CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).

Psychometric properties of the Diabetes Eating Problem Survey-Revised among Dutch adults with type 1 diabetes and implications for clinical use.

AIMS: Disordered eating behaviour (DEB) in people with type 1 diabetes (T1D) can be screened with the Diabetes Eating Problem Survey-Revised (DEPS-R). This study aimed to investigate the psychometric properties of the DEPS-R among Dutch adults with T1D and to explore the individual items alongside the standard cut-off score of ≥20 for clinical use. METHODS: The construct validity of the DEPS-R was assessed with an exploratory factor analysis, through principal axis factoring and with Spearman correlations between clinical variables and the DEPS-R. Backward logistic regression identified clinical predictors for DEPS-R scores above the cut-off. DEPS-R item responses were summarized with frequencies, means and standard deviations. RESULTS: Participants were 145 adults with T1D, of whom 79.3% were women and 35.9% presented with DEB based on the cut-off. A single-factor solution of the DEPS-R showed good internal consistency, while a three-factor solution showed acceptable to good internal consistency within the factors. A younger age, a higher BMI and more diabetes distress were predictors for a DEPS-R cut-off score of ≥20. Clinically relevant items were identified that contributed minimally to the DEPS-R score. CONCLUSIONS: This study supports a single-factor and a three-factor structure of the DEPS-R while also suggesting an item-specific or factor-specific approach in clinical practice.

Person-reported outcomes in registered randomised diabetes trials: A mapping review of constructs.

AIM: Recently, efforts have been made to use and report person-reported outcomes (PROs) in randomised clinical trials (RCTs). Here, we aim to (1) assess the status of inclusion of PROs in registered RCTs over 5 years in people with type 1 or 2 diabetes, and (2) map the PRO measures (PROMs) onto predefined domains. METHODS: The largest trial registries (Clinicatrials.gov, International Clinical Trial Platform and ISRCTN) were systematically searched for RCTs in people with type 1 and/or type 2 diabetes of all ages between 2018 and 2023. Coding of PROs comprised: (1) PRO measure(s) included yes or no; if yes: (2) PRO(s) as primary outcome yes or no; and (3) mapping PROMs onto predefined PRO domains and per type of intervention. RESULTS: N = 1543 trials met our inclusion criteria, of which n = 673 (44%) included PROs, assessed by 545 different measures. Twenty per cent of drug trials (n = 112) and 71% of behavioural interventions (n = 405) included PROs. In 149 trials (9.6%), a PRO was the primary outcome. The psychological functioning domain was most often assessed across all trials (21.6%), specifically in behavioural (44.8%) and medical device interventions (29.7%). In drug trials, the physical functioning and functional health domain was most included (9%). Across all trials, the social and family functioning domain was least assessed (3%). CONCLUSIONS: We noticed an increase in the inclusion of PROs in diabetes RCTs. However, PROs are rarely included as primary outcomes in the majority of studies, particularly in drug trials. The heterogeneity of PROMs used in RCTs underscores the need for standardisation of PROs.

Roles and competencies of the clinical psychologist in adult diabetes care-A consensus report.

AIMS: Psychological care is recognised as an integral part of quality diabetes care. We set out to describe the roles and competencies of the clinical psychologist as a member of the multidisciplinary adult diabetes care team, focused on secondary care. METHODS: The authors are clinically experienced psychologists involved in adult diabetes care, from Australia, Europe and North America, and active members of the international psychosocial aspects of diabetes study group. Consensus was reached as a group on the roles and competencies of the clinical psychologist working in adult diabetes secondary care, building both on expert opinion and a selective review and discussion of the literature on psychological care in diabetes, clinical guidelines and competency frameworks. RESULTS: The clinical psychologist fulfils multiple roles: (1) as a clinician (psychological assessment and therapy), (2) as advisor to the healthcare team (training, consulting), (3) as a communicator and promotor of person-centred care initiatives and (4) as a researcher. Four competencies that are key to successfully fulfilling the above-mentioned roles in a diabetes setting are as follows: (a) specialised knowledge, (b) teamwork and advice, (c) assessment, (d) psychotherapy (referred to as STAP framework). CONCLUSIONS: The roles and competencies of clinical psychologists working in diabetes extend beyond the requirements of most university and post-graduate curricula. There is a need for a comprehensive, accredited specialist post-graduate training for clinical psychologists working in diabetes care, building on the proposed STAP framework. This calls for a collaborative effort involving diabetes organisations, clinical psychology societies and diabetes psychology interest groups.

