Development Of T2DM Research Articles

The Potential of Metabolomics as a Tool for Identifying Biomarkers Associated with Obesity and Its Complications: A Scoping Review.

Obesity and its related diseases, such as type 2 diabetes (T2DM), cardiovascular disease (CVD), and metabolic fatty liver disease (MAFLD), require new diagnostic markers for earlier detection and intervention. The aim of this study is to demonstrate the potential of metabolomics as a tool for identifying biomarkers associated with obesity and its comorbidities in every age group. The presented systematic review makes an important contribution to the understanding of the potential of metabolomics in identifying biomarkers of obesity and its complications, especially considering the influence of branched-chain amino acids (BCAAs), amino acids (AAs) and adipokines on the development of T2DM, MAFLD, and CVD. The unique element of this study is the combination of research results from the last decade in different age groups and a wide demographic range. The review was based on the PubMed and Science Direct databases, and the inclusion criterion was English-language original studies conducted in humans between 2014 and 2024 and focusing on the influence of BCAAs, AAs or adipokines on the above-mentioned obesity complications. Based on the PRISMA protocol, a total of 21 papers were qualified for the review and then assigned to a specific disease entity. The collected data reveal that elevated levels of BCAAs and some AAs strongly correlate with insulin resistance, leading to T2DM, MAFLD, and CVD and often preceding conventional clinical markers. Valine and tyrosine emerge as potential markers of MAFLD progression, while BCAAs are primarily associated with insulin resistance in various demographic groups. Adipokines, although less studied, offer hope for elucidating the metabolic consequences of obesity. The review showed that in the case of CVDs, there is still a lack of studies in children and adolescents, who are increasingly affected by these diseases. Moreover, despite the knowledge that adipokines play an important role in the pathogenesis of obesity, there are no precise findings regarding the correlation between individual adipokines and T2DM, MAFLD, or CVD. In order to be able to introduce metabolites into the basic diagnostics of obesity-related diseases, it is necessary to develop panels of biochemical tests that will combine them with classical markers of selected diseases.

Graves' Disease and the Risk of Type 2 Diabetes: A Korean Population-Based Study.

Background: Several meta-analyses have found no association between Graves' disease (GD) and an increased risk of incident diabetes; however, the intricate relationship between thyroid dysfunction and diabetes remains underexplored. In this study, we aimed to evaluate the risk of incident type 2 diabetes (T2DM) in a population newly diagnosed with GD, focusing on different treatment methods and treatment duration. Methods: This was a retrospective population-based study utilizing data from the Korean National Health Insurance database. We included 36,243 patients with GD and 36,243 controls, matched with age and sex. We calculated the incidence of T2DM among patients and controls based on treatment methods, such as medical therapy, radioactive iodine therapy (RAIT), and surgery. We examined the cumulative dose and duration of antithyroid drug (ATD) use for each patient. Results: The majority of patients (34,867, 96.2%) were treated with ATDs, followed by RAIT (1093 patients, 3%), and surgery (283 patients, 0.8%). After adjusting for age; sex; income; comorbidities, including hypertension, dyslipidemia, and cancer; body mass index; smoking; drinking; and exercise, patients with GD exhibited a higher risk of developing diabetes (hazard ratio [HR] = 1.13 [95% confidence interval 1.06-1.21]) than controls (5.1% vs. 4.5%, respectively). While the risk was the highest within the first six months after GD diagnosis (HR = 3.21), it was significant between six months and two years (HR = 1.36) and was comparable with the controls two years after GD diagnosis (HR = 0.93). A longer duration of ATD treatment and a higher cumulative dose were associated with an increased risk of diabetes. However, the risks for T2DM did not differ according to treatment modality or clinical outcomes, which was probably related to the small number of patients in each subgroup. Conclusions: Our findings highlight the negative impact of GD on the development of T2DM. Patients newly diagnosed with GD can be considered for diabetes screening to facilitate early detection and intervention.

Cross-Sectional Analysis of Hypoxia-Regulated miRNA-181a, miRNA-199a, HIF-1α, and SIRT1 in the Development of Type 2 Diabetes in Patients with Obstructive Sleep Apnea-Preliminary Study.

