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)

There are two types of diabetes mellitus. Type I, insulin-dependent diabetes (IDDM), which becomes manifest before the age of 40, is the result of an absolute deficiency of insulin. Type II, the non-insulin-dependent diabetes (NIDDM), develops in the elderly and is caused by a relative insulin deficiency. Patients with type-I diabetes are prone to the development of ketoacidosis, while type II causes hyperglycaemic, hyperosmolar, nonketotic coma. Apart from these acute metabolic alterations, the long-term complications of diabetes are of concern to the anaesthesiologist. Hypertension, coronary artery disease, renal insufficiency and autonomic neuropathy are common and can result in myocardial ischaemia, cardiovascular instability and gastroparesis, with an increased risk of aspiration. Limited movement of the atlanto-occipital joint can cause difficult intubation. To avoid perioperative metabolic catastrophy, blood glucose concentration should be kept between 6.7 and 10 mmol.l-1 (120-180 mg.dl-1). Hypoglycaemia can result in neurological damage, whereas hyperglycaemia causes impaired wound healing and susceptibility to infections and worsens ischaemic damage to the myocardium and brain. Perioperative diabetes management depends on the severity of the surgical procedure and the type of diabetes. All type-I diabetics, whatever operation being performed, need insulin. The intravenous route is recommended as it allows better adjustment. After determination of the fasting blood glucose level, insulin is given at a dosage of 0.5-1 U.h-1 (at gluc < 11.1 mmol.l-1), 1.5-2 U.h-1 (at gluc 11.1-16.7 mmol.l-1) or 3 U.h-1 (at gluc > 16.7 mmol.l-1). In addition, 5-10 g glucose.h-1 is given. In type-II diabetes the oral antidiabetic drug is withheld. During minor surgery the blood glucose concentration is monitored frequently, and if necessary insulin (with gluc > 13.9 mmol.l-1) or glucose is given. In most cases of major surgery insulin therapy will be necessary. Administration should follow the guidelines listed for type-I diabetes. Whether the intravenous or the subcutaneous route is used for insulin, repeated glucose determinations are mandatory. If ketoacidosis develops the volume depletion is treated with normal saline. For hyperglycaemia and acidosis insulin (3-6 U.h-1) with 10-20 mmol.h-1 potassium phosphate is given. Bicarbonate is only indicated when the serum pH is lower than 7.1. It must be borne in mind that perioperative management of diabetes does not end with postanaesthesia care.
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PMID:[Anesthesia and diabetes mellitus]. 804 63

Gliclazide is the most commonly used sulfonylurea derivative for NIDDM therapy. Due to its prolonged therapy, there is always a likelihood of its use with other drugs. On the other hand antacids are commonly prescribed to encounter gastric acidity etc. Present paper deals with the in vitro availability studies of gliclazide in presence of antacids. These studies were carried out in simulated gastric juice and in buffer of pH 7.4 at body and accelerated temperature. The antacids used in these studies were aluminum hydroxide, aluminum trisilicate, magnesium oxide, magnesium trisilicate, sodium bicarbonate, calcium carbonate, magaldrate and simethicone (2,4-dimethoxypoly-siloxane). It has been found that in case of magnesium oxide, magnesium trisilicate and sodium bicarbonate, availability of gliclazide was enhanced while in rest of the antacids retarded the availability of gliclazide.
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PMID:In vitro availability of gliclazide in presence of antacids. 1641 65

A model of chronic kidney disease (CKD)-induced vascular calcification (VC) that complicates the metabolic syndrome was produced. In this model, the metabolic syndrome is characterized by severe atherosclerotic plaque formation, hypertension, type 2 diabetes, obesity, and hypercholesterolemia, and CKD stimulates calcification of the neointima and tunica media of the aorta. The CKD in this model is associated the adynamic bone disorder form of renal osteodystrophy. The VC of the model is associated with hyperphosphatemia, and control of the serum phosphorus both in this animal model and in humans has been preventive in the development of VC. This article reports studies that demonstrate reduction of established VC by the addition of sevelamer carbonate to the diets of this murine metabolic syndrome model with CKD. Sevelamer, besides normalizing the serum phosphorus, surprisingly, reversed the CKD-induced trabecular osteopenia. Sevelamer therapy increased osteoblast surfaces in the metaphyseal trabeculae of the tibia and femur. It also increased osteoid surfaces and, importantly, bone formation rates. In addition, sevelamer was found to be effective in decreasing serum cholesterol levels. These results suggest that sevelamer may have important actions in decreasing diabetic and uremic vasculopathy and that sevelamer carbonate may be capable of increasing bone formation rates that are suppressed by diabetic nephropathy.
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PMID:Reversal of the adynamic bone disorder and decreased vascular calcification in chronic kidney disease by sevelamer carbonate therapy. 1718 86

