Modeling the mechanisms of non-neurogenic dynamic cerebral autoregulation.

Objective: Dynamic cerebral autoregulation (dCA) refers to a collection of mechanisms that act to maintain steady state cerebral blood flow (CBF) near constant despite changes in arterial blood pressure (ABP), but which is known to become impaired in various cerebrovascular diseases. Currently, the mechanisms of dCA and how they are affected in different physiological conditions are poorly understood. The objective of this study was to disentangle the magnitudes and time scales of the myogenic and metabolic responses of dCA, in order to investigate how each mechanism is affected in impaired dCA.

Extracorporeal membrane oxygenation in South Africa: Experience from a single centre in the private sector.

Background: Extracorporeal membrane oxygenation (ECMO) is an advanced, resource-intensive technology used in a limited capacity in South Africa (SA). Minimal data on the use of ECMO in SA are available.

Objectives: To describe the indications, early outcome and comorbidities of patients placed on ECMO in the highest-volume ECMO centre in SA.

Lifestyle medicine for type 2 diabetes: practice-based evidence for long-term efficacy of a multicomponent lifestyle intervention (Reverse Diabetes2 Now).

Introduction: A wealth of evidence supports short-term efficacy of lifestyle interventions in type 2 diabetes (T2D). However, little is known about long-term effects of lifestyle interventions in real-life settings.

Methods: This observational, single-arm study evaluated long-term impact of 'Voeding Leeft: Reverse-Diabetes2-Now', a 6-month multicomponent lifestyle programme, on glycaemic control and glucose-lowering medication (GLmed) use, other T2D parameters and quality of life in 438 T2D participants at 6, 12, 18 and 24 months using paired sample t-tests, χ and generalised linear models.

Hydatid Disease With Pseudoaneurysm Formation of the Descending Thoracic Aorta.

Human Echinococcus disease is a zoonosis that primarily affects the liver and lungs. We report a rare case of hydatid disease in the posterior mediastinum with pseudoaneurysm formation of the descending thoracic aorta and erosion of thoracic vertebral bodies. The patient was surgically treated with removal of multiple daughter cysts and primary repair of the aorta.

Nutrition and lifestyle intervention in type 2 diabetes: pilot study in the Netherlands showing improved glucose control and reduction in glucose lowering medication.

Introduction: Prevalence of type 2 diabetes (T2D) is increasing rapidly and lifestyle interventions to reverse diabetes are seen as a possible solution to stop this trend. New practice-based evidence is needed to gain more insight in the actual, and above all scientific, basis for these claims.

Methods: This observational study with a pretest post-test design aimed to pilot a 6-month multicomponent outpatient group-based nutrition and lifestyle intervention programme on glycaemic control and use of glucose lowering medication in motivated T2D patients with a body mass index (BMI) >25 kg/m in the Netherlands (February 2015-March 2016).

Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose.

Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [²H₂]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-(13)C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG.

Metabolic changes in type 2 diabetes are reflected in peripheral blood cells, revealing aberrant cytotoxicity, a viral signature, and hypoxia inducible factor activity.

Background: Metabolic syndrome (MetS) is characterized by central obesity, insulin resistance, dysglycemia, and a pro-atherogenic plasma lipid profile. MetS creates a high risk for development of type 2 diabetes (T2DM) and cardiovascular disease (CVD), presumably by altering inflammatory responses. Presently, it is unknown how the chronic metabolic disturbances in acute hyperglycemia, MetS and T2DM affect the immune activity of peripheral blood cells.

Differential impact of subclinical carotid artery disease on cerebral structure and functioning in type 1 diabetes patients with versus those without proliferative retinopathy.

Background: Type 1 diabetes mellitus (T1DM) is associated with cerebral compromise, typically found in patients with microangiopathy. Associations between subclinical macroangiopathy and the brain, whether or not in the presence of microangiopathy, have not been fully explored in T1DM. We hypothesized that subclinical macroangiopathy in adult T1DM may affect the brain and interacts with microangiopathy.

The effects of long-term valsartan treatment on skeletal muscle fatty acid handling in humans with impaired glucose metabolism.

Context: Blocking the renin-angiotensin system reduces the incidence of type 2 diabetes mellitus in humans with impaired glucose metabolism (IGM). Nevertheless, underlying mechanisms remain to be established.

Objective: The purpose of this study was to investigate the effects of the angiotensin II type 1 receptor blocker valsartan (VAL) on skeletal muscle fatty acid (FA) handling in subjects with IGM.

Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized placebo-controlled double-blind trial.

Background: Blockade of the renin-angiotensin system (RAS) reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT) function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans.

