Female Type 2 Diabetes Mellitus Patients Research Articles

Osteoporosis as the Female-Specific Risk Factor for Dynapenia in Elderly Patients with Type 2 Diabetes

Aims: Dynapenia is a noteworthy health issue contributing to increased risk of falling, but its co-occurrence with osteoporosis in elderly individuals with type 2 diabetes mellitus (T2DM) has not been well explored. Therefore, this study aimed to establish the association between osteoporosis and dynapenia, focusing on T2DM females due to their high prevalence of osteoporosis and fragility. Methods: We conducted a cross-sectional study to recruit a total of 103 T2DM patients (43 males and 60 females), aged between 50 and 80 years with median 68.0 years. Dual-energy X-ray absorptiometry (DXA) and dominant hand grip strength measurements were performed to define body composition, osteoporosis, and dynapenia in a sex-specific manner. Results: Higher prevalence of dynapenia and dyna-osteoporosis was observed in female T2DM patients with a significantly positive correlation between osteoporosis and dynapenia even after adjustment of body mass index (BMI). By performing a multivariate logistic regression analysis, both BMI and osteoporosis were identified as risk predictors for the development of dynapenia in female T2DM patients with odds ratios (95% CIs) of 1.234 (1.029–1.480) and 4.883 (1.352–17.630), respectively. Conclusions: Our results point out there is high, female-specific co-occurrence of osteoporosis and dynapenia in T2DM patients. Moreover, having osteoporosis and increased BMI might boost the risk of dynapenia in elderly females with T2DM.

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.

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.

Relationship between advanced lung cancer inflammation index and long-term all-cause, cardiovascular, and cancer mortality among type 2 diabetes mellitus patients: NHANES, 1999-2018.

Type 2 diabetes mellitus (T2DM) was a major global health threat. As a chronic low-grade inflammatory disease, the prognosis of diabetes was associated with inflammation. The advanced lung cancer inflammation index (ALI) served as a comprehensive index to assess inflammation. This study aimed to estimate the association between ALI and all-cause, cardiovascular disease (CVD), and cancer mortality in T2DM patients. We extracted cohort data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2018 for analysis. The weighted Kaplan-Meier analysis and multivariate-adjusted Cox analysis were utilized to evaluate the relationship between ALI and all-cause, CVD, and cancer mortality in T2DM patients. Restricted cubic spline (RCS) analysis was employed to assess their non-linear relationship. Stratified analysis and interaction analysis were conducted to enhance the robustness of the results. The study incorporated a total of 3,888 patients. An increase in ALI was associated with a reduced risk of all-cause and CVD mortality in T2DM patients, but not related to cancer mortality. There were J-shaped and L-shaped non-linear relationships between ALI and all-cause, CVD mortality in T2DM patients, respectively. The inflection points were 90.20 and 93.06, respectively. For values below the inflection point, every 10U increase in ALI, both all-cause and CVD mortality risk decreased by 9%. Beyond the inflection point, all-cause mortality rose by 3%, while CVD mortality remained unaffected. Gender-stratified RCS analysis indicated a linear negative relationship between CVD mortality and ALI in female T2DM patients, whereas the trend in males aligned with the overall population. Our research initially identified a significant correlation between increased ALI levels with decreased all-cause and CVD mortality in T2DM patients. There were J-shaped and L-shaped non-linear relationships between ALI and all-cause, CVD mortality in T2DM patients, respectively. For female patients, there was a linear negative relation between CVD mortality and ALI, whereas the trend in males aligned with the overall population. These findings suggested that maintaining ALI (for example, control body weight and keep albumin in the normal range) within a certain range in the clinical settings was crucial for improving all-cause and CVD mortality in T2DM patients.

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.

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.

Serum 25-Hydroxyvitamin D Levels in Type 2 Diabetes Patients in North China: Seasonality and the Association between Vitamin D Status and Glycosylated Hemoglobin Levels.

