T2DM Controls Research Articles

CCN5/WISP2 serum levels in patients with coronary artery disease and type 2 diabetes and its correlation with inflammation and insulin resistance; a machine learning approach

IntroductionStudies have shown various effects of CCN5/WISP2 on metabolic pathways, yet no prior investigation has established a link between its serum levels and CAD and/or T2DM. Therefore, this study seeks to explore the relation between CCN5 and the risk factor of CAD and/or diabetes, in comparison to individuals with good health, marking a pioneering endeavor in this field. MethodsThis case-control study investigates serum levels of CCN5, TNF-α, IL-6, adiponectin, and fasting insulin in a population of 160 individuals recruited into four equal groups (T2DM, CAD, CAD-T2DM, and healthy controls). Statistical tests comprise Chi-square tests, ANOVA, Spearman correlation, and logistic regression. ROC curves were used to represent the diagnostic potential of CCN5. Disease states are predicted by machine learning algorithms: Decision Tree, Gradient Boosted Trees, Random Forest, Naïve Bayes, and KNN. These models' performance was evaluated by various metrics, all of which were ensured to be robust by applying 10-fold cross-validation. Analyses were done in SPSS and GraphPad Prism and RapidMiner software. ResultsThe CAD, T2DM, and CAD-T2DM groups had significantly higher CCN5 concentrations compared to the healthy control group (CAD: 336.87 ± 107.36 ng/mL, T2DM: 367.46 ± 102.15 ng/mL, CAD-T2DM: 404.68 ± 108.15 ng/mL, control: 205.62 ± 63.34 ng/mL; P < 0.001). A positive and significant correlation was observed between CCN5 and cytokines (IL-6 and TNF-α) in all patient groups (P < 0.05). Multinomial logistic regression analysis indicated a significant association between CCN5 and T2DM-CAD, T2DM, and CAD conditions (P < 0.001) even after adjusting for gender, BMI, and age (P < 0.001). Regarding the machine learning models, the Naïve Bayes model showed the best performance for classifying cases of T2DM, achieving an AUC value of 0.938±0.066. For predicting CAD, the Random Forest classifier achieved the highest AUC value of 0.994±0.020. In the case of CAD-T2DM prediction, the Naïve Bayes model demonstrated the highest AUC of 0.981±0.059, along with an Accuracy of 97.50 % ± 7.91 % and an F-measure of 96.67 % ± 10.54 %. ConclusionOur study has revealed, for the first time, a positive connection between CCN5 serum levels and the risk of developing T2DM and CAD. Nonetheless, more research is needed to ascertain whether CCN5 can serve as a predictive marker.

Polymorphism of 8-oxoguanine DNA glycosylase -1(OGG1)in Iraqi Patients with Type2 Diabetes Mellitus

Chronic hyperglycemia in type 2 diabetes mellitus leads to elevated oxidative stress. As a consequence , the accumulation of reactive oxygen species (ROS)may cause additional damage to various biological macromolecules, including DNA. Several studies have demonstrated that oxidative stress plays an important role in the pathogenesis of type2 diabetes mellitus. The aim of this study is to investigate the association of polymorphisms of 8- oxoguanine DNA glycosylase-1(OGG1) repair gene polymorphism to the susceptibility of type 2 DM in an Iraqi population with T2DM patients from Wasit Province. All samples were collected from the local community of Wasit province, Iraq. Forty five type 2 diabetes mellitus patients (22 males and 23 females) and 35 healthy controls (17 males and 18 females) were genotyped for 8-oxoguanine DNA glycosylase-1(OGG1) using PCR- RFLP technique. In both patients and control groups, the distribution frequencies of genotypes and alleles of 8-oxoguanine DNA glycosylase-1(OGG1) A/G was inconsistent with the Hardy-Weinberg equilibrium in T2DM patients(χ2=49.542,P=(0.00001); χ2=82.0185,P=(0.0001) respectively. The Cys/Cys(mt/mt) OGG1 genotype was significantly higher in patients than controls(mt/mt;33(37%)vs,0.00 in controls. The Ser/Cys (wt/mt) was 7(16%) and 6(17%) in patients and controls respectively and Ser/Ser genotypes wt/wt; decreased significantly in patients 5(11%) vs,29(83%) in controls. The wt and mt allele frequencies of OGG1were highly significant between the two groups P=0.00001. The wt allele was the major one in control group with a percent of (90.28) vs. (18.89) in patients group. Whereas the mt the frequent allele in patients with a percent of (81.11) vs. (18.89).This further analysis showed that the individuals carrying the homozygous Cys/Cys(mt/mt) genotype were more likely to have increased the risk of T2DM very significantly with OR= 190.02800 (CI95% 10.8329 to 3342.2603) ,P=0.0003. The genotypes Ser/Ser( wt/wt) and Ser/Cys(wt/mt) decrease the association with T2DM with OR=0.0259 (CI95% 0.0072 to 0.0930), and 0.8904 (CI95% 0.2701 to 2.9347 )respectively, P= 0.0001 and 0.08486 for each genotype respectively, These results suggest that mt allele may be considered as risk allele of T2DM whereas the wt allele is protective agent T2DM.Association analysis showed that the type2 diabetes mellitus risk of females with OGG1 gene Cys/Cys( mt/mt) genotype was highly significant 81.4000 fold higher than that in controls OR= 81.4000 (CI 95% 4.3089 to 1537.7322), P= 0.0033.Ser/Cys( wt/mt) genotype increase the probability of the disease with OR = 1.7647 (CI 95% 0.3745 to 8.3154), P = 0.4727.Similary,Ser/Ser(wt/wt) genotype decrease the association with T2DM with OR= 0.0091 (CI95% 0.0009 to 0.0959), P = 0.0001.Type2 diabetes mellitus patients particularly with Cys/Cys(mt/mt) genotype increases the association about more than 111 times in males patients than that in controls OR= 111.3636 ( CI95% 5.7135 to2170.6226), P = 0.0019 While, genotypes Ser/Cys(wt/mt) and Ser/Ser (wt/wt) reduce the likelihood of T2DM with OR= 0.2222 ( CI95% 0.0209 to 2.3585),P = 0.2120 and 0.0476( CI95% 0.0091 to 0.2484), P= 0.0003 respectively. the genetic model for OGG1 in comparison between T2DM patients and controls . The dominant model indicated that patients and controls of (wt/mt+mt/mt) genotype increased significantly the association with T2DM in patients: (5/7 and 33) comparing with control (29/6 and 0.00) with OR (38.666),P=0.0001.The recessive model revealed that patients carrier the genotype (wt/wt+wt/mt) declined significantly the association with the disease :(33/5 and 7) in patients versus (0.00/29 and 6) in controls,OR=0.0053,P=0.0003.The Over-dominant model showed that patients with the genotype (wt/wt+mt/mt) in creased non-significantly the association with the disease when compare patients (7/5 and 33) with controls(6/29 and 0.00) ,OR=1.123,P=0.848

