Comparisons of procyanidins with different low polymerization degrees on prevention of lipid metabolism in high-fat diet/streptozotocin-induced diabetic mice.

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.

The Relationship between physical activity, nutritional status, and sarcopenia in community- dwelling older adults with type 2 diabetes: a cross-sectional study.

AIM: This study was conducted in Urumqi, Xinjiang, to assess the prevalence of sarcopenia and to determine the relationship between physical activity, nutritional status, and sarcopenia among community-dwelling patients with type 2 diabetes mellitus. METHODS: Four hundred eight cases of older people patients with type 2 diabetes mellitus in the community in Urumqi, Xinjiang, from May to August 2022 were selected for a cross-sectional on-site survey, and general information questionnaires, clinical information surveys, physical function measurements, and criteria developed by the Asian sarcopenia working group in 2019 were selected for diagnosis of sarcopenia, and unifactorial and multifactorial binary Logistic regression were applied to analyze the influencing factors of T2DM combined with sarcopenia in patients with sarcopenia. RESULTS: Among the 408 patients, 84 (20.6%) had sarcopenia, with a prevalence of 12.6%, 32.1%, and 51.9% in those aged 60-70, 71- 80, and 81 or older respectively. The prevalence increased significantly with age. Adjusting for variables, the study found that FFM of the Left Leg (OR: 0.710, 95% CI: 0.612-0.804, P = 0.024), FFM of the Right Arm (OR: 0.710, 95% CI: 0.612-0.804, P < 0.001), Age (OR: 1.246, 95% CI: 1.031-1.505, P = 0.023), Fasting Blood Glucose (OR: 1.649, 95% CI: 1.066-2.550, P = 0.025), and Post-Prandial Blood Glucose (OR: 1.455, 95% CI: 0.999-2.118, P = 0.025) were independent associated factors. An increase in MNA score (OR: 0.398, 95% CI: 0.244-0.6500, P < 0.001), ASMI (OR: 0.000, 95% CI: 0.00-0.01, P < 0.001) walking energy expenditure (MET-min) (OR: 0.998, 95% CI: 0.996-0.999, P = 0.001) reduced the prevalence of sarcopenia. CONCLUSION: This study shows that increased age, increased skeletal muscle mass index, decreased right arm FFM, increased postprandial glucose, increased MNA scores, and increased walking energy expenditure (MET-min) were associated with type 2 diabetes with sarcopenia.

Correlation of serum Meteorin-like (Metrnl) level with type 2 diabetic peripheral neuropathy.

OBJECTIVE: Meteorin-like (Metrnl), a secreted myokine, is a newly discovered neurotrophic factor. The aim of this study was to determine if there is a correlation between the Metrnl level and diabetic peripheral neuropathy (DPN). METHODS: The investigation was conducted on a sample of 80 patients with type 2 diabetes mellitus (T2DM) and 60 healthy controls. The T2DM patients were categorized into two subgroups based on skin biopsy: the DPN subgroup (n = 20) and the diabetes without neuropathy subgroup (n = 60). RESULTS: The T2DM groups had higher serum Metrnl concentrations compared with the controls. The serum Metrnl concentration was significantly lower in the DPN group than in T2DM patients without neuropathy. Logistic regression analysis demonstrated a notable correlation between serum Metrnl and DPN (OR: 0.997, 95% CI: 0.995-1.000, P < 0.05). Serum Metrnl level was negatively correlated with age and SBP after a simple logistic regression analysis. CONCLUSION: Serum Metrnl concentration is independently correlated with DPN.

Evaluation of nail fold capillaroscopy changes in patients with diabetic retinopathy and healthy controls, and its correlation with disease duration, HbA1c levels and severity of diabetic retinopathy: An observational study.

