Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
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Elevated ferritin levels have been reported as a risk factor for coronary heart disease in Finnish and Italian studies. Studies in other populations have found no association between ferritin and cardiovascular disease raising the possibility of confounding with other cardiovascular risk factors. We determined ferritin levels, metabolic cardiovascular risk factors, C-reactive protein (CRP), anthropometric measurements and blood pressure in 815 men and women aged 26 years. In women serum ferritin correlated with CRP, waist measurement, body mass index (BMI), and triglycerides. In multiple regression analysis CRP alone was independently associated with serum ferritin. Serum ferritin in men correlated with waist measurement, BMI, triglycerides and high-density lipoprotein (HDL) cholesterol. After adjustment for the other variables, waist measurement was the only independent predictor of ferritin. Ferritin levels in young men and women are associated with obesity and serum triglycerides, HDL cholesterol in men and inflammation in women. Confounding may contribute to reports of associations between ferritin and cardiovascular disease.
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PMID:Relationship of serum ferritin with cardiovascular risk factors and inflammation in young men and women. 1261 82

The presence of steatosis and inflammatory infiltrate in liver biopsies is essential for the diagnosis of non-alcoholic steatohepatitis (NASH). These findings are similar to those with alcoholic liver disease. However, in the NASH-situation alcohol doesn't play an important role. Risk factors for the development of NASH are obesity and diabetes. Most of the patients are clinically asymptomatic. This means, that a diagnosis of NASH is a diagnosis of exclusion: Viral induced, autoimmune, metabolic and toxic liver disease have to be excluded. The disease has a benign clinical course. The risk of cirrhosis is low. So far, there is no established treatment. Preliminary reports suggest a positive effect of weight-loss and ursodeoxycholic acid. Wilson's disease, a copper storage disorder, in which biliary copper excretion is reduced, is inherited as an autosomal recessive trait. Most patients with Wilson disease become symptomatic between the ages of 6 and 15. In about 90% of patients serum ceruloplasmin levels and serum copper concentrations are reduced. Copper excreation is increased. Histologic examination of liver biopsy specimens reveals fatty infiltration, Mallory bodies and ballooned glycogen nuclei, abnormalities which are also found in alcoholic liver disease. The definitive diagnostic parameter is the quantitative determination of liver copper content (> 250 micrograms/g dryweight). Untreated Wilson disease is always fatal. Lifelong treatment with anti-copper drugs are essential, D-penicillamine being the firstline therapy. Hereditary hemochromatosis (HH) is an iron overload disease inherited as an autosomal recessive trait. The frequency of the disease is high. The first symptoms usually can be found at the age of 20-50 years. Arthralgia develops in up to 50% of the patients. Many organs are involved, most often the liver. The organ is usually enlarged, transaminases are always moderately elevated. Laboratory findings disclose a marked elevation in serum ferritin and transferrin saturation. More than 80% of HH-patients are homozygous for the C282Y-mutation in the HFE-gene. The firstline treatment of HH is phlebotomy. Treatment is lifelong. When serum ferritin drops below 50 micrograms/l, the frequency of phlebotomy should be reduced (4-12 per year). If the patient already has cirrhosis, the risk of HCC is very high.
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PMID:[Rare, but important chronic liver diseases]. 1250 71

The purpose of the study was a more thorough assessment of the nutrition state of patients admitted to hospitals in Poland. The study was carried out in four hospitals at teaching centre level, in four hospitals at province level, and in four county hospitals. The patients for the study were selected randomly from 3310 adult patients (every 10th patient admitted to these hospitals). For the study 210 patients (122 women and 88 men) were qualified. Their mean age was 54 +/- 16 years (range 15-82 years). The patients were subjected to various biochemical tests including determination of antioxidant vitamins (vitamins A, E and C), vitamin B12, folic acid, ferritin, and homocysteine and blood lipids. Vitamin deficiency accepted as vitamin malnutrition was found in the case of vitamin C in 51.8% of the patients, folic acid in 32%, vitamin E in 10%, vitamin B12 in 6.8%, vitamin A in 1.4%. Vitamin deficiency was equally frequent in patients with malnutrition, overweight or with obesity. Lipid profile disturbances were found in 51% and high homocysteine level in 63% of the studied patients.
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PMID:[Nutritional status of patients in hospitals in Poland. More thorough assessment of nutritional status of adult patients]. 1464 80

