Screening for diabetic peripheral neuropathy at community pharmacies in Slovakia.

AIM: To identify diabetic patients with a potential risk of developing diabetic peripheral neuropathy (DPN) in community pharmacies in Slovakia using a modified Michigan Neuropathy Screening Instrument questionnaire (MNSIq-12). METHODS: This cross-sectional study enrolled 703 patients with type 1 and type 2 diabetes mellitus who had not been diagnosed with DPN. The study took place in selected community pharmacies across Slovakia in October 2019. The MNSIq-12 was administered by pharmacy students, and a Michigan score <1.5 was considered risky. The groups divided based on the Michigan score were compared in terms of duration of diabetes, age, body mass index (BMI), sex, weekly physical activity, level of education, and smoking. RESULTS: The risk of developing DPN was detected in 6.6% of respondents with type 1 diabetes and 13.4% with type 2 diabetes. Patients with both types of diabetes (38.2%; 67.0%) reported fatigue and heaviness in the legs as the most common clinical symptoms that may indicate the development of DPN. Those with a Michigan score <1.5 were older (P<0.0001), had a higher BMI (P<0.0001), a lower level of education (P=0.0020), and were less physically active (P<0.0001). Conclusion Approximately one-eighth of patients with diabetes who visited community pharmacies were potentially at risk for developing DPN. The modified MNSIq-12 was shown to be a simple, time-effective, and non-invasive indicative screening tool that can be applied in the environment of community pharmacies.

PCI vs. CABG in left main with multi-vessel coronary artery disease and diabetes: Case report.

This case challenges the conventional preference for coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) in patients with diabetes, left main coronary artery disease (LMCAD) and multivessel disease. Current guidelines generally recommend CABG, especially in the context of LMCAD. However, our case involves a male patient with diabetes with LMCAD and extensive multivessel disease who was successfully treated with PCI, demonstrating a favorable outcome. Despite the high-risk profile, including a SYNTAX score of 28, the PCI approach was selected. This decision was supported by evidence suggesting comparable outcomes between PCI and CABG in similar patients. Our case highlights the potential of PCI as not just a viable, but potentially superior alternative in specific high-risk patients with diabetes, contrary to the prevailing belief in favor of CABG for all patients with left main involvement.

External validation of a minimal-resource model to predict reduced estimated glomerular filtration rate in people with type 2 diabetes without diagnosis of chronic kidney disease in Mexico: a comparison between country-level and regional performance.

Background: Patients with type 2 diabetes are at an increased risk of chronic kidney disease (CKD) hence it is recommended that they receive annual CKD screening. The huge burden of diabetes in Mexico and limited screening resource mean that CKD screening is underperformed. Consequently, patients often have a late diagnosis of CKD. A regional minimal-resource model to support risk-tailored CKD screening in patients with type 2 diabetes has been developed and globally validated. However, population heath and care services between countries within a region are expected to differ. The aim of this study was to evaluate the performance of the model within Mexico and compare this with the performance demonstrated within the Americas in the global validation. Methods: We performed a retrospective observational study with data from primary care (Clinic Specialized in Diabetes Management in Mexico City), tertiary care (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán) and the Mexican national survey of health and nutrition (ENSANUT-MC 2016). We applied the minimal-resource model across the datasets and evaluated model performance metrics, with the primary interest in the sensitivity and increase in the positive predictive value (PPV) compared to a screen-everyone approach. Results: The model was evaluated on 2510 patients from Mexico (primary care: 1358, tertiary care: 735, ENSANUT-MC: 417). Across the Mexico data, the sensitivity was 0.730 (95% CI: 0.689 - 0.779) and the relative increase in PPV was 61.0% (95% CI: 52.1% - 70.8%). These were not statistically different to the regional performance metrics for the Americas (sensitivity: p=0.964; relative improvement: p=0.132), however considerable variability was observed across the data sources. Conclusion: The minimal-resource model performs consistently in a representative Mexican population sample compared with the Americas regional performance. In primary care settings where screening is underperformed and access to laboratory testing is limited, the model can act as a risk-tailored CKD screening solution, directing screening resources to patients who are at highest risk.