Background Diabetic retinopathy (DR) is an important microvascular complication of long-term type 2 diabetes mellitus (T2DM) leading to blindness if not properly diagnosed and managed. It can develop as early as 7 years before the diagnosis of diabetes. Nail fold capillaroscopy (NFC) is a non-invasive technique for observing capillary microvasculature and there are few studies which have explored the use of NFC in diabetes mellitus patients. Objective To study the nail fold capillaroscopic alterations in patients with T2DM having diabetic retinopathy and compare them to healthy controls. The secondary objective was to correlate the NFC findings with the duration of diabetes, haemoglobin A1c (HbA1c) levels and the severity of DR. Materials and methods This cross-sectional observational study enrolled 200 patients - 100 cases with T2DM having diabetic retinopathy (as per the American Diabetes Association criteria and Diabetic Retinopathy Disease Severity Scale) and 100 healthy age and sex-matched controls. All patients were subjected to NFC and ophthalmological assessment. Results NFC revealed that patients with DR showed significantly higher frequencies of tortuous, dilated, bushy, meandering, angulated capillaries, avascular areas and micro-haemorrhages as compared to healthy controls (p < 0.05). In proliferative DR (PDR), the frequency of tortuous, bushy capillaries, and avascular areas was statistically high and the capillary density was reduced as compared to non-proliferative DR. The DR patients with longer disease duration (>20) years had a significantly higher frequency of tortuous capillaries, avascular areas, meandering, angulated and dilated capillaries. The frequency of tortuosity, avascular areas, and bushy areas was significantly higher in patients with poor glycaemic control (HbA1c >11). Limitations A larger sample size study with different demographic populations could have provided a broader picture of NFC changes in T2DM patients with DR. Discussion NFC may act as a surrogate marker of retinal involvement in patients with DM and should be performed at regular intervals. Conclusion NFC is a quick, simple, safe, and non-invasive method to assess the capillaroscopic alterations in diabetic patients which inturn can help in assessing the severity of DR.

Preventing Type 2 Diabetes after Gestational Diabetes: A Systematic Review Mapping Physical Activity Components using the Socio-Ecological Model.

OBJECTIVES: Gestational diabetes commonly occurs during pregnancy and increases lifetime risk of type 2 diabetes following pregnancy. Engaging in physical activity postnatally can reduce this subsequent risk. Interventions aiming to increase physical activity after gestational diabetes may not address the wide range of post-pregnancy barriers. A socio-ecological approach highlights the need to include multi-level factors such as social, community and organisational factors. The aim of the review was to map intervention components to prevent type 2 diabetes after gestational diabetes using the socio-ecological model as a framework and investigate how physical activity changes align with different intervention components utilised. METHODS: Eligible studies included any study type within 5 years of a gestational diabetes diagnosis and targeted physical activity. A systematic search of MEDLINE, Cochrane Library, Web of Science, CINAHL Complete, and Scopus was conducted in October 2022. Results were categorised based on whether findings demonstrated no increases, non-statistically significant increases or statistically significant increases in physical activity. RESULTS: Forty-eight studies were included (37 different interventions). Thirty-eight studies were assessed as "adequate" quality, only two studies were "good" quality, and the remaining were limited quality. Mixed physical activity outcomes were observed across components used at the intrapersonal level, with components across other levels of the socio-ecological model showing more increases in physical activity. Intervention components within the social and organisational levels, for example childcare provision, providing group-based sessions and offering remote delivery, were more often present in interventions with physical activity increases. CONCLUSIONS FOR PRACTICE: Future interventions targeting physical activity after gestational diabetes should aim to include social and organisational-level components in their intervention design. This systematic review was registered in PROSPERO (ID: CRD42021272044).

Determinants of Course of Type 2 Diabetes in Indian Adolescents.

OBJECTIVES: To identify determinants of the course of Type 2 diabetes in Indian adolescents. METHODS: Records of 37 adolescents (24 boys; 29 post pubertal and eight pubertal) with Type 2 diabetes (initial HbA1C 10.1 ± 1.9% and BMI SDS 2.0 ± 0.8; family history of diabetes in 33, 89.2%) diagnosed at 15.2 ± 2.5 y and followed up for 3.8 ± 2.2 y till 19.1 ± 3.3 y of age, were reviewed. RESULTS: Initial treatment included insulin in 11 (29.7%), metformin alone in 22 (59.5%), and a combination of anti-diabetic medication in four (10.8%). Eleven subjects (29.7%) achieved remission at a median period of 5.3 mo (IQR- 17.13) after diagnosis; six of these relapsed within 0.9 ± 0.3 (range 0.4-1.3) y. The proportion of subjects requiring multiple anti-diabetic agents increased over follow-up (19% at six months, 32.5% at one year, 50% at two years, 59.1% at three, and 64.8% at four years), with the need for combination therapy after 0.9 ± 1.4 y. At the last follow-up, five were off treatment (13.5%), 10 (27%) were on metformin alone, and 22 (59.5%) were on multiple medications. The need for combination therapy at the last follow-up was lower in subjects with remission (27% against 73.1%, p = 0.02). CONCLUSIONS: The findings of this study suggest delayed presentation and rapid progression of Type 2 diabetes in Indian adolescents. Diagnosis on screening and achievement of remission were predictors of good outcome.

