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The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD)

Fasting plasma glucose (FPG) is nowadays routinely measured during early pregnancy to detect preexisting diabetes (FPG ≥ 7 mmol/L). This screening has concomitantly led to identify early intermediate hyperglycemia, defined as FPG in the 5.1 to 6.9 mmol/L range, also early gestational diabetes mellitus (eGDM). Early FPG has been associated with poor pregnancy outcomes, but the recommendation by the IADPSG to refer women with eGDM for immediate management is more pragmatic than evidence based. Although eGDM is characterized by insulin resistance and associated with classical risk factors for type 2 diabetes and incident diabetes after delivery, it is not necessarily associated with preexisting prediabetes. FPG ≥ 5.1 mmol/L in early pregnancy is actually poorly predictive of gestational diabetes mellitus diagnosed after 24 weeks of gestation. An alternative threshold should be determined but may vary according to ethnicity, gestational age, and body mass index. Finally, observational data suggest that early management of intermediate hyperglycemia may improve prognosis, through reduced gestational weight gain and potential early introduction of hypoglycemic agents. Considering all these issues, we suggest an algorithm for the management of eGDM based on early FPG levels that would be measured in case of risk factors. Nevertheless, interventional randomized trials are still missing.

Abstract Prevalence of heart failure (HF) and diabetes are markedly increasing globally. In a population of HF patients, approximately 40% have diabetes which is associated with a more severe HF, poorer cardiovascular outcomes and higher hospitalization rates for HF than HF patients without diabetes. Similar trends were shown in HF patients with prediabetes. In addition, the association between HF and renal function decline was demonstrated in patients with or without diabetes. However, the exact prevalence of dysglycemia in HF patients requires further investigation aiming to clarify the most accurate test to detect dysglycemia in this population. The relationship between HF and diabetes is complex and probably bidirectional. In one way, patients with diabetes have a more than two-fold risk of developing incident HF with reduced or preserved ejection fraction than those without diabetes. In the other way, patients with HF, when compared with those without HF, show an increased risk for the onset of diabetes due to several mechanisms including insulin resistance (IR), which makes HF emerging as a precursor for diabetes development. This article provides epidemiological evidence of undetected dysglycemia (prediabetes or diabetes) in HF patients and reviews the pathophysiological mechanisms which favor the development of IR and the risks associated with these disorders in HF patients. This review also offers a discussion of various strategies for the prevention of diabetes in HF patients, based first on fasting plasma glucose and HbA1c measurement and if normal on an oral glucose tolerance test as diagnostic tools for prediabetes and unknown diabetes that should be performed more extensively in those patients. It discusses the implementation of diabetes prevention measures and well-structured management programs for HF patients who are generally overweight or obese, as well as current pharmacotherapeutic options for prediabetes, including sodium–glucose cotransporter 2 inhibitors which are among the pillars of HF treatment and which recently showed a benefit in the reduction of incident diabetes in HF patients. Thus, there is an urgent need of routine screening for dysglycemia in all HF patients, which should contribute to reduce the incidence of diabetes and to treat earlier diabetes when already present.

Abstract The Marine Isotope Stage (MIS) 11c interglacial and its preceding glacial termination represent an enigmatically intense climate response to relatively weak insolation forcing. So far, a lack of radiometric age control has confounded a detailed assessment of the insolation-climate relationship during this period. Here, we present 230Th-dated speleothem proxy data from northern Italy and compare them with palaeoclimate records from the North Atlantic region. We find that interglacial conditions started in subtropical to middle latitudes at 423.1 ± 1.3 thousand years (kyr) before present, during a first weak insolation maximum, whereas northern high latitudes remained glaciated (sea level ~ 40 m below present). Some 14.5 ± 2.8 kyr after this early subtropical onset, peak interglacial conditions were reached globally, with sea level 6–13 m above present, despite weak insolation forcing. We attribute this remarkably intense climate response to an exceptionally long (~15 kyr) episode of intense poleward heat flux transport prior to the MIS 11c optimum.

The variability of the northern westerlies has been considered as one of the key elements for modern and past climate evolution. Their multiscale behavior and underlying control mechanisms, however, are incompletely understood, owing to the complex dynamics of Atlantic sea-level pressures. Here, we present a multi-annually resolved record of the westerly drift over the past 6,500 years from northern Italy. In combination with more than 20 other westerly-sensitive records, our results depict the non-stationary westerly-affected regions over mainland Europe on multi-decadal to multi-centennial time scales, showing that the direction of the westerlies has changed with respect to the migrations of the North Atlantic centers of action since the middle Holocene. Our findings suggest the crucial role of the migrations of the North Atlantic dipole in modulating the westerly-affected domain over Europe, possibly modulated by Atlantic Ocean variability.

