The (cost) effectiveness of a very low-energy diet intervention with the use of eHealth in patients with type 2 diabetes and obesity: study protocol for a randomised controlled non-inferiority trial (E-diet trial).

BACKGROUND: Despite preventive measures, the number of people with type 2 diabetes and obesity is increasing. Obesity increases morbidity and mortality in people with type 2 diabetes, making weight loss a cornerstone of treatment. We previously developed a very low energy diet (VLED) intervention that effectively reduced weight in people with type 2 diabetes in the long term. However, this intervention requires considerable time and manpower, which reduces the number of people who can benefit from it. eHealth offers more efficient solutions but has proven to be less effective than face-to-face interventions. Therefore, we want to investigate whether a blended version of our VLED intervention (in which face-to-face contact is partly replaced by an eHealth (mobile) application (E-VLED)) would be more cost-effective than the current face-to-face intervention. METHODS: We will conduct a randomised, controlled trial with non-inferiority design in patients with type 2 diabetes and obesity (BMI > 30 kg/m2), aged 18-75 years. The control group will receive the usual care VLED intervention, while the intervention group will receive the E-VLED intervention for 1 year, where face-to-face contact will be partly replaced by an eHealth (mobile) application. The main study endpoint is the difference in weight (% change) between the control and intervention group after 1 year, plus the difference between the total costs (euro) of the treatment in the control and intervention groups. The secondary aims are to investigate the effectiveness of the E-VLED diet intervention regarding cardiovascular risk factors, quality of life, patient satisfaction, compliance, and to study whether there is a difference in effectiveness in pre-specified subgroups. General linear models for repeated measurements will be applied for the statistical analysis of the data. DISCUSSION: We hypothesise that the E-VLED intervention will be equally effective compared to the usual care VLED but lower in costs due to less time invested by the dietician. This will enable to help more people with type 2 diabetes and obesity to effectively lose weight and improve their health-related quality of life. TRIAL REGISTRATION: Netherlands Trial Register, NL7832, registered on 26 June 2019.

The effect of monomeric and oligomeric FLAVAnols in patients with type 2 diabetes and microalbuminuria (FLAVA-trial): A double-blind randomized controlled trial.

BACKGROUND & AIMS: Microalbuminuria is an early sign of vascular complications of type 2 diabetes and predicts cardiovascular disease and mortality. Monomeric and oligomeric flavanols (MOFs) are linked to improved vascular health. The aim of this study was to assess the effect of 3 months MOFs on albuminuria and endothelial function markers in patients with type 2 diabetes and microalbuminuria. METHODS: We conducted a double-blind, placebo-controlled trial among patients with type 2 diabetes and microalbuminuria. Patients with type 2 diabetes received either 200 mg MOFs or placebo daily on top of their habitual diet and medication. The primary endpoint was the between-group difference of the change in 24-h Albumin Excretion Rate (AER) over three months. Secondary endpoints were the between-group differences of the change in plasma levels of different markers of endothelial dysfunction. Mixed-modelling was applied for the longitudinal analyses. RESULTS: Participants (n = 97) were 63.0 ± 9.5 years old; diabetes-duration was 15.7 ± 8.5 years. Median baseline AER was 60 (IQR 20-120) mg/24 h. There was no within-group difference in median change of AER from baseline to 3 months in the intervention (0 (-35-21) mg/24 h, p = 0.41) or the control group (0 (-20-10) mg/24 h, p = 0.91). There was no between-group difference in the course of AER over three months (log-transformed data: ß = -0.02 (95%CI -0.23-0.20), p = 0.88), nor in the plasma levels of the endothelial dysfunction markers. CONCLUSION: Daily 200 mg MOFs for three months on top of habitual diet and usual care did not reduce AER and plasma markers of endothelial dysfunction compared to placebo, in patients with long-term type 2 diabetes and microalbuminuria. CLINICAL TRIALS REGISTRATION: NTR4669, www.trialregister.nl.

Acute dyspnea caused by hypocalcemia-related laryngospasm.