Correlation of Serum Sodium and Potassium With Thiamin Levels in Type 1 and Type 2 Diabetic Patients.

Introduction Chronic metabolic disorders such as diabetes mellitus (DM) are becoming a global health concern. According to recent studies, the pathophysiology of DM may involve factors other than traditional glycemic control, such as electrolyte balance and thiamin status. Therefore, this study evaluated the relationship between sodium and potassium and serum thiamin levels in patients with type 1 and type 2 DM. Methods This study was conducted in multiple diabetic outpatient clinics and centers in Karachi, Pakistan, using a non-probability convenience sampling method. The study lasted for approximately six months after the synopsis was approved. A total of 64 patients were selected, 32 of whom each had type 1 and type 2 DM. All patients who were between the ages of 25 and 46 years old and had either type 1 or type 2 DM were included in the study. A Mann-Whitney test and an independent t-test were used to compare the means between the two study groups. Pearson's correlation and chi-square tests were used to determine the variables, correlations, and associations with type 1 and type 2 DM. Results The study findings showed that the distribution of gender among diabetic patients revealed that among males, eight (25.0%) had type 1 DM, and 10 (31.2%) had type 2 DM. Among females, 24 (75.0%) had type 1 DM, and 22 (68.8%) had type 2 DM. Significant correlations were observed in the means of blood glucose levels, such as glycated hemoglobin (HbA1c), fasting blood sugar (FBS), and serum thiamin levels, among patients with type 1 and type 2 DM (p < 0.001). The HbA1c, FBS, and serum thiamin levels were significantly higher in type 2 DM patients than in type 1 DM patients. Among patients with type 1 DM, sodium levels were not substantially correlated with thiamin levels (p = 0.570, r = 0.104), whereas potassium levels were significantly correlated with thiamin levels (p = 0.005, r = 0.263). Conclusion We conclude that the sodium level was not significantly correlated with serum thiamin status in type 1 and type 2 DM, whereas a low positive correlation was observed between potassium and serum thiamin levels in type 1 DM. However, there was no significant correlation concerning potassium levels in type 2 DM.

Early Dinner Improves the Glycemic Profile in Habitual Late Eaters With Uncontrolled Type 2 Diabetes Mellitus in the Short Term.

Background Late dinner (LD) can worsen the glucose profile in type 2 diabetes (T2D). We assessed the short-term effect of early dinner (ED) on glycemic control in habitual late eaters with uncontrolled T2D. Methodology This interventional, single-arm, within-group trial recruited 10 habitual late eaters with uncontrolled T2D (glycosylated hemoglobin: 7-9% and either fasting plasma glucose (FPG): ≥140 mg/dl or post-prandial plasma glucose: ≥200 mg/dl). They had their usual LD (beyond 22:00 hours) on Days 0-3 and ED (before 20:00 hours) on Days 4-10. Continuous glucose monitoring system (CGMS) parameters, two-hour post-dinner, and fasting (10-hour post-dinner) investigations were analyzed. Bedtime hunger was assessed using a Labeled Magnitude Satiety Scale. Results The mean dinner time was reduced from 22:28 hours to 19:29 hours. CGMS revealed that ED lowered the 10-hour post-dinner incremental area under the curve (22,587.9 ± 5,168.3 mg/dl×mins vs. 15,886.3 ± 4,288.7 mg/dl×mins, P < 0.002), 10-hour post-dinner average blood glucose (ABG) (137.5 ± 9.3 mg/dl vs. 125 ± 7.9 mg/dl, P < 0.002), 24-hour ABG (132.2 ± 7.5 mg/dl vs. 124.8 ± 5.4 mg/dl, P = 0.037), and night mean amplitude of glucose excursion (83.7 ± 5.8 mg/dl vs. 69.3 ± 7.5 mg/dl, P = 0.027). ED also reduced FPG (119.8 ± 7.3 mg/dl vs. 105.2 ± 5.7 mg/dl, P = 0.015), fasting insulin (15.0 ± 4.3 µIU/ml vs. 9.7 ± 2.7 µIU/ml, P < 0.002), and HOMA-IR (4.36 ± 1.2 vs. 2.56 ± 0.79, P < 0.002). Post-dinner glucose, insulin, and inflammatory markers were unchanged. Bedtime hunger increased significantly on Days 4 and 5 but returned to baseline by Day 10. Conclusions A simple modification of dinner time in habitual late eaters with uncontrolled T2D improves FPG, glycemic control, and insulin resistance in the short term.