Background Moxonidine, an imidazoline I 1 receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic. Aims This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes. Methods Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment. Results Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP

BackgroundThe purpose of this document is to provide clinicians with guidance, using expert consensus, to help summarize evidence and offer practical recommendations.MethodsExpert Consensus Documents are intended to provide guidance for clinicians in areas in which there are no clinical practice guidelines, especially for new and evolving tests such as arterial stiffness measurements, until any formal guidelines are released.ResultsThis expert consensus document is intended as a source of information for decision-making and to guide clinician-patient discussions in various clinical scenarios.ConclusionsThe goal is to help clinicians and patients make a more informed decision together.

The Little Ice Age (LIA; ca. 1450-1850 C.E.) is the best documented cold period of the past millennium, characterized by high-frequency volcanism, low solar activity, and high variability of Arctic sea-ice cover. Past studies of LIA Atlantic circulation changes have referenced the North Atlantic Oscillation (NAO), but recent studies have noted that LIA climate patterns appear to possess complexity not captured by an NAO analogue. Here, we present a new precipitation-sensitive stalagmite record from northern Italy that covers the past 800 years. We show that in the early LIA (1470-1610 C.E.), increased atmospheric ridging over northern Europe split the climatological westerlies away from central and northern Europe, possibly caused by concurrent Artic sea-ice reduction. With ongoing ice melting in the northern high latitudes and decreasing solar irradiance in the coming years, the early LIA may potentially serve as an analogue for European hydroclimatic conditions in the coming decades.

In oil palm growth, planting density has a sustainable impact on its productivity. To enhance the long-term growth and production yield of oil palm, it is crucial to consider the establishment of appropriate planting densities during the initial planting phase. This research explores the relationship between planting density and productivity, highlighting the importance of determining optimal plant densities for optimal yields. The study was conducted at the Muara Tawang Estate (MTNE) in Kapuas Hulu Regency, West Kalimantan Province. Two blocks of oil palm land with three different planting densities (130, 136, and 143 plants per hectare) were observed to understand the relationship between planting density and agronomic characteristics. Measurements were taken on plant height, frond length, petiole width, number of male and female flowers, and sex ratio. The analysis unveiled consistent trends in oil palm production, which varied based on planting density. Planting densities of 130 and 136 showed superior production trends compared to 143, with 136 demonstrating production increases ranging from 19.8% to 29.8% relative to density 143, alongside enhancements in plant height and frond length by 4.6% and 5.4%, respectively. Additionally, petiole thickness and width were notably lower in density 143, experiencing reductions of 8.0% and 11.0%, respectively, compared to density 136, while the sex ratio exhibited a similar pattern, declining by 34.0% in density 143 compared to 136. This highlights the importance of determining appropriate planting densities to enhance oil palm productivity.

Adenosine deaminases acting on RNA (ADARs) are endogenous enzymes catalyzing the deamination of adenosines to inosines, which are then read as guanosines during translation. This ability to recode makes ADAR an attractive therapeutic tool to edit genetic mutations and reprogram genetic information at the mRNA level. Using the endogenous ADARs and guiding them to a selected target has promising therapeutic potential. Indeed, different studies have reported several site-directed RNA-editing approaches for making targeted base changes in RNA molecules. The basic strategy has been to use guide RNAs (gRNAs) that hybridize and form a double-stranded RNA (dsRNA) structure with the desired RNA target because of ADAR activity in regions of dsRNA formation. Here we report on a novel pipeline for identifying disease-causing variants as candidates for RNA editing, using a yeast-based screening system to select efficient gRNAs for editing of nonsense mutations, and test them in a human cell line reporter system. We have used this pipeline to modify the sequence of transcripts carrying nonsense mutations that cause inherited retinal diseases in the FAM161A, KIZ, TRPM1, and USH2A genes. Our approach can serve as a basis for gene therapy intervention in knockin mouse models and ultimately in human patients.

