Type 2 Diabetes Mellitus Cohort Research Articles

Role of serum endotoxin, FGF19, TLR2, TNF-α, IL-12 and IL-10 in NAFLD-associated T2DM pathogenesis: Insights into Th1 bias and protective mechanisms.

Non-alcoholic fatty liver disease (NAFLD) in non-obese patients is pathophysiologically distinct, exhibiting common immunological link with type-2 diabetes mellitus (T2DM). This study aims to delineate the role of Toll-like receptor 2 (TLR2)-mediated immuno-modulation along with its association with fibroblast growth factor receptor 4 (FGFR4) and its ligand fibroblast growth factor 19 (FGF19) in the pathogenesis of NAFLD without or with T2DM. Blood samples were collected from patients with NAFLD (n = 90), NAFLD with T2DM (n = 90) and healthy cohorts (n = 90) with consent and clinical records. Real-time polymerase chain reaction (PCR), enzyme-linked immunoassay (ELIZA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to analyze messenger ribonucleic acid (mRNA), protein expression and gene polymorphism. The molecular genetic analysis revealed the prevalence of variant allele(A) in FGFR4 gene in both cases compared to controls. The mRNA expression of FGF19 and TLR2 exhibited significant upregulation in NAFLD without T2DM compared to NAFLD with T2DM. Tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) showed upregulation in both disease cohorts compared to control while IL-10 showed significant downregulation in NAFLD with T2DM compared to the other two cohorts. Correlation analysis between FGF19 and TLR2 revealed significant positive association in both NAFLD with and without T2DM. The Th1:Th2 ratio showed significant upregulation in NAFLD with T2DM compared to NAFLD without T2DM. In conclusion, elevated serum endotoxin levels appear to contribute to NAFLD and T2DM development. Upregulated FGF19 seems to be protective against developing T2DM in NAFLD patients. Higher TLR2, TNF-α and IL-12 expression in NAFLD without T2DM suggests a Th1 bias in its pathogenesis, while reduced IL-10 in NAFLD with T2DM implies a more skewed Th1 state in this condition.

Combined serum CTRP7 and CTRP15 levels as a novel biomarker for insulin resistance and type 2 diabetes mellitus

AimsThis study aimed to examine the alterations in the serum CTRP7 and CTRP15 concentrations in patients newly diagnosed with type 2 diabetes mellitus (T2DM) and to assess the diagnostic potential of the log10 (CTRP7+CTRP15) for insulin resistance (IR) and T2DM. MethodsSerum CTRP7, CTRP15, and adiponectin levels were measured using an enzyme-linked immunosorbent assay (ELISA). Bioinformatics analysis was conducted to investigate CTRP7 and CTRP15-related genes and metabolic signaling pathways. ResultsLog10 (CTRP7+CTRP15) levels were notably elevated in the impaired glucose tolerance (IGT) and T2DM cohorts compared with those in the normal control (NGT) cohort. Log10(CTRP7+CTRP15) exhibited positive correlations with HOMA-IR, area under the glucose curve (AUCg), HbA1c%, triglyceride (TG), visceral adiposity index (VAI), body mass index (BMI), and free fatty acid (FFA), levels but negative correlations with adiponectin. Multivariate stepwise regression analysis revealed that HOMA-IR, BMI, HbA1c and FFA levels were independent factors affecting the log10 (CTRP7+CTRP15). Logistic regression analysis revealed that log10 (CTRP7+CTRP15) was independently associated with T2DM and significantly associated with increased risk. Receiver operating characteristic (ROC) curve analysis indicated that the predictive value of log10 (CTRP7+CTRP15) for T2DM and IR was superior to that of CTRP7 or CTRP15 alone. Intervention studies demonstrated that insulin, FFAs and acute exercise contribute to the elevation of serum CTRP7 levels, while hyperglycemia inhibited CTRP7 secretion. Short-term changes in blood glucose, insulin, FFA and acute exercise had minimal effects on serum CTRP15 levels. Bioinformatics analysis revealed that CTRP7 and CTRP15 interact with multiple metabolism-related genes and are enriched in glucose and lipid metabolism-related pathways. ConclusionLog10 (CTRP7+CTRP15) may serve as a valuable diagnostic marker for the management of metabolic-related diseases, particularly T2DM and IR.

Glucometabolic-Related Genes as Diagnostic Biomarkers and Therapeutic Targets for Alzheimer's Disease and Type 2 Diabetes Mellitus: A Bioinformatics Analysis.

