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Query: UMLS:C0011849 (diabetes)
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We analyzed survival and causes of death among 163 patients with primary hemochromatosis diagnosed between 1959 and 1983. The mean follow-up period was 10.5 +/- 5.6 years (+/- S.D.). Cumulative survival was 92 per cent at 5 years, 76 per cent at 10 years, 59 per cent at 15 years, and 49 per cent at 20 years. Life expectancy was reduced in patients with cirrhosis of the liver as compared with those without cirrhosis (P less than or equal to 0.05), in patients with diabetes mellitus as compared with those without diabetes (P less than or equal to 0.002), and in patients who could not be depleted of iron during the first 18 months of venesection therapy as compared with those who could be depleted (P less than or equal to 0.001). Prognosis was not influenced by sex (P less than or equal to 0.5). Patients without cirrhosis had a life expectancy that was not different from that expected in an age- and sex-matched normal population. Analysis of the causes of death in 53 patients, as compared with the normal population, showed that liver cancer was 219 times more frequent among the patients (16 patients), cardiomyopathy was 306 times more frequent (3 patients), liver cirrhosis was 13 times more frequent (10 patients), and diabetes mellitus was 7 times more frequent (3 patients). Death rates for other causes, including extrahepatic carcinomas (seven patients), were not different from the rates expected. We conclude that patients with hemochromatosis diagnosed in the precirrhotic stage and treated by venesection have a normal life expectancy, whereas cirrhotic patients have a shortened life expectancy and a high risk of liver cancer even when complete iron depletion has been achieved.
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PMID:Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. 405 6

The precision of CA 19-9 RIA kit was evaluated by recovery, reproducibility and dilution test with very satisfactory results. The CA 19-9 value in sera from 52 healthy individuals and from 224 patients with gastric intestinal cancer and other benign disease, showed an increased positive rate in several cases of gastric intestinal cancer. For example, the positive rate in pancreatic cancer, bile duct cancer, colo-rectal cancer, gastric cancer, esophagus cancer, primary biliary cirrhosis diabetes mellitus, liver cirrhosis and chronic hepatitis was 60%, 75%, 55.6%, 45.6%, 20%, 28.6%, 22.7%, 13.7% and 1.7% respectively. By contrast, values from patients with acute hepatitis, fulminant hepatitis, fatty liver, gastric duodenal ulcer, pancreatitis, and primary liver cancer were within the normal range. In this study, CA 19-9 RIA were found to be significant as an adjunct in the management of patients with gastrointestinal cancer, especially pancreatic cancer, and bile duct cancer.
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PMID:[Serum determination of CA 19-9 in patients with digestive cancers and its diagnostic evaluation]. 658 10

Although many viral agents may be associated with inflammatory hepatic changes, the vast majority of clinically important viral hepatitis is caused by hepatitis A, hepatitis B and the non A, non B agents. Infection of the liver of man by these hepatotropic agents is still a major public health problem in all parts of the world and constitutes a major hazard of the transfusion of blood and plasma derivatives. The magnitude of this hepatitis problem is not only documented by the about 200 million carriers of the hepatitis-B virus throughout the world, many of them asymptomatic, but also by the fact, that hepatitis B and non A, non B may progress to chronic liver disease, including cirrhosis and probably primary liver cancer. Potentially important pathogenetic determinants include viral factors such as subtype, dosage and mode of transmission and host factors such as age, sex, preexisting liver disease, coexisting non-liver disease (diabetes etc.), genetics and immune response to viral or autoantigens. As the virus itself seems not directly cytopathic, the diversity of lesions has been attributed to variation in the capacity of the host's response.
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PMID:[Virus-induced liver diseases in humans. I. Viral hepatitis]. 681 82

As reported previously, we have conducted studies on causes of death among diabetic patients during the 25-year period, from 1960 to 1984, in Osaka District, Japan. We have now added the most recent 5-year data, for 1985-1989, and analyzed changes in causes of death during the entire 30-year period as a whole. The subjects studied were those for whom a total of 32,222 death certificates had been filed in Osaka Prefecture, from 1960 to 1989, with diabetes mentioned either as the underlying cause or as a contributory condition. The relative number of death certificates mentioning diabetes as the underlying cause, which had been decreasing during the 25-year study period, showed a further decrease, reaching the lowest value, 33.4%, for the period 1985-1989. The mean age at death exceeded 70 years for all causes of death, showing a continuous increasing trend. An increase in disease of the heart and a decrease in cerebrovascular disease were observed, making the difference between the two causes greater since 1980-1984. Malignant neoplasms, ischemic heart disease, and pneumonia and bronchitis also showed steady increases. The O/E ratios (ratio of observed/expected number of deaths) for cirrhosis of the liver and tuberculosis were markedly increased, while that for malignant neoplasms was only about 0.5, suggesting extreme underestimation of the number of diabetic cases with cancer. Among malignant neoplasms, an increasing trend in liver cancer was remarkable and was associated with a relatively high O/E ratio.
Diabetes Res Clin Pract 1994 Jun
PMID:Changes in causes of death in diabetic patients based on death certificates during a 30-year period in Osaka District, Japan, with special reference to cancer mortality. 795 7

