Cardio-renal-metabolic disease in primary care setting.

In the primary care setting providers have more tools available than ever before to impact positively obesity, diabetes, and their complications, such as renal and cardiac diseases. It is important to recognise what is available for treatment taking into account diabetes heterogeneity. For those who develop type 2 diabetes (T2DM), effective treatments are available that for the first time have shown a benefit in reducing mortality and macrovascular complications, in addition to the well-established benefits of glucose control in reducing microvascular complications. Some of the newer medications for treating hyperglycaemia have also a positive impact in reducing heart failure (HF). Technological advances have also contributed to improving the quality of care in patients with diabetes. The use of technology, such as continuous glucose monitoring systems (CGM), has improved significantly glucose and glycated haemoglobin A1c (HbA1c) values, while limiting the frequency of hypoglycaemia. Other technological support derives from the use of predictive algorithms that need to be refined to help predict those subjects who are at great risk of developing the disease and/or its complications, or who may require care by other specialists. In this review we also provide recommendations for the optimal use of the new medications; sodium-glucose co-transporter-2 inhibitors (SGLT2i) and Glucagon-like peptide-receptor agonists 1 (GLP1RA) in the primary care setting considering the relevance of these drugs for the management of T2DM also in its early stage.

Performance of the 2019 ESC/EASD guideline strategy for the screening of silent coronary artery disease in patients with diabetes.

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.

Impact of Gastric Electrical Stimulation on Economic Burden of Refractory Vomiting: A French Nationwide Multicentre Study.

BACKGROUND & AIMS: Medico-economic data of patients suffering from chronic nausea and vomiting are lacking. In these patients, gastric electrical stimulation (GES) is an effective, but costly treatment. The aim of this study was to assess the efficacy, safety and medico-economic impact of Enterra therapy in patients with chronic medically refractory nausea and vomiting. METHODS: Data were collected prospectively from patients with medically refractory nausea and/or vomiting, implanted with an Enterra device and followed for two years. Gastrointestinal quality of life index (GIQLI) score, vomiting frequency, nutritional status and safety were evaluated. Direct and indirect expenditure data were prospectively collected in diaries. RESULTS: Complete clinical data were available for142 patients (60 diabetic, 82 non-diabetic) and medico-economic data were available for 96 patients (36 diabetic, 60 non-diabetic), 24 months after implantation. GIQLI score increased by 12.1 ± 25.0 points (p < .001), with a more significant improvement in non-diabetic than in diabetic patients (+15.8 ± 25.0 points, p < .001 versus 7.3 ± 24.5 points, p = .027, respectively). The proportion of patients vomiting less than once per month increased by 25.5% (p < .001). Hospitalisations, time off work and transport were the main sources of costs. Enterra therapy decreased mean overall healthcare costs from 8873 US$ to 5525 US$ /patient/year (p = .001), representing a saving of 3348 US$ per patient and per year. Savings were greater for diabetic patients (4096 US$ /patient/year) than for non-diabetic patients (2900 US$ /patient/year). CONCLUSIONS: Enterra therapy is an effective, safe and cost-effective option for patients with refractory nausea and vomiting. CLINICALTRIALS: gov Identifier: NCT00903799.

Effects of single and multiple sessions of lower body diastole-synchronized compressions using a pulsating pneumatic suit on endothelium function and metabolic parameters in patients with type 2 diabetes: two controlled cross-over studies.

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.

Prediabetes and insulin resistance in a population of patients with heart failure and reduced or preserved ejection fraction but without diabetes, overweight or hypertension.

