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Aims: Our study, employing a multi-omics approach, aimed to delineate the distinct gut microbiota and metabolic characteristics in individuals under 30 with unclassified diabetes, thus shedding light on the underlying pathophysiological mechanisms Methods: This age- and sex-matched case-control study involved 18 patients with unclassified diabetes, 18 patients with classic type 1 diabetes, 13 patients with type 2 diabetes, and 18 healthy individuals. Metagenomics facilitated the profiling of the gut microbiota, while untargeted liquid chromatography-mass spectrometry was used to quantify the serum lipids and metabolites. Results: Our findings revealed a unique gut microbiota composition in unclassified diabetes patients, marked by a depletion of Butyrivibrio proteoclasticus and Clostridium and an increase in Ruminococcus torques and Lachnospiraceae bacterium 8_1_57FAA. Comparative analysis identified the combined marker panel of five bacterial species, seven serum biomarkers, and three clinical parameters could differentiate patients with UDM from HCs with an AUC of 0.94 (95% CI 0.85–1). Notably, the gut microbiota structure of patients with unclassified diabetes resembled that of type 2 diabetes patients, especially regarding disrupted lipid and branched-chain amino acid metabolism. Conclusions: Despite sharing certain metabolic features with type 2 diabetes, unclassified diabetes presents unique features. The distinct microbiota and metabolites in unclassified diabetes patients suggest a significant role in modulating glucose, lipid, and amino acid metabolism, potentially influencing disease progression. Further longitudinal studies are essential to explore therapeutic strategies targeting the gut microbiota and metabolites to modify the disease trajectory. [ABSTRACT FROM AUTHOR]

Introduction: Women with type 2 diabetes mellitus (T2DM) face a greater risk of cardiovascular disease (CVD) and encounter challenges in managing cardiovascular risk factors (CVRF); however, limited data are available in individuals with newlydiagnosed T2DM. Methods: This study aimed to examine differences between women and men at the onset of T2DM in terms of clinical characteristics, glycaemic status, and CVRF management. This was a retrospective cohort study including subjects with newly-diagnosed T2DM from the System for the Development of Research in Primary Care (SIDIAP) database in Catalonia (Spain). Sex differences (Dif) were assessed at baseline and 1-year post-diagnosis, by calculating the absolute difference of means or proportions. Results: A total of 13,629 subjects with newly-diagnosed T2DM were analyzed. Women were older and had a higher BMI than men. At baseline, women had higher total cholesterol [Dif (95%CI) 10 mg/dL (9.1/10.8)] and low-density lipoprotein cholesterol (LDL-c) [Dif (95%CI) 7 mg/dL (6.3/7.7)], while men had higher rates of smoking and alcohol intake. Lipid target achievement was lower in women, in both primary prevention (LDL-c < 100 mg/dL) [Dif (95%CI) -7.3 mg/dL (-10.5/-4.1)] and secondary prevention (LDL-c < 70 mg/dL) [Dif (95%CI) -8.3 mg/dL (-17.3/0.7)], along with lower statin and antiplatelet prescriptions, especially one year after diagnosis. Changes in clinical and laboratory data one year postdiagnosis revealed that, in the primary prevention group, men experienced greater improvements in total cholesterol, LDL-c and triglycerides, while women had less success in achieving CVRF control targets compared to men. Additionally, cardiovascular events, such as coronary artery disease and peripheral artery disease increased more in men than in women within the first year of diagnosis, especially in primary prevention subjects. Conclusion: Differences between men and women CVRF are already apparent at the onset of T2DM, particularly in primary prevention, with notable differences in lipid profile and target level attainment. [ABSTRACT FROM AUTHOR]

Introduction: Yu--Ye Tang (YYT) is a classical formula widely used in treatment of type 2 diabetes mellitus (T2DM). However, the specific mechanism of YYT in treating T2DM is not clear. Methods: The aim of this study was to investigate the therapeutic effect of YYT on T2DM by establishing a rat model of T2DM. The mechanism of action of YYT was also explored through investigating gut microbiota and serum metabolites. Results: The results indicated YYT had significant therapeutic effects on T2DM. Moreover, YYT could increase the abundance of Lactobacillus, Candidatus_ Saccharimonas, UCG-005, Bacteroides and Blautia while decrease the abundance of and Allobaculum and Desulfovibrio in gut microbiota of T2DM rats. Nontargeted metabolomics analysis showed YYT treatment could regulate arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, phenylalanine metabolism, steroid hormone biosynthesis, terpenoid backbone biosynthesis, tryptophan metabolism, and tyrosine metabolism in T2DM rats. Discussion: In conclusion, our research showed that YYT has a wide range of therapeutic effects on T2DM rats, including antioxidative and anti-inflammatory effects. Furthermore, YYT corrected the altered gut microbiota and serum metabolites in T2DM rats. This study suggests that YYT may have a therapeutic impact on T2DM by regulating gut microbiota and modulating tryptophan and glycerophospholipid metabolism, which are potential key pathways in treating T2DM. [ABSTRACT FROM AUTHOR]

