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

Hemochromatosis is one of the most frequent genetic diseases among the white populations, affecting one in three hundred persons. Its diagnosis has been radically transformed by the discovery of the HFE gene. In a given individual, the diagnosis can, from now on, be ascertained on the sole association of a plasma transferrin saturation (TS) over 45% and homozygosity for the C282Y mutation. Liver biopsy is only required to search for cirrhosis whenever there is hepatomegaly and/or serum ferritin >1000 ng/ml and/or elevated serum AST. Family screening is mandatory, primarily centered on the siblings. The treatment remains based on venesection therapy which improves many features of the disease (one of the most refractory, however, being the joint signs) and permits normal life expectancy provided the diagnosis is established prior to the development of cirrhosis or of insulin-dependent diabetes. In view of the prevalence, the non-invasive diagnosis, the spontaneous severity and the efficacy of a very simple therapy, hemochromatosis should benefit from population screening. This screening could be based, first, on the assessment of transferrin saturation, followed - when elevated - by the search for the C282Y mutation. The discovery of the HFE gene has also paved the road for the individualization of other types of iron overload syndromes which are not HFE-related.
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PMID:Clinical aspects of hemochromatosis. 1109 95

Hyperlipidemia is a known risk factor for fatty infiltration of the liver, a condition that can progress to cirrhosis and liver failure. The objectives of this study were to document the prevalence of fatty infiltration in the livers of hyperlipidemic patients and to identify the predictor variables associated with this condition. Over an 18-month recruitment period, clinical, biochemical, and radiologic assessments were performed in a cross-sectional manner in 95 adult patients referred to an urban hospital-based lipid clinic for evaluation and management of hyperlipidemia. The mean (+/-SD) age of the patients was 55 +/- 13 years. Forty-eight (51%) were male. Fifty-two patients (55%) had hypercholesterolemia, 25 (26%) severe hypertriglyceridemia, 14 (15%) mixed hyperlipidemia, and 4 (4%) moderate hypertriglyceridemia. Obesity and diabetes were present in 36 (38%) and 12 (12%) of cases, respectively. A total of 61 (64%) patients had elevated liver enzyme tests. The most common enzyme abnormalities were an elevated serum ALT in 45 (47%) and GGT in 43 (45%) of patients. Ultrasound findings revealed diffuse fatty liver in 47 patients (50%), of which 21 cases (22%) were mild, 18 (19%) moderate, and 8 (9%) severe. The majority of patients with hypercholesterolemia [35/52 (67%)] had normal ultrasounds, whereas severe hypertriglyceridemia and mixed hyperlipidemia were frequently associated with radiologic evidence of fatty liver (odds ratios 5.9 and 5.1 respectively, P < 0.01). Independent predictors of fatty liver were; AST (P = 0.001), hyperglycemia (P = 0.02), and age (P = 0.04). In a model incorporating known risk factors for fatty liver, diabetes was the only risk factor other than hypertriglyceridemia that was significantly associated with fatty infiltration. No such effect was seen with age, gender, obesity, or alcohol consumption. In conclusions, the results of this study indicate that ultrasonographic evidence of fatty infiltration of the liver is evident in approximately 50% of patients with hyperlipidemia. Hypertriglyceridemia is the lipid profile most often associated with this condition. Serum AST values, hyperglycemia, and age independently predict the presence of fatty infiltration, while hypertriglyceridemia and diabetes are the only risk factors that significantly increase the risk of fatty infiltration in hyperlipidemic patients.
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PMID:Fatty infiltration of liver in hyperlipidemic patients. 1111 62

Otsuka Long-Evans Tokushima Fatty (OLETF) rats were established as a new model of non-insulin-dependent diabetes mellitus. An oral adsorbent, AST-120, is effective in removing such uremic toxins as indoxyl sulfate and delays the progression of chronic renal failure (CRF). This study was designed to determine the effects of AST-120 on the progression of CRF in uninephrectomized OLETF (1/2NxOLETF) rats and the localization of indoxyl sulfate in their kidneys. Four weeks after unilateral nephrectomy, 14 OLETF rats were divided into two groups; AST-120-administered and control 1/2NxOLETF rats. Long-Evans Tokushima Otsuka rats, which are genetically similar to the OLETF rats but not diabetic, were also included. After the administration of AST-120 for 36 weeks, we examined the effects of AST-120 on renal functional and pathological changes in the three groups. The control 1/2NxOLETF rats showed marked hyperglycemia, hyperlipidemia, renal failure, glomerular sclerosis, and tubulointerstitial injury. The administration of AST-120 to the 1/2NxOLETF rats retarded the progression of renal dysfunction and fibrosis, as well as hyperlipidemia, and reduced serum and urinary levels of indoxyl sulfate. Immunohistochemistry showed that AST-120 markedly reduced the overload of indoxyl sulfate in tubular epithelial cells, especially dilated tubules, of the 1/2NxOLETF rats. In conclusion, AST-120 delayed the progression of renal failure and fibrosis in 1/2NxOLETF rats and decreased the overload of indoxyl sulfate on renal tubular cells.
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PMID:An oral adsorbent ameliorates renal overload of indoxyl sulfate and progression of renal failure in diabetic rats. 1115 53