BACKGROUND: The relationships between glucose abnormalities, insulin resistance (IR) and heart failure (HF) are unclear, especially regarding to the HF type, i.e., HF with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Overweight, diabetes and hypertension are potential contributors to IR in persons with HF. This study aimed to evaluate the prevalence of prediabetes and IR in a population of Vietnamese patients with HFrEF or HFpEF but no overweight, diabetes or hypertension, in comparison with healthy controls, and the relation between prediabetes or IR and HF severity. METHODS: We conducted a prospective cross-sectional observational study in 190 non-overweight normotensive HF patients (114 with HFrEF and 76 with HFpEF, 92.6% were ischemic HF, mean age was 70.1 years, mean BMI 19.7 kg/m2) without diabetes (neither known diabetes nor newly diagnosed by OGTT) and 95 healthy individuals (controls). Prediabetes was defined using 2006 WHO criteria. Glucose and insulin levels were measured fasting and 2 h after glucose challenge. IR was assessed using HOMA-IR and several other indexes. RESULTS: Compared to controls, HF patients had a higher prevalence of prediabetes (63.2% vs 22.1%) and IR (according to HOMA-IR, 55.3% vs 26.3%), higher HOMA-IR, insulin/glucose ratio after glucose and FIRI, and lower ISIT0 and ISIT120 (< 0.0001 for all comparisons), with no difference for body weight, waist circumference, blood pressure and lipid parameters. Prediabetes was more prevalent (69.3% vs 53.9%, p = 0.03) and HOMA-IR was higher (p < 0.0001) in patients with HFrEF than with HFpEF. Among both HFrEF and HFpEF patients, those with prediabetes or IR had a more severe HF (higher NYHA functional class and NT-proBNP levels, lower ejection fraction; p = 0.04-< 0.0001) than their normoglycemic or non-insulinresistant counterparts, with no difference for blood pressure and lipid parameters. CONCLUSION: In non-diabetic non-overweight normotensive patients with HF, the prevalence of prediabetes is higher with some trend to more severe IR in those with HFrEF than in those with HFpEF. Both prediabetes and IR are associated with a more severe HF. The present data support HF as a culprit for IR. Intervention strategies should be proposed to HF patients with prediabetes aiming to reduce the risk of incident diabetes. Studies should be designed to test whether such strategies may translate into an improvement of further HF-related outcomes.

Metabolic syndrome screening in adolescents: New scores AI_METS based on artificial intelligence techniques.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) definitions in adolescents based on the percentiles of its components are rather complicated to use in clinical practice. The aim of this study was to test the validity of artificial intelligence (AI)-based scores (AI_METS) that do not use these percentiles for MetS screening for adolescents. METHODS AND RESULTS: This study included 1086 adolescents aged 12 to 18. The cohort underwent anthropometric measurements and blood tests. Mean blood pressure (MBP), and triglyceride glucose index (TyG) were calculated. Explainable AI methods are used to extract the learned function. Gini importance techniques were tested and used to build new scores for the screening of MetS. IDF, Cook, De Ferranti, Viner, and Weiss definitions of MetS were used to test the validity of these scores. MetS prevalence was 0.4%-4.7% according to these definitions. AI_METS used age, waist circumference, MBP, and TyG index. They offer area under the curves (AUCs) 0.91, 0.93, 0.89, 0.93, and 0.98; specificity 81%, 75%, 72%, 80%, and 97%; and sensitivity 90%, 100%, 90%, 100%, and 100%, respectively, for the detection of MetS according to these definitions. Considering only MBP offers a better specificity and sensitivity to detect MetS than considering only TyG index. MBP offers slightly lower performance than AI_METS. CONCLUSION: AI techniques have proven their ability to extract knowledge from data. They allowed us to generate new scores for MetS detection in adolescents without using specific percentiles for each component. Although these scores are less intuitive than the percentile-based definition, their accuracy is rather effective for the detection of MetS.

Gastric Electrical Stimulation Reduces Refractory Vomiting in a Randomized Crossover Trial.

