Complications In Type 2 Diabetes Mellitus Patients Research Articles

Clinical Profile and Risk Factors for Complication of Type 2 Diabetes Mellitus at the National Referral Hospital, Bhutan: A Descriptive Cross-Sectional Study.

Globally, diabetes mellitus is a major public health concern affecting 10.5% of the population. Nearly 90% of these people have Type 2 diabetes mellitus (T2DM). In Bhutan, T2DM is prevalent in 5.6% of the population, and around 60% are unaware of their diagnosis of diabetes. There is no baseline information on the rate and the risk factors for complications of diabetes in Bhutan. The study assessed the clinical profile and the risk factors for complications of T2DM at the Jigme Dorji Wangchuk (JDW) National Referral Hospital, Bhutan. A descriptive cross-sectional study was conducted at the JDW National Referral Hospital, Bhutan, from January to December 2019. Patients with T2DM attending diabetic clinics were included in the study. Demographic variables and metabolic profiles were recorded using a standard pro forma. Descriptive statistics were used to express the results. The association of clinical profiles with the microvascular complication was assessed using multivariate logistic analysis with statistical significance at p < 0.05. There were 292 patients with T2DM during the study period. The rate of microvascular complication is around 25% in T2DM. Among the complications, diabetic retinopathy occurred in over 51%, followed by neuropathy (29.7%) and nephropathy (18.9%). Over 1/3rd of patients had a duration of diabetes over 10 years with a mean duration of 6.3 (5.4) years, and around 44% (127/292) of them had poor glycemic control (HbA1C ≥ 7%). The age ≥ 60 years and the duration of diabetes ≥ 10 years were independent risk factors for microvascular complications in T2DM patients. Regular exercise prevents retinopathy (OR 0.4, 95%CI 0.2-0.9, p = 0.026). There is a microvascular complication in 1 in 4 of type 2 diabetic patients. Age over 60 years and a duration of diabetes of more than 10 years are independent risk factors for microvascular complications, and regular exercise is preventive for microvascular complications.

A Prospective Cross-Sectional Study on the Correlation of Adenosine Deaminase and HbA1c With Microvascular Complications in Type 2 Diabetes Mellitus at a Tertiary Care Hospital in Central India.

Background Type 2 diabetes mellitus (T2DM) is a prevalent chronic condition characterized by hyperglycemia, which can lead to various microvascular complications, including diabetic nephropathy, neuropathy, and retinopathy. Identifying reliable biomarkers for early detection and risk stratification of these complications is crucial for improving patient outcomes. Adenosine deaminase (ADA) and HbA1c have emerged as potential markers associated with immune function, inflammation, and long-term glycemic control. This study investigates the correlation between ADA and HbA1c levels and microvascular complications in patients with T2DM. Material and methods This prospective observational cross-sectional study involved 150 patients diagnosed with T2DM, focusing on those with diabetic nephropathy, neuropathy, and retinopathy. Clinical data were collected through patient interviews, clinical examinations, and laboratory tests, including measurements of fasting blood glucose, HbA1c, serum creatinine, ADA levels, and urine protein creatinine ratio (UPCR). Fundus examinations and nerve conduction velocity (NCV) tests were performed to assess diabetic retinopathy and neuropathy, respectively. Data were analyzed using SPSS version 25.0 (IBM Corp., Armonk, New York), with statistical tests to evaluate the correlation between ADA and HbA1c levels and microvascular complications. Results The study found a significant correlation between elevated ADA and HbA1c levels and microvascular complications in patients with T2DM. Higher ADA levels were particularly associated with diabetic nephropathy (p=0.003), while HbA1c levels showed a positive correlation with all three complications: nephropathy, neuropathy, and retinopathy. The findings suggest that ADA and HbA1c levels can serve as valuable biomarkers for identifying patients at higher risk of developing these complications. Conclusion This study highlights the potential of ADA and HbA1c as biomarkers for early detection and risk assessment of microvascular complications in T2DM patients. Routine monitoring of these markers could improve the management and prognosis of diabetic patients by enabling timely interventions to prevent or mitigate the progression of complications. Further research is needed to explore the underlying mechanisms linking ADA with diabetic complications and to validate its clinical utility.