Introduction: Obstructive sleep apnea (OSA) is recognized as an independent risk factor for diabetes mellitus type 2 (T2DM) development, which is twice as common in patients with OSA compared to non-OSA patients. Objectives: This study aimed to investigate changes in oxygen metabolism and their role in T2DM development among OSA patients through epigenetic processes via miRNA-181a, miRNA-199a, and enzymatic processes via SIRT1 and HIF-1α. Methods: Based on polysomnography, apnea-hypopnea index and the presence of T2DM patients were divided into three groups: control group (n = 17), OSA group (n = 11), OSA&T2DM (n = 20) group. Total RNA was extracted from the buffy coat. Moreover, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) was counted. Results: Morning miRNA-181a expression was significantly higher in the OSA&T2DM group than in the control group: 67.618 vs. 32.685 (p = 0.036). Evening miRNA-199a expression was significantly higher in the OSA group than in the control group: 5.043 vs. 2.081 (p = 0.042), while its morning expression was significantly higher in the OSA&T2DM group when compared to the control: 4.065 vs. 1.605 (p = 0.036). MiRNA-181a evening expression revealed a negative correlation with the SIRT1 evening and morning expressions (R = -0.367, p = 0.010 and R = -0.405, p = 0.004, respectively). Moreover, morning miRNA-181a was positively correlated with HOMA-IR (R = 0.321, p = 0.034). MiRNA-199a evening expression presented a moderate positive correlation with the SIRT1 morning expressions (R = 0.48, p < 0.001) and HOMA-IR (R = 0.35, p = 0.02). Conclusions: Patients suffering from OSA and T2DM had an increased expression of miRNA-181a. Moreover, a negative correlation between miRNA-181a and SIRT1 expression was observed, while a correlation between miRNA-181a and insulin resistance was positive. This phenomenon might suggest a possible epigenetic pathway for an increased incidence of T2DM in OSA patients however further research is needed.

Alteration of methylation pattern and gene expression of FTO, PPARγ and Slc2a4 on pre-diabetes-induced BALB/c mice.

T2DM is a serious global health problem and usually caused by unhealthy diet, such diet with high carbohydrate or monosodium glutamate (MSG). In this study, we used the T2DM mice (BALB/c) model by exposing the mice with foods high in carbohydrate (HCD) or MSG (HMD) to determine the changes in molecular expression and methylation pattern of genes correlated to the development of T2DM. The data including clinical data, i.e. body weight, fasting blood glucose, and glucose tolerance, as well as gene expression, methylation pattern of glucose transport related gene (Slc2a4, FTO, and PPARγ) and also collagen deposition were measured. HCD and HMD diet for 18weeks failed to show any clinical development of T2DM. However, it was shown that both diets significantly altered the methylation pattern and gene expression. A decrease in the expression level of Slc2a4 accompanied with a decreased methylation level in its NF-κB attachment site was observed in both groups. In addition, both treatments also showed a decrease in the expression of PPARγ in contrast to its elevated methylation level. On the other hand, a significant increase in the expression of FTO was apparent. Furthermore, an increase in collagen deposition in both groups was also detected. Overall, this study showed that an alteration on the expression and methylation pattern of the genes that are associated with glucose transportation was observed in HCD and HMD despite having no T2DM clinical development. It can potentially be a new biomarker for detection of pre-diabetes.

Fatty acid composition evaluation of abdominal adipose tissue using chemical shiftencoded MRI: Association with diabetes.

This study investigated the association between the fatty acid composition of abdominal adipose tissue in NAFLD patients using chemical shift-encoded MRI and the development of insulin resistance and T2DM. We enrolled 231 subjects with NAFLD who underwent both abdominal magnetic resonance spectroscopy and chemical shift-encoded MRI: comprising of 49 T2DM patients and 182 subjects without. MRI- and MRS-based liver fat fraction was measured from a circular region of interest on the right lobe of the liver. The abdominal fatty acid compositions were measured at the umbilical level with chemical shift-encoded MRI. Bland-Altman analysis, Student's t test, Mann-Whitney U test, and Spearman correlation analysis were performed. The logistic regression was applied to identify the independent factors for T2DM. Then, the predictive performance was assessed by Receiver operating characteristic curve analyses. An excellent agreement was found between liver fat fraction measured by MRS and MRI. (slope = 0.8; bias =-0.92%). In, patients with T2DM revealed lower fractions of mono-unsaturated fatty acid (Fmufa) (33.68 ± 10.62 vs 38.62 ± 12.21, P =.0089) and higher fractions of saturated fatty acid (Fsfa) (34.11 ± 9.746 vs 31.25 ± 8.66, P =.0351) of visceral fat tissue compared with patients without. BMI, HDL-c, Fmufa and Fsfa of visceral fat were independent factors for T2DM. Furthermore, Fsfa-S% was positively correlated with liver enzyme levels (P =.003 and 0.04). However, Fmufa-V% was negatively correlated with fasting blood glucose, HbA1c and HOMA-IR (P =.004, P =.001 and P =.03 respectively). Hence, the evaluation of fatty acid compositions of abdominal fat tissue using chemical shift-encoded MRI may have a predictive value for T2DM in patients with NAFLD.