BACKGROUND & AIMS: There have been conflicting results from trials of gastric electrical stimulation (GES) for treatment of refractory vomiting, associated or not with gastroparesis. We performed a large, multicenter, randomized, double-blind trial with crossover to study the efficacy of GES in patients with refractory vomiting, with or without gastroparesis. METHODS: For 4 months, we assessed symptoms in 172 patients (66% women; mean age ± standard deviation, 45 ± 12 years; 133 with gastroparesis) with chronic (>12 months) of refractory vomiting (idiopathic, associated with a type 1 or 2 diabetes, or postsurgical). A GES device was implanted and left unactivated until patients were randomly assigned, in a double-blind manner, to groups that received 4 months of stimulation parameters (14 Hz, 5 mA, pulses of 330 µs) or no stimulation (control); 149 patients then crossed over to the other group for 4 months. Patients were examined at the end of each 4-month period (at 5 and 9 months after implantation). Primary endpoints were vomiting score, ranging from 0 (daily vomiting) to 4 (no vomiting), and the quality of life, assessed by the Gastrointestinal Quality of Life Index scoring system. Secondary endpoints were changes in other digestive symptoms, nutritional status, gastric emptying, and control of diabetes. RESULTS: During both phases of the crossover study, vomiting scores were higher in the group with the device on (median score, 2) than the control group (median score, 1; P < .001), in diabetic and nondiabetic patients. Vomiting scores increased significantly when the device was ON in patients with delayed (P < .01) or normal gastric emptying (P = .05). Gastric emptying was not accelerated during the ON period compared with the OFF period. Having the GES turned on was not associated with increased quality of life. CONCLUSIONS: In a randomized crossover study, we found that GES reduced the frequency of refractory vomiting in patients with and without diabetes, although it did not accelerate gastric emptying or increase of quality of life. Clinicaltrials.gov, Number: NCT00903799.

Autonomic nervous system activity changes in patients with hypertension and overweight: role and therapeutic implications.

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.

Heart failure in type 2 diabetes: current perspectives on screening, diagnosis and management.

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.

Epicardial adipose tissue volume and myocardial ischemia in asymptomatic people living with diabetes: a cross-sectional study.

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 < 0.05). The association between EAT volume and myocardial ischemia remained significant after adjustment for gender, diabetes duration, peripheral macrovascular disease and CAC score. We also found that area under the ROC curve analysis showed that EAT volume (AROC: 0.771 [95% confidence interval 0.683-0.858]) did not provide improved discrimination of myocardial ischemia over the following classic factors: gender, diabetes duration, peripheral macrovascular disease, retinopathy, nephropathy, smoking, atherogenic dyslipidemia, and CAC score (AROC 0.773 [0.683-0.862]). CONCLUSIONS: EAT may play a role in coronary atherosclerosis and coronary circulation in patients with diabetes. However, considering EAT volume is not a better marker for discriminating the risk of asymptomatic myocardial ischemia than classic clinical data.

Acute and long-term effects of saxagliptin on a set of cardiovascular targets measured at fasting and post-prandially in obese patients with impaired glucose tolerance: A placebo-controlled study.

BACKGROUND AND AIMS: Studies of dipeptidyl peptidase inhibitors (DPP4is) report heterogeneous effects on cardiovascular targets in type 2 diabetes. This study aimed to investigate, in patients with impaired glucose tolerance (IGT), whether saxagliptin, a DPP4i, had beneficial cardiovascular effects at fasting and during the post-prandial state. METHODS AND RESULTS: In this randomized, placebo-controlled, double-blind, single-center pilot exploratory study, we included obese individuals with IGT. Twenty-four individuals (BMI 36.8 ± 4.8 kg/m2) were randomized to receive for 12 weeks either saxagliptin 5 mg a day or placebo. They were explored before and after a standardized breakfast for biological markers; microcirculatory blood flow at baseline and after transcutaneous administration of acetylcholine (Periflux System 5000® PERIMED); post-occlusive digital reactive hyperhemia (Endopat2000®); pulse wave velocity, augmentation index, central pulse pressure and subendocardial viability ratio (Sphygmocor®); cardiac hemodynamic parameters and cardiovascular autonomic nervous system activity (Task force monitor®). The results of all the investigations were similar after breakfast in the two groups at Visit 1 (acute post-prandial effects, after the first tablet) and Visit 2 (long-term post-prandial effects), and at fasting at Visit 1 and 2 (long-term effects, after 12 weeks of treatment). Only at Visit 2 the decrease in cardiac vagal activity occurring after breakfast was more sustained in the saxagliptin group than in the placebo group (interaction between treatment and time effect: p = 0.016). CONCLUSION: In obese patients with IGT, the effects of saxagliptin on the large set of cardiovascular parameters measured are neutral, except for a more marked post-prandial depression of vagal activity. CLINICAL TRIAL REGISTRATION NUMBER: NCT01521312.

