Brain imaging evidence of early involvement of subcortical regions in familial and sporadic Alzheimer's disease

Recent brain imaging studies have found changes in subcortical regions in presymptomatic autosomal dominant Alzheimer's disease (ADAD). These regions are also affected in sporadic Alzheimer's disease (sAD), but whether such changes are seen in early-stage disease is still uncertain. In this review, we discuss imaging studies published in the past 12 years that have found evidence of subcortical involvement in early-stage ADAD and/or sAD. Several papers have reported amyloid deposition in the striatum of presymptomatic ADAD mutation carriers, prior to amyloid deposition elsewhere. Altered caudate volume has also been implicated in early-stage ADAD, but findings have been variable. Less is known about subcortical involvement in sAD: the thalamus and striatum have been found to be atrophied in symptomatic patients, but their involvement in the preclinical phase remains unclear, in part due to the difficulties of studying this stage in sporadic disease. Longitudinal imaging studies comparing ADAD mutation carriers with individuals at high-risk for sAD may be needed to elucidate the significance of subcortical involvement in different AD clinical stages

Association of matrix γ-carboxyglutamic acid protein levels with insulin resistance and Lp(a) in diabetes: A cross-sectional study.

AIMS: The risk of cardiovascular disease (CVD) and mortality is increased in patients with chronic kidney disease (CKD), with a background role of vascular calcification in the development of CVD also reported. Studies have demonstrated that high lipoprotein(a) (Lp(a)) levels accelerate the development of atherosclerolsis and are potentially involved in the vascular calcification. Matrix Gla Protein (MGP) seems to play an important role in vascular calcification. The aim of the study was to examine the potential association of MGP concentrations with Lp(a) and insulin resistance. METHODS: The study involved 100patients divided in four groups: 25 with both CKD stage 4 and Type2 Diabetes (DM) (Group-A), 25 with CKD4 without DM (Group-B), 25 non uremic patients with DM (Group-C) and 25 healthy subjects (Group-D). Serum glucose, Lp(a), MGP, plasma HBA1c and insulin were measured in all patients. Insulin resistance was estimated by the homeostasis model assessment equation (HOMA-IR). RESULTS: A significant positive linear association between MGP and Lp(a) levels (r=0.272, p=0.006) was noted, as well as between MGP and HOMA-IR levels (r=0.308, p=0.002). However, no significant linear association between Lp(a) and HOMA-IR levels was recorded. A similar positive association between MGP and insulin levels (r=0.204, p=0.042) was also found. CONCLUSION: This study concluded that diabetes coexisting with renal disease leads to extreme vascular calcification expressed by elevated MGP levels, resulting in higher frequency of cardiovascular disease in comparison to CKD patients without diabetes. The detected Lp(a) and MGP association in CKD4 patients may also represent the key to the complicated mechanism of their coexisting accelerated atherosclerosis and vascular calcification

The Relationship of Metabolic Syndrome Traits with Beta-Cell Function and Insulin Sensitivity by Oral Minimal Model Assessment in South Asian and European Families Residing in the Netherlands

Background. There are different metabolic syndrome traits among patients with different ethnicities. Methods. We investigated this by studying 44 South Asians and 54 Europeans and classified them in three groups according to the occurrence of metabolic syndrome (MetS) and Type 2 Diabetes (T2D). Insulin sensitivity index (ISI), static, dynamic, and total beta-cell responsivity indices (Φ), and disposition indices (DIs) were calculated with the use of oral minimal model (

Are Large Physiological Reactions to Acute Psychological Stress Always Bad for Health?

How we react physiologically to stress has long been considered to have implications for our health. There is now persuasive evidence that individuals who show large cardiovascular reactions to stress are at increased risk of developing cardiovascular disease, particularly hypertension. By implication, low reactivity is protective or benign. However, there is recent evidence that low reactivity may predict elevated risk for a range of adverse health outcomes, such as depression, obesity, poor self-reported health, and compromised immunity. In addition, low cortisol and cardiovascular reactivity may be a characteristic of individuals with addictions to tobacco and alcohol, as well as those at risk of addiction and those who relapse from abstinence. Our ideas about reactivity may have to be revised in the light of such findings

Developing core sets for persons following amputation based on the International Classification of Functioning, Disability and Health as a way to specify functioning

Amputation is a common late stage sequel of peripheral vascular disease and diabetes or a sequel of accidental trauma, civil unrest and landmines. The functional impairments affect many facets of life including but not limited to: Mobility; activities of daily living; body image and sexuality. Classification, measurement and comparison of the consequences of amputations has been impeded by the limited availability of internationally, multiculturally standardized instruments in the amputee setting. The introduction of the International Classification of Functioning, Disability and Health (ICF) by the World Health Assembly in May 2001 provides a globally accepted framework and classification system to describe, assess and compare function and disability. In order to facilitate the use of the ICF in everyday clinical practice and research, ICF core sets have been developed that focus on specific aspects of function typically associated with a particular disability. The objective of this paper is to outline the development process for the ICF core sets for persons following amputation. The ICF core sets are designed to translate the benefits of the ICF into clinical routine. The ICF core sets will be defined at a Consensus conference which will integrate evidence from preparatory studies, namely: (a) a systematic literature review regarding the outcome measures of clinical trails and observational studies, (b) semi-structured patient interviews, (c) international experts participating in an internet-based survey, and (d) cross-sectional, multi-center studies for clinical applicability. To validate the ICF core sets field-testing will follow. Invitation for participation: The development of ICF Core Sets is an inclusive and open process. Anyone who wishes to actively participate in this process is invited to do so