Towards the standardisation of adult person-reported outcome domains in diabetes research: A Consensus Statement development panel.

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data.

Associations between disordered eating behaviour, diabetes distress and emotion regulation strategies in adults with type 1 diabetes: Results from a Dutch-Italian cross-sectional study.

AIMS: Disordered eating behaviour (DEB) and diabetes distress are prevalent in adults with type 1 diabetes (T1D). Emotion regulation strategies, such as cognitive reappraisal and expressive suppression, are associated with DEB and managing stress in general. Here we examine the associations between DEB, diabetes distress, and emotion regulation strategies in the context of T1D. METHODS: Adults with T1D in The Netherlands and Italy completed an online survey, covering DEB (DEPS-R), diabetes distress (PAID-5), and emotion regulation strategies (ERQ). Associations between DEB, diabetes distress, and emotion regulation strategies were examined using path analysis. RESULTS: N = 291 participants completed the survey (78.9% women, 39 ± 13 years, HbA1c : 55 ± 16 mmol/mol (7.2% [3.6%]); TIR: 66% ± 25). N = 79 participants (27.1%) reported DEB (DEPS-R ≥ 20) and n = 159 participants (54.6%) reported elevated diabetes distress (PAID-5 ≥ 8). The path analysis, with small-to-medium effect sizes, revealed that more diabetes distress was associated with more DEB (ß = 0.23, 95% CI [0.13, 0.34]). Less diabetes distress was associated with more use of cognitive reappraisal (ß = -0.24, 95% CI [-0.36, -0.12]). More DEB was associated with more use of expressive suppression (ß = 0.14, 95% CI [0.04, 0.24]). CONCLUSIONS: This cross-sectional study suggests an association between DEB and diabetes distress, between cognitive reappraisal and less diabetes distress and between expressive suppression and more DEB. The results suggest that it may prove beneficial to prioritize strengthening emotion regulation strategies in interventions for people with T1D and DEB. Future research should help clarify causality with regard to emotion regulation and DEB in adults with T1D.

Conversations and Reactions Around Severe Hypoglycemia (CRASH) Study: Results From People With Diabetes and Caregivers in the United States.

A survey was conducted in eight countries to examine conversations around, and experiences and treatments during, severe hypoglycemia among people with diabetes and caregivers of people with diabetes. This article reports a subgroup analysis from the United States involving 219 people with diabetes and 210 caregivers. Most respondents (79.7%) did not use professional health care services during their most recent severe hypoglycemic event, and 40.3% did not report the event to their health care providers at a subsequent follow-up visit. Hypoglycemic events left respondents feeling scared (70.9%), unprepared (42.7%), and helpless (46.9%). These clinically important psychosocial impacts on people with diabetes and caregivers underscore the need for conversations about hypoglycemia prevention and management.

The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycaemia, behavioural considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that healthcare professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors. Graphical abstract.

Less sedentary time is associated with a more favourable glucose-insulin axis in obese pregnant women-a secondary analysis of the DALI study.