Identification of plasma miR-4505, miR-4743-5p and miR-4750-3p as novel diagnostic biomarkers for coronary artery disease in patients with type 2 diabetes mellitus: a case-control study

BackgroundType 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are commonly coexisting clinical entities with still growing incidence worldwide. Recently, circulating microRNAs (miRNAs) have emerged as novel molecular players in cardiometabolic diseases. This study aimed to identify a specific miRNA signature as a candidate biomarker for CAD in T2DM and to delineate potential miRNA-dependent mechanisms contributing to diabetic atherosclerosis.MethodsA total of 38 plasma samples from T2DM patients with and without CAD, CAD patients and healthy controls were collected for expression profiling of 2,578 miRNAs using microarrays. To investigate the regulatory role of differentially expressed (DE)-miRNA target genes, functional annotation and pathway enrichment analyses were performed utilizing multiple bioinformatics tools. Then, protein-protein interaction networks were established leveraging the STRING database in Cytoscape software, followed by cluster analysis and hub gene identification. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was carried out for microarray data validation in the larger replication cohort of 94 participants. Receiver operating characteristic analysis was applied to evaluate the diagnostic values of miRNAs. Multivariate logistic regression analysis was used to develop miRNA-based diagnostic models.ResultsIn the discovery stage, overexpression of hsa-miR-4505, hsa-miR-4743-5p, hsa-miR-6846-5p, and down-regulation of hsa-miR-3613-3p, hsa-miR-4668-5p, hsa-miR-4706, hsa-miR-6511b-5p, hsa-miR-6750-5p, hsa-miR-4750-3p, hsa-miR-320e, hsa-miR-4717-3p, hsa-miR-7850-5p were detected in T2DM-CAD patients. The DE-miRNA target genes were significantly enriched in calcium ion binding, regulation of actin cytoskeleton, and gene expression. hsa-miR-4505, hsa-miR-4743-5p, and hsa-miR-4750-3p were found to be involved in fatty acid metabolism, leukocyte transendothelial migration, and neurotrophin signaling pathway. Dysregulation of hsa-miR-4505, hsa-miR-4743-5p, and hsa-miR-4750-3p in T2DM-CAD patients compared with T2DM subjects and controls (all p < 0.001) was further confirmed by RT-qPCR. All validated miRNAs demonstrated good discriminatory values for T2DM-CAD (AUC = 0.833–0.876). The best performance in detecting CAD in T2DM was achieved for a combination of three miRNAs (AUC = 0.959, 100% sensitivity, 86.67% specificity).ConclusionsOur study revealed a unique profile of plasma-derived miRNAs in T2DM patients with CAD. Potential miRNA-regulated pathways were also identified, exploring the underlying pathogenesis of CAD in T2DM. We developed a specific three-miRNA panel of hsa-miR-4505, hsa-miR-4743-5p and hsa-miR-4750-3p, that could serve as a novel non-invasive biomarker for CAD in patients with T2DM.

