Type 2 Diabetes Patients Research Articles

Association of overexpression of PLD6, CHRAC1 and PDCD5 with type 2 diabetes mellitus

<p><strong>Aim </strong>Diabetes type 2 (DT2) is a metabolic disease characterized by high blood sugar caused by insulin resistance and/or insufficient insulin production. The pathogenesis of DT2 is complicated by both genetic predisposition and environmental and lifestyle variables. At least 150 genetic variants have been linked to the probability of having DT2. The aim of this study was to determine the expression of PLD6, CHRAC1, and PDCD5 genes in type 2 diabetic patients. <br /><strong>Methods </strong>Information on 12 DT2 patients was obtained from the Gene Expression Omnibus (GEO) using the series identification (ID) (GSE34008). The analysis tools GEO2R, String Utils (STRING), University of Alabama at Birmingham Cancer data analysis (UAL-CAN), and the Cancer Genome Atlas (TCGA) were used. The human protein atlas provided details on gene cancer.<br /><strong>Results </strong>Only ten genes with expression differences ranging from low to high were selected. PLD6, CHRAC1, and PDCD5 were detected to have higher expression in patients compared to controls. The number of patients with primary pancreatic adenocarcinoma for SLC16A4, DERK2, and CHRAC1 was greater than that of healthy controls. Concerning the severity of cancer, all chosen genes demonstrated a greater proportion of affected individuals compared to the control group. <br /><strong>Conclusion </strong>There are multiple genes whose increased expression is linked to type 2 diabetes.</p>

P191 CO-EXISTING HYPERTENSION: AN INDEPENDENT RISK FACTOR FOR DIABETIC RETINOPATHY IN TYPE-2 DIABETES

Background and Objectives: Hypertension has plausible reason to be show the interaction due to its independent effect on retina. Epidemiological studies also provide clue that for hypertension as a possible effect modifier in the risk development of retinopathy in diabetic patients. It is worth exploring whether subgroup in diabetic population with Hypertension have different risk potential of developing retinopathy. The present study aimed to assess the association of hypertension as a risk factor for diabetic retinopathy (DR) in type 2 diabetes mellitus. Methods: A total of 977 type-2 diabetic patients recruited retrospectively in 2008 from Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorder (BIRDEM) based on hospital records for determining the incidence of diabetic retinopathy (DR), who were naı̈ve type-2 diabetes during 1993. At the end of 15 year follow-up 495 patients were diagnosed as DR by retinal colour photography. Data on diabetes and lipid profile with serum creatinine, blood pressure and biophysical measures were obtained at baseline, 5, 10 and 15 years follow-up. Binary logistic regression model was used to assess the associations of co-existing hypertension with retinopathy risk adjusting for clinical, biochemical and anthropometric variables. Results: In all three follow-up points, including at baseline, mean systolic and diastolic blood pressure were found to significantly higher among patients who developed DR (P<.001). Binary logistic regression model confirmed coexisting hypertension (OR 3.2; 95% CI 2.2 -4.7) as a significant risk factor of DR adjusting for possible confounders; serum creatinine (OR 21.9; 95% CI 14.0 -35.4) and glycemic control status (OR 17.2; 95% CI 9.4 -31.4). Interaction between hypertension, glycemic control and raised serum creatinine did not appear to be statistically significant (P>0.05). Conclusions: Co-existing hypertension is a significant risk factor of DR irrespective of nephropathy or glycolic control status among Type 2 diabetes mellitus.

Generalizability and treatment with sodium-glucose co-trasporter-2 inhibitors (SGLT2i) among patients with type 2 diabetes: an assessment using an Italian primary care database.