Abstract Background The 2019 guidelines for cardiovascular risk stratification by the European Society of Cardiology and European Association for the Study of Diabetes (ESC-EASD) suggested screening for silent coronary disease in very high risk patients with severe target organ damage (TOD) (i.e. peripheral occlusive arterial disease or severe nephropathy) or high coronary artery calcium (CAC) score. This study aimed to test the validity of this strategy. Methods In this retrospective study, we included 385 asymptomatic patients with diabetes and no history of coronary disease but with TOD or ≥ 3 risk factors in addition to diabetes. CAC score was measured using computed tomography scan and a stress myocardial scintigraphy was performed to detect silent myocardial ischemia (SMI), with subsequent coronary angiography in those with SMI. Various strategies to select patients to be screened for SMI were tested. Results CAC score was ≥ 100 Agatston units (AU) in 175 patients (45.5%). SMI was present in 39 patients (10.1%) and among the 30 patients who underwent angiography, 15 had coronary stenoses and 12 had a revascularization procedure. The most effective strategy consisted in performing myocardial scintigraphy in the 146 patients with severe TOD and, among the 239 other patients without severe TOD, in those with CAC ≥ 100 AU: this strategy provided 82% sensitivity for SMI diagnosis, and identified all the patients with stenoses. Conclusion The ESC-EASD guidelines suggesting SMI screening in asymptomatic patients with very high risk assessed by severe TOD or high CAC score appears effective and could identify all the patients with stenoses eligible for revascularization.

Abstract Background Endothelium function is often impaired in patients with type 2 diabetes. We hypothesized that by improving endothelial function using diastole-synchronized compressions/decompressions (DSCD) to the lower body may improve the metabolic profile. The objective of this research was to evaluate the effects of single and multiple DSCD sessions on microcirculation, endothelium function and metabolic parameters of patients with type 2 diabetes. Methods Two monocentric, controlled, randomized cross-over studies (Study 1 and Study 2) were performed. In Study 1, 16 patients received one 20 min DSCD and one simulated (control) session at 2 week intervals; continuous glucose monitoring and cutaneous blood flow were recorded continuously before, during and after DSCD or Control session; other vascular assessments were performed before and after DSCD and control sessions. In Study 2, 38 patients received 60 min DSCD sessions three times/week for three months followed by a 4–6 week washout and 3 month control period (without simulated sessions); vascular, metabolic, body composition, physical activity and quality of life assessments were performed before and after 3 months. Results Both studies showed significant, multiplex effects of DSCD sessions. In Study 1, cutaneous blood flow and endothelium function increased, and plasma and interstitial glucose levels after a standard breakfast decreased after DSCD sessions. In Study 2, cutaneous endothelium function improved, LDL-cholesterol and non-HDL cholesterol decreased, extra-cell water decreased and SF-36 Vitality score increased after 3 months of DSCD sessions. Conclusions Our findings support the beneficial effect of DSCD on the endothelium and show concomitant beneficial metabolic and vitality effects. Future clinical trials need to test whether DSCD use translates into a preventive measure against microvascular diabetic complications and its progression. Trial registration ClinicalTrials.gov identifiers: NCT02293135 and NCT02359461.

Combined with other westerly-sensitive records, a new stalagmite hydroclimate record from northern Italy reveals changing westerly wind directions over the past 6500 years that correspond to a migration of the North Atlantic centres of action.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity in individuals with type 2 diabetes mellitus (T2DM). Accordingly, several scientific societies have released clinical practice guidelines to assist health professionals in ASCVD risk management in patients with T2DM. However, some recommendations differ from each other, contributing to uncertainty about the optimal clinical management of patients with T2DM and established ASCVD or at high risk for ASCVD. Thus, the purpose of this paper is to discuss recent evidence-based guidelines on ASCVD risk stratification and prevention in patients with T2DM, in terms of disparities and similarities. To close the gap between different guidelines, a multidisciplinary approach involving general practitioners, endocrinologists, and cardiologists may enhance the coordination of diagnosis, therapy, and long-term follow-up of ASCVD in patients with T2DM.

Eggplant cultivation displays versatility across various soil types. However, nutrient depletion, a result of excessive chemical fertilizer utilization, presents a growing concern. The integration of green manure into agricultural practices, catering to diverse soil types, can remediate this nutrient loss. The purpose of this study was to investigate eggplant growth and yield responses to differing green manure quantities across varying soil types. Employing a factorial experimental method, this research was structured in a completely randomized design (CRD). Two independent variables were evaluated: green manure dosage, with three levels (30 g/plant (D1), 60 g/plant (D2), 90 g/plant (D3)), and soil type, also classified into three categories: Latosol (T1), Grumusol (T2), and Regosol (T3). Data interpretation was conducted using analysis of variance, followed by the Tukey test, each executed at α = 5% significance level. Outcomes indicated a notable interaction between green manure dosage and soil type concerning the leaf area and root fresh weight parameters. The optimal combination emerged as a 30 g/plant green manure dosage applied to Regosol soil type. Notably, individual treatments exerted divergent effects on eggplant growth parameters, though no significant impact on eggplant yield parameters was observed. This research underscores the interplay between green manure usage and soil type in cultivating eggplants, adding value to sustainable agricultural practices.