Novel subtype of obesity influencing the outcomes of sleeve gastrectomy: Familial aggregation of obesity.

BACKGROUND: Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy (SG) between patients with familial aggregation of obesity (FAO) and patients with sporadic obesity (SO) have not been elucidated. AIM: To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO. METHODS: A total of 193 patients with obesity who underwent SG were selected. Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity (1SO vs 1FAO, 2SO vs 2FAO). The baseline characteristics, weight loss outcomes, prevalence of obesity-related comorbidities and incidence of major surgery-related complications were compared between groups. RESULTS: We defined FAO as the presence of two or more first-degree relatives with obesity. Patients with FAO did not initially show significant differences in baseline data, short-term postoperative weight loss, or obesity-related comorbidities when compared to patients with SO preoperatively. However, distinctions between the two groups became evident at the two-year mark, with statistically significant differences in both percentage of total weight loss (P = 0.006) and percentage of excess weight loss (P < 0.001). The FAO group exhibited weaker remission of type 2 diabetes mellitus (T2DM) (P = 0.031), hyperlipidemia (P = 0.012), and non-alcoholic fatty liver disease (NAFLD) (P = 0.003) as well as a lower incidence of acid reflux (P = 0.038). CONCLUSION: FAO patients is associated with decreased mid-to-long-term weight loss outcomes; the alleviation of T2DM, hyperlipidemia and NAFLD; and decreased incidence of acid reflux postoperatively.

Undiagnosed type 2 diabetes is common - intensified screening of established risk groups is imperative in Sweden: the SDPP cohort.

BACKGROUND: Undiagnosed type 2 diabetes (T2D) is a global problem. Current strategies for diagnosis in Sweden include screening individuals within primary healthcare who are of high risk, such as those with hypertension, obesity, prediabetes, family history of diabetes, or those who smoke daily. In this study, we aimed to estimate the proportion of individuals with undiagnosed T2D in Stockholm County and factors associated with T2D being diagnosed by healthcare. This information could improve strategies for detection. METHODS: We used data from the Stockholm Diabetes Prevention Programme (SDPP) cohort together with information from national and regional registers. Individuals without T2D aged 35-56 years at baseline were followed up after two ten-year periods. The proportion of diagnosed T2D was based on register information for 7664 individuals during period 1 and for 5148 during period 2. Undiagnosed T2D was assessed by oral glucose tolerance tests at the end of each period. With logistic regression, we analysed factors associated with being diagnosed among individuals with T2D. RESULTS: At the end of the first period, the proportion of individuals with T2D who had been diagnosed with T2D or not was similar (54.0% undiagnosed). At the end of the second period, the proportion of individuals with T2D was generally higher, but they were less likely to be undiagnosed (43.5%). The likelihood of being diagnosed was in adjusted analyses associated with overweight (OR=1.85; 95% CI 1.22-2.80), obesity (OR=2.73; 95% CI 1.76-4.23), higher fasting blood glucose (OR=2.11; 95% CI 1.67-2.66), and self-estimated poor general health (OR=2.42; 95% CI 1.07-5.45). Socioeconomic factors were not associated with being diagnosed among individuals with T2D. Most individuals (>71%) who developed T2D belonged to risk groups defined by having at least two of the prominent risk factors obesity, hypertension, daily smoking, prediabetes, or family history of T2D, including individuals with T2D who had not been diagnosed by healthcare. CONCLUSIONS: Nearly half of individuals who develop T2D during 10 years in Stockholm County are undiagnosed, emphasizing a need for intensified screening of T2D within primary healthcare. Screening can be targeted to individuals who have at least two prominent risk factors.

A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus.

BACKGROUND: Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. METHODS: Multidisciplinary professionals from The Association of Children's Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. RESULTS AND DISCUSSION: Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. CONCLUSIONS: This evidence-based guideline aims to provide a practical approach in managing this condition in the UK.

Mitochondrial Fraction of Circulating Cell-Free DNA as an Indicator of Human Pathology.