This study aimed to assess the proportions of type 2 diabetes (T2D) subjects meeting cardiovascular outcome trials (CVOTs) criteria for sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and estimate SGLT2i utilization, along with associated demographic and clinical characteristics, in a primary care setting. T2D patients in Italy were selected between January 1, 2021, and December 31, 2022, from The Health Improvement Network (THIN®) database. Representativeness was determined by dividing patients meeting key inclusion criteria for four CVOTs (CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, VERTIS-CV) to the total T2D population. Demographic and clinical characteristics of eligible T2D subjects and SGLT2i users were compared, and logistic regression models assessed the likelihood of receiving SGLT2i. Out of 17,102 T2D patients, 8,828 met eligibility criteria for at least one CVOT. DECLARE-TIMI 58 exhibited the highest representativeness (51.1%), compared to CANVAS (21.1%), EMPA-REG OUTCOME (5.5%), and VERTIS-CV (4.9%) trials. Eligible CVOTs patients were older (74.6 vs. 68.3 years), with a longer disease duration (10.2 vs. 9.7 years), and higher established cardiovascular disease (CVD) prevalence (36.0 vs. 27.3%) compared to SGLT2i users. Less than 10% of eligible T2D patients received SGLT2i. Males (OR: 1.43; 95%CI: 1.24-1.66) were more likely to be prescribed SGLT2i than other antidiabetic drugs, while the elderly (80 + vs. 40-64 years, OR: 0.17; 95% CI: 0.14-0.22) were less likely. Eligible T2D patients with CVD reported an increased likelihood of receiving SGLT2is compared to other antidiabetics. This study highlights significant variability in the proportion of T2D subjects meeting SGLT2i CVOT inclusion criteria, with DECLARE-TIMI-58 being the most represented. Low SGLT2i prescription rates in the Italian primary care setting, along with substantial demographic and clinical differences between SGLT-2i users and T2D eligible patients, emphasize the need for targeted interventions to optimize the use of these medications in primary care settings.

Optimizing physician-encounter frequency for type 2 diabetes patients in primary care based on cardiovascular risk assessment: A target trial emulation study.

To investigate whether the physician-encounter interval for patients with type 2 diabetes (T2D) can be optimized from 2-3 to 4-6 months among those with a calculated 10-year cardiovascular disease (CVD) risk score of less than 20% without compromising their long-term outcomes. Using territory-wide public electronic medical records in Hong Kong, we emulated a target trial to compare the effectiveness of the physician-encounter intervals of 4-6 versus 2-3 months for T2D patients without prior CVDs and with a predicted risk for CVDs of less than 20% (i.e. those patients not in the high-risk category). Propensity score matching was used to emulate the randomization of participants at baseline, where 42 154 matched individuals were included for analysis. The marginal structural model was applied to estimate the hazard ratio (HR) for CVD incidence and all-cause mortality, the incidence rate ratio of secondary and tertiary care utilization, as well as the between-group differences in HbA1c, blood pressure and cholesterol levels. During a follow-up period of up to 12 (average: 5.1) years, there was no significantly increased risk of CVD in patients with physician-encounter intervals of 4-6 months compared with those patients with physician-encounter intervals of 2-3 months (HR [95% confidence interval {CI}]: 1.01 [0.90, 1.14]; standardized 10-year risk difference [95% CI]: -0.1% [-0.7%, 0.6%]), nor for all-cause mortality (HR: 1.00 [0.84, 1.20]; standardized 10-year risk difference: -0.1% [-0.5%, 0.3%]). Additionally, there was no observable difference in the utilization of secondary and tertiary care or key clinical parameters between these two follow-up frequencies. For T2D patients with a calculated 10-year CVD risk of less than 20%, the interval of regular physician encounters can be optimized from 2-3 to 4-6 months without compromising patients' long-term outcomes and saving substantial service resources in primary care.

Islet amyloid polypeptide fibril catalyzes amyloid-β aggregation by promoting fibril nucleation rather than direct axial growth