New Pro-inflammatory Cytokines in Children and Adolescents with Type 1 Diabetes Patients with Microvascular Complications

Abstract Background Type 1 diabetes mellitus has become a global health burden, and poor glycemic control, in combination with prolonged diabetes duration, leads to the early development of microvascular complications, including diabetic kidney disease, retinopathy, and neuropathy. Therefore, it is urgent to establish new biomarkers for the early identification of at-risk patients. Objectives To investigate the role of inflammatory proteins (human growth differentiation factor 15 and interleukin 29) in the course of microvascular complications and glycemic control in T1DM. Patients and Methods Our study included 40 children with T1DM (18 T1DM patients had microvascular complications and 22 T1DM patients were free of these complications; their ages ranged from 8 to 18 years); there was also another T1DM subgroup based on glycemic control (11 T1DM patients had controlled HbA1c &amp;lt; 7% and 29 patients had uncontrolled HbA1C &amp;gt; 7%). 40 children of the same age were selected as a control group. The diagnosis of TIDM was made based on the criteria of the International Society of Pediatric and Adolescent Diabetes (ISPAD) (2022). A detailed medical history was collected, including the age of onset of diabetes, disease duration, and symptoms of diabetic complications. In the study, GDF15 and IL29 values in serum blood were investigated using the ELISA method. Results The mean age was 14.05 years in the diabetic group and 13.25 years in the control group (P = 0.178). In the T1DM patient group, the GDF15 and IL29 values were found to be significantly higher than those in the control group (P = 0.041 and 0.013, respectively). In diabetic patients, GDF15 was significantly higher in the complicated T1DM group versus the uncomplicated group (P = 0.001). Furthermore, GDF15 levels were significantly higher in uncontrolled patients with HbA1C &amp;gt; 7% than in the control group with HbA1C &amp;lt; 7% (P = 0.004); however, no significant statistical differences in IL29 levels were found between diabetic patient subgroups (P &amp;gt; 0.05). Conclusion The data from this study showed that GDF15 has an impact on glycemic control and that the presence of microvascular complications in the course of T1DM is very possible, but IL29 does not appear to play a role in the course of microvascular complications.

Exploring Salivary Metabolic Alterations in Type 2 Diabetes: Implications for Dental Caries and Potential Influences of HbA1c and Vitamin D Levels.

Stimulated whole-mouth saliva (SWS) samples were collected from T2DM and ND (n = 30 in each case) participants randomly selected from a group of 128 participants recruited for this case-control study. All participants were advised to refrain from eating, drinking, and smoking for at least 1-2 h prior to sample collection. Following preparation, SWS supernatants underwent 1H NMR analysis at an operating frequency of 800 MHz, and the dataset acquired was analysed using a range of multivariate metabolomics techniques. Metabolomics analysis of data acquired demonstrated that, together with up- and downregulated blood HbA1c and vitamin D levels, key salivary discriminators between these two classifications included lactate, taurine, creatinine, α-glucose, and formate to a lesser extent. The bacterial catabolites lactate and formate were both significantly upregulated in the T2DM group, and these have previously been implicated in the pathogenesis of dental caries. Significance analysis of metabolites (SAM)-facilitated AUROC analysis yielded an 83% accuracy for this distinction. In conclusion, this study highlights the significant differences in salivary metabolites between individuals with T2DM and healthy controls. Such differences appear to be related to the development and progression of dental caries in T2DM patients.

Level of biochemical parameters in patients with type 2 diabetes mellitus depending on the genotype of the FokI polymorphism in the vitamin D3 receptor (VDR gene).

Diabetes mellitus type 2 (T2DM) is a multifactorial and polygenic disorder characterised by chronic hyperglycaemia accompanied by impaired lipid, carbohydrate, and protein metabolism. The disease is associated with several genetic polymorphisms, including the FokI polymorphism in the vitamin D receptor (VDR) gene. We conducted a study of 327 probands (191 T2DM patients, 136 controls), with a mean age 65.06 (SD ± 10.88) years of patients with T2DM and 58.89 (SD ± 6.59) years in the healthy probands. We investigated the association between FokI polymorphism and biochemical parameters in T2DM patients in the Slovak population. Anthropometric measurements, biochemical, and genetic analysis were statistically evaluated by Statistica ver.13 software using t-tests. Biochemical analysis confirmed significantly higher mean values of total cholesterol (TC), triglyceride (TG), glucose (GLU), and uric acid (UA) (p < 0.001) in T2DM probands and statistically significantly lower values of high-density lipoprotein (HDL), cholesterol and vitamin D (p < 0.001). Allele frequencies and genotype distributions of the FokI (rs2228570) polymorphism were not significantly different between T2DM patients and controls (p = 0.909). Patients with T2DM and TT genotype had the highest glucose level of 11.39 (SD ± 2.32) uU/ml (p < 0.001). Our study did not provide evidence for an association of the investigated FokI polymorphism of the VDR gene with T2DM in the Slovak population. Further research is needed to evaluate the impact of single nucleotide polymorphisms (SNPs) in the VDR gene, focusing on related genetic analyses in a larger T2DM cohort.