Circulating cell-free DNA (ccfDNA) of mitochondrial origin (ccf-mtDNA) consists of a minor fraction of total ccfDNA in blood or in other biological fluids. Aberrant levels of ccf-mtDNA have been observed in many pathologies. Here, we introduce a simple and effective standardized Taqman probe-based dual-qPCR assay for the simultaneous detection and relative quantification of nuclear and mitochondrial fragments of ccfDNA. Three pathologies of major burden, one malignancy (Breast Cancer, BrCa), one inflammatory (Osteoarthritis, OA) and one metabolic (Type 2 Diabetes, T2D), were studied. Higher levels of ccf-mtDNA were detected both in BrCa and T2D in relation to health, but not in OA. In BrCa, hormonal receptor status was associated with ccf-mtDNA levels. Machine learning analysis of ccf-mtDNA datasets was used to build biosignatures of clinical relevance. (A) a three-feature biosignature discriminating between health and BrCa (AUC: 0.887) and a five-feature biosignature for predicting the overall survival of BrCa patients (Concordance Index: 0.756). (B) a five-feature biosignature stratifying among T2D, prediabetes and health (AUC: 0.772); a five-feature biosignature discriminating between T2D and health (AUC: 0.797); and a four-feature biosignature identifying prediabetes from health (AUC: 0.795). (C) a biosignature including total plasma ccfDNA with very high performance in discriminating OA from health (AUC: 0.934). Aberrant ccf-mtDNA levels could have diagnostic/prognostic potential in BrCa and Diabetes, while the developed multiparameter biosignatures can add value to their clinical management.

Factors influencing hospitalization or emergency department visits and mortality in type 2 diabetes following the onset of new cardiovascular diagnoses in a population-based study.

BACKGROUND: Individuals with type 2 diabetes (T2D) are at increased risk of developing cardiovascular disease (CVD) which necessitates monitoring of risk factors and appropriate pharmacotherapy. This study aimed to identify factors predicting emergency department visits, hospitalizations, and mortality among T2D patients after being newly diagnosed with CVD. METHODS: In a retrospective observational study conducted in Region Halland, individuals aged > 40 years with T2D diagnosed between 2011 and 2019, and a new diagnosis of CVD between 2016 and 2019, were followed for one year from the date of CVD diagnosis. The first encounter for CVD diagnosis was categorized as inpatient-, outpatient-, primary-, or emergency department care. Follow-up included laboratory tests, blood pressure, pharmacotherapies, and healthcare utilization. Hazard ratios (HR) in two Cox regression analyses determined relative risks for emergency visits/hospitalization and mortality, adjusting for age, sex, glucose regulation, lipid levels, kidney function, blood pressure, pharmacotherapy, and healthcare utilization. RESULTS: The study included a total of 1759 T2D individuals who received a new CVD diagnosis, with 67% diagnosed during inpatient care. The average hospitalization stay was 6.5 days, and primary care follow-up averaged 10.1 visits. Patients with CVD diagnosed in primary care had a HR 0.52 (confidence interval [CI] 0.35-0.77) for emergency department visits/hospitalization, but age had a HR 1.02 (CI 1.00-1.03). Pharmacotherapy with insulin, DPP4-inhibitors, aldosterone antagonists, and beta-blockers had a raised HR. Highest mortality risk was observed when CVD was diagnosed inpatient care, systolic blood pressure < 100 mm Hg and elevated HbA1c. Age had a HR 1.05 (CI 1.03-1.08), eGFR < 30 ml/min HR 1.46 (CI 1.01-2.11), and LDL-Cholesterol > 2,5 h 1.46 (CI 1.01-2.11) and associated with increased mortality risk. Pharmacotherapy with metformin had a HR 0.41 (CI 0.28-0.62), statins a HR 0.39 (CI 0.27-0.57), and a primary care follow-up < 30 days a HR 0.53 (CI 0.37-0.77) and associated with lower mortality risk. CONCLUSIONS: T2D individuals who had a new diagnosis of CVD were predominantly diagnosed when hospitalized, while follow-up typically occurred in primary care. Identifying factors that predict risks of mortality and hospitalization should be a focus of follow-up care, underscoring the critical role of primary care in the effective management of T2D and CVD.

