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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well recognised that the metabolic syndrome, a constellation of risk factors including obesity, hypertension, insulin resistance and dyslipidaemia, is associated with an increased risk of cardiovascular complications and the development of Type 2 diabetes. Consequently, timely identification and management of all components of the metabolic syndrome is warranted. In particular, guidelines have emphasised the importance of targeting elevated blood pressure (BP) and dyslipidaemia as a method of reducing global cardiovascular risk. Findings from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial show that the angiotensin receptor blocker, valsartan, reduces cardiovascular events and the development of Type 2 diabetes in high-risk individuals. This profile is being further explored in the ongoing Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Given the potential advantages to patients and physicians of tackling more than one of the components of the metabolic syndrome, antihypertensive agents such as valsartan would appear to be and important addition to the management of vulnerable patients at high risk of cardiovascular events.
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PMID:Angiotensin receptor blockers: Cardiovascular protection in the metabolic syndrome. 1698 30

Nateglinide (Starlix((R))) is licensed for the treatment of Type 2 diabetes in patients inadequately controlled with metformin. The study objective was to monitor the safety and use of nateglinide prescribed by primary care physicians (GPs) in England, using the observational cohort technique, Prescription-Event Monitoring. Exposure data were derived from dispensed nateglinide prescriptions issued October 2001-June 2004; demographic and outcome data, from questionnaires sent to patients' GPs at least 6 months after patients' first prescription. Incidence densities (IDs; number of first reports of an event/1,000 patient-months exposure) were calculated for month 1 (ID(1)), months 2-6 (ID(2-6)); rate differences [ID(1)-ID(2-6) (+99% CI)] were examined. Cohort comprised 4,557 patients, median age 60 (IQR 51, 68 years); 2,439 (53.5%) male; 3,463 (76.0%) received nateglinide in combination with metformin. GPs reported 1,625 reasons for stopping in 1,474 (32.3%) patients and 80 events as adverse drug reactions in 66 (1.5%) patients. Events associated with starting treatment included nausea/vomiting [ID(1)-ID(2-6) 9.6 (99% CI 5.3, 13.9)], malaise/lassitude [ID(1)-ID(2-6) 6.03 (99% CI 2.2, 9.9)]. No serious hypersensitivity reactions were reported. Two pregnancies (< 0.1%) and 73 deaths (1.6%) were reported. Nateglinide appeared to be generally well tolerated when used in combination with metformin for the treatment of Type 2 diabetes.
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PMID:Safety of nateglinide as used in general practice in England: results of a prescription-event monitoring study. 1787 23

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 beta-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.
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PMID:A review of nateglinide in the management of patients with type 2 diabetes. 1820 Aug

We studied the effects of nateglinide on serum adiponectin in 26 patients with type 2 diabetes mellitus. The changes in serum insulin at 30min significantly correlated with those in serum high-molecular weight adiponectin. Nateglinide may ameliorate hypoadiponectinemia as well as postprandial hyperglycemia in patients with type 2 diabetes mellitus.
Diabetes Res Clin Pract 2008 Dec
PMID:Nateglinide may increase high-molecular weight adiponectin in type 2 diabetic patients with hypoadiponectinemia. 1884 86

Patients with impaired glucose tolerance (IGT) have increased risk for developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Lifestyle modification and medication can prevent or delay progression to diabetes (PD), but whether such interventions also reduce the risk of CVD has not been rigorously tested. The Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is a multinational, randomized, double-blind, 2 x 2 factorial trial in subjects with IGT (on a screening oral glucose tolerance test [OGTT]) aged > or = 50 years with known CVD or aged > or = 55 years with > or = 1 CVD risk factor. Enrollment began in January 2002 and was completed January 2004, with 9,518 patients randomized to receive 1 of 4 possible treatment combinations as follows: nateglinide with valsartan, nateglinide with valsartan-placebo, nateglinide-placebo with valsartan, or nateglinide-placebo with valsartan-placebo. All subjects are participating in a clinic-based and telephone-based lifestyle intervention aimed at reducing weight and dietary fat and increasing physical activity. The 3 coprimary end points are new onset of T2DM, a "core" composite of major cardiovascular events (death, myocardial infarction, stroke, or hospitalization for heart failure), and an "extended" composite including the components of the core composite plus coronary revascularization and hospitalization for unstable angina. The study was designed to evaluate whether reducing postprandial hyperglycemia, blockade of the renin-angiotensin-aldosterone system, or both interventions reduce the risk of T2DM or cardiovascular events in patients with IGT.
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PMID:Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial. 1894 90

Drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) are the cornerstone of therapy for cardiovascular and renal disease because they protect against worsening outcomes in the respective target organs. Recent results from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) have confirmed that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) confer similar cardioprotection and renoprotection, showing little to no benefit from the combination in cardiovascular disease. It is not yet clear whether one class is superior to another for renoprotection. Whether dual RAAS blockade is more advantageous than single blockade, and in which patients, is also yet to be clearly determined. The Long-Term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) study will compare the cardiorenoprotective effects of ACE inhibitors and ARBs in patients with albuminuria, and clarify the role of dual blockade. Preliminary evidence that RAAS inhibitors reduce incident diabetes is intriguing. Whether ARBs can reduce incident diabetes and related cardiovascular outcomes is awaited with the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.
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PMID:Are renin-angiotensin-aldosterone system blockers distinguishable based on cardiovascular and renal outcomes in nephropathy? 1933 65

