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)

The purpose of this study was to evaluate whether etching, bonding and filling with composite a cavity increase tooth resistance to fracture, considering that in posterior teeth stressed cusps are likely to bend. MOD conservative cavities (isthmus width/intercuspal distance = 0.25) were made in 10 extracted upper premolars, filled with P30 (3M) and tested by using a MTS machine. A metal bar (5 mm in diameter and 10 mm in length) was employed to load the cusps and their fracture resistance was recorded. The control group consisted of 16 extracted upper premolars: MOD cavities were made in only 9 teeth, then filled with amalgam. As a result, MOD cavities treated with Scotchbond, filled with P30 and tested by a MTS machine don't seem to be more resistant to a static load than cavities filled with amalgam.
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PMID:[Resistance of cavity walls of composite filled teeth]. 182 68

Non-insulin-dependent diabetes mellitus (NIDDM), or type II diabetes is rapidly becoming one of the most common chronic disease in the United States and worldwide, with more than 7% of the adult population affected. NIDDM is even more common in the elderly and in minority population including Hispanic Americans, African Americans, Asian and Pacific Island Americans, and Native Americans. In these populations, NIDDM may be present in 10% to as much as 50% of the adult population. However diagnosed NIDDM is only the tip of the iceberg of an epidemic of glucose intolerance. Impaired glucose intolerance (IGT) is even more prevalent that NIDDM; and in addition to be a major risk factor for the development of NIDDM, IGT is associated with an increased risk of macrovascular disease. Recent advances in research into the etiology and natural history of diabetes have increased the knowledge to such an extent that primary prevention of NIDDM is becoming a reality. This primary prevention can be implemented a) through a population strategy, i.e. changing the lifestyle and environmental determinants that are known to be risk factors for diabetes, and b) through high-risk strategy, i.e. targeting preventive measures only at those specific individuals or groups that are at high risk for the future development of NIDDM. The latter is the strategy of the Diabetes Prevention Program (DDP), a clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Disease in USA. Twenty five centers were selected to participate in this program. The purpose of DPP is prevent or delay the development of NIDDM in those persons who are at high risk because they have IGT. DPP will also evaluate if the interventions selected to prevent the development of NIDDM can decrease the frequency of cardiovascular events and the occurrence and magnitude of the cardiovascular risk factors that accompany NIDDM and IGT. Four thousand volunteers will be recruited from populations known to be at particular high risk fo IGT and NIDDM including the following: elderly, overweight individuals, persons with family history of NIDDM, women with history of gestational diabetes, and minority populations. In order to be eligible, persons who are older than 25 years will have to demonstrate IGT with plasma glucose levels 100-139 mg/dl fasting and 140-199 mg/dL two hours after a 75 g OGTT. Three study intervention were selected based on their potential efficacy in ameliorating abnormal glucose metabolism in IGT and on their safety and tolerable profile of side-effects. The interventions include: intensive lifestyle intervention which focuses on a healthy diet to achieve and maintain at least a 7% loss of body weight and an increase in caloric expenditure of at least 700 kcal per week. The drug therapy interventions include the biguanide metformin and the thiazolidinedione troglizatone. Standard life-style recommendations, which include conventional instructions regarding diet and exercise, will be provided to all participants, including a placebo treated group which will serve as the control group for the study. After randomization, participants will have quarterly evaluations and have, in addition, a fasting plasma glucose at semi-annual visits and a 75 g OGTT at annual visits. All participants will be followed for three years after the study-wide closing date for recruitment, resulting in 3 to 6 years of participant follow-up. The primary outcome is the development of NIDDM according to WHO criteria (fasting plasma glucose level 140 mg/dL or 2-hour plasma glucose 200 mg/dL after a 75 g OGTT). Secondary outcome will focus en cardiovascular disease and its risk factors and change of glycemia, insulin secretion and sensitivity, obesity, physical activity and nutrient intake, quality of life, and the occurrence of adverse events.
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PMID:[Steps toward the primary prevention of type II diabetes mellitus. Various epidemiological considerations]. 923 72