Thyroid disorders are clinically characterized by alterations of L-3,5,3’,5’- tetraiodothyronine (T4), L-3,5,3’-triiodothyronine (T3), and/or thyroidstimulating hormone (TSH) levels in the blood. The most frequent thyroid disorders are hypothyroidism, hyperthyroidism, and hypothyroxinemia. These conditions affect cell differentiation, function, and metabolism. It has been reported that 40% of the world’s population suffers from some type of thyroid disorder and that several factors increase susceptibility to these diseases. Among them are iodine intake, environmental contamination, smoking, certain drugs, and genetic factors. Recently, the intestinal microbiota, composed of more than trillions of microbes, has emerged as a critical player in human health, and dysbiosis has been linked to thyroid diseases. The intestinal microbiota can affect host physiology by producing metabolites derived from dietary fiber, such as short-chain fatty acids (SCFAs). SCFAs have local actions in the intestine and can affect the central nervous system and immune system. Modulation of SCFAsproducing bacteria has also been connected to metabolic diseases, such as obesity and diabetes. In this review, we discuss how alterations in the production of SCFAs due to dysbiosis in patients could be related to thyroid disorders. The studies reviewed here may be of significant interest to endocrinology researchers and medical practitioners. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to examine the effects of leptin and melatonin intervention on bone metabolism in ovariectomize (OVX) rodents, as well as their potential mechanisms of action. Methods: Prepare anOVXmodel of osteoporosis in rodents and validate themodel by collecting bilateral tibia samples for Micro-CT scanning and histological analysis. A control group of normal size, the OVX group, the OVX+Sema4D (Semaphorin 4D) group, the OVX+Sema4D+Leptin group, the OVX+Sema4D+ Melatonin(MT) group and the OVX+Sema4D+Leptin+ MT group were the experimental groups. Adenovirus vector construction and tibial medullary injection validation were conducted in accordance with the aforementioned experimental groups. Four groups of rats were injected with the Sema4D overexpression adenovirus vector into the tibial medullary cavity, and two groups were injected with the Leptin overexpression adenovirus vector. The repair of osteoporosis was observed using micro-CT and histological analysis. Immunohistochemical detection of bone morphogenetic protein-2 (BMP-2) expression in bone tissue was employed to ascertain the amount of osteoclasts in the upper tibial metaphysis, utilizing TRAP (tartrate-resistant acid phosphatase) staining. Results: Increased levels of BV/TV, Tb.N, BMD, and BMC were seen in the OVX+ Sema4D+Leptin, OVX+ Sema4D+MT, and OVX+ Sema4D+Leptin+ MT groups compared to the OVX group, whereas Tb. Sp levels were lowered. When compared to the Sema4D overexpression group, the trabecular bone structure of the OVX + Sema4D + Leptin, OVX + Sema4D + MT, and OVX + Sema4D + Leptin + MT groups is largely intact, tends to be closer, and the amount of trabecular bone increases. The OVX + Sema4D + Leptin + MT group in particular.The expression of BMP-2 was dramatically upregulated (p<0.05), the number of TRAP-stained osteoclasts was significantly reduced (p<0.05), and BALP(bone-derived alkaline phosphatase) and TRAP-5b(tartrate-resistant acid phosphatase-5b) activities were significantly downregulated (p<0.05). Conclusion: In rats with osteoporosis, leptin and melatonin can be seen to augment the trabecular microstructure of the bone, augment bone growth, diminish trabecular harm, and mend the bone. The combined effect is more powerful. [ABSTRACT FROM AUTHOR]