The correlation between patients with type 2 diabetes mellitus and chronic microvascular complications during the glucose peak time

IntroductionTo assess the Type 2 Diabetes Mellitus (T2DM) patients in association with Chronic Microvascular Complications at Glucose Peak Time and the association among chronic microvascular complications in T2DM patients and the glucose peak period in the typical steamed bread meal test. MethodsOverall 1095 T2DM patients were classified as three groups: (1) Group G1: glucose peak time ≤ 1 h (n = 84), Group G2: 1 h < glucose peak time ≤ 2 h (n = 648) and Group G3: glucose peak time > 2 h (n = 363). The clinical characteristics, insulin characteristics and glucose peak time and chronic microvascular complications markers of patients in each group was analyzed and compared. Statistical analyses were performed using SPSS 23.0, employing chi-square tests, Kruskal-Wallis tests, one-way ANOVA, and binary logistic regression analysis, with significance set at P < 0.05. ResultsAge, length of disease, glycated hemoglobin (HbA1c), urine albumin-creatinine ratio (UACR), and the number of patients with diabetic retinopathy (DR) increased (all P < 0.05) in those with postponed glucose peak time, while insulinogenic indexes, the AUC for C-p (AUCC-p), fasting, and 120-min C-peptide (C-p) decreased (all P < 0.05). Only age was connected to patients with diabetic kidney disease (DKD) independently in binary logistic regression analysis, although delayed glucose peak time was related to the presence of patients with DR. (all P < 0.05). ConclusionDelayed glucose peak time contributed to DR. Attention should be paid to condition of chronic microvascular complications in T2DM patients with a postponed peak glucose timing.

Beyond Blood Sugar: How Left Atrium Strain Predicts Cardiac Outcomes in Type 2 Diabetes.

Speckle tracking echocardiography is an innovative imaging technique that evaluates myocardial motion, including the function of the left atrium (LA). The assessment of the left atrium's function across its dimensions can have diagnostic and prognostic roles in various cardiovascular conditions. Left atrial strain has been recognized as a valuable predictor of mortality and cardiovascular incidents in the general population across various conditions. For individuals with type 2 diabetes mellitus (T2DM), left atrial dysfunction, as gauged by speckle tracking echocardiography, appears particularly prognostic. Parameters such as peak atrial longitudinal strain (PALS) and left atrial stiffness have been linked with heightened risks of severe cardiovascular events, including atrial fibrillation (AF), heart failure (HF) hospitalizations, or mortality. Consequently, recognizing left atrial dysfunction early is crucial for accurate diagnosis, guiding treatment choices, comprehensive patient management, and prognosis evaluation. Using two-dimensional (2D) speckle tracking echocardiography, results from recent studies report that treatment with empagliflozin significantly enhanced LA function in patients with type 2 diabetes mellitus, improving left atrial strain (LAS) contraction and reservoir values. Furthermore, treatments with glucagon-like peptide-1 (GLP)-1 receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors were shown to improve LA reservoir strain more effectively than insulin alone, suggesting their potential in reducing cardiovascular complications in T2DM patients. This narrative review further addresses ongoing challenges and potential enhancements needed to boost the clinical value of left atrium strain, emphasizing its significance in managing and improving outcomes for diabetic patients.

Relationship between serum 1, 5-anhydroglucitol level and insulin resistance, microvascular complications in type 2 diabetes mellitus

