Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relative hypoparathyroidism (parathyroid hormone [PTH] < or = 200 pg/mL) is prevalent in hemodialysis (HD) patients, with unknown pathogenesis and prognosis. Thus, to clarify risk factors and prognosis of time-dependent relative hypoparathyroidism in HD patients, a retrospective cohort study was performed for 126 HD patients with four or more PTH determinations and no previous total or subtotal parathyroidectomy. Values for intact PTH, ionized calcium, phosphate, magnesium, albumin, creatinine, urea reduction ratio (URR), glucose, hemoglobin A1c (HbA1c), aluminum, and 1,25(OH)2D were obtained at enrollment and at some time during follow-up. The prevalence of relative hypoparathyroidism at entry was 76 of 126 patients (60.3%). Univariate analysis showed that patients with hypoparathyroidism were older, more likely to have diabetes, and had greater ionized calcium levels and lower phosphate, albumin, blood urea nitrogen (BUN), and creatinine levels. Patients with diabetes were older and had a shorter duration of dialysis therapy and lower PTH, phosphate, albumin, BUN, and creatinine levels and URRs. Conversely, multivariate analysis showed that PTH levels at entry were associated directly with creatinine levels and inversely with age and ionized calcium levels (but not diabetes). During follow-up, PTH levels fluctuated concomitantly with ionized calcium and phosphate levels over time in all patients. Time-dependent PTH levels were associated directly with duration of dialysis therapy and use of vitamin D and phosphate and albumin levels, but inversely with age and ionized calcium and magnesium levels (but not glucose or HbA1c levels). Interestingly, time-dependent PTH levels were independently associated with survival after adjusting for traditional risk factors (diabetes, age, albumin and creatinine levels, and URR) and duration of dialysis therapy. We conclude that in HD patients, relative hypoparathyroidism was not associated with diabetes per se. Time-dependent PTH levels were associated with age, duration of dialysis, and levels of ionized calcium, phosphate, albumin, and magnesium. Moreover, relative hypoparathyroidism at entry and lower time-dependent PTH levels predict mortality.
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PMID:Risk factors and risk for mortality of mild hypoparathyroidism in hemodialysis patients. 1204 38

Cardiovascular diseases are the leading causes of mortality among patients with end-stage renal disease (ESRD), with arterial disease and left ventricular hypertrophy being the two principal factors of the high mortality rate in this population. In addition to traditional risk factors (age, gender, diabetes, hypertension, lifestyle, hyperlipidemia, smoking, hyperhomocystinemia), inflammation, oxidative stress and disorders of mineral metabolism may contribute to cardiovascular risk in patients with uremic syndrome. High serum phosphate may influence vascular calcifications directly and indirectly, by worsening secondary hyperparathyroidism. Several treatment options are available for the treatment of hyperphosphatemia and secondary hyperparathyroidism in patients with ESRD. The treatment approach includes a diet low in phosphorus, with less than 1 g/kg/day of protein. Vitamin D supplementation is an important part of treatment. Phosphate binding agents are in most of the patients necessary in addition to diet. Aluminum hydroxide has been widely used for many years. It is very potent, but also very toxic, with severe encephalopathy as the most dangerous side effect. Calcium salts are less potent, and were considered safe for use in patients on dialysis. However, improvement in the understanding of vascular calcifications has demonstrated that calcium overload significantly contributes to widespread atherosclerosis in patients with ESRD. Sevelamer-hydrochloride is a novel non-aluminum, non-calcium containing phosphate binder, which is capable of reducing the levels of phosphorus as well as of low-density lipoprotein cholesterol, and increasing high-density lipoprotein cholesterol.
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PMID:[Hyperphosphatemia and cardiovascular risk in patients on dialysis]. 1550 84

