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

Prevalence of obesity in the United Kingdom has tripled in the last 20 years and this is driving an epidemic of type 2 diabetes. Indeed, today the vast majority of patients with type 2 diabetes are overweight or obese. Effective weight management leading to modest weight loss to the order of 5-10% of body weight can lead to significant clinically meaningful benefits provided it can be maintained. Thus weight management can lead to improved glycaemic control, better blood pressure control and lipid control in addition to other benefits. Management of diabetic patients who are obese requires management also of other associated co-morbid conditions and it is important to ensure that glycaemic control does not deteriorate during weight management. An integrated approach to weight management in the diabetic patient is recommended which helps to promote lifestyle modification for all patients. Drug therapy may be appropriate for many obese patients who do not reach target weight loss with lifestyle modification alone. Surgery should be reserved for those wfth BMI >40 only after failed medical therapy.
 ...
PMID:The management of obesity in type 2 diabetes mellitus. 1236 21

Adequate control of blood sugar has been repeatedly shown to translate into reductions in diabetic complications. Although insulin therapy in patients with type 2 diabetes can achieve and maintain near-normal glycemic goals associated with reductions in microvascular and macrovascular end points, it is often reserved for the later stages of management of these patients because of real or perceived concerns; these include fear and anxiety about worsening diabetes, failure of self-management, loss of quality of life, the pain of self-injection, and the possibility of multiple daily injections. Risks of hypoglycemia, weight gain, and cardiovascular disease may be concerns of physicians, but these risks are either manageable or, in the case of cardiovascular disease, unfounded. Taken together, the barriers to insulin therapy frequently compel physicians to consider it a treatment of last resort. Some of the more common barriers have been addressed through device options such as insulin pens and jet injectors, which may improve convenience but do not alleviate pain and discomfort. Transdermal delivery options using iontophoresis or ultrasound are in early stages of development, but methods based on transmucosal delivery-including buccal, nasal, and pulmonary routes-are further advanced. In particular, recent evidence shows that pulmonary forms of insulin are as safe and effective as rapid-acting injected insulin, and are well accepted by patients even over long-term periods of use. These innovative delivery systems may help overcome the barriers to insulin use.
 ...
PMID:Evaluation of alternative strategies for optimizing glycemia: progress to date. 1243 59

Neuropeptide Y (NPY) in the central nervous system is a major regulator of food consumption and energy homeostasis. It also regulates blood pressure, induces anxiolysis, enhances memory retention and affects circadian rhythms, as well as modulates hormone release. Five Y receptors are known that mediate the action of NPY and its two other family members, peptide YY and pancreatic polypeptide. Increased NPY signaling due to elevated NPY expression in the hypothalamus leads to the development of obesity and its related phenotypes, type 2 diabetes and cardiovascular disease. Dysregulation in NPY signaling also causes alterations in bone formation. The large number of Y receptors has made it difficult to delineate their individual contributions to these physiological processes. However, recent studies analyzing Y-receptor knockout models have started to unravel some of the individual functions of these Y receptors. Particularly, the use of conditional knockout models has made it possible to pinpoint a specific functional contribution to an individual Y receptor in a particular location. From these studies, the predominantly presynaptically expressed Y2 receptor in the arcuate nucleus of the hypothalamus has emerged as a prime candidate for mediating satiety as well as a candidate for regulating bone formation. (c) 2002 Prous Science. All rights reserved.
 ...
PMID:Hypothalamic Y2 Receptors: Central Coordination of Energy Homeostasis and Bone Mass Regulation. 1267 89

Current therapy for type 2 diabetes relies mainly on several approaches intended to reduce hyperglycemia. Several major studies have shown that the appropriate long-term management of glycemia is critical to reduce the risk of vascular complications. Thus, the goal of future treatments of the disease will be to intervene when early clinical signs, such as impaired glucose tolerance, first manifest and to exploit the knowledge of the molecular mechanisms of insulin secretion by the beta-cells as well as insulin action in its target tissues to develop new drugs to accomplish a tight glycemic control. (c) 2002 Prous Science. All rights reserved.
 ...
PMID:Molecular Mechanisms Leading to the Development of Diabetes. 1267 30

