Male Type 2 Diabetes Mellitus Research Articles

Telomere shortening and cardiac alterations in asymptomatic type 2 diabetes patients: impact of sex

Abstract Background Telomere shortening is associated with the occurrence of deleterious events in the context of cardiometabolic disorders, including type 2 diabetes mellitus (T2DM). However, no evidence is available on the link between leukocyte telomere length (LTL) and subclinical cardiac alterations in T2DM patients. Purpose Our aim is to evaluate the relation between LTL and cardiovascular function in asymptomatic T2DM patients, taking into consideration the impact of the sex. Methods We analyzed a cohort of asymptomatic T2DM patients free from any overt cardiovascular disease (including coronary artery disease) and other T2DM comorbidities. A detailed metabolic and echocardiographic evaluation was performed together with LTL measurements at inclusion and after 2 years of follow-up. Univariate analyses in regard of the comparison of three graded LTL tertiles and different gender were used to test individual relationships betweenbioclinical and echocardiographic parameters and LTL measures. Subsequently, an unsupervised clustering method (self-organizing maps [SOM]) was used to identify cluster at risk of cardiomyopathy. Results We studied 89 T2DM patients aged 50±4 years (43% female) with a mean T2DM duration of 10±5.8 years and an average follow-up of 2.1±0.2 years. Leukocyte TL analysis demonstrated a slight but significant attrition after 2 years. The analysis of echocardiographic variables (transmitral flow velocities, velocity of mitral annular motion, left ventricular ejection fraction) did not show any evidence for ouvert cardiomyopathy. However, in the lower LTL tertile a higher proportion of patients with global longitudinal strain [GLS]<18% was found [41.6% vs. 22.8% vs. 21.6%]. Interestingly, leukocyte TL was associated with T2DM duration, FIB-4, a noninvasive indice used to assess fibrosis associated with non-alcoholic fatty liver disease (NAFLD), and usage of GLP-1 agonists. Comparison of men and women by univariate analysis did not show any differences in both LTL and echocardiographic parameters. However, unsupervised cluster method (SOM) unmasked a subgroup of female T2DM patients with diastolic alterations (e’ mean) and systolic alteration (GLS) both linked with lower LTL, whereas no specific subgroup in male T2DM patients could be distinguished. Conclusion Our study identifies subclinical diastolic and systolic dysfunction together with shorter LTL in a subgroup of female T2DM patients. These findings raise the importance of considering sex effect in the understanding of diabetic cardiomyopathy.

Diabetes-Related Changes in Carotid Wall Properties: Role of Triglycerides.

Background/Objectives: This study compares the power of the radiofrequency (RF) signal reflected from the media layer (media power) of the common carotid artery (CCA) and the CCA stiffness between individuals with and without type 2 diabetes mellitus (T2DM). It also evaluates the associations of CCA media power with plasma glucose and lipid levels, as well as carotid stiffness. Methods: A total of 540 individuals, 115 with and 425 without T2DM (273 males, mean age = 64 ± 8 years) were studied using RF-based tracking of the right CCA. The following parameters were measured: CCA media thickness, luminal diameter, wall tensile stress (WTS), local pulse wave velocity (PWV), and media power. Results: Compared to the non-diabetic individuals, the T2DM patients had significantly higher CCA media thickness (652 ± 122 vs. 721 ± 138 microns, p < 0.005), luminal diameter (6.12 ± 0.78 vs. 6.86 ± 0.96 mm, p < 0.0005), media power (36.1 ± 4.8 vs. 39.3 ± 4.6, p < 0.0001), and PWV (7.65 ± 1.32 vs. 8.40 ± 1.89 m/s; p < 0.01), but comparable WTS (32.7 ± 10.4 vs. 33.1 ± 10.7 kPa; p = 0.25). In the entire population, CCA media power was independently associated with male sex, pulse pressure, current smoking, and T2DM; when T2DM was not included in the model, triglycerides emerged as an independent determinant of media power. The CCA PWV was independently associated with age, pulse pressure, media power, and T2DM. Conclusions: Our findings suggest the presence of structural changes in the arterial media of T2DM patients, leading to carotid stiffening and remodeling, aiming to preserve WTS. T2DM-related changes in arterial wall composition may be driven by high plasma triglyceride levels, which have previously been associated with both arterial stiffening and the incidence of CV events.

