Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endpoint studies have been performed with fibrates in coronary heart disease since 1971. The results have been confusing - starting with initial benefits in small studies, but contradicted by either minimal benefits in the Coronary Drug Project or adverse noncardiovascular (non-CV) effects in the World Health Organization Clofibrate Study. Fibrates returned for patients with low HDL-C and low LDL-C after a 25% event reduction were seen in the Veterans Affairs HDL Intervention Trial. The greater prominence ascribed to the lipid triad of the metabolic syndrome and the increasing prevalence of diabetes increased the topicality of fibrates given their main action of converting small dense to light buoyant LDL. The Fenofibrate Intervention in Event Lowering in Diabetes (FIELD) Study has carried on the tradition. Fenofibrate therapy in 9795 patients comprising a mixed low-risk primary and a medium-risk secondary prevention cohort resulted in an 11% reduction in coronary events (p = 0.16), a similar but significant reduction in CV events (p = 0.04; number needed to treat = 70). The benefits were concentrated in primary prevention and on nonfatal myocardial events, but the study was confounded by asymmetrical statin drop-in due to the LDL-C-lowering effect of fenofibrate. Safety was generally good, including in combination with statins, but old concerns about sudden death, pancreatitis and venous thrombosis returned. Unexpected benefits were seen with fenofibrate on microvascular endpoints including microalbuminuria and retinopathy. Fenofibrate is a reasonable second-line therapy for dyslipidaemia in diabetes and safe in combination therapy. Its benefits on microvascular disease and in combination therapy require further confirmation.
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PMID:FIELDS of dreams, fields of tears: a perspective on the fibrate trials. 1662 Mar 58

The peroxisome proliferator-activated receptor (PPAR) family of genes plays a major role in metabolic regulation. Unfortunately, the results of two recent, large event trials of PPAR agonists have been mixed. High rates of crossover to statin use confound the interpretation of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, which found a less than expected reduction in coronary and stroke events with fenofibrate. Of concern, nonsignificant increases in coronary and sudden deaths, thrombotic events, and pancreatitis occurred in the fenofibrate group. The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROACTIVE) also found a reduction in coronary and stroke events with pioglitazone compared with placebo in a population with diabetes and cardiovascular disease, but this benefit was counterbalanced by an increase in congestive heart failure as well as symptomatic edema. Further research is needed to determine the role of PPAR agonists in the prevention of cardiovascular disease.
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PMID:Update on PPAR agonists: the clinical significance of FIELD and PROACTIVE. 1716 49

The use of fibrates in the management of lipoprotein disorders has a history dating back to the mid-1960s. This group of drugs has now been tested in several large long-term trials with cardiovascular end points. Overall, there is good evidence for the reduction of cardiovascular disease in primary prevention studies and in those of subjects with manifest disease. More recent trials have suffered from high interference due to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) introduction, particularly in their placebo control groups. However, there is very good evidence for overall safety from a combined study of >20,000 patients in these controlled clinical trials lasting approximately 5 years. Abdominal pain has been observed more frequently in the statin vs placebo group. Myopathy, liver enzyme elevations, and cholecystitis have been potential adverse reactions of interest. However, these have occurred at a very low rate and are rarely found to be statistically more frequent in the active-treatment group compared with the subjects taking placebo. The recent Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study found a slightly higher incidence of pancreatitis, deep venous thrombosis, and pulmonary embolism. Small creatinine and homocysteine elevations are observed in many patients taking fibrates, and the effect of this on long-term outcomes is under study. The FIELD study also described a significant reduction in the rates of progression of proteinuria and vascular retinopathy with fibrate therapy. To date, there has been no study exclusive to patients with elevated triglycerides, raising the question of the potential benefit of these drugs in patients with the lipid abnormalities most effectively treated with fibrates.
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PMID:Expert commentary: the safety of fibrates in lipid-lowering therapy. 1736 73

Authors present a clinical case review of a 46-years-old, otherwise healthy female patient, presented with acute abdominal pain. Examination and full work-up established a diagnosis of acute pancreatitis, T2DM and hypertriglyceridemia; based on family history, inherited hypertriglyceridemia was suspected. Elevated TG values associated with diabetes dramatically increase the risk of developing MI. Subsequent to the pancreatitis treatment protocol completion, the patient has fully recovered from acute pancreatitis. Prescribed anti-diabetes and Fenofibrate treatment has achieved satisfactory glycemic and TG values. The patient is under close ambulatory control and monitoring at the National Center for Diabetes Research. T2DM and hypertriglyceridemia often coexist. Intensive treatment of both conditions with diet, physical activity, fenofibrates and insulin is important, as it aims to reduce TG values and normalize glucose profile.
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PMID:CLINICAL CASE REPORT ON ACUTE PANCREATITIS WITH CONCOMITANT T2DM AND HYPERTRIGLYCERIDEMIA. 2974 12