Vascular calcifications are more frequent in dialysis patients than in the general population or in patients with cardiovascular disease (CVD) and normal renal function. The reasons for this high incidence are multiple; they include traditional factors such as hypertension, diabetes, dyslipidemia, and specific factors such as sodium overload, hyperomocysteinemia, chronic inflammation and oxidative stress, as well as mineral metabolism disturbances. Specifically, hyperphosphatemia and the elevated calcium (Ca) x phosphate product have been associated with an increased risk for the development of vascular calcification and death. Treatment with Ca salts can induce hypercalcemia, increased Ca x phosphate product and Ca overload. Sevelamer substitution for Ca salts has been documented to attenuate the progression of coronary artery and aortic calcification. A possible mechanism explaining this observation could be ongoing Ca loading related to oral Ca ingestion. Treatment with Ca salts could induce Ca overload, particularly in patients dialyzed against a high dialysate Ca (>1.5 mmol/L) solution, which is known to determine a positive dialysis balance. Conversely, an overall negative Ca balance can result from low Ca dialysate use (1.25 mmol/L) when the patients do not receive Ca supplements or vitamin D metabolites. Maintaining normal Ca and phosphate balances remains a primary goal in the management of dialysis patients. Control of hyperphopshataemia should be achieved either using Ca and aluminum-free phosphate binders, such as sevelamer, or Ca salts, alone or in combination, provided that a daily oral elemental Ca intake of 1.5 g is not exceeded.
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PMID:[Control of calcium and phosphate metabolism and prevention of vascular calcifications in uremic patients]. 1578 2

The heme pathway enzyme delta-aminolevulinate dehydratase is a good marker for oxidative stress and metal intoxication. This sulfhydryl enzyme is inhibited in such oxidative pathologies as lead, mercury and aluminum intoxication, exposure to selenium organic species and diabetes. Oxidative stress is a complicating factor in diabetes, inducing non-enzymatic glucose-mediated reactions that change protein structures and impair enzyme functions. We have studied the effects of high glucose, fructose and ribose concentrations on delta-ALA-D activity in vitro. These reducing sugars inhibited delta-ALA-D with efficacies in the order fructose=ribose>glucose. The possible mechanism of glucose inhibition was investigated using lysine, DTT, and t-butylamine. Oxidation of the enzyme's critical sulfhydryl groups was not involved because DTT had no effect. We concluded that high concentrations of reducing sugars or their autoxidation products inhibit delta-ALA-D by a mechanism not related to thiol oxidation. Also, we are not able to demonstrate that the formation of a Schiff base with the critical lysine residue of the enzyme is involved in the inhibition of delta-ALA-D by hexoses.
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PMID:Human erythrocyte delta-aminolevulinate dehydratase inhibition by monosaccharides is not mediated by oxidation of enzyme sulfhydryl groups. 1595 Apr 99

In this article, we summarize the results of six different tomographic/biomechanical rat studies involving hypophysectomy (Hx), ovariectomy, treatment with rhGH, olpadronate, alendronate, and toxic doses of aluminum and the development of a genetic diabetes in the eSS strain. All these conditions induced some interesting and rarely reported effects on postyield bone strength. These effects were generally related neither to the degree of mineralization or the elastic modulus of the bone tissue nor to the preyield behavior of the bones. In two particular cases (Hx, eSS), the elastic modulus of bone tissue varied independently of its degree of mineralization. These results suggest the involvement of some microstructural factor(s) of bone tissue resistance to crack progression (a postyield feature of bone behavior), rather than to crack initiation (the yield-determining factor) in the corresponding mechanism. Changes in collagen or crystal structure may play that role. These changes are relevant to the mechanism of fracture production during plastic deformation, a feature of bone strength that might be independent from mineralization. Therefore, these changes might help to explain some effects of novel treatments on bone strength unrelated to bone mineralization. This questions the belief that the remaining bone mass in metabolic osteopenias is biologically and mechanically normal.
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PMID:Novel experimental effects on bone material properties and the pre- and postyield behavior of bones may be independent of bone mineralization. 1598 11