BACKGROUND/OBJECTIVES: Obese pregnant women are at high risk of developing gestational diabetes mellitus (GDM), which might be reduced by sufficient physical activity (PA) and reduced sedentary time (ST). We assessed whether PA and ST are longitudinally associated with the glucose-insulin axis in obese pregnant women. SUBJECTS/METHODS: In this secondary analysis of the DALI (vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention) study, pregnant women, <20 weeks gestation, with a pre-pregnancy body mass index (BMI) ≥ 29 kg/m2, without GDM on entry were included. Time spent in moderate-to-vigorous PA (MVPA) and ST were measured objectively with accelerometers at <20 weeks, 24-28 weeks and 35-37 weeks of gestation. Fasting glucose (mmol/l) and insulin (mU/l), insulin resistance (HOMA-IR) and first-phase and second-phase insulin release (Stumvoll first and second phase) were assessed at the same time. Linear mixed regression models were used to calculate between-participant differences and within-participant changes over time. Analyses were adjusted for gestational age, randomisation, pre-pregnancy BMI, education and age. MVPA, Insulin, HOMA-IR and Stumvoll first and second phase were log-transformed for analyses due to skewness. RESULTS: 232 women were included in the analysis. Concerning differences between participants, more ST was associated with higher fasting glucose (Estimate: 0.008; 95% CI: 0.002, 0.014), fasting insulin (0.011; 0.002, 0.019), HOMA-IR (0.012; 0.004, 0.021) and Stumvoll first and second phase (0.008; 0.001, 0.014 and 0.007; 0.001, 0.014). Participants with more MVPA had lower Stumvoll first and second phase (-0.137; -0.210, -0.064 and -0.133; -0.202, -0.063). Concerning changes over time, an increase in ST during gestation was associated with elevated Stumvoll first and second phase (0.006; 0.000, 0.011). CONCLUSIONS: As the glucose-insulin axis is more strongly associated with ST than MVPA in our obese population, pregnant women could be advised to reduce ST in addition to increasing MVPA. Moreover, our findings suggest that behaviour change interventions aiming at GDM risk reduction should start in early or pre-pregnancy.

Efficacy and Moderators of Internet-Based Interventions in Adults with Subthreshold Depression: An Individual Participant Data Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Evidence on effects of Internet-based interventions to treat subthreshold depression (sD) and prevent the onset of major depression (MDD) is inconsistent. OBJECTIVE: We conducted an individual participant data meta-analysis to determine differences between intervention and control groups (IG, CG) in depressive symptom severity (DSS), treatment response, close to symptom-free status, symptom deterioration and MDD onset as well as moderators of intervention outcomes. METHODS: Randomized controlled trials were identified through systematic searches via PubMed, PsycINFO, Embase and Cochrane Library. Multilevel regression analyses were used to examine efficacy and moderators. RESULTS: Seven trials (2,186 participants) were included. The IG was superior in DSS at all measurement points (posttreatment: 6-12 weeks; Hedges' g = 0.39 [95% CI: 0.25-0.53]; follow-up 1: 3-6 months; g = 0.30 [95% CI: 0.15-0.45]; follow-up 2: 12 months, g = 0.27 [95% CI: 0.07-0.47], compared with the CG. Significantly more participants in the IG than in the CG reached response and close to symptom-free status at all measurement points. A significant difference in symptom deterioration between the groups was found at the posttreatment assessment and follow-up 2. Incidence rates for MDD onset within 12 months were lower in the IG (19%) than in the CG (26%). Higher initial DSS and older age were identified as moderators of intervention effect on DSS. CONCLUSIONS: Our findings provide evidence for Internet-based interventions to be a suitable low-threshold intervention to treat individuals with sD and to reduce the incidence of MDD. This might be particularly true for older people with a substantial symptom burden.

Executive function mediates the link between externalizing behavior and HbA1c in children and adolescents with type 1 diabetes: A cross-national investigation.

OBJECTIVE: Externalizing behavior (i.e., conduct problems, hyperactivity) and executive function (EF) problems in children and adolescents with type 1 diabetes (T1D) have been associated with worse diabetes-related and psychosocial outcomes but have not been examined in relationship to each other. We aimed to examine whether externalizing behavior is associated with HbA1c and whether this relationship is mediated by EF problems, specifically metacognition (i.e., ability to initiate, plan, organize and monitor behavior) and behavioral regulation (i.e., impulse control, regulation of emotion and behavior). RESEARCH DESIGN AND METHODS: Cohorts of Belgian and Dutch parents of children and adolescents (6-18 years) with T1D filled out questionnaires on externalizing behavior (Strengths and Difficulties Questionnaire; SDQ) and EF (Behavior Rating Inventory of Executive Function; BRIEF) composite scales. Treating physicians collected HbA1c values. Mediation analyses were performed separately for the BRIEF composite Metacognition and Behavior Regulation scales, correcting for age, sex and diabetes duration. RESULTS: The 335 parents of children and adolescents with T1D (mean age 12.3 ± 2.8 SD; mean HbA1c 7.6% ± 1.1 SD [60 mmol/mol ± 12.0 SD]; mean diabetes duration 5.3 ± 3.6 SD; 49.6% female) participated. Analyses showed that the association between externalizing behavior and HbA1c is mediated by metacognition (ab path Point estimate = 0.05 BCa CI 95% 0.02-0.08), and not behavioral regulation. CONCLUSIONS: Results uncovered the influence externalizing behavior may have on EF problems in the metacognition domain, which in turn seem to influence HbA1c. Clinicians should be mindful of these EF problems when working with children and adolescents displaying externalizing behavior, and not only target behavioral but also cognitive processes.

