Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adiponectin and resistin are recently described secretory products of adipose tissue. Adiponectin is secreted by fat cells and circulates in the blood. Plasma adiponectin concentration is reduced in obese animals and humans and in patients with type 2 diabetes mellitus. Adiponectin stimulates fatty acids oxidation, decreases plasma triglycerides, and improves glucose metabolism by increasing insulin sensitivity. In addition, adiponectin inhibits the inflammatory process and possibly atherogenesis by suppressing the migration of monocytes/macrophages and their transformation into foam cells. Plasma adiponectin is lower in patients with ischemic heart disease than in body mass index-matched healthy individuals. Hypoadiponectinemia may contribute to insulin resistance and accelerated atherogenesis associated with obesity. Resistin/FIZZ3 is a member of the newly discovered cysteine-reach secretory protein family, referred to as 'resistin-like molecules' (RELM) or 'found in inflammatory zone' (FIZZ), together with FIZZ1/RELMalpha and FIZZ2/RELMbeta. Each of these has unique tissue distribution. Both resistin and FIZZ1/RELMalpha are expressed in adipose tissue. Initial studies in rodents suggested that resistin is upregulated in obesity and may be involved in the development of insulin resistance. Later studies failed to confirm this hypothesis and demonstrated reduced resistin expression in adipose tissue of obese animals. In human adipose tissue resistin is detectable at a very low level, and there is no relationship between resistin expression and obesity. Although the role of resistin in linking human obesity with type 2 diabetes is thus questionable, this protein is detected in peripheral blood monocytes,
Med Sci Monit 2003 Feb
PMID:Adiponectin and resistin--new hormones of white adipose tissue. 1458 85

The excess risk of cardiovascular disease in patients with Type 2 diabetes mellitus remains largely unexplained. Arterial stiffness, an early feature of diabetic vasculopathy involving several mechanisms, results in impaired arterial compliance, and has recently been proposed as a powerful independent predictor of cardiovascular disease. Increased arterial stiffness can contribute to the development and progression of hypertension, left ventricular hypertrophy and dysfunction, and to decreased myocardial perfusion, all of which are highly prevalent in Type 2 diabetes mellitus. Large artery stiffening has been demonstrated in Type 2 diabetes using several different methods including measurement of central pulse wave velocity, or estimation of aortic compliance, a technically demanding technique requiring the simultaneous measurement of stroke volume and diastolic pressure decay. Increased arterial stiffness of smaller arteries is also an important contributor to systemic arterial stiffness and cardiovascular risk. Increasing demand by clinical researchers for measurement of arterial stiffness has led to the development and commercial availability of highly practicable techniques. These new techniques, which utilise different aspects of the pulse pressure waveform, are simple, reliable and reflect both large and small vessel stiffness. They offer new tools for identifying patients at increased risk of developing cardiovascular complications including those with established diabetes. In this article we introduce the reader to the concepts of arterial stiffness, the significance of arterial stiffness for diabetes, and the new techniques that may potentially be useful for clinical researchers or practitioners.
Med Sci Monit 2003 May
PMID:Measurement and application of arterial stiffness in clinical research: focus on new methodologies and diabetes mellitus. 1276 66

Over the past three decades, we have witnessed an improvement of survival in those patients with the trio of metabolic syndrome, prediabetes, and overt type 2 diabetes mellitus. Revolutionary changes in technology and an improved understanding of the mechanisms involved in acute coronary syndromes have resulted in this observation. Due to advances in coronary care, we are currently at a crossroads, wherein, the mortality from acute cardiovascular events have been declining and the mortality associated with this trio has been increasing due to congestive heart failure (CHF). This intersect between the two causes of death represent a challenge for the future, as the numbers of patients with this deadly trio are undergoing exponential growth not only in the U.S. but also abroad as more countries undergo urbanization and adopt a western-type lifestyle of over nutrition and under exercise. Thus, we live to die another day. There are multiple metabolic toxicities in this toxic trio, which predispose to an increase in reactive oxygen species and resultant redox stress within the vascular intima and myocardium. By aggressively reducing the elevated substrates producing reactive oxygen species we may be able to restore our individual, endogenous, potent, antioxidant (antiredoxidant) network. Appropriately, we need to examine the mechanisms that result in the development and transition from diastolic and systolic dysfunction to the clinical syndrome of overt CHF with its inherent increase in morbidity and mortality.
Med Sci Monit 2003 Jul
PMID:Myocardial redox stress and remodeling in metabolic syndrome, type 2 diabetes mellitus, and congestive heart failure. 1288 68

