Complications In T2DM Patients Research Articles

The predictive value of TyG and lipid ratios on the development of complications and hyperuricemia in patients with type 2 diabetes mellitus.

Investigate the predictive value of TyG and lipid ratios on the development of complications and HUA in patients with T2DM. A retrospective cross-sectional study involving 9488 T2DM patients was conducted. They were divided into HUA and NUA group base on SUA level and divided into with and without complications groups according to the diagnosis of the endocrinologist. Necessary information and biochemical parameters were recorded during outpatient visit. TyG index and lipid ratios were calculated, and statistical analysis was carried out to correlate the calculated values and HUA using SPSS version 26.0 for Windows. TyG and lipid ratios were significantly higher in T2DM with HUA or with complications than those with NUA or without complications (p < 0.05). Regression analysis adjusting for confounding factors found TyG (adjusted OR = 1.54; 95% CI: 1.31-1.82; p < 0.05), TG/HDL-C (adjusted OR = 1.21; 95% CI: 1.04-1.40; p < 0.05) and TC/HDL (adjusted OR = 1.36; 95% CI: 1.17-1.57; p < 0.05) was risk factor of HUA in T2DM patients. TyG (adjusted OR = 1.21; 95% CI: 1.02-1.44; p < 0.05), TG/HDL (adjusted OR = 1.19; 95% CI: 1.03-1.38; p < 0.05) and Apo A/Apo B (adjusted OR = 1.41; 95% CI: 1.26-1.58; p < 0.05) was risk factor of complications in T2DM patients. TyG, TG/HDL-C, and TC/HDL can be used as early sensitive target in the occurrence of HUA in T2DM patients and TyG was the most influential risk factor. TyG, TG/HDL-C, and Apo A/Apo B can be used as early sensitive target in the occurrence of complications in T2DM patients and Apo A/Apo B was the most influential risk factor.

Prevalence and Determinants of Gastroparesis Symptoms among T2DM Patients in Tabuk City

Background: Development and progression of gastrointestinal complications in T2DM patients are one of the main contributors in the clinical course of the disease. Therefore, early recognition of gastroparesis is an important issue, despite this is not an easy task.&#x0D; Objectives: To estimate the prevalence and identify determinants of gastroparesis symptoms among T2DM patients.&#x0D; Patients and Methods: A cross-sectional study was conducted in Tabuk city, Saudi Arabia among all patients diagnosed with T2DM patients and attended the chronic illness clinics of King Khalid Armed Forces hospital throughout the period April-May, 2022. An interview questionnaire was utilized including 5 main parts: Demographic data of patients, medical history, weight and height measurements, the most recent hemoglobin A1c, and the Gastroparesis Cardinal Symptoms Index (GCSI) to estimate the prevalence of gastroparesis.&#x0D; Results: The study included 348 T2DM patients. More than half of them (57.8%) were females. Their age ranged between 23 and 75 years with an arithmetic mean±standard deviation of 54±11.3 years. The commonest reported gastroparesis symptoms were stomach fullness (45.1%), nausea (42%), loss of appetite (42%)and feeling excessively full after meals (41.1%). Overall, the prevalence of gastroparesis symptoms among T2DM patients was 11.8%. Multivariate logistic regression analysis revealed that females were at high significant risk for developing gastroparesis symptoms compared to males (Adjusted odds ratio “AOR”==2.49, 95% confidence interval “CI”: 1.18-5.27), p=0.016. Participants` glycated hemoglobin level was not significantly associated with gastroparesis symptoms after controlling for confounder effect.&#x0D; Conclusion: The prevalence of gastroparesis symptoms among T2DM patients was not high. Symptoms were more likely to affect female than male patients. However, they were not independently associated with glycemic control or treatment with metformin.

Galectin-3 as a Potential Biomarker of Microvascular Complications in Patients with Type 2 Diabetes.

