Postprandial dysmetabolism and cardiovascular disease in type 2 diabetes

The worldwide prevalence of type 2 diabetes mellitus has reached epidemic proportions. The so-called traditional risk factors cannot fully explain the excessive cardiovascular disease risk of type 2 diabetic patients. Numerous studies indicate that postprandial metabolic derangements, most notably hyperglycaemia and hypertriglyceridaemia, which are exaggerated and prolonged in type 2 diabetes, are important cardiovascular disease risk factors since they induce oxidative stress and endothelial dysfunctions. This review discusses the current evidence showing that postprandial dysmetabolism may indeed constitute an important cardiovascular disease risk factor as well as the mechanisms underlying this association. Finally, some possible therapeutic options and recommendations for future research are discussed

Postprandial dysmetabolism and cell-derived microparticles as cardiovascular risk factors in metabolic syndrome and type 2 diabetes mellitus

Diamant, M. [Promotor]Sturk, A. [Promotor]Nieuwland, R. [Copromotor

Sigmoid volvulus in myotonic dystrophy type I (Steinert disease)

Myotonic dystrophy (MD) is a progressive multisystem genetic disorder that is characterized by progressive muscle weakness and wasting. MD1 (also known as Steinert disease) is associated with various clinical entities such as skeletal muscle weakness, myotonia, cardiac abnormalities, respiratory dysfunction, gastrointestinal involvement, and cognitive impairment. In this case report, we present a 32-year-old woman with MD1 who presented with a sigmoid volvulus, which was treated with endoscopic decompression

Referral care paths for non-alcoholic fatty liver disease-Gearing up for an ever more prevalent and severe liver disease

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent and potentially severe liver disease, emphasizing the need for implementation of widely supported care paths for patients at risk for advanced stages of NAFLD. In particular, the distinction of patients with a progressive and/or advanced, fibrotic NAFLD from those with simple steatosis requires improvement, as well as the awareness for NAFLD among health care professionals. Broad acceptance and implementation of interdisciplinary care paths in the near future will bring enhanced identification of those patients that benefit from surveillance, intensive lifestyle management, and empirical or investigational pharmacotherapy and enhance our epidemiological grasp of NAFLD in relation to lifestyle, genetic background, and cardiometabolic comorbidities related to NAFLD.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Non-alcoholic fatty liver disease: a multidisciplinary approach towards a cardiometabolic liver disease

Non-alcoholic fatty liver disease (NAFLD) is a growing health p roblem with a global prevalence of over 25% and prevalence rates of over 60% in high-risk populations. It is co nsidered the hepatic component of the metabolic syndrome and is associated with an increased risk of the develo pment of various liver-associated and cardiometabolic complications. Given the complexity of NAFLD and associated com orbidities and complications, treatment requires interventions from a variety of different healthcare specialties . However, many clinicians are currently insufficiently aware of the potential harm and severity of NAFLD and associate d comorbidities, complications and the steps that should be taken when NAFLD is suspected. Recognizing which pati ents suffer from non-progressive simple steatosis, metabolically active NASH with high risk of developing cardiova scular disease and which patients have a high risk of developing cirrhosis and hepatocellular carcinoma is important. Unfortunately, this can be difficult and guidelines towards the optimal diagnostic and therapeutic approach are amb ivalent. Here we review the pathogenesis, diagnostics and treatment of NAFLD and discuss how multidiscipl inary care path development could move forward. Nephrolog

Tacrolimus 4-hour monitoring in liver transplant patients is non-inferior to trough monitoring: The randomized controlled FK04 trial

Background After liver transplantation (LT), tacrolimus and ciclosporin treatment can lead to, partially concentration-dependent, chronic kidney disease. Monitoring ciclosporin with two-hour levels reduced overexposure and led to better renal function than trough-monitoring (C0). For tacrolimus, a 4-hour level (C4) can give a reasonable approximation of total drug exposure. We evaluated whether monitoring tacrolimus in stable patients after LT by C4 was superior to C0 regarding renal function, rejection and metabolic parameters. Methods This open label randomized controlled trial compared C4 monitoring of tacrolimus BID (Prograft) to trough (C0) monitoring in stable LT recipients. The target range for C4 of 7.8-16 ng/ml was calculated to be comparable with target C0 of 4-8 ng/ml. Primary endpoint was the effect on renal function and secondary endpoints were the occurrence of treated biopsy-proven acute rejection, blood pressure and metabolic parameters, during 3 months of follow-up. Results Fifty patients were randomized to C0 (n = 25) or C4 (n = 25) monitoring. There was no difference in renal function between the C0 and the C4 group (p = .98 and p = .13 for CG and MDRD at 3 months). Also, the amount of proteinuria was similar (p = .59). None of the patients suffered from graft loss or was treated for rejection. Metabolic parameters did not differ between the two groups. Conclusion Tacrolimus 4-hour monitoring in stable LT patients is not superior to trough monitoring, regarding the effect on renal function, but is safe for use to facilitate tacrolimus monitoring in an afternoon outpatient clinic.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Replacement of dietary saturated fat with unsaturated fats increases numbers of circulating endothelial progenitor cells and decreases number of microparticles: findings from the randomized, controlled DIVAS study

Background Endothelial progenitor cells (EPC) and microparticles (MP) are emerging novel markers of cardiovascular disease (CVD) risk, which could potentially be modified by dietary fat. We have previously shown that replacing dietary saturated fat (SFA) with monounsaturated (MUFA) or n-6 polyunsaturated fat (PUFA) improved lipid biomarkers, blood pressure and markers of endothelial activation, but their effects on circulating EPCs and MPs are unclear. Objective The Dietary Intervention and VAScular function (DIVAS) study investigated the replacement of 9.5-9.6% total energy (%TE) SFA with MUFA or n-6 PUFA for 16 weeks on EPC and MP numbers in UK adults with moderate CVD risk. Design In this randomized, controlled, single-blind, parallel group dietary intervention, men and women aged 21-60 y (n=190) with moderate CVD risk (≥50% above the population mean) consumed one of three 16-week isoenergetic diets. Target compositions for total fat, SFA, MUFA and n-6 PUFA (%TE) were: SFA-rich diet (36:17:11:4, n=64), MUFA-rich diet (36:9:19:4, n=62) and n-6 PUFA-rich diet (36:9:13:10, n=66). Circulating EPC, endothelial MP (EMP) and platelet MP (PMP) numbers were analysed by flow cytometry. Dietary intake, vascular function and other cardio-metabolic risk factors were determined at baseline. Results Relative to the SFA-rich diet, MUFA and n-6 PUFA-rich diets decreased EMP (-47.3%, -44.9%) and PMP numbers (-36.8%, -39.1%) (overall diet effects P<0.01). The MUFA-rich diet increased EPC numbers (+28.4%; P=0.023). Additional analyses using stepwise regression models identified the augmentation index (measuring arterial stiffness determined by pulse wave analysis) as an independent predictor of baseline EPC and MP numbers. Conclusions Replacing 9.5-9.6%TE dietary SFA with MUFA increased EPC numbers and replacement with either MUFA or n-6 PUFA decreased MP numbers, suggesting beneficial effects on endothelial repair and maintenance. Further studies are warranted to determine the mechanisms underlying the favourable effects on EPC and MP numbers following SFA replacement