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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU. m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2). Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs. -84% in control subjects; P = 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P = 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance.
Diabetes 2001 Aug
PMID:Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. 1147 47

Hereditary hemochromatosis (HHC) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and deposition in the liver, pancreas, heart, joints, and pituitary gland. Without treatment, death may occur from cirrhosis, primary liver cancer, diabetes, or cardiomyopathy. In 1996, HFE, the gene for HHC, was mapped on the short arm of chromosome 6 (6p21.3). Two of the 37 allelic variants of HFE described to date (C282Y and H63D) are significantly correlated with HHC. Homozygosity for the C282Y mutation was found in 52-100% of previous studies on clinically diagnosed probands. In this review, 5% of HHC probands were found to be compound heterozygotes (C282Y/H63D), and 1.5% were homozygous for the H63D mutation; 3.6% were C282Y heterozygotes, and 5.2% were H63D heterozygotes. In 7% of cases, C282Y and H63D mutations were not present. In the general population, the frequency of the C282Y/C282Y genotype is 0.4%. C282Y heterozygosity ranges from 9.2% in Europeans to nil in Asian, Indian subcontinent, African/Middle Eastern, and Australasian populations. The H63D carrier frequency is 22% in European populations. Accurate data on the penetrance of the different HFE genotypes are not available. Extrapolating from limited clinical observations in screening studies, an estimated 40--70% of persons with the C282Y homozygous genotype will develop clinical evidence of iron overload. A smaller proportion will die from complications of iron overload. To date, population screening for HHC is not recommended because of uncertainties about optimal screening strategies, optimal care for susceptible persons, laboratory standardization, and the potential for stigmatization or discrimination.
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PMID:HFE gene and hereditary hemochromatosis: a HuGE review. Human Genome Epidemiology. 1147 83

The content of body iron is regulated primarily by absorption since humans have no physiological mechanism by which excess iron is excreted. This regulation, however, is not absolute. Many factors such as the content of diets, iron doses, life styles, etc. influence iron absorption. In the past, nutrition programs for iron fortification and the ingestion of iron preparations have been widely practiced because of the seriousness of worldwide iron deficiency. Also, we now know that a significant number of asymptomatic people carry the hemochromatosis gene, HFE, indicating that these people have the potential to accumulate excess body iron in their lifetime. Excess body iron can be highly toxic. This toxicity involves many organs leading to a variety of serious diseases such as liver disease, heart disease, diabetes mellitus, hormonal abnormalities, dysfunctional immune system, etc. The tissue damage associated with iron overload is believed to result primarily from free radical reactions mediated by iron. Iron is an effective catalyst in free radical reactions. The diseases associated with iron overload can be managed effectively or prevented. Therefore, early diagnosis of iron overload and appropriate therapy are critical. By providing the necessary laboratory data, clinical chemistry laboratories can play the pivotal role in the management of these health problems.
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PMID:Chronic iron overload and toxicity: clinical chemistry perspective. 1151 32

Hemochromatosis is a genetic disease of iron overload due to intestinal hyperabsorption of iron. It is one of the most prevalent autosomal recessive diseases in Caucasian populations. Hemochromatosis causes severe visceral and metabolic complications at adulthood, which include cirrhosis, diabetes, arthropathy and cardiac failure. A major breakthrough has been the discovery, in 1996, of the HFE gene which is strongly associated with the phenotypic expression of the disease. This discovery has, very quickly, provided a powerful genetic blood test which permits, in most cases, to establish the diagnosis in a non invasive way (i.e. without a liver biopsy). Hemochromatosis can be cured by repeated venesections provided the diagnosis has been detected sufficiently early. Moreover, an efficient preventive strategy can be applied to family members and should now be proposed to the general population. Finally, the identification of the HFE gene has paved the way for the identification of new iron overload entities.
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PMID:Hemochromatosis at the intersection of classical medicine and molecular biology. 1155 26