Aberrant aggregation of amyloid-β (Aβ) and islet amyloid polypeptide (IAPP) into amyloid fibrils underlies the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes (T2D), respectively. T2D significantly increases AD risk, with evidence suggesting that IAPP and Aβ co-aggregation and cross-seeding might contribute to the cross-talk between two diseases. Experimentally, preformed IAPP fibril seeds can accelerate Aβ aggregation, though the cross-seeding mechanism remains elusive. Here, we computationally demonstrated that Aβ monomer preferred to bind to the elongation ends of preformed IAPP fibrils. However, due to sequence mismatch, the Aβ monomer could not directly grow onto IAPP fibrils by forming multiple stable β-sheets with the exposed IAPP peptides. Conversely, in our control simulations of self-seeding, the Aβ monomer could axially grow on the Aβ fibril, forming parallel in-register β-sheets. Additionally, we showed that the IAPP fibril could catalyze Aβ fibril nucleation by promoting the formation of parallel in-register β-sheets in the C-terminus between bound Aβ peptides. This study enhances our understanding of the molecular interplay between Aβ and IAPP, shedding light on the cross-seeding mechanisms potentially linking T2D and AD. Our findings also underscore the importance of clearing IAPP deposits in T2D patients to mitigate AD risk.

Okinawa-Based Nordic Diet Decreases Plasma Glial Fibrillary Acidic Protein Levels in Type 2 Diabetes Patients.

Elevated levels of glial fibrillary acidic protein (GFAP) in plasma reflect neuroinflammation and are linked to cognitive decline. Preclinical studies show that dietary change can attenuate astrocyte reactivity and neuroinflammation. In the current study, we investigate if the Okinawa-based Nordic (O-BN) diet alters plasma GFAP levels in patients with Type 2 Diabetes (T2D), a metabolic disorder associated with cognitive disturbances and an increased risk of dementia. Plasma GFAP levels were measured in T2D patients (n = 30) at baseline, after 3 months of the diet, and after a subsequent 4 months of unrestricted diets. The GFAP levels decreased significantly after 3 months of the diet (p = 0.048) but reverted to baseline levels after 4 months of unrestricted diets. At baseline, the GFAP levels correlated significantly with levels of the neurodegeneration marker neurofilament light polypeptide (r = 0.400*) and, after correcting for age, sex, and body mass index, with proinflammatory plasma cytokines (ranging from r = 0.440* to r = 0.530**) and the metabolic hormone islet amyloid polypeptide (r = 0.478*). We found no correlation with psychological well-being. These results suggest that the O-BN diet reduces neuroinflammation in T2D patients and may thus be an important preventive measure for managing T2D and reducing the risk of neurodegenerative disorders.

Psychometrics properties of type 2 diabetes treatment adherence questionnaire (DTAQ): a study based on Pender’s health promotion model

BackgroundManagement of type 2 diabetes (T2D) as a chronic disease requires treatment adherence such as controlling the blood glucose level and adopting a healthy lifestyle. The present study aimed to develop and psychometrically evaluate a questionnaire based on the Pender’s Health Promotion Model (HPM) to measure treatment adherence and the associated factors among T2D patients.MethodsThe present study was conducted in qualitative and the quantitative phases between March 2022 and March 2023. The participants were T2D patients visiting Shahid Mohammadi hospital Diabetes Clinic in Bandar Abbas in the south of Iran. The first draft of items was extracted from the qualitative phase. The present study used interviews with T2D patients, item construction, validity and reliability evaluation of the instrument, and the relevant statistical analyses. It emphasized the significance of content, face, and construct validity, along with reliability testing using Cronbach’s alpha and test-retest method. Data were analyzed using SPSS software, V16 and AMOS, V23.ResultsA 97-item questionnaire was developed through the qualitative phase and, after content validity, it was reduced to 86 items. Five items were removed in face validation, and after the test-retest method, 79 items were retained. The confirmatory factors analysis confirmed a 65-item model with appropriate fitness of data. Cronbach’s alpha coefficient showed an acceptable reliability of the diabetes treatment adherence questionnaire (α = 0.92).ConclusionThe questionnaire developed based on the HPM model provides a standard and comprehensive measurement of the degree of adherence to treatment and the associated factors among Iranian T2D patients. This is especially valuable in the Iranian healthcare context, where effective management of chronic diseases such as diabetes is of a top priority. Questionnaires can help identify barriers and facilitators of treatment adherence to inform systematic and goal-oriented interventions. The proposed questionnaire had good psychometric properties, and can be used as a valid and practical instrument to measure the factors related to treatment adherence behaviors.