Intracerebroventricular insulin injection acutely normalizes the augmented exercise pressor reflex in male rats with type 2 diabetes mellitus.

The exercise pressor reflex (EPR) is exaggerated in type 2 diabetes mellitus (T2DM), but the underlying central nervous system aberrations have not been fully delineated. Stimulation of muscle afferents within working skeletal muscle activates the EPR, by sending information to neurons in the brainstem, where it is integrated and results in reflexively increased mean arterial pressure (MAP) and sympathetic nerve activity. Brain insulin is known to regulate neural activity within the brainstem. We hypothesize that brain insulin injection in T2DM rats attenuates the augmented EPR, and that T2DM is associated with decreased brain insulin. Using male Sprague-Dawley rats, T2DM and control rats were generated via an induction protocol with two low doses of streptozotocin (35 and 25mg/kg, i.p.) in combination with a 14-23-week high-fat diet or saline injections and a low-fat diet, respectively. After decerebration, MAP and renal sympathetic nerve activity (RSNA) were evaluated during EPR stimulation, evoked by electrically induced muscle contraction via ventral root stimulation, before and after (1 and 2h post) intracerebroventricular (i.c.v.) insulin microinjections (500mU, 50nl). i.c.v. insulin decreased peak MAP (ΔMAP Pre (36±14mmHg) vs. 1h (21±14mmHg) vs. 2h (11±6mmHg), P<0.05) and RSNA (ΔRSNA Pre (107.5±40%), vs. 1h (75.4±46%) vs. 2h (51±35%), P<0.05) responses in T2DM, but not controls. In T2DM rats, cerebrospinal fluid insulin was decreased (0.41±0.19 vs. 0.11±0.05ng/ml, control (n=14) vs. T2DM (n=4), P<0.01). The results demonstrated that insulin injections into the brain normalized the augmented EPR in brain hypoinsulinaemic T2DM rats, indicating that the EPR can be regulated by brain insulin. KEY POINTS: The reflexive increase in blood pressure and sympathetic nerve activity mediated by the autonomic nervous system during muscle contractions is also known as the exercise pressor reflex. The exercise pressor reflex is dangerously augmented in type 2 diabetes, in both rats and humans. In type 2 diabetic rats both cerebrospinal fluid insulin and phosphoinositide 3-kinase signalling within cardiovascular brainstem neurons decrease in parallel. Brain insulin injections decrease the magnitude of the reflexive pressor and sympathetic responses to hindlimb muscle contraction in type 2 diabetic rats. Partial correction of low insulin within the central nervous system in type 2 diabetes may treat aberrant exercise pressor reflex function.

Comparisons of the risks of new-onset prostate cancer in type 2 diabetes mellitus between SGLT2I and DPP4I users: a population-based cohort study

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2I) have been suggested to reduce new-onset cancer amongst type-2 diabetes mellitus (T2DM) patients. This study aims to compare the risks of prostate cancer between SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I) amongst T2DM patients. Design, setting and participantsThis was a retrospective population-based cohort study of prospectively recorded data on male patients with T2DM who were prescribed either SGLT2I or DPP4I between 1st January 2015 and 31st December 2020 from Hong Kong. MethodsThe primary outcome was new-onset prostate cancer. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbor search was performed and multivariable Cox regression was applied. A three-arm analysis including the glucagon-like peptide-1 receptor agonist (GLP1a) cohort was conducted. ResultsThis study included 42129 male T2DM patients (median age: 61.0 years old [SD: 12.2]; SGLT2I: n = 17,120; DPP4I: n = 25,009). In the propensity score matched cohort, the number of prostate cancers was significantly lower in SGLT2I users (n = 60) than in DPP4I (n = 102). Over a follow-up duration of 5.61 years, SGLT2I was associated with lower prostate cancer risks (HR: 0.45; 95% CI: 0.30-0.70) than DPP4I after adjustments. The subgroup analyses showed that the interactions between SGLT2I and age, hypertension, heart failure, and GLP-1a were not statistically significant. The result remained consistent in the sensitivity analysis. ConclusionThe study demonstrated SGLT2I was associated with lower risks of new-onset prostate cancer after propensity score matching and adjustments compared to DPP4I amongst T2DM patients.