Assessment of the Spatial QRS-T Angle by Vectorcardiography: Current Data and Perspectives

The concept of the ventricular gradient (VG) was conceived in the 1930s and its calculation yielded information that was not otherwise obtainable. The VG was not utilized by clinicians at large because it was not easy to understand and its computation time-consuming. Spatial vectorcardiography is based on the concept of the VG. Its current major clinical use is to identify primary [heterogeneity of ventricular action potential (VAP) morphology] in the presence of secondary [heterogeneity in ventricular depolarization instants] T-wave abnormalities in an ECG. Nowadays, the calculation of the spatial VG can be computed on the basis of a regular routine ECG and contributes to localization of arrhythmogenic areas in the heart by assessing overall and local VAP duration heterogeneity. Recent population-based studies suggest that the spatial VG is a dominant ECG predictor of future cardiovascular events and death and it is superior to more conventional ECG parameters. Its assessment warrants consideration for intensified primary and secondary prevention efforts and can be included in everyday clinical practice. This review addresses the nature and diagnostic potential of the spatial VG. The main focus is the role of the spatial VG in ECG assessment of dispersion of repolarization, a key factor in arrhythmogeneity

Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies

Diabetic cardiomyopathy (DCM), although a distinct clinical entity, is also a part of the diabetic atherosclerosis process. It may be independent of the coexistence of ischemic heart disease, hypertension, or other macrovascular complications. Its pathological substrate is characterized by the presence of myocardial damage, reactive hypertrophy, and intermediary fibrosis, structural and functional changes of the small coronary vessels, disturbance of the management of the metabolic cardiovascular load, and cardiac autonomic neuropathy. These alterations make the diabetic heart susceptible to ischemia and less able to recover from an ischemic attack. Arterial hypertension frequently coexists with and exacerbates cardiac functioning, leading to the premature appearance of heart failure. Classical and newer echocardiographic methods are available for early diagnosis. Currently, there is no specific treatment for DCM; targeting its pathophysiological substrate by effective risk management protects the myocardium from further damage and has a recognized primary role in its prevention. Its pathophysiological substrate is also the objective for the new therapies and alternative remedies

A review of nateglinide in the management of patients with type 2 diabetes

Impaired insulin secretion occurs early in the pathogenesis of type 2 diabetes mellitus (T2DM) and is chronic and progressive, resulting initially in impaired glucose tolerance (IGT) and eventually in T2DM. As most patients with T2DM have both insulin resistance and insulin deficiency, therapy for T2DM should aim to control not only fasting, but also postprandial plasma glucose levels. While oral glucose-lowering treatment with metformin and thiazolidinediones corrects fasting plasma glucose, these agents do not address the problem of mealtime glucose spikes that have been shown to trigger atherogenic processes. Nateglinide is a derivative of the amino acid D-phenylalanine, which acts directly on the pancreatic β-cells to stimulate insulin secretion. Nateglinide monotherapy controls significantly mealtime hyperglycemia and results in improved overall glycemic control in patients with T2DM by reducing glycosylated hemoglobin (HbA1c) levels. The combination of nateglinide with insulin-sensitising agents, such as metformin and thiazolidinediones, targets both insulin deficiency and insulin resistance and results in reductions in HbA1c that could not be achieved by monotherapy with other antidiabetic agents. In prediabetic subjects with IGT, nateglinide restores early insulin secretion and reduces postprandial hyperglycemia. Nateglinide has an excellent safety and tolerability profile and provides a lifetime flexibility that other antidiabetic agents could not accomplish. The aim of this review is to identify nateglinide as an effective “gate-keeper” in T2DM, since it restores early-phase insulin secretion and prevents mealtime glucose spikes throughout the day and to evaluate the results of ongoing research into its potential role in delaying the progression to overt diabetes and reducing its complications and mortality

The Effect of Ingested Macronutrients on Postprandial Ghrelin Response: A Critical Review of Existing Literature Data

Ghrelin is a powerful orexigenic gut hormone with growth hormone releasing activity. It plays a pivotal role for long-term energy balance and short-term food intake. It is also recognized as a potent signal for meal initiation. Ghrelin levels rise sharply before feeding onset, and are strongly suppressed by food ingestion. Postprandial ghrelin response is totally macronutrient specific in normal weight subjects, but is rather independent of macronutrient composition in obese. In rodents and lean individuals, isoenergetic meals of different macronutrient content suppress ghrelin to a variable extent. Carbohydrate appears to be the most effective macronutrient for ghrelin suppression, because of its rapid absorption and insulin-secreting effect. Protein induces prolonged ghrelin suppression and is considered to be the most satiating macronutrient. Fat, on the other hand, exhibits rather weak and insufficient ghrelin-suppressing capacity. The principal mediators involved in meal-induced ghrelin regulation are glucose, insulin, gastrointestinal hormones released in the postabsorptive phase, vagal activity, gastric emptying rate, and postprandial alterations in intestinal osmolarity