Iron Status and Risk of Heart Disease, Stroke, and Diabetes: A Mendelian Randomization Study in European Adults.

BACKGROUND: The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases. METHODS AND RESULTS: Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank. Iron biomarkers included transferrin saturation, serum iron, ferritin, and total iron binding capacity. MR analyses assessed associations with CAD (CARDIOGRAMplusC4D [Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus The Coronary Artery Disease Genetics], n=181 522 cases), HF (HERMES [Heart Failure Molecular Epidemiology for Therapeutic Targets), n=115 150 cases), IS (GIGASTROKE, n=62 100 cases), and T2D (DIAMANTE [Diabetes Meta-Analysis of Trans-Ethnic Association Studies], n=80 154 cases) genome-wide consortia. Observational analyses demonstrated J-shaped associations of hemoglobin with CAD, HF, IS, and T2D. In contrast, MR analyses demonstrated linear positive associations of higher genetically predicted hemoglobin levels with 8% higher risk per 1 SD higher hemoglobin for CAD, 10% to 13% for diabetes, but not with IS or HF in UK Biobank. Bidirectional MR analyses confirmed the causal relevance of iron biomarkers for hemoglobin. Further MR analyses in global consortia demonstrated modest protective effects of iron biomarkers for CAD (7%-14% lower risk for 1 SD higher levels of iron biomarkers), adverse effects for T2D, but no associations with IS or HF. CONCLUSIONS: Higher levels of iron biomarkers were protective for CAD, had adverse effects on T2D, but had no effects on IS or HF. Randomized trials are now required to assess effects of iron supplements on risk of CAD in high-risk older people.

Apolipoprotein E E3/E4 genotype is associated with an increased risk of type 2 diabetes mellitus complicated with coronary artery disease.

OBJECTIVE: Dyslipidemia is a co-existing problem in patients with diabetes mellitus (DM) and coronary artery disease (CAD), and apolipoprotein E (APOE) plays an important role in lipid metabolism. However, the relationship between the APOE gene polymorphisms and the risk of developing CAD in type 2 DM (T2DM) patients remains controversial. The aim of this study was to assess this relationship and provide a reference for further risk assessment of CAD in T2DM patients. METHODS: The study included 378 patients with T2DM complicated with CAD (T2DM + CAD) and 431 patients with T2DM alone in the case group, and 351 individuals without DM and CAD were set as controls. The APOE rs429358 and rs7412 polymorphisms were genotyped by polymerase chain reaction (PCR) - microarray. Differences in APOE genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for age, gender, body mass index (BMI), history of smoking, and history of drinking to access the relationship between APOE genotypes and T2DM + CAD risk. RESULTS: The frequencies of the APOE ɛ3/ɛ4 genotype and ε4 allele were higher in the T2DM + CAD patients, and the frequencies of the APOE ɛ3/ɛ3 genotype and ε3 allele were lower than those in the controls (all p < 0.05). The T2DM + CAD patients with ɛ4 allele had higher level in low-density lipoprotein cholesterol (LDL-C) than those in patients with ɛ2 and ɛ3 allele (p < 0.05). The results of logistic regression analysis showed that age ≥ 60 years old, and BMI ≥ 24.0 kg/m2 were independent risk factors for T2DM and T2DM + CAD, and APOE ɛ3/ɛ4 genotype (adjusted odds ratio (OR) = 1.93, 95% confidence interval (CI) = 1.18-3.14, p = 0.008) and ɛ4 allele (adjusted OR = 1.97, 95% CI = 1.23-3.17) were independent risk factors for T2DM + CAD. However, the APOE genotypes and alleles were not found to have relationship with the risk of T2DM. CONCLUSIONS: APOE ε3/ε4 genotype and ε4 allele were independent risk factors for T2DM complicated with CAD, but not for T2DM.

Study of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 in Patients with Type 2 Diabetes Mellitus Nephropathy.