KIR2DL5+CD8+ T cells associate with dietary lipid intake and are active in type 1 diabetes

BackgroundRecent studies have shown that KIR+CD8+ T cells play a role in suppressing autoimmunity by eliminating pathogenic CD4+ T cells. However, their specific role in type 1 diabetes (T1D) remains unclear. MethodsIn this study, we enrolled 108 patients diagnosed with T1D and 86 healthy individuals. We conducted flow cytometric analysis to examine the various subtypes of KIR+CD8+ T cells derived from peripheral blood mononuclear cells. Additionally, CD8+ T cells were isolated from the peripheral blood of T1D patients to assess the functions of different KIR+CD8+ T cell subtypes. To investigate the influence of lipids on the characteristics and activities of these T cell subtypes, the isolated CD8+ T cells were cultured with varying concentrations of palmitic acid (PA). Furthermore, we utilized an NSG (NOD scid gamma) mouse adoptive transfer model to assess the impact of dietary lipid intake on the functionality of KIR2DL5+CD8+ T cells in vivo. ResultsWe observed variations in circulating KIR+CD8+ T cell subtypes between patients with T1D and healthy controls. Notably, we observed a significant negative correlation between the frequencies of circulating KIR+CD8+ T cells and the titers of ZnT8 autoantibodies in individuals with T1D. Among these subtypes, KIR2DL5+CD8+ T cells demonstrated a positive association with dietary fat intake, characterized by increased perforin expression and reduced PD-1 expression. Importantly, KIR2DL5+CD8+ T cells exhibited enhanced proliferative capacity compared to other KIR+CD8+ T cell subsets. Palmitic acid (PA) was found to enhance the activation of KIR2DL5+CD8+ T cells and strengthened their ability to suppress CD4+ T cell proliferation in T1D patients. Moreover, dietary lipid intake significantly enhanced the functionality of KIR2DL5+CD8+ T cells in an NSG mouse adoptive transfer model. ConclusionOur findings suggest that lipid intake enhances the functionality of human KIR2DL5+CD8+ T cells and may offer implications for immunotherapy in T1D.

The microbiota-dependent tryptophan metabolite alleviates high-fat diet–induced insulin resistance through the hepatic AhR/TSC2/mTORC1 axis

Type 2 diabetes (T2D) is potentially linked to disordered tryptophan metabolism that attributes to the intricate interplay among diet, gut microbiota, and host physiology. However, underlying mechanisms are substantially unknown. Comparing the gut microbiome and metabolome differences in mice fed a normal diet (ND) and high-fat diet (HFD), we uncover that the gut microbiota-dependent tryptophan metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) is present at lower concentrations in mice with versus without insulin resistance. We further demonstrate that the microbial transformation of tryptophan into 5-HIAA is mediated by Burkholderia spp. Additionally, we show that the administration of 5-HIAA improves glucose intolerance and obesity in HFD-fed mice, while preserving hepatic insulin sensitivity. Mechanistically, 5-HIAA promotes hepatic insulin signaling by directly activating AhR, which stimulates TSC2 transcription and thus inhibits mTORC1 signaling. Moreover, T2D patients exhibit decreased fecal levels of 5-HIAA. Our findings identify a noncanonical pathway of microbially producing 5-HIAA from tryptophan and indicate that 5-HIAA might alleviate the pathogenesis of T2D.

Bidirectional association between type 2 diabetes and irritable bowel syndrome: A large-scale prospective cohort study.