In addition to their stimulatory action on neuronal differentiation and survival, the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) improve glucose and lipid metabolism and control energy balance and feeding behavior. These latter activities are referred to here as the metabotrophic potential of neurotrophins. We recently reported that circulating NGF and BDNF levels are reduced in the metabolic syndrome and in acute coronary syndromes, and that the tissue content of NGF is reduced in atherosclerotic coronary arteries. Thus we hypothesize that a metabotrophic deficit due to reduction of neurotrophin availability may be implicated in the pathogenesis of obesity and related metabolic diseases, such as metabolic syndrome, type 2 diabetes, and atherosclerosis. The metabotrophic deficit hypothesis also considers metabolism-related beneficial effects exerted by other neurotrophic factors, particularly ciliary neurotrophic factor, leukemia inhibitory factor, and bone morphogenetic proteins.
Med Sci Monit 2003 Oct
PMID:Metabotrophic potential of neurotrophins:implication in obesity and related diseases? 1452 35

Recent research has demonstrated that ambulatory BP is a superior means to predict cardiovascular outcomes in treated patients with hypertension. Ambulatory blood pressure monitoring has been utilized to evaluate the efficacy of all anti-hypertensive drugs including the angiotensin II receptor blockers (ARBs). This paper reviews the relationship of clinic and ambulatory blood pressures to cardiovascular outcomes and the benefits of ARBs to maximize improvement in clinical end-points in patients with hypertension. Clinical trial evidence has demonstrated that ARBs are a preferred class in patients with electrocardiographic evidence of left ventricular hypertrophy, in patients with type 2 diabetes, patients with chronic kidney disease, and in individuals with heart failure who have clinically relevant intolerability to angiotensin converting enzyme inhibitors. In addition, there is increasing evidence from clinical trials that many of the ARBs provide adequate 24 h blood pressure control alone or in combination with other anti-hypertensive agents. We conclude that the combination of event reduction from large-scale clinical trials, adequate 24 h BP reduction, and improved tolerability compared to most other classes of anti-hypertensive agents, make the ARBs a suitable initial treatment for patients with hypertension.
Blood Press Monit 2003 Oct
PMID:Evaluation of the 24 h effects of the angiotensin II receptor blockers: means to improve cardiovascular outcomes? 1462 72

Both omega-6 and omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) modulate TH1 and TH2 cell generation, their cytokine production, and cell proliferation and thus may serve as endogenous anti-inflammatory molecules. LCPUFAs suppress the production of tumor necrosis factor-alpha (TNF-alpha) (and so also of OX40, since it belongs to the family of TNFR) and the expression of Bcl-2, suggesting that these fatty acids have the ability to prevent/suppress autoimmune diseases. Human breast milk contains substantial amounts of both omega-3 and omega-6 fatty acids. This indicates that LCPUFAs present in human breast milk suppress the levels of OX40 and decrease the expression of Bcl-xL and Bcl-2 on exposure to self-antigens and thus, protects against the development of autoimmune diseases in later life. In view of this, I propose that supplementation of appropriate amounts of LCPUFAs during perinatal period protects against atopy, asthma, auto-immune diseases, type 1 and type 2 diabetes mellitus, hypertension, coronary heart disease, metabolic syndrome X, lymphomas, leukemias and other cancers, schizophrenia, depression and other adult diseases in which low-grade systemic inflammation plays a significant role. It is also likely that perinatal supplementation of LCPUFAs in adequate amounts modulates the expression of genes concerned with immune response, angiogenesis, central osmo/sodium and glucose sensors etc. This renders various tissues and organs including T cells and macrophages, endothelial cells, hypothalamic neurons, and various cardiovascular tissues to be able to counteract the pathological mechanisms that tend to induce various adult diseases by blunting the inflammatory responses in those who received adequate amounts of LCPUFAs during the perinatal period compared to those who did not.
Med Sci Monit 2004 May
PMID:Perinatal supplementation of long-chain polyunsaturated fatty acids, immune response and adult diseases. 1511 76

Diabetic polyneuropathy (DPN) is the most common complication of diabetes and may frequently be the presenting symptom in type 2 diabetes mellitus (T2DM). Metabolic syndrome and T2DM are associated with multiple metabolic toxicities. These substrate toxicities support the formation of reactive oxygen species (ROS), which are so damaging to cells, tissues and organs and play an important role in the development of multiple diabetic complications. The importance of redox stress (ROS) and their effect on the neuronal unit are discussed. There are at least 5 major pathways involved in the development of DPN: metabolic, vascular, immunologic-autoimmune, neurohormonal growth factor deficiency, and extracellular matrix neuronal unit remodeling. Each of these five pathways are reviewed and related to neural redox stress and the role of ROS. The identification of the toxic substrates (A-FLIGHT acronym), earlier diagnosis of T2DM at the stage of impaired glucose tolerance or impaired fasting glucose, and aggressive global risk reduction with the use of a simple RAAS acronym will assist the clinician in slowing the natural progressive history, and possibly preventing the complications associated with DPN. The pain, foot ulceration, limb loss, organ dysfunction, and the associated morbidity and financial burden all contribute to the need for a better understanding of DPN and the role of redox stress and global risk reduction.
Med Sci Monit 2004 Dec
PMID:Neural redox stress and remodeling in metabolic syndrome, type 2 diabetes mellitus, and diabetic neuropathy. 1556 93