BACKGROUND: There is a need for accurate and rapid biomarkers for the early diagnosis of diabetic nephropathy (DN). We aimed to study the accuracy of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1), and blood NGAL (bNGAL) in type 2 diabetics as biomarkers for diagnosis of DN. METHODS: The study was a retrospective case-control study that included 30 control subjects, 40 diabetics with normo-albuminuria < 30 mg/g and eGFR > 60 mL/minute/1.73 m2, and 30 diabetics with albuminuria > 30mg/g and eGFR < 60mL/minute/1.73 m2. Blood and urine samples were obtained to determine levels of bNGAL, uNAGAL, and uKIM1. RESULTS: There was a significant increase in bNGAL, uNGAL, uKIM 1, uNGAL/creatinine and uKIM 1/creatinine among diabetics with albuminuria compared to diabetics with normoalbuminuria and normal control (p < 0.001 for all markers). For diagnosis of early DN, both bNGAL and uKIM 1 had sensitivity and specificity of 100% for each at cutoff values of 322.5 pg/mL and 74.25 ng/mL, respectively. uNGAL had a sensitivity of 97.5% and a spec-ificity of 100% at a cutoff point of 565 ng/mL. uKIM1/creatinine at a cutoff of 51.2 had a sensitivity of 100% and specificity of 100%. CONCLUSIONS: The present study highlights the accuracy of urinary KIM1 and NGAL and blood NGAL as biomarkers for the diagnosis of nephropathy in the early stage of diabetic nephropathy. There were positive correlations with kidney function tests creatinine, blood urea nitrogen, and the presence of albuminuria.

The potential impact and diagnostic value of inflammatory markers on diabetic foot progression in type II diabetes mellitus: A case-control study.

BACKGROUND: The wound-healing process in diabetic foot is affected by pro and anti-inflammatory markers, and any disruption in the inflammatory reaction interferes with tissue homeostasis, leading to chronic non-wound healing. AIM: This study aimed to determine the diagnostic value and effect of CRP, IL-6, TNF, and HbA1c on initiation the and progression of diabetic foot ulcers. METHOD: ELISA was used to quantify IL-6, TNF, CRP, and HbA1c in 205 patients with diabetes, and 105 were diabetic foot free. The prevalence and progression of diabetic foot were also evaluated. The area under the curve (AUC) was calculated using the receiver operating characteristic (ROC) curve to analyze the predictive values. Forward stepwise logistic regression analysis was used to compute the odds ratio (OR) and the corresponding 95% confidence intervals (CIs). RESULTS: CRP, IL-6, and FBS were found to be significant predictors of diabetic foot (OR=1.717, 95% CI=1.250-2.358, P=0.001; OR=1.434, 95% CI=1.142-1.802, P=0.002; and OR=1.040, 95% CI=1.002-1.080, P=0.037), respectively. The AUCs for CRP, IL-6, and HbA1c in predicting diabetic foot were 0.839, 0.728, and 0.834, respectively, demonstrating a good predictive value for each diagnostic marker. CONCLUSION: The current study demonstrated that IL-6, CRP, and HbA1c may be useful biomarkers to indicate diabetic foot progression. Furthermore, our findings showed a substantial relationship between CRP and HbA1c in individuals with diabetic foot conditions.

Integration of polygenic and gut metagenomic risk prediction for common diseases.

Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.

International Diabetes Federation Position Statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes.