Packable resin composites may offer improved properties and clinical performance over conventional resin composites or dental amalgam. This in vitro study examined the cuspal stiffness of molars restored with a packable resin composite, a conventional posterior microfilled resin composite and amalgam. Forty-eight intact caries-free human third molars were distributed into four treatment groups (n=12) so that the mean cross-sectional areas of all groups were equal. Standardized MOD cavity preparations were made and specimens restored using one of four restorative materials: (1) a spherical particle amalgam (Tytin); (2) Tytin amalgam with a dentin adhesive liner (OptiBond Solo); (3) a conventional microfilled posterior resin composite (Heliomolar); (4) a packable posterior resin composite (Prodigy Posterior). Cuspal stiffness was measured using a Bionix 200 biomaterials testing machine (MTS). Specimens were loaded vertically to 300 N at a crosshead speed of 1.0 mm/minute. Stiffness was measured at 10 intervals: (1) prior to cavity preparation (intact); (2) following cavity preparation, but before restoration; (3) seven days after restoration; then (4) 1, 2, 3, 4, 5, 6 and 12 months after restoration. All specimens were stored at 37 degrees C in deionized water throughout the study and thermocycled (5 degrees/55 degrees C; 2000 cycles) monthly for 12 months. Repeated Measures ANOVA revealed significant differences among treatment groups over time (p<0.0001). Cavity preparation reduced cuspal stiffness by more than 60%. At 12 months, the cuspal stiffness of restored teeth was, on average, 58% that of intact specimens. Neither the packable nor the conventional resin composite increased cuspal stiffness over that of amalgam.
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PMID:The influence of a packable resin composite, conventional resin composite and amalgam on molar cuspal stiffness. 1221 72

GLP-1 is a peptide hormone from the intestinal mucosa. It is secreted in response to meal ingestion and normally functions in the so-called ileal brake i. e. inhibition of upper gastrointestinal motility and secretion when nutrients are present in the distal small intestine. It also induces satiety and promotes tissue deposition of ingested glucose by stimulating insulin secretion. Thus, it is an essential incretin hormone. In addition, the hormone has been demonstrated to promote insulin biosynthesis and insulin gene expression and to have trophic effects on the beta cells. The trophic effects include proliferation of existing beta cells, maturation of new cells from duct progenitor cells and inhibition of apoptosis. Furthermore glucagon secretion is inhibited. Because of these effects, the hormone effectively improves metabolism in patients with type 2 diabetes mellitus. However, continuous administration of the peptide is necessary because of an exceptionally rapid rate of degradation catalyzed the enzyme dipeptidyl peptidase IV. With inhibitors of this enzyme, it is possible to protect the endogenous hormone and thereby elevate both fasting and postprandial levels of the active hormone. This leads to enhanced insulin secretion and glucose turnover. But will DPP-IV inhibition enhance all effects of the endogenous peptide? The mode of action of GLP-1 is complex involving also interactions with sensory neurons and the central nervous system, where a DPP-IV mediated degradation does not seem to occur. Therefore, it is as yet uncertain wether DDP-IV inhibitors will affect gastrointestinal motility, appetite and food intake. Even the effects of GLP-1 effects on the pancreatic islets may be partly neurally mediated and therefore uninfluenced by DPP-IV inhibition.
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PMID:Implementation of GLP-1 based therapy of type 2 diabetes mellitus using DPP-IV inhibitors. 1267 49

With increasing rates of obesity driving the incidence of type 2 diabetes and cardiovascular diseases to epidemic levels, understanding of the biology of adipose tissue expansion is a focus of current research. Identification and characterization of secreted proteins of the adipose tissue could provide further insights into the function of adipose tissue and might help to therapeutically influence the development of obesity and associated metabolic disorders. In the present study, we identified human epidermal growth factor-like domain multiple-6 (EGFL6) as an adipose tissue-secreted protein. EGFL6 expression in human subcutaneous adipose tissue significantly increased with obesity and decreased after weight loss. Further, expression and secretion of EGFL6 increased with in vitro differentiation of human preadipocytes, suggesting that mature adipocytes are the main source of EGFL6. Containing epidermal growth factor (EGF)-like repeats, an Arg-Gly-Asp (RGD) integrin binding motif and a mephrin, A5 protein and receptor protein-tyrosine phosphatase mu (MAM) domain, EGFL6 was suggested to be an extra-cellular matrix protein. Recombinant human EGFL6 protein mediated cell adhesion of human adipose tissue-derived stromal vascular cells (AD-SVC) in an RGD-dependent manner. FACS analyses revealed specific binding of the protein to the cell surface of AD-SVC with the binding being predominantly mediated by the EGF-like repeats. Recombinant EGFL6 enhanced proliferation of human AD-SVC as measured by MTS assay and [(14)C]-thymidine incorporation. These results indicate that human EGFL6 is a paracrine/autocrine growth factor of adipose tissue up-regulated in obesity and potentially involved in the process of adipose tissue expansion and the development of obesity.
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PMID:EGFL6 is increasingly expressed in human obesity and promotes proliferation of adipose tissue-derived stromal vascular cells. 2057 86