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two widespread chronic disorders characterized by shared risk factors and molecular pathways. Glucose metabolism, pivotal for cellular homeostasis and energy supply, plays a critical role in these diseases. Its disturbance has been linked to the pathogenesis of both AD and T2DM. However, a comprehensive investigation into the specific roles of glucometabolic genes in the onset and progression of AD and T2DM has yet to be conducted. By analyzing microarray datasets from the Gene Expression Omnibus (GEO) repository, we identified differentially expressed glucometabolic genes (DEGs) in AD and T2DM cohorts. A range of bioinformatics tools were employed for functional annotation, pathway enrichment, protein interaction network construction, module analysis, ROC curve assessment, correlation matrix construction, gene set enrichment analysis, and gene-drug interaction mapping of these DEGs. Key genes were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) in AD and T2DM murine models. Our investigation identified 41 glucometabolic-related DEGs, with six prominent genes (G6PD, PKM, ENO3, PFKL, PGD, and TALDO1) being common in both AD and T2DM cohorts. These genes play crucial roles in metabolic pathways including glycolysis, pentose phosphate pathway, and amino sugar metabolism. Their diagnostic potential was highlighted by area under curve (AUC) values exceeding 0.6 for AD and 0.8 for T2DM. Further analysis explored the interactions, pathway enrichments, regulatory mechanisms, and potential drug interactions of these key genes. In the AD murine model, quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed significant upregulation of G6pd, Eno3, and Taldo1. Similarly, in the T2DM murine model, elevated expression levels of G6pd, Pfkl, Eno3, and Pgd were observed. Our rigorous research sheds light on the molecular interconnections between AD and T2DM from a glucometabolic perspective, revealing new opportunities for pharmacological innovation and therapeutic approaches. This study appears to be the first to extensively investigate glucometabolic-associated DEGs and key genes in both AD and T2DM, utilizing multiple datasets. These insights are set to enhance our understanding of the complex pathophysiology underlying these widespread chronic diseases.

The association between TyG and all-cause/non-cardiovascular mortality in general patients with type 2 diabetes mellitus is modified by age: results from the cohort study of NHANES 1999–2018

BackgroundThe prognostic value of triglyceride-glucose (TyG) index in general type 2 diabetes mellitus (T2DM) patients is still unclear. Therefore, we aimed to determine the associations between TyG and all-cause/cause-specific death in a T2DM cohort and explore whether such associations would be modified by age.MethodsA total of 3,376 patients with T2DM from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were selected and divided into the younger group (< 65 yrs) and the older group (≥ 65 yrs). Baseline TyG was calculated and cause-specific mortality status [cardiovascular (CV), cancer, and non-CV] was determined by the NHANES Public-Use Linked Mortality Files through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were used to evaluate the association between TyG and all-cause/cause-specific mortality. Interaction between TyG and age to mortality was also evaluated. Sensitivity analyses were performed in patients without cardiovascular disease, chronic kidney disease, or insulin treatment.ResultsDuring a median follow-up of 107 months, 805 all-cause deaths occurred, of which 250 and 144 were attributed to CV and cancer deaths. There was a significant age interaction to the association between TyG and all-cause/non-CV mortality. After fully adjusting for potential confounding factors, higher TyG was associated with an increased risk of all-cause [TyG per unit increase Hazard Ratio (HR) 1.33, 95% Confidence Interval (CI) 1.06–1.66, p = 0.014] and non-CV mortality (TyG per unit increase HR 1.54, 95% CI 1.18–2.01, p = 0.002) only in the younger group, but not in the older group. There was no significant association between TyG and CV/cancer death in the total cohort and two age subgroups. Similar results were found in RCS and sensitivity analyses.ConclusionIn a national sample of patients with T2DM in the United States, we found that the association between TyG and all-cause/non-CV death was modified by age. Higher TyG was only associated with an increased risk of all-cause/non-CV only in T2DM patients younger than 65 years old, but not in older patients.

Association Between Age at Diabetes Diagnosis and Subsequent Incidence of Cancer: A Longitudinal Population-Based Cohort.

Diabetes presenting at a younger age has a more aggressive nature. We aimed to explore the association of age at type 2 diabetes mellitus (T2DM) diagnosis with subsequent cancer incidence in a large Chinese population. The prospective population-based longitudinal cohort included 428,568 newly diagnosed T2DM patients from 2011 to 2018. Participants were divided into six groups according to their age at diagnosis: 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years. The incidence of overall and 14 site-specific cancers was compared with the Shanghai general population including 100,649,346 person-years. A total of 18,853 and 582,643 overall cancer cases were recorded in the T2DM cohort and the general population. The age-standardized rate of overall cancer in T2DM patients was 501 (95% CI: 491, 511) per 100,000 person-years, and the standardized incidence ratio (SIR) was 1.10 (1.09, 1.12). Younger age at T2DM diagnosis was associated with higher incidence of overall and site-specific cancers. SIRs for overall cancer with T2DM diagnosis at ages 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years were 1.48 (1.41, 1.54), 1.30 (1.25, 1.35), 1.19 (1.15, 1.23), 1.16 (1.12, 1.20), 1.06 (1.02, 1.10), and 0.86 (0.84, 0.89), respectively. Similar trends were observed for site-specific cancers, including respiratory, colorectum, stomach, liver, pancreatic, bladder, central nervous system, kidney, and gallbladder cancer and lymphoma among both males and females. Our findings highlight the necessity of stratifying management for T2DM according to age of diagnosis. As with a range of vascular outcomes, age-standardized cancer risks are greater in earlier compared with later onset T2DM.