The mechanism(s) determining the progression from fatty liver to steatohepatitis is currently unknown. Our goal was to define the relative impact of iron overload, genetic mutations of HFE, and insulin resistance on the severity of liver fibrosis in a population of subjects with nonalcoholic fatty liver disease (NAFLD) who had low prevalence of obesity and no overt symptoms of diabetes. In a cohort of 263 prospectively enrolled patients with NAFLD, 7.4% of patients had signs of peripheral iron overload and 9% had signs of hepatic iron overload, but 21.1% had hyperferritinemia. The prevalence of C282Y and H63D HFE mutations was similar to the general population and mutations were not associated with iron overload. Although subjects were on average only moderately overweight, insulin sensitivity, measured both in the fasting state and in response to oral glucose, was lower. Univariate analysis demonstrated that the presence of severe fibrosis was independently associated with older age, female sex, overweight, aspartate/alanine aminotransferase ratio, serum ferritin level, fasting glucose and insulin levels, decreased insulin sensitivity, and with histologic features (degree of necroinflammation and steatosis). After adjustment for body mass index (BMI), age, sex, and degree of steatosis, ferritin levels (odds ratio [OR] = 1.77; 95% CI = 1.21- 2.58; P =.0032) and the oral glucose insulin sensitivity (OR = 0.53; CI = 0.33-0.87; P =.0113) were independent predictors of severe fibrosis. In conclusion, the current study indicates that insulin resistance is a major, independent risk factor for advanced fibrosis in patients with NAFLD. Increased ferritin levels are markers of severe histologic damage, but not of iron overload. Iron burden and HFE mutations do not contribute significantly to hepatic fibrosis in the majority of patients with NAFLD.
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PMID:Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. 1518 21

Obesity as well as low physical fitness and inactivity are associated with an increased incidence of cardiovascular risk factors and coronary artery disease (CAD). Increased inflammation has recently been addressed to play an important role for the relationship between obesity and CAD, as adipose tissue expresses and releases pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). As this relationship is less clear in childhood, we investigated 197 children aged 10-15 years assessing obesity, physical fitness, and a metabolic cardiovascular risk profile including markers of inflammation. Obese children had significantly higher concentrations of inflammatory parameters such as fibrinogen, ferritin, IL-6, and TNF-alpha than non-obese subjects (P<0.01). When dividing the children into groups regarding obesity (BMI < 22.5 kg/mz, BMI > or = 22.5 kglm2) and fitness (< 5 MET, > or = 5 MET), we found that obese, unfit children showed the highest systemic inflammation, whereas fit but obese individuals had as low levels as lean and fit children. These data reveal that even in childhood inflammatory parameters are elevated in obesity and that physical fitness counteracts this association.
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PMID:Low-grade systemic inflammation in overweight children: impact of physical fitness. 1563 87

The purpose of the study was to determine clinical importance of high serum levels of ferritin, fibrinogen and C-reactive protein (CRP) in patients with various forms of coronary heart disease (CHD) such as stable angina, painless myocardial ischemia (PMI) and instable angina (IA). The subjects of the study were 60 patients with CHD, whose clinical variant (stable angina, PMI or IA) had been determined by stress echocardiography. The control group consisted of 20 patients, not suffering from CHD, but having cardiovascular risk factors (arterial hypertension, dyslipoproteinemia, male gender, obesity, elderly age). All patients underwent routine clinical examination and biochemical blood tests. Serum levels of CRP, fibrinogen and ferritin were highest in the patients with IA and significantly differed from those in the control group. The difference in serum iron levels and total iron-binding capacity in serum (TIBC) between the groups were insignificant. Correlations between serum level of iron, TIBC and ferritin level were found neither in CHD patients (r = 0.1) nor in the control group (r = 0.15). No correlation between serum level of ferritin and CRP level was observed in the control group, but in all CHD groups this correlation was significant. The strongest correlation between these values was observed in the patients with IA. Besides, correlations between serum levels of ferritin and CRP (r = 0.46, p < 0.02) and between ferritin and fibrinogen levels (r = 0.39, p < 0.05) were found in the patients with IA. In patients with CHD, especially those who have IA, serum ferritin should be considered among acute phase proteins, reflecting destabilization of atherosclerotic plaque.
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PMID:[Ferritin and other acute phase proteins in various forms of coronary heart disease]. 1580 27

The aim of this study was to determine whether there is an association between the nutritional status of the mother and that of her 2-year-old to 5-year-old child in a rural village in South Africa where there is a high prevalence of childhood malnutrition (in particular, deficiencies of vitamin A and iron) and of maternal obesity. A blood sample and anthropometric measurements were obtained for 118 child-mother pairs. There was a positive mother-child correlation for serum ferritin (R=0.2304, P<0.05) and haemoglobin (R=0.2664, P<0.01) concentrations, respectively. The child of an anaemic mother had a relative risk of 1.632 of also being anaemic. There was no mother-child association for either serum retinol concentration or anthropometric measurements. Serum retinol concentrations showed a positive correlation with both serum ferritin (mothers only; R=0.2161, P<0.01) and haemoglobin (R=0.2807, P<0.01 for mothers; and R=0.2710, P < 0.01 for children) concentrations. The mother-child association for iron status is probably because of an inadequate dietary intake and low bioavailability of dietary iron, which are major causes of iron deficiency. The lack of mother-child association for serum retinol concentration could probably be ascribed to the fact that children are more susceptible to vitamin A deficiency than adults because of childhood diseases.
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PMID:Is there an association between the nutritional status of the mother and that of her 2-year-old to 5-year-old child? 1609 35