To examine the bidirectional association between type 2 diabetes (T2D) and irritable bowel syndrome (IBS) in a large prospective population cohort. Participants free of IBS at baseline in the UK Biobank were included in the analysis of T2D and incident IBS (cohort 1), with 11 140 T2D patients and 413 979 non-T2D patients. Similarly, those free of T2D at baseline were included in the analysis of IBS and incident T2D (cohort 2), with 21 944 IBS patients and 413 979 non-IBS patients. Diagnoses of T2D and IBS were based on International Classification of Disease-10 codes. The Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs). In cohort 1, 8984 IBS cases were identified during a median 14.5-year follow-up. Compared with non-T2D, T2D patients had a 39.0% increased risk of incident IBS (HR = 1.39, 95% confidence interval [CI]: 1.23-1.56, P < .001), with a higher IBS risk in those with higher fasting blood glucose levels (HR = 1.43, 95% CI: 1.19-1.72, P < .001) or longer T2D duration (HR = 1.47, 95% CI: 1.23-1.74, P < .001). In cohort 2, 29 563 incident T2D cases were identified. IBS patients had an 18.0% higher risk of developing T2D versus non-IBS patients (HR = 1.18, 95% CI: 1.12-1.24, P < .001). A similar excess T2D risk was observed in IBS patients with a duration of either less than 10 years, or of 10 years or longer. Further sensitivity analysis and subgroup analysis indicated consistent findings. T2D and IBS exhibit a bidirectional association, with an increased risk of co-morbidity. Awareness of this association may improve the prevention and management of both diseases.

Periphery Biomarkers Predicting Conversion of Type 2 Diabetes to Pre-Alzheimer-Like Cognitive Decline: A Multicenter Follow-Up Study.

The prevalence of Alzheimer's disease (AD) is increasing, therefore, identifying biomarkers to predict those vulnerable to AD is imperative. Type 2 diabetes (T2D) serves as an independent risk factor for AD. Early prediction of T2D patients who may be more susceptible to AD, so as to achieve early intervention, is of great significance to reduce the prevalence of AD. To establish periphery biomarkers that could predict conversion of T2D into pre-AD-like cognitive decline. A follow-up study was carried out from 159 T2D patients at baseline. The correlations of cognitive states (by MMSE score) with multi-periphery biomarkers, including APOE genotype, plasma amyloid-β level, platelet GSK-3β activity, and olfactory score were analyzed by logistic regression. ROC curve was used for establishing the prediction model. Additionally, MRI acquired from 38 T2D patients for analyzing the correlation among cognitive function, biomarkers and brain structure. Compared with the patients who maintained normal cognitive functions during the follow-up period, the patients who developed MCI showed worse olfactory function, higher platelet GSK-3β activity, and higher plasma Aβ42/Aβ40 ratio. We conducted a predictive model which T2D patients had more chance of suffering from pre-AD-like cognitive decline. The MRI data revealed MMSE scores were positively correlated with brain structures. However, platelet GSK-3β activity was negatively correlated with brain structures. Elevated platelet GSK-3β activity and plasma Aβ42/Aβ40 ratio with reduced olfactory function are correlated with pre-AD-like cognitive decline in T2D patients, which used for predicting which T2D patients will convert into pre-AD-like cognitive decline in very early stage.

Healthcare Utilization and Discrepancies by Income Level Among Patients With Newly Diagnosed Type 2 Diabetes in Korea: An Analysis of National Health Insurance Sample Cohort Data.

The use of qualitative healthcare services or its discrepancy between different income levels of the type 2 diabetes (T2D) patients has seldom been studied concurrently. The present study is unique that regarding T2D patients of early stages of diagnosis. Aimed to assess the utilization of qualitative healthcare services and influence of income levels on the inequality of care among newly diagnosed patients with T2D. A retrospective cohort study of 7590 patients was conducted by the National Health Insurance Service National Sample Cohort 2.0 from 2002 to 2015. Insured employee in 2013 with no history of T2D between 2002 and 2012 were included. The standard of diabetes care includes hemoglobin A1c (HbAlc; 4 times/y), eyes (once/y) and lipid abnormalities (once/y). Multivariate logistic regression analysis was performed to examine the difference between income levels and inequality of care. From years 1 to 3, rates of appropriate screening fell from 16.9% to 14.1% (HbA1c), 15.8% to 14.5% (eye), and 59.2% to 33.2% (lipid abnormalities). Relative to income class 5 (the highest-income group), HbA1 screening was significantly less common in class 2 (year 2: odds ratio [OR], 0.78; 95% confidence interval [CI], 0.61 to 0.99; year 3: OR, 0.79; 95% CI, 0.69 to 0.91). In year 1, lipid screening was less common in class 1 (OR, 0.84; 95% CI, 0.73 to 0.98) than in class 5, a trend that continued in year 2. Eye screening rates were consistently lower in class 1 than in class 5 (year 1: OR, 0.73; 95% CI, 0.60 to 0.89; year 2: OR, 0.63; 95% CI, 0.50 to 0.78; year 3: OR, 0.81; 95% CI, 0.67 to 0.99). Newly diagnosed T2D patients have shown low rate of HbA1c and screening for diabetic-related complications and experienced inequality in relation to receiving qualitative diabetes care by income levels.