The Combined Effect of Systemic Immune-Inflammation Index and Type 2 Diabetes Mellitus on the Prognosis of Patients Undergoing Percutaneous Coronary Intervention: A Large-Scale Cohort Study.

Chronic low-grade inflammation is the common mechanism of both atherosclerosis and type 2 diabetes mellitus (T2DM), and systemic immune-inflammation index (SII) has been emerged as a novel and simple inflammatory biomarker. However, the association between SII and glycemic metabolism and their synergetic effect on the prognosis of coronary artery disease (CAD) patients remains unclear. A total of 8602 patients hospitalized for percutaneous coronary intervention (PCI) were included. The primary endpoint was major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction (MI), and target vessel revascularization. According to the optimal cut-off value of SII for MACEs, patients were grouped into higher levels of SII (SII-H) and lower levels of SII (SII-L) and further divided by the concomitance of T2DM into four groups: SII-H/T2DM, SII-H/Non-T2DM, SII-L/T2DM, SII-L/Non-T2DM. During a median 2.4-year follow-up, 522 MACEs occurred. The optimal cut-off value of SII for MACEs was 502.5. A 1-unit increase of SII (transformed by natural logarithm) was associated with a 29% increase of MACE risks in the T2DM cohort [adjusted hazard ratio (HR): 1.29, 95% confidence interval (CI): 1.03 to 1.61, P = 0.024], while had no effect in the non-T2DM cohort (HR: 1.03, 95% CI: 0.80 to 1.34, P = 0.800). Compared to those in SII-H/T2DM group, patients in SII-H/Non-T2DM, SII-L/T2DM, SII-L/Non-T2DM had significantly decreased risk of MACEs [adjusted HR: 0.77, 95% CI: 0.61 to 0.98, P = 0.036; adjusted HR: 0.66, 95% CI: 0.50 to 0.87, P = 0.003; adjusted HR: 0.58, 95% CI: 0.45 to 0.74, P < 0.001; respectively]. Multivariable Cox regression analysis also indicated the highest risk in T2DM patients with higher levels of SII than others (P for trend < 0.001). In this large-scale real-world study, diabetic patients with elevated SII levels were associated with worse clinical outcomes after PCI.

Impact of the first COVID-19 lockdown in Austria on laboratory and mental parameters in diabetic patients: a retrospective analysis highlighting the importance of regular medical consultations in a patient cohort.

Due to the COVID-19 pandemic, the first lockdown was implemented in Austria for almost 7 weeks. In contrast to many other countries, medical consultations were permitted, either by telemedicine or at doctors' offices. Nevertheless, restrictions related to this lockdown could possibly cause an increased risk of deterioration in health, especially in diabetes. This study aimed to assess the impact of Austria's first lockdown on laboratory and mental parameters in a type-2 diabetes mellitus cohort. Overall 347 mainly elderly patients with type-2 diabetes (56% male; aged 63.7±10.1 years) were included in this retrospective practitioner-based analysis. Laboratory as well as mental parameters were compared from before and after the lockdown. The lockdown showed no significant effect on HbA1c levels. On the other hand, total cholesterol (P<0.001) and LDL cholesterol (P<0.001) levels improved significantly, whereas body weight (P<0.01) and mental well-being based on the EQ-5D-3L questionnaire (P<0.01) increased significantly in terms of worsening. Lack of movement and staying at home resulted in a significant weight gain and worsening of mental well-being in type-2 diabetes during the first lockdown in Austria. Thanks to regular medical consultations, laboratory parameters remained stable or even improved. Thus, routine health check-ups in mainly elderly type 2 diabetic patients are essential to minimize the deterioration of health conditions during lockdowns.

HSD73 Characteristics of Type 2 Diabetes Patients That Used Virtual Care Since COVID-19 Pandemic: Evidence from a Large Commercial Healthcare Claims Database in the US

The use of virtual care has accelerated since the emergence of COVID-19 pandemic. This study aims to analyze the differences in patient characteristics between new and existing type 2 diabetes mellitus (T2DM) patients that utilized virtual care. Adult patients (age³18 years) with T2DM who had a virtual care (phone or video) visit between April 1, 2020 and March 31, 2022 from the OptumLabs Data Warehouse® were identified. The date of the first virtual visit was defined as the index date. Patients were required to be continuously insured at least 1 year prior to their index date (baseline) and at least 90 days of follow-up coverage. T2DM patients were categorized as newly diagnosed and as existing T2DM patients based on whether a diabetes diagnosis was observed in the baseline or not. A total of 1,864,203 unique T2DM patients were eligible, with18.5% identified as newly diagnosed and 81.5% as existing T2DM patients. On average, newly diagnosed T2DM patients were younger than existing T2DM patients. Majority (54.5%) of newly diagnosed T2DM patients were commercially insured compared to only 38.6% existing T2DM patients. Among the existing T2DM patients, 61.2% were White, 17.9% Non-Hispanic Black, 12.7% Hispanic and 8.2% others. Of this population, 12.7 % had a household income ≥ $125,000, 13.3% had at least a Bachelor’s degree, and 80.3% reside in a metropolitan area. For the newly diagnosed T2DM cohort, 59.7% were White, 15.3% Non-Hispanic Black, 13.4% Hispanic, and 11.6% others. More of the newly diagnosed T2DM cohort had higher household income, higher education, and resided in a metropolitan area compared to patients with existing T2DM. T2DM patients that used virtual care were heterogenous in terms of their baseline characteristics. This underscores the emerging trend that virtual care can potentially play a complementary role in managing patients with diabetes.