Glimepiride and nateglinide are two common oral hypoglycemic agents currently being used with humans suffering from Type 2 diabetes mellitus. Neither drug has been tested with cats thus far and it is currently unknown whether either of these drugs exert any effect in cats or not. The objective of this study was to determine the effect of glimepiride and nateglinide on glucose and insulin responses in healthy control cats, in order to determine their potential use in diabetic cats. The intravenous glucose tolerance tests was carried out since it is an excellent test for evaluating pancreatic beta-cell function for insulin secretion. Alterations in the insulin secretion pattern can be perceived as the earliest sign of beta-cell dysfunction in many species, including cats. Nateglinide demonstrated a quick action/short duration type effect with serum glucose nadiring and insulin response peaking at 60 and 20 minutes, respectively. Alternatively, glimepiride is medium-to-long acting with serum glucose nadiring and insulin response peaking at 180 minutes and 60 minutes, respectively. Nateglinide's potency was evident allowing it to induce a 1.5-2 higher preliminary insulin peak (3.7 +/- 1.1 pg/ml) than glimepiride's (2.5 +/- 0.1 pg/ml), albeit only for a short period of time. Because glimepiride and nateglinide have a shared mode of action, no significant differences in overall glucose AUC(0-360 min) (24,435 +/- 2,940 versus 24,782 +/- 2,354 mg min/dl) and insulin AUC(0-360 min) (410 +/- 192 versus 460 +/- 159) in healthy control cats were observed. These findings may provide useful information when choosing a hypoglycemic drug suited for the treatment of diabetic cats depending on the degree of diabetes mellitus the cat is suffering from.
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PMID:Effect of glimepiride and nateglinide on serum insulin and glucose concentration in healthy cats. 1972 31

The investigators review the evidence of the potential role of renin-angiotensin system (RAS) blockers in delaying or preventing the onset and progression of diabetes mellitus (DM) and cardiovascular disease and the suggested mechanisms by which these agents exert their favorable metabolic and cardiovascular effects. Data from clinical trials suggest that RAS blockade not only reduces cardiovascular risk in patients with DM but also may prevent or delay DM onset in at-risk subjects. These observations set the stage for further studies evaluating the risk for developing DM as a primary end point: the Diabetes Reduction Approaches With Ramipril And Rosiglitazone Medications (DREAM) trial, in which ramipril significantly increased regression to normoglycemia (although it did not reduce the primary end point of new-onset DM or death), and the ongoing Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, the only DM prevention trial also powered to evaluate whether a reduced risk for DM is associated with a reduction in cardiovascular disease events. In conclusion, overwhelming evidence suggests that the RAS plays an important role in the pathogenesis of DM and its associated cardiovascular risks.
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PMID:Role of renin-angiotensin system blockade in patients with diabetes mellitus. 1973 20

The Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is exploring two pharmacological strategies (nateglinide and valsartan, both alone and in combination) in the prevention of overt diabetes mellitus (DM) and the reduction of cardiovascular disease (CVD) in subjects at high risk for these events. In this analysis, we provide baseline characteristics of the randomized NAVIGATOR study population and contrast them with those from other trials of DM prevention. Key eligibility criteria include impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), a history of CVD (in patients aged > or =50 years), and > or =1 cardiovascular risk factor (in patients aged > or =55 years). Baseline demographic characteristics, laboratory findings, cardiovascular risk factors, CVD history, and medication use are described and compared with other trials of DM prevention. The full analysis set of subjects (N = 9306) showed a clustering of risk factors consistent with the metabolic syndrome: high rates of hypertension (77.5%), dyslipidemia (44.7%), increased waist circumference (101.0 cm), and high body mass index (BMI) (47.5% with BMI > or =30 kg/m(2)). A minority of patients had a history of CVD (24.3%); of these, 11.7% had a history of myocardial infarction and most of the remainder had evidence of coronary artery disease. Subjects also had elevated blood pressure (BP) (predominantly systolic) (139.7/82.6 mm Hg), increased serum low-density lipoproteins cholesterol levels (3.27 mmol/L), and borderline elevation of triglyceride levels (1.97 mmol/L). Demographic data, BP, and lipid profiles in NAVIGATOR were similar to those of previous DM prevention trials, which were also based largely on meeting criteria for IGT. Medication use at baseline among NAVIGATOR subjects, which frequently included aspirin, beta-blockers, calcium channel blockers, diuretics, and lipid-lowering agents, reflects enhanced CVD risk. However, little prescribing of renin-angiotensin-aldosterone system blockers was observed, likely due to protocol exclusion criteria. In conclusion, the NAVIGATOR study comprises prediabetic subjects who typically have concurrent BP and metabolic disturbances and an enhanced risk of CVD, and are thus at higher risk for cardiovascular events than subjects in previous DM prevention trials.
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PMID:Baseline characteristics of the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial population: comparison with other diabetes prevention trials. 2018 89

NAVIGATOR ("Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research") is a large international placebo-controlled trial that randomised 9,031 individuals at high risk because of impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors. This trial aimed at investigating whether valsartan (a selective AT1 receptor antagonist) and/or nateglinide (a short-acting insulin-secreting agent) are able to reduce the incidence of type 2 diabetes and cardiovascular events. After a median follow up of 6.5 years, neither valsartan nor nateglinide improved cardiovascular prognosis in the tested population, which already benefited from a protective pharmacotherapy at baseline and a reinforcement of lifestyle modification throughout the trial. Nateglinide did not diminish the risk of new onset diabetes. In contrast, valsartan reduced the incidence of type 2 diabetes by 14%, confirming the potential interest of the blockade of the renin-angiotensin system in this high-risk population.
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PMID:[NAVIGATOR: A trial of prevention of cardiovascular complications and type 2 diabetes with valsartan and/or nateglinide]. 2049 25


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