The importance of maternal insulin resistance throughout pregnancy on neonatal adiposity.

BACKGROUND: Although previous studies evaluated the association of maternal health parameters with neonatal adiposity, little is known regarding the complexity of the relationships among different maternal health parameters throughout pregnancy and its impact on neonatal adiposity. OBJECTIVES: To evaluate the direct and indirect associations between maternal insulin resistance during pregnancy, in women with obesity, and neonatal adiposity. In addition, associations between maternal fasting glucose, triglycerides (TG), non-esterified fatty acids (NEFA), and neonatal adiposity were also assessed. METHODS: This is a longitudinal, secondary analysis of the DALI study, an international project conducted in nine European countries with pregnant women with obesity. Maternal insulin resistance (HOMA-IR), fasting glucose, TG, and NEFA were measured three times during pregnancy (<20, 24-28, and 35-37 weeks of gestation). Offspring neonatal adiposity was estimated by the sum of four skinfolds. Structural equation modelling was conducted to evaluate the direct and indirect relationships among the variables of interest. RESULTS: Data on 657 mother-infant pairs (50.7% boys) were analysed. Neonatal boys exhibited lower mean sum of skinfolds compared to girls (20.3 mm, 95% CI 19.7, 21.0 vs 21.5 mm, 95% CI 20.8, 22.2). In boys, maternal HOMA-IR at <20 weeks was directly associated with neonatal adiposity (ß = 0.35 mm, 95% CI 0.01, 0.70). In girls, maternal HOMA-IR at 24-28 weeks was only indirectly associated with neonatal adiposity, which implies that this association was mediated via maternal HOMA-IR, glucose, triglycerides, and NEFA during pregnancy (ß = 0.26 mm, 95% CI 0.08, 0.44). CONCLUSIONS: The timing of the role of maternal insulin resistance on neonatal adiposity depends on fetal sex. Although the association was time-dependent, maternal insulin resistance was associated with neonatal adiposity in both sexes.

The statistical approach in trial-based economic evaluations matters: get your statistics together!

BACKGROUND: Baseline imbalances, skewed costs, the correlation between costs and effects, and missing data are statistical challenges that are often not adequately accounted for in the analysis of cost-effectiveness data. This study aims to illustrate the impact of accounting for these statistical challenges in trial-based economic evaluations. METHODS: Data from two trial-based economic evaluations, the REALISE and HypoAware studies, were used. In total, 14 full cost-effectiveness analyses were performed per study, in which the four statistical challenges in trial-based economic evaluations were taken into account step-by-step. Statistical approaches were compared in terms of the resulting cost and effect differences, ICERs, and probabilities of cost-effectiveness. RESULTS: In the REALISE study and HypoAware study, the ICER ranged from 636,744€/QALY and 90,989€/QALY when ignoring all statistical challenges to - 7502€/QALY and 46,592€/QALY when accounting for all statistical challenges, respectively. The probabilities of the intervention being cost-effective at 0€/ QALY gained were 0.67 and 0.59 when ignoring all statistical challenges, and 0.54 and 0.27 when all of the statistical challenges were taken into account for the REALISE study and HypoAware study, respectively. CONCLUSIONS: Not accounting for baseline imbalances, skewed costs, correlated costs and effects, and missing data in trial-based economic evaluations may notably impact results. Therefore, when conducting trial-based economic evaluations, it is important to align the statistical approach with the identified statistical challenges in cost-effectiveness data. To facilitate researchers in handling statistical challenges in trial-based economic evaluations, software code is provided.

