Impact of depression and cardiovascular risk factors on cognitive impairment in patients with atrial fibrillation: A Systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia associated with significant cardiovascular morbidity and mortality, as well as cognitive impairment (CI). The interplay between AF and CI is complex, involving various pathophysiological changes and numerous risk factors. Among them, depression has emerged as a significant contributor to both AF and CI, further complicating the relationship between these conditions. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the influence of depression on the development of cognitive impairment in AF patients and assess the predictive value of the CHA2DS2-VASc score for CI risk. METHODS: We searched PubMed, Scopus, and Web of Science for relevant studies without language or date restrictions. Ten studies, comprising 1,605,577 participants, were included. A random-effects model was used for meta-analysis, and heterogeneity was assessed using I2 statistics. Funnel plots and Egger's test evaluated publication bias. RESULTS: Depression significantly increased the risk of CI in AF patients (OR: 2.23, 95 % CI: 1.54-3.21, p < 0.01; I2=99 %). This association persisted in studies excluding baseline CI (OR: 1.95, 95 % CI: 1.33-2.85, p < 0.01; I2=88 %). Subgroup analysis confirmed these results for both prospective (OR: 1.78, 95 % CI: 0.92-3.44, p = 0.02; I2=65 %) and retrospective studies (OR: 2.63, 95 % CI: 1.75-3.93, p < 0.01; I2=100 %). Analysis of CHA2DS2-VASc risk factors showed associations with CI, particularly cerebrovascular disease (OR: 1.86, 95 % CI: 1.61-2.16). CONCLUSIONS: Our findings support the association between depression and cognitive impairment in AF patients, demonstrating the importance of addressing mental health in cardiovascular care. Future research is necessary for a comprehensive understanding of this association.

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.

Whole Cell Patch Clamp Electrophysiology in Human Neuronal Cells.

Whole cell patch clamp recording techniques are commonly used to assay membrane excitability, ion channel function, and synaptic activity in neurons. However, assaying these functional properties of human neurons remains difficult because of the difficulty in obtaining human neuronal cells. Recent advents in stem cell biology, especially the development of the induced pluripotent stem cells, made it possible to generate human neuronal cells in both 2-dimensional (2D) monolayer cultures and 3D brain-organoid cultures. Here, we describe the whole cell patch clamp methods of recording neuronal physiology from human neuronal cells.

Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids.

De novo mutations and copy number deletions in NRXN1 (2p16.3) pose a significant risk for schizophrenia (SCZ). It is unclear how NRXN1 deletions impact cortical development in a cell type-specific manner and disease background modulates these phenotypes. Here, we leveraged human pluripotent stem cell-derived forebrain organoid models carrying NRXN1 heterozygous deletions in isogenic and SCZ patient genetic backgrounds and conducted single-cell transcriptomic analysis over the course of brain organoid development from 3 weeks to 3.5 months. Intriguingly, while both deletions similarly impacted molecular pathways associated with ubiquitin-proteasome system, alternative splicing, and synaptic signaling in maturing glutamatergic and GABAergic neurons, SCZ-NRXN1 deletions specifically perturbed developmental trajectories of early neural progenitors and accumulated disease-specific transcriptomic signatures. Using calcium imaging, we found that both deletions led to long-lasting changes in spontaneous and synchronous neuronal networks, implicating synaptic dysfunction. Our study reveals developmental-timing- and cell-type-dependent actions of NRXN1 deletions in unique genetic contexts.

Comparative Analysis of Clinical Practice Guidelines for the Pharmacological Treatment of Type 2 Diabetes Mellitus in Latin America.

PURPOSE OF REVIEW: Type 2 diabetes mellitus (T2DM) is one of the leading causes of death and disability in the world. The majority of diabetes deaths (> 80%) occur in low- and middle-income countries, which are predominant in Latin America. Therefore, the purpose of this article is to compare the clinical practice guideline (CPG) for the pharmacological management of T2DM in Latin America (LA) with international reference guidelines. RECENT FINDINGS: Several LA countries have recently developed CPGs. However, the quality of these guidelines is unknown according to the AGREE II tool and taking as reference three CPGs of international impact: American Diabetes Association (ADA), European Diabetes Association (EASD), and Latin American Diabetes Association (ALAD). Ten CPGs were selected for analysis. The ADA scored > 80% on the AGREE II domains and was selected as the main comparator. Eighty percent of LA CPGs were developed before 2018. Only one was not recommended (all domains < 60%). The CPGs in LA have good quality but are outdated. They have significant gaps compared to the reference. There is a need for improvement, as proposing updates every three years to maintain the best available clinical evidence in all guidelines.

Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes. METHODS: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 µSiemens) and estimated glomerular filtration rate (eGFR). RESULTS: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin (p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo (p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo (p = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, p = 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo (p = 0.0002). CONCLUSIONS: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.

Interprofessional Identity in Health and Social Care: Analysis and Synthesis of the Assumptions and Conceptions in the Literature.

Interprofessional identity (IPI) development is considered essential in reducing incongruency and improving interprofessional collaboration. However, noticeable differences in conceptualizations are being put forward in the literature, hindering interpretation of research findings and translation into practice. Therefore, a Concept Analysis and Critical Interpretative Synthesis of empirical research articles were conducted to explore the assumptions and conceptions of IPI. Independent literature screening by two researchers led to the inclusion and extraction of 39 out of 1334 articles. Through critical analysis, higher order themes were constructed and translated to a synthesizing argument and a conceptual framework depicting what constitutes IPI (attributes), the boundary conditions (antecedents) and the outcomes (consequences) of its development. The attributes refer to both IPI's structural properties and the core beliefs indicative of an interprofessional orientation. The antecedents inform us on the importance of IPI-fitting constructivist learning environments and intergroup leadership in enabling its development. This development may lead to several consequences with regard to professional wellbeing, team effectiveness and the quintuple aim. Given the educational orientation of this study, ways for facilitating and assessing the development of IPI among learners across the professional continuum have been proposed, although empirical research is needed to further validate links and mediating and moderating variables.

CASK loss of function differentially regulates neuronal maturation and synaptic function in human induced cortical excitatory neurons.

Loss-of-function (LOF) mutations in CASK cause severe developmental phenotypes, including microcephaly with pontine and cerebellar hypoplasia, X-linked intellectual disability, and autism. Unraveling the pathological mechanisms of CASK-related disorders has been challenging owing to limited human cellular models to study the dynamic roles of this molecule during neuronal maturation and synapse development. Here, we investigate cell-autonomous functions of CASK in cortical excitatory induced neurons (iNs) generated from CASK knockout (KO) isogenic human embryonic stem cells (hESCs) using gene expression, morphometrics, and electrophysiology. While immature CASK KO iNs show robust neuronal outgrowth, mature CASK KO iNs display severe defects in synaptic transmission and synchronized network activity without compromising neuronal morphology and synapse numbers. In the developing human cortical excitatory neurons, CASK functions to promote both structural integrity and establishment of cortical excitatory neuronal networks. These results lay the foundation for future studies identifying suppressors of such phenotypes relevant to human patients.

Health-related quality of life (HRQoL) in a population at risk of type 2 diabetes: a cross-sectional study in two Latin American cities.

PURPOSE: The purpose of this study was to describe the health-related quality of life (HRQoL) characteristics in a population at risk of developing type 2 diabetes in Barranquilla and Bogotá, Colombia. METHODS: A cross-sectional study with 1135 participants older than 30 years-of-age recruited in Bogotá D.C., and Barranquilla by cluster sampling in 2018 to 2019. The Finnish Diabetes Risk Score (FINDRISC) was used to detect participants at risk of developing type 2 diabetes (T2D). HRQoL was assessed using the EQ-5D-3L questionnaire. Unadjusted and adjusted logistic regression models were used to calculate odds ratios (OR) and their corresponding 95% confidence intervals CI). RESULTS: Moderate or extreme problems appeared more frequently in the dimensions of Pain/Discomfort (60.8%) and Anxiety/Depression (30.8%). The mean score of the EQ-VAS was 74.3 (± 17.3), significantly larger in the state of complete health (11111) compared with those with problems in more than one of the quality-of-life dimensions. Being female and living in Bogota D.C., were associated with greater odds of reporting problems in the Pain (OR 1.6; 95% CI 1.2-2.2) and Discomfort dimensions (OR 1.6; 95% CI 1.2-2.0) respectively and Anxiety/Depression (OR 1.9; 95% CI 1.3-2.7), (OR 9.1; 95% CI 6.6-12.4), respectively. CONCLUSIONS: As living place and sex were associated with dimensions of Pain/Discomfort and Anxiety/Depression in the HRQoL in people at risk of T2D, greater attention should be paid to these determinants of HRQoL to design and reorient strategies with a territorial and gender perspective to achieve better health outcomes. Diabetes is one of the four non-communicable diseases with increasing prevalence in the world, which has made it a serious public health problem. In Colombia, in 2019 diabetes affected 8.4% of the Colombian adult population and more than one million Colombian adults of this age group have hidden or undetected diabetes. This disease is not only characterized by increased premature mortality, loss of productivity, and economic impact, but it also involves a deterioration in the quality of life of people with diabetes with their respective families. However, very Little is known about health-related quality of life (HRQoL) in a population at risk or with prediabetes. This study has evaluated the quality of life in patients at risk of diabetes and their behavior with some variables as sociodemographic, lifestyle, history, and established their difference in two territories of the Colombian Caribbean. The results of this study indicate that the HRQoL of people at risk of type 2 diabetes is affected by factors such as gender, city, dysglycemia, medication for hypertension and education level. Therefore, greater attention should be paid to these determinants of HRQL to design and implement strategies that reduce this risk of developing type 2 diabetes, prevent prediabetes and improve the quality of life in prediabetic or diabetic patients.