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the nuclear hormone receptor superfamily. PPAR has three isoforms designated PPARalpha, PPARbeta/delta and PPARgamma. Although all three isoforms share similar protein sequence and structure, they differ in tissue distribution, ligand selectivity and biological actions. As ligand-activated transcription factors, PPARs participate in a broad spectrum of biological processes, including cell differentiation, energy balance, lipid metabolism, insulin sensitivity, bone formation, inflammation and tissue remodeling. PPARalpha is the molecular target of the hypolipidemic fibrates including benzafibrate and clofibrate. In general, PPARalpha is expressed in tissues with high mitochondrial and beta-oxidation activity corresponding to its role in regulating lipid metabolism. In contrast, PPARbeta/delta is ubiquitously expressed and has been suggested to be involved in bone formation, oocyte implantation and lipid catabolism. PPARbeta/delta ligands have been found to effectively improve lipid profile and insulin resistance. PPARgamma is a key player in adipogenesis and plays an important role in diverse cellular processes such as cell cycle regulation, cell differentiation and insulin sensitivity. Synthetic PPARgamma ligands, including thiazolidinediones and non-thiazolidinedione compounds, have been shown to increase insulin sensitivity and improve hyperglycemia in insulin resistance and noninsulin dependent diabetes mellitus. The biological effects of PPARs indicate that both agonists and antagonists for PPARs may provide new therapeutic options in a variety of human diseases. (c) 2002 Prous Science. All rights reserved.
 ...
PMID:The Role of PPARs in the Transcriptional Control of Cellular Processes. 1267 57

Type 2 diabetes mellitus is a chronic metabolic disorder associated with high morbidity and mortality from long-term microvascular and macrovascular complications. Evidence from randomized controlled trials indicates that aggressive treatment directed at improving glycemic control reduces the incidence of diabetes-related microvascular complications. Traditionally, oral monotherapy for type 2 diabetes is initiated when diet and exercise do not control hyperglycemia, followed by the sequential, stepwise addition of oral agents as glycemic control deteriorates. Insulin is the last therapeutic option used, generally reserved for advanced stages of the disease when multiple oral combination treatment fails. Despite a better understanding of the pathophysiologic disease mechanisms in the past decade, the expanded armamentarium of targeted oral antidiabetic drugs, and the conclusive evidence of the benefits of stringent glycemic control, actual treatment outcomes in clinical practice remain suboptimal relative to established treatment goals (glycosylated hemoglobin A1c level <7%). Earlier detection and aggressive treatment are critical to address the natural progression of diabetes because multiple defects (insulin resistance, insulin insufficiency, glucotoxicity, and lipotoxicity) and vascular complications may be present at the time of diagnosis. Acknowledging the inadequacy of traditional strategies and underscoring the importance of insulin as an integral part of the therapeutic armamentarium, clinical trends are moving toward earlier use of insulin combined with 1 or more oral agents. Such strategies can address the multiple abnormalities present early in the disease course and may restore optimal control. A new treatment paradigm for patients with type 2 diabetes to achieve and maintain near-normal glycemic control is warranted.
 ...
PMID:Pharmacological management of type 2 diabetes mellitus: rationale for rational use of insulin. 1268 92

