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

Non-insulin-dependent (type II) diabetes mellitus is an inherited metabolic disorder characterized by hyperglycemia with resistance to ketosis. The onset is usually after age 40 years. Patients are variably symptomatic and frequently obese, hyperlipidemic and hypertensive. Clinical, pathological and biochemical evidence suggests that the disease is caused by a combined defect of insulin secretion and insulin resistance. Goals in the treatment of hyperglycemia, dyslipidemia and hypertension should be appropriate to the patient's age, the status of diabetic complications and the safety of the regimen. Nonpharmacologic management includes meal planning to achieve a suitable weight, such that carbohydrates supply 50% to 60% of the daily energy intake, with limitation of saturated fats, cholesterol and salt when indicated, and physical activity appropriate to the patient's age and cardiovascular status. Follow-up should include regular visits with the physician, access to diabetes education, self-monitoring of the blood or urine glucose level and laboratory-based measurement of the plasma levels of glucose and glycated hemoglobin. If unacceptably high plasma glucose levels (e.g., 8 mmol/L or more before meals) persist the use of orally given hypoglycemic agents (a sulfonylurea agent or metformin or both) is indicated. Temporary insulin therapy may be needed during intercurrent illness, surgery or pregnancy. Long-term insulin therapy is recommended in patients with continuing symptoms or hyperglycemia despite treatment with diet modification and orally given hypoglycemic agents. The risk of pancreatitis may be reduced by treating severe hypertriglyceridemia (fasting serum level greater than 10 mmol/L) and atherosclerotic disease through dietary and, if necessary, pharmacologic management of dyslipidemia. Antihypertensive agents are available that have fewer adverse metabolic effects than thiazides and beta-adrenergic receptor blockers. New drugs are being developed that will enhance effective insulin secretion and action and inhibit the progress of complications.
 ...
PMID:Non-insulin-dependent (type II) diabetes mellitus. 174 94

No single pathophysiologic factor has been identified as the cause of recurrent acute pancreatitis. A systematic search should be undertaken in every patient to identify one of a myriad of factors that have been shown to play a part in causing this distressing illness. The abuse of alcohol remains the likeliest cause, and further research may reveal an inborn error of metabolism that jeopardizes some people. Biliary tract disease, gallstones, choledochal cyst, papillary stenosis, and duodenal diverticula show a clear relationship. Metabolic disorders such as hypercalcemia, hyperlipidemia, and hyperparathyroidism remain suspect. Systemic illnesses such as systemic lupus erythematosus and cystic fibrosis must be considered. Development anomalies such as pancreas divisum may precipitate acute pancreatitis through aberrant anatomic structures. Cancer must always be disproved. Not yet firmly established but worthy of thorough investigation are uncommon causes, such as the ingestion of certain drugs or combinations of drugs and trauma, either recent or past. Pancreatitis remains frightening for those with the disease and puzzling and frustrating for the medical people who treat it. A careful history and investigation in accordance with a systematic diagnostic plan that includes many disparate factors will lead to identification of the cause in the majority of patients.
 ...
PMID:Pathophysiologic factors in recurrent acute pancreatitis. 393 40

A five-year-old-girl with a history of recurrent hypoglycemia presented with acidosis, intractable vomiting, and abdominal tenderness; the diagnosis of acute pancreatitis was made by abdominal ultrasonography and supportive biochemical studies. Urinary organic acid analysis revealed metabolites suggestive of HMG-CoA lyase deficiency, and subsequent enzyme assays of lymphocytes and fibroblasts confirmed this diagnosis. Acute pancreatitis, an uncommon condition in childhood, is seen with increased frequency in patients with Reye syndrome, a metabolic disorder with which HMG-CoA lyase deficiency may be confused. The pathogenesis of pancreatitis in Reye syndrome or in HMG-CoA lyase deficiency has not been determined.
 ...
PMID:A child with acute pancreatitis and recurrent hypoglycemia due to 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. 648 80