Objective: To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data of 836 patients with T2DM admitted to the Changsha Central Hospital Affiliated to University of South China from May to December 2023 were retrospectively and cross-sectionally analyzed. Serum 1, 5-AG levels were detected by pyranose oxidase method. According to the microvascular complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy), the patients were divided into simple group (no microvascular complications, n=490), complication group 1 (1 microvascular complications, n=217), and complication group 2 (2 or more microvascular complications, n=129). The relationship between serum 1, 5-AG level and the related indicators of insulin resistance in T2DM patients were explored by Spearman correlation analysis, and the influencing factors of microvascular complications in T2DM patients were explored by multiple ordered logistic regression analysis. Results: The levels of FBG(fasting blood glucose) [(7.37±0.56) mmol/L], FINS(fasting insulin) [(11.34±1.86) mU/L] and HOMA-IR(homeostatic model assessment of insulin resistance) (0.96±0.31) in simple group were lower than those in complication group 1 [(8.37±1.02) mmol/L, (16.26±2.32) mU/L, (1.32±0.41)], complication group 2 [(10.25±2.13) mmol/L, (18.53±2.67) mU/L, (1.54±0.44)], and FBG, FINS and HOMA-IR in complication group 1 were lower than those in complication group 2, and the differences were statistically significant (F=537.470, 791.690, 136.340, P<0.001). Serum 1, 5-AG level in simple group [77.16 (16.30, 128.07) μg/ml] was higher than that in complication group 1 [51.05 (14.67, 63.18) μg/ml] and complication group 2 [30.42 (12.53, 47.26) μg/ml], and the serum level of 1, 5-AG in complication group 1 was higher than that in complication group 2, and the difference was statistically significant (H=210.020, P<0.001). The results of Spearman correlation analysis showed that serum 1, 5-AG level was negatively correlated with FBG, FINS and HOMA-IR in T2DM patients (r=-0.431, -0.372, -0.546, P<0.001). The results of multiple ordered logistic regression analysis showed that Longer duration of diabetes (OR=2.261, 95%CI: 1.564-3.269), increased HbA1c (OR=2.040, 95%CI: 1.456-2.858), and increased HOMA-IR (OR=2.158, 95%CI: 1.484-3.137) and decreased 1, 5-AG (OR=2.512, 95%CI: 1.691-3.732) were independent risk factors for microvascular complications in T2DM patients (P<0.05). The results of ROC curve analysis showed that the area under the curve of serum 1, 5-AG in the identification of one microvascular complication was 0.763 (95%CI: 0.731-0.795), and the area under the curve of serum 1, 5-AG in the identification of two or more microvascular complications was 0.730 (95%CI: 0.692-0.767). Conclusion: Serum 1, 5-AG level is negatively correlated with insulin resistance in T2DM patients. Low serum 1, 5-AG level may be an independent risk factor for microvascular complications in T2DM patients.

Potential role of serum copeptin among smoker T2DM patients with emphasis to ACE I/D gene polymorphism predicting DN

Diabetic nephropathy represents one of the main long-term complications in T2DM patients. Cigarette smoking represents one of modifiable renal risk factors to kidney damage due to lead (Pb) exposure in these patients. Our goal is to investigate serum copeptin and Kidney injury molecule-1 (KIM-1) and urinary lead (UPb) in type 2 diabetes mellitus (T2DM) patients even smokers and non-smokers groups and compared to corresponding health controls and assess its associations with Angiotensin-Converting enzyme Insertion/Deletion polymorphism [ACE (I/D)] polymorphism in diabetic nephropathy progression in those patients. In present study, 106 T2DM patients and 102 healthy control individuals were enrolled. Serum glucose, copeptin, KIM-1, total cholesterol (TChol), triglycerides (TG), estimated glomerular filtration rate (eGFR) and UPb levels and ACE (I/D) polymorphisms were assessed in both groups. Results mentioned to significant variations in all parameters compared to in T2DM group compared to control group. Serum copeptin and UPb demonstrated significant difference in diabetic smokers (DS) and diabetic non-smokers (DNS) groups while KIM-1 exhibited significant change between DNS and healthy control non-smokers (CNS) groups. Positive relation was recorded between serum glucose and KIM-1 while negative one was found between serum copeptin and TChol. D allele was associated with significant variation in most parameters in T2DM, especially insertion/deletion (ID) polymorphism. ROC curve analysis (AUC) for serum copeptin was 0.8, p < 0.044 and for Kim-1 was 0.54, p = 0.13 while for uPb was 0.71, p < 0.033. Serum copeptin and UPb might be a prognostic biomarker for renal function decline in smoker T2DM patients while KIM-1 was potent marker in non-smoker T2DM with association with D allele of ACE I/D gene polymorphism.

Association of RASGRP1 polymorphism with vascular complications in Chinese diabetic patients with glycemic control and antihypertensive treatment

BackgroundStudies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated.ObjectiveThis study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients.MethodsWe retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL).ResultsOur study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21–0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20–0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25–0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11–4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03–4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15–0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02).ConclusionWe found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.

Dulaglutide restores endothelial progenitor cell levels in diabetic mice and mitigates high glucose-induced endothelial injury through SIRT1-mediated mitochondrial fission

Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.

