this study, we describe genetic deletion of Cpt1a in pancreatic tissue (Cpt1aPdx1-/-) using C57BL/6J mice. Islet morphology, β-cell transcription factor abundance, islet ATP levels, glucose transporter 2 abundance, and expression of the dedifferentiation marker ALDH1A3 were analyzed by immunofluorescent staining. Glucose and insulin tolerance were assessed to investigate the metabolic status of genetic reductions in Cpt1a. Glucose-stimulated insulin secretion was evaluated in vivo and in isolated islets ex vivo by perifusion. Pancreatic deletion of Cpt1a reduced glucose tolerance but did not alter insulin sensitivity. Glucose-stimulated insulin secretion was reduced both in vivo and in islets isolated from Cpt1aPdx1-/- mice relative to control islets. Pancreatic islets from Cpt1aPdx1-/- mice displayed elevations in ALDH1A3, a marker of dedifferentiation, but no reduction in nuclear abundance of the β-cell transcription factors MafA and Nkx6.1 or the GLUT2 glucose transporter. However, intracellular ATP abundance was markedly decreased in islets isolated from Cpt1aPdx1-/- relative to littermate control mice. We conclude that there is an important physiological role for pancreatic CPT1A to maintain whole body glucose homeostasis by supporting glucose-stimulated insulin secretion and maintaining intracellular ATP levels in male mice.

Diabetes, a chronic condition affecting millions of individuals, is divided into type 1 diabetes (T1D) and type 2 diabetes (T2D), each with unique pathophysiological characteristics. While the impact of diabetes on vision is established, its relationship with other special senses, balance, hearing, and olfaction, remains uncertain. This study utilized a 2-sample Mendelian randomization (MR) approach to investigate the associations between diabetes subtypes and specific sensory disorders. We performed MR analysis using various methods (inverse variance weighting [IVW], MR-Egger, simple mode, weighted mode, weighted median, MR-PRESSO) to assess the causal relationships between diabetes subtypes and sensory disorders (vestibular dysfunction, sensorineural hearing loss, conductive hearing loss, and olfactory dysfunction). Different diabetes genome-wide association studies datasets were utilized for validation. MR analysis revealed no significant correlations between T1D or T2D and the sensory disorders studied. Interestingly, an initial signal suggested that T1D might increase the risk of conductive hearing loss (IVW: odds ratio = 1.120, 95% CI: 1.035-1.211, P = .005), but this finding was not supported by validation studies. No evidence of horizontal pleiotropy or heterogeneity was found (P > .05). Our MR analysis and subsequent validation revealed no significant associations between diabetes subtypes and special senses. The initial suggestion of an increased risk of conductive hearing loss in T1D patients was not confirmed. Future research should further explore the intricate relationships among diabetes, sensory functions, and other factors, as well as the potential effects of diabetes management on sensory health.

Previous studies highlighted the association between the triglyceride-glucose (TyG) index and cardiovascular events in patients with diabetes. However, whether diabetes affects TyG-cardiovascular diseases (CVD) is still unclear. This study aimed to evaluate the association between the TyG index and CVD risk, stratified by diabetes status, as well as the potential modifying effect of diabetic status.

The PubMed, Cochrane Library, and Embase databases were searched for studies on the associations between the TyG index and cardiovascular events and mortality in patients with and without diabetes from inception to December 2, 2024. The random effects model was employed to pool the effect sizes.

A total of 50 cohort studies (7,239,790 participants) were included. The mean age of participants was 31.46 years (diabetes mellitus [DM]: 65.18; non-DM: 31.23), and 40.66% of participants were female (DM: 36.07%; non-DM: 40.70%). The associations between the TyG index and cardiovascular events (HR: 1.72 vs. 1.55, P = 0.55), major adverse cardiovascular and cerebrovascular events (HR: 2.02 vs. 1.91, P = 0.84), stroke (HR: 1.46 vs. 1.39, P = 0.77) and cardiovascular death (HR: 1.85 vs. 1.60, P = 0.56) were similar among DM and non-DM individuals. However, the associations between the TyG index and ischemic heart disease (IHD) (HR: 2.20 vs. 1.57, P = 0.03) as well as all-cause mortality (HR: 1.94 vs. 1.24, P = 0.01) were stronger in DM patients than in non-DM patients.