Influence of consuming coffee and other beverages in adolescence on risk of type 2 diabetes in adulthood.

Dietary strategies for type 2 diabetes (T2DM) prevention have mainly focused on solid foods and nutrients. Emanating evidence suggests that beverage consumption in adulthood may also influence T2DM development, whereas the role of beverages during adolescence remains unknow. To examine adolescent beverages consumption, and their changes from adolescence to adulthood in relation to T2DM risk in adulthood. This prospective cohort study, conducted within the Nurses' Health Study II (NHS II), enrolled 41,317 women who completed a food-frequency questionnaire (FFQ) regarding their diet in high school and had no diabetes, cardiovascular disease, or cancer at baseline (1997). Beverage consumption including coffee, tea, regular or diet soda, fruit juice or milk, was assessed using the FFQ. Cox proportional hazards models were utilized to estimate hazard ratios (HRs) for the association between beverage consumption in adolescence and risk of incident type 2 diabetes (T2DM) in adulthood, adjusting for potential confounders. During 725,650 person-years of follow-up, 2,844 participants developed T2DM. After adjustment for demographic, lifestyle and dietary risk factors, comparing ≥ 1 serving/day with non-consumers, adolescent coffee [HR, 0.86 (95% confidence interval: 0.75 to 0.98); P-trend = 0.02)] and orange juice [HR, 0.83 (0.71 to 0.96); P-trend = 0.0008)] consumption was associated with lower T2DM risk, whereas, regular soda [HR, 1.37 (1.20 to 1.57); P-trend < 0.0001)] and iced tea [HR, 1.41 (1.21 to 1.65); P-trend < 0.0001)] intake was associated with higher T2DM risk. Increased coffee intake from adolescence to adulthood in 1991 was associated with a lower T2DM risk [HR, 0.70 (0.61 to 0.80); P-trend < 0.0001), comparing ≥ + 3 servings/day with no change], whereas the opposite was observed for increased regular soda [HR, 1.20 (1.06 to 1.35); P-trend = 0.004), comparing ≥ + 1 or more servings/week with no change)] and diet soda consumption [HR, 1.59 (1.41 to 1.80); P-trend = 0.0002), comparing ≥ + 2 servings/day with no change]. Adolescent consumption of coffee or orange juice intake was associated with a lower risk of T2DM, whereas the opposite was observed for intake of regular soda or iced tea. In addition, increased coffee intake was associated with a lower diabetes risk, whereas the opposite was observed for regular or diet soda intake. These data highlight a potentially important role of beverage intake at early life in the etiology of diabetes during adulthood.

Protective Effect of High Adherence to Mediterranean Diet on the Risk of Incident Type-2 Diabetes in Subjects with MAFLD: The Di@bet.es Study.

Background/Objectives: Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) increases the risk of Type-2 Diabetes (T2DM). The Mediterranean diet (MD) has shown advantages in the management of MAFLD and preventing co-morbidities; however, its relationship with T2DM development in MAFLD has been less investigated. We aimed to evaluate the association of MD adherence with the risk of incident T2DM in the Spanish adult population with MAFLD and according to their weight gain at 7.5 years follow-up. Methods: A cohort of 714 participants (without weight increment: 377; with weight increment: 337) from the Di@bet.es cohort study with MAFLD and without T2DM at baseline were investigated. Anthropometric, sociodemographic, clinical data, and a survey on habits were recorded. OGTT and fasting blood biochemistry determinations were made. Baseline adherence to MD was estimated by the adapted 14-point MEDAS questionnaire and categorized as high and low adherence. Results: In total, 98 people developed T2DM at follow-up. The high adherence to MD was inversely associated with the development of T2DM in both the overall population (0.52 [0.31-0.87]) and subjects without weight gain at follow-up (0.35 [0.16-0.78]). Conclusions: Our results suggest the protective effect of high adherence to MD regarding the risk of T2DM in subjects with MAFLD, with this health benefit being more evident in men with the absence of weight gain. These results support the recommendations for MD use in these patients.