Acute and long-term effects of saxagliptin on post-prandial glycemic response in obese patients with impaired glucose tolerance.

BACKGROUND AND AIMS: Dipeptidyl-peptidase inhibitors might be useful in type 2 diabetes prevention. ACCES (ACute and Chronic Effects of Saxagliptin) was a randomized, placebo-controlled, double-blind, controlled phase 2, pilot study aiming to examine in obese patients with impaired glucose tolerance (IGT) the acute effects and the effects after 12 weeks of treatment by saxagliptin on glucose levels at fasting and postprandially after a standard breakfast, and on glucose tolerance. METHODS AND RESULTS: We included 24 obese patients with IGT. Patients were randomized to receive saxagliptin 5 mg or placebo in the morning. The treatment was taken on Visit 1 before breakfast, then continued for 12 weeks. Biochemical measurements were performed before, one, two and three hours after a standard breakfast including 75 g of carbohydrates, during Visit 1 and Visit 2 (12 weeks). Glucose variability (GV) was evaluated at Visit 1 from 24-h continuous glucose monitoring including the breakfast. A second OGTT was performed at Visit 3 (3-5 days after Visit 2). Compared with placebo-treated patients, saxagliptin-treated patients had lower 1 h and 2 h post-meal plasma glucose levels at Visit 1 and similar changes at Visit 2 (p < 0.01 to p < 0.004), with lower GV indexes after breakfast at Visit 1. At Visit 3, all patients but one in saxagliptin group and only 4 patients in placebo group turned to normal glucose tolerance. Lower glucose response to breakfast at Visit 1 was predictive of recovery of glucose tolerance. CONCLUSION: Saxagliptin has metabolically beneficial effects in glucose-intolerant obese patients by significantly lowering postprandial blood glucose levels. CLINICAL TRIAL REGISTRATION NUMBER: NCT01521312: https://clinicaltrials.gov/ct2/show/NCT01521312.

Triglyceride glucose index for the detection of asymptomatic coronary artery stenosis in patients with type 2 diabetes.

BACKGROUND: Triglyceride Glucose (TyG) index has been associated with an increased risk in cardiovascular events. Silent coronary disease is common in patients with type 2 diabetes. In Vietnam, a low-middle income country, the burden of cardiovascular disease is growing simultaneously with the epidemiologic transition. Our aim was to assess the prevalence of coronary stenoses (CS) in patients with type 2 diabetes and no history or symptom of cardiovascular disease and to investigate the association between TyG index and cardiovascular risk factors and both the presence and severity of CS. Futhermore, we assessed the value of TyG index in predicting subclinical CS. METHODS: This was a cross-sectional observational study. We recruited 166 patients at Ninh Thuan General Hospital, Vietnam. TyG index and HOMA-IR were calculated, and a coronary computed tomography angiography (CCTA) was performed. RESULTS: The population was classified according to tertiles of TyG index. The highest TyG values were associated with higher BMI, waist circumference, total cholesterol, LDL-cholesterol, triglycerides, plasma glucose, HbA1c levels and HOMA-IR, lower HDL-cholesterol, a higher incidence of metabolic syndrome and less frequent physical activity (p < 0.05 to < 0.0001). TyG index correlated with logHOMA-IR (p < 0.0001). CS ≥ 50% were present in 60 participants and 32 had coronary artery stenosis ≥ 70%. TyG index and HOMA-IR were significantly higher in patients with CS ≥ 70%. The number of narrowed coronary arteries and the degree of stenosis were associated with higher TyG index levels (p = 0.04 and < 0.005 respectively). A TyG index ≥ 10 was significantly associated with an increased risk of multiple coronary artery disease and of more severe CS. After adjusting for confounding factors, including logHOMA-IR, these risks remained mostly significant. A TyG index threshold at 10 resulted in 57% sensitivity and 75% specificity for predicting the presence of CS ≥ 70%. In subgroup analysis TyG index ≥ 10 was associated with an increased risk in CS ≥ 70% in patients treated with statin or antiplatelet therapy. CONCLUSION: More than one third of asymptomatic patients with type 2 diabetes had significant CS on CCTA. TyG index may be considered as a marker for insulin resistance and increased TyG index could identify patients with high risk of coronary artery stenoses and is associated with the number and the severity of artery stenoses.