TyG index showed association with cardiovascular events, mortality, and all-cause mortality independent of diabetic status, with low to moderate certainty. The associations for IHD and all-cause death were stronger in diabetic patients than in individuals without diabetes. Future studies should explore the role of diabetes in the TyG index-associated CVD outcomes and mortality.

Diabetes is a major risk factor for compromised visual health, leading to retinal vasculopathy and neuropathy, both of which are hallmarks of neurovascular unit dysfunction. Despite the critical impact of diabetic retinopathy, the precise mechanism underlying neurovascular coupling and effective strategies to suppress neurovascular dysfunction remain unclear. In this study, the up-regulation of a tRNA-derived stress-induced RNA, 5'tiRNA-His-GTG, in response to diabetic stress is revealed. 5'tiRNA-His-GTG directly regulates Müller glia action and indirectly alters endothelial angiogenic effects and retinal ganglion cell (RGC) survival in vitro. Downregulation of 5'tiRNA-His-GTG alleviates diabetes-induced retinal neurovascular dysfunction, characterized by reduced retinal vascular dysfunction, decreased retinal neurodegeneration, and improved visually-guided behaviors in vivo. Mechanistically, 5'tiRNA-His-GTG acts as a key regulator of retinal neurovascular dysfunction, primarily by modulating arachidonic acid (AA) metabolism via the CYPs pathway. The 5'tiRNA-His-GTG-CYP2E1-19(S)-HETE signaling axis is identified as a key driver of retinal neurovascular dysfunction. Thus, targeting 5'tiRNA-His-GTG presents a promising therapeutic strategy for treating vasculopathy and neuropathy associated with diabetes mellitus. Modulating this novel signaling pathway can open up new avenues for intervention in diabetic retinopathy and its related complications.

Living with chronic conditions like diabetes mellitus (DM) or insulin resistance (IR) requires significant self-management, adding to daily life stressors. This stress, known as diabetes distress, along with health empowerment from proper diet and lifestyle, and motivation to eat healthily, greatly impacts quality of life and disease outcomes. Different patient subgroups (type 1 diabetic (T1DM), type 2 diabetic (T2DM), and insulin resistant (IR) individuals) face these challenges differently. This research aims to compare people with IR and DM to those without, and to compare IR, T1DM and T2DM subgroups on psychological factors. Data was collected via an online questionnaire from 746 participants (average age 37.5 years). Among them, 405 had IR (N = 177) or DM (Type 1: N = 116; Type 2: N = 112), and 341 were controls. Results showed that T2DM individuals scored lower than controls on Identified Regulation, Interoceptive Awareness, and Search for Meaning in Life, while the IR group had higher body-mind disconnection. T1DM individuals experienced the highest emotional distress due to the disease but the lowest distress from regular check-ups compared to T2DM and IR groups. The gradient boosting classification model indicated that IR and T1DM groups are homogeneous, whereas T2DM is heterogeneous, with significant within-group variation in disease experience and management. Despite similarities in daily life challenges, significant differences exist in disease experience among the groups. Individual characteristics of T2DM individuals further diversify their attitudes towards disease management.

This study aims to analyze baseline profiles and longitudinal changes in Atherogenic Index of Plasma (AIP) among individuals with prediabetes to identify distinct AIP trajectories and assess their significance in predicting diabetes onset.

This retrospective cohort study analyzed data from 8346 participants who underwent multiple general health checks. Utilizing latent class trajectory modeling and Cox proportional hazards analyses, it examined the association between the AIP index and health outcomes.