The authors performed a survey in 3,615 Shinawatra employees aged 18-60 years to determine the abnormalities found with routine checkup. The annual checkup included: history taking. anthropometric measurement, physical examination, complete blood count, urine analysis, chest roentgenography, blood chemistry (fasting blood glucose, BUN, creatinine, uric acid, AST/ALT, cholesterol, triglyceride and HDL-cholesterol). The prevalence of abnormalities with management change detected by complete blood count, urine analysis was low and we did not recommend the routine use of complete blood count and urine analysis. The prevalence of hypertension was more common in males and the prevalence increased sharply after the age of 25 years in males and 40 years in females. The prevalence of abnormalities of BUN, creatinine (both males and females) and uric acid (in females) was very low. There was high prevalence of high AST/ALT which suggested hepatitis in our population, and the prevalence was more common in males beginning at a young age. Diabetes mellitus was more common in males especially after the age of 45 years. Chest roentgenography abnormalities were found in 9.4 per cent and the prevalence of abnormalities increased with age and was common after the age of 44 years. Most of the abnormalities found by chest roentgenography were pulmonary infiltration and cardiomegaly. The authors' findings did not recommend the routine use of complete blood count, urine analysis, fasting BUN and creatinine. We recommend routine blood pressure measurement in males aged 25 years or more and in females aged 40 years or more. We suggest routine blood cholesterol measurement in both sexes, blood triglyceride measurement in males aged 25 years or more and fasting blood sugar tests in males aged more than 44 years, chest roentgenography in males and females after the age of 45 years.
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PMID:Are routine checkups necessary?: The Shinawatra's employee study. 1119 9

In light of evidence that some complications of diabetes mellitus may be caused or exacerbated by oxidative damage, we investigated the effects of subacute treatment with the antioxidant quercetin on tissue antioxidant defense systems in streptozotocin-induced diabetic Sprague-Dawley rats (30 days after streptozotocin induction). Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, was administered at a dose of 10mg/kg/day, ip for 14 days, after which liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Treatment of normal rats with quercetin increased serum AST and increased hepatic concentration of oxidized glutathione. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Quercetin treatment of diabetic rats reversed only the diabetic effects on brain oxidized glutathione concentration and on hepatic glutathione peroxidase activity. By contrast, a 20% increase in hepatic lipid peroxidation, a 40% decline in hepatic glutathione concentration, an increase in renal (23%) and cardiac (40%) glutathione peroxidase activities, and a 65% increase in cardiac catalase activity reflect intensified diabetic effects after treatment with quercetin. These results call into question the ability of therapy with the antioxidant quercetin to reverse diabetic oxidative stress in an overall sense.
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PMID:Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic rats. 1142 24

Nonalcoholic fatty liver disease (NAFLD) is most often associated with obesity, type II Diabetes mellitus, hyperlipidemia and chronic viral hepatitis C. The spectrum of changes encompasses fatty liver, steatohepatitis, liver fibrosis and cirrhosis. Most patients are asymptomatic. The aminotransferases are only slightly elevated (ALT > AST). Grade of inflammation and stage of fibrosis can be assessed accurately only by histologic examination of liver biopsy. In most cases prognosis is favourable but in a subgroup of patients NAFLD may progress to cirrhosis. Recent data suggest that up to 70% of cryptogenic cirrhoses are accounted for by nonalcoholic steatohepatitis. At the moment therapeutic modalities of proven value are not available.
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PMID:[Nonalcoholic fatty liver]. 1193 60

It has been proposed that liver dysfunction may contribute to the development of type 2 diabetes. The aim of the present study was to examine whether elevated hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma -glutamyltranspeptidase [GGT]) are associated with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians. We measured ALT, AST, and GGT in 451 nondiabetic (75-g oral glucose tolerance test) Pima Indians (aged 30 +/- 6 years, body fat 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l [mean +/- SD]) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output [HGO] during the low-dose insulin infusion of a hyperinsulinemic clamp) and acute insulin response (AIR) (25-g intravenous glucose challenge). Sixty-three subjects developed diabetes over an average follow-up of 6.9 +/- 4.9 years. In 224 subjects, who remained nondiabetic, follow-up measurements of M and AIR were available. At baseline, ALT, AST, and GGT were related to percent body fat (r = 0.16, 0.17, and 0.11, respectively), M (r = -0.32, - 0.28, and -0.24), and HGO (r = 0.27, 0.12, and 0.14; all P < 0.01). In a proportional hazard analysis with adjustment for age, sex, body fat, M, and AIR, higher ALT [relative hazard 90th vs. 10th centiles (95% CI): 1.9 (1.1-3.3), P = 0.02], but not AST or GGT, predicted diabetes. Elevated ALT at baseline was associated prospectively with an increase in HGO (r = 0.21, P = 0.001) but not with changes in M or AIR (both P = 0.1). Higher ALT concentrations were cross-sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of type 2 diabetes. Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver in the pathogenesis of type 2 diabetes.
Diabetes 2002 Jun
PMID:High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. 1203 78