Issues for the management of people with diabetes and COVID-19 in ICU.

In the pandemic "Corona Virus Disease 2019" (COVID-19) people with diabetes have a high risk to require ICU admission. The management of diabetes in Intensive Care Unit is always challenging, however, when diabetes is present in COVID-19 the situation seems even more complicated. An optimal glycemic control, avoiding acute hyperglycemia, hypoglycemia and glycemic variability may significantly improve the outcome. In this case, intravenous insulin infusion with continuous glucose monitoring should be the choice. No evidence suggests stopping angiotensin-converting-enzyme inhibitors, angiotensin-renin-blockers or statins, even it has been suggested that they may increase the expression of Angiotensin-Converting-Enzyme-2 (ACE2) receptor, which is used by "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to penetrate into the cells. A real issue is the usefulness of several biomarkers, which have been suggested to be measured during the COVID-19. N-Terminal-pro-Brain Natriuretic-Peptide, D-dimer and hs-Troponin are often increased in diabetes. Their meaning in the case of diabetes and COVID-19 should be therefore very carefully evaluated. Even though we understand that in such a critical situation some of these requests are not so easy to implement, we believe that the best possible action to prevent a worse outcome is essential in any medical act.

Prenatal education of overweight or obese pregnant women to prevent childhood overweight (the ETOIG study): an open-label, randomized controlled trial.

BACKGROUND: We aimed to evaluate whether pre and perinatal education of pregnant women would reduce childhood overweight. METHODS: Four French centers included women at ≤21 gestational weeks (GWs) with body mass index (BMI) >25 kg/m2 before pregnancy. Patients were randomized to a control group (routine care including at least one dietary visit) or an intervention group (2 individuals (26 and 30 GW) and 4 group sessions (21, 28, 35 GW, 2 months postpartum)) aimed at educating the future mother regarding infant and maternal nutrition. The primary objective was to reduce post-natal excessive weight gain in the infant from birth to 2 years (NCT00804765). This project was funded by a grant from the National Programme for Hospital Research (PHRC-2007 French Ministry of Health). RESULTS: We included 275 women (BMI: 32.5 kg/m2). The rate of post-natal excessive weight gain was similar in the intervention (n = 132) and control (n = 136) groups by intention to treat (ITT: 59.1% vs 60.3% respectively, p = 0.84) in available data (AD, n = 206) and by per-protocol analysis (PP, n = 177). Two years after delivery, normalization of maternal BMI and number of infants with BMI < 19 kg/m2 were not significantly different in the interventional group in ITT and in the control group. Although not significantly different in ITT, normalization of maternal BMI was more frequent in AD (n = 149: 12.9% vs 3.8%, p = 0.04) and 2-year-old infant BMIs were less likely to be >19 kg/m2 in the intervention group in AD (n = 204: 0% vs 6.8%, p = 0.014) and PP (n = 176: 0% vs 6.4%, p = 0.03). CONCLUSIONS: An education and nutritional counseling program for overweight women, starting after 3 months of gestation, did not significantly change post-natal excessive weight gain of infants or prevent overweight in mothers and children 2 years after delivery.

Report from the 4th Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group.

The 4th Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group was held in Munich on 25-26 October 2018. As in previous years, this summit served as a reference meeting for in-depth discussions on the topic of recently completed and presented CVOTs. This year, focus was placed on the CVOTs CARMELINA, DECLARE-TIMI 58 and Harmony Outcomes. Trial implications for diabetes management and the impact of the new ADA/EASD consensus statement treatment algorithm were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists and general practitioners. Discussions evolved from CVOTs to additional therapy options for heart failure (ARNI), knowledge gained for adjunct therapy of type 1 diabetes and, on the occasion of the 10 year anniversary of the FDA's "Guidance for Industry: "should CVOTs be continued and/or modified?" The 5th Cardiovascular Outcome Trial Summit will be held in Munich on 24-25 October 2019 ( http://www.cvot.org ).