Efficacy and Safety of Vildagliptin and Remogliflozin as Add-on Therapy to Metformin in Patients of Type 2 Diabetes Mellitus: An open-label comparative study.

Objectives: This study aimed to evaluate the safety and efficacy of remogliflozin compared to vildagliptin as an add-on drug to metformin in type 2 diabetes mellitus (T2DM) treatment. Metformin is considered a first-line drug in T2DM. However, as the disease progresses with heightened insulin resistance and declining ß-cell function, the use of metformin alone is often inadequate to achieve optimum glucose levels. Methods: This prospective, randomised study was conducted at Maulana Azad Medical College and Associated Hospital in New Delhi, India, between February 2020 to January 2021. This study recruited 60 T2DM patients aged 35-70 years with glycated haemoglobin (HbA1c) >6.5% taking metformin at a daily dosage of 1,500-3,000 mg for ≥3 months. Patients were randomly assigned in a 1:1 ratio to receive either vildagliptin (50 mg) or remogliflozin (100 mg) twice daily for 90 days. The primary endpoint was a change in HbA1c levels from baseline to the end of 90 days whereas secondary endpoints were changes in lipid profile and weight. Results: The decrement in mean HbA1c levels was significantly higher in the remogliflozin group than in the vildagliptin group (-8.1% versus -2.4%; P <0.001). In addition, more significant weight loss was found in remogliflozin-treated patients (-5.2% versus -0.6%; P <0.01). Both treatments were well tolerated throughout the study. Conclusion: Compared to vildagliptin, remoglilflozin was significantly more effective in glycaemic control and weight loss in patients with T2DM and can therefore be considered as an add-on drug in T2DM not adequately controlled by metformin monotherapy.

Alterations of Gut Microbiota in Pyogenic Liver Abscess Patients with and without Type 2 Diabetes Mellitus.

Purpose: The clinical manifestations of pyogenic liver abscess (PLA) vary between patients with and without diabetes mellitus (DM). However, the relationship between PLA and the gut microbiome remains unknown. This study analyzed the composition of gut microbiota in PLA patients with and without DM and healthy controls (HCs) with the goal of identifying potential reasons for the observed variations in clinical manifestations. Patients and Methods: Using 16S ribosomal RNA(16S rRNA) gene sequencing, we analyzed the compositions of gut microbiota in 32 PLA patients with DM, 32 PLA patients without DM, and 29 matched HCs. Results: In PLA patients with DM, the D-dimer level, fibrinogen degradation products, and thrombin time were significantly higher compared to the PLA patients without DM (P < 0.05). The abundance and diversity of intestinal flora were reduced in both groups of PLA patients compared with the HCs (P < 0.05). Specifically, the PLA patients with DM showed significant decreases in the relative abundances of Bacteroides, Blautia, Prevotella9, and Faecalibacterium, whereas Enterococcus and Escherichia-Shigella were relatively more abundant (P < 0.05). Compared to PLA patients without DM, those with DM had lower relative abundances of Lactobacillus and Klebsiella (P < 0.05) and showed different bacterial flora, including Anaerosporobacter and Megamonas. Conclusion: PLA patients with DM exhibited more severe clinical manifestations of PLA compared to patients without DM. It is important to monitor blood coagulation in PLA patients with DM to prevent the development of thrombotic diseases. Additionally, PLA patients with DM exhibit distinct differences in the composition and diversity of their intestinal flora compared to both PLA patients without DM and HCs.