Association of antipsychotic drugs on type 2 diabetes mellitus risk in patients with schizophrenia: a population-based cohort and in vitro glucose homeostasis-related gene expression study

BackgroundType 2 diabetes mellitus (T2DM) and its related complications are associated with schizophrenia. However, the relationship between antipsychotic medications (APs) and T2DM risk remains unclear. In this population-based, retrospective cohort study across the country, we investigated schizophrenia and the effect of APs on the risk of T2DM, and glucose homeostasis-related gene expression.MethodsWe used information from the Longitudinal Health Insurance Database of Taiwan for individuals newly diagnosed with schizophrenia (N = 4,606) and a disease-free control cohort (N = 4,606). The differences in rates of development of T2DM between the two cohorts were assessed using a Cox proportional hazards regression model. The effects of APs on the expression of glucose homeostasis-related genes in liver and muscle cell lines were assessed using quantitative real-time PCR.ResultsAfter controlling potential associated confounding factors, the risk of T2DM was higher in the case group than that in the control group [adjusted hazard ratio (aHR), 1.80, p < 0.001]. Moreover, the likelihood of T2DM incidence in patients with schizophrenia without AP treatment (aHR, 2.83) was significantly higher than that in non-schizophrenia controls and those treated with APs (aHR ≤ 0.60). In an in vitro model, most APs did not affect the expression of hepatic gluconeogenesis genes but upregulated those beneficial for glucose homeostasis in muscle cells.ConclusionThis study demonstrates the impact of schizophrenia and APs and the risk of developing T2DM in Asian populations. Unmeasured confounding risk factors for T2DM may not have been included in the study. These findings may help psychiatric practitioners identify patients at risk of developing T2DM.

Decreased neutrophils are associated with reduced risk of Type 2 Diabetes Incidence: Results from the CORDIOPREV study.

Numerous studies have reported an association between neutrophils and T2DM, although this relationship remains unclear. This study aims to investigate the interaction of neutrophils and a dietary intervention on T2DM incidence after 60 months of follow-up. A comprehensive analysis was conducted on the framework of the CORDIOPREV study, which included 462 patients without T2DM at the beginning of the study. They were randomly assigned to either a Mediterranean or a low-fat diet, of whom 107 developed T2DM. Absolute neutrophil counts and other related-ratio, were measured. Kaplan-Meier curves showed that the lowest tertile of basal neutrophils was associated with a reduced likelihood of T2DM incidence when compared to the middle [HR=0.499 (95%CI, 0.287-0.866)] and the highest tertiles [HR=0.442 (95%CI, 0.255-0.768)] in overall population, after adjusting for clinical variables. This association only remained significant in patients who follow a Mediterranean diet when compared the lowest to the middle [HR=0.423 (95% CI, 0.213-0.842)] and the highest tertiles [HR=0.371 (95% CI, 0.182-0.762)]. The predictive capacity yielded an AUC of 0.711 (95%CI: 0.652-0.769), being neutrophils the most important variable in the in the model. Decrease in neutrophils over the 60 months were associated with increased insulin sensitivity index (ISI) (R=-0.31; p=0.019), particularly in patients who followed the Mediterranean diet. These findings suggest that monitoring neutrophils can help prevent the development of T2DM, as a reduction in neutrophil counts could be associated with improved insulin sensitivity. Following a Mediterranean diet might be a potential strategy to reduce the incidence of T2DM by lowering neutrophil levels. Further research is necessary to gain a deeper understanding regarding this mechanism.

Anti-Diabetic Effects of Oleuropein.