Association between triglyceride to HDL cholesterol ratio and a risk of diabetes mellitus: a systematic review and meta-analysis.

The aim of this study was to investigate the link between the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) and the occurrence of type 2 diabetes mellitus (T2DM). PubMed, Embase, and Scopus databases were searched for cohort and case-control studies that reported on the link between TG/HDL-C and a risk of T2DM, with no restrictions on criteria used for the definition and categorization of low and high TG/HDL-C ratios. A total of 20 studies were included. There was considerable variability in terms of categorization of low or normal and higher TG/HDL-C ratio among the studies. Patients with high TG/HDL-C ratio had markedly higher risk of developing T2DM compared with patients with low or normal TG/HDL-C. Each unit increase in the ratio correlated with the increased risk of diabetes. Subgroup analysis based on sex showed an increased risk of T2DM in males and females with a high ratio compared with the group with a low/normal ratio. Higher TG/HDL-C ratio correlates with increased risk of T2DM. Despite limitations, the study demonstrates a possible value of using TG/HDL-C ratio as a biomarker for diabetes risk.

Prevalence of Hypogonadism in Male Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study

Background: Type 2 Diabetes Mellitus (T2DM) is a widespread metabolic disorder linked with various complications, including hypogonadism—a condition marked by reduced testosterone levels and symptoms such as erectile dysfunction, decreased libido, and increased fatigue. Hypogonadism remains underdiagnosed in diabetic populations, posing significant challenges to healthcare systems, especially in regions with high diabetic populations such as India. Methods: This cross-sectional study comprised 173 male T2DM patients aged 35 to 65. The study employed the Androgen Deficiency in Aging Males (ADAM) questionnaire to screen for hypogonadism, alongside physical examinations and biochemical tests to assess testosterone levels and other metabolic parameters. Results: The incidence of hypogonadism was found to be 27.2% among the study participants. Higher prevalence rates were related with older age, higher body mass index, greater waist circumference, and longer period of diabetes. Elevated fasting blood sugar and poor glycemic control (HbA1c ? 7%) were also significantly correlated with low testosterone levels. Conclusion: The significant association between T2DM and hypogonadism underscores the need for routine screening for testosterone deficiency in diabetic care, particularly given the condition’s impact on quality of life and metabolic health. Recommendations: Based on the findings, it is recommended that screening for hypogonadism be integrated into the regular management protocols for T2DM, particularly for patients presenting with metabolic syndrome features or those with poor glycemic control. Keywords: Type 2 Diabetes Mellitus, Hypogonadism, Testosterone, Metabolic Health, Indian Population

The value of lipid accumulation products in predicting type 2 diabetes mellitus: a cross-sectional study on elderlies over 65 in Shanghai

PurposeAs lifestyle changes, there is an increasing number of type 2 diabetes mellitus (T2DM) patients in China. The present study aimed to investigate the predictive value of the lipid accumulation product (LAP) for T2DM in Chinese elderlies over 65 years.MethodsThe present cross-sectional study recruited 2,092 adults from communities of Pudong New Area of Shanghai. Questionnaires were filled and anthropometric and laboratory examinations were completed by all participants. The predictive value of different risk factors for T2DM was analyzed using the receiver operating characteristics curve (ROC).ResultsLAP was found to be closely related to T2DM (adjusted OR: 0.613, 95% CI: 0.581–0.645). Fasting plasma glucose (FPG), LAP, and urea nigrogen (UN) were associated with T2DM in females, whereas FPG, LAP, neck circumference (NC) were associated with T2DM in males. When the cut-off value was 33.8, LAP displayed the optimal predictive performance. A gender difference was observed with an LAP of 37.95 demonstrating the best predictive value in males (AUC = 0.604, 95% CI: 0.577–0.652) and 60.2 in females (AUC = 0.617, 95% CI: 0.574–0.660), respectively.ConclusionLAP is more significantly associated with the risk of T2DM in elderlies than FPG, UN or NC, and it serves as a strong predictor of T2DM. However, this is impacted by FPG and neck circumference to a certain extent. Future large-scale studies are needed to confirm its efficacy in predicting diabetes.