Gene Polymorphisms of the antioxidant enzymes NOX, GSTP, and GPX and diabetic nephropathy risk in Saudi patients with type 2 diabetes

Oxidative stress has been hypothesized to play a crucial role in the complications of type 2 diabetes (T2D). Hyperglycaemia-mediated increases in free radicals have a deleterious effect on cellular compartments and nucleic acids, leading to imbalances between free radicals and antioxidant enzymes. This case–control study comprised two groups with 100 participants (50 T2D and 50 DN patients) and aimed to examine the association between single-nucleotide polymorphisms (SNPs) in the genes encoding nicotinamide adenine dinucleotide phosphate oxidase (NOX), glutathione S-transferase P (GSTP1), and glutathione peroxidase 1(GPX1) and diabetic nephropathy (DN) risk in patients with T2D. An SNP genotyping assay was performed using TaqMan assay and real-time PCR to identify the SNPs (NOX rs4673, GSTP rs1695, GPX1 rs1050450). The Sanger method was used to validate our findings. Fisher chi-square analyses revealed no significant differences in these genes when comparing T2D patients with and without DN. Our findings suggest no association between the rs4673, rs1695, and rs1050450 SNPs and DN in Saudi patients with T2D.

The Association of Sociodemographic Factors and Utilization of Diabetes Technologies with Diabetes Management: An Investigation in Children and Adolescents with Type 1 Diabetes.

We aimed to investigate the relationship between sociodemographic and clinical characteristics, as well as the utilization of diabetes technologies, with diabetes management in individuals with type 1 diabetes (T1D). Our study included 134 cases diagnosed with T1D who were followed for at least 1 year with T1D. Of the cases, 67.2% were using insulin pens as their insulin regimen, while 37.8% were using insulin pumps. The rate of continuous glucose monitoring (CGM) usage was 29.9%. The rate of CGM usage was 5% in families with low income levels. Glycosylated hemoglobin A1c(HbA1c) level of children with working mothers was found to be higher compared to those with non-working mothers (median 9.2% vs. 8%; P = .009). Cases with 3 or more siblings had higher HbA1c levels compared to those with 2 or fewer siblings (median 8.7% vs. 8.1%; P = .044).The median HbA1c was 8.7% in cases using insulin pens and checking fingerstick blood glucose (SMBG); 8.3% in cases using insulin pumps and SMBG; 7.6% in cases using insulin pens with CGM, and 7.5% in cases using insulin pumps with CGM (P = .003). The utilization of insulin pumps with CGM in T1D cases exhibited lower HbA1clevels. Similarly, even the usage of insulin pens with CGM demonstrated improved diabetes management. Maternal employment and having a higher number of siblings may negatively affect diabetes management due to increased caregiver burden. We believe that personalized healthcare delivery tailored to the individual needs of T1D patients based on family and clinical characteristics could have positive effects on diabetes management.