Background/Objectives: Oleuropein, a secoiridoid polyphenol found in olive oil as well as the fruit and leaves of the olive tree, has been reported to have antioxidant, cardioprotective, anti-inflammatory, anti-cancer, and anti-diabetic properties. Type 2 diabetes mellitus (TD2M) is a chronic metabolic disease characterized by impaired insulin action, termed insulin resistance. The development of T2DM is closely associated with obesity and chronic low-grade inflammation. In recent years, a rise in sedentary lifestyles and diets rich in refined carbohydrates and saturated fats has contributed to an increase in the prevalence of obesity and TD2M. Currently, the strategies for treating T2DM and its prevention lack efficacy and are associated with adverse side effects. Hence, there is an urgent need for novel treatment strategies, including naturally occurring compounds possessing hypoglycemic and insulin-sensitizing properties. Methods: This review summarizes the evidence of the anti-inflammatory and anti-diabetic properties of oleuropein from in vitro and in vivo animal studies, as well as the available clinical trials. Results: The existing evidence indicates that oleuropein may exert its anti-inflammatory effects by downregulating the levels of pro-inflammatory cytokines in hepatic and adipose tissue. Additionally, the evidence suggests that oleuropein targets skeletal muscle and enhances glucose uptake and its related protein signalling cascades, improving glucose tolerance and insulin sensitivity. Conclusions: Despite the evidence of oleuropein's anti-inflammatory and anti-diabetic potential, more animal and clinical studies are needed to proceed towards its clinical/therapeutic use for metabolic diseases confidently.

Investigations of associations between TNF-α promoter polymorphisms and genetic susceptibility to type 2 diabetes mellitus: A cross-sectional study in Chinese Han population.

Type 2 diabetes (T2DM) is characterised by insulin resistance and a relative shortage of insulin secretion. Tumour necrosis factor-α (TNF-α) plays an important role in insulin resistance by impairing insulin signal transduction. The variants of the TNF-α promoter region are considered to influence its transcription and are associated with the TNF-α level. Therefore, it is worth detecting the association of the variants in the TNF-α gene with the development of T2DM. The aim of this study was to investigate the association of five variants (rs1799964, rs1800630, rs1799724, rs1800629 and rs361525) in the TNF-α gene promoter region with T2DM in a Chinese Han population. A total of 713 subjects with T2DM and 751 nondiabetic subjects were genotyped using the TaqMan method. The associations of the five variants with the development of T2DM were evaluated. The associations of the five variant genotypes with metabolic traits in nondiabetic subjects were analysed. Our data showed that the A allele of rs1800629 could increase the risk of developing T2DM (p=.002, OR=1.563; 95% CI: 1.18-2.08). According to inheritance mode analysis, compared with the G/G genotype, the G/A+2A/A genotype of rs1800629 showed a risk effect on T2DM in the log-additive mode (p=.002, OR=1.56; 95% CI: 1.17-2.07). The haplotypes analysis identified that the rs1799724-rs1800629CA was associated with high risk of the development of T2DM (p=.002, OR=1.559, 95% CI: 1.173-2.072). Conversely, the rs1799724-rs1800629CG was a protective haplotype of T2DM (p=.001, OR=0.732, 95% CI: 0.607-0.884). Moreover, compared with the rs1799964 (T/T+C/T) genotype, the rs1799964 C/C genotype was associated with higher glycosylated haemoglobin (HbA1c) levels in nondiabetic subjects (p=.017). Our results revealed that the rs1800629 in the TNF-α gene promoter region was associated with T2DM in a Chinese Han population.

Role of toll-like receptor 4/mutant myeloid differentiation primary response 88/nuclear factor kappa-B mediated inflammation in diabetes mellitus with Northwest dryness syndrome.