A Novel Variant Of Regenerating Iα Gene (REG) In Type II Diabetics Among Pakistani Targeted Population

Objective: Regeneration of pancreatic β-cells, is an essential step towards diabetes management. The regenerating (REG) Iα gene is secreted from damaged β-cell for the synthesis of β-cell. This study aimed to identify REG Iα gene polymorphisms and their association with Type II diabetes (T2DM). Methods: Patients (110) with T2DM and age-related controls were selected from PNS Shifa Hospital, Karachi. DNA was extracted PCR was performed and amplified products were sequenced to identify polymorphisms. For six exons of the REG 1a gene, 6 sets of primers were designed. The selected (51) samples were amplified and sequenced for 306 (51x6) times. Odds ratios were calculated through logistic regression analysis. The correlation was used to find an association between REG Iα and diseases. p&lt; 0.05 was considered significant. Results: Blood samples were drawn from 90 finalized patients, including 70 diabetics and 20 controls with an M: F ratio of 12:8. Twenty patients opted to withdraw. The REG Iα and disease duration in type II diabetics showed a negative correlation (r= -0.355, p=0.005). The single nucleotide polymorphisms (SNPs) of eight sites were detected: g.-385T&gt;C, g.-243T&gt;G, g.-145G&gt;A, g.+142A, g.+209G&gt;T, g.+226A&gt;G, g.+2199G&gt;A, g.+2360A&gt;G. The novel SNP g.-145G&gt;A was found in all patients (controls, T2DM). Among all SNPs, only g.+209G&gt;T showed a positive association (OR= 2.4, p=0.01) with T2DM. Whereas, g.-243T&gt;G showed a positive association (OR=8.06, p=0.0003) with smoking. Conclusion: A novel variant g.-145G&gt;A REG Iα gene was found among all participants. The SNPs g.+209G&gt;T had a significant positive association with T2DM and SNP g.-243T&gt;G showed an increased risk of the disease among smokers. Keywords: REG Iα gene, Type II diabetes, β-cells regeneration, Polymorphisms.

To evaluate the prevalence, subtypes and risk associations of mild cognitive impairment in elderly Indian individuals with type 2 diabetes

AbstractBackgroundDiabetes is an important modifiable risk factor for dementia. The prevalence of mild cognitive impairment (MCI) in type 2 diabetes (T2D) is high (You et al, 2021). This data is largely derived using screening tools (MMSE or MoCA), with little information on MCI subtypes. Evidence from the South Asian region is particularly scarce, where prevalence of diabetes is high, and is seen a decade earlier compared to Caucasians.MethodWe have established a cohort of elders (³ 60 years of age), with and without diabetes, visiting a tertiary care hospital in North India (from 2019, ongoing). The participants underwent an interview to collect information on their demographic profile, risk associations, vascular health, and other comorbidities. Culturally validated neuropsychological battery was used for cognitive evaluation. MoCA was done in a subset of patients.ResultWe recruited 840 participants in the cohort, 683 with T2DM and 157 without T2DM (controls). The mean age of the cohort was 65.3±4.5 years, 65.2% were males. Risk profile is described in Table 1. The cognitive z scores of participants with T2DM ranged from ‐0.25 to +0.44. The worst affected domain was attention, working memory and executive functions (Table 2). Using an actuarial definition of MCI (Bondi MW et al, 2014), the prevalence in participants with T2D was 29.7%. 17.3% had amnestic impairment, 14.8% dysexecutive, 14.2% language, 2.4% visuo‐perceptual and 9.1% multidomain impairment. The cognitive raw scores (by dementia risk stratification) are provided in Table 3. On logistic regression, lower education 3.45(2.09,5.68), depression 2.04(1.26,3.29), poor sleep quality 1.77(1.15,2.71), family income 1.70(1.22,2.38), followed by age 1.05(1.00,1.10) had a significant association with global low cognition.ConclusionRoughly one‐third of elders with T2D visiting tertiary care services in North India have mild cognitive impairment. Amnestic subtype is the most frequent. Attention, working memory and executive functions are worst affected. Enhancing the cognitive reserve, mood and sleep quality may be important targets in prevention of cognitive decline in the elderly population with T2D.

The impact of duration and control of type 1 diabetes mellitus on microvascular function is strongly modified by the gene for connexin 37

Abstract Introduction Type 1 diabetes mellitus (T1DM) is almost inevitably accompanied by microvascular dysfunction. This could be responsible for cardiovascular events and is supposed to be caused mainly by long-term exposure to hyperglycemia. Nevertheless, relationship between duration and control of T1DM with microvascular complications can be modified by genetic factors; one of frequently discussed candidate genes is connexin37 (cx37), namely its rs1764391 (C1019&amp;gt;T (Pro319&amp;gt;Ser) polymorphism. We already observed sex specific association between cx37 polymorphism with macrovascular changes but also with retinopathy, neuropathy and diabetic foot. In the recent study, we analyzed if the impact of duration and control of T1DM on directly measured microvascular function is modified by cx37 gene polymorphism. Methods In 235 men and 227 women with T1DM (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years) wide spectrum of clinical, laboratory and hemodynamic parameters was measured. Establishment of microvascular function measured by photoplethysmography (detection of blood volume changes in the microvasculature in lower extremities) and calculated as Oliva/Roztocil index (ORI), was analyzed. Cx37 gene polymorphism was measured by PCR-RFLP. The correlation (Pearson’s correlation coefficient) between duration of T1DM and ORI was calculated including analysis of potential modification by control of diabetes (HbA1c) and by cx37 gene polymorphism and standardized for potential confounders (sex, age, smoking, presence of hypertension, central obesity …) by multiple regression. The analysis was conducted separately for duration of T1DM below (n=256) and above (n=206) 20 years as the linear relationship between ORI and T1DM duration tends to change accordingly. Results In patients with T1DM, distribution of Cx37 genotypes did not differ from the already described populations (TT/CT/CC: 9.7/44.4/45.9%). In patients with satisfactory control of diabetes (HbA1c&amp;lt;53 mmol/mol; n=105) we detected worsening (increase) of ORI with duration of diabetes only in TT homozygotes and CT heterozygotes for duration of at least 20 years (r=0.6, p=0.006), while in patients with unsatisfactory control (HbA1c&amp;gt;60 mmol/mol;n=270), we detected worsening of ORI with duration of diabetes only in CC homozygotes, both for duration 0-20 years (r=0.35, p=0.03) and for duration of at least 20 years (r=0.47, p=0.03). Conclusion Microvascular function in satisfactory controlled T1DM was worsening with diabetes duration only in T allele carriers of Cx37 gene, the worsening was detected only for patients with duration longer than 20 years. However, if T1DM control was insufficient, microcirculation was worsening only in CC homozygotes.

