Effect of diet-induced weight loss on lipoprotein(a) levels in obese individuals with and without type 2 diabetes

_Aims/hypothesis:_ Elevated levels of lipoprotein(a) [Lp(a)] are an independent risk factor for cardiovascular disease (CVD), particularly in individuals with type 2 diabetes. Although weight loss improves conventional risk factors for CVD in type 2 diabetes, the effects on Lp(a) are unknown and may influence the long-term outcome of CVD after diet-induced weight loss. The aim of this clinical study was to determine the effect of diet-induced weight loss on Lp(a) levels in obese individuals with type 2 diabetes. _Methods:_ Plasma Lp(a) levels were determined by immunoturbidimetry in plasma obtained before and after 3–4 months of an energy-restricted diet in four independent study cohorts. The primary cohort consisted of 131 predominantly obese patients with type 2 diabetes (cohort 1), all participants of the Preven

Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2):study protocol for an international multicenter patient-blinded randomized controlled trial

Background: Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design: The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion: The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration: ISRCTN27483786. Registered on August 2, 2023.</p

Vitamin D and type 2 diabetes

Vitamin D deficiency is associated with a decreased insulin release, insulin resistance and type 2 diabetes in experimental and epidemiological studies. Animal studies show that 1α,25–dihydroxyvitamin D3 (1,25(OH)2D3) stimulates the pancreatic β-cell to secrete insulin. The relationship between vitamin D deficiency and insulin resistance could develop through inflammation, as vitamin D deficiency is associated with increased inflammatory markers. In addition, genetic polymorphisms of vitamin D −related genes may predispose to impaired glycemic control and type 2 diabetes. Epidemiologic studies showed an association between low serum 25-hydroxyvitamin D3 (25(OH)D3) concentration and an increased risk for the metabolic syndrome and type 2 diabetes. This may be partly explained by an increased fat mass. A possible causal relationship between vitamin D deficiency and type 2 diabetes should be proven by randomized clinical trials showing that either type 2 diabetes can be prevented or insulin release and insulin sensitivity can be improved by vitamin D supplements. The results of randomized clinical trials on the effect of vitamin D versus placebo, sometimes combined with calcium, in patients with impaired glucose tolerance (“prediabetes”) or type 2 diabetes are inconsistent. Some studies showed a slight decrease of fasting plasma glucose or improvement of insulin resistance, but often only in posthoc analyses. These effects are mainly visible in patients with vitamin D deficiency and impaired glucose tolerance at baseline. Meta-analyses of randomized clinical trials in general did not show significant effects of vitamin D supplementation on glycemic control. Currently, several large scale randomized clinical trials with vitamin D supplementation in doses of 1600–4000 IU/d are ongoing with glycemic control or incidence of diabetes mellitus as outcome. Vitamin D deficiency needs to be prevented or cured, but until the results of these trials are published, high-dose vitamin D supplementation cannot be recommended for prevention or amelioration of type 2 diabetes

Increased PUFA Content and 5-Lipoxygenase Pathway Expression Are Associated with Subcutaneous Adipose Tissue Inflammation in Obese Women with Type 2 Diabetes

Obese women with type 2 diabetes mellitus (T2DM) have more inflammation in their subcutaneous white adipose tissue (sWAT) than age-and-BMI similar obese women with normal glucose tolerance (NGT). We aimed to investigate whether WAT fatty acids and/or oxylipins are associated with the enhanced inflammatory state in WAT of the T2DM women. Fatty acid profiles were measured in both subcutaneous and visceral adipose tissue (vWAT) of 19 obese women with NGT and 16 age-and-BMI similar women with T2DM. Oxylipin levels were measured in sWAT of all women. Arachidonic acid (AA) and docosahexaenoic acid (DHA) percentages were higher in sWAT, but not vWAT of the T2DM women, and AA correlated positively to the gene expression of macrophage marker CD68. We found tendencies for higher oxylipin concentrations of the 5-LOX leukotrienes in sWAT of T2DM women. Gene expression of the 5-LOX leukotriene biosynthesis pathway was significantly higher in sWAT of T2DM women. In conclusion, AA and DHA content were higher in sWAT of T2DM women and AA correlated to the increased inflammatory state in sWAT. Increased AA content was accompanied by an upregulation of the 5-LOX pathway and seems to have led to an increase in the conversion of AA into proinflammatory leukotrienes in sWAT