The complexity of the human plasma proteome is greatly increased by post-translational modifications. Besides physiological modifications, pathological conditions such as diabetes are responsible for adding to this complexity by producing advanced glycation endproducts (AGEs). When searching for specific biomarkers it is a prerequisite to reduce this complexity prior to analysis. To do this, agarose hydrogel was used to create a high-capacity affinity layer on the modified aluminum surface of MALDI (matrix-assisted laser desorption/ionization) targets. 3-Aminophenylboronic acid was immobilized via cyanogen bromide activation as a ligand for affinity sorption of glycated proteins, followed by their direct detection by MALDI. High protein capacity of prepared MALDI chips, efficient separation and low non-specific protein binding were demonstrated. The results show that phenylboronic acid modified hydrogels are very suitable for creating affinity surfaces for the high-throughput analysis of AGEs.
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PMID:Application of phenylboronic acid modified hydrogel affinity chips for high-throughput mass spectrometric analysis of glycated proteins. 1712 56

Sevelamer hydrochloride, as a phosphate binder that contains neither aluminum nor calcium, is expected to improve the prognosis of dialysis patients. However, sevelamer hydrochloride has been reported to lower the serum bicarbonate level. In the present study, we performed a retrospective study on the potential influences of sevelamer hydrochloride on metabolic acidosis in hemodialysis patients. The subjects were 72 patients who underwent hemodialysis at our hospital. Thirty-six patients taking sevelamer hydrochloride and 36 patients matched for sex, diabetes mellitus, age and duration of dialysis who were not taking sevelamer hydrochloride were studied. We assigned the 36 patients who had been taking sevelamer hydrochloride to the 'sevelamer group', and the 36 patients not taking sevelamer hydrochloride were the control group. Statistical significance was evaluated by a t-test and Pearson's correlation coefficient. In the sevelamer group, the mean levels of bicarbonate, base excess and pH decreased significantly after administration, compared with the values before administration, but in the control group, aggravation of acidosis was not seen. The levels of bicarbonate, base excess and pH after the medication of sevelamer hydrochloride were found to be significantly and negatively correlated with the daily dose of sevelamer hydrochloride. The levels were also found to be significantly and negatively correlated with the cumulative dose of sevelamer hydrochloride; however, the value of the mean levels of chlorine and the anion gap did not increase with sevelamer hydrochloride. Sevelamer hydrochloride caused metabolic acidosis in a dose-dependent manner in hemodialysis patients without hyperchloremia.
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PMID:Sevelamer hydrochloride exacerbates metabolic acidosis in hemodialysis patients, depending on the dosage. 1738 31

A key factor in the development of Type II diabetes is the loss of insulin producing pancreatic beta-cells. The amyloidogenic human Islet Amyloid Polypeptide (hIAPP also known as human amylin) is believed to play a crucial role in this biological process. Previous studies have shown that hIAPP forms small aggregates that kill beta-cells by disrupting the cellular membrane. In this study, we report membrane fragmentation by hIAPP using solid-state NMR experiments on nanotube arrays of anodic aluminum oxide containing aligned phospholipid membranes. In a narrow concentration range of hIAPP, an isotropic (31)P chemical shift signal indicative of the peptide-induced membrane fragmentation was detected. Solid-state NMR results suggest that membrane fragmentation is related to peptide aggregation as the presence of Congo Red, an inhibitor of amyloid formation, prevented membrane fragmentation and the non-amyloidogenic rat-IAPP did not cause membrane fragmentation. The disappearance of membrane fragmentation at higher concentrations of hIAPP suggests an alternate kinetic pathway to fibril formation in which membrane fragmentation is inhibited.
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PMID:Membrane fragmentation by an amyloidogenic fragment of human Islet Amyloid Polypeptide detected by solid-state NMR spectroscopy of membrane nanotubes. 1766 57