Associations between Skin Autofluorescence Levels with Cardiovascular Risk and Diabetes Complications in Patients with Type 2 Diabetes.

Advanced Glycation End Products (AGEs) contribute to the pathophysiology of type 2 diabetes mellitus (T2DM) and cardiovascular (CV) diseases (CVDs), making their non-invasive assessment through skin autofluorescence (SAF) increasingly important. This study aims to investigate the relationship between SAF levels, cardiovascular risk, and diabetic complications in T2DM patients. We conducted a single-center, cross-sectional study at Consultmed Hospital in Iasi, Romania, including 885 T2DM patients. The assessment of SAF levels was performed with the AGE Reader™, (Diagnoptics, Groningen, The Netherlands). CVD prevalence was 13.9%, and according to CV risk category distribution, 6.1% fell into the moderate-risk, 1.13% into the high-risk, and 92.77% into the very-high-risk category. The duration of DM averaged 9.0 ± 4.4 years and the mean HbA1c was 7.1% ± 1.3. After adjusting for age and eGFR, HbA1c values showed a correlation with SAF levels in the multivariate regression model, where a 1 SD increase in HbA1c was associated with a 0.105 SD increase in SAF levels (Nagelkerke R2 = 0.110; p < 0.001). For predicting very high risk with an SAF cut-off of 2.35, sensitivity was 67.7% and specificity was 56.2%, with an AUC of 0.634 (95% CI 0.560-0.709, p = 0.001). In T2DM, elevated SAF levels were associated with higher CV risk and HbA1c values, with 2.35 identified as the optimal SAF cut-off for very high CV risk.

Machine learning reveals serum myristic acid, palmitic acid and heptanoylcarnitine as biomarkers of coronary artery disease risk in patients with type 2 diabetes mellitus

BackgroundCoronary heart disease (CHD) is the most important complication of type 2 diabetes mellitus (T2DM) and the leading cause of death. Identifying the risk of CHD in T2DM patients is important for early clinical intervention. MethodsA total of 213 participants, including 81 healthy controls (HCs), 69 T2DM patients and 63 T2DM patients complicated with CHD were recruited in this study. Serum metabolomics were conducted by using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Demographic information and clinical laboratory test results were also collected. ResultsMetabolic phenotypes were significantly altered among HC, T2DM and T2DM-CHD. Acylcarnitines were the most disturbed metabolites between T2DM patients and HCs. Lower levels of bile acids and higher levels of fatty acids in serum were closely associated with CHD risk in T2DM patients. Artificial neural network model was constructed for the discrimination of T2DM and T2DM complicated with CHD based on myristic acid, palmitic acid and heptanoylcarnitine, with accuracy larger than 0.95 in both training set and testing set. ConclusionAltogether, these findings suggest that myristic acid, palmitic acid and heptanoylcarnitine have a good prospect for the warning of CHD complications in T2DM patients, and are superior to traditional lipid, blood glucose and blood pressure indicators.

Genetic and Transcriptomic Background of Oxidative Stress and Antioxidative Therapies in Late Complications of Type 2 Diabetes Mellitus: A Systematic Review.

This systematic review extensively investigated the role of the genetic and transcriptomic factors in late complications of type 2 diabetes mellitus (T2DM) and the current approaches targeting oxidative-stress-related pathways with antioxidant therapies. To cover our broad research area, we have conducted two systematic searches, the first focusing on genetic and transcriptomic factors affecting oxidative stress and the second one focusing on the antioxidant therapies in late complications of T2DM. The final review included 33 genetic and transcriptomic studies and 23 interventional randomized clinical trials. The conducted systematic review highlights the important role of oxidative stress in the development of late complications in T2DM patients. However, the current level of evidence does not support the use of genetic and transcriptomic factors as predictive and prognostic biomarkers for the development of T2DM late complications. Further studies are needed to elucidate the potential of targeting oxidative-stress-related pathways for novel preventative and therapeutic approaches. Additionally, antioxidants both in dietary and supplement form have been shown to improve different metabolic and biochemical parameters in T2DM patients with developed late complications. In recent years, studies have improved in methodological quality despite still mainly focusing on microvascular late complications of T2DM. Furthermore, the observed interventional studies suggest non-homogeneity in the duration of observation. As many studies do not provide post-intervention follow-up testing, it is difficult to assess the long-term health benefits of antioxidant supplementation.