BACKGROUND: Laryngospasm is a rare cause of stridor in adults, and laryngospasm due to hypocalcemia is an unusual finding. CASE REPORT: We present a case of an adult woman with acute dyspnea. A week prior to presentation, she experienced short episodes of a pinching feeling in her throat and difficulty breathing. On primary assessment, stridor and a positive Trousseau sign were noted. Laboratory examination showed hypocalcemia. We concluded that the dyspnea was caused by laryngospasm due to hypocalcemia. Hypocalcemia was treated promptly, and stridor and dyspnea resolved rapidly. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Laryngospasm is a rare, but serious and potentially lethal, complication of hypocalcemia in adults. In every adult presenting with acute dyspnea and stridor, the possibility of hypocalcemia should be considered. Hypocalcemia should be treated promptly.

Self-reported time spent watching television is associated with arterial stiffness in young adults: the Amsterdam Growth and Health Longitudinal Study.

OBJECTIVES: To investigate whether time spent watching television (a marker of sedentary behaviour) is associated with arterial stiffness, a major determinant of cardiovascular disease, and whether any such association could be explained by related deleterious levels of habitual physical activity (HPA) and/or other lifestyle and biological risk factors. METHODS: Prospective measures (ages 32 and 36 years) of television time and risk factors were retrieved from 373 participants (196 women) in whom stiffness of the carotid, brachial and femoral arteries was assessed by means of ultrasonography at age 36 years. Data were analysed with generalised estimating equations. RESULTS: Participants with stiffer carotid arteries spent more time (in min/day) watching television during the four preceding years than did those with less stiff arteries, as defined on the basis of the highest compared with the lowest gender-specific tertiles of the distensibility or compliance coefficients (reversed) or the Young's elastic modulus: +22.4 (95%CI 8.7 to 36.1), +18.4 (4.2 to 32.5) and +19.7 (6.0 to 33.4), respectively. These differences were independent of potential confounders, such as vigorous intensity HPA and other lifestyle risk factors, and could only in part (up to 31%) be explained by the adverse associations of television time with traditional biological risk factors. Qualitatively similar results were found for femoral, but not brachial, stiffness estimates. CONCLUSIONS: Given the independent associations of time spent watching television and vigorous intensity HPA with arterial stiffness, our study suggests that not only promotion of physical activity, but also discouragement of sedentary behaviours should be targeted in younger adults to prevent arterial stiffening.

Lower lifetime dietary fiber intake is associated with carotid artery stiffness: the Amsterdam Growth and Health Longitudinal Study.

BACKGROUND: Fiber intake is associated with lower cardiovascular disease risk. Whether arterial stiffness is influenced by lifetime fiber intake is not known. Any such association could explain, at least in part, the cardioprotective effects attributed to fiber intake. OBJECTIVE: The objective was to investigate whether a lower intake of fiber (and fiber-rich foods) throughout the course of young life (ie, from adolescence to adulthood) is associated with arterial stiffness in adulthood. DESIGN: This was a longitudinal cohort study among 373 participants in whom dietary intake was assessed between the ages of 13 to 36 y (2-8 repeated measures, median of 5), and arterial stiffness estimates of 3 large arteries (ultrasonography) were ascertained at age 36 y. RESULTS: After adjustment for sex, height, total energy intake, and other lifestyle variables, subjects with stiffer carotid arteries consumed less fiber (in g/d) during the 24-y study than did those with less stiff carotid arteries, as defined on the basis of the highest compared with the lowest sex-specific tertiles of the distensibility and compliance coefficients (reversed) and Young's elastic modulus: -1.9 (95% CI: -3.1, -0.7), -2.3 (-3.5, -1.1), and -1.3 (-2.5, -0.0), respectively. Furthermore, subjects with stiffer carotid arteries were characterized by a lower lifetime consumption of fruit, vegetables, and whole grains-deleterious associations that could be explained, to a great extent, by related low fiber intake. CONCLUSIONS: Lower lifetime intake of fiber during the course of young age is associated with carotid artery stiffness in adulthood. Promoting consumption of fiber-rich foods among the young may offer a means to prevent accelerated arterial stiffening in adulthood and related cardiovascular sequelae.

Carotid stiffness in young adults: a life-course analysis of its early determinants: the Amsterdam Growth and Health Longitudinal Study.