The epidemiology of maintenance dialysis patients and heart failure patients has striking similarities. Both groups have a high prevalence of comorbid conditions, a high hospitalization rate, a low self-reported quality of life, and an excessively high mortality risk, mostly because of cardiovascular causes. Observational studies in both dialysis and heart failure patients have indicated the lack of a significant association between the traditional cardiovascular risk factors and mortality, or the existence of a paradoxic or reverse association, in that obesity, hypercholesterolemia, and hypertension appear to confer survival advantages. The time discrepancy between the 2 sets of risk factors, that is, overnutrition (long-term killer) versus undernutrition (short-term killer) may explain the overwhelming role of malnutrition, inflammation, and cachexia in causing the reverse epidemiology, which may exist in more than 20 million Americans. We have reviewed the opposing views about the concept of reverse epidemiology in dialysis and heart failure patients, the recent Die Deutsche Diabetes Dialyze study findings, and the possible role of racial disparities. Contradictory findings on hyperhomocysteinemia in dialysis patients are reviewed in greater details as a possible example of publication bias. Additional findings related to intravenous iron and serum ferritin, calcium, and leptin levels in dialysis patients may enhance our understanding of the new paradigm. The association between obesity and increased death risk in kidney transplanted patients is reviewed as an example of the reversal of reverse epidemiology. Studying the epidemiology of dialysis patients as the archetypical population with such paradoxic associations may lead to the development of population-specific guidelines and treatment strategies beyond the current Framingham cardiovascular risk factor paradigm.
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PMID:Epidemiology of dialysis patients and heart failure patients. 1653 Jun 5

OBJECTIVE- We examined the influence of a moderately elevated serum ferritin level at entry to care on the risk of gestational diabetes mellitus (GDM) and a possible mechanism (increased iron stores versus inflammation). RESEARCH DESIGN AND METHODS- In a prospective observational study with 1,456 healthy pregnant women in Camden, New Jersey, serum ferritin and anthropometric measurements were determined. Serum C-reactive protein (CRP) concentration was measured in a nested case-control study of 172 subjects. RESULTS- Women who developed GDM had a higher concentration of serum ferritin than women who did not develop GDM (P < 0.001). Elevated serum ferritin level (highest quintile) was significantly and positively correlated with prepregnant BMI and skinfold measurements. Women in the highest quintile of serum ferritin had a twofold increased risk of developing GDM adjusted for several known risk factors (adjusted odds ratio, 2.02 [95% CI 1.04-3.92], P < 0.05). Similar results were obtained with a nested case-control study, in which women in the highest tertile of serum ferritin (2.35 [1.06-5.22], P < 0.05) or CRP (2.67 [1.16-6.17], P < 0.001) had a greater than twofold increased risk of GDM. However, these effects were modified and became nonstatistically significant after additional adjustment for prepregnant BMI. CONCLUSIONS- Elevated serum ferritin concentrations early in gestation are associated with an increased risk of GDM. The association, at least in part, is mediated by the maternal fat mass and obesity. These data suggest a possible link between elevated serum ferritin and low-grade inflammation.
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PMID:Association of elevated serum ferritin levels and the risk of gestational diabetes mellitus in pregnant women: The Camden study. 1664 40

Authors evaluated the prevalence of symptoms of the metabolic syndrome and insulin resistance in 25 patients with adrenal incidentalomas (10 men, 15 women) of the mean age 57.9+/-15 years. 15 patients had adrenal adenoma determined by CT or MR scan and 10 had unilateral or bilateral hyperplasia. The prevalence of obesity was 72%, arterial hypertension 60%, diabetes mellitus or impaired glucose tolerance 28%, hyperlipidemia 56% and hyperuricemia 20%, respectively, which is more frequent occurrence than that in normal human population. Patients with adrenal adenomas had mildly but significantly higher body mass index (BMI, p<0.05) and insulin resistance calculated as HOMA IR (p<0.05) and FIRI (p<0.05) and significantly higher values of serum ferritin (p<0.01). Plasma cortisol values were slightly but not significantly higher in the group with adrenal adenomas. Authors conclude that adrenal adenomas are probably more related to the metabolic syndrome than adrenal hyperplasia.
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PMID:Adrenal incidentalomas and the metabolic syndrome--are there any differences between adenoma and hyperplasia? 1683 60


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