Type 1 diabetes (T1D) is characterized by autoimmunity against pancreatic islets, and autoantibodies may be present for years before diagnosis. Environmental factors during early life, including drinking water, may play a role in pathogenesis of T1D. The German BABYDIAB study is a prospective observational study that followed newborn offspring of mothers or fathers with T1D from birth to 17 years of age. The present study was a nested case-control analysis, where subjects with islet autoimmunity were defined as cases (n=95), those without as controls (n=139). Drinking water quality was obtained from the German Water Supply Authorities for the participating families for the first year of the child's life. There was no significant association between water acidity or drinking water quality (concentration of minerals and elements) and islet autoimmunity risk. Increased progression to diabetes in islet autoantibody-positive children was associated with exposure to water with lower pH values (less than cohort median, 7.62; odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.1-5.7; p=0.03) but was not significant after correction for multiple comparisons. Concentrations of nitrate, nitrite, iron, aluminum, and manganese were not associated with risk of T1D progression. This is the first prospective study with water quality measured before the onset of islet autoimmunity and T1D. Consistent with a previous cross-sectional case-control study, we found an association between drinking water pH and the rate of T1D development in at-risk children. The association is marginal and requires validation in other prospective cohorts.
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PMID:Exposure to environmental factors in drinking water: risk of islet autoimmunity and type 1 diabetes--the BABYDIAB study. 1850 Jun 77

Aluminum phosphide (AlP) is a solid fumigant widely used in Iran as a grain preservative. When reacted with water or acids, AIP produces phosphine gas, a mitochondrial poison that interferes with oxidative phosphorylation and protein synthesis. Poisoning by AIP is one of the most important causes of fatal chemical toxicity in Iran. There are few studies in the medical literature addressing prognostic factors associated with AlP poisoning. In this prospective study conducted across a 14-month period commencing on 21st March 2006, we enrolled all patients admitted to the ICU of Loghman-Hakim Hospital Poison Center (Tehran, Iran) with AIP poisoning, no history of diabetes mellitus diagnosed before hospitalization, and normal body mass index. We recorded patient-specific demographic information, blood glucose level on presentation (before treatment), arterial blood gas (ABG) analysis, time elapsed between ingestion and presentation, ingested dose, duration of intensive care admission, and outcome data related to each presentation. We enrolled the group of patients who survived the intoxication as a control group and compared their blood glucose levels with those who died because of AlP poisoning. Data were analyzed by Statistical Product and Service Solutions (SPSS) software (Version 12; Chicago, Ilinois, USA) using logistic regression, Pearson correlation coefficient and Student's t-test. P values of 0.05 or less were considered as the statistical significant levels. Forty-five patients (21 women and 24 men) with acute AlP poisoning were included in the study. The mean age was 27.3 +/- 11.5 years (range: 14-62 years). Thirteen patients survived (29%) and 32 expired (71%). AlP poisoning followed deliberate ingestion in all patients. The time elapsed between ingestion and arrival at the hospital was 3.2 +/- 0.4 h. There was no significant difference between survived and non-survived groups according to age, gender, and time to treatment. However, the difference between mean blood glucose levels in survived (143.4 +/- 13.7 mg/dL) and non-survived (222.6 +/- 20 mg/dL) cases was statistically significant (P = 0.021). There was no significant correlation between blood glucose level and time to treatment, age, gender, pH, HCO3 concentration, and ingested dose. Twenty-three (71.9%) of non-survived and four (30.8%) of survived patients had a blood glucose level greater than 140 mg/dL. After adjusting according to age, gender, ingested dose, pH and HCO3 concentration The odds ratio for hyperglycemia as a risk factor for death was 5.7 (CI of 1.4-23.4). In our study, patients who succumbed to AIP poisoning had significantly higher mean blood glucose levels than those who survived. This correlation of hyperglycemic effect and mortality suggests that it may be useful in guiding risk assessment and treatment of AIP poisoning. Management of hyperglycemia may have a useful role in treatment of these patients by allowing increased entrance of glucose into cells and reducing oxygen consumption.
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PMID:Hyperglycemia in acute aluminum phosphide poisoning as a potential prognostic factor. 1882 36


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