Correction to: The Effects of Lifestyle and/or Vitamin D Supplementation Interventions on Pregnancy Outcomes: What Have we Learned from the DALI Studies?

The original version of this review article unfortunately contained a mistake.

Clinical assessment of emotions in patients with cancer: Diagnostic accuracy compared with two reference standards.

BACKGROUND: Previous research has suggested that clinical assessment of emotions in patients with cancer is suboptimal. However, it is a possibility that well-trained and experienced doctors and nurses do recognize emotions but that they do not evaluate all emotions as necessitating professional mental health care. This implies that the sensitivity of clinical assessment should be tested against the need for professional mental health care as reference standard, instead of emotional distress. We hypothesized that the observed sensitivity of clinical assessment of emotions would be higher when tested against need for professional mental health care as reference standard, compared with emotional distress as reference standard. PATIENTS AND METHODS: A consecutive series of patients starting with chemotherapy were recruited during their routine clinical care, at a department of medical oncology. Clinical assessment of emotions by medical oncologists and nurses was derived from the patient file. Emotional distress and need for professional mental health care were assessed using the Distress Thermometer and Problem List. RESULTS: Clinical assessment resulted in notes on emotions in 42.2% of the patient files with 36.2% of patients experiencing emotional distress and 10.8% expressing a need for professional mental health care (N = 185). As expected, the sensitivity of clinical assessment of emotions was higher with the reference standard "need for professional mental health care" compared with "emotional distress" (P < .001). For specificity, equivalent results were obtained with the two reference standards (P = .63). CONCLUSIONS: Clinical assessment of emotions in patients with cancer may be more accurate than previously concluded.

Comparing the EQ-5D-5L crosswalks and value sets for England, the Netherlands and Spain: Exploring their impact on cost-utility results.

This study compares the five-level EuroQol five-dimension questionnaire (EQ-5D-5L) crosswalks and the 5L value sets for England, the Netherlands, and Spain and explores the implication of using one or the other for the results of cost-utility analyses. Data from two randomized controlled trials in depression and diabetes were used. Utility value distributions were compared, and mean differences in utility values between the EQ-5D-5L crosswalk and the 5L value set were described by country. Quality-adjusted life years (QALYs) were calculated using the area-under-the-curve method. Incremental cost-effectiveness ratios (ICERs) were calculated, and uncertainty around ICERs was estimated using bootstrapping and graphically shown in cost-effectiveness acceptability curves. For all countries investigated, utility value distributions differed between the EQ-5D-5L crosswalk and 5L value set. In both case studies, mean utility values were lower for the EQ-5D-5L crosswalk compared with the 5L value set in England and Spain, but higher in the Netherlands. However, these differences in utility values did not translate into relevant differences across utility estimation methods in incremental QALYs and the interventions' probability of cost-effectiveness. Thus, our results suggest that EQ-5D-5L crosswalks and 5L value sets can be used interchangeably in patients affected by mild or moderate conditions. Further research is needed to establish whether these findings are generalizable to economic evaluations among severely ill patients.

#DiabetesPsychologyMatters.

Editor's Note: This article was adapted from the address Dr. Snoek delivered as the recipient of the American Diabetes Association's Richard R. Rubin Award for 2019. This award recognizes a behavioral researcher who has made outstanding, innovative contributions to the study and understanding of the behavioral aspects of diabetes in diverse populations. Dr. Snoek delivered the address in June 2019 at the Association's 79th Scientific Sessions in San Francisco, CA.

A reduction in sedentary behaviour in obese women during pregnancy reduces neonatal adiposity: the DALI randomised controlled trial.