Abstract 13074: Incremental Value of Abnormal Quantitative Myocardial Perfusion and Myocardial Infarction Using Cardiovascular Magnetic Resonance as Prognostic Markers in Type 2 Diabetes Mellitus

Introduction: Abnormal myocardial perfusion and MI are each associated with cardiovascular events in individuals with diabetes mellitus (DM). Hypothesis: We hypothesised that, in patients with T2DM, CMR determined quantitative myocardial perfusion and MI are independent predictors of major adverse cardiovascular and cerebrovascular events (MACCE) and that the presence of both offers incremental prognostic value. Methods: A prospective multicentre cohort of individuals with T2DM and healthy controls underwent stress CMR with inline quantitative myocardial perfusion and late gadolinium enhancement (LGE). Adjusted cox proportional hazard models (adjusted for age, sex, LVEF, LV end diastolic volume (LVEDV) and LV mass quantified associations between quantitative myocardial perfusion and MI with MACCE (composite of all-cause death, MI, stroke, heart failure hospitalisation and coronary revascularisation). Results: A total of 572 participants with T2DM from four centres and 52 healthy controls were followed for a median of 851 (IQR 765-935) days, during which 82 (14%) participants accrued at least one MACCE, including 25 (4%) deaths. Presence of either CMR pathology was associated with increased MACCE (normal quantitative myocardial perfusion and no MI: 7% MACCE; abnormal quantitative myocardial perfusion or MI: 13% MACCE (adjusted HR compared with normal 2.06 (95% CI 1.07-3.97, p=0.03)); and both abnormal quantitative myocardial perfusion and MI was associated with the highest event rate: 28% MACCE (adjusted HR compared with normal quantitative myocardial perfusion and no MI 4.55 (95% CI 2.32-8.90, p&lt;0.001)). Conclusion: In individuals with T2DM, the presence of either abnormal quantitative myocardial perfusion or MI is associated with MACCE and the presence of both offers strong incremental prognostic value.

SAT042 Impact Of Aerobic Exercise On The Circulating Endothelial Progenitor Cells And Inflammation Markers In Type 1 Diabetes

Abstract Disclosure: C.K. Maraschin: None. P.M. Bock: None. R.B. Monteiro: None. A. Alegretti: None. P.L. Lopes: None. L.P. Santos: None. L. Helal: None. R. Moraes: None. D.U. de Moraes: None. B.D. Schaan: None. The circulating levels of endothelial progenitor cells (EPCs) is a marker of endothelial dysfunction in many chronic diseases, including diabetes mellitus. Increasing the amount of circulating EPCs through exercise may be a viable strategy for improving endothelial function. However, differences in EPC levels between individuals with and without diabetes and the responses of EPCs to exercise sessions were not previously studied. We sought to determine the number of circulating EPCs by flow cytometry in subjects with or without type 1 diabetes (T1DM), and to elucidate the independent or combined responses of EPC populations and inflammatory markers in response to one bout of intense aerobic exercise. This was a non-randomized controlled trial. Fifteen adult males, ages 18–65, with T1DM were included. Patients with high glycemia in the morning of the study or with chronic diabetic complications that made it difficult to perform the protocol were excluded. Fifteen healthy, non-obese, non-smoking individuals were recruited as controls. All included subjects underwent an aerobic exercise session on a cycle ergometer for 30 minutes at 60% of the predetermined peak heart rate. Blood samples were collected to evaluate plasma glucose levels, glycated hemoglobin (HbA1c), total and HDL cholesterol, tumor necrosis factor alpha (TNFa), interleukin 6 (IL-6), and EPCs (CD45dim/CD34+/KDR+) before and after the exercise session. Individuals with T1DM presented higher fasting plasma glucose (197.3 ± 90.0 mg/dL vs. 88 ± 11.2 mg/dL, p &amp;lt; 0.01) and HbA1c levels (7.9 ± 1.5 vs. 5.0 ± 0.3%, p &amp;lt; 0.01), while peak VO2 was higher in controls (37.6 ± 8.4 vs. 29.1 ± 10.9 mL.kg-1.min-1, p = 0.03). A complete blood count analysis showed increases in white blood cells [0.8 (0.1, 1.4) and 1.0 (0.4, 1.6) x103/µL, p &amp;lt; 0.001] and neutrophils [0.9 (0.3, 1.4) and 0.9 (0.3, 1.4) x103/µL, p &amp;lt; 0.001] in both groups after exercise. There was no difference within and between groups for EPCs before and after the aerobic exercise session - delta 0.02 (-0.04, 0.08) among controls and 0.00 (-0.01, 0.01) among individuals with T1DM]. No difference was observed in the levels of TNF-α among controls [210.2 (142.1 - 401.2); 191.3 (136.4 - 350.5) pg/mL] and individuals with T1DM [463.8 (201.4 - 4306.0); 482.7 (143.8 – 4304.3) pg/mL], before and 60 minutes after the exercise session, respectively. The IL-6 did not show any difference in controls [148.2 (147.5 – 148.6); 148.2 (147.7 – 148.6) pg/mL] and in those with T1DM [147.2 (145.9 – 147.7); 147.2 (146.8 – 147.8) pg/mL], before and 60 minutes after exercise, respectively. Patients with T1DM and healthy controls did not show a different response on EPCs levels after an acute session of aerobic exercise, most likely because they do not have a chronic inflammatory state. Hence, our study suggests that aerobic exercise (peak of 60% VO2) has the same effect on endothelial function in patients with or without T1DM. Presentation: Saturday, June 17, 2023