A new stalagmite record from northern Italy and other published data from Europe and northern Africa reveals a split in the climatological westerlies during the early LIA, possibly attributed to sea ice melting.

Open-sea testing of a two-phase marine ramjet vehicle has been conducted. This experimental phase was accomplished following comprehensive theoretical research. The concept of two-phase marine ramjet propulsion consists of a submerged propulsor acquiring water through an inlet due to the vehicle’s motion. Thrust is generated by injecting and dispersing air (or gas) bubbles within the water flowing through the propulsion unit channel and expelling a jet of the two-phase flow through an exit nozzle. The bubbles injected into the internal flow transmit their expansion work to the outgoing jet, resulting in an increase in the jet velocity, hence generating thrust. The article briefly describes the thrust generation concept, then it presents the overall system and thrust units attached to the test vessel, and finally, it summarizes the open-sea experimental results. Good correspondence between the theoretical prediction and actual test data is shown, revealing the feasibility of the two-phase ramjet concept at the low to intermediate cruise velocity range and a smaller relative thrust margin over the hydrodynamic resistance at the high-speed range.

Abstract Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.

Abstract Background Epicardial adipose tissue (EAT) is considered a novel diagnostic marker for cardiometabolic disease. This study aimed to evaluate whether EAT volume was associated with stress-induced myocardial ischemia in asymptomatic people living with diabetes—independently of confounding factors—and whether it could predict this condition. Methods We included asymptomatic patients with diabetes and no coronary history, who had undergone both a stress a myocardial scintigraphy to diagnose myocardial ischemia, and a computed tomography to measure their coronary artery calcium (CAC) score. EAT volume was retrospectively measured from computed tomography imaging. Determinants of EAT volume and asymptomatic myocardial ischemia were evaluated. Results The study population comprised 274 individuals, including 153 men. Mean (± standard deviation) age was 62 ± 9 years, and 243, 23 and 8 had type 2, type 1, or another type of diabetes, respectively. Mean body mass index was 30 ± 6 kg/m2, and mean EAT volume 96 ± 36 cm3. Myocardial ischemia was detected in 32 patients (11.7%). EAT volume was positively correlated with age, body mass index and triglyceridemia, but negatively correlated with HbA1c, HDL- and LDL-cholesterol levels. Furthermore, EAT volume was lower in people with retinopathy, but higher in men, in current smokers, in patients with nephropathy, those with a CAC score > 100 Agatston units, and finally in individuals with myocardial ischemia (110 ± 37 cm3 vs 94 ± 37 cm3 in those without myocardial ischemia, p

Abstract The incidence and prevalence of hypertension is increasing worldwide, with approximately 1.13 billion of people currently affected by the disease, often in association with other diseases such as diabetes mellitus, chronic kidney disease, dyslipidemia/hypercholesterolemia, and obesity. The autonomic nervous system has been implicated in the pathophysiology of hypertension, and treatments targeting the sympathetic nervous system (SNS), a key component of the autonomic nervous system, have been developed; however, current recommendations provide little guidance on their use. This review discusses the etiology of hypertension, and more specifically the role of the SNS in the pathophysiology of hypertension and its associated disorders. In addition, the effects of current antihypertensive management strategies, including pharmacotherapies, on the SNS are examined, with a focus on imidazoline receptor agonists.

Tourism growth is an important component for welfare improvement in the host destination, but it can be associated with environmental degradation. The aim of the current study is to assess the environmental impacts of tourism growth in Tanzania, using time series data for the period 1995–2017. It utilizes ecological footprints as a proxy for environmental damage, tourism receipt as an economic indicator, and primary energy consumption, urban population, and trade openness as control variables. The study employs Autoregressive Distributed Lag Bounds Testing, Vector Error Correction Model (VECM), and Granger causality test for analysis and the Wild Bootstrap approach to check the accuracy of the computed statistics. The VECM Granger causality test shows that in the case of Tanzania, international tourism revenue and trade openness compact environmental degradation, while urbanization and primary energy consumption accelerate it. Besides, while long run cointegration exists among the variables, the environmental Kuznets curve hypothesis was not ascertained in Tanzania. Therefore, Tanzania must adopt more proactive urban planning strategies to achieve sustainable urbanization thereby improving the quality of the environment. Additionally, it is important for Tanzania to make strategic use of trade and tourism receipts, such as investment on renewable energy, to lessen dependence on fossil fuels, and improve environmental sustainability. So, the study opens new policy perspectives with wide international relevancy as outlined in the policy implication section.