AIMS/HYPOTHESIS: Offspring of obese women are at increased risk of features of the metabolic syndrome, including obesity and diabetes. Lifestyle intervention in pregnancy might reduce adverse effects of maternal obesity on neonatal adiposity. METHODS: In the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus (GDM) Prevention (DALI) lifestyle trial, 436 women with a BMI ≥29 kg/m2 were randomly assigned to counselling on healthy eating (HE), physical activity (PA) or HE&PA, or to usual care (UC). In secondary analyses of the lifestyle trial, intervention effects on neonatal outcomes (head, abdominal, arm and leg circumferences and skinfold thicknesses, estimated fat mass, fat percentage, fat-free mass and cord blood leptin) were assessed using multilevel regression analyses. Mediation of intervention effects by lifestyle and gestational weight gain was assessed. RESULTS: Outcomes were available from 334 neonates. A reduction in sum of skinfolds (-1.8 mm; 95% CI -3.5, -0.2; p = 0.03), fat mass (-63 g; 95% CI -124, -2; p = 0.04), fat percentage (-1.2%; 95% CI -2.4%, -0.04%; p = 0.04) and leptin (-3.80 µg/l; 95% CI -7.15, -0.45; p = 0.03) was found in the HE&PA group, and reduced leptin in female neonates in the PA group (-5.79 µg/l; 95% CI -11.43, -0.14; p = 0.05) compared with UC. Reduced sedentary time, but not gestational weight gain, mediated intervention effects on leptin in both the HE&PA and PA groups. CONCLUSIONS/INTERPRETATION: The HE&PA intervention resulted in reduced adiposity in neonates. Reduced sedentary time seemed to drive the intervention effect on cord blood leptin. Implications for future adiposity and diabetes risk of the offspring need to be elucidated. TRIAL REGISTRATION: ISRCTN70595832.

The presence of cerebral white matter lesions and lower skin microvascular perfusion predicts lower cognitive performance in type 1 diabetes patients with retinopathy but not in healthy controls-A longitudinal study.

OBJECTIVE: Cognitive impairments in type 1 diabetes may result from hyperglycemia-associated cerebral microangiopathy. We aimed to identify cerebral microangiopathy and skin microvascular dysfunction-as a surrogate marker for generalized microvascular function-as predictors of cognitive performance over time. METHODS: In this prospective cohort study, 25 type 1 diabetes patients with proliferative retinopathy and 25 matched healthy controls underwent neurocognitive testing at baseline and after follow-up (3.8 ± 0.8 years). At baseline, 1.5-T cerebral magnetic resonance imaging was used to detect WML and cerebral microbleeds. Skin capillary perfusion was assessed by means of capillary microscopy. RESULTS: In type 1 diabetes patients, but not in healthy controls, the presence of WML (ß = -0.419; P = 0.037) as well as lower skin capillary perfusion (baseline: ß = 0.753; P < 0.001; peak hyperemia: ß = 0.743; P = 0.001; venous occlusion: ß = 0.675; P = 0.003; capillary recruitment: ß = 0.549; P = 0.022) at baseline was associated with lower cognitive performance over time, independent of age, sex, HbA1c, and severe hypoglycemia. The relationship between WML and lower cognitive performance was significantly reduced after adjusting for capillary perfusion. CONCLUSIONS: These data fit the hypothesis that cerebral microangiopathy is a manifestation of generalized microvascular dysfunction, leading to lower cognitive performance.

The Effects of Lifestyle and/or Vitamin D Supplementation Interventions on Pregnancy Outcomes: What Have We Learned from the DALI Studies?

PURPOSE OF REVIEW: The DALI (vitamin D and lifestyle intervention in the prevention of gestational diabetes mellitus (GDM)) study aimed to prevent GDM with lifestyle interventions or Vitamin D supplementation (1600 IU/day). This review summarizes the learnings from the DALI studies among pregnant women with a BMI ≥ 29 kg/m2. RECENT FINDINGS: Women diagnosed with GDM earlier in pregnancy had a worse metabolic profile than those diagnosed later. A combined physical activity (PA) and healthy eating (HE) lifestyle intervention improved both behaviours, limited gestational weight gain (GWG) and was cost-effective. Although GDM risk was unchanged, neonatal adiposity was reduced due to less sedentary time. Neither PA nor HE alone limited GWG or GDM risk. Fasting glucose was higher with HE only intervention, and lower with Vitamin D supplementation. Our combined intervention did not prevent GDM, but was cost-effective, limited GWG and reduced neonatal adiposity.