Glucagon-like peptide-1 (GLP-1) is produced both in the human and rat intestine and brain. The release of GLP-1 into the blood is mediated by factors of neural and hormonal origin and is stimulated by the presence of nutrients in the digestive tract, while the enzyme dipeptidyl peptidase IV and the kidneys are responsible for, respectively, the rapid degradation and excretion of the hormone. Peripherally secreted GLP-1 enhances insulin synthesis and release and maintains the normal anatomical status of pancreatic islets. Diminished GLP-1 response to ingested food, associated with attenuated insulin release and glucose intolerance, was found in non-insulin-dependent diabetes mellitus. GLP-1 replacement in diabetic subjects normalized these parameters, thus indicating a role for this peptide in the pathogenesis of type 2 diabetes. GLP-1 might also be involved in the pathophysiology of obesity and stress to some extent. Both peripheral and central GLP-1 are probably involved in the control of feeding centers as an anorexic agent. GLP-1 affects the activity of the hypothalamo-pituitary-adrenal axis both under basal and stress conditions, including taste aversion learning. Hence, GLP-1-dependent pathophysiological mechanisms may participate in the pathogenesis of the most common metabolic and behavioral disorders.
Med Sci Monit 2005 Aug
PMID:Physiology and pathophysiology of glucagon-like peptide-1 (GLP-1): the role of GLP-1 in the pathogenesis of diabetes mellitus, obesity, and stress. 1604 95

Dyslipemia is a clear risk factor (RF) for ischemic heart disease and peripheral artery disease, but its relation with ischemic stroke (IS) is not so clear. HMG-CoA reductase inhibitor drugs or statins (simvastatin, atorvastatin, pravastatin) reduce the relative risk of IS by between 18 and 51% in patients with IHD, in patients with high vascular disease risk and in hypertensive patients with other RFs, acute coronary syndrome, and type 2 diabetes mellitus. According to the guidelines for use, statins are indicated in the majority of patients with IS since the risk is equivalent to that of IHD or high vascular disease risk. In view of the existing clinical evidence of benefit, it would not seem unreasonable to proceed with treatment of patients using statins while awaiting specific studies justifying their use. The non-lipid-lowering mechanisms of the statins and results of studies, such as the Heart Protection Study, provide evidence for widening the indications of statins beyond the prevention of dyslipemia, as a new therapeutic approach in the prevention of IS in patients with plasma levels of total cholesterol or low density lipoproteins currently considered within the normal distribution. The neuroprotective role, which these drugs may play in the acute phase of cerebral ischemia, remains to be clarified, but very recent evidence suggests that such patients may also benefit.
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PMID:Lipids and stroke: the opportunity of lipid-lowering treatment. 1632 54

The pharmacokinetic disposition of metformin in late pregnancy was studied together with the level of fetal exposure at birth. Blood samples were obtained in the third trimester of pregnancy from women with gestational diabetes or type 2 diabetes; 5 had a previous diagnosis of polycystic ovary syndrome. A cord blood sample also was obtained at the delivery of some of these women, and also at delivery of others who had been taking metformin during pregnancy but from whom no blood had been taken. Plasma metformin concentrations were assayed by a new, validated, reverse-phase HPLC method. A 2-compartment, extravascular maternal model with transplacental partitioning of drug to a fetal compartment was fitted to the data. Nonlinear mixed-effects modeling was performed in NONMEM using FOCE with INTERACTION. Variability was estimated using logarithmic interindividual and additive residual variance models; the covariance between clearance and volume was modeled simultaneously. Mean (range) metformin concentrations in cord plasma and in maternal plasma were 0.81 (range, 0.1-2.6) mg/L and 1.2 (range, 0.1-2.9) mg/L, respectively. Typical population values (interindividual variability, CV%) for allometrically scaled maternal clearance and volume of distribution were 28 L/h/70 kg (17.1%) and 190 L/70 kg (46.3%), giving a derived population-wide half-life of 5.1 hours. The placental partition coefficient for metformin was 1.07 (36.3%). Neither maternal age nor weight significantly influenced the pharmacokinetics. The variability (SD) of observed concentrations about model-predicted concentrations was 0.32 mg/L. The pharmacokinetics were similar to those in nonpregnant patients and, therefore, no dosage adjustment is warranted. Metformin readily crosses the placenta, exposing the fetus to concentrations approaching those in the maternal circulation. The sequelae to such exposure, eg, effects on neonatal obesity and insulin resistance, remain unknown.
Ther Drug Monit 2006 Feb
PMID:Population pharmacokinetics of metformin in late pregnancy. 1641 96


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