The civil war in Syria, which has been ongoing for more than a decade, is considered the greatest humanitarian catastrophe of the twenty-first century. President Bashar al-Assad remains in power, but Syria is far from a functioning or stable country. Out of a population of about 22 million people, the war has taken the lives of more than half a million residents and left about 15 million in need of humanitarian aid. The war has also led to the worst refugee crisis since World War II. More than six million Syrian refugees who were forced to leave their homes moved to live in neighboring countries--mainly Turkey, Lebanon, Jordan, and European countries. About 90% of them do not receive basic living necessities in the host countries and are seen as an economic and political burden. So far about 750,000 refugees have returned to Syria since 2016, but despite the regime's declared policy that they should be repatriated, the return of millions of refugees to Syria is far from the reality. The reasons for this are related to the refugees' fear of the regime taking revenge on them or of forced conscription, and to the perception that there is no future for them given the dismal situation in Syria, which has been devastated by the war. With the end of the battles, refugee flight is being replaced by emigration, and many Syrians are interested in leaving the country for a better future. This article discusses the Syrian refugee issue from the perspective of a war that has continued for more than a decade and the implications of the refugees for the host countries, including for their geopolitical environment. The study examines the refugees' degree of integration in the host countries and also discusses the question of their return to Syria and its potential rehabilitation. [ABSTRACT FROM AUTHOR]

After the economic liberalization in mid-2000, Tanzania has assumed that tourism growth spars economic growth due to the consistent significant contribution of tourism sector to the country's annual income. However, there are limited empirical studies that investigated tourism-economic growth relationship in Tanzania. This study aims to investigate an empirical insight into the actual nature of tourism-economic growth in Tanzania by applying the Granger causality and Wald test methods where annual time series data on international tourism receipt, real Gross Domestic Product, and real effective exchange rate over the period 1989–2018 are used. Further, the Impulse Response Function approach is utilized to provide insight into the qualitative nature of the relationships and the length of time necessary for the causal effect to take place. The findings confirm a unidirectional causality from tourism development to economic growth. The study concludes that Tanzania ought to focus on economic strategies that encourage sustainable tourism development as a feasible source of economic growth.

Different weeding frequencies (WFs)―0WF, 2WF, 4WF, 6WF, and 8WF―were adopted in an organic rice field to investigate their influence on weed types, rice and weed biomass, rice tiller and weed number, N concentration, and N uptake. The study field was located in Tsuruoka, Yamagata, Japan. Rice (cv. Sasanishiki) was planted from May to September 2019, and all weeding events were carried out until 49 days after transplantation (DAT) using a rotary weeder. Rice and weed samples were collected at 60, 88, and 110 DAT. Echinochloa crus-galli (E. crus-galli), Schoenoplectus juncoides, and Monochoria vaginalis (Burm. f.) were the most commonly found weeds. High weed diversity was observed at both 6WF and 8WF, E. crus-galli was the dominant weed at 0WF. Compared to 0WF, 2WF displayed a significantly decreased weed biomass. However, at 8WF, the weed biomass was reduced by 79.0%, the rice biomass was increased by 277%, and the rice tiller number was almost three times higher than that at 0WF and 110 DAT. Compared to 0WF, a significantly increased rice N uptake was observed at 4WF, and rice N uptakes achieved at 6WF and 8WF were two and four times higher than those at 0WF, respectively. Higher weeding frequencies provide notable benefits in suppressing weeds and supporting rice growth, especially in N uptake competition with weeds.

Transglutaminases are calcium-dependent enzymes that catalyze the formation of ε-(γ-glutamyl)lysine isopeptide bonds between specific glutamine and lysine residues. Some transglutaminase isoforms are present in the brain and are thought to participate in the protein aggregation characteristic of neurological diseases such as Huntington, Alzheimer's and Parkinson's disease. We have developed a functional proteomics strategy in which biotinylated amine-donor and amine-acceptor probes were used to identify the transglutaminase substrates present in brain. Bioinformatics analyses revealed that most of the 166 brain substrates identified interacted with huntingtin, the amyloid precursor protein or α-synuclein and that neurological disease was the most significant canonical pathway associated with the substrates. The physiological relevance of the substrates identified by mass spectrometry was confirmed by the fact that three of them (actin, β-tubulin and a neurofilament subunit) were polymerized in neuronal cells when cytosolic calcium concentration was raised. We also showed by in-situ immunolabeling that some of the substrates were part of the protein aggregates found in neurological diseases. These results strongly support the idea that the crosslinking activity of brain transglutaminase participates in the formation of the protein aggregates found in diseases of the central nervous system.