To investigate the role of toll-like receptor 4 (TLR4)/mutant myeloid differentiation primary response 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway-mediated inflammation in diabetes mellitus with Northwest dryness syndrome. Rats were randomly divided into the normal control, type 2 diabetes (T2DM) model, Northwest dryness syndrome + T2DM (Northwest dryness), and simple internal dampness + T2DM (internal dampness) groups. Enzyme-linked immunosorbent assay was used to detect biochemical indexes and inflammatory factors. The histopathological observation was performed. Quantitative real-time polymerase chain reaction and Western blot analysis were used to detect the mRNA and protein expression levels, respectively. Compared with the T2DM group, the glycosylated hemoglobin A1c, insulin, glucose tolerance, the homeostasis model assessment of insulin resistance, tumor necrosis factor-α, interleukin 1β, interleukin 16, malondialdehyde, blood lipid, alanine aminotransferase, and aspartate aminotransferase were significantly elevated in the internal dampness group. Their levels were significantly elevated in the Northwest dryness group than in the T2DM and internal dampness groups. The superoxide dismutase, glutathione peroxidase, liver glycogen, and organ-to-weight ratio were significantly declined in the internal dampness group and the Northwest dryness group than in the T2DM group. However, these levels were elevated in the Northwest dryness group than in the internal dampness group. Moreover, the mRNA expression levels of interferon regulatory factor 5 and NF-κB p65, and the protein expression levels of TLR4, MyD88, and NF-κB were significantly higher in the internal dampness and the Northwest dryness groups than the T2DM group. Additionally, the mRNA and protein levels were significantly higher in the Northwest dryness group than in the internal dampness group. Northwest dryness syndrome-mediated TLR4/MyD88/NF-κB pathway and chronic inflammation might be associated with the occurrence and development of T2DM.

Cold Exposure Alleviates T2DM Through Plasma-Derived Extracellular Vesicles.

Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4-8°C) likely influences the organism's blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM. The effects of CT (4-8°C) or room temperature (RT, 22-25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot. CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting β-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect. Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.

Single nucleotide polymorphisms (SNPs) that are associated with obesity and type 2 diabetes among Asians: a systematic review and meta-analysis

Single nucleotide polymorphisms (SNPs) could increase the susceptibility of individuals to develop obesity and type 2 diabetes (T2DM). Obesity and T2DM are closely related pathophysiologically, thus similar SNPs could mediate both these diseases, but this is rarely reported. Furthermore, limited studies have been performed to summarize SNP data in the Asian population compared to the Western population. In this study, we aimed to summarize SNPs that are associated with the development of obesity and T2DM among Asian populations. We searched six literature databases and Review Manager (RevMan) was used for meta-analysis. The pooled odds ratios (ORs) and 95% CIs were calculated with a random effects model for the heterogeneity among studies. The pooled analysis showed that rs9939609 (FTO gene) and rs17782313 and rs571312 (MC4R gene) are associated with obesity with an odd ratio (OR) of 1.37, 1.36 and 1.29 respectively. For T2DM, five SNPs, rs7903146 and rs12255372 (TCF7L2 gene), rs13266634 and rs11558471 (SLC30A8 gene) and rs2283228 (KCNQ1 gene) have also shown strong associations with T2DM at OR of 1.64, 1.61, 1.22, 1.29 and 1.60 respectively. This data could be used to develop a gene screening panel for assessing obesity and T2DM susceptibility.

Molecular Aspects in the Development of Type 2 Diabetes and Possible Preventive and Complementary Therapies.

The incidence of diabetes, including type 2 diabetes (T2DM), is increasing sharply worldwide. To reverse this, more effective approaches in prevention and treatment are needed. In our review, we sought to summarize normal insulin action and the pathways that primarily influence the development of T2DM. Normal insulin action involves mitogenic and metabolic pathways, as both are important in normal metabolic processes, regeneration, etc. However, through excess energy, both can be hyperactive or attenuated/inactive leading to disturbances in the cellular and systemic regulation with the consequence of cellular stress and systemic inflammation. In this review, we detailed the beneficial molecular changes caused by some important components of nutrition and by exercise, which act in the same molecular targets as the developed drugs, and can revert the damaged pathways. Moreover, these induce entire networks of regulatory mechanisms and proteins to restore unbalanced homeostasis, proving their effectiveness as preventive and complementary therapies. These are the main steps for success in prevention and treatment of developed diseases to rid the body of excess energy, both from stored fats and from overnutrition, while facilitating fat burning with adequate, regular exercise in healthy people, and together with necessary drug treatment as required in patients with insulin resistance and T2DM.