Human Galectin-3 is a 32- to 35-kDa size lectin, mainly comprises a C-terminal carbohydrate recognition binding domain (CRD) and N-terminal domain. It acts as a powerful pro-inflammatory signalling factor, which plays an important role in the activation, chemotaxis, and cytokine release of inflammatory cells. Galectin-3 has also been studied in relation to development of insulin resistance. The levels of galectin-3 have been observed to be associated with both diabetes prevalence and incidence, independent of traditional diabetes risk factors. It is also associated with development of microvascular complications of diabetes mellitus like retinopathy, nephropathy and neuropathy. Tertiary care hospital-based cross-sectional prospective study. 150 patients selected by simple random sampling and were divided into 3 groups., Group A - Patients of Type 2 Diabetes mellitus without microvascular complications (n=50), Group B - patients of Type 2 diabetes mellitus with microvascular complications (n=50) and Group C - Healthy control (n=50). Descriptive statistics was performed by calculating mean and standard deviation for the continuous variables. chi-square goodness-to-fit test, Student T test (unpaired) and Analysis of variance (ANOVA) and multivariate analysis were used to compare means. The p-value was taken significant when less than 0.05 (P<0.05) and a confidence interval of 95%. In group A, B and C majority of patients were between 56-60 years with 34%, 40% and 36% cases, respectively. The mean BMI shows that the Patients with complications had significantly higher BMI than those without complications and controls had significantly lower BMI than patients having diabetes. The data shows statistical significance with deranged biochemical profile in patients with DM with complications as compared to patients without complications and control group. In both groups A and B patients with HbA1c between 9.1-12 had mean serum galectin level (20.2 in group A, 25.9 in group B) significantly higher than patients with HbA1c between 6.5-9 (18.5 in group A and 20.4 in group B). patients with deranged lipid profile had significantly higher serum galectin level in all 3 groups, with cases from group B having higher values than group A. While controls had the lowest value of serum galectin (P value<0.001). There was a highly significant correlation between high serum galectin levels and the incidence of both non-progressive and progressive retinopathy (P value=0.0001). The mean galectin of patients with neuropathy was 28.3 ± 3.1 ng/ml, which was significantly higher than patients from group B without neuropathy (24.5 ± 2.6 ng/ml). The mean serum galectin level of patients with macroalbuminuria was 30.1± 1.3 ng/ml which was significantly higher than those with microalbuminuria having mean galectin level of 22.8 ±4.8 ng/ml. There was a highly significant correlation between high serum galectin levels and the incidence of both micro and macroalbuminuria (P value=0.0001). This study concludes that elevated serum Galectin-3 levels are associated with diabetes-related chronic inflammatory processing pathway, and closely relates to the severity of diabetes in T2DM both with and without complications. Therefore, Galectin-3 may be helpful in the diagnosis and prognosis of microvascular and macrovascular complications in T2DM patients.

Prediction of Micro Vascular and Macro Vascular Complications in Type-2 Diabetic Patients using Machine Learning Techniques

A collection of metabolic conditions known as diabetes mellitus are defined by hyperglycemia brought on by deficiencies in insulin secretion, action, or both. In terms of mortality rate, type-2 diabetes is 20 times higher when compared with type-1. Based on the earlier research, there is still scope to identify different risk levels of type-2 diabetes complications. To achieve this, we have proposed a T2DC machine learning-based prediction system using a decision tree as a base estimator with random forest to identify the severity of T2-DM complications at an early stage. Our proposed model achieved accuracies of 95.43%, 94.62%, 96.25%, 97.55%, and 97.83% for Nephropathy, Neuropathy, Retinopathy, Cardiovascularand Peripheral Vascu-lar complications in T2-DM patients. The proposed model has the potential to improve clinical outcomes by promoting the delivery of early and personalized care to T2-DM patients.