Relationship of lncRNA FTX and miR-186-5p levels with diabetic peripheral neuropathy in type 2 diabetes and its bioinformatics analysis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) frequently occurs as a secondary condition in individuals with type 2 diabetes mellitus (T2DM). OBJECTIVE: To explore the relationship of lncRNA FTX and miR-186-5p levels with DPN in T2DM. METHODS: The study enrolled 50 patients with T2DM and 45 patients with DPN. Expression levels of FTX and miR-186-5p were measured by RT-qPCR. The levels of MDA, GSH, and SOD in the serum were measured to assess the patients' oxidative stress levels. In addition, the target genes of miR-186-5p were analyzed by bioinformatics. RESULTS: Serum FTX levels were increased and miR-186-5p levels were decreased in patients with T2DM and DPN. Both of them had high diagnostic value for T2DM and DPN. In addition, FTX and miR-186-5p were risk factors for the onset of DPN in people with T2DM and were significantly correlated with oxidative stress indicators in patients. CONCLUSION: FTX and miR-186-5p are closely related to the disease progression of DPN in people with T2DM and may become therapeutic targets for DPN in people with T2DM.

Lipid profile changes induced by glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a systematic review and network meta-analysis.

OBJECTIVE: This study was conducted to investigate the effects of glucagon-like peptide-1 receptor (GLP-1) agonists on the lipid profiles of patients with type 2 diabetes. METHODS: We retrieved the data of phase 3 randomized controlled trials on GLP-1 agonists in patients with type 2 diabetes from the PubMed, Embase, and Cochrane library up to 11 February 2024. We extracted % changes in low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol/total cholesterol (T-CHO) and triglycerides levels from baseline. Using Bayesian network meta-analysis, mean differences and 95% credible intervals for lipid changes were estimated as a unit of percentage points (%p) by class. RESULTS: Twenty-six studies covering 22,290 participants were included. The glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 dual agonist showed significant differences in LDL-C (range of mean differences: -11.61 to -6.77%p), triglycerides (-19.94 to -13.31%p), and T-CHO (-7.94 to -5.09%p) levels compared to placebo, insulin, and sodium-glucose co-transporter 2 (SGLT2) inhibitors. The GLP-1 agonist significantly reduced T-CHO (-5.20%p; -6.39%p) and LDL-C (-4.32%p; -8.17%p) levels compared to placebo and SGLT2 inhibitors, respectively. CONCLUSIONS: The GIP/GLP-1 dual agonist positively affects the lipid profiles of patients with type 2 diabetes. This may contribute to a lower risk of cardiovascular disease in patients with type 2 diabetes. PROTOCOL REGISTRATION: PROSPERO (CRD42021282668).

The relationship between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus.

OBJECTIVE: Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM). DESIGN, PATIENTS AND MEASUREMENTS: This retrospective single-centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut-off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia. RESULTS: The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p = .001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = -.117, r = -.131, r = .117, p < .001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p < .001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76-7.52, p = .001). CONCLUSION: Albuminuria is more frequently observed in patients with hypomagnesemia.

The role of small dense LDL-C/large buoyant LDL-C ratio as an independent risk factor in patients with type 2 diabetes mellitus and metabolic syndrome

Dyslipidemia plays a key role in metabolic syndrome (MS), intricately linked to type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences in low-density lipoprotein cholesterol (LDL-C) subfraction levels between T2DM and T2DM with MS, and identify the risk factors associated with the disease. A total of 246 individuals diagnosed with T2DM, including 144 T2DM patients with MS, and 147 healthy subjects were recruited. All participants underwent a comprehensive clinical evaluation. Lipoprotein subfraction analysis was performed using the Lipoprint LDL system. Multivariate logistic regression analysis revealed that several lipid markers, including triglyceride (TG), LDL-C, large buoyant LDL-C (lbLDL-C), small dense LDL-C (sdLDL-C), LDLC2-5, and sdLDL-C/lbLDL-C ratio, were identified as independent risk factors for T2DM. Additionally, TG, sdLDL-C, LDLC-4, LDLC-5, and sdLDL-C/lbLDL-C ratio were found to be independent risk factors for T2DM with MS. Furthermore, the results of the receiver operating characteristic (ROC) curves demonstrated that sdLDL-C, LDLC-4, LDLC-3, and sdLDL-C/lbLDL-C ratio exhibited excellent predictive performance for the risk of T2DM (AUC > 0.9). The sdLDL-C/lbLDL-C ratio emerges as a shared independent risk factor for T2DM and MS complications. Furthermore, sdLDL-C/lbLDL-C ratio, along with LDL-4 and LDL-3, exhibits noteworthy predictive capabilities for T2DM.