Blood-based Migration Signature Biomarker Panel Discriminates Early Stage New Onset Diabetes related Pancreatic Ductal Adenocarcinoma from Type 2 Diabetes

Background and aimsWhile type 2 diabetes is a well-known risk factor for pancreatic ductal adenocarcinoma (PDAC), PDAC-induced new-onset diabetes (PDAC-NOD) is a manifestation of underlying PDAC. In this study, we sought to identify potential blood-based biomarkers for distinguishing PDAC-NOD from type 2 diabetes (T2DM) without PDAC. Materials and methodsBy ELISA analysis, a migration signature biomarker panel comprising tissue factor pathway inhibitor (TFPI), tenascin C (TNC-FNIII-C) and CA 19–9 was analyzed in plasma samples from 50 PDAC-NOD and 50 T2DM controls. ResultsBoth TFPI (area under the curve (AUC) 0.71) and TNC-FNIII-C (AUC 0.69) outperformed CA 19–9 (AUC 0.60) in distinguishing all stages of PDAC-NOD from T2DM controls. The combined panel showed an AUC of 0.82 (95% CI = 0.73–0.90) (p = 0.002). In the PDAC-NOD early stage II samples, the three biomarkers had an AUC of 0.84 (95% CI = 0.73–0.93) vs CA 19-9, AUC = 0.60, (95% CI = 0.45–0.73), which also improved significance (p = 0.0123). ConclusionThe migration signature panel adds significantly to CA 19–9 to discriminate PDAC-NOD from T2DM controls and warrants further validation for high-risk group stratification.

The Relationship Between Phase Angle Obtained from the Maximum Reactance and Fasting Glucose, Hemoglobin A1c in Type 2 Diabetes Mellitus

Aim: The phase angle obtained from the maximum reactance (PA max) is a better potential indicator than the phase angles obtained from multiple frequencies. Our aim in this study is to investigate the correlation of PA max with fasting glucose and hemoglobin A1c in Type-2 Diabetes Mellitus (T2 DM).&#x0D; Material and Methods: The study was conducted prospectively, two groups were formed as T2 DM (n=75) and healthy controls (n=32) and their demographic variables were examined. Right hand, left hand, right leg, left leg, hand leg and leg leg segment measurements were taken with electrical impedance method and phase angle was obtained at maximum reactance. Correlations with fasting glucose, hemoglobin A1c and other variables were examined.&#x0D; Results: Fasting glucose, glycated hemoglobin A1c, age, body mass index, body fat percentage were found to be significantly higher in the T2 DM group compared with the healthy group. However, RH PA max, RL PA max, LL PA max, H_L PA max, and L_L PA max values were found to be significantly lower than in the healthy group. In T2 DM group, hemoglobin A1c was found significantly negative correlated with PA max in all segments, while fasting glucose is negatively correlated with all segments except LH Pamax.&#x0D; Conclusion: PA max is significantly reduced by the impaired glycemic index in T2 DM and is a potential marker reflecting metabolic status.

286 Gait speed—a useful addition to dementia risk prediction in midlife? Results from ENBIND

Abstract Background Midlife Type 2 Diabetes (T2DM) is associated with a two-fold increased risk of dementia in later life. The utility of spatiotemporal gait characteristics to identify those with midlife T2DM at greatest risk of later cognitive decline has not been assessed. This may aid in selecting-out those at greatest risk for preventative brain-health interventions. Methods ENBIND is a longitudinal study of cognitively-healthy individuals with midlife T2DM (free from microvascular/macrovascular complications) and healthy controls. At baseline, gait speed was measured across three tasks (usual gait speed, maximal gait speed and cognitive dual-task—whilst reciting alternate letters of the alphabet). Domain-specific neuropsychological performance was assessed using the Montreal Cognitive Assessment (MoCA) and a custom CANTAB battery with identical assessments repeated at a 4-year interval. Linear regression was used to analyse results with adjustment for important clinical confounders. Results 30 individuals (aged 55.5 ± 9 years; 50% female) were followed up, of whom three-quarters (n = 23, 76.7%) had midlife T2DM. Individuals with midlife T2DM did not experience greater cognitive decline over 4 years. Slower ‘usual’ gait speed (but not dual-task or maximal speed) at baseline was associated with greater likelihood of incident errors on the MoCA at 4 years, which persisted on controlling for T2DM status, age, sex and baseline cognition (B: -0.22 [95% Confidence Interval: −0.41, −0.03, p = 0.03]). Slower maximal (B: −3.07, −6.06, −0.08, p = 0.04) and cognitive dual-task (B:-1.98, −3.61, −0.17, p = 0.03) speed were both associated with significantly poorer delayed memory performance after 4 years. Conclusion In middle-aged individuals with known dementia risk factors, gait speed may be a useful adjunct to identify those at greatest risk of longitudinal cognitive decline. Whilst usual gait speed was associated with a decline in global cognition, fast and dual task gait speed were associated with longitudinal decline in delayed memory performance.