Dietary pattern and gut microbiota in type 2 Diabetes Mellitus: A literature review

Nutrition has been identified as the primary modifiable factor The type of food, the macronutrient and micronutrient composition of the diet has distinct effects on gut microbiota and related metabolites. These impacts significantly influence mechanisms that regulate hyperglycemia and insulin resistance influencing gut microbiota remodeling and the development of T2DM. This study aimed to gather information on changes in gut microbiota composition (Lactobacillus and Bifidobacterium) and describe the beneficial or detrimental effects, impacts, and outcomes of macronutrients (carbohydrate, protein, and fat) and fiber on gut microbiota composition in T2DM. A total of 9 English articles were obtained from the results of the literature review. Lactobacillus and Bifidobacterium can positively reduce the blood glucose levels. Changes in the gut microbiota and its metabolites, which are influenced by carbohydrate, protein, lipid, and fiber intake, can worsen or decrease biochemical parameters and improve complications of T2DM. The conclusion of this literature review was gut microbiota can be crucial in the future treatment of diabetes mellitus, especially in combination with other therapeutic options.

Relationship between types and levels of free fatty acids, peripheral insulin resistance, and oxidative stress in T2DM: A case-control study.

Free Fatty Acids (FFAs) are vital for energy homeostasis and the pathogenesis of a variety of diseases, including diabetes. For the first time, we presumed and investigated the types and levels of FFAs and their links to Insulin Resistance (IR) and Oxidative Stress (OS) in T2DM. A case-control study was conducted on 60 individuals with diabetes, 60 prediabetics with IFG, and 60 control groups. A Gas Chromatography Flame Ionization Detector (GC-FID) was used to estimate FFAs, which were then classified based on length and saturation. Indeed, antioxidant parameters such as TAC, MDA levels, PON-1, SOD-3, and CAT activity were assessed. Higher levels of LCFFA, SFFA, USFFA, and total FFA were found in people with diabetes and prediabetes. These levels were also linked to higher levels of HOMA-IR, BMI, FBS, HbA1C, and MDA, but lower levels of antioxidants. Furthermore, adjusting the above FFAs with age, sex, and antihypertensive medication increased T2DM development. SCFFA and ω3/6 fatty acids had a negative relationship with HOMA-IR, FBS, and insulin and a positive relationship with TAC. Adjusted SCFFA reduces T2DM risk. According to our models, total FFA is utilized to diagnose diabetes (AUC = 83.98, cut-off > 919 μM) and SCFFA for prediabetes (AUC = 82.32, cut-off < 39.56 μM). Total FFA (≥ 776 μM), LCFFA (≥ 613 μM), SFFA (≥ 471 μM), and USFFA (≥ 398 μM) all increase the risk of T2DM by increasing OS, BMI, and HOMA-IR. On the other hand, SCFFAs (≥ 38.7 μM) reduce the risk of T2DM by reducing BMI, HOMA-IR, and OS. SCFFAs and total FFAs can be used for the diagnosis of prediabetes and diabetes, respectively.

Genetic Variants in Vitamin-D Metabolism Genes (rs1155563, rs12785878 and rs10500804) among Females with Type-2 Diabetes Mellitus in Saudi Arabia.

Hypovitaminosis D has shown to be linked with T2DM development and control in numerous studies. The association of SNPs in genes related to VitD metabolism with T2DM has not been sufficiently studied. Consequently, our aim in the present study was to explore the association between genetic variants in genes connected with VitD, mainly a SNP in GC (rs1155563), a SNP in DHCR7 (rs12785878) and a SNP in CYP2R1 (rs10500804) with glycaemic parameters in females with T2DM in Saudi Arabia. The cross-sectional study included 149 females (age 38-52 years) with T2DM from Jeddah, Saudi Arabia (September 2022-March 2023). Blood was extracted from the participants for biochemical tests including measuring VitD [25(OH)D] concentration, parameters of glycaemia (HbA1c, insulin, fasting glucose and insulin sensitivity indices including HOMA2-IR and HOMA2-%β), and for genomic DNA isolation. Sanger DNA sequencing was used to screen for VitD genetic polymorphisms (rs1155563, rs12785878 and rs10500804). Minor allele frequency for rs1155563C, rs12785878T and rs10500804G was 0.21, 0.23 and 0.37, respectively. Levels of 25(OH)D and glycaemic parameters as well did not show any significant difference between the genotypes of each SNP. This study showed lack of association of rs1155563 in GC, rs12785878 in DHCR7 and rs10500804 in CYP2R1 with VitD level primarily and with glycaemic parameters secondarily. Additional research is required to explore further other VitD genetic polymorphisms influencing T2DM which might lead consequently to genetically-based personalized management for T2DM.