Whether hyperlipidemia is a pre-existing metabolic disorder or a consequence of acute pancreatitis is still debated. Mild to moderate elevation of serum triglyceride levels are likely to be an epiphenomenon of the pancreatic disease. A marked hyperchylomicronemia and hypertrygliceridemia would be needed to trigger acute pancreatitis; a relevant defect in the lipid catabolism and clearance should therefore pre-exist. The aim of the present study was to investigate whether patients with acute pancreatitis and marked hyperlipidemia have an impaired clearance capacity of exogenous lipids, which would define the hyperlipidemia as a preexistent abnormality and therefore a potential cause of the pancreatic disease. With this aim, the kinetics of the removal of exogenous triglycerides from the circulation have been analyzed. Twenty patients with acute pancreatitis have been studied. Ten of them suffered from an episode of acute pancreatitis with marked hyperlipidemia (serum triglyceride levels > 20 mmol/L). Four to six months after recovery from the pancreatitis, a two-stage infusion of Intralipid 20% was carried out and the fractional removal rate (K2) and the maximal clearance capacity (K1) of exogenous triglycerides were calculated. At low infusion rates a first order kinetics for removal was observed, whereas at high infusion rates a zero order kinetics was operating. All patients with a previous attack of normolipidemic acute pancreatitis had normal K2 and K1 values. Five patients with previous hyperlipidemic acute pancreatitis had an abnormally low clearance capacity of exogenous triglycerides, whereas the remaining five had normal removal values. The present study provides new information in the association between hyperlipidemia and acute pancreatitis by showing that even a marked elevation of serum lipid levels should not be invariably considered as the etiological factor of the pancreatic disease, even if other potential causes are not evident.
 ...
PMID:Hyperlipidemia in acute pancreatitis. Cause or epiphenomenon? 853 Aug 25

The hyperosmolar hyperglycemic nonketotic state (HHNS) is an acute metabolic complication occurring characteristically in elderly type-2 diabetic patients. It may account for 10 up to 47% of cases of severe hyperglycemia with or without ketoacidosis. Many factors associated with advanced age may explain the predilection of both elderly subjects in general and older diabetics in particular to develop hyperosmolar coma, including reduced glomerular filtration rate and elevated renal threshold for glucose (which fail to correct hyperglycemia by osmotic diuresis), lack of thirst appropriate to the state of hydratation and some iatrogenic factors. In HHNS the age of the patients is the best known prognostic indicator. The increased mortality rate in the elderly diabetics depends on the severity of precipitating acute diseases (gastrointestinal hemorrhage, cardiovascular accident, pneumonia, pancreatitis, etc.), but the frequent compromises of the hemodynamic state and renal function of aged subjects substantially contributes. However, the role of erroneous management is not negligible and difficulties may be encountered in conciliating correction of metabolic disorder with treatment of precipitating illness. Insulin, water and electrolytes are the most important therapeutical tools for the treatment of hyperglycemic emergencies. In HHNS, the aggressive fluid replacement with isotonic or hypotonic NaCl solutions have first priority. Such a type of strategy is difficult to perform in patients suffering from cerebral stroke (which needs of anti-edema therapy) or congestive heart failure (necessitating to avoid fluid excess). According to the literary data, in our experience these two precipitating factors are frequent causes of death. We outline the validity of prefixed protocols of management; on the other hand, we think that the pathophysiological understanding of HHNS in the single patient is essential to decide the proper corrections and to permit a successful outcome. The primary way aiming at diminishing mortality by HHNS is its prevention; it is fundamental to warrant an appropriate fluid intake and to utilize with caution some drugs (thiazides, steroids, phenytoin, etc.) in aged diabetics, especially when nephropathic or unable, or living in nursing homes.
 ...
PMID:Diabetic non ketotic hyperosmolar state: a special care in aged patients. 1865 40

Lipoprotein lipase deficiency (LLD) is a rare metabolic disorder that typically presents with skin xanthomas and pancreatitis in childhood. We report a case of LLD in an infant who presented with jaundice caused by a pancreatic head mass. Abdominal imaging also incidentally revealed hyperechoic renal masses caused by renal xanthomas. This appearance of the multiple abdominal masses makes this a unique infantile presentation of LLD.
 ...
PMID:Lipoprotein lipase deficiency with visceral xanthomas. 2014 60