The Study of Relationship between Plasma Fibrinogen Level and the Macrovascular Complications in Type 2 Diabetes Mellitus patients in a Tertiary Health Care Centre in Eastern India

Introduction: The macrovascular complications in patients of Type 2 Diabetes Mellitus (T2DM) are an expression of the generalized atherosclerotic process affecting the blood vessels of the body. Studies have revealed cardinal role of inflammation in the development of atherosclerosis. Literature review suggests that the level of plasma fibrinogen, an inflammatory marker, is elevated in T2DM and more so in those with the macrovascular complications. Therefore, this study was taken up with the aim to determine the association of plasma fibrinogen level with the macrovascular complications in patients of T2DM. Methods and aterials: This was a prospective observational study undertaken in Tata Main Hospital from November 2020 to October 2022. It included T2DM out-patients and those admitted in the Department of Medicine between the age group of 40 to 80 years. Patient’s clinical history and detailed physical examination were noted. Relevant blood tests (including HbA1c, lipid profile) and plasma fibrinogen levels were done. All patients were evaluated for complications of Coronary Artery Disease (CAD), cerebrovascular disease and peripheral vascular disease using appropriate investigations. The statistical association was determined by chi -square (χ2) and independent sample t-tests where appropriate. The relationship between plasma fibrinogen level and the macrovascular complications was determined using binary logistic regression. Results: The study involved 180 patients. Their mean age was 58.63 ± 7.177 years with most patients in 51-60 years age group. Male preponderance was seen and the male to female ratio was 1.86:1. While the average duration of T2DM in the study population was 6.744 ± 2.376 years, mean HbA1c level was 8.2 ± 1.9% (range: 6.2% to 9.8%). The mean Body Mass Index (BMI) was 24.57 ± 2.49 Kg/m2, with 61.67 % of cases having BMI of 25-29.9. The mean fibrinogen level in patients was 446.50 ± 28.449 mg/dl (ranged: 358.3 mg/dl to 513.0 mg/d). Diabetics without complications had mean fibrinogen level of 443.3 ± 28.3 mg/dl while those with complications had level of 469.6 ± 16.8 mg/dl (P = 0.000). 43 (23.9%) patients had macrovascular complications. Peripheral vascular disease was observed in 31(17.2%), cerebrovascular disease in 16 (8.9%) and CAD in 20 (11.1%) patients while hypertension was observed in 68 (37.8%) patients. Fibrinogen level showed a positive relation with age (R- 0.541, P &lt;0.001), male gender, BMI (R- 0.515, P=0.0001), total cholesterol levels more than 200 mg/dl (R-0.365, P = 0.0001) and HbA1c (R-0.355 with P = 0.0001). Binomial logistic regression demonstrated significant association between plasma fibrinogen level with macrovascular complications of diabetes (Wald test: 7.482, odds ratio-1.062, P&lt;0.01). Furthermore, the association was found to be independent after adjusting for the confounding factors. Conclusion: Our study suggests that plasma fibrinogen level may be viewed as an independent risk factor for the development of macrovascular complications in T2DM patients. Hence, in these patients, it can be used as a marker for the prediction of the macrovascular complications.

Mitochondrial dysfunction and onset of type 2 diabetes along with its complications: a multi-omics Mendelian randomization and colocalization study.