Aberrant DNA methylation of CDKN2B gene in the Type 1 diabetes mellitus and analysis of epigenetic markers

IntroductionAberrant DNA methylation is one of the important molecular markers in acute lymphoblastic leukemia (ALL). ObjectivesTo determine Aberrant DNA methylation profiles of the CDKN2A and CDKN2B genes in ALL samples from T1DM cases. ResultsAberrant hypermethylation of CDKN2B gene and cytogenetic abnormalities were analyzed in >60% of subjected cases. Total cholesterol, triglycerides and low-density lipoprotein cholesterol were not significantly varied between experimental and control (p >0.05). Expression analysis of human peripheral blood mononuclear cells revealed decreased mRNA levels of CDKN2B. The decreased level of p21 and CDK4 expression in the T1DM cases than control. The number of monocytes, lymphocytes and neutrophils significantly varied in T1DM samples and control (p < 0.05). ConclusionsAberrant methylation is one of the important mechanisms involved in the expression of CDKN2B genes and is an important prognostic marker for the early detection of ALL risks.

1342-P: Are Plasma Aminotransferases of Value in Screening Patients with T2DM for NAFLD or Fibrosis?

The ADA recommends to screen for NASH and liver fibrosis individuals with type 2 diabetes (T2DM), obesity (OB) and/or elevated alanine aminotransferase (ALT). However, recent studies have questioned the clinical value of measuring ALT and AST for the detection of patients at risk of nonalcoholic fatty liver disease (NAFLD) or advanced liver fibrosis or cirrhosis. The aim of this study was to assess the clinical value of ALT and AST ≥40 IU/L, or their lower cut-offs ≥30 IU/L as recommended by recent AACE guidelines, to screen populations at risk. To this end, we recruited 714 participants (age: 56 ± 11 years, male: 42%; BMI: 30.8 ± 6.5 kg/m2; T2DM: 35%; A1c: 6.0 ± 1.2%) from primary care or endocrinology clinics, unaware of having NAFLD/fibrosis. Screening for NAFLD included laboratory tests and imaging with elastography (steatosis by controlled attenuation parameter [CAP]; fibrosis by liver stiffness measurement [LSM]). Elevated transaminases were more common in patients with vs. without T2DM, with ALT ≥40 IU/L occurring in 13% vs. 8% and AST in 9% vs. 3% of patients (both p&amp;lt;0.05). If using a cutoff of ≥30 IU/L: 25% vs. 18% and 20% vs. 13%; respectively (both p&amp;lt;0.05). Elevated ALT ≥30 IU/L was the highest in patients with T2DM and OB (n=164) vs. controls (without T2DM or OB; n=269; 27% vs 15%; p=0.02). The sensitivity for diagnosing steatosis by ALT or AST was very low, with ALT and AST ≥40 IU/L present in only 16% and 9%, respectively. However, steatosis by imaging (CAP) was often present if ALT or AST were high (81 and 90%, respectively). An ALT ≥40 IU/L was also not useful for diagnosing patients with fibrosis of any stage (LSM ≥7.0), missing the diagnosis in 63% of patients, and this did not improve when examining only those with more advanced fibrosis (≥F3) being elevated in only 40%. Conclusions: Plasma aminotransferases are of limited diagnostic value when screening patients with T2DM for NAFLD or fibrosis. This supports the ADA recent guidelines for using FIB-4 and additional noninvasive testing for screening. Disclosure A. Ortiz Rocha: None. E. Godinez Leiva: None. S. Kalavalapalli: None. R. Lomonaco: None. S.S. Shetty: None. S.A. Marangi: None. E. Valdez Saenz: None. S. Shrestha: None. M.A. Gonzalez: None. X. Chi: None. M.J. Gurka: None. D. Barb: None. K. Cusi: Research Support; Echosens, Inventiva. Consultant; Poxel SA. Research Support; LabCorp, Zydus. Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck &amp; Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns. Funding National Institutes of Health (R01120331-01A1)

Left ventricular longitudinal systolic dysfunction in children with type 1 diabetes mellitus: A systematic review and meta-analysis

