Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the prevalence of mutations in the HFE (hemochromatosis) gene in unselected male patients with type 2 diabetes, we examined 220 white men without known diabetes and 220 age-matched white men with type 2 diabetes for mutations in the HFE gene. Nucleotide 845 (C282Y) and 187(H63D) alleles were amplified by polymerase chain reaction (PCR) with lymphocyte DNA. The PCR products were analyzed by restriction enzyme digestion. One of the 220 patients (0.45%) with diabetes was homozygous for the HFE 845A (C282Y) mutation and 25 (11.3%) were heterozygous for the same mutation, of whom 3 (1.3%) were compound heterozygotes also carrying the HFE 187G (H63D) mutation. These frequencies did not differ significantly from the control population without diabetes. There is no evidence that HFE mutations are found in excess in unselected male patients with type 2 diabetes, and there is no indication for a population-based search for an excess of these alleles in type 2 diabetes.
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PMID:Prevalence of HFE (hemochromatosis gene) mutations in unselected male patients with type 2 diabetes. 1069 62

Genetic hemochromatosis (GH) is associated with two mutations of the HFE gene (Cys282Tyr and His63Asp). Heterozygosity for GH is associated with a mild increase in iron metabolism parameters, and increased iron stores are associated with abnormal glucose tolerance and decreased insulin sensitivity in the general population. We have previously shown that the frequency of the two HFE mutations is not increased in patients with type 2 diabetes. However, to assess whether the presence of HFE mutations modulates the clinical presentation of type 2 diabetes, we studied the clinical characteristics and iron metabolism indexes according to the presence of the two mutations in 266 patients with type 2 diabetes. The Cys282Tyr mutation and the His63Asp mutation were present in 9. 8% and 26% of the patients, respectively. Serum iron, transferrin saturation and ferritin concentrations were significantly increased in patients expressing either HFE mutations, compared to those without any mutation. There was no difference in the clinical characteristics in the two groups except that obesity was significantly less frequent in the patients with at least one mutation than in those without any mutation (27.6% vs 42.8%, p=0.02). This finding suggests that, in the absence of obesity, HFE mutations, through the insulin resistance associated with the increase in iron stores, may contribute to the onset of type 2 diabetes.
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PMID:Clinical characteristics of type 2 diabetes in patients with mutations of HFE. 1070 6

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.
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PMID:Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. 1147 47

Aims of the study were: (i) to determine the prevalence of mutations C282Y and H63D in the HFE gene causing hereditary hemochromatosis in patients with type 2 diabetes mellitus and non-diabetics, (ii) to investigate the relationship among HFE genotypes, serum ferritin and glucose intolerance and (iii) to assess possible association of HFE mutations with the susceptibility to develop late diabetic complications in the Czech population. Two approaches were employed - the case-control study comprising diabetics and non-diabetic controls (n = 326) and the cross-sectional study comprising subjects with a previously unknown defect of glucose tolerance (n = 113, oral glucose tolerance test performed in each subject). Allele frequencies of C282Y and H63D did not differ between diabetic and control groups nor among subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes. Ferritin levels significantly differed between diabetic and non-diabetic women (P<1.10 (-3)) and among subjects with NGT, IGT and diabetes (P<0.05). Differences in ferritin levels related to particular genotypes of C282Y and H63D were not detected. Prevalence of diabetes in the first and second quartiles of ferritin distribution differed highly significantly from the prevalence in the third and fourth quartiles in women (P = 0.000037), OR = 3.50 (95% CI, 1.89-6.48). The extent of diabetic late complications did not correlate with ferritin plasma levels.
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PMID:Relations among serum ferritin, C282Y and H63D mutations in the HFE gene and type 2 diabetes mellitus in the Czech population. 1214 86

The relationship between high dietary iron intake, mutations of the HFE gene, and iron status, and their effects on human health are reviewed. Prolonged high dietary intakes of iron are unlikely to result in iron overload in the general population. Homozygotes for the C282Y mutation of the HFE gene have elevated body iron levels. Heterozygotes have normal iron stores but some may be at increased risk for cardiovascular disease. There is no convincing evidence that elevated iron status increases the risk of coronary heart disease or type 2 diabetes, but high iron intakes may increase the risk of colorectal cancer. The dietary levels of iron associated with health risks in different HFE genotypes must be determined.
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PMID:Health implications of iron overload: the role of diet and genotype. 1267 37

Diabetes mellitus is a recognized consequence of hereditary haemochromatosis. Whether the common HFE mutations, that associate with this condition and pre-dispose to increases in serum iron indices, are over-represented in diabetic populations remains controversial. We present data from the largest case-control study of the C282Y and H63D HFE allele frequencies in typical type 2 diabetes mellitus, as defined by an age of onset greater than 30 years and no requirement for insulin in the first year post-diagnosis. We also present a meta-analysis of all similar studies to date. We see no evidence for over-representation of iron loading HFE alleles in type 2 diabetes mellitus, suggesting that screening for HFE mutations in this population is of no value.
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PMID:Typical type 2 diabetes mellitus and HFE gene mutations: a population-based case - control study. 1278 44