Previous studies have reported a correlation between vitamin D levels and seasonality in healthy populations. However, there are few studies on the seasonal variation in vitamin D levels and its relationship with glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to investigate seasonal changes in serum 25-hydroxyvitamin D [25(OH)D] levels and the associations between these vitamin D concentrations and HbA1c levels in T2DM patients in Hebei, China. A cross-sectional study of 1,074 individuals with T2DM was conducted from May 2018 to September 2021. Levels of 25(OH)D in these patients were assessed based on both sex and season, and relevant clinical or laboratory variables that could impact vitamin D status were also considered. In the T2DM patient cohort, the mean blood 25(OH)D levels were 17.05 ng/mL. A total of 698 patients (65.0%) had insufficient serum 25(OH)D levels. The vitamin D deficiency rates were significantly higher in the winter and spring compared to the autumn (P < 0.05), indicating that seasonal fluctuations can have a significant impact on 25(OH)D levels. The levels of vitamin D inadequacy were highest in the winter (74%), and females were more likely than males to be deficient (73.4% vs. 59.5%, P < 0.001). In comparison to the winter and spring, both males and females showed higher 25(OH)D levels in the summer (P < 0.001). HbA1c levels were 8.9% higher in those with vitamin D deficiencies than in nondeficient patients (P < 0.001). HbA1c and vitamin D levels were negatively correlated (r = -0.119, P < 0.001). Vitamin D deficiencies are particularly prevalent among T2DM patients in Hebei, China, with exceptionally high rates in the winter and spring. Female T2DM patients were at an elevated risk of vitamin D deficiency, and vitamin D levels were negatively correlated with HbA1c.

Preliminary study of the interactive effects of coronary heart disease and lacunar infarction on renal function in patients with type 2 diabetes mellitus by gender

BackgroundCoronary heart disease (CHD) and lacunar infarction (LI) are the most common cardio- cerebrovascular complications of type 2 diabetes mellitus (T2DM) and a recognized risk factor for renal injury. Although a unidirectional association of CHD or LI with T2DM or the kidney has been demonstrated, however, it remains unknown whether there is an interactive effect of the coexistence of CHD and LI on renal function in T2DM patients. The aim of our study was to investigate the interaction between CHD and LI on renal function in gender-specific patients with T2DM and the association between cardio-cerebrovascular disease-related conventional serum markers and the estimated glomerular filtration rate (eGFR). MethodsWe conducted a cross-sectional study in Beijing and Tianjin from April 2019 to August 2021. Participants with T2DM aged ≥18 years were asked to complete a one-to-one questionnaire and physical examination. ResultsIn this study, 389 eligible patients with T2DM were included, with a mean age of 63.04 ± 9.41 years, of whom 200 (51.41 %) were male. The proportions of patients with CHD, LI, and both CHD and LI were 28.53 %, 24.42 %, and 11.05 %, respectively. Compared to T2DM patients without either CHD or LI, those with both CHD and LI were found to have a significantly greater risk of reduced eGFR (OR: 12.82, 95 % CI 5.06–32.52, P < 0.001) than those with CHD alone (OR: 2.42, 95 % CI 1.37–3.00, P = 0.004) or LI alone (OR: 1.15, 95 % CI 0.61–2.18, P = 0.664). The combined presence of CHD and LI is associated with a significantly greater risk of decreased eGFR in female T2DM patients compared to their male counterparts. We found both multiplicative and additive effects in all T2DM patients; however, when stratified by sex, only multiplicative effects were observed. After controlling for interference from CHD, LI, and age, we found that total cholesterol (TC) was negatively correlated with eGFR in females (r = −0.156, P = 0.034), and low-density lipoprotein cholesterol (LDL-C) was negatively correlated with eGFR in males (r = −0.229, P = 0.001). ConclusionThis study provides novel evidence that the synergistic effect of CHD and LI on renal injury in patients with T2DM is significantly greater than their individual effects. Women with T2DM who have both CHD and LI are at a 4.85-fold higher risk of decreased eGFR than men. Therefore, increased clinical attention should be given to preventing and treating vascular complications in T2DM patients, as well as aggressively reducing lipid levels, particularly TC and LDL-C, to delay or prevent renal dysfunction in T2DM patients.

Relationship between plasma glutamate and cardiovascular disease risk in Chinese patients with type 2 diabetes mellitus by gender.