Over about 2 years, 2897 people progressed from prediabetes to diabetes. Individuals in the highest quartile of AIP had a higher diabetes risk compared to the lowest quartile (HR = 1.138, 95% CI1.013-1.278). Trajectory analysis revealed three groups: low-stable, moderate-stable, and high-stable, based on AIP index. The moderate-stable group showed a 1.117-fold risk of diabetes progression (95% CI1.026-1.217), while the high-stable group had an elevated risk (HR = 1.224, 95% CI1.059-1.415).

The study highlights a clear association between higher AIP index levels at baseline and an increased risk of diabetes progression. It underscores the significance of utilizing the AIP index as a predictive tool to identify those at risk, emphasizing the need for targeted preventive measures in managing diabetes progression.

Background: Gestational diabetes mellitus (GDM) is a transient elevation of blood glucose during pregnancy. It is typically not associated with diabetic retinopathy. However, certain investigators revealed retinal microvascular injury. In this study, we aimed to assess the ophthalmic findings, optical coherence tomography (OCT) parameters, and retinal vascular thickness and macular density through fundus autofluorescence (FAF). Methods: Prospectively, women diagnosed with GDM were enrolled in this study. All the participants underwent comprehensive ophthalmic examination. Furthermore, macular OCT with analysis of the central subfield thickness (CST) and total thickness was carried out. Moreover, FAF was performed, and the macular density and retinal vascular thickness were extracted using ImageJ software. Results: Thirty-four women were enrolled. The mean maternal age was 32.7 years. No participant had diabetic retinopathy, nine eyes had early cataract, and two eyes had keratoconus. Higher levels for the 1 h oral glucose tolerance test (OGTT) were associated with a drop in the CST and total thickness. Moreover, women who underwent CS had higher levels of total thickness. Higher levels for the fasting OGTT were associated with a thinner inferior temporal retinal artery. Pregnant women with miscarriages had lower macular density on FAF, as represented by lower values of integrated density and mean gray values. Higher levels for the fasting OGTT were associated with higher values of integrated density. Conclusions: Although GDM is typically not associated with diabetic retinopathy, microscopic changes involving the microvascular environment and the macula may occur. Regular ophthalmic screening for women with GDM may be advised. Larger studies with more investigations may reveal further findings.

Diabetic cardiomyopathy (DCM) is defined as cardiac dysfunction involving changes in structure, function, and metabolism in the absence of coronary artery disease, which eventually developed into heart failure. There is still a lack of effective drugs for the treatment of DCM, while the ameliorative effects of traditional herbs on DCM have been commonly reported. Polydatin (PD) is a glucoside derivative of traditional herbs of resveratrol, which has been shown to ameliorate the pathological development of DCM. However, the cardioprotective effect and mechanism of PD in the improvement of myocardial injury are still unclear.

This study aimed to investigate the cardio-protective role of PD on DCM and reveal the critical effect of Cav1 in PD' regulation of DCM.

The Cav1-/- and Cav1+/+mice and H9C2 cells were used to induce DCM models and then given PD treatment (150 mg/kg) or not. The cardiac functions of all mice were checked via echocardiography, and myocardial histological changes were measured by H&E, periodic acid-schiff (PAS) and Masson staining. The markers expression of heart fibrosis and inflammation, and hypertrophic factors were detected using western blotting. The NF-κB signaling activation was performed by confocal, immunohistochemical, Electrophoretic mobility shift assay (EMSA) and western blotting.

Here, we found that PD significantly improved the cardiac function and injury of diabetic Cav1+/+ mice, and enhanced the expression of Cav1 in the cardiac tissues of diabetic Cav1+/+ mice and HG-induced H9C2 cells. Further investigation showed that when Cav1 was knocked down, PD no longer plays the cardioprotective effect and inhibits the NF-κB signaling pathway activation in HFD/stz-treated diabetic mice and HG-induced H9C2 cells.