The burden of nonalcoholic steatohepatitis (NASH) in the United States

BackgroundThere is limited data on the comparative economic and humanistic burden of non-alcoholic steatohepatitis (NASH) in the United States. The objective was to examine the burden of disease comparing NASH to a representative sample of the general population and separately to a type 2 diabetes mellitus (T2DM) cohort by assessing health-related quality of life (HRQoL) measures, healthcare resource use (HRU) and work productivity and activity impairment (WPAI).MethodsData came from the 2016 National Health and Wellness Survey, a nationally representative patient-reported outcomes survey conducted in the United States. Respondents with physician-diagnosed NASH, physician-diagnosed T2DM, and respondents from the general population were compared. Humanistic burden was examined with mental (MCS) and physical (PCS) component summary scores from the Short-Form (SF)-36v2, concomitant diagnosis of anxiety, depression, and sleep difficulties. Economic burden was analysed based on healthcare professional (HCP) and emergency room (ER) visits, hospitalizations in the past six months; absenteeism, presenteeism, overall work impairment, and activity impairment scores on WPAI questionnaire. Bivariate and multivariable analysis were conducted for each outcome and matched comparative group.ResultsAfter adjusting for baseline demographics and characteristics, NASH (N = 136) compared to the matched general population cohort (N = 544), reported significantly lower (worse) mental (MCS 43.19 vs. 46.22, p = 0.010) and physical (PCS 42.04 vs. 47.10, p < 0.001) status, higher % with anxiety (37.5% vs 25.5%, p = 0.006) and depression (43.4% vs 30.1%, p = 0.004), more HCP visits (8.43 vs. 5.17), ER visits (0.73 vs. 0.38), and hospitalizations (0.43 vs. 0.2) all p’s < 0.05, and higher WPAI scores (e.g. overall work impairment 39.64% vs. 26.19%, p = 0.011). NASH cohort did not differ from matched T2DM cohort (N = 272) on mental or work-related WPAI scores, but had significantly worse physical status (PCS 40.52 vs. 44.58, p = 0.001), higher % with anxiety (39.9% vs 27.8%, p = 0.043), more HCP visits (8.63 vs. 5.68, p = 0.003) and greater activity impairment (47.14% vs. 36.07%, p = 0.010).ConclusionThis real-world study suggests that burden of disease is higher for all outcomes assessed among NASH compared to matched general controls. When comparing to T2DM, NASH cohort has comparable mental and work-related impairment but worse physical status, daily activities impairment and more HRU.

MP10-05 LITHOPROTECTIVE EFFECT OF GLP-1 AGONISTS IN DIABETIC STONE FORMERS

You have accessJournal of UrologyCME1 Apr 2023MP10-05 LITHOPROTECTIVE EFFECT OF GLP-1 AGONISTS IN DIABETIC STONE FORMERS Kelley Zhao, Brian Shkolnik, Jennifer Lu, Joshua Miller, and David Schulsinger Kelley ZhaoKelley Zhao More articles by this author , Brian ShkolnikBrian Shkolnik More articles by this author , Jennifer LuJennifer Lu More articles by this author , Joshua MillerJoshua Miller More articles by this author , and David SchulsingerDavid Schulsinger More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Type 2 Diabetes mellitus (T2DM) is associated with increased risk of calcium oxalate and uric acid (UA) stones. The most commonly prescribed medication for T2DM, Metformin, worsens this risk by increasing urinary oxalate, increasing urinary calcium and decreasing urine pH. With the increasing popularity of next-generation hypoglycemic agents, it is important to study the risk of stone formation with these newer medications. This study aims to assess the effects of various hypoglycemic agents on 24-hour urine studies in diabetic stone formers. METHODS: A retrospective review was conducted for all patients with a history of nephrolithiasis and a 24-hour urine study seen between July 2017-December 2019 for an outpatient visit. Patients with T2DM were assessed for use of hypoglycemic agents (metformin, sulfonylurea, GLP-1 agonist, DPP-4 inhibitors, SGLT-2 inhibitors, insulin), stone analysis, BMI, HbA1c, and 24-hour urine study. Two-tailed t-tests were used for mean comparison and chi square tests for stone rate comparison. RESULTS: Among the included 510 patients, 86 had T2DM (45 males, 41 females, mean age 63.6 years). Compared to the non-T2DM cohort, T2DM patients had lower urine pH (5.62 vs 6.14, p<0.00001), higher urine oxalate (41.7 vs 36.14, p=0.013) and higher UA supersaturation (1.45 vs 0.94, p<0.00001). Patients on GLP-1 agonists had greater urinary citrate than both the T2DM cohort (927.94 vs 544.59, p=0.007) and the non-T2DM cohort (566.55, p<0.0001). Between diabetic GLP-1 agonist users and non-users, there was no significant difference in BMI (non-GLP 33.1 vs GLP 35.4, p=0.34) or HbA1c (non-GLP 7.0 vs GLP 7.2, p=0.74). Though T2DM patients had higher rates of UA stones (31.7% vs 12.1%, p<0.0001), GLP-1 agonists users did not have a higher rate of UA stones compared to non-T2DM patients (18.2% vs 12.1%, p=0.54). There were no significant differences found with Metformin, sulfonylurea, DPP-4 inhibitors, SGLT-2 inhibitors, or insulin. CONCLUSIONS: T2DM is a known risk factor for nephrolithiasis, however, treatment with GLP-1 agonists may be litho-protective. The significant increase in urine citrate and reduction in UA stone formation suggests a lithoprotective effect of GLP-1 agonists independent of weight or diabetes control. Consideration should be made to recommend GLP-1 agonists to T2DM patients with nephrolithiasis. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e115 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kelley Zhao More articles by this author Brian Shkolnik More articles by this author Jennifer Lu More articles by this author Joshua Miller More articles by this author David Schulsinger More articles by this author Expand All Advertisement PDF downloadLoading ...