The relationship between family history of selected neoplasms in first-degree relatives and the risk of pancreatic, liver, and gallbladder cancer was investigated using data from a case-control study conducted in northern Italy on 320 histologically confirmed incident cases of liver cancer, 58 of gallbladder cancer, 362 of pancreatic cancer, and 1408 controls admitted to the hospital for acute, nonneoplastic, nondigestive tract disorders. Significant associations were observed between family history of hepatocellular carcinoma and primary liver cancer [relative risk (RR) = 2.4; 95% confidence interval (CI), 1.3 to 4.4], between family history of pancreatic cancer and pancreatic cancer (RR = 3.0; 95% CI, 1.4 to 6.6), and between family history of gallbladder cancer and gallbladder cancer (RR = 13.9; 95% CI, 1.2 to 163.9). The elevated risk of liver cancer associated with family history was not materially modified by adjustment for tobacco, alcohol, and personal history of cirrhosis and hepatitis (RR = 2.9; 95% CI, 1.5 to 5.3). Similarly, the risk for pancreatic cancer did not appreciably change after allowance for tobacco, alcohol, dietary factors, and medical history of diabetes and pancreatitis (RR = 2.8; 95% CI, 1.3 to 6.3). This pattern of risk would support the existence of a genetic component in the familial aggregation of liver and pancreatic cancer. In terms of population attributable risk, approximately 3% of the newly diagnosed liver and pancreatic cancers would be related to this familial component.
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PMID:Family history and the risk of liver, gallbladder, and pancreatic cancer. 801 68

Over the last couple of decades a reduction of estrogen by at least 80% in combined oral contraceptives (OCs) and much research have resulted in effective and safe contraception. We still do not know longterm effects of OCs however. OCs may protect against endometrial and ovarian cancer. A link between current OC use and liver cancer exists in areas where liver cancer is rare. An association between OC use and cervical cancer disappears when researchers control for sexual activity and barrier method use. Some research shows OC use increases the risk of breast cancer, while other research does not. There does appear to be an increased risk of breast cancer developing in women younger than 46 years of age and who have used OCs for at least 10 years. Women who have a preexisting cardiovascular condition and/or smoke should not use OCs. OC progestogens may impair glucose metabolism in healthy women, but just for 6 months. Women with diabetes mellitus can use OCs, but may need to increase insulin intake. OCs can cause hypertension in 4-5% of healthy women and worsen hypertension in about 9-16% of hypertensive women. Progestogen-only OCs have fewer systemic side effects than combined OCs, but often cause menstrual changes. Their long term effects are not yet known. Injectables containing a progestogen cause few, if any, adverse effects. The subdermal implant, Norplant, tends to cause menstrual disturbances, but is safe and effective. Progestogen - only vaginal rings are as effective as progestogen-only OCs, but menstrual irregularities are common. Failure rates for combined vaginal rings match those of combined OCs. Long-term effects of vaginal rings are not known. Postcoital contraception does not cause serious side effects, but may cause vomiting and menstrual irregularities. A levonorgestrel-releasing IUD is effective and reduces menstrual blood loss, sometimes resulting in amenorrhea. Hormonal injections in men are unlikely in the near future.
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PMID:Hormonal contraception. 829 64

The population attributable risks (ARs) for hepatocellular carcinoma (HCC) were estimated in relation to low education level, heavy alcohol consumption, low vegetable and fruit intake, history of hepatitis, diabetes, liver cirrhosis and oral contraceptive use, using data from a case-control study conducted between 1984 and 1993 in Northern Italy. Cases were 320 patients (235 males and 85 females) with histologically or serologically confirmed HCC, and controls were 1408 patients (1031 males and 377 females) admitted to the same network of hospitals for acute, non-neoplastic or non-digestive tract conditions, unrelated to any of the known or likely risk factors for primary liver cancer. The ARs were 40% for low vegetable and fruit consumption, 31% for low education, 18% for liver cirrhosis, 16% for hepatitis, 8% for diabetes and 7% for heavy alcohol consumption. Together, these factors explained 74% of hepatocellular cancer cases. Compared with females, males had higher ARs for cirrhosis (21% versus 11%), diabetes (10% versus 2%) and heavy alcohol consumption (9% versus 1%). The percentage of HCC attributable to all factors considered together was 78% for males and 67% for females. Thus, even if available information on hepatitis and dietary factors was limited, and the AR estimates were based on several arbitrary assumptions, available knowledge could, in principle, reduce the burden of the disease in Italy from 3300 deaths to approximately 750 for males, and from 1600 to approximately 500 for females.
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PMID:Attributable risks for hepatocellular carcinoma in northern Italy. 927 46