Correlation between fat-to-muscle mass ratio and cognitive impairment in elderly patients with type 2 diabetes mellitus: a cross-sectional study

BackgroundFat to muscle mass ratio (FMR), a novel index integrating fat and muscle composition, has garnered attention in age-related conditions such as type 2 diabetes mellitus (T2DM) and neurodegenerative diseases. Despite this research on the relationship between FMR and cognitive impairment (CI) in T2DM remains scarce. This study aimed to investigate the sex-specific association between FMR and CI in elderly T2DM patients.MethodsA total of 768 elderly (> 60 years) T2DM in-patients (356 men and 412 women) were recruited from the Department of Endocrinology at Tianjin Nankai University affiliated hospital. Bioelectrical Impedance Analysis (BIA) was used to assess body composition, and Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive performance. T2DM patients were categorized into normal cognitive function (NC) and cognitive impairment (CI) groups based on MoCA scores and stratified by sex. Binary logistic regression was employed to examine the association between FMR and CI.ResultsAmong the participants, 42.7% of men and 56.3% of women experienced cognitive deterioration. Women with CI exhibited lower body mass index (BMI) and skeletal muscle mass index (SMI), while men with cognitive disorders showed lower SMI, FMR, and higher fat mass index (FMI). FMR was consistently unrelated to cognition in females, irrespective of adjustment made. However, in males, FMR was significantly associated with an increasing risk of cognitive dysfunction after adjusting for demographic and clinical variables (OR: 1.175, 95% CI: 1.045–1.320, p = 0.007). Furthermore, for each 0.1 increase in FMR, the incidence of CI rose by 31.1% after additional adjustment for BMI. In males, the prevalence of CI increased sequentially across FMR quartiles (p < 0.05).ConclusionElderly T2DM men with high FMR had unfavorable cognitive function. FMR is independently associated with an increased risk of CI in male T2DM patients regardless of BMI.

Liraglutide promotes UCP1 expression and lipolysis of adipocytes by promoting the secretion of irisin from skeletal muscle cells

Although Liraglutide (Lira) increases serum irisin levels in type 2 diabetes mellitus (T2DM), it is unclear whether it induces expression of uncoupling protein 1 (UCP1) of adipocytes via promoting irisin secretion from skeletal muscle. Male T2DM rats were treated with 0.4 mg/kg/d Lira twice a day for 8 weeks, and the protein expression of phosphorylated AMP kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase 1 (p-ACC1) and UCP1 in white adipose tissues were detected. Differentiated C2C12 cells were treated with palmitic acid (PA) and Lira to detect the secretion of irisin. Differentiated 3T3-L1 cells were treated with irisin, supernatant from Lira-treated C2C12 cells, Compound C or siAMPKα1, the triglyceride (TG) content and the related gene expression were measured. The transcriptome in irisin-treated differentiated 3T3-L1 cells was analyzed. Lira elevated serum irisin levels, decreased the adipocyte size and increased the protein expression of UCP1, p-AMPK and p-ACC1 in WAT. Moreover, it promoted the expression of PGC1α and FNDC5, the secretion of irisin in PA-treated differentiated C2C12 cells. The irisin and supernatant decreased TG synthesis and promoted the expression of browning- and lipolysis-related genes in differentiated 3T3-L1 cells. While Compound C and siAMPKα1 blocked AMPK activities and expression, irisin partly reversed the pathway. Finally, the transcriptome analysis indicated that differently expressed genes are mainly involved in browning and lipid metabolism. Overall, our findings showed that Lira modulated muscle-to-adipose signaling pathways in diabetes via irisin-mediated AMPKα/ACC1/UCP1/PPARα pathway. Our results suggest a new mechanism for the treatment of T2DM by Lira.