Nateglinide is a short-acting, pancreatic, beta-cell-selective, K(ATP) potassium channel blocker that improves overall glycemic control in type 2 diabetes. Although nateglinide's mechanism of action is related to that of sulphonyl-ureas and repaglinide, important differences do exist. Nateglinide binds rapidly to the sulfonylurea SUR1 receptor with a relatively low affinity, and it dissociates from it extremely rapidly in a manner of seconds. This rapid association and dissociation gives nateglinide a unique "fast on-fast off" effect. Thus, nateglinide has a rapid onset and short duration of action stimulating insulin secretion in vivo and providing good control of postprandial hyperglycemia when taken immediately prior to meals. The rapid action of nateglinide on the beta cells stimulates and restores the normal physiological first and early phase of insulin secretion, consequently reducing postprandial hyperglycemia. This hypoglycemic effect of nateglinide leads to improved glycemic control, while the short duration avoids delayed hyperinsulinemia and hypoglycemia after meals. Nateglinide is not a sulfonylurea, but it shares the mechanism of action of commonly used oral hypoglycemic agents such as glibenclamide and glipizide. Like the recently introduced, short-acting agent, repaglinide, it does not incorporate a sulfonylurea moiety. However, nateglinide's effects on insulin secretion and glycemic control differ significantly from the sulfonylureas and repaglinide in that it preferentially stimulates acute phase insulin, better controls postprandial glucose excursions and spikes, and causes less hyperinsulinemia and hypoglycemia. Compounds with such a profile should not only achieve improved overall glucose control, but also reduce the risk of vascular complications which is the most important feature of nateglinide. Clinical studies with nateglinide have confirmed that it acts rapidly and both restores insulin release and attenuates the postprandial glucose spike. Nateglinide is both effective and well tolerated in the treatment of type 2 diabetes. The reported overall profile of adverse effects appears to be superior to that of other K(ATP) potassium channel blockers, the glucose modulator metformin and PPARgamma agonists such as troglitazone. Clinical comparisons of these agents have shown nateglinide to be more effective in attenuating postprandial glucose than any other oral hypoglycemic agent, and that treatment with both nateglinide and metformin provides additive effects that afford improved control of plasma glucose levels. The administration regimen for nateglinide, immediately prior to meals, also facilitates patient compliance. (c) 2001 Prous Science. All rights reserved.
 ...
PMID:Nateglinide: A structurally novel, short-acting, hypoglycemic agent. 1276 27

Traditionally, practitioners have reserved insulin therapy for patients with type 2 diabetes until diet, exercise, and treatment with oral agents have failed to maintain glycemic control. Increasing evidence, however, supports advancing insulin therapy earlier in treating diabetes, not only to normalize glycemic control and emulate normal physiologic insulin secretion, but also to delay or prevent disease-associated comorbidity.
 ...
PMID:Type 2 diabetes: treat to target. 1472 86

The oral glucose tolerance test (OGTT) has been widely used for the diagnosis of diabetes mellitus, gestational diabetes or impaired glucose tolerance. However, since 1997, OGTT is not considered anymore as the first choice test for the diagnosis of diabetes mellitus or impaired glucose tolerance, being replaced by fasting glycaemia. Numerous studies, however, stressed the discrepancies between these two diagnostic approaches, so that OGTT still has defenders as a useful tool to diagnose diabetes. Besides, emphasis has been recently put on both postprandial hyperglycaemia, considered as a major cardiovascular risk factor, and impaired glucose tolerance as a predictor of progression toward overt type 2 diabetes, two parameters well addressed by the OGTT. Thus, even if the place to be reserved to the OGTT is controversial, in our opinion, this test still has a place in clinical biology.
 ...
PMID:[How I explore ... the controversy concerning the role of oral glucose tolerance test in clinical practice]. 1474 99

Early detection of latent autoimmune diabetes in adults (LADA) is important in that the earlier insulin therapy is initiated, the greater the preservation of pancreatic beta cells. This study assessed whether a random C-peptide level is an effective screening test for LADA. Random C-peptide levels were measured in 39 subjects with LADA and 39 subjects with type 2 diabetes who were matched for age, race, gender, and duration of diabetes. LADA was definitively diagnosed by the presence of antiglutamic acid decarboxylase antibodies. The mean C-peptide level in the LADA group was 1.0 +/- 0.2 ng/mL and 5.1 +/- 0.4 ng/mL in the group with type 2 diabetes. Only 1 LADA subject had a C-peptide level above the normal range, and all subjects with type 2 diabetes had a C-peptide level within or above the normal range. LADA can be ruled out in adult-onset diabetes by the presence of elevated C-peptide. The more expensive testing for anti-GAD antibodies to definitively diagnose LADA should be reserved for patients who on screening have a low or normal random C-peptide level.
 ...
PMID:The role of C-peptide levels in screening for latent autoimmune diabetes in adults. 1526 24


<< Previous 1 2 3 4 5 6 Next >>