Background: The prevalence of type 2 diabetes (T2D) continues to increase in the Americas. Identifying people at risk for T2D is critical to the prevention of T2D complications, especially cardiovascular disease. This study gauges the ability to implement large population-based organized screening campaigns in 19 Latin American and Caribbean countries to detect people at risk for T2D using the Finnish Diabetes Risk Score (FINDRISC). Methods: This cross-sectional descriptive analysis uses data collected in a sample of men and women 18 years of age or older who completed FINDRISC via eHealth during a Guinness World Record attempt campaign between October 25 and November 1, 2021. FINDRISC is a non-invasive screening tool based on age, body mass index, waist circumference, physical activity, daily intake of fruits and vegetables, history of hyperglycemia, history of antihypertensive drug treatment, and family history of T2D, assigning a score ranging from 0 to 26 points. A cut-off point of = 12 points was considered as high risk for T2D. Results: The final sample size consisted of 29,662 women (63%) and 17,605 men (27%). In total, 35% of subjects were at risk of T2D. The highest frequency rates (FINDRISC = 12) were observed in Chile (39%), Central America (36.4%), and Peru (36.1%). Chile also had the highest proportion of people having a FINDRISC =15 points (25%), whereas the lowest was observed in Colombia (11.3%). Conclusions: FINDRISC can be easily implemented via eHealth technology over social networks in Latin American and Caribbean populations to detect people with high risk for T2D. Primary healthcare strategies are needed to perform T2D organized screening to deliver early, accessible, culturally sensitive, and sustainable interventions to prevent sequelae of T2D, and reduce the clinical and economic burden of cardiometabolic-based chronic disease. [ABSTRACT FROM AUTHOR]

Lifestyle changes have made metabolic disorders as one of the major threats to life. Growing evidence demonstrates that obesity and diabetes disrupt the reproductive system by affecting the gonads and the hypothalamus-pituitarygonadal (HPG) axis. Apelin, an adipocytokine, and its receptor (APJ) are broadly expressed in the hypothalamus nuclei, such as paraventricular and supraoptic, where gonadotropin-releasing hormone (GnRH) is released, and all three lobes of the pituitary, indicating that apelin is involved in the control of reproductive function. Moreover, apelin affects food intake, insulin sensitivity, fluid homeostasis, and glucose and lipid metabolisms. This review outlined the physiological effects of the apelinergic system, the relationship between apelin and metabolic disorders such as diabetes and obesity, as well as the effect of apelin on the reproductive system in both gender. The apelin-APJ system can be considered a potential therapeutic target in the management of obesityassociated metabolic dysfunction and reproductive disorders. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined the role of iodine in extrathyroidal function. Recent research has shown an association between iodine and metabolic syndromes (MetS) in Chinese and Korean populations, but the link in the American participants remains unknown. Purpose: This study aimed to examine the relationship between iodine status and metabolic disorders, including components associated with metabolic syndrome, hypertension, hyperglycemia, central obesity, triglyceride abnormalities, and low HDL. Methods: The study included 11,545 adults aged = 18 years from the US National Health and Nutrition Examination Survey (2007-2018). Participants were divided into four groups based on their iodine nutritional status(ug/L), as recommended by the World Health Organization: low UIC, < 100; normal UIC, 100-299; high UIC, 300-399; and very high, = 400. The Odds ratio (OR) for MetS basing the UIC group was estimated using logistic regression models for our overall population and subgroups. Results: Iodine status was positively associated with the prevalence of MetS in US adults. The risk of MetS was significantly higher in those with high UIC than in those with normal UIC [OR: 1.25; 95% confidence intervals (CI),1.016-1.539; p = 0.035). The risk of MetS was lower in the low UIC group (OR, 0.82; 95% CI: 0.708-0.946; p = 0.007). There was a significant nonlinear trend between UIC and the risk of MetS, diabetes, and obesity in overall participants. Participants with high UIC had significantly increased TG elevation (OR, 1.24; 95% CI: 1.002-1.533; P = 0.048) and participants with very high UIC had significantly decreased risk of diabetes (OR, 0.83; 95% CI: 0.731-0.945, p = 0.005). Moreover, subgroup analysis revealed an interaction between UIC and MetS in participants aged < 60 years and = 60 years, and no association between UIC and MetS in older participants aged = 60 years. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is one of the most common chronic autoimmune diseases, characterized by absolute insulin deficiency caused via inflammatory destruction of the pancreatic b-cell. Genetic, epigenetic, and environmental factors play a role in the development of diseases. Almost 1/5 of cases involve people under the age of 20. In recent years, the incidence of both T1D and obesity has been increasing, especially among children, adolescents, and young people. In addition, according to the latest study, the prevalence of overweight or obesity in people with T1D has increased significantly. The risk factors of weight gain included using exogenous insulin, intensifying insulin therapy, fear of hypoglycemia and related decrease in physical activity, and psychological factors, such as emotional eating and binge eating. It has also been suggested that T1D may be a complication of obesity. The relationship between body size in childhood, increase in body mass index values in late adolescence and the development of T1D in young adulthood is considered. Moreover, the coexistence of T1D and T2D is increasingly observed, this situation is called double or hybrid diabetes. This is associated with an increased risk of the earlier development of dyslipidemia, cardiovascular diseases, cancer, and consequently a shortening of life. Thus, the purpose of this review was to summarize the relationships between overweight or obesity and T1D. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the use of once-weekly semaglutide in a real population of people with type 2 diabetes mellitus (T2DM) in three Spanish hospitals. Method: An observational, retrospective and multicenter clinical study was designed that included 166 participants with T2DM, distinguishing between a group naïve to GLP-1RA (n=72) and another switching from another GLP-1RA (n=94), all managed in the outpatient clinical setting. The primary endpoint was the change in HbA1c from baseline to the end of the study. The secondary endpoints included changes in body weight and the proportion of people with T2DM, achieving HbA1c <7.0% and body weight loss >5%. Results: After 24 months of follow-up, the reductions in HbA1c were -0.91 ± 0.7% (p<0.001) in the total cohort, -1.13 ± 1.38% (p<0.019) for GLP-1RA-naïve participants, and -0.74 ± 0.9% (p<0.023) for GLP-1RA-experienced participants. Body weight reductions were -12.42 ± 9.1% in GLP-1RA-naïve participants vs. -7.65 ± 9.7% in GLP-1RA-experienced participants (p<0.001). In the total cohort, 77.1% reached the objective of an HbA1c level <7%, and 12.7% reached between 7.1% and 7.5%. Additionally, 66.9% achieved a weight reduction ≥5%. Of all cohort, 90% received 1 mg of semaglutide once a week. The reported adverse events were consistent with the known safety profile of semaglutide. Conclusions: In routine clinical practice in Spain, the use of semaglutide once a week was associated with statistically significant and clinically relevant improvements in HbA1c and body weight in a wide range of adults with T2DM, without notable adverse effects, which supports real-world use. [ABSTRACT FROM AUTHOR]

The prevalence of overweight and obesity among youth patients with diabetes type 1 is increasing. It is estimated, that even up to 35% of young patients with this type of diabetes, considered so far to be characteristic for slim figure, are overweight or even obese. General increase of obesity in children's population complicates differential diagnosis of the type of diabetes in youths. Coexistence of obesity has clinical implications for all stages of diabetes course. It is confirmed that obesity is the risk factor for autoimmune diabetes, and is connected with the earlier onset of diabetes in predisposed patients. Many diabetic patients with obesity present additional risk factors for macroangiopathy, and are recognised to present metabolic syndrome, insulin resistance, and typical for diabetes type 2 - polycystic ovary syndrome, or non-alcoholic fatty liver disease. The prevalence of obesity rises dramatically in adolescence of diabetic child, more often in girls. It has negative impact on metabolic control, glycaemic variability and insulin demand. The risk for microangiopathic complications increases as well. The treatment is difficult and includes not only insulinotherapy and non-pharmacological trials. Recently treatment of insulin resistance with biguanids, and treatment with typical for type 2 new diabetes drugs like GLP-1 analogues, SGLT-2 receptor inhibitors, or even cases of bariatric surgery also has been reported. [ABSTRACT FROM AUTHOR]