Validation of the Finnish Type 2 Diabetes Risk Score (FINDRISC) with the OGTT in Health Care Practices in Europe.

AIMS: /hypothesis. To determine the best cut-off threshold value of the Finnish Diabetes Risk Score (FINDRISC) for the detection of diabetes and non-diabetic hyperglycaemia in people 35 years or older at primary health care settings in Europe. METHODS: Cross-sectional study in 11,444 adults from primary health care centres using community and opportunistic screening approaches. All participants completed the FINDRISC questionnaire and underwent a 2-hour oral glucose tolerance test (OGTT). The FINDRISC performance was assessed by the area under the curve (AUC) using receiver operating characteristics (ROC) analysis. The sensitivity, specificity, Youdens index, positive and negative prediction values for different FINDRISC cut-offs were calculated. RESULTS: The optimal FINDRISC value for detecting both diabetes or glucose impairment in the community - screened sample was 14 point with the associated AUC 0.75,5 (95 %CI 0.73,7-0.77,3). The optimal score in the opportunistic screening sample was 16 with the associated AUC only 0.60,4 (95% CI 0.56, 4-0.64, 4). CONCLUSIONS/INTERPRETATION: The FINDRISC is a non-invasive tool useful for detecting people with unknown diabetes and glucose impairment in people visiting primary health centres in Europe.

Perceptions of physicians, medical and nursing students concerning shared decision-making: a cross-sectional study.

Objective: The purpose of this study was to evaluate the attitudes of Flemish physicians and medical/nursing trainees regarding shared decision-making (SDM) and to determine possible differences based on sex, age, rank, occupation and specialty. Methods: A cross-sectional study was conducted between June and September 2017 in which the Patient-Practitioner Orientation Scale (PPOS) was translated and administered. Higher scores on the six-point scale indicate a patient-centered respondent. Independent t-tests, One and Two-way ANOVA and multivariate regression analysis with the variables sex, age, occupation and specialty were performed. Results: 266 responses from 93 physicians, 147 medical and 26 nursing students were analyzed. Mean sharing scores were 4,24 ± 0,64; 4,30 ± 0,61; and 4,30 ± 0,67, respectively. In the regression model, female sex (p < 0,10) and employment (p < 0,05) in general practice or internal medicine is predictive for higher sharing among physicians. Bivariate analysis revealed significant differences between specialisms (p < 0,05): pediatricians (4,79 ± 0,69), psychiatrists (4,74 ± 0,47), obstetricians/gynecologists (4,40 ± 0,38) and general practitioners (4,31 ± 0,59) scored higher on the PPOS than surgeons (3,84 ± 0,58). Conclusion: Flemish providers and trainees are disease-centered. Physicians' attitudes vary depending on their specialism, presumably due to prolonged exposure to the specific clinical context. Additionally, academic-trained nurses share the belief that the physician should decide and the patient should rely on his knowledge rather than his own. There is an urgent need for health policy and educational institutions to facilitate an environment in which SDM is supported.

The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale.

Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, -ankle-brachial index, pulse wave velocity, and coronary -artery calcium. The Prospective Studies of Atherosclerosis -(Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. In summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. The consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences.

Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data.

OBJECTIVES: To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes. METHODS: Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial. PARTICIPANTS: Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey. INTERVENTION: Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function. RESULTS: One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%. CONCLUSIONS: ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes. REGISTRATION: - ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39.

Comparing different definitions of prediabetes with subsequent risk of diabetes: an individual participant data meta-analysis involving 76 513 individuals and 8208 cases of incident diabetes.