Many individuals with intermediate hyperglycaemia (IH), including impaired fasting glycaemia (IFG) and impaired glucose tolerance (IGT), as presently defined, will progress to type 2 diabetes (T2D). There is confirmatory evidence that T2D can be prevented by lifestyle modification and/or medications, in people with IGT diagnosed by 2-h plasma glucose (PG) during a 75-gram oral glucose tolerance test (OGTT). Over the last 40 years, a wealth of epidemiological data has confirmed the superior value of 1-h plasma glucose (PG) over fasting PG (FPG), glycated haemoglobin (HbA1c) and 2-h PG in populations of different ethnicity, sex and age in predicting diabetes and associated complications including death. Given the relentlessly rising prevalence of diabetes, a more sensitive, practical method is needed to detect people with IH and T2D for early prevention or treatment in the often lengthy trajectory to T2D and its complications. The International Diabetes Federation (IDF) Position Statement reviews findings that the 1-h post-load PG ≥ 155 mg/dL (8.6 mmol/L) in people with normal glucose tolerance (NGT) during an OGTT is highly predictive for detecting progression to T2D, micro- and macrovascular complications, obstructive sleep apnoea, cystic fibrosis-related diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and mortality in individuals with risk factors. The 1-h PG of 209 mg/dL (11.6 mmol/L) is also diagnostic of T2D. Importantly, the 1-h PG cut points for diagnosing IH and T2D can be detected earlier than the recommended 2-h PG thresholds. Taken together, the 1-h PG provides an opportunity to avoid misclassification of glycaemic status if FPG or HbA1c alone are used. The 1-h PG also allows early detection of high-risk people for intervention to prevent progression to T2D which will benefit the sizeable and growing population of individuals at increased risk of T2D. Using a 1-h OGTT, subsequent to screening with a non-laboratory diabetes risk tool, and intervening early will favourably impact the global diabetes epidemic. Health services should consider developing a policy for screening for IH based on local human and technical resources. People with a 1-h PG ≥ 155 mg/dL (8.6 mmol/L) are considered to have IH and should be prescribed lifestyle intervention and referred to a diabetes prevention program. People with a 1-h PG ≥ 209 mg/dL (11.6 mmol/L) are considered to have T2D and should have a repeat test to confirm the diagnosis of T2D and then referred for further evaluation and treatment. The substantive data presented in the Position Statement provides strong evidence for redefining current diagnostic criteria for IH and T2D by adding the 1-h PG.

Clinical characteristics and degree of cardiovascular risk factor control in patients with newly-diagnosed type 2 diabetes in Catalonia.

Introduction: Women with type 2 diabetes mellitus (T2DM) face a greater risk of cardiovascular disease (CVD) and encounter challenges in managing cardiovascular risk factors (CVRF); however, limited data are available in individuals with newlydiagnosed T2DM. Methods: This study aimed to examine differences between women and men at the onset of T2DM in terms of clinical characteristics, glycaemic status, and CVRF management. This was a retrospective cohort study including subjects with newly-diagnosed T2DM from the System for the Development of Research in Primary Care (SIDIAP) database in Catalonia (Spain). Sex differences (Dif) were assessed at baseline and 1-year post-diagnosis, by calculating the absolute difference of means or proportions. Results: A total of 13,629 subjects with newly-diagnosed T2DM were analyzed. Women were older and had a higher BMI than men. At baseline, women had higher total cholesterol [Dif (95%CI) 10 mg/dL (9.1/10.8)] and low-density lipoprotein cholesterol (LDL-c) [Dif (95%CI) 7 mg/dL (6.3/7.7)], while men had higher rates of smoking and alcohol intake. Lipid target achievement was lower in women, in both primary prevention (LDL-c < 100 mg/dL) [Dif (95%CI) -7.3 mg/dL (-10.5/-4.1)] and secondary prevention (LDL-c < 70 mg/dL) [Dif (95%CI) -8.3 mg/dL (-17.3/0.7)], along with lower statin and antiplatelet prescriptions, especially one year after diagnosis. Changes in clinical and laboratory data one year post-diagnosis revealed that, in the primary prevention group, men experienced greater improvements in total cholesterol, LDL-c and triglycerides, while women had less success in achieving CVRF control targets compared to men. Additionally, cardiovascular events, such as coronary artery disease and peripheral artery disease increased more in men than in women within the first year of diagnosis, especially in primary prevention subjects. Conclusion: Differences between men and women CVRF are already apparent at the onset of T2DM, particularly in primary prevention, with notable differences in lipid profile and target level attainment.

Impact of MAFLD criteria on postoperative recurrence of non-B, non-C HCC.