Association between Novel Biomarkers Galectin-3 and NT-BNP with Cardiovascular Complication in Type-2 Diabetic among Palestinian Patients-Gaza Strip

The number of patients with T2DM is progressively increasing all over the world, and one of the most severe chronic complications of diabetes is the development of Cardiovascular Disease (CVD). The burden of diabetes is now a huge Palestinian public health challenge increase substantially in the next two decades. The aim of the study to investigate the relationship between plasma Galactin-3 and NT-BNP level with the development of CVD in T2DM in Palestinian patients. Case-control study design, this study was conducted in the laboratory of Central laboratory in Remal Clinic, Gaza Strip-Palestine in the period from July to October 2018, included 180 subjects divided to the three groups control, T2DM patients and T2DM with CVD, 60 individual in each group, matching for age. Vacutainer serum and EDTA blood samples were collected from all participants for the laboratory analysis. These results showed that there were highly significant differences (P&gt;0.01) in serum Galectin-3 level in the T2DM group compared with T2DM and CVD group, while NT-BNP results there was no significant difference between the T2DM group and T2DM with CVD group. Also, the study revealed that Galectin-3 was found to be more sensitive and specific by using Roc curve statistical test (sensitivity was 83.3%, specificity was 75.0%, p &lt;0.01), than NT-BNP (sensitivity was 81.7%, specificity was 23.3% p &gt;0.05) in predicting cardiovascular complications in T2DM patients We concluded that the Galectin-3 is the best novel biomarkers in comparison with NT-BNP that aid in the early diagnostic and prognostic evaluation either alone or in combination with other biomarkers for cardiovascular complications in a patient with T2DM.

Methylene Tetrahydrofolate Reductase Gene Polymorphism C677T &amp; Risk of Type two Diabetes Mellitus in Beni-Suef Governorate

Background: Methylene Tetrahydrofolate Reductase (MTHFR) is known to be a regulatory enzyme of homocysteine metabolism. In many ethnic groups point mutations in MTHFR gene are implicated in the pathogenesis of diabetic nephropathy (DN) and other complications of type II diabetes mellitus (T2DM). Aim of the work: The aim of this study was to assess if MTHFR C677T gene polymorphism was one of the risk factors for the development of diabetic nephropathy as well as other complications in type 2 diabetes mellitus patients. Subjects and methods: The MTHFR C6777T polymorphisms were detected in 50 persons by PCR-RFLP. Subjects were divided into 2 groups; 30 patients with type II DM and 20 persons who were non-diabetic healthy controls. Results: The presence of MTHFR 677T allele did not increase the risk of complications in T2DM patients. The presence of mutant genotypes CT and TT did not increase the risk of nephropathy or other complications in the subjects having a C677T mutation. Conclusion: Methylene Tetrahydrofolate Reductase (MTHFR) C677T gene mutation was neither associated with an increased risk of diabetic nephropathy nor other complications of type II diabetes mellitus.

Association of RASGRP1 Polymorphism with Vascular Complications in Chinese Diabetic Patients with Glycemic Control and Antihypertensive Treatment

Background: Studies have shown that RASGRP1 was strongly associated with the onset of type 2 diabetes, and RASGRP1 rs7403531 was significantly correlated with islet function in type 2 diabetes (T2DM) patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment is still unclear. Methods: We retrospectively analyzed a large multicenter drug clinical study cohort that based on a 2×2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, and follow-up for 5 years. The major vascular endpoint events in our study included cardiovascular death, non-fatal stroke, coronary heart disease, new or worsening kidney disease, and diabetic retinopathy. Mixed linear model and Cox hazard ratio model were used for data analysis with SPSS. Findings: A total of 1357 patients were included in our research with an average follow-up time of 4.8 years. RASGRP1 rs7403531 T allele could reduce the risk of major microvascular events (HR=0.41, 55%CI 0.21-0.80, P =0.009) and major eye diseases(HR=0.44, 95% CI 0.20-0.94, P =0.03) in T2DM patients . In the group based on antihypertensive therapy, active antihypertensive therapy for CC patients reduced the risk of all cerebrovascular events (placebo vs. antihypertensive: HR=2.35, 95% CI 1.06-5.12, P =0.035). For RASGRP1 (rs56254815), compared with the AA genotype carriers, the SBP of AG/GG carriers in the hypotensive 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). Interpretation: Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients. Trial Registration: (Registration number NCT00145925). Funding Statement: Supported by the National Natural Science Foundation of China (NSFC, No 81573511, 81874329, 81522048), the National Key R&D Plan of China (No. 2016YFC0905000). Declaration of Interests: All authors declare no conflict of interest relevant to the subject matter or materials discussed in the article. Ethics Approval Statement: Approval to conduct the trial was obtained from the ethics committee of each study center, and all participants provided written informed consent.