Several publications have raised the issue that the development of diabetes precedes the alteration of the microbiome (dysbiosis) and the role of environmental factors. Antibiotic use induces dysbiosis, and we wanted to estimate the associations between the consumption of antibiotics and the prevalence of diabetes (both types 1 and 2; T1D and T2D, respectively) in European countries. If such an association exists, the dominant use antibiotic classes might be reflected in the prevalence rates of T1D and T2D in different countries. Comparisons were performed between the prevalence of diabetes estimated for 2019 and featured in the Diabetes Atlas and the average yearly consumption of antibiotic classes between 2010 and 2109, calculated from the European Centre for Disease Prevention and Control (ECDC) yearly reports on antibiotic consumption in Europe. Pearson's correlation and variance analyses were used to estimate the possible relationship. Strong positive (enhancer) associations were found between the prevalence of T1D and the consumption of tetracycline (J01A: p = 0.001) and the narrow-spectrum penicillin (J01CE: p = 0.006; CF: p = 0.018). A strong negative (inhibitor) association was observed with broad-spectrum, beta-lactamase-resistant penicillin (J01CR: p = 0.003), macrolide (J01F: p = 0.008), and quinolone (J01M: p = 0.001). T2D showed significant positive associations with cephalosporin (J01D: p = 0.048) and quinolone (J01M: p = 0.025), and a non-significant negative association was detected with broad-spectrum, beta-lactamase-sensitive penicillin (J01CA: p = 0.067). Countries showing the highest prevalence rates of diabetes (top 10) showed concordance with the higher consumption of "enhancer" and the lower consumption of "inhibitor" antibiotics (top 10), as indicated by variance analysis. Countries with high prevalence rates of T1D showed high consumption of tetracycline (p = 0.015) and narrow-spectrum, beta-lactamase sensitive penicillin (p = 0.008) and low consumption of "inhibitor" antibiotics [broad-spectrum, beta-lactamase-resistant, combination penicillin (p = 0.005); cephalosporin (p = 0.036); and quinolone (p = 0.003)]. Countries with high prevalence rates of T2D consumed more cephalosporin (p = 0.084) and quinolone (p = 0.054) and less broad-spectrum, beta-lactamase-sensitive penicillin (p = 0.012) than did other countries. The development of diabetes-related dysbiosis might be related to the higher consumption of specific classes of antibiotics, showing positive (enhancer) associations with the prevalence of diabetes, and the low consumption of other classes of antibiotics, those showing negative (inhibitory) associations. These groups of antibiotics are different in T1D and T2D. [ABSTRACT FROM AUTHOR]

Nowadays, diabetes and obesity are two main health-threatening metabolic disorders in the world, which increase the risk for many chronic diseases. Apelin, a peptide hormone, exerts its effect by binding with angiotensin II protein J receptor (APJ) and is considered to be linked with diabetes and obesity. Apelin and its receptor are widely present in the body and are involved in many physiological processes, such as glucose and lipid metabolism, homeostasis, endocrine response to stress, and angiogenesis. In this review, we summarize the literatures on the role of the Apelin–APJ system in diabetes and obesity for a better understanding of the mechanism and function of apelin and its receptor in the pathophysiology of diseases that may contribute to the development of new therapies. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to compare the diagnostic accuracy of the metabolic syndrome with the Finnish Diabetes Risk Score (FINDRISC) to screen for type 2 diabetes mellitus (T2DM) in a Shanghai population. Methods: Participants aged 25-64 years were recruited from a Shanghai population from July 2019 to March 2020. Each participant underwent a standard metabolic work-up, including clinical examination with anthropometry. Glucose status was tested using hemoglobin A1c (HbAlc), 2h-post-load glucose (2hPG), and fasting blood glucose (FBG). The FINDRISC questionnaire and the metabolic syndrome were examined. The performance of the FINDRISC was assessed using the area under the receiver operating characteristic curve (AUC-ROC). Results: Of the 713 subjects, 9.1% were diagnosed with prediabetes, whereas 5.2% were diagnosed with T2DM. A total of 172 subjects had the metabolic syndrome. A higher FINDRISC score was positively associated with the prevalence of T2DM and the metabolic syndrome. Multivariable linear regression analysis demonstrated that the FINDRISC had a linear regression relationship with 2hPG levels (b'= 036, p < 0.0001). The AUC-ROC of the FINDRISC to identify subjects with T2DM among the total population was 0.708 (95% CI 0.639–0.776), the sensitivity was 44.6%, and the specificity was 90.1%, with 11 as the cut-off point. After adding FBG or 2hPG to the FINDRISC, the AUC-ROC among the total population significantly increased to 0.785 (95% CI 0.671–0.899) and 0.731 (95% CI 0.619–0.843), respectively, while the AUC-ROC among the female group increased to 0.858 (95% CI 0.753–0.964) and 0.823 (95% CI 0.730–0.916), respectively (p < 0.001). The AUC-ROC of the metabolic syndrome to identify subjects with T2DM among the total and female population was 0.805 (95% CI 0.767–0.844) and 0.830 (95% CI 0.788–0.872), respectively, with seven as the cut-off point. Conclusions: The metabolic syndrome performed better than the FINDRISC model. The metabolic syndrome and the FINDRISC with FBG or 2hPG in a two-step screening model are both efficacious clinical practices for predicting T2DM in a Shanghai population. [ABSTRACT FROM AUTHOR]