The Prevalence of Chronic Kidney Disease and Albuminuria in Patients With Type 1 and Type 2 Diabetes Attending a Single Centre.

Background Diabetes is the leading cause of chronic kidney disease worldwide. Diabetic kidney disease is one of the microvascular complications of diabetes and it involves changes in glomerular hemodynamics, interstitial fibrosis, and tubular atrophy. Early detection and management of Diabetic kidney disease (DKD) help to reduce morbidity and mortality. This study aims to assess the prevalence of nephropathy and albuminuria in the diabetic population attending an Irish tertiary care center. Methods Retrospective data collection and analysis of patients diagnosed with Type 1 diabetes mellitus(T1DM) and Type 2 diabetes mellitus (T2DM) through the Development and Integration of Accurate Mathematical Operations in Numerical Data-Processing (DIAMOND) database in a single Irish tertiary care center. An audit tool was used to collect patients' information including gender, age, type of diabetes, serum creatinine, urinary albumin excretion, albumin creatinine ratio (ACR), body mass index, and last available glycated hemoglobin (HbA1c). Results Out of 7394 subjects with T2DM, 3139 (42%) were identified with chronic kidney disease (CKD).There were 1866 subjects with positive ACR out of 3139 subjects with CKD in the T2DM cohort.This shows that 25% of subjects have diabetic kidney disease and 17% have CKD of undetermined etiology.In the T1DM cohort with 1166 subjects, 209 (18%) were identified with CKD.Out of these 209 subjects with CKD, 164 (14%) were ACR-positive.The prevalence of CKD and albuminuria were related to age in both T1DM and T2DM populations. Albuminuria showed a linear relationship with age in subjects with no known CKD, which shows that age causally relates to albuminuria independent of type and duration of diabetes. Conclusion CKD is more prevalent in patients with T2DM as compared to T1DM, whereas the prevalence of albuminuria is higher in the T1DM population.

Assessment of QRISK3 as a predictor of cardiovascular disease events in type 2 diabetes mellitus.

The risk of cardiovascular disease (CVD) in diabetes mellitus (DM) patients is two- to three-fold higher than in the general population. We designed a 10-year cohort trial in T2DM patients to explore the performance of QRESEARCH risk estimator version 3 (QRISK3) as a CVD risk assessment tool and compared to Framingham Risk Score (FRS). This is a single-center analysis of prospective data collected from 566 newly-diagnosed patients with type 2 DM (T2DM). The risk scores were compared to CVD development in patients with and without CVD. The risk variables of CVD were identified using univariate analysis and multivariate cox regression analysis. The number of patients classified as low risk (<10%), intermediate risk (10%-20%), and high risk (>20%) for two tools were identified and compared, as well as their sensitivity, specificity, positive and negative predictive values, and consistency (C) statistics analysis. Among the 566 individuals identified in our cohort, there were 138 (24.4%) CVD episodes. QRISK3 classified most CVD patients as high risk, with 91 (65.9%) patients. QRISK3 had a high sensitivity of 91.3% on a 10% cut-off dichotomy, but a higher specificity of 90.7% on a 20% cut-off dichotomy. With a 10% cut-off dichotomy, FRS had a higher specificity of 89.1%, but a higher sensitivity of 80.1% on a 20% cut-off dichotomy. Regardless of the cut-off dichotomy approach, the C-statistics of QRISK3 were higher than those of FRS. QRISK3 comprehensively and accurately predicted the risk of CVD events in T2DM patients, superior to FRS. In the future, we need to conduct a large-scale T2DM cohort study to verify further the ability of QRISK3 to predict CVD events.