Elevated Vascular Endothelial Growth Factor Level in Association with Mean Platelet Volume Are Emerging Risk Factors for Vascular Complications in T2DM Patients

Increasing evidence in both experimental and clinical studies suggests oxidative stress (OS) plays a major role in the pathogenesis of type 2 diabetes mellitus and its complications. In a physiological condition, appropriate levels of ROS, generated either in restricted amounts or transient fashion, are required to promote physiological angiogenesis and homeostatic maintenance of healthy vasculature. Uncontrolled continuous ROS production will ultimately contribute to pathology and cause tissue damage. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF) which plays a key role in diabetic endothelial dysfunction, which ultimately leads to pathogenesis of vascular complications. As VEGF is released by activated platelets, hence platelet activation could be the source of VEGF in plasma samples. Increased platelet activity is emphasized to play a role in the development of vascular complications in T2DM patients and platelet volume, a marker of the platelet function and activation, is measured as mean platelet volume (MPV). Therefore, we aimed to investigate the association between plasma VEGF levels and MPV levels that may lead to vascular complications. A case-control study of one hundred patients with T2DM (n = 100) and thirty control subjects (n = 30) were screened from different areas of West Bengal. All procedures were done with the informed consent of participants. Elevated VEGF level was found in T2DM patients (526.8 ± 34.3 pg/ml) compared to healthy controls (317.9 ± 12.9 pg/ml) which was statistically significant. T2DM patients had higher MPV (12.5 ± 0.2 fl) compared to controls (11.4 ± 0.2 fl). Thus the present study showed a significant association between VEGF level in plasma and MPV indicating the severity of vascular complications. Hence, in conclusion, it suggested that VEGF levels along with MPV are a reliable biomarker for evaluating the development and progression of vascular complications.

Knowledge, attitude and practices about diabetes mellitus and its complications in T2DM patients attending the UHC in Mumbai

Background: Diabetes Mellitus has become a major public health problem in India and also the major cause of disability through complications such as blindness, renal failure, lower limb gangrene etc. People suffering from Diabetes related complications are many times unaware about the measures to curb the onset of the complications. The aim of the study was to assess knowledge, attitude and practices about diabetes and its complications in the diabetic patientsMethods: This was a cross sectional descriptive study conducted at an Urban Health Centre attached to the parent medical college in Mumbai. The knowledge, attitude and practices of the 116 participants who were registered at the non-communicable disease (NCD) OPD were assessed via a pre-designed, pre-tested interviewer administered questionnaire. Statistical analysis used: SPSS version 20.Results: Majority belonged the age groups of 40-60 years (69%), 63.8% were women, 91.4% were married and 44.4% were illiterate. 13.8% of the respondents had correct knowledge about the causes of diabetes and 62.9% could correctly identify the symptoms of diabetes. Knowledge regarding the complications in diabetics was found to be quite low with only 52.6% correctly identifying one or more complications. The most commonly known complication was neuropathy (83.6%) followed by nephropathy (57.3%). The attitude of the patients with respect to screening of complications was found to be poor and the same reflected in their practicesConclusions: There is a lack of understanding of the basics of the disease, its prevention as well as prevention of complications in those suffering from the disease.

Reduced serum milk fat globule-epidermal growth factor 8 (MFG-E8) concentrations are associated with an increased risk of microvascular complications in patients with type 2 diabetes