Aminoacetone (AA) is a threonine and glycine catabolite long known to accumulate in cri-du-chat and threoninemia syndromes and, more recently, implicated as a contributing source of methylglyoxal (MG) in diabetes mellitus. Oxidation of AA to MG, NH(4)(+), and H(2)O(2) has been reported to be catalyzed by a copper-dependent semicarbazide sensitive amine oxidase (SSAO) as well as by Cu(II) ions. We here study the mechanism of AA aerobic oxidation, in the presence and absence of iron ions, and coupled to iron release from ferritin. Aminoacetone (1-7 mM) autoxidizes in Chelex-treated phosphate buffer (pH 7.4) to yield stoichiometric amounts of MG and NH(4)(+). Superoxide radical was shown to propagate this reaction as indicated by strong inhibition of oxygen uptake by superoxide dismutase (SOD) (1-50 units/mL; up to 90%) or semicarbazide (0.5-5 mM; up to 80%) and by EPR spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which detected the formation of the DMPO-(*)OH adduct as a decomposition product from the DMPO-O(2)(*)(-) adduct. Accordingly, oxygen uptake by AA is accelerated upon addition of xanthine/xanthine oxidase, a well-known enzymatic source of O(2)(*)(-) radicals. Under Fe(II)EDTA catalysis, SOD (<50 units/mL) had little effect on the oxygen uptake curve or on the EPR spectrum of AA/DMPO, which shows intense signals of the DMPO-(*)OH adduct and of a secondary carbon-centered DMPO adduct, attributable to the AA(*) enoyl radical. In the presence of iron, simultaneous (two) electron transfer from both Fe(II) and AA to O(2), leading directly to H(2)O(2) generation followed by the Fenton reaction is thought to take place. Aminoacetone was also found to induce dose-dependent Fe(II) release from horse spleen ferritin, putatively mediated by both O(2)(*)(-) and AA(*) enoyl radicals, and the co-oxidation of added hemoglobin and myoglobin, which may be viewed as the initial step for potential further iron release. It is thus tempting to propose that AA, accumulated in the blood and other tissues of diabetics, besides being metabolized by SSAO, may release iron and undergo spontaneous and iron-catalyzed oxidation with production of reactive H(2)O(2) and O(2)(*)(-), triggering pathological responses. It is noteworthy that noninsulin-dependent diabetes has been frequently associated with iron overload and oxidative stress.
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PMID:Aerobic oxidation of aminoacetone, a threonine catabolite: iron catalysis and coupled iron release from ferritin. 1155 49

The aim of this study was to compare the frequencies of HFE mutations in African-American women with non-insulin-dependent diabetes mellitus (NIDDM) to that of controls and to determine whether these mutations are associated with NIDDM and iron overload. We studied 167 African-American women with NIDDM. The 71 non-diabetic controls were African-American female controls. HLA-A and -B typing and HFE mutation analysis for C282Y and H63D alleles were performed using standard molecular genetic techniques. The frequencies of C282Y and H63D were not significantly different in NIDDM patients and controls. C282Y was observed in 0.59% of patients and 1.41% of controls. H63D was observed in 2.99% of patients and 3.08% of controls. All of the NIDDM patients who possessed either C282Y or H63D mutations had normal values of serum ferritin, serum iron and transferrin saturation. A woman who inherited C282Y also possessed HLA-A3, -B7 which is considered part of the ancestral haplotype containing the gene predisposing to hemochromatosis in Caucasians. The frequencies of C282Y and H63D vary in African Americans from different geographic regions of the United States; this variance can be explained by Caucasian admixture. Although most iron overload cases in African Americans bear more resemblance to cases of African iron overload than to those of Caucasian hemochromatosis, rare cases resembling Caucasian hemochromatosis have been observed in African Americans.
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PMID:HFE mutations in African-American women with non-insulin-dependent diabetes mellitus. 1176 82

The object was to analyze, in a nationwide survey, the incidence and course of hereditary hemochromatosis in relation to the degree of iron overload and the presence of organ damage. The study included 179 Danish Caucasian patients with clinically overt hemochromatosis diagnosed between 1948 and 1985. A cohort of 158 patients was followed for a median of 8.5 years (range: 0.2-29.5). From 1951 to 1975, the yearly relative incidence rate was constant: 0.58/100,000 persons >20 years of age. From 1981 to 1985, the yearly relative incidence rate rose to 1.40/100,000 persons >20 years of age. Survival was reduced in the entire series when compared with a matched control population ( p<0.0001). There was a steady increase in survival from 1948 to 1985 ( p<0.002). Survival was significantly reduced in patients with liver cirrhosis and/or diabetes mellitus ( p<0.01). In contrast, survival in patients without cirrhosis or diabetes was similar to rates expected. Survival in patients with arthropathy was higher than in patients without joint affection ( p<0.004). Patients adequately treated with phlebotomy ( n=66) had a higher survival than inadequately treated patients ( n=62; p<0.0001). Adequately treated patients with cirrhosis and/or diabetes had better survival than inadequately treated patients with similar organ damage ( p<0.001). The main causes of death were hepatic failure due to cirrhosis (32.0%) and cirrhosis with liver cancer (23.1%). Sharpened diagnostic awareness has improved early diagnosis and increased the diagnostic frequency of clinical hemochromatosis. Adequate phlebotomy treatment was the major determinant of survival and markedly improved prognosis. Early detection and treatment of this common iron overload disorder is crucial and can completely prevent any excess mortality caused by hemochromatosis.
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PMID:Clinically overt hereditary hemochromatosis in Denmark 1948-1985: epidemiology, factors of significance for long-term survival, and causes of death in 179 patients. 1179 15