Patients with type 2 diabetes mellitus (T2DM) are generally treated with many pharmacological compounds and are exposed to a high risk of drug-drug interactions. Indeed, blood glucose control usually requires a combination of various glucose-lowering agents, and the recommended global approach to reduce overall cardiovascular risk generally implies administration of several protective compounds, including HMG-CoA reductase inhibitors (statins), antihypertensive compounds and antiplatelet agents. New compounds have been developed to improve glucose-induced beta-cell secretion and glucose control, without inducing hypoglycaemia or weight gain, in patients with T2DM. Dipeptidylpeptidase-4 (DPP-4) inhibitors are novel oral glucose-lowering agents, which may be used as monotherapy or in combination with other antidiabetic compounds, metformin, thiazolidinediones or even sulfonylureas. Sitagliptin, vildagliptin and saxagliptin are already on the market, either as single agents or in fixed-dose combined formulations with metformin. Other compounds, such as alogliptin and linagliptin, are in a late phase of development. This review summarizes the available data on drug-drug interactions reported in the literature for these five DDP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, alogliptin and linagliptin. Possible pharmacokinetic interferences have been investigated between each of these compounds and various pharmacological agents, which were selected because there are other glucose-lowering agents (metformin, glibenclamide [glyburide], pioglitazone/rosiglitazone) that may be prescribed in combination with DPP-4 inhibitors, other drugs that are currently used in patients with T2DM (statins, antihypertensive agents), compounds that are known to interfere with the cytochrome P450 (CYP) system (ketoconazole, diltiazem, rifampicin [rifampin]) or with P-glycoprotein transport (ciclosporin), or agents with a narrow therapeutic safety window (warfarin, digoxin). Generally speaking, almost no drug-drug interactions or only minor drug-drug interactions have been reported between DPP-4 inhibitors and any of these drugs. The gliptins do not significantly modify the pharmacokinetic profile and exposure of the other tested drugs, and the other drugs do not significantly alter the pharmacokinetic profile of the gliptins or exposure to these. The only exception concerns saxagliptin, which is metabolized to an active metabolite by CYP3A4/5. Therefore, exposure to saxagliptin and its primary metabolite may be significantly modified when saxagliptin is coadministered with specific strong inhibitors (ketoconazole, diltiazem) or inducers (rifampicin) of CYP3A4/5 isoforms. The absence of significant drug-drug interactions could be explained by the favourable pharmacokinetic characteristics of DPP-4 inhibitors, which are not inducers or inhibitors of CYP isoforms and are not bound to plasma proteins to a great extent. Therefore, according to these pharmacokinetic findings, which were generally obtained in healthy young male subjects, no dosage adjustment is recommended when gliptins are combined with other pharmacological agents in patients with T2DM, with the exception of a reduction in the daily dosage of saxagliptin when this drug is used in association with a strong inhibitor of CYP3A4/A5. It is worth noting, however, that a reduction in the dose of sulfonylureas is usually recommended when a DPP-4 inhibitor is added, because of a pharmacodynamic interaction (rather than a pharmacokinetic interaction) between the sulfonylurea and the DPP-4 inhibitor, which may result in a higher risk of hypoglycaemia. Otherwise, any gliptin may be combined with metformin or a thiazolidinedione (pioglitazone, rosiglitazone), leading to a significant improvement in glycaemic control without an increased risk of hypoglycaemia or any other adverse event in patients with T2DM. Finally, the absence of drug-drug interactions in clinical trials in healthy subjects requires further evidence from large-scale studies, including typical subjects with T2DM - in particular, multimorbid and geriatric patients receiving polypharmacy.
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PMID:Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. 2069 Jul 81

Janumet(TM,) a fixed dose combination of sitagliptin/metformin HCL manufactured by Merck Pharmaceuticals, has received US Food and Drug Administration approval for treatment of patients with type 2 diabetes, that are inadequately controlled, either by sitagliptin or metformin alone or together in free-dose combination form. Sitagliptin, an inhibitor of the enzyme DDP-4, assists patients with type 2 diabetes mellitus to achieve glycemic control. It has been shown to be safe and effective at 100 mg daily doses. The effect of giving sitagliptin in combination with metformin is thought to have a complimentary and possibly additive effect on glycemic control.
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PMID:Fixed-dose combination of sitagliptin and metformin for the treatment of type 2 diabetes. 2143 26