BackgroundThe association between serum milk fat globule-epidermal growth factor 8 (MFG-E8) concentrations and vascular complications in T2DM remains unclear. MethodsA total of 149 patients with T2DM were included. The serum concentrations of MFG-E8, glycosylated hemoglobin (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured. ResultsThere was no significant difference in serum MFG-E8 concentrations between the T2DM group and the T2DM with subclinical atherosclerosis (AS) group (615.49±143.54 vs. 596.22±79.46ng/ml, P=0.365), while the serum concentrations of MFG-E8 in the T2DM with microvascular complications group (446.70±61.53ng/ml) and the T2DM with subclinical AS and microvascular complications group (200.87±38.86ng/ml) were significantly lower than those in the T2DM group (P=0.000 for both). In addition, hs-CRP and HbAlc concentrations were independently associated with serum MFG-E8 concentrations (P=0.024 and P=0.01, respectively), and low serum MFG-E8 concentrations were significantly associated with an increased risk of microvascular complications in T2DM patients. ConclusionsSerum concentrations of MFG-E8 were negatively associated with the risk of microvascular complications in patients with T2DM. Thus, it might be a potential candidate biomarker for diabetic microvascular complications.

Evidences of +896 A/G TLR4 polymorphism as an indicative of prevalence of complications in T2DM patients.

T2DM is today considered as world-wide health problem, with complications responsible of an enhanced mortality and morbidity. Thus, new strategies for its prevention and therapy are necessary. For this reason, the research interest has focused its attention on TLR4 and its polymorphisms, particularly the rs4986790. However, no conclusive findings have been reported until now about the role of this polymorphism in development of T2DM and its complications, even if a recent meta-analysis showed its T2DM association in Caucasians. In this study, we sought to evaluate the weight of rs4986790 polymorphism in the risk of the major T2DM complications, including 367 T2DM patients complicated for the 55.6%. Patients with A/A and A/G TLR4 genotypes showed significant differences in complication's prevalence. In particular, AG carriers had higher risk prevalence for neuropathy (P = 0.026), lower limb arteriopathy (P = 0.013), and the major cardiovascular pathologies (P = 0.017). Their cumulative risk was significant (P = 0.01), with a threefold risk to develop neuropathy, lower limb arteriopathy, and major cardiovascular events in AG cases compared to AA cases. The adjusted OR for the confounding variables was 3.788 (95% CI: 1.642–8.741). Thus, the rs4986790 polymorphism may be an indicative of prevalence of complications in T2DM patients.

RAGE gene polymorphism and expression: risk factor for vascular complications in type 2 diabetes mellitus

Background Advanced glycation end products (AGEs) are formed due to hyperglycemia in T2DM. Interaction of AGEs with its receptor RAGE induces signal transduction that culminates in vascular complications, the major cause of morbidity and mortality in diabetic subjects. Some functional polymorphism of this gene show differential activity of this receptor and therefore may be associated with the development of diabetic complications. In the present study we investigated the association of expression of RAGE gene and its polymorphism namely -374T/A and -429T/C in the promoter region and Gly82Ser polymorphism in the exon 3 region with vascular complications in T2DM patients.

Association between serum uric acid level and microalbuminuria to chronic vascular complications in Thai patients with type 2 diabetes

AimsTo investigate an association between serum uric acid/microalbuminuria and chronic micro/macro-vascular complications in type 2 diabetic patients. MethodsThis cross-sectional study enrolled 608 patients with type 2 diabetes. All subjects were examined and basic information on health of the subjects was recorded for inclusion criteria. Several chemical parameters (fasting plasma glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, uric acid, and microalbuminuria), and related chronic vascular complications were measured and recorded in data forms. ResultsLogistic regressions were used to analyse odds ratios between uric acid/microalbuminuria levels and several chronic vascular complications. Prevalence of chronic vascular complications in T2DM patients, namely coronary arterial disease, cerebrovascular disease, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy was significantly correlated with increase of uric acid level [2.29 (1.01–5.2), 16.01 (4.74–54.09), 9.99 (4.4–22.8), 4.43 (1.3–15.1), 4.37 (1.5–12.9)], and of microalbuminuria level [7.0 (3.6–13.8), 3.2 (1.2–8.7), NA, 14.7 (5.1–42.7), 7.2 (2.9–17.7)]. ConclusionBoth elevated uric acid and microalbuminuria levels were significantly associated with diabetic chronic micro/macro-vascular complications. Monitoring of uric acid and microalbuminuria levels provides a predictive value for a presence of chronic micro/macro-vascular complications in patients with type 2 diabetes.