BACKGROUND: This study aimed to clarify the population in whom the presence of metabolic dysfunction-associated fatty liver disease (MAFLD) especially contributes to recurrence after liver resection for non-B, non-C hepatocellular carcinoma (NBNC-HCC). METHODS: Of the 199 patients who underwent liver resection for NBNC-HCC, those who exceeded Milan criteria and with pathologically proven vascular invasion, intrahepatic metastasis, and positive resection margins were excluded, and the remaining 94 were eligible for this study. We explored factors contributing to postoperative recurrence in populations with and without advanced liver fibrosis. RESULTS: Independent factors contributing to postoperative recurrence in the study population were male sex ( P  = 0.023) and presence of type 2 diabetes (DM) ( P  = 0.006) and advanced liver fibrosis ( P  < 0.001). Factors in cases with advanced liver fibrosis (n = 43) were non-overweight ( P  = 0.02), type 2 DM ( P  = 0.006), and preoperative alpha-fetoprotein level of 8.2 ng/ml or higher ( P  = 0.021). In cases without advanced liver fibrosis (n = 51), only presence of all three MAFLD criteria was related to recurrence. CONCLUSION: Liver fibrosis is a strong factor contributing to postoperative recurrence of NBNC-HCC, as previously reported. In patients with advanced liver fibrosis, presence of type 2 DM was the only factor associated with recurrence among MAFLD criteria. On the other hand, in patients without advanced liver fibrosis, the combination of all MAFLD criteria, rather than a specific criterion alone, contributed to recurrence. MAFLD criteria were found to have utility as predictors of postoperative recurrence in NBNC-HCC.

Harnessing the power of proteomics in precision diabetes medicine.

Precision diabetes medicine (PDM) aims to reduce errors in prevention programmes, diagnosis thresholds, prognosis prediction and treatment strategies. However, its advancement and implementation are difficult due to the heterogeneity of complex molecular processes and environmental exposures that influence an individual's disease trajectory. To address this challenge, it is imperative to develop robust screening methods for all areas of PDM. Innovative proteomic technologies, alongside genomics, have proven effective in precision cancer medicine and are showing promise in diabetes research for potential translation. This narrative review highlights how proteomics is well-positioned to help improve PDM. Specifically, a critical assessment of widely adopted affinity-based proteomic technologies in large-scale clinical studies and evidence of the benefits and feasibility of using MS-based plasma proteomics is presented. We also present a case for the use of proteomics to identify predictive protein panels for type 2 diabetes subtyping and the development of clinical prediction models for prevention, diagnosis, prognosis and treatment strategies. Lastly, we discuss the importance of plasma and tissue proteomics and its integration with genomics (proteogenomics) for identifying unique type 2 diabetes intra- and inter-subtype aetiology. We conclude with a call for action formed on advancing proteomics technologies, benchmarking their performance and standardisation across sites, with an emphasis on data sharing and the inclusion of diverse ancestries in large cohort studies. These efforts should foster collaboration with key stakeholders and align with ongoing academic programmes such as the Precision Medicine in Diabetes Initiative consortium.

Restoration of blood vessel regeneration in the era of combination SGLT2i and GLP-1RA therapy for diabetes and obesity.

Ischaemic cardiovascular diseases, including peripheral and coronary artery disease, myocardial infarction, and stroke, remain major comorbidities for individuals with type 2 diabetes (T2D) and obesity. During cardiometabolic chronic disease (CMCD), hyperglycaemia and excess adiposity elevate oxidative stress and promote endothelial damage, alongside an imbalance in circulating pro-vascular progenitor cells that mediate vascular repair. Individuals with CMCD demonstrate pro-vascular 'regenerative cell exhaustion' (RCE) characterized by excess pro-inflammatory granulocyte precursor mobilization into the circulation, monocyte polarization towards pro-inflammatory vs. anti-inflammatory phenotype, and decreased pro-vascular progenitor cell content, impairing the capacity for vessel repair. Remarkably, targeted treatment with the sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin in subjects with T2D and coronary artery disease, and gastric bypass surgery in subjects with severe obesity, has been shown to partially reverse these RCE phenotypes. SGLT2is and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have reshaped the management of individuals with T2D and comorbid obesity. In addition to glucose-lowering action, both drug classes have been shown to induce weight loss and reduce mortality and adverse cardiovascular outcomes in landmark clinical trials. Furthermore, both drug families also act to reduce systemic oxidative stress through altered activity of overlapping oxidase and antioxidant pathways, providing a putative mechanism to augment circulating pro-vascular progenitor cell content. As SGLT2i and GLP-1RA combination therapies are emerging as a novel therapeutic opportunity for individuals with poorly controlled hyperglycaemia, potential additive effects in the reduction of oxidative stress may also enhance vascular repair and further reduce the ischaemic cardiovascular comorbidities associated with T2D and obesity.