Does interference with the renin-angiotensin system protect against diabetes? Evidence and mechanisms.

Agents interfering with the renin-angiotensin system (RAS) were consistently shown to lower the incidence of type 2 diabetes mellitus (T2DM), as compared to other antihypertensive drugs, in hypertensive high-risk populations. The mechanisms underlying this protective effect of RAS blockade using angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on glucose metabolism are not fully understood. In this article, we will review the evidence from randomized controlled trials and discuss the proposed mechanisms as to how RAS interference may delay the onset of T2DM.

Glucose tolerance, insulin sensitivity and β-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids.

Objectives: To compare glucose tolerance and parameters of insulin sensitivity and β-cell function between chronic glucocorticoid (GC)-using and GC-naive patients with rheumatoid arthritis (RA).

Methods: Frequently sampled 75 g oral glucose tolerance tests were performed in 58 chronic GC-using and 82 GC-naive patients with RA with established disease, with no known type 2 diabetes mellitus (T2DM), and 50 control subjects of comparable age with normal glucose tolerance. The associations between cumulative GC dose and disease characteristics and glucose tolerance state, insulin sensitivity and β-cell function were tested using multivariate linear and logistic regression models, correcting for patient characteristics.

Valsartan-induced improvement in insulin sensitivity is not paralleled by changes in microvascular function in individuals with impaired glucose metabolism.

Background: Individuals with impaired glucose metabolism (IGM) are at high risk of developing type 2 diabetes (T2DM). The renin-angiotensin system (RAS) is activated in insulin-resistant states and its inhibition resulted in delayed onset of T2DM. The underlying mechanisms may include improvement in microvascular structure and function, which may increase glucose and insulin delivery to insulin-sensitive tissues.

Impaired insulin sensitivity is accompanied by disturbances in skeletal muscle fatty acid handling in subjects with impaired glucose metabolism.

Objective: To determine insulin sensitivity and skeletal muscle fatty acid (FA) handling at baseline and after a high-fat mixed meal in impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT and normal glucose tolerance (NGT) subjects.

Design: In this multi-center study, insulin sensitivity and β-cell function were assessed (n=102), using a euglycemic-hyperinsulinemic and hyperglycemic clamp with additional arginine stimulation and a 75 g oral glucose tolerance test. Fasting and postprandial skeletal muscle FA handling was examined in a substudy using the forearm balance technique (n=35).

Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial.

Aim/hypothesis: To assess whether low-dose glucocorticoid treatment induces adverse metabolic effects, as is evident for high glucocorticoid doses.

Methods: In a randomised placebo-controlled double-blind (participants and the investigators who performed the studies and assessed the outcomes were blinded) dose-response intervention study, 32 healthy men (age 22 ± 3 years; BMI 22.4 ± 1.

Valsartan improves {beta}-cell function and insulin sensitivity in subjects with impaired glucose metabolism: a randomized controlled trial.

Objective: Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes.

Research Design And Methods: In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT).

Ectopic fat storage in the pancreas, liver, and abdominal fat depots: impact on β-cell function in individuals with impaired glucose metabolism.

Context: Pancreatic fat content (PFC) may have deleterious effects on β-cell function.

Objective: We hypothesized that ectopic fat deposition, in particular pancreatic fat accumulation, is related to β-cell dysfunction in individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT).

Design, Setting And Participants: This was a cross-sectional study in 64 age- and body mass index-matched individuals, with normal glucose tolerance (NGT; n = 16, 60% males), IFG (n = 29, 52% males), or IFG/IGT (n = 19, 63% males) was conducted.

Pancreatic steatosis in humans: cause or marker of lipotoxicity?

Purpose Of Review: Type 2 diabetes mellitus (T2DM) is characterized by impaired insulin secretion. Chronically increased levels of plasma nonesterified fatty acids (NEFA) and triglyceride-rich lipoproteins impair beta-cell function, a process referred to as lipotoxicity. Furthermore, when NEFA supply exceeds metabolic capacity, lipids accumulate in nonadipose tissues, such as pancreatic islets, inducing organ dysfunction.

Urinary matrix metalloproteinase-8 and -9 activities in type 2 diabetic subjects: A marker of incipient diabetic nephropathy?

Matrix metalloproteinases (MMPs) may play a pathophysiological role in the development of diabetic nephropathy (DN). We hypothesized that urinary MMP activity in patients with type 2 diabetes mellitus (T2DM) is related to a decline in renal function. We determined MMP-2, -8 and -9 activity in 24-h urine collections in relation to risk factors for DN in T2DM patients with (UA, n=27) and without albuminuria (NA, n=48) and controls (CO, n=28).