PRM208 - Using Multi-Criteria Decision Analysis to Support Allocation Decisions in Large Translational Research Projects

Large translational research projects often have abstract objectives, such as reducing the burden of disease and health care costs from type-2 diabetes (T2DM). Such an abstract objective entails: i) a very large number of possible strategies to reach the objective and ii) a lack of detailed data and high levels in uncertainty. Currently, no methods to support project selection and resource allocation decisions in such a setting are available. As a case study, we supported a resource allocation decision for the remaining funds in a large Dutch translational research consortium with the aforementioned objective, and compared the results to the decision made at the start of the project. We used the problem structuring, model building methods from multi-criteria decision analysis to identify four different alternative research strategies, and a set of evaluation criteria. Consequently, we used a combination of judgment from experts involved in the project and previously published data on the burden of disease and health care costs to evaluate the alternatives. Finally, a decision analysis was performed using Stochastic Multicriteria Acceptability Analysis for ordinal data (SMAA-O), which allows for the combined use of quantitative and qualitative (ranked) data. Using our method, it was decided to allocate remaining resources to the identification of biomarkers and development of technologies that can be used in the prevention of macrovascular complications in T2DM patients. This decision differed from the one made at the start of the project, which was not supported by any formal decision analysis. Our study shows that our method using SMAA-O can be a practical and valuable tool to support decisions on the allocation of research funds within large translational research consortia.

Impact of metabolic syndrome and its severity on microvascular complications in type 2 diabetes

Aims It is much debated whether metabolic syndrome (MetS) is a predictor for microvascular disease in hyperglycemic states. Whether present scoring systems for MetS provide additional risk assessment knowledge related to the severity of the score (from 1/5 to 5/5) remains to be determined for macro- and microangiopathy. Moreover, atherogenic dyslipidemia (low HDL-C and high triglycerides), which provides 2 out of 5 identifying MetS components, is increasingly considered as an emerging risk factor for residual vascular risk. Material and Methods We therefore analyzed a T2DM cohort (M:F ratio 63:37) with comparable age and diabetes duration with (MetS (+); n = 593) or without MetS (MetS (−); n = 145) regarding both macro- and microangiopathy prevalence and risk factors of both types of complications. MetS was defined according to AHA/NHLBI criteria. Blood pressure, glycemic control, insulin resistance (IR), hyperbolic product (B × S) and B × S loss rate, atherogenic dyslipidemia and low-grade systemic inflammatory markers were compared. We also determined whether there was a gradient for microangiopathy alongside MetS scores. Results Mean MetS score was 1.8 in MetS (−) vs. 4.0 in MetS (+), with hypertension as paramount non-glycemic contributor in MetS (−). BMI, waist, relative/absolute fat mass, visceral fat, conicity and IR were all significantly increased in MetS (+). Current triglycerides levels were almost twice as high in MetS (+) than in MetS (−), while HDL-C was lower by 20%. Mean HbA 1c was higher by 0.54% in MetS (+). Hypertension prevalence was twice higher in MetS (+) patients, who had increased systolic blood pressure by +7 mm Hg. Albuminuria was markedly elevated in MetS (+). Inflammatory markers ( hsCRP, leucocytes and urate) were significantly higher in MetS (+). Retinopathy was diagnosed in 14% of MetS (−) vs. 27% of MetS (+), polyneuropathy in 21% of MetS (−) vs. 31% of MetS (+) and macroangiopathy in 17% of MetS (−) vs. 36% of MetS (+), either as peripheral artery disease (PAD), coronary artery disease (CAD) and/or TIA (transient ischaemic attack)/stroke: 7, 10, and 5% (PAD, CAD, TIA/stroke) in MetS (−) vs. 11, 26, and 8% in MetS (+) (NS, p < 0.0001, and NS, respectively). Significant trends for increasing prevalence of all three types of microvascular complications were observed according to MetS scores severity from 1/5 to 5/5. Conclusion Further to macroangiopathy, there was a marked association between MetS and the presence of all types of microvascular complications in T2DM patients. Microangiopathy prevalence was also associated with MetS score severity in a gradient-type relationship.