Association of vaspin rs2236242 with type 2 diabetes mellitus and obesity: a meta-analysis of case-control studies.

Elevated circulating vaspin levels is linked with type 2 diabetes mellitus (T2DM) and obesity. The genetic basis of the association between vaspin rs2236242 and T2DM and obesity is still being investigated. We executed a meta-analysis to evaluate the magnitude of effect caused by vaspin rs2236242 on T2DM and obesity. We searched Pubmed, Embase, MEDLINE, Scopus, Web of Science, and Google Scholar for relevant articles published up to 19 February 2022. Data were extracted and summary estimates of the association between vaspin rs2236242 and T2DM and obesity were assessed. Odds ratios (ORs) and confidence intervals (CIs) were used to measure the effect. This meta-analysis included 2206 cases and 2715 controls in the T2DM cohort, meanwhile 271 cases and 444 controls in the obesity cohort. The pooled estimates revealed no link between vaspin rs2236242 and T2DM, but allele-A was significantly higher in the controls of the obesity cohort, showing that this single nucleotide polymorphism (SNP) has a reduced obesity risk effect. Sensitivity analysis revealed no studies that would modify the estimates or the heterogeneity. Begg and Mazumdar's and Egger's tests indicated no substantial publication bias. Our meta-analysis provides evidence of significant association between vaspin rs2236242 and reduced risk of obesity but not T2DM. The online version contains supplementary material available at 10.1007/s40200-022-01119-8.

Twenty-Year Temporal Trends in Risk of Ischemic Stroke in Incident Type 2 Diabetes: A Danish Population-Based Cohort Study.

We examined temporal trends in risk of first-time ischemic stroke in patients with incident type 2 diabetes mellitus (T2DM) and no prior atherosclerotic cardiovascular disease (ASCVD). Using nationwide health registries, we identified all patients with incident T2DM without a prior hospital diagnosis of ASCVD from 1996 to 2015 in Denmark. Patients were assigned to 5-year periods based on the date of T2DM diagnosis and were followed for 5 years. Each patient was matched by sex and age with up to three individuals from the general population. Temporal trends in ischemic stroke were examined using Cox regression to compute hazard ratios (HRs). Temporal use of prophylactic cardiovascular medications was also assessed. The study comprised 288,825 patients with incident T2DM and 782,232 general population individuals. From 1996-2000 to 2011-2015, the 5-year risk of first-time ischemic stroke was approximately halved in the T2DM cohort (5.2% vs. 2.7%; sex- and age-adjusted HR 0.52 [95% CI 0.49-0.55]). Patients diagnosed in 2011-2015 had increased risk of ischemic stroke compared with individuals in the general population; however, the risk difference narrowed over time (5.2% vs. 2.9% in 1996-1999 [difference 2.3%]; 2.7% vs. 2.0% in 2011-2015 [difference 0.7%]). Use of prophylactic cardiovascular medications increased markedly during the overall study period, especially use of statins (from 5% to 50%) and multiple antihypertensive drugs (from 18% to 33%). From 1996 to 2015, the 5-year risk of first-time ischemic stroke was approximately halved in patients with incident T2DM and no prior ASCVD, coinciding with markedly increased use of prophylactic cardiovascular medications.

CLINICAL EVENT REDUCTIONS IN HIGH-RISK HYPERTENSION PATIENTS TREATED WITH RENAL DENERVATION: 10-YEAR PROJECTIONS BASED ON 3-YEAR FOLLOW-UP FROM THE GLOBAL SYMPLICITY REGISTRY

Objective: Clinical event rates over 3 years have been published for patients with uncontrolled hypertension treated with radiofrequency renal denervation (RDN) in the Global SYMPLICITY Registry (GSR). We estimated 10-year clinical event reductions following RDN vs. a simulated control group without RDN, for two high-risk subgroups and the full GSR cohort. Design and method: A Markov model was used to compare projected 10-year clinical events [stroke, myocardial infarction (MI), cardiovascular death (CVD), heart failure (HF), all-cause death (ACD), and a composite of major adverse cardiac events (MACE, calculated as sum of stroke, MI, and CVD)] for RDN patients vs. a hypothetical control for the high atherosclerotic vascular disease risk (ASCVD) subgroup (n = 737; 69 ± 8 years), the type-2 diabetes mellitus (T2DM) subgroup (n = 1,007; 64 ± 10 years), and for all GSR patients (n = 2,651; 61 ± 12 years). The simulated control assumed maintenance of baseline office systolic blood pressure (oSBP) over time. The model was calibrated to 3-year stroke and MI events reported in the GSR and used published meta-regression data to calculate risk reduction based on cohort-specific changes in oSBP from baseline. Relative risks (RRs), events avoided, and numbers needed to treat (NNTs) were calculated at 3 and 10 years, along with the ratio of 10- vs. 3-year projected events avoided. Results: 10-year MACE events were 35.8% vs. 48.5% (-12.7%, RR = 0.74) for RDN vs. control for all GSR patients, 37.8% vs. 52.4% (-14.6%, RR = 0.72) for the high ASCVD risk cohort, and 40.5% vs. 54.0% (-13.5%, RR = 0.75) for the T2DM cohort. Across all three cohorts, events avoided were highest for stroke and lowest for MI. 10-year NNTs for MACE were comparable between the three cohorts, estimated between 7 to 8. The ratio of model-projected MACE at 10- vs. 3-years was 5.20, 5.46, and 5.03 for the full GSR, high ASCVD risk, and T2DM cohorts, respectively. Conclusions: Model-based projections based on 3- year events observed in the GSR suggest meaningful event reductions after treatment with radiofrequency RDN at 10 years that might be up to 5-times higher than the projected events avoided at 3 years under the assumption of maintained treatment effect versus baseline.

