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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity has reached epidemic proportions in many countries and is an established risk factor in many chronic illnesses, but its role in acute illness is less clear. Pancreatologists have long recognized obesity as a risk factor for a poor outcome in severe acute pancreatitis. There are now several studies that have identified obesity as a primary risk factor for developing local complications (abscess, pseudocyst, necrosis), organ failure, and death. Indeed, meta-analysis of these studies gives a relative risk of 4.3 for local complications, 2.0 for systemic complications, and 2.1 for death. This has led to proposed modifications of acute pancreatitis scoring systems to include obesity as an independent primary predictive factor of severe disease. Obesity is associated with a low-grade inflammatory state, which may predispose obese patients to such complications. Furthermore, visceral obesity and visceral adipose tissue may be particularly important in underlying the pathophysiology of these observations.
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PMID:The impact of obesity on the course and outcome of acute pancreatitis. 1820 95

Over the past decades several epidemiological studies have been published reporting on incidence trends, hospital admissions, etiological factors and outcome of both acute and chronic pancreatitis. Over time, the incidence of acute pancreatitis has increased in the Western countries. Also, the number of hospital admissions for both acute and chronic pancreatitis have increased. These upward time trends possibly reflect a change in the prevalence of main etiological factors (e.g. gallstones and alcohol consumption) and cofactors such as obesity and genetic susceptibility. Acute and chronic pancreatitis are associated with significant morbidity and mortality and a substantial use of health care resources. Although the case-fatality rate of acute pancreatitis decreased over time, the overall population mortality did not change for both acute and chronic pancreatitis. This chapter will focus on recent developments in the epidemiology, aetiology, natural course and outcome of both acute and chronic pancreatitis.
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PMID:Epidemiology, aetiology and outcome of acute and chronic pancreatitis: An update. 1820 12

Obesity has become epidemic in the United States, in Europe, and in many urban areas in the developing world. The globalization of certain 'fast foods' and 'soft drinks' may, in part, be contributing to this epidemic. Diets high in saturated fatty acids and trans fats as well as drinks that have high fructose corn syrup levels may be particularly harmful. Recent research suggests that fat is a dynamic endocrine organ and that visceral fat is associated with the metabolic syndrome. Central obesity leads to organ steatosis and altered serum adipokines including reduced adiponectin and markedly elevated leptin. This abnormal adipokine milieu results in increased tissue infiltration of monocytes and macrophages which produce proinflammatory cytokines that alter organ function. Over many years, the combination of steatosis and local inflammation leads to fibrosis and eventually to cancer. Nonalcoholic fatty liver disease (NAFLD) is a precursor for nonalcoholic steatohepatitis (NASH). NAFLD and NASH (1) lead to cirrhosis and hepatocellular carcinoma, (2) increase the risk of liver resection, and (3) compromise the outcome of liver transplantation. Similarly, in the pancreas nonalcoholic fatty pancreas disease (NAFPD) may lead to nonalcoholic steatopancreatitis (NASP). NAFPD and NASP may (1) promote the development of chronic pancreatitis and pancreatic cancer, (2) exacerbate the severity of acute pancreatitis, and (3) increase the risk of pancreatic surgery. In the gallbladder nonalcoholic fatty gallbladder disease (NAFGBD, cholecystosteatosis) may lead to steatocholecystitis. Cholecystosteatosis may be an explanation for (1) the increased incidence of chronic acalculous cholecystitis and (2) the increased number of cholecystectomies.
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PMID:Hepato-pancreato-biliary fat: the good, the bad and the ugly. 1833 22