This study aimed to assess the association between plasma glutamate (Glu) and the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) and whether this association differs by gender. We retrieved clinical information on 1032 consecutive patients with T2DM from a same tertiary care center from May 2015 to August 2016. Glu was quantified by liquid chromatography-tandem mass spectrometry analysis. Glu was converted into a categorical variable based on the median concentration in the whole population, while logistic regression was used to obtain the odds ratio (OR) and 95% confidence interval (CI), and the correlation between Glu and various biochemical indices was analyzed. We found that Glu was positively associated with the risk of CVD in patients with T2DM. This correlation was more significant in women. In T2DM patients, the higher the age, body mass index (BMI), weight and systolic blood pressure (SBP), the lower the glycosylated hemoglobin (HbA1C) concentration and the higher the Glu. In female patients, the correlation between age, weight, BMI, SBP, and plasma Triglycerides (TG), and Glu was also statistically significant. In conclusion, female T2DM patients with high levels of Glu have a higher risk of developing CVD.

Identification of stable reference genes in peripheral blood mononuclear cells from type 2 diabetes mellitus patients

Reference genes are obligatory for accurate normalization of mRNA transcript levels across samples and experimental conditions in Real Time-polymerase chain reaction (qRT-PCR) based quantitative gene expression assays. Selection of stably expressed reference genes is therefore crucial for ensuring reproducibility of such assays. However, there is a complete dearth of data on stability of commonly used reference genes in Peripheral Blood Mononuclear Cells (PBMCs) from Type 2 diabetes mellitus (T2DM) patients. We have evaluated the gene expression stability of 4 widely used reference genes (Beta-actin, ACTB; Peptidylprolyl Isomerase B, PPIB; Tyrosine 3 Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Zeta, YWHAZ; and Glyceraldehyde-3-Phosphate Dehydrogenase, GAPDH); in PBMCs from 39 T2DM patients and 47 normoglycemic (NGT) subjects. ACTB and YWHAZ were found to be the most stable genes in PBMCs from T2DM patients and therefore, can be recommended as suitable reference genes in similar contexts. GAPDH and PPIB expressions were not stable in PBMCs from T2DM patients. On using ACTB and YWHAZ as reference genes for measuring relative expression of GAPDH and PPIB in these subjects, relative GAPDH expression was found to be significantly lower in female T2DM patients, compared to female NGT subjects [GAPDH relative normalization unit (RNU): female T2DM (n = 19), median (Q1, Q3): 9.0 (8.1, 9.9); female NGT (n = 18): median (Q1, Q3): 10.1 (9.1, 11.0); P = 0.034]. Dysregulation of GAPDH in PBMCs from female T2DM patients could be associated with sex-specific differences in pathogenesis and outcomes of T2DM.

The correlation between serum creatine kinase with low muscle mass in type 2 diabetes patients.

Creatine kinase (CK), the key enzyme in regulating energy metabolism, is demonstrated to be correlated with insulin resistance. Type 2 diabetes mellitus (T2DM) is considered as a risk factor for developing low muscle mass. The purpose of this investigation was to evaluate whether serum CK is associated with low muscle mass in T2DM patients. This cross-sectional study enrolled a consecutive population of 1086 T2DM patients recruited from the inpatients in our department. Dual-energy X-ray absorptiometry was utilized to detect the skeletal muscle index (SMI). In all, 117 males (20.24%) and 72 females (16.51%) showed low muscle mass in T2DM patients. CK was associated with a reduced risk of low muscle mass in male and female T2DM patients. SMI was correlated with age, duration of diabetes, body mass index (BMI), diastolic blood pressure (DBP), triglyceride, high-density lipoprotein cholesterol, and CK in male subjects analyzed using linear regression. Linear regression analysis showed that SMI was correlated with age, BMI, DBP, and CK in female subjects. In addition, CK was correlated with BMI and fasting plasma glucose in male and female T2DM groups. CK is inversely correlated with low muscle mass in T2DM patients.

Cost of cardiovascular diseases and renal complications in people with type 2 diabetes mellitus in the Kingdom of Saudi Arabia: A retrospective analysis of claims database.