Risk of diabetes mellitus based on the interactive association between G6PD rs72554664 polymorphism and sex in Taiwan Biobank individuals.

The presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may increase the risk of type 2 diabetes mellitus (T2DM), with differing prevalence between males and females. Although G6PD deficiency is an X-linked genetic condition, its interaction with sex regarding T2DM risk among the Taiwanese population has not been fully explored. This study aimed to investigate the association between G6PD deficiency and T2DM risk in the Taiwanese population, focusing on the potential influence of sex. Data were obtained from the Taiwan Biobank (TWB) database, involving 85,334 participants aged 30 to 70 years. We used multiple logistic regression analysis to assess the interaction between G6PD rs72554664 and sex in relation to T2DM risk. The T2DM cohort comprised 55.35% females and 44.65% males (p < 0.001). The TC + TT genotype of rs72554664 was associated with an increased risk of T2DM, with an odds ratio (OR) of 1.95 (95% CI: 1.39-2.75), and males showed an OR of 1.31 (95% CI: 1.19-1.44). Notably, the G6PD rs72554664-T allelic variant in hemizygous males significantly elevated the T2DM risk (OR), 4.57; p < 0.001) compared to females with the CC genotype. Our findings suggest that the G6PD rs72554664 variant, in conjunction with sex, significantly affects T2DM risk, particularly increasing susceptibility in males. The association of the G6PD rs72554664-T allelic variant with a higher risk of T2DM highlights the importance of sex-specific mechanisms in the interplay between G6PD deficiency and T2DM.

The predictive value of lesion-specific pericoronary fat attenuation index for major adverse cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The purpose of this study was to explore the prognostic significance of the lesion-specific pericoronary fat attenuation index (FAI) in forecasting major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). METHODS: This study conducted a retrospective analysis of 304 patients diagnosed with T2DM who underwent coronary computed tomography angiography (CCTA) in our hospital from December 2011 to October 2021. All participants were followed for a period exceeding three years. Detailed clinical data and CCTA imaging features were carefully recorded, encompassing lesion-specific pericoronary FAI, FAI of the three prime coronary arteries, features of high-risk plaques, and the coronary artery calcium score (CACS). The MACE included in the study comprised cardiac death, acute coronary syndrome (which encompasses unstable angina pectoris and myocardial infarction), late-phase coronary revascularization procedures, and hospital admissions prompted by heart failure. RESULTS: Within the three-year follow-up, 76 patients with T2DM suffered from MACE. The lesion-specific pericoronary FAI in patients who experienced MACE was notably higher compared to those without MACE (-84.87 ± 11.36 Hounsfield Units (HU) vs. -88.65 ± 11.89 HU, p = 0.016). Multivariate Cox regression analysis revealed that CACS ≥ 100 (hazard ratio [HR] = 4.071, 95% confidence interval [CI] 2.157-7.683, p < 0.001) and lesion-specific pericoronary FAI higher than - 83.5 HU (HR = 2.400, 95% CI 1.399-4.120, p = 0.001) were independently associated with heightened risk of MACE in patients with T2DM over a three-year period. Kaplan-Meier analysis showed that patients with higher lesion-specific pericoronary FAI were more likely to develop MACE (p = 0.0023). Additionally, lesions characterized by higher lesion-specific pericoronary FAI values were found to have a greater proportion of high-risk plaques (p = 0.015). Subgroup analysis indicated that lesion-specific pericoronary FAI higher than - 83.5 HU (HR = 2.017, 95% CI 1.143-3.559, p = 0.015) was independently correlated with MACE in patients with T2DM who have moderate to severe coronary calcification. Moreover, the combination of CACS ≥ 100 and lesion-specific pericoronary FAI>-83.5 HU significantly enhanced the predictive value of MACE in patients with T2DM within 3 years. CONCLUSIONS: The elevated lesion-specific pericoronary FAI emerged as an independent prognostic factor for MACE in patients with T2DM, inclusive of those with moderate to severe coronary artery calcification. Incorporating lesion-specific pericoronary FAI with the CACS provided incremental predictive power for MACE in patients with T2DM.