Objective: There are currently five widely used definition of prediabetes. We compared the ability of these to predict 5-year conversion to diabetes and investigated whether there were other cut-points identifying risk of progression to diabetes that may be more useful. Research design and methods: We conducted an individual participant meta-analysis using longitudinal data included in the Obesity, Diabetes and Cardiovascular Disease Collaboration. Cox regression models were used to obtain study-specific HRs for incident diabetes associated with each prediabetes definition. Harrell's C-statistics were used to estimate how well each prediabetes definition discriminated 5-year risk of diabetes. Spline and receiver operating characteristic curve (ROC) analyses were used to identify alternative cut-points. Results: Sixteen studies, with 76 513 participants and 8208 incident diabetes cases, were available. Compared with normoglycemia, current prediabetes definitions were associated with four to eight times higher diabetes risk (HRs (95% CIs): 3.78 (3.11 to 4.60) to 8.36 (4.88 to 14.33)) and all definitions discriminated 5-year diabetes risk with good accuracy (C-statistics 0.79-0.81). Cut-points identified through spline analysis were fasting plasma glucose (FPG) 5.1 mmol/L and glycated hemoglobin (HbA1c) 5.0% (31 mmol/mol) and cut-points identified through ROC analysis were FPG 5.6 mmol/L, 2-hour postload glucose 7.0 mmol/L and HbA1c 5.6% (38 mmol/mol). Conclusions: In terms of identifying individuals at greatest risk of developing diabetes within 5 years, using prediabetes definitions that have lower values produced non-significant gain. Therefore, deciding which definition to use will ultimately depend on the goal for identifying individuals at risk of diabetes.

Prevalence, Treatment, and Associated Factors of Hypertension in Spain: A Comparative Study between Populations.

The prevalence and related factors of hypertensive subjects according to the resident area (rural versus urban) were investigated in two population-based studies from Spain. Medical questionnaires were administered and anthropometrics were measured, using standardized protocols. Hypertension was diagnosed in pharmacology treated subjects or those with blood pressure (BP) ≥140/90 mm Hg. Regarding BP control, it was defined as under control if BP was <140/90 or <140/85 mm Hg in type 2 diabetic subjects. Information on educational status, social class, smoking habit, and alcohol intake was obtained. 3,816 subjects (54.38 % women) were included. Prevalence of diagnosed hypertension was higher in women and showed no differences according to the living area (men: urban 21.88 versus rural 21.92 %, p = 0.986; women: urban 28.73 versus rural 30.01 %, p = 0.540). Women living in rural areas and men with secondary or tertiary education levels had a lower probability of being BP uncontrolled (OR (95 % CI): 0.501 (0.258-0.970)/p=0.040, 0.245 (0.092-0.654)/p=0.005, and 0.156 (0.044-0.549)/p=0.004, respectively). Urban young men (31-45 years) and medium aged women (46-60 years) were less BP controlled than their rural counterparts (41.30 versus 65.79 %/p=0.025 and 35.24 versus 53.27 %/p=0.002, respectively).

HAPT2D: high accuracy of prediction of T2D with a model combining basic and advanced data depending on availability.

OBJECTIVE: Type 2 diabetes arises from the interaction of physiological and lifestyle risk factors. Our objective was to develop a model for predicting the risk of T2D, which could use various amounts of background information. RESEARCH DESIGN AND METHODS: We trained a survival analysis model on 8483 people from three large Finnish and Spanish data sets, to predict the time until incident T2D. All studies included anthropometric data, fasting laboratory values, an oral glucose tolerance test (OGTT) and information on co-morbidities and lifestyle habits. The variables were grouped into three sets reflecting different degrees of information availability. Scenario 1 included background and anthropometric information; Scenario 2 added routine laboratory tests; Scenario 3 also added results from an OGTT. Predictive performance of these models was compared with FINDRISC and Framingham risk scores. RESULTS: The three models predicted T2D risk with an average integrated area under the ROC curve equal to 0.83, 0.87 and 0.90, respectively, compared with 0.80 and 0.75 obtained using the FINDRISC and Framingham risk scores. The results were validated on two independent cohorts. Glucose values and particularly 2-h glucose during OGTT (2h-PG) had highest predictive value. Smoking, marital and professional status, waist circumference, blood pressure, age and gender were also predictive. CONCLUSIONS: Our models provide an estimation of patient's risk over time and outweigh FINDRISC and Framingham traditional scores for prediction of T2D risk. Of note, the models developed in Scenarios 1 and 2, only exploited variables easily available at general patient visits.

Diabetes and Prediabetes Classification Using Glycemic Variability Indices From Continuous Glucose Monitoring Data.