Effect of Sarcopenia on 10-Year Risk of Atherosclerotic Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM). This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression. The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model. This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.

Race/Ethnicity and Other Predictors of Early-Onset Type 2 Diabetes Mellitus in the US Population.

Among US adults aged 20 + years in the USA with previously diagnosed type 2 diabetes mellitus (T2DM), we aimed to estimate the prevalence of early-onset T2DM (onset at age < 50.5years) and to test associations between early-onset T2DM and race/ethnicity, and other hypothesized predictors. We pooled data from the annual National Health and Nutrition Examination Surveys (NHANES) over the years 2001 through 2018. We tested hypotheses of association and identified predictors using stepwise logistic regression analysis, and 11 supervised machine learning classification algorithms. After appropriate weighting, we estimated that among adults in the USA aged 20 + years with previously diagnosed T2DM, the prevalence of early-onset was 52.9% (95% confidence intervals, 49.6 to 56.2%). Among Non-Hispanic Whites (NHW) the prevalence was 48.6% (95% CI, 44.6 to 52.6%), among Non-Hispanic Blacks: 56.9% (95% CI, 51.8 to 62.0%), among Hispanics: 62.7% (95% CI, 53.2 to 72.3%). In the final multivariable logistic regression model, the top-3 markers predicting early-onset T2DM in males were NHB ethnicity (OR = 2.97; 95% CI: 2.24-3.95) > tobacco smoking (OR = 2.79; 95% CI: 2.18-3.58) > high education level (OR = 1.65; 95% CI: 1.27-2.14) in males. In females, the ranking was tobacco smoking (OR = 2.59; 95% CI: 1.90-3.53) > Hispanic ethnicity (OR = 1.49; 95% CI: 1.08-2.05) > obesity (OR = 1.30; 95% CI: 0.91-1.86) in females. The acculturation score emerged from the machine learning approach as the dominant marker explaining the race disparity in early-onset T2DM. The prevalence of early-onset T2DM was higher among NHB and Hispanic people, than among NHW people. Independently of race/ethnicity, acculturation, tobacco smoking, education level, marital status, obesity, and hypertension were also predictive.

The relationship between advanced liver fibrosis and osteoporosis in type 2 diabetes patients with MAFLD.

To investigate the relationship between advanced liver fibrosis and osteoporosis in metabolic-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). A total of 1144 T2DM patients were divided into the MAFLD and non-MAFLD groups, 460 T2DM patients with MAFLD (277 males aged ≥50 years and 183 postmenopausal females) were divided into N1 (advanced liver fibrosis excluded), N2 (indeterminate advanced liver fibrosis), and N3 (advanced liver fibrosis) groups according to the non-alcoholic fatty liver fibrosis score (NFS), the differences in bone mineral density (BMD) levels and prevalence of osteoporosis were compared. Based on the tertile levels of BMD of the lumbar spine (L), T2DM patients were divided into three groups (T1, T2, and T3), and the differences in the prevalence of advanced liver fibrosis were compared. The BMD levels of the L4, and L1-4 in the MAFLD group were lower than those of the non-MAFLD groups in male and female T2DM patients .The BMD levels of the total hip, L4, and L1-4 in the N3 group were lower than those of the N2 and N1 groups in male and female T2DM patients with MAFLD, and the prevalence of osteoporosis in the N3 group of males was higher than that in the N1 group. The BMD levels of the total hip, L4, and L1-4 were negatively correlated with NFS in both males and females. The BMD levels of the total hip and L4 in males, and the BMD level of L4 in females were negatively associated with NFS. The prevalence of advanced liver fibrosis was higher in the T1 group than in the T2 and T3 groups in T2DM patients with MAFLD. The BMD levels in male aged ≥50 years or postmenopausal female diabetic patients with MAFLD were negatively correlated with the degree of advanced liver fibrosis, which means an increased risk of liver fibrosis with decreasing BMD.