Mitochondrial dysfunction plays a crucial role in Type 2 Diabetes Mellitus (T2DM) and its complications. However, the genetic pathophysiology remains under investigation. Through multi-omics Mendelian Randomization (MR) and colocalization analyses, we identified mitochondrial-related genes causally linked with T2DM and its complications. Summary-level quantitative trait loci data at methylation, RNA, and protein levels were retrieved from European cohort studies. GWAS summary statistics for T2DM and its complications were collected from the DIAGRAM and FinnGen consortiums, respectively. Summary-data-based MR was utilized to estimate the causal effects. The heterogeneity in dependent instrument test assessed horizontal pleiotropy, while colocalization analysis determined whether genes and diseases share the same causal variant. Enrichment analysis, drug target analysis, and phenome-wide MR were conducted to further explore the biological functions, potential drugs, and causal associations with other diseases. Integrating evidence from multi-omics, we identified 18 causal mitochondrial-related genes. Enrichment analysis revealed they were not only related to nutrient metabolisms but also to the processes like mitophagy, autophagy, and apoptosis. Among these genes, Tu translation elongation factor mitochondrial (TUFM), 3-hydroxyisobutyryl-CoA hydrolase (HIBCH), and iron-sulfur cluster assembly 2 (ISCA2) were identified as Tier 1 genes, showing causal links with T2DM and strong colocalization evidence. TUFM and ISCA2 were causally associated with an increased risk of T2DM, while HIBCH showed an inverse causal relationship. The causal associations and colocalization effects for TUFM and HIBCH were validated in specific tissues. TUFM was also found to be a risk factor for microvascular complications in T2DM patients including retinopathy, nephropathy, and neuropathy. Furthermore, drug target analysis and phenome-wide MR underscored their significance as potential therapeutic targets. This study identified 18 mitochondrial-related genes causally associated with T2DM at multi-omics levels, enhancing the understanding of mitochondrial dysfunction in T2DM and its complications. TUFM, HIBCH, and ISCA2 emerge as potential therapeutic targets for T2DM and its complications.

Association of serum omentin levels with microvascular complications of type 2 diabetes mellitus: a systematic review and meta-analysis.

Type 2 diabetes mellitus (T2DM) is a chronic condition associated with various microvascular complications, including neuropathy, retinopathy, and nephropathy. Recent studies have suggested a potential association between serum omentin levels and the risk of developing microvascular complications in patients with T2DM. However, the existing evidence remains inconclusive. Therefore, we conducted a systematic review and meta-analysis to examine the association between serum omentin levels and microvascular complications in T2DM patients. A comprehensive search was conducted in PubMed, Scopus, and Google Scholar databases to retrieve relevant articles published up to May 2023. Observational studies investigating omentin levels association with microvascular complications in T2DM patients were included. Data was extracted and hence analyzed. A total of seven cross-sectional articles met the inclusion criteria, with a total population of 1587 participants. The meta-analysis revealed a significant association between serum omentin levels and microvascular complications in patients with T2DM. Serum omentin levels were lower in patients with microvascular complications than in those without complications (Mean difference, 95% confidence interval: -1.31 [-2.50, -0.13], I2 = 99.62%). This systematic review and meta-analysis provides evidence supporting an association between serum omentin levels and microvascular complications in patients with T2DM. The findings suggest that Omentin may be lower in T2DM patients with microvascular complications. Further research is warranted to elucidate the underlying mechanisms and explore the clinical implications of these findings. The online version contains supplementary material available at 10.1007/s40200-023-01359-2.

Lifetide biofeedback intervention in type 2 diabetic patients: a pilot observation

To evaluate the therapeutic efficacy of lifetide biofeedback intervention in patients with type 2 diabetes mellitus (T2DM). We analyzed the changes in average blood glucose, estimated glycosylated hemoglobin (HbA1c), fasting blood glucose and HbA1c levels in 5 patients with T2DM undergoing lifetide biofeedback intervention without the use of hypoglycemic drugs. A transient blood glucose monitoring system was used for drug withdrawal management during the intervention. Compared with those before the intervention, the average blood glucose and fasting blood glucose and HbA1c levels showed no significant changes after the intervention without using hypoglycemic drugs (P>0.05), but the estimated HbA1c was significantly decreased after the intervention (P<0.05). Two patients achieved complete remission, two showed partial remission, and one had substantially improved blood glucose levels. One patient showed a marked increase in extremity temperature after the intervention (P<0.05). Another patient had a significantly increased heart rate variability index (P<0.05) without obvious changes in heart rate after the intervention (P>0.05). By reestablishing the balance in autonomic nervous system regulation and enhancing peripheral microcirculation, lifetide biofeedback intervention helps to maintain stable blood glucose levels, achieve disease remission, and reduce the occurrence of complications in T2DM patients after discontinuation of hypoglycemic drugs without changing their lifestyles.

Serum Lipoprotein(a) and High-Density Lipoprotein Cholesterol Associate with Diabetic Nephropathy: Evidence from Machine Learning Perspectives.