Bioinformatics analysis to disclose shared molecular mechanisms between type-2 diabetes and clear-cell renal-cell carcinoma, and therapeutic indications

Type 2 diabetes (T2D) and Clear-cell renal cell carcinoma (ccRCC) are both complicated diseases which incidence rates gradually increasing. Population based studies show that severity of ccRCC might be associated with T2D. However, so far, no researcher yet investigated about the molecular mechanisms of their association. This study explored T2D and ccRCC causing shared key genes (sKGs) from multiple transcriptomics profiles to investigate their common pathogenetic processes and associated drug molecules. We identified 259 shared differentially expressed genes (sDEGs) that can separate both T2D and ccRCC patients from control samples. Local correlation analysis based on the expressions of sDEGs indicated significant association between T2D and ccRCC. Then ten sDEGs (CDC42, SCARB1, GOT2, CXCL8, FN1, IL1B, JUN, TLR2, TLR4, and VIM) were selected as the sKGs through the protein–protein interaction (PPI) network analysis. These sKGs were found significantly associated with different CpG sites of DNA methylation that might be the cause of ccRCC. The sKGs-set enrichment analysis with Gene Ontology (GO) terms and KEGG pathways revealed some crucial shared molecular functions, biological process, cellular components and KEGG pathways that might be associated with development of both T2D and ccRCC. The regulatory network analysis of sKGs identified six post-transcriptional regulators (hsa-mir-93-5p, hsa-mir-203a-3p, hsa-mir-204-5p, hsa-mir-335-5p, hsa-mir-26b-5p, and hsa-mir-1-3p) and five transcriptional regulators (YY1, FOXL1, FOXC1, NR2F1 and GATA2) of sKGs. Finally, sKGs-guided top-ranked three repurposable drug molecules (Digoxin, Imatinib, and Dovitinib) were recommended as the common treatment for both T2D and ccRCC by molecular docking and ADME/T analysis. Therefore, the results of this study may be useful for diagnosis and therapies of ccRCC patients who are also suffering from T2D.

Association of Helicobacter pylori infection with complications of diabetes: a single-center retrospective study

BackgroundPrevious studies examined the association of Helicobacter pylori infection (H. pylori) with complications of diabetes, but the results have been inconsistent. The aim of this study of patients with type-2 diabetes (T2D) was to determine the association of H. pylori infection with the major complications of diabetes.MethodsThis single-center retrospective study examined patients with T2D who received H. pylori testing between January 2016 and December 2021. Logistic regression analyses were used to evaluate the association of H. pylori infection with four major complications of diabetes.ResultsWe examined 960 patients with T2D, and 481 of them (50.1%) were positive for H. pylori. H. pylori infection was significantly associated with diabetic nephropathy (odds ratio [OR] = 1.462; 95% confidence interval [CI]: 1.006,2.126; P = 0.046). In addition, the co-occurrence of H. pylori positivity with hypertension (OR = 4.451; 95% CI: 2.351,8.427; P < 0.001), with glycated hemoglobin A1c (HbA1c) of at least 8% (OR = 2.925; 95% CI: 1.544,5.541; P = 0.001), and with diabetes duration of at least 9 years (OR = 3.305; 95% CI:1.823,5.993; P < 0.001) further increased the risk of diabetic nephropathy. There was no evidence of an association of H. pylori infection with retinopathy, neuropathy, or peripheral vascular disease.ConclusionsOur study of T2D patients indicated that those with H. pylori infections had an increased risk of nephropathy, and this risk was greater in patients who also had hypertension, an HbA1c level of 8% or more, and diabetes duration of 9 years or more.

Development and validation of a nomogram for screening patients with type 2 diabetic ketoacidosis

Objective and backgroundThe early detection of diabetic ketoacidosis (DKA) in patients with type 2 diabetes (T2D) plays a crucial role in enhancing outcomes. We developed a nomogram prediction model for screening DKA in T2D patients. At the same time, the input variables were adjusted to reduce misdiagnosis.MethodsWe obtained data on T2D patients from Mimic-IV V0.4 and Mimic-III V1.4 databases. A nomogram model was developed using the training data set, internally validated, subjected to sensitivity analysis, and further externally validated with data from T2D patients in Aviation General Hospital.ResultsBased on the established model, we analyzed 1885 type 2 diabetes patients, among whom 614 with DKA. We further additionally identified risk factors for DKA based on literature reports and multivariate analysis. We identified age, glucose, chloride, calcium, and urea nitrogen as predictors in our model. The logistic regression model demonstrated an area under the curve (AUC) of 0.86 (95%CI: 0.85–0.90]. To validate the model, we collected data from 91 T2D patients, including 15 with DKA, at our hospital. The external validation of the model yielded an AUC of 0.68 (95%CI: 0.67–0.70). The calibration plot confirmed that our model was adequate for predicting patients with DKA. The decision-curve analysis revealed that our model offered net benefits for clinical use.ConclusionsOur model offers a convenient and accurate tool for predicting whether DKA is present. Excluding input variables that may potentially hinder patient compliance increases the practical application significance of our model.