Cardiovascular risk factors affecting arterial stiffness in adulthood may develop at different critical periods earlier in life. We examined whether the trajectories, from adolescence to young adulthood, of blood pressure, body fatness and fat distribution, blood lipids, cardiorespiratory fitness, and heart rate determined levels of arterial stiffness in young adults. We investigated 373 apparently healthy adults in whom cardiovascular risk factors were repeatedly examined between the ages of 13 and 36 years and carotid stiffness estimates were obtained at the age of 36 years. Differences in the mean levels and the trajectories of risk factors throughout the 24-year longitudinal period between subjects with different levels of carotid stiffness at age 36 years were analyzed with generalized estimating equations. Compared with individuals with less stiff carotid arteries, those with stiffer carotid arteries at the age of 36 years were characterized from ages 13 to 36 years by greater levels of and steeper increases in blood pressure and central fatness, independently of each other and other risk factors. These increases were already present in adolescence, preceded the development of poorer levels of blood lipids, cardiorespiratory fitness, and heart rate, which were evident during adulthood only, and explained to a great extent the deleterious association between these risk factors and carotid stiffness at the age of 36 years. Multiple and intertwined mechanisms involved in the pathogenesis of arterial stiffness have their origins in early life. Blood pressure and central fatness have a pivotal role herein and should be specifically targeted to prevent arterial stiffening and its cardiovascular sequelae.

The change in arterial stiffness over the cardiac cycle rather than diastolic stiffness is independently associated with left ventricular mass index in healthy middle-aged individuals.

BACKGROUND: The current standard for arterial stiffness assessment, aortic pulse wave velocity (aPWV), is measured at diastolic pressure. Arterial stiffness, however, is pressure dependent. At the carotid artery level, the degree of this dependency can be quantified as the difference (ΔPWV) between systolic and diastolic (cPWVd) carotid pulse wave velocity. Biomechanically, a greater ΔPWV implies greater increases in left ventricular afterload with physical activity. Therefore, we hypothesized, that ΔPWV is more strongly associated with left ventricular mass index (LVMI) than aPWV and cPWVd. METHODS: In 1776 healthy individuals from the Asklepios cohort (age 35-55 years), ΔPWV was obtained from combined carotid artery ultrasound and tonometry recordings. Multiple linear regression analysis was performed to investigate the associations of ΔPWV, cPWVd and aPWV with LVMI, adjusting for age, sex, mean blood pressure (MBP), central pulse pressure, and other possible confounders. RESULTS: ΔPWV was 2.4 ±â€Š1.2 m/s (mean ±â€ŠSD), ranging from 0.8 m/s, indicating almost constant arterial stiffness over the cardiac cycle, to 4.4 m/s, reflecting substantial pressure dependency. ΔPWV was significantly associated with LVMI (ß of 2.46 g/m per m/s, P < 0.001), even after full adjustment (ß of 0.56 g/m per m/s, P = 0.03). cPWVd and aPWV had clear crude associations with LVMI (P < 0.001), but lost significance after adjustment (ß of -0.48 and -0.33 g/m per m/s, with P = 0.11 and 0.2, respectively). CONCLUSION: The change in arterial stiffness over the cardiac cycle, rather than diastolic stiffness, is independently associated with LVMI in healthy middle-aged individuals. Therefore, the pressure dependency of arterial stiffness should be considered in cardiovascular risk assessment.

Continuing smoking between adolescence and young adulthood is associated with higher arterial stiffness in young adults: the Northern Ireland Young Hearts Project.

OBJECTIVES: To investigate the associations between smoking in adolescence and adulthood, and changes in smoking behaviour between these age periods, with arterial stiffness in young adults; and whether any such associations could be explained by concomitant smoking-related levels of inflammation and endothelial dysfunction. METHODS: We studied 424 individuals (216 women) in whom smoking status was assessed in adolescence (age 15 years) and again in young adulthood (mean age of 22.6 ± 1.6 years), along with aorto-iliac, aorto-radial, and aorto-dorsalis pedis pulse wave velocity (PWV), and markers of inflammation (i.e. C-reactive protein and fibrinogen) and endothelial dysfunction (i.e. von Willebrand factor and tissue-plasminogen activator antigen) in young adulthood only. RESULTS: Smoking in adolescence was associated with higher aorto-iliac PWV, as well as with inflammation and endothelial dysfunction levels (expressed as two scores), independently of other adolescent and adult lifestyles. Compared with never smokers, continuing smokers, but not starters nor quitters, showed higher aorto-iliac PWV, independent of changes in other lifestyle variables: +0.157 m/s (95% confidence interval 0.026-0.288). This difference was attenuated to 0.124 m/s (-0.009 to 0.257) after adjustment for changes in traditional biological risk factors, but was not materially affected when adjusted for the inflammation and endothelial dysfunction scores, despite the continuing smoking-related higher levels of inflammation and endothelial dysfunction. Smoking was not associated with aorto-radial and aorto-dorsalis pedis PWV. CONCLUSION: Starting to smoke in adolescence and continuing to do so up to young adulthood is adversely associated with aortic stiffness. The continuing smoking-related aortic stiffness was not explained by concomitant higher inflammation and endothelial dysfunction. Prevention of smoking should target the young to prevent arterial stiffness in young adults.