The burden of macro- and microvascular complications in patients with Type 2 diabetes mellitus (T2DM) is substantial in Middle East countries. The current study assessed the healthcare resource utilization (HCRU) and costs related to cardiovascular and renal complications among patients with T2DM. This non-interventional, longitudinal, retrospective, cohort study collected secondary data from three insurance claims databases across Kingdom of Saudi Arabia (KSA) of patients diagnosed with T2DM. The study included adult patients aged ≥18 years diagnosed with first cardiovascular disease (CVD) during index time period and at least one T2DM claim anytime during the study time period. The primary analyses were conducted per database, stratified by three cohorts; patients with at least one claim every six months during the 1-year pre-index and 1-year post-index period (cohort 1), patients with at least one claim every six months during the 1-year pre-index, and two years post-index period (cohort 2) and patients with at least one claim every six months during the 1-year pre-index and 3-year post-index period (cohort 3). For each Payer database, demographics, CVD subgroups, HCRU, and costs were analysed. Descriptive statistics were used to analyse the data. The study sample comprised of 72-78% male and 22-28% female T2DM patients with CVD and renal complications. Patients in the age group of 35-65 years or above contributed to the significant disease burden. Nearly 68 to 80% of T2DM patients developed one CVD event, and 19 to 31% of patients developed multiple CVD events during the follow-up period. For most patients with comorbid CVD and renal disease, the average HCRU cost for post‑index periods was higher compared to 1-year pre-index period across the different visit types and activities. The study findings elucidates the need for early initiation of therapies that would reduce the long-term cardiovascular and renal outcomes and the associated costs in patients with T2DM.

COVID-19-Related Trends and Characteristics of Type 2 Diabetes Mellitus and Metabolic Syndrome.

BackgroundAlthough there have been several studies associating obesity with severe coronavirus disease 2019 (COVID-19) outcomes, the potential impact of the pandemic on type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) incidence is less clear. Furthermore, reports on the characteristics of these patients during the pandemic have been scarce.ObjectivesThe purpose of this retrospective study was 1) to explore the impact of the COVID-19 pandemic on T2DM and MetS incidence, and 2) to describe sex-based differences in the characteristics of T2DM and MetS patients during the COVID-19 pandemic.MethodsUsing electronic health records (EHRs) obtained from the USA-based TriNetX research database (TriNetX, Cambridge, MA), the incidence and the total number of patients with “T2DM (ICD-10-CM: E11)” and “MetS (ICD-10-CM: E88.81)” prior to and during the COVID-19 pandemic were determined. Aggregate lab data from EHRs were extracted and statistical analyses on the lab values and patient demographics including sex, race/ethnicity, and comorbidities were performed.ResultsAfter analyzing T2DM and MetS patient data from 2018, 2019, and 2020, we observed a considerable decrease in both T2DM and MetS incidence, with data in April 2020 exhibiting the largest decrease when compared to other months. Furthermore, monthly male T2DM and MetS patients’ lab data revealed worsening parameters in April 2020, such as hemoglobin A1c (HbA1C) and blood glucose, when compared to females. Demographic data during 2020 revealed that male T2DM and MetS patients had a significantly higher prevalence of comorbidities including hypertension, ischemic heart disease, and heart failure, but female T2DM and MetS patients had significantly higher asthma comorbidity.ConclusionsDuring 2020, there was a marked decrease in T2DM and MetS diagnosis. Due to a lack of screening, these data may suggest a subsequent increase in T2DM and MetS-related heart disease in the future and may magnify the existing sex-related differences identified in these patients.

Association between glycemic control and risk of venous thromboembolism in diabetic patients: a nested case\u2013control study

BackgroundPrevious studies suggested an elevated risk of venous thromboembolism (VTE) among patients with type 2 diabetes mellitus (T2DM), with a possible sex difference. The impact of glycemic control on the risk of VTE is unclear. Our objective was to analyze the association between glycemic control and the risk of unprovoked (idiopathic) VTE in men and women with T2DM.MethodsWe conducted a nested case–control analysis (1:4 matching) within a cohort of patients with incident T2DM between 1995 and 2019 using data from the CPRD GOLD. We excluded patients with known risk factors for VTE prior to onset of DM. Cases were T2DM patients with an unprovoked treated VTE. The exposure of interest was glycemic control measured as HbA1c levels. We conducted conditional logistic regression analyses adjusted for several confounders.ResultsWe identified 2′653 VTE cases and 10′612 controls (53.1% females). We found no association between the HbA1c level and the risk of VTE in our analyses. However, when the most recent HbA1c value was recorded within 90 days before the index date, women with HbA1c levels > 7.0% had a 36–55% increased relative risk of VTE when compared to women with HbA1c > 6.5–7.0%.ConclusionsOur study raises the possibility that female T2DM patients with HbA1c levels > 7% may have a slightly higher risk for unprovoked VTE compared to women with HbA1c levels > 6.5–7.0%. This increase may not be causal and may reflect differences in life style or other characteristics. We observed no effect of glycemic control on the risk of VTE in men.