Diabetic nephropathy (DN) is a common complication of type 2 diabetes mellitus (T2DM) that significantly impacts the quality of life for affected patients. Dyslipidemia is a known risk factor for developing cardiovascular complications in T2DM patients. However, the association between serum lipoprotein(a) (Lp(a)) and high-density lipoprotein cholesterol (HDL-C) with DN requires further investigation. For this cross-sectional study, we randomly selected T2DM patients with nephropathy (DN, n = 211) and T2DM patients without nephropathy (T2DM, n = 217) from a cohort of 142,611 patients based on predefined inclusion and exclusion criteria. We collected clinical data from the patients to identify potential risk factors for DN using binary logistic regression and machine learning. After obtaining the feature importance score of clinical indicators by building a random forest classifier, we examined the correlations between Lp(a), HDL-C and the top 10 indicators. Finally, we trained decision tree models with top 10 features using training data and evaluated their performance with independent testing data. Compared to the T2DM group, the DN group had significantly higher serum levels of Lp(a) (p < 0.001) and lower levels of HDL-C (p = 0.028). Lp(a) was identified as a risk factor for DN, while HDL-C was found to be protective. We identified the top 10 indicators that were associated with Lp(a) and/or HDL-C, including urinary albumin (uALB), uALB to creatinine ratio (uACR), cystatin C, creatinine, urinary ɑ1-microglobulin, estimated glomerular filtration rate (eGFR), urinary β2-microglobulin, urea nitrogen, superoxide dismutase and fibrinogen. The decision tree models trained using the top 10 features and with uALB at a cut-off value of 31.1 mg/L showed an average area under the receiver operating characteristic curve (AUC) of 0.874, with an AUC range of 0.870 to 0.890. Our findings indicate that serum Lp(a) and HDL-C are associated with DN and we have provided a decision tree model with uALB as a predictor for DN.

Metabolic Syndrome in Type 2 Diabetes Mellitus Patients: Prevalence, Risk Factors, and Associated Microvascular Complications.

Background The chronic macro and microvascular complications of diabetes mellitus pose serious health challenges. Metabolic syndrome (MetSy) is characterized by central obesity, glucose intolerance, hyperinsulinemia, low high-density lipoproteins (HDLs), high triglycerides (TGs), and hypertension. MetSy precedes or accompanies diabetes, and it has been linked to an increased risk of cardiovascular disease and premature death. This study aimed to estimate prevalence, identify risk factors, and evaluate associated microvascular complications among MetSy patients with type 2 diabetes mellitus (T2DM). Methodology Over the period of March 20, 2022, to March 31, 2023, a prospective cohort study was conducted at the Outdoor Clinic and Medicine Department of Sheikh Zayed Hospital, Rahim Yar Khan. Based on the International Diabetes Federation MetSy criteria, a total of 160 patients fulfilling the inclusion criteria were selected. A special proforma was used to obtain sociodemographic, clinical, and laboratory variables of MetSy in diabetic participants. Blood pressure and anthropometric measurements such as waist circumference (WC) and body mass index (BMI) were measured. Fasting venous blood was collected to analyze biochemical variables such as fasting blood sugar (FBS), TG, and high-density lipoprotein-cholesterol (HDL-C). The microvascular complications of T2DM were established using fundus ophthalmoscopy and neurological and kidney function assessments with the help oflaboratory tests. These variables were matched between MetSy and no MetSy groups along with the presence or absence of diabetes microvascular complications. This information was analyzed based on these assessments and patient interviews. Results Of the 160 T2DM patients, the mean age was 52 years with a predominance of females (51.8%) in the 50-59-year age group (56.8%). The average BMI for females was 29.38 ± 0.54 kg/m², and 32 (20%) had obesity. Females exhibited a large WC of 93.52 ± 1.58 cm, and 48 of 83 females had reported diabetes microvascular complications. A significant p-value was observed for hypertension, high TG, low HDL-C, large WC, obesity, BMI, age, and female gender on comparing diabetics with metabolic syndrome (MetSy+) and those without metabolic syndrome (MetSy-). The prevalence of microvascular complications in T2DM patients with MetSy+ was 52.5% compared with 47.5% in MetSy-. The prevalence of diabetic retinopathy was 24.9% (95% confidence interval (CI) = 20.3%-29.6%), nephropathy was 16.8% (95% CI = 12.8%-20.7%), and neuropathy was 10.8% (95% CI = 7.4%-13.3%). Conclusions The prevalence of MetSy observed among T2DM patients was 65%, with married obese females in the 50-59-year age group being more likely to be affected than males. Hypertension, poor glycemic control, high TG, low HDL-C, and greater anthropometric waist measurements and BMI were additional risk factors that tended to increase the MetSy burden in T2DM. Diabetic retinopathy, nephropathy, and neuropathy were the most prevalent microvascular complications of diabetes, and immediate attention is needed to stop their detrimental effects. Longer uncontrolled diabetes, increasing age, and hypertension were independent predictors of microvascular complications. To further reduce the risks of complications that threaten healthy aging and prognosis for these patients, MetSy screening, health education, and better diabetic management are crucial.