Predictors of non-obstructive coronary slow flow in poorly controlled type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Coronary slow flow (CSF) can occur due to various factors, such as inflammation, small vessel disease, endothelial dysfunction, and inadequate glucose control. However, the exact pathological mechanisms behind CSF remain incompletely understood. The objective of this study was to identify the risk factors associated with slow coronary flow in individuals with Type 2 Diabetes Mellitus (T2DM) who have non-obstructive coronary artery disease (CAD) and experience CSF. METHODS: We conducted a prospective cohort study involving 120 patients with T2DM who were referred for invasive coronary angiography due to typical chest pain or inconclusive results from non-invasive tests for myocardial ischemia. Using a 2 × 2 design, we categorized patients into groups based on their glycemic control (adequate or poor) and the presence of CSF (yes or no), defined by a TIMI frame count > 27. All patients had non-obstructive CAD, characterized by diameter stenosis of less than 40%. We identified many variables associated with CSF. RESULTS: Our investigation revealed no significant differences in age, sex, family history of coronary artery disease, ECG ischemia abnormalities, or echocardiographic (ECHO) data between the groups. In patients with adequate glycemic control, hypertension increased the risk of CSF by 5.33 times, smoking by 3.2 times, while dyslipidemia decreased the risk by 0.142. Additionally, hematocrit increased the risk by 2.3, and the platelet-to-lymphocyte ratio (PLR) increased the risk by 1.053. Among patients with poor glycemic control, hematocrit increased the risk by 2.63, and the Neutrophil-to-Lymphocyte Ratio (NLR) by 24.6. Notably, NLR was positively correlated with glycemic control parameters in T2DM patients with CSF. CONCLUSIONS: In T2DM patients with CSF, various factors strongly correlate with glycemic control parameters and can be employed to predict the likelihood of CSF. These factors encompass hypertension, smoking, increased body mass index (BMI), elevated platelet count, hematocrit, NLR, PLR, and C-reactive protein (CRP). TRIAL REGISTRATION: Registry: ZU-IRB (ZU-IRB#9419-3-4-2022), Registered on: 3 April 2022, Email: IRB_123@medicine.zu.edu.eg.

Postoperative Insulin Dose for Cardiac Artery Bypass Graft and Other Cardiac Surgeries in Patients with Type 2 Diabetes: A Retrospective Study.

Purpose: Recommendations on perioperative glycemic control in cardiac surgery are based on coronary artery bypass graft surgery (CABG), though coronary artery disease and valvular disease are pathologically distinct. We aimed to compare the postoperative insulin requirement between CABG and other cardiac surgeries in type 2 diabetic patients and identify predictive factors for the maximum postoperative insulin dose. Patients and Methods: We retrospectively included 60 Japanese patients with diabetes/glucose intolerance (HbA1c > 37 mmol/mol [5.6%]) who were hospitalized for cardiovascular surgery between April 2017 and March 2019. We categorized the subjects into the CABG and non-CABG groups, and performed subgroup analysis on patients who received postoperative insulin therapy. Results: The CABG group required a significantly higher insulin dose on postoperative days 2, 5, 6, and 7, and a significantly higher maximum postoperative insulin dose (24.6 U vs 9.7 U, P < 0.001) than the non-CABG group. Multivariate linear regression analyses showed that the independent determinants of the maximum postoperative insulin dose were HbA1c and duration of diabetes in the non-CABG group, and HbA1c in the CABG group. Conclusion: CABG had a higher postoperative insulin requirement than other cardiovascular surgeries; early aggressive insulin therapy is indicated, especially for patients with higher HbA1c levels/longer duration of diabetes.