The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics.

Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case-control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications. APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N = 1274; N = 829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR-RFLP in healthy nondiabetic controls (N = 2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI] = 0.88 [0.71-1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI] = 0.65 [0.42-0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI] = 0.50 [0.25-0.99]); and remains significant (P = 0.044) after adjustment for diabetes duration and BMI. Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.

Hypomethylation of IL1RN and NFKB1 genes is linked to the dysbalance in IL1β/IL-1Ra axis in female patients with type 2 diabetes mellitus

Inflammation has received considerable attention in the pathogenesis of type 2 diabetes mellitus (T2DM). Supporting this concept, enhanced expression of interleukin (IL)-1β and increased infiltration of macrophages are observed in pancreatic islets of patients with T2DM. Although IL-1 receptor antagonist (IL-1Ra) plays a major role in controlling of IL-1β-mediated inflammation, its counteraction effects and epigenetic alterations in T2DM are less studied. Thus, we aimed to analyze the DNA methylation status in IL1RN, RELA (p65) and NFKB1 (p50) genes in peripheral blood mononuclear cells (PBMCs) from treated T2DM patients (n = 35) and age-/sex- matched healthy controls (n = 31). Production of IL-1β and IL-1Ra was analyzed in plasma and supernatants from LPS-induced PBMCs. Immunomodulatory effects of IL-1β and IL-1Ra were studied on THP-1 cells. Average DNA methylation level of IL1RN and NFKB1 gene promoters was significantly decreased in T2DM patients in comparison with healthy controls (P< 0.05), which was associated with the increased IL-1Ra (P< 0.001) and IL-1β (P = 0.039) plasma levels in T2DM patients. Negative association between average methylation of IL1RN gene and IL-1Ra plasma levels were observed in female T2DM patients. Methylation of NFKB1 gene was negatively correlated with IL-1Ra levels in the patients and positively with IL-1β levels in female patients. LPS-stimulated PBMCs from female patients failed to raise IL-1β production, while the cells from healthy females increased IL-1β production in comparison with unstimulated cells (P< 0.001). Taken together, the findings suggest that hypomethylation of IL1RN and NFKB1 gene promoters may promote the increased IL-1β/IL-1Ra production and regulate chronic inflammation in T2DM. Further studies are necessary to elucidate the causal direction of these associations and potential role of IL-1Ra in anti-inflammatory processes in treated patients with T2DM.

The relationship between atherosclerosis and bone mineral density in patients with type 2 diabetes depends on vascular calcifications and sex.

Atherosclerosis is considered associated with low bone mineral density (BMD). However, most previous studies focus on patients with arterial atherosclerosis with vascular calcification. It is still unknown whether a relationship exists between atherosclerosis and BMD in patients without calcification. It is also unknown if sex plays a role in this relationship. We performed a retrospective cross-sectional study, which included 1459 type 2 diabetes mellitus (T2DM) patients (648 males ≥ 50years old, and 811 postmenopausal females). They were assigned to three groups: group 1 (patients without carotid plaques and without carotid calcification), group 2 (patients with carotid plaques but without carotid calcification), and group 3 (patients with carotid plaques and with carotid calcification). Clinical characteristics and BMD were compared. The relationship between atherosclerosis and BMD was determined by binary logistic regression analysis. Statistical analysis was performed using SPSS 25.0. Significant differences were only observed in women. The percentage of osteoporosis was higher in group 3 (43.64%) than in groups 1 (34.82%) and 2 (32.14%) (P = 0.016). Low BMD was found in the lumbar (P = 0.032), hip (P < 0.001), and femoral neck (P < 0.001). The odds ratio for osteoporosis increased significantly in a score-dependent manner in postmenopausal female patients with calcified atherosclerosis, but not in uncalcified patients. In men, no differences or relationships were identified. A negative correlation between carotid atherosclerosis and BMD was found in female T2DM patients with vascular calcification, but not in those without calcification. A similar relationship was not observed in male patients with or without calcification. Thus, the relationship between atherosclerosis and bone mineral density in patients with type 2 diabetes depends on vascular calcifications and sex.

Moderation effects of food intake on the relationship between urinary microbiota and urinary interleukin-8 in female type 2 diabetic patients.