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.

A Clinical Study on Musculoskeletal Changes Seen in Type 2 Diabetes Mellitus: A Single-Center Study

Abstract Background: Type 2 Diabetes mellitus (T2DM) may affect the musculoskeletal (MSK) system in a variety of ways. The impacts can be debilitating enough to impair functional ability and quality of life. MSK complications are the most common endocrine arthropathies which are often under-recognized and poorly treated. This study was done to evaluate the prevalence of MSK complications and its correlation with microvascular complications of T2DM given the paucity of similar studies in India particularly South India. Materials and Methods: A cross-sectional study was conducted on 130 diabetic patients at a tertiary care hospital in Bengaluru. The patient’s demographic details, clinical profile including history, general physical examination, systemic examination, and relevant investigations were done to record microvascular complications. A thorough MSK system examination along with imaging of bones and joints was also performed. Results: Out of 130 diabetic patients, 21 patients (16.2%) had MSK complications of which 47.6% (n = 10) of them had carpal tunnel syndrome and 42.8% (n = 9) had frozen shoulder and 9.5% (n = 2) had diabetic amyotrophy. It was also noted that patients who were on oral hypoglycemic agents alone were more likely to develop MSK complications (57.14%) than patients solely on insulin (14.2%). Poor glycemic control, existing microvascular complications, and low high-density lipoprotein were found to be associated with increased risk of MSK complications. Conclusion: The prevalence of MSK complications in T2DM patients is quite significant and is also associated with microvascular complications. Improved glycemic control in T2DM was found to reduce the burden of such complications. Early identification of MSK complications can improve the quality of life in diabetic patients and hence demands proper screening and follow-up.

Relationship of liver fat content with systemic metabolism and chronic complications in patients with type 2 diabetes mellitus

ObjectiveThis study investigated the correlation of liver fat content (LFC) with metabolic characteristics and its association with chronic complications in type 2 diabetes mellitus (T2DM) patients.MethodsEighty-one prospectively enrolled T2DM patients were divided into non-alcoholic fatty liver disease (NAFLD) group and the non-NAFLD group according to the presence of NAFL complications. LFC was determined by MRI IDEAL-IQ Sequence, and patients were divided into 4 groups according to LFC by quartile method. Basic information, metabolic indexes, and occurrence of chronic complications in different groups were analyzed and compared.ResultsBMI, SBP, DBP, TG, ALT, AST, GGT, UA, HbA1c, FCP, 2 h CP, HOMA-IR, and HOMA-IS in the NAFLD group were significantly higher than the non-NAFLD group (P < 0.05). The incidences of chronic complications in the NAFLD group were higher than in the non-NAFLD group but not statistically significant (P > 0.05). BMI, SBP, DBP, TC, TG, ALT, AST, FCP, 2 h CP, HOMA-IR, and HOMA-IS showed significant differences between the patients with different LFC, and these indexes were significantly higher in patients with higher LFC than those with lower LFC (P < 0.05). Moreover, diabetes duration, TC, HOMA-IR, and LFC were the risk factors for ASCVD complications, while diabetes duration, TG, and LDL-C were risk factors for DN complications. Also, diabetes duration and SBP were risk factors for both DR and DPN complications in T2DM patients (P < 0.05).ConclusionLFC is positively correlated with the severity of the systemic metabolic disorder and chronic complications in T2DM patients.