Iron metabolism might be involved in the pathogenesis of type 2 diabetes and in the pathogenesis of diabetic retinopathy. C282Y and H63D mutations in the hemochromatosis (HFE) gene are associated with increased serum iron levels and consequently with hereditary hemochromatosis. In the present study, we searched for a relationship between C282Y and H63D gene mutations and the development of proliferative diabetic retinopathy in Caucasians with type 2 diabetes. For this purpose, 90 subjects with type 2 diabetes with proliferative diabetic retinopathy (PDR) were compared to 133 diabetic subjects without PDR. There was a significantly higher frequency of the C282Y heterozygotes in patients with PDR compared to subjects without it (OR=3.0, 95% CI=1.2-8.0; p=0.02), whereas no association was demonstrated between PDR and H63D genotypes (OR=1.1, 95% CI=0.6-2.2; p=0.7). Logistic regression analysis revealed that the C282Y mutation was a significant independent risk factor for the development of PDR (OR=6.1, 95% CI=1.2-30.5; p=0.027). These data suggest that heterozygosity for C282Y might be a novel risk factor for PDR in Caucasians with type 2 diabetes.
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PMID:A hemochromatosis-causing mutation C282Y is a risk factor for proliferative diabetic retinopathy in Caucasians with type 2 diabetes. 1461 19

Iron metabolism might be involved in the pathogenesis of CAD, and C282Y and H63D mutations in the HFE gene are associated with increased serum iron levels and net iron accumulation. The aim of this study was to look for a relationship between the C282Y and H63D gene mutations of the HFE gene and coronary artery disease (CAD) in a group of patients with type 2 diabetes lasting more than 10 years. The C282Y and H63D gene mutations were tested in 338 Caucasians with type 2 diabetes: 156 cases with CAD and 182 subjects with no history of CAD. The C282Y and the H63D HFE gene distributions in patients with CAD (C282Y: YY 0.6%, CY 9.0%, CC 90.4%; H63D: DD 3.8%, HD 21.8%, HH 74.4%) were not significantly different from those of diabetic subjects without CAD (C282Y: YY 0%, CY 8.2%, CC 91.8%; H63D: DD 2.2%, HD 20.3%, HH 77.5%). In conclusion, we failed to demonstrate that the C282Y and H63D HFE gene mutations were risk factors for CAD in Caucasians with type 2 diabetes lasting longer than 10 years.
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PMID:Haemochromatosis-causing mutations C282Y and H63D are not risk factors for coronary artery disease in Caucasians with type 2 diabetes. 1522 29

There is increasing evidence that moderately elevated body iron stores, below levels commonly found in genetic hemochromatosis, may be associated with adverse health outcomes. Genetic hemochromatosis, characterized by transferrin saturation (TS) greater than 45%, is most often linked to homozygosity of the HFE C282Y allele. The phenotype is also modulated by mutations of more recently discovered genes (including ferroportin, hemojuvelin, hepcidin, and transferrin receptor) and environmental factors (including alcohol, viruses, diet, blood loss). Iron overload without hemochromatosis is characterized by high levels of serum ferritin and normal TS, as seen in dysmetabolic hepatosiderosis. Elevated serum ferritin levels predict incident type 2 diabetes in prospective studies and have been associated with hypertension, dyslipidemia, glucose tolerance disturbances, central adiposity, and metabolic syndrome. High ferritin levels are not synonymous with iron overload and may in some cases be a simple marker of insulin resistance.
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PMID:[Iron overload and insulin resistance]. 1629 93

To determine whether the HFE gene variants H63D and C282Y are associated with body iron stores and the risk of type 2 diabetes, we conducted a nested case-control study of 714 incident cases of type 2 diabetes and 1,120 matching control subjects in a prospective cohort, the Nurses' Health Study. In both healthy control and diabetic case subjects, H63D homozygosity, C282Y, and the compound heterozygotes were associated with significantly higher levels of plasma ferritin and significantly lower ratios of transferrin receptors to ferritin. Such effects were independent of age, BMI, and lifestyle factors. Overall, there were no significant differences in genotypes of H63D and C282Y between the case and control subjects. A meta-analysis of 4,245 case and 5,982 control subjects indicated a null association of C282Y with diabetes risk, whereas carriers of H63D or the compound heterozygotes had marginally increased risk (odds ratio [OR] 1.11 [95% CI 1.00-1.25] and 1.60 [0.99-2.60], respectively). In addition, we found a significant interaction between HFE variants and heme iron intake (P for interaction = 0.029). The ORs of type 2 diabetes across increasing quartiles of heme iron were 1.00, 1.21 (0.72-2.01), 1.72 (1.03-2.88), and 1.49 (0.91-2.46) among the participants with either the H63D or C282Y variant, whereas the ORs were 1.00, 0.71 (0.49-1.05), 1.12 (0.76-1.66), and 0.96 (0.65-1.42) among those with wild-type genotypes. Our data indicate significant effects of H63D and C282Y on body iron stores and suggest a potential interaction between HFE genotypes and heme iron intake in relation to the risk of type 2 diabetes.
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PMID:HFE genetic variability, body iron stores, and the risk of type 2 diabetes in U.S. women. 1630 77


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