Combined effects of organochlorine pesticides on type 2 diabetes mellitus: Insights from endocrine disrupting effects of hormones

Association between organochlorine pesticides (OCPs) exposure and type 2 diabetes mellitus (T2DM) remains contradictory, and the evidence is mostly focused on a single exposure. Here, we assessed the associations between individual and combined OCPs exposure and T2DM, and explored the underlying mechanism of sex hormones and the methylation levels of sex hormone receptors in above associations. A case-control study with 1812 participants was performed. Gas chromatography mass spectrometry, liquid chromatography-tandem mass spectrometry, and pyrosequencing were used to measure plasma OCPs, serum sex hormones, and whole blood methylation levels of sex hormone receptors, respectively. Generalized linear models were used to analyze the relationships between OCPs, sex hormones, the methylation levels of sex hormone receptors, and T2DM. Quantile based g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) were employed to assess the combined OCPs exposure. The roles of sex hormones and the methylation levels of their receptors were evaluated by moderating mediation models. After adjusting for covariates, each unit (2.718 ng/ml) increase in p,p’-DDE was associated with a higher risk of T2DM in males (odds ratio (OR) and 95% confidence interval (CI): 1.066 (1.023, 1.112)). QGC and BKMR showed a positive combined effect in the associations of OCPs mixtures on T2DM among premenopausal females, and positive effects but not statistically significant among males and postmenopausal females. p,p'-DDE was the largest contributor for the positive associations. Furthermore, testosterone mediated 21.149% of the associations of p,p’-DDE with T2DM moderated by the androgen receptor methylation (ARm) located in CpG island 1. Individual and mixtures of OCPs exposure were positively linked to elevated risk of T2DM. Testosterone and ARm may participate in the related processes of OCPs with T2DM, providing new insights into the adverse endocrine effects caused by OCPs and specific pathways for the etiology and control of diabetes.

Sex Modifies the Impact of Type 2 Diabetes Mellitus on the Murine Whole Brain Metabolome.

Type 2 diabetes mellitus (T2DM) leads to the development of cardiovascular diseases, cognitive impairment, and dementia. There are sex differences in the presentation of T2DM and its associated complications. We sought to determine the impact of sex and T2DM on the brain metabolome to gain insights into the underlying mechanisms of T2DM-associated cognitive complications. Untargeted metabolomic analysis was performed, using liquid chromatography-mass spectrometry, on whole brain tissue from adult male and female db/db mice (a T2DM model) compared to wild-type (WT) C57Bl6/J mice. Regardless of sex, T2DM increased free fatty acids and decreased acylcarnitines in the brain. Sex impacted the number (103 versus 65 in males and females, respectively), and types of metabolites shifted by T2DM. Many choline-containing phospholipids were decreased by T2DM in males. Female-specific T2DM effects included changes in neuromodulatory metabolites (γ-aminobutyric acid, 2-linoleoyl glycerol, N-methylaspartic acid, and taurine). Further, there were more significantly different metabolites between sexes in the T2DM condition as compared to the WT controls (54 vs. 15 in T2DM and WT, respectively). T2DM alters the murine brain metabolome in both sex-independent and sex-dependent manners. This work extends our understanding of brain metabolic sex differences in T2DM, cognitive implications, and potential sex-specific metabolic therapeutic targets.

Risk factors of foot ulcers in patients with end-stage renal disease on dialysis: A meta-analysis.

The present study aims to assess the risk factors for foot ulcers in patients undergoing dialysis for end-stage renal disease (ESRD) and to provide evidence-based guidance for prevention and treatment. A systematic search was conducted on PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang Data from the database inception until May 2023 to identify relevant studies investigating the risk factors for foot ulcers in dialysis patients with ESRD. Two independent researchers conducted the literature screening and data extraction. The meta-analysis was performed using STATA 17.0 software. Ultimately, six articles comprising 1620 patients were included for analysis. The meta-analysis revealed that male (OR, 1.464; 95% CI: 1.082-1.980, p = 0.013), hypertension (OR, 1.781; 95% CI: 1.293-2.4550, p < 0.001), peripheral artery disease (PAD) (OR, 5.014; 95% CI: 2.514-9.998, p < 0.001), type 1 diabetes mellitus (T1DM) (OR, 2.993; 95% CI: 1.477-6.065, p = 0.002) and type 2 diabetes mellitus (T2DM) (OR, 2.498; 95% CI:1.466-4.256, p = 0.001) were risk factors for foot ulcers in dialysis patients with ESRD. Conversely, the female sex (OR, 0.683; 95% CI: 0.505-0.924, p = 0.013) was a protective factor against foot ulcers. Our analysis revealed that male sex, hypertension, PAD, T1DM and T2DM were risk factors for foot ulcers in patients undergoing dialysis for ESRD. Conversely, the female sex was a protective factor against foot ulcers. Therefore, it is crucial to strengthen health education that targets patients with these risk factors and regularly screen high-risk individuals. Early detection and treatment can help delay disease progression.