These results demonstrated that PD inhibited the hyperglycemia-induced myocardial injury and inflammatory fibrosis of DCM models in vivo and in vitro, and targeting Cav1 may provide a novel understanding the mechanism of the treatment of PD in DCM.

This study aimed to evaluate the relationship between plant protein, animal protein and biological aging through different dimensions of biological aging indices. Then explore the effects of substitution of plant protein, animal protein, and their food sources on biological aging.

The data came from 79,294 participants in the UK Biobank who completed at least two 24-h dietary assessments. Higher Klemera-Doubal Method Biological Age (HKDM-BA), higher PhenoAge (HPA), higher allostatic load (HAL), and longer telomere length (LTL) were estimated to assess biological aging. Logistic regression was used to estimate protein-biological aging associations. Substitution model was performed to assess the effect of dietary protein substitutions.

Plant protein intake was inversely associated with HKDM-BA, HPA, HAL, and positively associated with LTL (odds ratios after fully adjusting and comparing the highest to the lowest quartile: 0.83 (0.79-0.88) for HKDM-BA, 0.86 (0.72-0.94) for HPA, 0.90 (0.85-0.95) for HAL, 1.06 (1.01-1.12) for LTL), while animal protein was not correlated with the four indices. Substituting 5% of energy intake from animal protein with plant protein, replacing red meat or poultry with whole grains, and replacing red or processed meat with nuts, were negatively associated with HKDM-BA, HPA, HAL and positively associated with LTL. However, an inverse association was found when legumes were substituted for yogurt. Gamma glutamyltransferase, alanine aminotransferase, and aspartate aminotransferase mediated the relationship between plant protein and HKDM-BA, HPA, HAL, and LTL (mediation proportion 11.5-24.5%; 1.9-6.7%; 2.8-4.5%, respectively).

Higher plant protein intake is inversely associated with biological aging. Although there is no association with animal protein, food with animal proteins displayed a varied correlation.

This study explores the correlation between site-specific methylation levels of the KCNJ11 promoter and type 2 diabetes mellitus (T2DM), analyzing potential molecular mechanisms.

Thirty patients newly diagnosed with T2DM and 30 healthy controls were selected to determine the CpG methylation levels in the promoter region of the KCNJ11 gene using the bisulfite assay. The online software JASPAR was used to predict transcription factors binding to differentially methylated sites. Key transcription factors were further validated through quantitative PCR (q-PCR) and chromatin immunoprecipitation followed by PCR (ChIP-PCR).

Methylation at multiple CpG sites within the KCNJ11 gene promoter was generally reduced in newly diagnosed T2DM patients compared with healthy individuals. The methylation status of CpG-471, a site crucial for the binding of the transcription factor TCF12, emerged as potentially influential in T2DM pathogenesis. This reduction in methylation at CpG-471 may enhance TCF12 binding, thereby altering KCNJ11 expression.

Hypomethylation of specific CpG sites in the promoter region of the KCNJ11 gene in patients with incipient T2DM potentially contributes to the disease's pathogenesis. This hypomethylation may influence TCF12 binding, with potential regulatory effects on KCNJ11 expression and pancreatic beta-cell function, though further studies are needed to confirm the exact mechanisms involved.

This review examines the impact of combining acupuncture with drug therapy on abnormal glucose metabolism and investigates their underlying mechanisms. Conditions like diabetes pose significant health risks due to irregular glucose metabolism. Traditional drug treatments often encounter challenges related to side effects and drug resistance. Acupuncture, as a non-pharmacological intervention, is thought to enhance glucose metabolism and mitigate medication side effects. We selected the relevant studies of acupuncture or electroacupuncture combined with drugs in the treatment of abnormal glucose metabolism in the past five years, and the results indicate that the combination of acupuncture or electroacupuncture and drug therapy markedly enhances glucose metabolism and mitigates medication-related side effects such as gastrointestinal discomfort and hypoglycemia. Overall, this review underscores the synergistic benefits of acupuncture and drug therapy in improving treatment efficacy and reducing adverse effects, offering promising new approaches for managing abnormal glucose metabolism. Our review provides evidence for the potential benefits of combining acupuncture with drug therapy for abnormal glucose metabolism, which could lead to improved treatment outcomes and reduced side effects for patients with type 2 diabetes mellitus.