Serological Phenotyping Analysis Uncovers a Unique Metabolomic Pattern Associated With Early Onset of Type 2 Diabetes Mellitus.

Background: Type 2 diabetes mellitus (T2DM) is a multifaceted disorder affecting epidemic proportion at global scope. Defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond effectively to insulin are the underlying biology of T2DM. However, circulating biomarkers indicative of early diabetic onset at the asymptomatic stage have not been well described. We hypothesized that global and targeted mass spectrometry (MS) based metabolomic discovery can identify novel serological metabolic biomarkers specifically associated with T2DM. We further hypothesized that these markers can have a unique pattern associated with latent or early asymptomatic stage, promising an effective liquid biopsy approach for population T2DM risk stratification and screening. Methods: Four independent cohorts were assembled for the study. The T2DM cohort included sera from 25 patients with T2DM and 25 healthy individuals for the biomarker discovery and sera from 15 patients with T2DM and 15 healthy controls for the testing. The Pre-T2DM cohort included sera from 76 with prediabetes and 62 healthy controls for the model training and sera from 35 patients with prediabetes and 27 healthy controls for the model testing. Both global and targeted (amino acid, acylcarnitine, and fatty acid) approaches were used to deep phenotype the serological metabolome by high performance liquid chromatography-high resolution mass spectrometry. Different machine learning approaches (Random Forest, XGBoost, and ElasticNet) were applied to model the unique T2DM/Pre-T2DM metabolic patterns and contrasted with their effectiness to differentiate T2DM/Pre-T2DM from controls. Results: The univariate analysis identified unique panel of metabolites (n = 22) significantly associated with T2DM. Global metabolomics and subsequent structure determination led to the identification of 8 T2DM biomarkers while targeted LCMS profiling discovered 14 T2DM biomarkers. Our panel can effectively differentiate T2DM (ROC AUC = 1.00) or Pre-T2DM (ROC AUC = 0.84) from the controls in the respective testing cohort. Conclusion: Our serological metabolite panel can be utilized to identifiy asymptomatic population at risk of T2DM, which may provide utility in identifying population at risk at an early stage of diabetic development to allow for clinical intervention. This early detection would guide ehanced levels of care and accelerate development of clinical strategies to prevent T2DM.

Association of metformin treatment and outcome in adult patients with ITP and pre-existing T2DM.

Primary immune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease that could manifest with comorbid type 2 diabetes mellitus (T2DM). However, the exact impact of T2DM in patients with ITP remains uncertain. In this study, we performed a retrospective cohort study of 458 participants with ITP. The prevalence of T2DM was 7.6% in this population (35 patients), which was slightly lower than the Chinese nationwide prevalence of T2DM, calculated to be approximately 10.9%. The participants with pre-existing T2DM displayed a significantly higher response to therapy than those without T2DM (71% vs. 53%). Furthermore, in the T2DM cohort, the response rate reached 88% when metformin was included in the treatment regimen. This clinical evidence suggests that metformin therapy might improve the clinical outcomes of ITP.

Association between body mass index changes and other risk factors for cardiovascular disease in patients with type 2 diabetes mellitus