Inhibitors of type 4 dipeptidyl peptidase (DDP-4) were developed and approved for the oral treatment of type 2 diabetes. Its mode of action is to inhibit the degradation of incretins, such as type 1 glucagon like peptide (GLP-1), and GIP. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells and suppresses glucagon release from alpha-cells, thereby improving glucose control. Besides its action on the pancreas type 1 glucagon like peptide has direct effects on the heart, vessels and kidney mainly via the type 1 glucagon like peptide receptor (GLP-1R). Moreover, there are substrates of DPP-4 beyond incretins that have proven renal and cardiovascular effects such as BNP/ANP, NPY, PYY or SDF-1 alpha. Preclinical evidence suggests that DPP-4 inhibitors may be effective in acute and chronic renal failure as well as in cardiac diseases like myocardial infarction and heart failure. Interestingly, large cardiovascular meta-analyses of combined phase II/III clinical trials with DPP-4 inhibitors point all in the same direction: a potential reduction of cardiovascular events in patients treated with these agents. A pooled analysis of pivotal phase III, placebo-controlled, registration studies of linagliptin further showed a significant reduction of urinary albumin excretion after 24 weeks of treatment. The observation suggests direct renoprotective effects of DPP-4 inhibition that may go beyond its glucose-lowering potential. Type 4 dipeptidyl peptidase inhibitors have been shown to be very well tolerated in general, but for those excreted via the kidney dose adjustments according to renal function are needed to avoid side effects. In conclusion, the direct cardiac and renal effects seen in preclinical studies as well as meta-analysis of clinical trials may offer additional potentials - beyond improvement of glycemic control - for this newer class of drugs, such as acute kidney failure, chronic kidney failure as well as acute myocardial infarction and heart failure.
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PMID:Renal and cardiac effects of DPP4 inhibitors--from preclinical development to clinical research. 2294 20

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antihyperglycemic drugs for the treatment of type 2 diabetes. They are also called "incretins" because they act inhibiting the degradation of endogenous incretin hormones, in particular glucagon-like peptide-1 that mediates their main metabolic effects. DPP-4 is a ubiquitous protease that regulates not only glucose and lipid metabolism, but also exhibits several systemic effects at different site levels. DPP-4 inhibition improves endothelial function, reduces the pro-oxidative and pro-inflammatory state, and exerts renal effects. These actions are mediated by different DPP-4 ligands, such as cytokines, growth factors, and neurotransmitters. Clinical and experimental studies have demonstrated that DPP-4 inhibitors are effective in protecting cardiac, renal and vascular systems, through antiatherosclerotic and vasculoprotective mechanisms. For these reasons, DDP-4 inhibitors should be considered "cardiovascular" as well as antidiabetic drugs. Clinical trials aimed at demonstrating that DPP-4 inhibitors are effective in reducing cardiovascular events, independent of their antihyperglycemic action, are ongoing. These trials will also provide necessary information on their safety.
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PMID:[Towards evidence-based medicine: large-scale intervention trials with dipeptidyl peptidase-4 inhibitors]. 2325 26

Over the last decades, an escalating rate of type 2 diabetes has paralleled an epidemic rise in the prevalence of obesity. Both diabetes and obesity confer an increased risk of cardiovascular comorbidities, including hypertension, coronary artery disease and stroke. Vascular dysfunction, represented by impaired endothelial release of vasodilator substances or defective smooth muscle vasodilator reactivity, is the early stage of the process leading to atherosclerosis and a common finding in patients with diabesity. It is understandable, therefore, that effective treatments for diabesity should restore vascular function to prevent the development of cardiovascular disease. Recent evidence from clinical studies supports the efficacy of incretin-based antidiabetic therapies for vascular protection. Thus, glucose control with either DDP-4 inhibitor or GLP-1 receptor therapies seems associated with favorable effects on vascular function in diabetes and the metabolic syndrome. Another mechanism to counter excess plasma glucose and reduce body weight in these patients may rely on drug therapies targeting gut hormones, as suggested by the efficacy of bariatric surgery to produce both sustained weight loss and high diabetes remission rates. Also, as knowledge of the multifaceted vascular actions of adipokines and their dysregulation in patients with diabesity increases, these substances become attractive targets for treatments aimed at cardiovascular prevention. The increasing coexistence of diabetes and obesity presents complex treatment challenges owing to the elevated risk of developing cardiovascular complications. Hence, therapeutic strategies integrating glycemic control, weight loss and vascular protection are of the greatest importance to successfully counteract the health and economic burden posed by diabesity.
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PMID:Drug treatments to restore vascular function and diabesity. 2334 53


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