Prediction of the Risk of Bone Mineral Density Decrease in Type 2 Diabetes Mellitus Patients Based on Traditional Multivariate Logistic Regression and Machine Learning: A Preliminary Study.

There remains a lack of a machine learning (ML) model incorporating body composition to assess the risk of bone mineral density (BMD) decreases in type 2 diabetes mellitus (T2DM) patients. We aimed to use ML algorithms and the traditional multivariate logistic regression to establish prediction models for BMD decreases in T2DM patients over 50 years of age, and compare the performance of the two methods. This cross-sectional study was conducted among 450 patients with T2DM from 1 August 2016 to 31 December 2022. The participants were divided into a normal BMD group and a decreased BMD group. Traditional multivariate logistic regression and six ML algorithms were selected to construct male and female models. Two nomograms were constructed to evaluate the risk of BMD decreases in the male and female T2DM patients, respectively. The ML models with the highest area under the curve (AUC) were compared with the traditional multivariate logistic regression models in terms of discriminant ability and clinical applicability. The optimal ML model was the extreme gradient boost (XGBoost) model. The AUCs of the traditional multivariate logistic regression and the XGBoost models were 0.722 and 0.800 in the male testing dataset, respectively, and 0.876 and 0.880 in the female testing dataset, respectively. The decision curve analysis results suggested that using the XGBoost models to predict the risk of BMD decreases obtained more net benefits compared with the traditional models in both sexes. We preliminarily proved that the XGBoost models outperformed most other ML models in both sexes and achieved higher accuracy than traditional analyses. Due to the limited sample size in the study, it is necessary to validate our findings in larger prospective cohort studies.

Elevated circulating follicle stimulating hormone level is associated with dyslipidemia in male type 2 diabetes mellitus patients: A cross-sectional study.

Type 2 diabetes mellitus (T2DM) commonly combines with dyslipidemia, and both are known as the risk factors of cardiovascular events and aggravate the arteriosclerosis progression. In this study, we investigated the relationship between follicle-stimulating hormone (FSH) and lipid profiles in male T2DM patients. We collected clinical data of male T2DM patients in the Chinese Han population hospitalised from January 2018 to June 2020. A total of 963 patients with a mean age of 58.89±12.25years old were enroled in this study. The results showed that the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL)-C levels were decreased gradually from the highest quartile groups (Q4) to Q1 group relevant to luteinising hormone and FSH, and no significant difference was observed in high-density lipoprotein-C levels among Q4-Q1 groups. Sub-groups analysis showed that, with the increased FSH level, TC, TG, and LDL-C levels were increased in the elder group (40-59years old) than those in the younger group (20-39years old). Spearman's analysis revealed a positive correlation between FSH and the levels of TC, TG, and LDL-C (r=0.354, r=0.336, r=0.312, p<0.001, respectively). The effect of FSH is independent of the changes in total testosterone level. Multivariate analysis found that increased FSH levels (≥9.26mIU/mL) and decreased total testosterone levels (<13.30nmol/L) were positively correlated with high TC, TG, and LDL-Cemia (OR=4.014, 1.565, 1.602, 1.660, 2.127, 1.322, respectively, p<0.05). Our data suggest that high serum FSH level in male T2DM patients could be a potential independent risk factor correlated with the elevated TC, TG, and LDL-C.