The optimal maternal levels of thyroid hormones (TH) during the first trimester of gestation have not been established, nor has the ideal moment to initiate levothyroxine treatment (LT) to improve the evolution of gestation and fetal development. Cut-off points for Thyroid-stimulating hormone (TSH) <2.5 µIU/mL and free thyroxine (FT4)>7.5 pg/mL have been recommended. There are no data on whether initiation of LT <9th Gestational Week (GW) can have a favourable impact. Objective: To define the TSH/FT4 percentiles corresponding with 2.5 µIU/mL and 7.5 pg/mL levels, respectively, at GW8 (Study 1), and evaluate the effects of protocol-based LT before GW9 on gestation evolution, in women with TSH ≥2.5 µIU/mL and/or FT4≤ 7.5 pg/mL (study 2). Subjects: 2768 consecutive pregnant women attending the first gestational visit from 2013-2014 and 3026 from 2015-2016 were eligible for Study I and 2 respectively. A final 2043 (study 1) and 2069 (study 2) women were assessed in these studies. Results: Study 1: The FT4 level of 7.5 pg/mL corresponds with the 17.9th percentile, a TSH level of 2.5 µIU/mL with the 75.8th. Women with TSH ≥2.5 µIU/mL had a history of fetal losses more frequently than those <2.5 (OR 2.33 (95%CI): 1.58-3.12), as did those with FT4 ≤7.5 pg/ml compared to those >7.5 (OR 4.81; 3.25-8.89). Study 2: A total of 1259 women had optimal TSH/FT4 levels (Group 1), 672 (32.4%, Group 2) had suboptimal TSH or T4l, and 138 (6.7%, Group 3) had suboptimal values of both. 393 (58.5%) in Group 2 and 88 (63.8%) in Group 3 started LT before GW9. Mean (SD) GW24 levels were TSH: 1.96 ± 1.22 µIU/mL and FT4: 7.07 ± 1.25 pg/mL. The highest FT4 value was 12.84 pg/mL. The adjusted risk for an adverse event if LT was started early was 0.71 (0.43-0.91) for Group 2 and 0.80 (0.66-0.94) for Group 3. Conclusions: Early LT in women with suboptimum levels of TSH/FT4 (≥2.5µIU/mL/≤7.5 pg/ml) at or before GW9 is safe and improves gestation progression. These data support the recommendation to adopt these cut-off points for LT initiation, which should be started as early as possible. [ABSTRACT FROM AUTHOR]

Background: Metabolically healthy obese (MHO) individuals and their association with cardiometabolic diseases have remained controversial. We aimed to explore the risk of incident heart failure (HF) based on the baseline metabolic health and obesity status as well as their transition over 2 years. Methods: The Korean National Health Insurance Service-National Health Screening Cohort data of 514,886 participants were analyzed. Obesity was defined as BMI ≥25 kg/m2 according to the Korean Centers for Disease Control and Prevention. The metabolic health and obesity status were evaluated at baseline and after two years. Study participants were followed to either the date of newly diagnosed HF or the last follow-up visit, whichever occurred first. Results: The MHO group comprised 9.1% of the entire population and presented a better baseline metabolic profile than the metabolically unhealthy non-obese (MUNO) and metabolicavlly unhealthy obese (MUO) groups. During the median 71.3 months of follow-up, HF developed in 5,406 (1.5%) participants. The adjusted hazard ratios [HRs (95% CI)] of HF at baseline compared with the metabolically healthy non-obese (MHNO) group were 1.29 [1.20–1.39], 1.37 [1.22–1.53], and 1.63 [1.50–1.76] for MUNO, MHO, and MUO groups, respectively. With the stable MHNO group as reference, transition into metabolically unhealthy status (MUNO and MUO) increased the risk of HF, regardless of the baseline status. Subjects who were obese at both baseline and follow-up showed an increased risk of HF, regardless of their metabolic health status. Conclusions: Metabolic health and obesity status and their transition can predict the risk of incident HF. Losing metabolic health in baseline non-obese and obese individuals and remaining obese in baseline obese individuals showed a significantly increased risk of incident HF. Maintaining good metabolic health and a lean body may prevent the development of HF. [ABSTRACT FROM AUTHOR]