We used ENU mutagenesis in the mouse for the rapid generation of novel mutant phenotypes for both gene function studies and use as new animal models of human disease (Nolan et al. 2000b). One focus of the program was the development of a blood biochemistry screen. At 8-12 weeks of age, approximately 300 ml of blood was collected from F1 offspring of ENU mutagenized male mice. This yielded approximately 125 ml of plasma, used to perform a profile of 17 standard biochemical tests on an Olympus analyzer. Cohorts of F1 mice were also aged and then retested to detect late onset phenotypes. In total, 1,961 F1s were screened. Outliers were identified by running means and standard deviations. Of 70 mice showing consistent abnormalities in plasma biochemistry, 29 were entered into inheritance testing. Of these, 9 phenotypes were confirmed as inherited, 10 found not to be inherited, and 10 are still being tested. Inherited mutant phenotypes include abnormal lipid profiles (low total and HDL cholesterol, high triglycerides); abnormalities in bone and liver metabolism (low ALP, high ALP, high ALT, and AST); abnormal plasma electrolyte levels (high sodium and chloride); as well as phenotypes of interest for the study of diabetes (high glucose). The gene loci bearing the mutations are currently being mapped and further characterized. Our results have validated our biochemical screen, which is applicable to other mutagenesis projects, and we have produced a new set of mutants with defined metabolic phenotypes.
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PMID:Novel phenotypes identified by plasma biochemical screening in the mouse. 1242 Jan 38

A 66-year-old man with erysipelas was admitted with complaints of oliguria and massive proteinuria/hematuria. He was diagnosed as having acute poststreptococcal glomerulonephritis(APSGN) due to erysipelas infected by group A streptococcus pyogenes. On admission, his white cell count increased to 31,000, and CRP was 27.3 mg/dl. Serum urea nitrogen and creatinine were increased to 90.1 mg/dl and 4.5 mg/dl, respectively. He had diabetes mellitus(HbA1c 7.9%) and liver dysfunction(total bilirubin 3.5 mg/dl, AST 76 IU, ALT 41 IU) caused by alcoholic liver cirrhosis. Hypocomplementemia was found in addition to ASO 216 U/ml and ASK 10,240 x. After antibiotics treatment was initiated, inflammation of the erysipelas began to improve. Disseminated intravascular coagulation syndrome, probably due to sepsis, occurred on the 5th hospital day. He died of gastrointestinal bleeding on the 18th hospital day. Renal autopsy revealed 37% formation of fibrocellular crescents, and marked mesangiolysis was noted by light microscopy. Granular deposition of C3 and IgG was seen along the capillary walls on immunofluorescence study. Intramembranous deposits were scattered on electron microscopy. This case illustrates a fulminant type of APSGN, which was in part attributed to the presence of diabetes and alcoholic liver cirrhosis. Histological findings of crescent formation and marked mesangiolysis may account for the fulminant clinical course.
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PMID:[A case of fulminant acute poststreptococcal glomerulonephritis showing mesangiolysis and crescent formation preceded by erysipelas]. 1247 94

The purpose of this study was to clarify the clinicopathological features of nonalcoholic steatohepatitis (NASH) and identify risk factors for severe hepatic fibrosis. MATERIALS AND METHODS: Eighty-one patients with biopsy-proven NASH were studied. In all patients, the diagnosis of NASH was established on the basis of following criteria: (1) the presence of steatosis, lobular inflammation, and ballooning degeneration on liver biopsy, (2) intake of less than 20 g of ethanol per week, and (3) appropriate exclusion of other liver diseases. RESULTS: The median age was 54 years (range: 21-82 years) and 41 patients were women (51%). Obesity was present in 58 patients (72%), while 25 patients (31%) had diabetes mellitus and 33 patients (41%) had hyperlipidemia. Histologically, 58 patients (72%) had trivial to moderate fibrosis, 6 patients (7%) had bridging fibrosis, and 17 patients (21%) had established cirrhosis. Multiple logistic regression analysis assessed clinical, laboratory and histological factors showed that the risk factors for fibrosis were a low platelet count (P=0.0016), a high AST/ALT ratio (P=0.0229), and the presence of Mallory bodies (P=0.0209). To exclude factors that were a consequence of liver cirrhosis, variables included in the multiple logistic analysis were age, gender, diabetes, obesity, and hyperlipidemia. This showed that older age (P=0.0037) and the absence of hyperlipidemia (P=0.0150) were risk factors for fibrosis. CONCLUSIONS: We found that a low platelet count, a high AST/ALT ratio, and the presence of Mallory bodies were significant predictors of severe liver fibrosis.
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PMID:Nonalcoholic steatohepatitis: risk factors for liver fibrosis. 1247 42


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