Diabetes-induced neuropathy represents a major etiology of dementia, highlighting an urgent need for the development of effective therapeutic interventions. In this study, we explored the role of fibronectin type III domain containing 5 (FNDC5)/Irisin in mitigating hyperglycemia-induced neurotoxicity in HT22 cells and investigated the underlying mechanisms. Our findings reveal that high glucose conditions are neurotoxic, leading to reduced viability of HT22 cells and increased apoptosis. Furthermore, the elevated expression of the intracellular ferroptosis marker Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), along with increased levels of ferrous ions and malondialdehyde (MDA), suggests that high glucose conditions may induce ferroptosis in HT22 cells. FNDC5/Irisin treatment effectively mitigates high glucose-induced neurotoxicity and ferroptosis in HT22 cells. Mechanistically, FNDC5/Irisin enhances cellular antioxidant capacity, regulates ACSL4 expression, and improves intracellular redox status, thereby inhibiting ferroptosis and increasing HT22 cell survival under high-glucose conditions. These results highlight the neuroprotective potential of FNDC5/Irisin in high glucose environments, offering a promising avenue for developing treatments for diabetes-related neurodegenerative diseases.

Glycogenic hepatopathy is associated with significant psychosocial consequences and health costs. Metabolic Dysfunction-Associated Steatotic Liver Disease and glycogenic hepatopathy are frequently confused as "fatty liver" when seen on ultrasonography. We wished to examine liver fat and glycogen content in groups defined based on metabolic and liver disease phenotypes.

This case-control study undertaken in a tertiary hospital used nuclear proton magnetic resonance spectroscopy (1H-MRS) to examine liver fat and glycogen content in five clinical groups, each containing five participants: 1. type 1 diabetes with glycogenic hepatopathy, 2. satisfactorily controlled type 1 diabetes with no liver disease, 3. poorly controlled type 1 diabetes without liver disease, 4. a control group of body mass index- and age-matched individuals without diabetes or liver disease, and 5. hepatic steatosis.

Fat content was highest in the hepatic steatosis (median 15.4 %, IQR 10.0-19.3) and glycogenic hepatopathy (median 6.5 %, IQR 4.5-9.1) groups and compared to both of these groups was lower in the control group (median 1.0 %, IQR 0.7-1.1, p 0.002 and 0.022), the T1DM group with satisfactory control (median 0.3 %, IQR 0.2-0.6, p < 0.001 and <0.001), and the T1DM group with poor control without liver disease (median 1.1 %, IQR 0.9-1.1, p 0.001 and 0.012). No participants from the type 1 diabetes poor control, type 1 diabetes satisfactory control or the no diabetes groups had 1H-MRS-diagnosed hepatic steatosis. 1H-MRS glycogen content could not be interpreted in the majority of those with glycogenic hepatopathy because of interference from the fat signal.

In cases diagnosed with glycogenic hepatopathy there may be significant concomitant fat accumulation, compounding the already elevated cardiovascular risk in this cohort. The technique of 1H-MRS has not been demonstrated to be useful for diagnosing glycogenic hepatopathy.