Aims: Abnormal glucose regulation, which can present as diabetes and prediabetes, has become one of the most common chronic conditions. However, sex differences in the prevalence of and factors associated with abnormal glucose regulation remain unclear. Thus, we aimed to explore sex differences in the prevalence of and factors associated with abnormal glucose regulation in low-income adults in China aged ≥50 years with normal fasting plasma glucose levels. Materials and Methods: A total of 2,175 individuals aged ≥50 years with normal fasting plasma glucose levels were recruited into this study. After an overnight fast of at least 10 h, individuals underwent an oral glucose tolerance test. Fasting and 2-h plasma glucose levels were measured to determine the state of glucose regulation. Results: Women were more likely than men to have isolated-impaired glucose tolerance (i-IGT) overall (24.7% vs 20.8%; P= 0.034), among individuals aged <65 years (21.7% vs 15.9%; P= 0.012). Among men, independent risk factors for i-IGT were an age of ≥65 years, hypertension, and high serum uric acid (SUA) and triglyceride levels; independent risk factors for diabetes mellitus (DM) were an age of ≥75 years and alcohol consumption. Among women, independent risk factors for i-IGT were central obesity and high levels of high-sensitivity C-reactive protein and SUA; independent risk factors for DM were low education and an elevated white blood cell count. Conclusions: Our findings suggest that conventional cardiovascular disease risk factors (i.e., age, hypertension, and dyslipidemia) associated with high risk of developing DM in men, but poor life style (i.e., obesity) and low education attainment in women. It is necessary for delay or stopping the development of DM among low-income adults in China to implement the personalized scheme of prevention DM between men and women, especially highlight control the risk factors in young and middle aged women. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). In insulin resistant states such as the metabolic syndrome, overproduction and impaired clearance of liver-derived very-low-density lipoproteins and gut-derived chylomicrons (CMs) contribute to hypertriglyceridemia and elevated atherogenic remnant lipoproteins. Although ingested fat is the major stimulus of CM secretion, intestinal lipid handling and ultimately CM secretory rate is determined by numerous additional regulatory inputs including nutrients, hormones and neural signals that fine tune CM secretion during fasted and fed states. Insulin resistance and T2D represent perturbed metabolic states in which intestinal sensitivity to key regulatory hormones such as insulin, leptin and glucagon-like peptide-1 (GLP-1) may be altered, contributing to increased CM secretion. In this review, we describe the evidence from human and animal models demonstrating increased CM secretion in insulin resistance and T2D and discuss the molecular mechanisms underlying these effects. Several novel compounds are in various stages of preclinical and clinical investigation to modulate intestinal CM synthesis and secretion. Their efficacy, safety and therapeutic utility are discussed. Similarly, the effects of currently approved lipid modulating therapies such as statins, ezetimibe, fibrates, and PCSK9 inhibitors on intestinal CM production are discussed. The intricacies of intestinal CM production are an active area of research that may yield novel therapies to prevent atherosclerotic CVD in insulin resistance and T2D. [ABSTRACT FROM AUTHOR]

Type 1 Diabetes (T1D) is regarded as an autoimmune disease characterized by insulin deficiency resulting from destruction of pancreatic β-cells. The incidence rates of T1D have increased worldwide. Over the past decades, progress has been made in understanding the complexity of the immune response and its role in T1D pathogenesis, however, the trigger of T1D autoimmunity remains unclear. The increasing incidence rates, immigrant studies, and twin studies suggest that environmental factors play an important role and the trigger cannot simply be explained by genetic predisposition. Several research initiatives have identified environmental factors that potentially contribute to the onset of T1D autoimmunity and the progression of disease in children/young adults. More recently, the interplay between gut microbiota and the immune system has been implicated as an important factor in T1D pathogenesis. Although results often vary between studies, broad compositional and diversity patterns have emerged from both longitudinal and cross-sectional human studies. T1D patients have a less diverse gut microbiota, an increased prevalence of Bacteriodetes taxa and an aberrant metabolomic profile compared to healthy controls. In this comprehensive review, we present