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

Report from the 3rd Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group.

The 3rd Cardiovascular Outcome Trial Summit of the Diabetes & Cardiovascular Disease EASD Study Group was held on the 26-27 October 2017 in Munich. As in 2015 and 2016, this summit was organised in light of recently completed and published CVOTs on diabetes, aiming to serve as a reference meeting for in-depth discussions on the topic. Amongst others, the CVOTs EXSCEL, DEVOTE, the CANVAS program and the ACE-trial, which released primary outcome results in 2017, were discussed. Trial implications for diabetes management and recent perspectives of diabetologists, cardiologists, endocrinologists, nephrologists and general practitioners were highlighted. The clinical relevance of cardiovascular outcome trials and its implications regarding reimbursement were compared with real-world studies. The 4th Cardiovascular Outcome Trial Summit will be held in Munich 25-26 October 2018 ( http://www.dcvd.org ).

Effects of insulin analogs as an add-on to metformin on cutaneous microcirculation in type 2 diabetic patients.

BACKGROUND: A single insulin injection was shown to improve microcirculatory blood flow. Our aim was to examine the effects of 4weeks of insulin therapy by three randomly assigned insulin analog regimens (Detemir, Aspart, and their combination) on cutaneous blood flow (CBF) and microcirculatory endothelial function as an add-on to metformin in type 2 diabetic patients poorly controlled on oral antidiabetic treatment. METHODS: Fourty-two type 2 diabetic patients with no history of cardiovascular disease in secondary failure to oral antidiabetic agents had CBF measurements before and after acetylcholine (Ach) iontophoretic administration. CBF measurements were performed at fasting and after a standardized breakfast during the post-prandial period. Before randomization (Visit 1, V1) during the tests, participants took only metformin. The same tests were repeated after 4weeks of insulin treatment (Visit 2, V2). RESULTS: Thirty-four patients had good quality recordings for both visits. During V1, CBF and CBF response to Ach increased in the post-prandial period. After 4weeks of insulin treatment, metabolic parameters improved. Compared to V1, CBF at fasting did not increase at V2 but there was an improvement in endothelial function at fasting after Ach iontophoresis, without difference across insulin regimens. Oxidative stress markers were not modified, and E-selectin and vascular cell adhesion molecule 1 levels decreased after insulin treatment, without differences between insulin groups. CONCLUSIONS: A strategy of improving glycemic control for 4weeks with insulin analogs improves microcirculatory endothelial reactivity and reduces endothelial biomarkers at fasting, whatever the insulin regimen used. Insulin therapy associated to metformin is able to improve fasting microvascular endothelial function even before complete metabolic control.

[HDL-C/apoA-I]: A multivessel cardiometabolic risk marker in women with T2DM.

AIMS: Although women have higher high-density lipoprotein cholesterol (HDL-C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL-C to its main apolipoprotein (apoA-I) as [HDL-C/apoA-I]. This ratio estimates HDL sizes and provides indices as to their number, cholesterol load, and density. METHODS: We stratified 280 Caucasian T2DM women according to [HDL-C/apoA-I] quartiles (Q) to determine how they are segregated according to cardiometabolic risk, ß-cell function, glycaemic control, and vascular complications. Five parameters were derived from combined determination of HDL-C and apoA-I: HDL size, HDL number, cholesterol load per particle (pP), apoA-I pP, and HDL density. RESULTS: An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA-I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and ß-cell function (32% vs 23%); exogenous insulin (44 vs 89 U·d-1 ); and glycaemic control (glycated haemoglobin, 56 vs 61 mmol·mol-1 ), associated with lower prevalence of microvascular/macrovascular complications: all-cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all-cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P < .05). CONCLUSION: [HDL-C/apoA-I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, ß-cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women.