Genetically predicted 1091 blood metabolites and 309 metabolite ratios in relation to risk of type 2 diabetes: a Mendelian randomization study.

Metabolic dysregulation represents a defining characteristic of Type 2 diabetes (T2DM). Nevertheless, there remains an absence of substantial evidence establishing a direct causal link between circulating blood metabolites and the promotion or prevention of T2DM. In addressing this gap, we employed Mendelian randomization (MR) analysis to investigate the potential causal association between 1,091 blood metabolites, 309 metabolite ratios, and the occurrence of T2DM. Data encompassing single-nucleotide polymorphisms (SNPs) for 1,091 blood metabolites and 309 metabolite ratios were extracted from a Canadian Genome-wide association study (GWAS) involving 8,299 participants. To evaluate the causal link between these metabolites and Type 2 diabetes (T2DM), multiple methods including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode were employed. p-values underwent correction utilizing False Discovery Rates (FDR). Sensitivity analyses incorporated Cochran's Q test, MR-Egger intercept test, MR-PRESSO, Steiger test, leave-one-out analysis, and single SNP analysis. The causal effects were visualized via Circos plot, forest plot, and scatter plot. Furthermore, for noteworthy, an independent T2DM GWAS dataset (GCST006867) was utilized for replication analysis. Metabolic pathway analysis of closely correlated metabolites was conducted using MetaboAnalyst 5.0. The IVW analysis method utilized in this study revealed 88 blood metabolites and 37 metabolite ratios demonstrating a significant causal relationship with T2DM (p < 0.05). Notably, strong causal associations with T2DM were observed for specific metabolites: 1-linoleoyl-GPE (18:2) (IVW: OR:0.930, 95% CI: 0.899-0.962, p = 2.16 × 10-5), 1,2-dilinoleoyl-GPE (18:2/18:2) (IVW: OR:0.942, 95% CI: 0.917-0.968, p = 1.64 × 10-5), Mannose (IVW: OR:1.133, 95% CI: 1.072-1.197, p = 1.02 × 10-5), X-21829 (IVW: OR:1.036, 95% CI: 1.036-1.122, p = 9.44 × 10-5), and Phosphate to mannose ratio (IVW: OR:0.870, 95% CI: 0.818-0.926, p = 1.29 × 10-5, FDR = 0.008). Additionally, metabolic pathway analysis highlighted six significant pathways associated with T2DM development: Valine, leucine and isoleucine biosynthesis, Phenylalanine metabolism, Glycerophospholipid metabolism, Alpha-Linolenic acid metabolism, Sphingolipid metabolism, and Alanine, aspartate, and glutamate metabolism. This study identifies both protective and risk-associated metabolites that play a causal role in the development of T2DM. By integrating genomics and metabolomics, it presents novel insights into the pathogenesis of T2DM. These findings hold potential implications for early screening, preventive measures, and treatment strategies for T2DM.

Research progress of traditional Chinese medicines and active ingredients targeting M1/M2 macrophage polarization balance in intervening obese with type 2 diabetes

Type 2 diabetes(T2DM) is a metabolic disorder marked by glucose toxicity, lipotoxicity, insulin resistance, and other pathological manifestations, representing a pressing global health concern. Obesity stands out as a pivotal risk factor for T2DM development. When combined with T2DM, obesity exacerbates insulin resistance and metabolic abnormalities. The disturbance in the inflammatory microenvironmental balance between adipose and pancreatic islet tissue emerges as a significant contributor to obese with T2DM development. Macrophages play a crucial role in maintaining immune homeostasis and responding to inflammation in adipose and pancreatic islet tissue. Individuals with obese with T2DM exhibit an imbalanced M1/M2 macrophage polarization, contributing to the progression of glycolipid metabolism abnormalities. Hence, restoring the equilibrium of macrophage polarization becomes imperative for obese with T2DM treatment. Scientific researchers have demonstrated that traditional Chinese medicine(TCM) therapies can effectively modulate macrophage polarization, offering a viable approach for treating obese with T2DM. In light of the existing evidence, this study systematically reviewed the research progress of TCM targeting the balance of M1/M2 macrophage polarization to ameliorate obese with T2DM, so as to furnish evidence supporting the clinical diagnosis and treatment of obese with T2DM with TCM while also contributing to the exploration of the biological basis of obese with T2DM.