Association between COVID-19 and the incidence of type 1 diabetes in Portugal – a registry study

BackgroundViral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D.MethodsHospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers.ResultsIn total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25–75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356–568), 11.8% (10.1–13.4) and 0.50 µg/L (0.30–0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period.ConclusionThe T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change.

Time above range and no coefficient of variation is associated with diabetic retinopathy in individuals with type 1 diabetes and glycated hemoglobin within target.

This study aimed to investigate the association between glucose metrics and diabetic retinopathy in type 1 diabetes (T1D) patients using flash continuous glucose monitoring (FGM) systems, including those maintaining glycated hemoglobin (HbA1c) within the target range. We conducted a cross-sectional study involving 1070 T1D patients utilizing FGM systems. Data on clinical, anthropometric, and socioeconomic characteristics were collected and retinopathy was classified based on international standards. Patients' mean age was 47.6 ± 15.0 years, with 49.4% of them being females. Within the cohort, 24.8% of patients presented some form of retinopathy. In the analysis involving the entire sample of subjects, male gender (OR = 1.51, p = 0.027), Time Above Range (TAR) > 250mg/dL (OR = 1.07, p = 0.025), duration of diabetes (OR = 1.09, p < 0.001), smoking (OR = 2.30, p < 0.001), and history of ischemic stroke (OR = 5.59, p = 0.025) were associated with diabetic retinopathy. No association was observed between the coefficient of variation and diabetic retinopathy (p = 0.934). In patients with HbA1c < 7%, the highest quartile of TAR > 250 was independently linked to diabetic retinopathy (OR = 8.32, p = 0.040), in addition to smoking (OR = 2.90, p = 0.031), duration of diabetes (OR = 1.09, p < 0.001), and hypertension (OR = 2.35, p = 0.040). TAR > 250mg/dL significantly emerges as a modifiable factor associated with diabetic retinopathy, even among those patients maintaining recommended HbA1c levels. Understanding glucose metrics is crucial for tailoring treatment strategies for T1D patients.

Patients with type 2 diabetes who achieve reduced postprandial glucose levels during insulin intensive therapy may have a better recovery of β-cell function

ObjectivesTo explore parameters that may determine the improvement in C-peptide levels in patients with type 2 diabetes (T2D) receiving continuous subcutaneous insulin infusion (CSII) therapy. MethodsThe trial included a lead-in period for collecting baseline parameters and correcting hyperglycemia, a 4-day CGM period, and a 2–3 weeks treatment period. After screening, patients were hospitalized and randomized to the metformin add-on NovoRapid group or the Prandilin group. Once the glycemic target was reached, all patients underwent a 4-day CGM, with treatments maintained for 2–3 weeks. OGTTs were performed at baseline and endpoint. The primary endpoint was identifying factors contributing to better β-cell function recovery after CSII therapy. ResultsA total of 99 recruited patients were admitted as inpatients and achieved glycemic control within 3.8 ± 1.1 days. Of these, 83 (84 %) patients showed improvement in C-peptide levels, while 16 (16 %) did not show any change in C-peptide levels at the endpoint. Pearson analysis showed a negative correlation between the incremental AUC of glucose concentration (from 0700 to 1000) and the increase in incremental AUC of C-peptide levels (r = −0.199, P < 0.05). ConclusionsDrug-naïve T2D patients with lower postprandial glucose concentration during CSII therapy exhibit better β-cell function recovery.