Obesity is associated with increased severity of acute pancreatitis (AP). The cytokines IL-18 and IL-12 are elevated in patients with AP, and IL-18 levels are high in obesity. We aimed to develop a pathologically relevant model to study obesity-associated severe AP. Lean WT and obese leptin-deficient ob/ob mice received two injections of IL-12 plus IL-18. Survival, pancreatic inflammation, and biochemical markers of AP were measured. Dosing with IL-12 plus IL-18 induced 100% lethality in ob/ob mice; no lethality was observed in WT mice. Disruption of pancreatic exocrine tissue and acinar cell death as well as serum amylase and lipase levels were significantly higher in ob/ob than in WT mice. Edematous AP developed in WT mice, whereas obese ob/ob mice developed necrotizing AP. Adipose tissue necrosis and saponification were present in cytokine-injected ob/ob but not in WT mice. Severe hypocalcemia and elevated acute-phase response developed in ob/ob mice. The cytokine combination induced high levels of regenerating protein 1 and pancreatitis-associated protein expression in the pancreas of WT but not of ob/ob mice. To differentiate the contribution of obesity to that of leptin deficiency, mice received short- and long-term leptin replacement therapy. Short-term leptin reconstitution in the absence of major weight loss did not protect ob/ob mice, whereas leptin deficiency in the absence of obesity resulted in a significant reduction in the severity of the pancreatitis. In conclusion, we developed a pathologically relevant model of AP in which obesity per se is associated with increased severity.
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PMID:Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice. 1851 22

Obesity is clearly an independent risk factor for increased severity of acute pancreatitis (AP), although the mechanisms underlying this association are unknown. Adipokines (including leptin and adiponectin) are pleiotropic molecules produced by adipocytes that are important regulators of the inflammatory response. We hypothesized that the altered adipokine milieu observed in obesity contributes to the increased severity of pancreatitis. Lean (C57BL/6J), obese leptin-deficient (LepOb), and obese hyperleptinemic (LepDb) mice were subjected to AP by six hourly intraperitoneal injections of cerulein (50 microg/kg). Severity of AP was assessed by histology and by measuring pancreatic concentration of the proinflammatory cytokines IL-1beta and IL-6, the chemokine MCP-1, and the marker of neutrophil activation MPO. Both congenitally obese strains of mice developed significantly more severe AP than wild-type lean animals. Severity of AP was not solely related to adipose tissue volume: LepOb mice were heaviest; however, LepDb mice developed the most severe AP both histologically and biochemically. Circulating adiponectin concentrations inversely mirrored the severity of pancreatitis. These data demonstrate that congenitally obese mice develop more severe AP than lean animals when challenged by cerulein hyperstimulation and suggest that alteration of the adipokine milieu exacerbates the severity of AP in obesity.
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PMID:A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis. 1858 60

Acute pancreatitis is a dynamic, often progressive disease; 14-20% require intensive care in its severe form due to multiorgan dysfunction and/or failure. This review was created using systematic literature review of articles published on this subject in the last 5 years. The outcome of severe acute pancreatitis is determined by the inflammatory response and multiorgan dysfunction - the prognostic scores (Acute Physiology and Chronic Health Evaluation, Glasgow Prognostic Index, Sepsis-related Organ Failure Assessment, Multi Organ Dysfunction Syndrome Scale, Ranson Scale) can be used to determine outcome. Clinical signs (age, coexisting diseases, confusion, obesity) and biochemistry values (serum amylase, lipase, C-reactive protein, procalcitonin, creatinine, urea, calcium) have important prognostic roles as well. Early organ failure increases the risk of late abdominal complications and mortality. Intensive care can provide appropriate multi-function patient monitoring which helps in early recognition of complications and appropriate target-controlled treatment. Treatment of severe acute pancreatitis aims at reducing systemic inflammatory response and multiorgan dysfunction and, on the other side, at increasing the anti-inflammatory response. Oral starvation for 24-48 hours is effective in reducing the exocrine activity of the pancreas; the efficacy of protease inhibitors is questionable. Early intravascular volume resuscitation and stable haemodynamics improve microcirculation. Early oxygen therapy and mechanical ventilation provide adequate oxygenation. Electrolyte and acid-base control can be as important as tight glucose control. Adequate pain relief can be achieved by thoracic epidural catheterization. Early enteral nutrition with immunonutrition should be used. There is evidence that affecting the coagulation cascade by activated protein C can play a role in reducing the inflammatory response. The complex therapy of acute pancreatitis includes appropriate antibiotics, thrombo-embolic prophylaxis and in certain cases plasmapheresis and/or haemofiltration. Reducing intraabdominal pressure may be necessary in the acute phase. Intensive care multidisciplinary teamwork can reduce the mortality of severe acute pancreatitis from 30% to 10%.
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PMID:[Principles of intensive care in severe acute pancreatitis in 2008]. 1900 43