Alipogene tiparvovec is the first adeno-associated virus (AAV)-mediated gene therapy to be approved for the treatment of a metabolic disorder. Lipoprotein lipase (LPL) deficiency (LPLD) is a rare autosomal-recessive disorder in which gene mutations cause the production of a catalytically inactive enzyme required for plasma triglyceride hydrolysis. The resultant hypertriglyceridemia causes frequent abdominal pain, fatty deposits in the skin and retina, and can lead to potentially fatal pancreatitis. In addition, patients with LPLD can develop diabetes and cardiovascular disease. Past therapies to lower plasma triglycerides in these patients have been ineffective. Intramuscular injection of alipogene tiparvovec delivers a natural gain-of-function LPL gene variant, LPLS447X, to muscle tissue and has demonstrated efficacy in animal models of LPLD. In phase I/II and phase II/III clinical evaluations, alipogene tiparvovec significantly lowered plasma triglycerides and increased LPL activity, resulting in a reduction in plasma chylomicron and a decrease in the frequency of pancreatitis episodes. The therapy is well tolerated in animals and humans and produces no serious treatment-related adverse effects.
 ...
PMID:Alipogene tiparvovec for the treatment of lipoprotein lipase deficiency. 2352 20

A 27-year-old woman with vitamin B12 responsive form of methylmalonic acidaemia (MMA) was pregnant with her first child. Treatment was unaltered during pregnancy: a low-protein diet and supplements. Her pregnancy was uncomplicated. She had a spontaneous delivery of a healthy girl with no MMA. The postpartum period was uneventful. MMA is a rare autosomal recessive metabolic disorder caused by a deficiency of methylmalonyl coenzyme A mutase or its vitamin B12-dependent cofactor, leading to a toxic accumulation of methylmalonyl acid in plasma and urine. Clinical presentation involves otherwise unexplained deterioration and neurological dysfunction, recurrent vomiting, dehydration, lethargy, respiratory distress and muscular hypotonia. Long-term sequelae are neurological problems, renal failure, pancreatitis and cardiomyopathy. This is the 11th reported case of pregnancy in a woman with MMA.
...
PMID:Methylmalonic acidaemia in pregnancy. 2468 5

This Review discusses new developments in understanding the basis of chylomicronaemia--a challenging metabolic disorder for which there is an unmet clinical need. Chylomicronaemia presents in two distinct primary forms. The first form is very rare monogenic early-onset chylomicronaemia, which presents in childhood or adolescence and is often caused by homozygous mutations in the gene encoding lipoprotein lipase (LPL), its cofactors apolipoprotein C-II or apolipoprotein A-V, the LPL chaperone lipase maturation factor 1 or glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1. The second form, polygenic late-onset chylomicronaemia, which is caused by an accumulation of several genetic variants, can be exacerbated by secondary factors, such as poor diet, obesity, alcohol intake and uncontrolled type 1 or type 2 diabetes mellitus, and is more common than early-onset chylomicronaemia. Both forms of chylomicronaemia are associated with an increased risk of life-threatening pancreatitis; the polygenic form might also be associated with an increased risk of cardiovascular disease. Treatment of chylomicronaemia focuses on restriction of dietary fat and control of secondary factors, as available pharmacological therapies are only minimally effective. Emerging therapies that might prove more effective than existing agents include LPL gene therapy, inhibition of microsomal triglyceride transfer protein and diacylglycerol O-acyltransferase 1, and interference with the production and secretion of apoC-III and angiopoietin-like protein 3.
 ...
PMID:Chylomicronaemia--current diagnosis and future therapies. 2573 19

Hypertriglyceridemia (HTG) is a common metabolic disorder with both genetic and lifestyle factors playing significant roles in its pathophysiology. HTG poses a risk for the development of cardiovascular disease (CVD) in the population at large and for pancreatitis in about two percent of individuals with extremely high levels of triglycerides (TG). This manuscript summarizes the mechanisms underlying the development of HTG as well as its management, including emerging therapies targeted at specific molecular pathways.
 ...
PMID:Hypertriglyceridemia-Causes, Significance, and Approaches to Therapy. 3298 91


1