Risk of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Among Patients with Type 2 Diabetes Mellitus on Anti-Hyperglycemic Medications.

Background: Observed activity of metformin in reducing the risk of severe COVID-19 suggests a potential use of the anti-hyperglycemic in the prevention of post-acute sequelae of SARS-CoV-2 infection (PASC). We assessed the 3-month and 6-month risk of PASC among patients with type 2 diabetes mellitus (T2DM) comparing metformin users to sulfonylureas (SU) or dipeptidyl peptidase-4 inhibitors (DPP4i) users. Methods: We used de-identified patient level electronic health record data from the National Covid Cohort Collaborative (N3C) between October 2021 and April 2023. Participants were adults ≥ 18 years with T2DM who had at least one outpatient healthcare encounter in health institutions in the United States prior to COVID-19 diagnosis. The outcome of PASC was defined based on the presence of a diagnosis code for the illness or using a predicted probability based on a machine learning algorithm. We estimated the 3-month and 6-month risk of PASC and calculated crude and weighted risk ratios (RR), risk differences (RD), and differences in mean predicted probability. Results: We identified 5596 (mean age: 61.1 years; SD: 12.6) and 1451 (mean age: 64.9 years; SD 12.5) eligible prevalent users of metformin and SU/DPP4i respectively. We did not find a significant difference in risk of PASC at 3 months (RR = 0.86 [0.56; 1.32], RD = -3.06 per 1000 [-12.14; 6.01]), or at 6 months (RR = 0.81 [0.55; 1.20], RD = -4.91 per 1000 [-14.75, 4.93]) comparing prevalent users of metformin to prevalent users of SU/ DPP4i. Similar observations were made for the outcome definition using the ML algorithm. Conclusion: The observed estimates in our study are consistent with a reduced risk of PASC among prevalent users of metformin, however the uncertainty of our confidence intervals warrants cautious interpretations of the results. A standardized clinical definition of PASC is warranted for thorough evaluation of the effectiveness of therapies under assessment for the prevention of PASC.

Previous research suggests that metformin, due to its anti-viral, anti-inflammatory, and anti-thrombotic properties may reduce the risk of severe COVID-19. Given the shared etiology of COVID-19 and the post-acute sequelae of SARS-CoV-2 (PASC), and the proposed inflammatory processes of PASC, metformin may also be a beneficial preventive option. We investigated the benefit of metformin for PASC prevention in a population of type 2 diabetes mellitus patients with a COVID-19 diagnosis who were on metformin or two other anti-hyperglycemic medications prior to infection with SARS-CoV-2. Our results were consistent with a reduction in the risk of PASC with the use of metformin, however, the imprecise confidence intervals obtained warrants further investigation of this association of the potential beneficial effect of metformin for preventing PASC in patients with medication-managed diabetes.

Type 2 diabetes mellitus aggravates coronary atherosclerosis in hypertensive individuals based on coronary CT angiography: a retrospective propensity score-based study.