Diabetes, a metabolic disorder characterized by hyperglycemia, underscores the importance of normal pancreatic β-cell development and function in maintaining glucose homeostasis. Poly(A)-specific ribonuclease (PARN) serves as the principal regulator of messenger RNA (mRNA) stability, yet its specific role in pancreatic β cells remains unclear. This study utilizes mice with targeted PARN deficiency in β cells to elucidate this role. Notably, Parn conditional knockout mice present unaltered β-cell development and insulin sensitivity but reduced glucose-stimulated insulin secretion (GSIS). The observed outcomes are corroborated in NIT-1 cells. Furthermore, transcriptomic analyses reveal aberrant mRNA expression of genes crucial for insulin secretion in PARN-deficient β cells. Insights from linear amplification of complementary DNA ends and sequencing and coimmunoprecipitation experiments reveal an interaction between PARN and polypyrimidine tract-binding protein 1 (PTBP1), regulating the RNA stability of solute carrier family 30, member 8 (Slc30a8) and carbohydrate sulfotransferase 3 (Chst3). Interference with either PARN or PTBP1 disrupts this stability. These data indicate that PARN deficiency hampers GSIS and insulin maturation by destabilizing Slc30a8 and Chst3 RNAs. These findings provide compelling evidence indicating that PARN is a potential therapeutic target for enhancing insulin maturation and secretion.

To investigate the epidemiological characteristics of hypothyroidism in Qinghai Province, analyze its related influencing factors, establish the normal reference range of thyroid function, and explore the relationship between thyroid hormone (THs), thyroid stimulating hormone (TSH) and metabolic syndrome (MS) in Qinghai population within the normal range, so as to provide some scientific basis for the prevention and treatment of hypothyroidism in Qinghai Province.

A total of 2790 residents aged 18 and over from Qinghai were selected through stratified cluster random sampling. Data were collected via questionnaires, physical examinations, and laboratory tests.

1. A total of 2628 eligible residents in Qinghai were included in this study, and the total prevalence of hypothyroidism was 30.25%, among which the prevalence of subclinical hypothyroidism was 29.22%, and the prevalence of clinical hypothyroidism was 1.03%. 2. The prevalence of hypothyroidism in women was significantly higher than that in men (36.69% vs 24.30%); smoking and drinking were risk factors for hypothyroidism. 3. In the excluded subjects, 1544 were abnormal thyroid ultrasound, abnormal thyroid function and/or positive thyroid autoantibodies, and the remaining 1084 were reference populations. According to the reference population data, the 95% reference ranges of TSH, FT4, FT3 were 0.43-5.51 mIU/L, 11.0-20.4 pmol/L, 3.63-5.73 pmol/L, respectively. 4. In the normal thyroid function population in Qinghai, MS and its related components were positively correlated with FT3 and FT4 levels, but not significantly correlated with TSH levels.

1. The prevalence of hypothyroidism in adults in Qinghai is relatively high, accounting for about one-thirtieth of the total population. Smoking and drinking have a certain impact on the incidence of hypothyroidism. 2. It provides a reference range for the diagnosis of thyroid diseases in Qinghai province, which is different from that of reagent suppliers, and has certain promotion significance in the western region. 3. MS and its related components are positively correlated with FT3 and FT4 levels, but not with TSH levels in people with normal thyroid function in Qinghai. Early thyroid function screening is of great significance for the prevention of MS.

The cardiometabolic index (CMI) has emerged as a novel marker for evaluating the distribution and dysfunction of visceral adipose tissue, yet its correlation with numerous diseases, particularly new-onset chronic conditions, remains underexplored. Therefore, we aim to explore the association of cardiometabolic index (CMI) and new-onset chronic diseases.

The analysis utilized data from the China Health and Retirement Longitudinal Study, with a baseline in 2011 and follow-ups biennially until 2020. Fourteen new-onset chronic diseases were diagnosed based on self-report, and separate cohorts were created for each disease. CMI was calculated as triglycerides/high-density lipoprotein cholesterol multiplied by the waist-to-height ratio. Cox proportional hazards models were used to assess the association between CMI and new-onset chronic diseases, while restricted cubic spline (RCS) models were employed to explore potential nonlinear effects. Additional and sensitivity analyses included Kaplan-Meier survival curves, subgroup analyses, multiple imputations, and exclude outcome events at the first follow-up.