The relationship between diabetes mellitus and primary liver cancer was investigated in a case-control study conducted in Italy between 1984 and 1996 on 428 cases with incident, histologically confirmed hepatocellular carcinoma, 59 with gallbladder and bile duct cancer, and 1,502 control subjects in the hospital for acute non-neoplastic diseases. Sixty-four cases of hepatocellular carcinoma vs. 87 controls reported a history of diabetes, corresponding to an odds ratio (OR) of 2.3 after allowance for age, sex and area of residence, and of 2.1 [95% confidence interval (CI) = 1.4-3.2] after further allowance for alcohol and tobacco consumption, history of hepatitis and liver cirrhosis, body mass index and history of liver cancer in first-degree relatives. The ORs were similar both for subjects diagnosed with diabetes below age 45, who most likely had insulin-dependent diabetes, and for those diagnosed later, who were likelier to have non-insulin-dependent diabetes. The OR was 2.3 for subjects whose diabetes was diagnosed <5 years before diagnosis of liver cancer, 1.9 for those diagnosed 5-9 years in advance and 2.2 for those diagnosed since 10 years or more. Five cases of gallbladder and bile duct cancer reported a history of diabetes: the corresponding OR was 1.2 (95% CI 0.5-2.9). The OR of hepatocellular carcinoma was 2.4 for males and 2.0 for females, 3.0 for subjects diagnosed with liver cancer under age 60 and 1.8 for those diagnosed at age 60 or over. None of the other covariates considered, including education, history of hepatitis, liver cirrhosis and alcohol drinking showed any meaningful modifying effect or interaction. The potential pathogenic mechanisms include liver alteration-and consequent cell proliferation-in subjects with diabetes. Thus a history of diabetes mellitus could explain about 8% (95% CI 5-11) of cases of liver cancer in this population.
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PMID:Diabetes mellitus and the risk of primary liver cancer. 933 43

The complications of iron overload in hemochromatosis can be avoided by early diagnosis and appropriate management. Therapeutic phlebotomy is used to remove excess iron and maintain low normal body iron stores, and it should be initiated in men with serum ferritin levels of 300 microg/L or more and in women with serum ferritin levels of 200 microg/L or more, regardless of the presence or absence of symptoms. Typically, therapeutic phlebotomy consists of 1) removal of 1 unit (450 to 500 mL) of blood weekly until the serum ferritin level is 10 to 20 microg/L and 2) maintenance of the serum ferritin level at 50 microg/L or less thereafter by periodic removal of blood. Hyperferritinemia attributable to iron overload is resolved by therapeutic phlebotomy. When applied before iron overload becomes severe, this treatment also prevents complications of iron overload, including hepatic cirrhosis, primary liver cancer, diabetes mellitus, hypogonadotrophic hypogonadism, joint disease, and cardiomyopathy. In patients with established iron overload disease, weakness, fatigue, increased hepatic enzyme concentrations, right upper quadrant pain, and hyperpigmentation are often substantially alleviated by therapeutic phlebotomy. Patients with liver disease, joint disease, diabetes mellitus and other endocrinopathic abnormalities, and cardiac abnormalities often require additional, specific management. Dietary management of hemochromatosis includes avoidance of medicinal iron, mineral supplements, excess vitamin C, and uncooked seafoods. This can reduce the rate of iron reaccumulation; reduce retention of nonferrous metals; and help reduce complications of liver disease, diabetes mellitus, and Vibrio infection. This comprehensive approach to the management of hemochromatosis can decrease the frequency and severity of iron overload, improve quality of life, and increase longevity.
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PMID:Management of hemochromatosis. Hemochromatosis Management Working Group. 986 45

Population screening for hemochromatosis done by using the transferrin saturation test has been advocated by experts to permit the initiation of therapeutic phlebotomy before the onset of clinical disease. The discovery of a gene associated with hemochromatosis has made DNA testing another option for screening and diagnosis. In this paper, U.S. Preventive Services Task Force criteria are used to evaluate the evidence for the usefulness of population screening done by using iron measures or genetic testing. Published clinical research offers little evidence to suggest that population screening for hemochromatosis done by using genetic testing improves clinical outcomes. Although one recently discovered mutation, C282Y, accounts for 60% to 92% of cases of the disease in series of patients with hemochromatosis, uncertainties remain about the clinical penetrance of various genotypes; the accuracy of genetic testing; and the ethical, legal, and social effects of genetic testing. Before population screening for hemochromatosis done by using transferrin saturation testing can be recommended, laboratory standardization needs to be addressed and questions about risk for clinical disease in asymptomatic persons with mutations or early biochemical expression of disease require resolution. Evidence from case series suggests that hemochromatosis may be associated with liver cancer, other liver disease, diabetes, bradyarrhythmias, and arthritis. In all studies but one, however, estimation of the magnitude and significance of this risk is limited by lack of adequate comparison groups. The need for population data to answer questions about penetrance among asymptomatic persons should not impede efforts to increase the detection and treatment of hemochromatosis in persons found to have elevated iron measures a family history of hemochromatosis, or consistent early signs and symptoms of the disease.
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PMID:Iron overload, public health, and genetics: evaluating the evidence for hemochromatosis screening. 986 50


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