Common and distinct components in data fusion

In many areas of science, multiple sets of data are collected pertaining to the same system. Examples are food products that are characterized by different sets of variables, bioprocesses that are online sampled with different instruments, or biological systems of which different genomic measurements are obtained. Data fusion is concerned with analyzing such sets of data simultaneously to arrive at a global view of the system under study. One of the upcoming areas of data fusion is exploring whether the data sets have something in common or not. This gives insight into common and distinct variation in each data set, thereby facilitating understanding of the relationships between the data sets. Unfortunately, research on methods to distinguish common and distinct components is fragmented, both in terminology and in methods: There is no common ground that hampers comparing methods and understanding their relative merits. This paper provides a unifying framework for this subfield of data fusion by using rigorous arguments from linear algebra. The most frequently used methods for distinguishing common and distinct components are explained in this framework, and some practical examples are given of these methods in the areas of medical biology and food science

Fusing metabolomics data sets with heterogeneous measurement errors

Combining different metabolomics platforms can contribute significantly to the discovery of complementary processes expressed under different conditions. However, analysing the fused data might be hampered by the difference in their quality. In metabolomics data, one often observes that measurement errors increase with increasing measurement level and that different platforms have different measurement error variance. In this paper we compare three different approaches to correct for the measurement error heterogeneity, by transformation of the raw data, by weighted filtering before modelling and by a modelling approach using a weighted sum of residuals. For an illustration of these different approaches we analyse data from healthy obese and diabetic obese individuals, obtained from two metabolomics platforms. Concluding, the filtering and modelling approaches that both estimate a model of the measurement error did not outperform the data transformation approaches for this application. This is probably due to the limited difference in measurement error and the fact that estimation of measurement error models is unstable due to the small number of repeats available. A transformation of the data improves the classification of the two groups.status: publishe

Daily-Life Gait Quality as Predictor of Falls in Older People: A 1-Year Prospective Cohort Study.

Falls can have devastating consequences for older people. We determined the relationship between the likelihood of fall incidents and daily-life behavior. We used wearable sensors to assess habitual physical activity and daily-life gait quality (in terms of e.g. stability, variability, smoothness and symmetry), and determined their predictive ability for time-to-first-and-second-falls. 319 older people wore a trunk accelerometer (Dynaport MoveMonitor, McRoberts) during one week. Participants further completed questionnaires and performed grip strength and trail making tests to identify risk factors for falls. Their prospective fall incidence was followed up for six to twelve months. We determined interrelations between commonly used gait characteristics to gain insight in their interpretation and determined their association with time-to-falls. For all data -including questionnaires and tests- we determined the corresponding principal components and studied their predictive ability for falls. We showed that gait characteristics of walking speed, stride length, stride frequency, intensity, variability, smoothness, symmetry and complexity were often moderately to highly correlated (r > 0.4). We further showed that these characteristics were predictive of falls. Principal components dominated by history of falls, alcohol consumption, gait quality and muscle strength proved predictive for time-to-fall. The cross-validated prediction models had adequate to high accuracy (time dependent AUC of 0.66-0.72 for time-to-first-fall and 0.69-0.76 for -second-fall). Daily-life gait quality obtained from a single accelerometer on the trunk is predictive for falls. These findings confirm that ambulant measurements of daily behavior contribute substantially to the identification of elderly at (high) risk of falling

Energy restriction and Roux-en-Y gastric bypass reduce postprandial alpha-dicarbonyl stress in obese women with type 2 diabetes

Conclusions/interpretation This study shows that type 2 diabetes is characterised by increased fasting and postprandial plasma alpha-dicarbonyl stress, which can be reduced by improving glucose metabolism through a VLCD or RYGB. These data highlight the potential to reduce reactive alpha-dicarbonyls in obese individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT01167959Functional Genomics of Systemic Disorder