We report here a revue of hemodialysis catheter-related infections data published since 1985. The reported prevalence of bacteremia is 1 to 20% of catheters, and incidence is 0.72 to 9/1000 catheter-days. Local infection is reported in 6 to 63% of catheters and in 1 to 5/1000 catheter-days. Tunneled catheters and implantables chambers reported less infection rate. The most severe complication is endocarditis (4% rate). Death occurs in 8 to 20% of cases. Reported microbial data show that Staphylococcus aureus (SA) is responsible for most infections ahead of non-aureus Staphylococcus. SA skin colonisation is a risk factor for catheter colonisation and the first step of infection. On the other hand, the host immunity impairment in hemodialysis patients seems a significant risk factor. Iron overload, specially after blood transfusions, older age, diabetes mellitus, low serum albumin level, previous history of bacteremia and immunosuppressive treatment have been frequently involved. Other catheter-related factors are time of use, absence of tunnel and use for parenteral nutrition. Nurses plans, dressing type and frequency, nurses work experience are also important. In spite of recent progress in risk factor understanding, hemodialysis-related infection remains frequent. Multicentre studies are necessary to better evaluated care protocols and new catheter material.
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PMID:[Incidence and risk factors for infections from hemodialysis catheters]. 1181 Oct 6

In patients with nonalcoholic steatohepatitis (NASH), age, obesity, and diabetes mellitus are independent predictors of the degree of fibrosis. The relative risk for fibrosis adjusted for sex was also associated with increasing grade of Perls stain. The aim of this study was to determine whether the risk factors for fibrosis described in NASH are also risk factors in alcohol-induced liver disease. A total of 268 alcoholic patients with negative hepatitis B virus and hepatitis C virus serology underwent liver biopsy. Fibrosis was assessed semiquantitatively by a score fluctuating between 0 to 8. Liver iron overload was assessed by Perls staining and graded in 4 classes. We have used multivariate regression with partial correlation analysis to assess the variability of fibrosis score according to the value of 7 variables: sex, age, body mass index (BMI) in the past year before the hospitalization when the patient was asymptomatic, daily alcohol intake over the past 5 years, total duration of alcohol abuse, Perls grade, and blood glucose level. In the multivariate regression, fibrosis score was positively correlated with age (P =.001), BMI (P =.002), female sex (P <.05), Perls grade (P <.05), and blood glucose level (P <.05). Twenty percent of the variability of fibrosis score was explained by the 7 variables. In conclusion, after adjustment for daily alcohol intake and total duration of alcohol abuse, BMI, Perls grade, and blood glucose are also independent risk factors for fibrosis in alcohol-induced liver disease, raising therapeutic implications for the management of these patients.
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PMID:Risk factors of fibrosis in alcohol-induced liver disease. 1187 Mar 78

Hereditary hemochromatosis is the most common inherited single-gene disorder in people of northern European descent. It is characterized by increased intestinal absorption of iron, with deposition of the iron in multiple organs. Previously, the classic description was combined diabetes mellitus, cutaneous hyperpigmentation and cirrhosis. Increasingly, however, hereditary hemochromatosis is being diagnosed at an earlier, less symptomatic stage. The diagnosis is based on a combination of clinical, laboratory and pathologic findings, including elevated serum transferrin saturation. Life expectancy is usually normal if phlebotomy is initiated before the development of cirrhosis or diabetes mellitus. Hereditary hemochromatosis is associated with mutations in the HFE gene. Between 60 and 93 percent of patients with the disorder are homozygous for a mutation designated C282Y. The HFE gene test is useful in confirming the diagnosis of hereditary hemochromatosis, screening adult family members of patients with HFE mutations and resolving ambiguities concerning iron overload.
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PMID:Recognition and management of hereditary hemochromatosis. 1189 57


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