Objectives: To investigate the association between body mass index (BMI) changes and other risk factors for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Methods: Based on the T2DM cohort in rural communities of Zhejiang province, baseline and follow up information of height, weight, blood pressure, glycated hemoglobin (HbA1c), TC, TG, LDL-C and HDL-C of the T2DM patients were collected. After excluding those who died during the follow-up period, lost follow-up or had incomplete information, a total of 8 953 T2DM patients were included in the final analysis. Multiple linear regression and Cox proportional hazards regression models were used for analysis. Results: At baseline survey, 40.97% of the T2DM patients were overweight and obese. Compared with those with normal BMI, the SBP, DBP and TG level were significantly higher, while HDL-C level was significantly lower in the overweight and obese T2DM patients (P<0.01). During the follow-up period, the blood glucose control rate in the patients increased by 15%, and the levels of HbA1c decreased in the patients with different BMI changes at different degrees. Compared with the patients who kept normal BMI, the HbA1c level decrease had a smaller range, while the SBP and DBP increase had a larger range in the patients with persistent overweight and obesity, and their substandard rates of HbA1c, SBP, DBP, TG, HDL-C levels were 1.142 (1.057-1.233) times, 1.123 (1.055-1.196) times, 1.220 (1.128-1.320) times, 1.400 (1.282-1.528) times and 1.164 (1.069-1.267) times higher. The changes of blood pressure, blood lipids and other related indicators in the patients whose BMI became abnormal were similar to those of the patients with persistent overweight and obesity; Compared with the patients whose BMI were kept normal, the differences in changes and substandard rate of blood glucose level, blood pressure level in the patients whose BMI became normal were not significant (P>0.05). The change value of BMI was positively correlated with the change value of SBP, DBP, TG and LDL-C, while negatively correlated with the change value of HDL-C (P<0.05). Conclusions: Abnormal changes in BMI are associated with the adverse changes of blood glucose level, blood pressure, and blood lipids level and other cardiovascular disease risk factors. Keeping normal BMI would benefit the positive outcome of cardiovascular adverse factors.

Adherence to a Mediterranean diet and health-related quality of life: a cross-sectional analysis of overweight and obese middle-aged and older adults with and without type 2 diabetes mellitus.

The relationship between adherence to a Mediterranean diet (MedDiet) and health-related quality of life (HRQoL) is unclear, particularly in vulnerable older adults. This cross-sectional analysis explored the association between adherence to a MedDiet and subscales of HRQoL in two independent cohorts of overweight and obese middle-aged to older adults with and without type 2 diabetes mellitus (T2DM). Both cohorts were community-dwelling (T2DM aged ≥ 50 years; non-T2DM aged ≥ 60 years) with a BMI ≥ 25 kg/m2. Adherence to a MedDiet was assessed using the Mediterranean Diet Adherence Screener, and HRQoL was determined using the 36-item short-form health survey. Multiple regression analysis was used to examine the association between adherence to a MedDiet and HRQoL subscales. A total of 152 middle-aged to older adults were included (T2DM: n 87, 71·2 (sd 8·2) years, BMI: 29·5 (sd 5·9) kg/m2; non-T2DM: n 65, 68·7 (sd 5·6) years, BMI: 33·7 (sd 4·9) kg/m2). Mean adherence scores for the entire cohort were 5·3 (sd 2·2) (T2DM cohort: 5·6(sd 2·3); non-T2DM cohort: 4·9 (sd 2·0)). In the adjusted model, using pooled data from both study cohorts, adherence to a MedDiet was significantly associated with the general health subscale of HRQoL (β = 0·223; 95 % CI 0·006, 0·044; P = 0·001). Similar findings were also observed in the T2DM cohort (β = 0·280; 95 % CI 0·007, 0·054; P = 0·001). However, no additional significant associations between adherence to a MedDiet and HRQoL subscales were observed. We showed that adherence to a MedDiet was positively associated with the general health subscale of HRQoL in middle-aged to older adults with T2DM. However, larger longitudinal data in older adults with a wider range of adherence scores, particularly higher adherence, are required to better understand the direction of this relationship.

Pyogenic Liver Abscess Risk in Patients With Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide, Population-Based Cohort Study.

Background: To date, no comprehensive epidemiological study exists on pyogenic liver abscess (PLA) risk in patients with newly diagnosed type 2 diabetes mellitus (T2DM) worldwide.Methods: We conducted a retrospective cohort study by using data from Taiwan National Health Insurance Research Database (NHIRD) to examine the association between newly diagnosed T2DM and PLA. The T2DM cohort included patients newly diagnosed as having T2DM (ICD-9-CM:250) from 2000 to 2009, with follow-up until December 31, 2011. The comparison cohort was then recruited through 1:4 random frequency matching with the T2DM cohort. Finally, the adjusted hazard ratios for PLA were compared between the T2DM and comparison cohorts, which included 44,728 patients with T2DM and 178,912 patients without DM respectively.Results: In T2DM cohort, 166 patients were diagnosed as having PLA (incidence rate = 5.87 per 10,000 person-years) and in comparison cohort, 238 patients were diagnosed as having PLA (incidence rate = 2.06 per 10,000 person-years). The T2DM cohort exhibited higher PLA risk than did the comparison cohort (hazard ratio = 2.83, 95% confidence interval = 2.32–3.46). Furthermore, the adjusted hazard ratio for PLA risk in T2DM cohort was the highest in those who were younger, man and with duration of DM <2 years. In the T2DM cohort, the most common PLA causative agent was Klebsiella pneumonia (KP). In addition, PLA risk was high in T2DM patients with gallstone and cholecystitis. Compared with comparison cohort, patients with T2DM prescribed acarbose has a lower PLA risk, however glyburide significantly increased PLA risk in T2DM cohort.Conclusion: In patients with newly diagnosed T2DM, PLA risk was high and acarbose might reduce PLA risk.