The Relationship Between Non-HDL-C /HDL-C Ratio (NHHR) and Vitamin D in Type 2 Diabetes Mellitus.

The objective of this research was to examine the relationship between non-HDL cholesterol/HDL cholesterol ratio (NHHR) and vitamin D in type 2 diabetes mellitus (T2DM). This study enrolled 617 T2DM participants. Participants were separated into two groups: no vitamin D deficiency and vitamin D deficiency. Participants were split into two categories: individuals who had a high NHHR and those with a low NHHR, with the median NHHR serving as the cut-off. Eventually, the study participants were classified into two groups by gender, which were further classified into vitamin D deficient and non-vitamin D deficient groups. NHHR values were substantially greater in vitamin D deficient group than in the non-deficient group in both male and female T2DM patients (P<0.05). The high NHHR group displayed substantially lower vitamin D levels than the low NHHR group [16.21 (12.55,21.35) vs 19.05 (14.59,24.07), P<0.001]. NHHR was discovered to be negatively and independently associated with vitamin D levels, and there was no sex difference. For the first time, our research revealed a negative relationship between NHHR and vitamin D in patients with T2DM.

Association of Low Serum Bilirubin Concentrations and Promoter Variations in the UGT1A1 and HMOX1 Genes with Type 2 Diabetes Mellitus in the Czech Population.

Bilirubin has potent biological beneficial effects, protecting against atherosclerosis, obesity, and metabolic syndrome. The aim of this study was to assess serum bilirubin concentrations and (TA)n and (GT)n microsatellite variations in the promoter regions of the UGT1A1 and HMOX1 genes, respectively, in patients with type 2 diabetes mellitus (T2DM). The study was carried out in 220 patients with T2DM and 231 healthy control subjects, in whom standard biochemical tests were performed. The (TA)n and (GT)n dinucleotide variations were determined by means of fragment (size-based) analysis using an automated capillary DNA sequencer. Compared to controls, both male and female patients with T2DM had lower serum bilirubin concentrations (9.9 vs. 12.9 μmol/L, and 9.0 vs. 10.6 μmol/L, in men and women, respectively, p < 0.001). Phenotypic Gilbert syndrome was much less prevalent in T2DM patients, as was the frequency of the (TA)7/7UGT1A1 genotype in male T2DM patients. (GT)nHMOX1 genetic variations did not differ between diabetic patients and controls. Our results demonstrate that the manifestation of T2DM is associated with lower serum bilirubin concentrations. Consumption of bilirubin due to increased oxidative stress associated with T2DM seems to be the main explanation, although (TA)n repeat variations in UGT1A1 partially contribute to this phenomenon.

Hyperuricemia as an independent risk factor for MAFLD in nonobese patients without T2DM.

Objective According to the latest consensus statement, fatty liver complicated by specific metabolic abnormalities can be diagnosed as metabolic dysfunction-associated fatty liver disease (MAFLD) in nonobese patients without type 2 diabetes mellitus (T2DM). However, hyperuricemia (HUA), a manifestation of metabolic disorders, is excluded from diagnostic criteria. This study explored the association between HUA and MAFLD in nonobese patients without T2DM. Methods A total of 28187 participants were recruited from the Examination Center of the China-Japan Friendship Hospital from 2018 to 2022 and divided into 4 subgroups: nonobese patients without T2DM, obese patients without T2DM, nonobese patients with T2DM, and obese patients with T2DM. MAFLD was diagnosed by ultrasound combined with laboratory examinations. The association of HUA with MAFLD subgroups was performed by logistical regression analysis. The predictive ability of UA for MAFLD subgroups was assessed by receiver operating characteristics (ROC). Results HUA was positively associated with MAFLD in nonobese patients without T2DM in both males and females, even after adjusting for sex, BMI, dyslipidemia, and abnormal liver function. The association increased gradually with aging, especially in those over 40 years old. Conclusions HUA was an independent risk factor for MAFLD in nonobese patients without T2DM. We suggest that UA abnormalities might be considered in the diagnosis of MAFLD.in nonobese patients without T2DM.