BACKGROUND: Tens of glycemic variability (GV) indices are available in the literature to characterize the dynamic properties of glucose concentration profiles from continuous glucose monitoring (CGM) sensors. However, how to exploit the plethora of GV indices for classifying subjects is still controversial. For instance, the basic problem of using GV indices to automatically determine if the subject is healthy rather than affected by impaired glucose tolerance (IGT) or type 2 diabetes (T2D), is still unaddressed. Here, we analyzed the feasibility of using CGM-based GV indices to distinguish healthy from IGT&T2D and IGT from T2D subjects by means of a machine-learning approach. METHODS: The data set consists of 102 subjects belonging to three different classes: 34 healthy, 39 IGT, and 29 T2D subjects. Each subject was monitored for a few days by a CGM sensor that produced a glucose profile from which we extracted 25 GV indices. We used a two-step binary logistic regression model to classify subjects. The first step distinguishes healthy subjects from IGT&T2D, the second step classifies subjects into either IGT or T2D. RESULTS: Healthy subjects are distinguished from subjects with diabetes (IGT&T2D) with 91.4% accuracy. Subjects are further subdivided into IGT or T2D classes with 79.5% accuracy. Globally, the classification into the three classes shows 86.6% accuracy. CONCLUSIONS: Even with a basic classification strategy, CGM-based GV indices show good accuracy in classifying healthy and subjects with diabetes. The classification into IGT or T2D seems, not surprisingly, more critical, but results encourage further investigation of the present research.

Exploring the Frequency Domain of Continuous Glucose Monitoring Signals to Improve Characterization of Glucose Variability and of Diabetic Profiles.

BACKGROUND: Continuous glucose monitoring (CGM) devices measure interstitial glucose concentrations (normally every 5 minutes), allowing observation of glucose variability (GV) patterns during the whole day. This information could be used to improve prescription of treatments and of insulin dosages for people suffering diabetes. Previous efforts have been focused on proposing indices of GV either in time or glucose domains, while the frequency domain has been explored only partially. The aim of this work is to explore the CGM signal in the frequency domain to understand if new indexes or features could be identified and contribute to a better characterization of glucose variability. METHODS: The direct fast Fourier transform (FFT) and the Welch method were used to analyze CGM signals from three different profiles: people at risk of developing type 2 diabetes (P@R), T2D patients, and type 1 diabetes (T1D) patients. RESULTS: The results suggests that features extracted from the FFT (ie, the localization and power of the maximum peak of the power spectrum and the bandwidth at 3 dB) are able to provide a characterization for all the three populations under study compared with the Welch approach. CONCLUSIONS: Such preliminary results can represent a good insight for futures investigations with the possibility of building and using new indexes of glucose variability based on the frequency features.

Shape of the OGTT glucose curve and risk of impaired glucose metabolism in the EGIR-RISC cohort.

OBJECTIVE: To study whether the shape of the oral glucose tolerance test (OGTT)-glucose curve is a stable trait over time; it is associated with differences in insulin sensitivity, ß-cell function and risk of impaired fasting glucose (IFG) and glucose tolerance (IGT) in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort. METHODS: OGTT-glucose curve shape was classified as monophasic, biphasic, triphasic and anomalous in 915 individuals. Oral glucose insulin sensitivity (OGIS), Matsuda insulin sensitivity index (ISI) and ß-cell function were assessed at baseline and 3years apart. RESULTS: The OGTT-glucose curve had the same baseline shape after 3years in 540 people (59%; κ=0.115; p<0.0001). Seventy percent of the participants presented with monophasic OGTT-glucose curve shape at baseline and after 3years (percent positive agreement 0.74). Baseline monophasic shape was associated with significant increased risk of IFG (OR 1.514; 95% CI 1.084-2.116; p=0.015); biphasic shape with reduced risk of IGT (OR 0.539; 95% CI 0.310-0.936) and triphasic shape with reduced risk of IFG (OR 0.493; 95% CI 0.228-1.066; P=0.043) after 3years. Increased risks of IFG (OR 1.509; 95% CI 1.008-2.260; p=0.05) and IGT (OR 1.947; 95% CI 1.085-3.494; p=0.02) were found in people who kept stable monophasic morphology over time and in switchers from biphasic to monophasic shape (OR of IGT=3.085; 95% CI 1.377-6.912; p=0.001). CONCLUSION: After 3years follow-up, the OGTT-glucose shape was stable in 59% of the RISC cohort. Shapes were associated with different OGIS and ß-cell function; persistence over time of the monophasic shape and switch from biphasic to monophasic shape with increased risk of impaired glucose metabolism.

Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration.

OBJECTIVE: Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes. RESEARCH DESIGN AND METHODS: In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis. RESULTS: Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08). CONCLUSIONS: Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.