Higher levels of CMI were associated with an increased risk of new-onset hypertension (HR=1.05, 95% CI=1.04-1.06, P<0.001), diabetes (HR=1.08, 95% CI=1.06-1.09, P<0.001), dyslipidemia (HR=1.07, 95% CI=1.06-1.09, P<0.001), liver disease (HR=1.05, 95% CI=1.03-1.07, P<0.003), and stroke (HR=1.04, 95% CI=1.02-1.06, P<0.001), although the association with stroke was not significant after adjusting for confounders (HR=1.02, 95% CI=1.00-1.05, P=0.054). Participants in the highest quartile of CMI had a significantly higher risk of these diseases compared to those in the lowest quartile. RCS analyses showed a significant nonlinear relationship between CMI and the risk of these diseases above.

CMI showed a significant positive association with the risk of new-onset chronic diseases such as hypertension, diabetes, dyslipidemia, and liver disease. Future applications of CMI hold promise as an effective marker for early identification of chronic disease risk.

This study aimed to examine the cumulative effects of body mass index (BMI), body roundness index (BRI), pulse pressure (PP), triglycerides (TG), high-density lipoprotein cholesterol (HDL) and fasting plasma glucose (FPG) on Type 2 diabetes (T2D) morbidity.

A total of 78,456 participants aged older than 45 years were extracted from basic public health services in China. During the 2-year follow-up, 6,942 individuals had developed T2D. The binary logistic regression models and multinomial logistic regression models were conducted to investigate the effects of cumulative metabolic parameters on incident T2D, prediabetes regression and progression.

We found statistically deleterious impacts of exposure to high cumulative BMI, BRI, PP, TG and low cumulative HDL on T2D morbidity and prediabetes progression. Compared to the group with low cumulative of all five parameters, the adjusted ORs for new-onset T2D for participants presenting with 1-2, 3, and 4-5 elevated metabolic parameters were 1.41(1.31,1.52), 1.93(1.74,2.13) and 2.21(1.94,2.51), respectively. There was additive interaction between FPG level and cumulative metabolic parameters with T2D. Compared with participants with the lowest quartile of FPG and low cumulative of all 5 parameters, those with the highest quartile of FPG and high cumulative of 4-5 parameters had a 14.63 [95% CI (12.27, 17.42)] higher risk of incident T2D.

Participants with more numbers of high-cumulative metabolic parameters were associated with a higher risk of incident T2D and prediabetes progression. A high level of normal FPG could enhance these risks.

Type 2 diabetes (T2D) is a disease characterized by heterogeneously progressive loss of islet β cell insulin secretion usually occurring after the presence of insulin resistance (IR) and it is one component of metabolic syndrome (MS), and we named it metabolic dysfunction syndrome (MDS). The pathogenesis of T2D is not fully understood, with IR and β cell dysfunction playing central roles in its pathophysiology. Dyslipidemia, hyperglycemia, along with other metabolic disorders, results in IR and/or islet β cell dysfunction via some shared pathways, such as inflammation, endoplasmic reticulum stress (ERS), oxidative stress, and ectopic lipid deposition. There is currently no cure for T2D, but it can be prevented or in remission by lifestyle intervention and/or some medication. If prevention fails, holistic and personalized management should be taken as soon as possible through timely detection and diagnosis, considering target organ protection, comorbidities, treatment goals, and other factors in reality. T2D is often accompanied by other components of MDS, such as preobesity/obesity, metabolic dysfunction associated steatotic liver disease, dyslipidemia, which usually occurs before it, and they are considered as the upstream diseases of T2D. It is more appropriate to call "diabetic complications" as "MDS-related target organ damage (TOD)", since their development involves not only hyperglycemia but also other metabolic disorders of MDS, promoting an up-to-date management philosophy. In this review, we aim to summarize the underlying mechanism, screening, diagnosis, prevention, and treatment of T2D, especially regarding the personalized selection of hypoglycemic agents and holistic management based on the concept of "MDS-related TOD".