ObjectiveChildren with type one diabetes mellitus (T1DM) may have subclinical myocardial insults but large heterogeneity exists among the reports. This study aimed to compare myocardial strain values of the left ventricle (LV) in paediatric patients with T1DM without overt cardiac disease and healthy controls. MethodsFive databases (MEDLINE, Embase, Scopus, Web of Science and Cochrane central register of controlled trials) were searched from inception to March 30, 2020. The studies reporting two-dimensional speckle tracking echocardiography in asymptomatic T1DM paediatric patients and control groups were included. Pooled mean strain values in each group and mean difference (MD) between the two groups for LV global longitudinal strain (LVGLS) and LV global circumferential strain (LVGCS) were assessed using a random effects model. ResultsTen studies (755 T1DM and 610 control) with LVGLS were included with 6 studies having LVGCS (534 T1DM and 403 control). Patients with T1DM had overall 3 percentage points lower LVGLS than healthy subjects (18.4 %, 95 % confidence interval [17.1, 19.6] vs 21.5 % [20.3, 22.7], MD = −3.01 [−4.30, −1.71]). A similar result was seen in LVGCS (18.7 % [15.4, 22.0] vs. 21.4 % [18.1, 24.6], MD = −3.10[−6.47, 0.26]) but not statistically significant. Meta-regression identified those with higher Haemoglobin A1c (HbA1c) had worse GLS. ConclusionsSubclinical LV dysfunction among patients with T1DM occurs as early as in their childhood, while even EF is preserved. The longitudinal cardiac function is altered, but not the circumferential. GLS can be used to detect subclinical LV systolic dysfunction in paediatric population.

Evaluation of structural brain changes and their correlation with cognitive functions in adults with type 1 diabetes stratified by the age of diabetes onset: A cross-sectional study

Background and aimT1DM has a significant effect on brain structure and function. Age of onset of diabetes may be a critical factor mediating this impairment. We evaluated young adults with T1DM, stratified by the age of onset, for structural brain changes, hypothesizing that there may be a spectrum of white matter damage in these participants, compared to controls. MethodsWe recruited adult patients (20–50 years of age at the time of study enrolment) with onset of T1DM before 18 years of age and at least ten years of schooling, along with controls having normoglycaemia. We compared the Diffusion Tensor Imaging parameters between patients and controls and evaluated their correlations with cognitive z scores, and glycemic measures. ResultsWe evaluated 93 individuals, 69 [age: 24.1 (±4.5) years, gender: 47.8% men, education: 14.7 ± 1.6 years] with T1DM and 24 [age: 27.8 (±5.4) years, gender: 58.3% men, education: 14.6 ± 1.9 years] without T1DM (controls). We did not find any significant correlation of fractional anisotropy (FA) with age at T1D diagnosis, duration of diabetes, current glycemic status, or domain-wise cognitive z scores. The FA was lower (but not statistically significant) in participants with T1DM when evaluated for the whole brain, individual lobes, hippocampi and amygdala. ConclusionParticipants with T1DM do not show a significant difference in the brain white matter integrity when evaluated in a cohort of young adults with relatively few microvascular complications compared to controls.

Peripheral arterial disease among children with type 1 diabetes mellitus in a Nigerian teaching hospital

The study aimed to determine the prevalence of PAD in children with T1DM and to correlate PAD with clinical characteristics in children with T1DM. A comparative cross-sectional study was conducted involving 90 subjects (forty-five with T1DM and 45 apparently healthy comparative subjects that were matched for age and gender). Systolic blood pressure was measured in all limbs using the pocket Doppler machine (Norton Doppler scan machine). Ankle brachial index (ABI) was calculated as a ratio of ankle to arm systolic blood pressure. Peripheral arterial disease was defined as ABI less than 0.9. The prevalence of PAD was significantly higher in children with T1DM than in the matched comparison group (37.8% vs. 6.7%, p<0.001). Average values of waist circumference, hip circumference, weight, height and body mass index were comparable in subjects with TIDM and the comparison group (p>0.05). Subjects with PAD had a poorer glucose control evident by higher average values of glycated haemoglobin than those without PAD (13.47±3.2% vs. 8.16±2.3%, p<0.001). There is a strong negative correlation between ABI scores and glycated haemoglobin among subjects with T1DM (r=-0.626, p<0.001). With these findings, it is recommended that screening for PAD in children who have T1DM and poor glycaemic control should be doneearly to prevent cardiovascular complications before they arise.

N-glycomic profiling reveals dysregulated N-glycans of peripheral neuropathy in type 2 diabetes

Given the increasing morbidity of diabetes mellitus type 2 (T2DM) with peripheral neuropathy (PN), efficient screening for T2DM-PN is of great significance. Altered N-glycosylation is closely associated with T2DM progression, whereas its association with T2DM-PN remains uncharacterized. In this study, N-glycomic profiling was performed to identify the N-glycan features between T2DM patients with (n = 39, T2DM-PN) and without PN (n = 36, T2DM-C). Another independent set of T2DM patients (n = 29 for both T2DM-C and T2DM-PN) were utilized to validate these N-glycomic features. There were 10 N-glycans varied significantly between T2DM-C and T2DM-PN (p < 0.05 and 0.7 < AUC < 0.9), of which T2DM-PN was associated with increased oligomannose and core-fucosylation of sialylated glycans, and decreased bisected mono-sialylated glycan. Notably, these results were validated by an independent set of T2DM-C and T2DM-PN. This is the first profiling for N-glycan features in T2DM-PN patients, which reliably differentiates them from T2DM controls, thus providing a prospective profile of glyco-biomarkers for the screening and diagnosis of T2DM-PN.