the data obtained from both animal and human studies focusing on the large longitudinal human studies. These studies are particularly valuable in elucidating the environmental factors that lead to aberrant gut microbiota composition and potentially contribute to T1D. We also discuss how environmental factors, such as birth mode, diet, and antibiotic use modulate gut microbiota and how this potentially contributes to T1D. In the final section, we focus on existing recent literature on microbiota-produced metabolites, proteins, and gut virome function as potential protectants or triggers of T1D onset. Overall, current results indicate that higher levels of diversity along with the presence of beneficial microbes and the resulting microbial-produced metabolites can act as protectors against T1D onset. However, the specifics of the interplay between host and microbes are yet to be discovered. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a chronic autoimmune disorder that leads to progressive pancreatic ß-cell destruction and culminates in absolute insulin deficiency and stable hyperglycaemia. It is very likely that environmental factors play a role in triggering islet autoimmunity. Knowing whether they have true relevance in favoring T1D development is essential for the effective prevention of the disease. Moreover, prevention could be obtained directly interfering with the development of autoimmunity through autoantigen-based immunotherapy. In this narrative review, the present possibilities for the prevention of T1D are discussed. Presently, interventions to prevent T1D are generally made in subjects in whom autoimmunity is already activated and autoantibodies against pancreatic cell components have been detected. Practically, the goal is to slow down the immune process by preserving the normal structure of the pancreatic islets for as long as possible. Unfortunately, presently methods able to avoid the risk of autoimmune activation are not available. Elimination of environmental factors associated with T1D development, reverse of epigenetic modifications that favor initiation of autoimmunity in subjects exposed to environmental factors and use of autoantigen-based immunotherapy are possible approaches, although for all these measures definitive conclusions cannot be drawn. However, the road is traced and it is possible that in a not so distant future an effective prevention of the disease to all the subjects at risk can be offered. [ABSTRACT FROM AUTHOR]

The incidence of type 2 diabetes significantly increases with age. The relevance of this association is dramatically magnified by the concomitant global aging of the population, but the underlying mechanisms remain to be fully elucidated. Here, some recent advances in this field are reviewed at the level of both the pathophysiology of glucose homeostasis and the cellular senescence of pancreatic islets. Overall, recent results highlight the crucial role of beta-cell dysfunction in the age-related impairment of pancreatic endocrine function and delineate the possibility of new original therapeutic interventions. [ABSTRACT FROM AUTHOR]

Over a third of the US population is obese and at high risk for developing type 2 diabetes, insulin resistance, and other metabolic disorders. Obesity is considered a chronic low-grade inflammatory condition that is primarily attributed to expansion and inflammation of adipose tissues. Indeed, adipocytes produce and secrete numerous proinflammatory and anti-inflammatory cytokines known as adipokines. When the balance of these adipokines is shifted toward higher production of proinflammatory factors, local inflammation within adipose tissues and subsequently systemic inflammation occur. These adipokines including leptin, visfatin, resistin, apelin, vaspin, and retinol binding protein-4 can regulate inflammatory responses and contribute to the pathogenesis of diabetes. These effects are mediated by key inflammatory signaling molecules including activated serine kinases such as c-Jun N-terminal kinase and serine kinases inhibitor κB kinase and insulin signaling molecules including insulin receptor substrates, protein kinase B (PKB, also known as Akt), and nuclear factor kappa B. Bariatric surgery can decrease body weight and improve insulin resistance in morbidly obese subjects. However, despite reports suggesting reduced inflammation and weight-independent effects of bariatric surgery on glucose metabolism, mechanisms behind such improvements are not yet well understood. This review article focuses on some of these novel adipokines and discusses their changes after bariatric surgery and their relationship to insulin resistance, fat mass, inflammation, and glucose homeostasis. [ABSTRACT FROM AUTHOR]