Habitual physical activity and peripheral arterial compliance in young adults: the Amsterdam growth and health longitudinal study.

BACKGROUND: It remains unclear whether the impact of habitual physical activity (HPA) differs for central vs. peripheral arterial stiffness, both of which are detrimental to cardiovascular health. We investigated the associations of lifetime HPA of different intensities on brachial and femoral stiffness in young adults, and compared these with those previously obtained for the carotid artery in the same study population. METHODS: Prospectively measured data (eight repeated measures between ages 13 and 36 years) on HPAs, and other lifestyle and biological variables, were retrieved for 373 subjects in whom stiffness of the brachial and femoral, as well as the carotid, arteries was assessed at age 36 years. Generalized estimating equations were used to examine the differences in time spent in HPAs (min/week) across sex-specific tertiles of the brachial and femoral distensibility (DC) and compliance (CC) coefficients. RESULTS: After adjustment for potential confounders, subjects in the highest (more compliant) vs. those in the lowest tertiles of the brachial and femoral CCs (less compliant) at age 36 years had spent on average more time in vigorous (+21.2 (95%CI:2.0; 40.4) and +24.4 (5.0; 43.8), respectively) but not in light-to-moderate HPAs throughout the longitudinal period. These differences were explained by 28 and 62%, respectively, by vigorous-HPA-related favorable impacts on other cardiovascular risk factors. No such associations were observed for the brachial and femoral DCs, however. CONCLUSIONS: Lifetime vigorous, but not light-to-moderate, HPA is favorably associated with brachial and femoral compliance, but not DC. Altogether, these and our previous findings thus suggest generalized vigorous-HPA-related adaptations, although of different nature, throughout the arterial tree.

Lifetime vigorous but not light-to-moderate habitual physical activity impacts favorably on carotid stiffness in young adults: the amsterdam growth and health longitudinal study.

Higher levels of habitual physical activity favorably impact on arterial stiffness. It is not clear, however, whether lifetime habitual physical activities of different intensities carry the same protective effect and to what extent any such effect is mediated by other biological cardiovascular risk factors. We, therefore, examined longitudinal data on habitual physical activity and cardiovascular risk factors (8 repeated measures between the ages of 13 and 36 years) in 373 subjects in whom stiffness estimates of the carotid artery were assessed at age 36 years using noninvasive ultrasonography. The time spent in habitual physical activities (in minutes per week) throughout the longitudinal period was compared between subjects across tertiles of the following stiffness estimates: beta-stiffness index, distensibility and compliance coefficients, and the Young's elastic modulus. After adjustments for sex, body height, and other lifestyle variables, subjects in the highest tertile of the beta-stiffness index (ie, with stiffer arteries) had spent, on average, throughout the longitudinal period, less time in vigorous (-26.5 [95% CI: -45.9 to -7.1]) but less so in light-to-moderate habitual physical activities (-11.2 [95% CI: -53.5 to 31.1]) as compared with subjects in the lowest tertile. The difference in time spent in vigorous activities was greatly attenuated when further adjusted for blood lipids, cardiorespiratory fitness, fat distribution, resting heart rate, and mean arterial pressure (to -11.2 [95% CI: -29.4 to 7.0]). Similar results were found for the other stiffness estimates. Promoting vigorous intensity physical activities among the healthy young may, therefore, prevent arterial stiffness and related cardiovascular sequelae later in life, partly through its favorable impact on other biological cardiovascular risk factors.