Background: The effect of type 2 diabetes mellitus (T2DM) on coronary atherosclerosis detected on coronary computed tomography angiography (CCTA) in hypertensive patients has attracted increasing attention. This study investigated the relationships of T2DM with coronary artery plaque characteristics and semiquantitative CCTA scores in hypertensive patients. Materials and methods: In this single-center study, 1,700 hypertensive patients, including 850 T2DM [HT(T2DM+)] and 850 non-T2DM [HT(T2DM-)] individuals, were retrospectively analyzed after propensity matching. Plaque type, extent, coronary stenosis, segment involvement score (SIS), segment stenosis score (SSS), and CT-based Leaman score (CT-LeSc) based on CCTA were assessed and compared between the two groups. Results: HT(T2DM+) patients had more coronary segments with calcified plaque (2.08 ± 2.20 vs. 1.40 ± 1.91), mixed plaque (2.90 ± 2.87 vs. 2.50 ± 2.66), nonobstructive stenosis (4.23 ± 2.44 vs. 3.62 ± 2.42), and obstructive stenosis (1.22 ± 2.18 vs. 0.78 ± 1.51), a lower proportion of 1-vessel disease (15.3% vs. 25.5%), a higher proportion of 3-vessel disease (59.6% vs. 46.7%), and higher SIS (5.5 ± 3.1 vs. 4.4 ± 3.0), SSS (10.3 ± 8.5 vs. 7.7 ± 7.1), and CT-LeSc (9.4 ± 5.6 vs. 7.9 ± 5.2) than HT(T2DM-) patients (all P-values <0.05). Multivariable analysis revealed that T2DM was an independent risk factor for calcified plaque [odds ratio (OR) = 2.213], obstructive coronary artery disease (CAD) (OR = 1.271), multivessel disease (OR = 1.838), SIS > 4 (OR = 1.910), SSS > 6 (OR = 1.718), and CT-LeSc > 5 (OR = 1.584) in hypertension population (all P-values <0.05). Conclusion: T2DM was independently associated with the presence of calcified coronary artery plaque and increased the risk of obstructive CAD, multivessel disease, and CT-LeSc > 5 in hypertensive patients. More attention should be given to the assessment and management for coronary atherosclerosis in hypertensive patients with T2DM, as this population may have a higher risk of cardiovascular events.

Epigenetics of hypertension as a risk factor for the development of coronary artery disease in type 2 diabetes mellitus.

Hypertension, a multifaceted cardiovascular disorder influenced by genetic, epigenetic, and environmental factors, poses a significant risk for the development of coronary artery disease (CAD) in individuals with type 2 diabetes mellitus (T2DM). Epigenetic alterations, particularly in histone modifications, DNA methylation, and microRNAs, play a pivotal role in unraveling the complex molecular underpinnings of blood pressure regulation. This review emphasizes the crucial interplay between epigenetic attributes and hypertension, shedding light on the prominence of DNA methylation, both globally and at the gene-specific level, in essential hypertension. Additionally, histone modifications, including acetylation and methylation, emerge as essential epigenetic markers linked to hypertension. Furthermore, microRNAs exert regulatory influence on blood pressure homeostasis, targeting key genes within the aldosterone and renin-angiotensin pathways. Understanding the intricate crosstalk between genetics and epigenetics in hypertension is particularly pertinent in the context of its interaction with T2DM, where hypertension serves as a notable risk factor for the development of CAD. These findings not only contribute to the comprehensive elucidation of essential hypertension but also offer promising avenues for innovative strategies in the prevention and treatment of cardiovascular complications, especially in the context of T2DM.

Causal association between type 2 diabetes mellitus and acute suppurative otitis media: insights from a univariate and multivariate Mendelian randomization study.

Background: Type 2 diabetes mellitus (T2DM) and hearing loss (HL) constitute significant public health challenges worldwide. Recently, the association between T2DM and HL has aroused attention. However, possible residual confounding factors and other biases inherent to observational study designs make this association undetermined. In this study, we performed univariate and multivariable Mendelian Randomization (MR) analysis to elucidate the causal association between T2DM and common hearing disorders that lead to HL. Methods: Our study employed univariate and multivariable MR analyses, with the Inverse Variance Weighted method as the primary approach to assessing the potential causal association between T2DM and hearing disorders. We selected 164 and 9 genetic variants representing T2DM from the NHGRI-EBI and DIAGRAM consortium, respectively. Summary-level data for 10 hearing disorders were obtained from over 500,000 participants in the FinnGen consortium and MRC-IEU. Sensitivity analysis revealed no significant heterogeneity of instrumental variables or pleiotropy was detected. Results: In univariate MR analysis, genetically predicted T2DM from both sources was associated with an increased risk of acute suppurative otitis media (ASOM) (In NHGRI-EBI: OR = 1.07, 95% CI: 1.02-1.13, P = 0.012; In DIAGRAM: OR = 1.14, 95% CI: 1.02-1.26, P = 0.016). Multivariable MR analysis, adjusting for genetically predicted sleep duration, alcohol consumption, body mass index, and smoking, either individually or collectively, maintained these associations. Sensitivity analyses confirmed the robustness of the results. Conclusion: T2DM was associated with an increased risk of ASOM. Strict glycemic control is essential for the minimization of the effects of T2DM on ASOM.