BackgroundOur previous study demonstrated that the composition of the urinary microbiota in female patients with type 2 diabetes mellitus (T2DM) was correlated with the concentration of urinary interleukin (IL)-8. As the composition of urine is mainly determined by diet, diet might mediate the correlation.MethodsSeventy female T2DM patients and 70 healthy controls (HCs) were recruited. Midstream urine was used for the urine specimens. Urinary IL-8 was determined by enzyme-linked immunosorbent assay. A Chinese Food Frequency Questionnaire was used to collect food intake data. The independent variables in the hierarchical regression analysis were the relative abundances of the bacterial genera and species that were significantly different between the T2DM and HCs and between the T2DM patients with and without detectable urinary IL-8, and the bacterial genera associated with IL-8 concentration in the multiple regression model reported in our previous research. IL-8 concentration was the dependent variable, and nutrient intakes were moderator variables.ResultsFiber and vitamin B3 and E intake exerted enhancing effects, and water intake exerted a buffering effect, on the positive relationship between the relative abundance of Ruminococcus and IL-8 concentration (p < 0.05). Cholesterol and magnesium intake exerted enhancing effects on the positive relationship between the relative abundance of Comamonas and IL-8 concentration (p < 0.05).ConclusionModulating T2DM patients’ dietary patterns may prevent bladder inflammation.

Sex-influenced association of metabolic syndrome with lower extremity arterial disease in type 2 diabetes

AimThe present study is undertaken to investigate the relationship between metabolic syndrome (MS) and lower extremity arterial disease (LEAD) in type 2 diabetes mellitus (T2DM) patients. MethodsA multi-center cross-sectional study was conducted on 8374 T2DM patients (4521 males and 3853 females) from 30 hospitals across China from June 2016 to January 2017. The odds ratios (ORs) and 95% confidence intervals (CIs) were presented to show the association between MS and LEAD. The univariate and multiple logistic analyses were performed to examine the association between MS and the prevalence of LEAD. Furthermore, the relationship was analyzed in different sex groups. Subgroup analysis was performed based on the number and individual of MS components. ResultsFinally, 1809(21.60%) T2DM patients meet the diagnostic criteria of LEAD. Of the 3853 female subjects, 841(21.83%) patients were in the LEAD group and of the 4521 male subjects, 968(21.41%) patients were in the LEAD group. When adjusting for confounding variables, MS was significantly associated with the prevalence of LEAD in all enrolled T2DM patients (OR = 1.22, 95%CI: 1.09–1.37, P = 0.001). However, upon analyzing LEAD in different sex groups, the significant association remained in females (OR = 1.33, 95%CI: 1.12–1.58, P < 0.001), but not in males (OR = 1.11, 95%CI: 0.95–1.29, P = 0.202). ConclusionsOur results suggest that MS is specifically associated with an increased risk of LEAD in female T2DM patients. However, MS may not be a significant factor in the prevalence of LEAD in male T2DM patients.

The Performance of Different Artificial Intelligence Models in Predicting Breast Cancer among Individuals Having Type 2 Diabetes Mellitus.

Objective: Early reports indicate that individuals with type 2 diabetes mellitus (T2DM) may have a greater incidence of breast malignancy than patients without T2DM. The aim of this study was to investigate the effectiveness of three different models for predicting risk of breast cancer in patients with T2DM of different characteristics. Study design and methodology: From 2000 to 2012, data on 636,111 newly diagnosed female T2DM patients were available in the Taiwan’s National Health Insurance Research Database. By applying their data, a risk prediction model of breast cancer in patients with T2DM was created. We also collected data on potential predictors of breast cancer so that adjustments for their effect could be made in the analysis. Synthetic Minority Oversampling Technology (SMOTE) was utilized to increase data for small population samples. Each datum was randomly assigned based on a ratio of about 39:1 into the training and test sets. Logistic Regression (LR), Artificial Neural Network (ANN) and Random Forest (RF) models were determined using recall, accuracy, F1 score and area under the receiver operating characteristic curve (AUC). Results: The AUC of the LR (0.834), ANN (0.865), and RF (0.959) models were found. The largest AUC among the three models was seen in the RF model. Conclusions: Although the LR, ANN, and RF models all showed high accuracy predicting the risk of breast cancer in Taiwanese with T2DM, the RF model performed best.