Acute pancreatitis continues to be a diagnostic and therapeutic challenge for physicians and surgeons. It ranks third in the list of hospital discharges for gastro-intestinal diseases. In most patients the cause is either gallstones or alcoholism. The overall mortality is less than 5%, but severe acute pancreatitis leads to prolonged hospitalization and much higher mortality. There are important differences in disease susceptibility and case fatality rates: the incidence is higher in blacks than in whites, and mortality is higher in older patients than in younger patients. Reports from various countries reveal that the frequency of acute pancreatitis is increasing, perhaps in relation to rising obesity rates, which would increase the likelihood of gallstone pancreatitis. Conversely, mortality rates for acute pancreatitis are declining in many, but not all, reports.
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PMID:The changing character of acute pancreatitis: epidemiology, etiology, and prognosis. 1928 96

Hypertriglyceridemia (HTG) is reported to cause 1-4% of acute pancreatitis (AP) episodes. HTG is also implicated in more than half of gestational pancreatitis cases. Disorders of lipoprotein metabolism are conventionally divided into primary (genetic) and secondary causes, including diabetes, hypothyroidism, and obesity. Serum triglyceride (TG) levels above 1,000 mg/dl are usually considered necessary to ascribe causation for AP. The mechanism for hypertriglyceridemic pancreatitis (HTGP) is postulated to involve hydrolysis of TG by pancreatic lipase and release of free fatty acids that induce free radical damage. Multiple small studies on HTGP management have evaluated the use of insulin, heparin, or both. Many series have also reported use of apheresis to reduce TG levels. Subsequent control of HTG with dietary restrictions, antihyperlipidemic agents, and even regular apheresis has been shown anecdotally in case series to prevent future episodes of AP. However, large multicenter studies are needed to optimize future management guidelines for patients with HTGP.
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PMID:Hypertriglyceridemic pancreatitis: presentation and management. 1929 88

Familial hypertriglyceridaemia is inherited in an autosomal dominant manner. The responsible genetic abnormality is unknown but recently, a novel gene encoding apolipoprotein AV has been linked to familial hypertriglyceridaemia. All patients develop the same phenotype with elevated levels of very low density lipoproteins (VLDL) in plasma. The main disorder of this dyslipidaemia is decreased intestinal absorption of biliary acids, leading to a compensatory increase of VLDL production. In familial hypertriglyceridaemia, a marked increase in plasma triglyceride (TG) levels can cause acute pancreatitis. Moreover, patients with other genetic factors, like familial chylomicronaemia, familial combined hyperlipidaemia, familial dysbetalipoproteinaemia and other rare disorders (e.g. Tangier disease and fish eye disease) may present increase of TG levels or cholesterol levels or both. Secondary hypertriglyceridaemias include hypothyroidism, kidney abnormalities (e.g. nephrotic syndrome or chronic kidney failure), diabetes mellitus, heavy alcohol consumption and obesity. In men and postmenopausal women, it seems that estrogen deficiency is responsible for higher TG levels compared with premenopausal women postprandially. In every state -fasting or postprandial-, women demonstrate lower plasma TG levels compared with men. This fact is due not only to increased muscular TG uptake and storage but also to higher TG clearance. Many studies demonstrated an age impact on plasma TG increase and larger variation of fasting TG levels caused by age. Also, hypertriglyceridaemia (TG >150 mg/dl; 1.7 mmol/l) is one of the diagnostic criteria of metabolic syndrome. Finally, several drugs may increase TG levels (e.g. chlorthalidone or beta-blockers).
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PMID:Primary and secondary hypertriglyceridaemia. 1935 54

Pancreatitis is a condition characterized by painful inflammation of the pancreas and can be either chronic or acute. The most common causes of acute pancreatitis (AP) in the United States are gallstones and excessive alcohol consumption. In addition, significantly elevated serum triglyceride levels can precipitate episodes of AP. Genetic defects are associated with severe elevations in serum triglyceride levels, whereas poorly controlled diabetes, obesity, and high-fat diets can contribute to elevated triglyceride levels substantial enough to provoke pancreatitis (secondary hypertriglyceridemia). Treatment of hypertriglyceridemia-induced AP consists of immediate reduction in serum triglyceride levels and long-term medications and lifestyle modifications. Nurses are instrumental in patient education about lifelong treatment strategies.
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PMID:Acute pancreatitis and hypertriglyceridemia. 1935 69


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