We report the first kinetic characterization of human liver cytosolic GTP-dependent phosphoenolpyruvate carboxykinase (GTP-PEPCK), which plays a major role in the development of type 2 diabetes in human. In this work two recombinant forms of the enzyme were studied. One form had a His10-tag and the other was His-tag-free, and with one exception, both exhibited similar kinetic properties. When Mn2+ was used as the sole divalent cation, the His10-tagged enzyme, but not the His-tag-free enzyme, was increasingly inhibited at Mn2+ concentrations greater than 0.7 mM. This inhibition did not pose any problem in kinetic analysis, for within the relevant Mn2+ concentration range the His-tagged human PEPCK behaved almost identically to the tag-free enzyme. This property will bring simplicity and speed to purifying and studying multiple structural variants of this important enzyme. Apparent Km values of tag-free enzyme for phosphoenolpyruvate, GDP and bicarbonate were 450, 79 and 20,600 microM, respectively, while those for oxaloacetate and GTP were 4 and 23 microM, respectively, emphasizing the enzyme's gluconeogenic character. Bicarbonate (>100 mM) inhibited OAA-forming activity, which was a new observation with a GTP-PEPCK. The apparent Km for Mn2+ in the PEP-forming direction was 30-fold lower than that for the OAA-forming direction. Mn2+ and bicarbonate or CO2 might regulate the enzyme in vivo.
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PMID:Kinetic characterization of recombinant human cytosolic phosphoenolpyruvate carboxykinase with and without a His10-tag. 1788 79

The gut hormone glucagon-like peptide-1 (GLP-1) is proposed for treatment of Type II diabetes mellitus. However, the short half life of GLP-1 in vivo is a major limitation for its application due to the frequent invasive administrations. To provide a optimal formulation to overcome this limitation, we developed a GLP-1 entrapped microspheres to achieve sustained release GLP-1 for 4-week. GLP-1 was stabilized by GLP-1-zinc complexation with zinc carbonate and encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA) with S/O/O solvent extraction to obtain GLP-1 loaded PLGA microspheres (MS). The characteristics of MS were evaluated as follows: The surface morphology was assessed by scanning electron microscopy (SEM); The drug encapsulation efficiency and GLP-1 controlled release profile was tested by HPLC; The sustained release of GLP-1 MS in vivo and pharmacological efficacy were studied in normal mice and streptozotocin (STZ)-induced diabetic mice model after subcutaneous administration of GLP-1 MS. GLP-1-zinc complexation significantly reduced initial burst release from 37.2 to 7.5%. The controlled release bioactive GLP-1 in vitro was achieved for 4-week period by zinc complexation and addition of ZnCO(3). The optimal and complete cumulative release of GLP-1 from MS was increased from 23 to 63% in 28 d by using low MW PLGA (MW 14000). The in vivo testing in normal mice and diabetic mice suggest that this zinc-stabilized technique combined with S/O/O method in the presence of water insoluble antacid additive ZnCO(3) preserve the biological activity of GLP-1. GLP-1 MS formulation achieved controlled released in vivo for 28 d and exhibit sustained long term pharmacological efficacy to decrease blood glucose level in diabetic mice. This GLP-1 MS formulation provides a practical formulation for long-term sustained delivery of GLP-1 to treat Type II diabetes.
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PMID:Preparation of glucagon-like peptide-1 loaded PLGA microspheres: characterizations, release studies and bioactivities in vitro/in vivo. 1823 99

Metformin is a biguanide commonly used in type 2 diabetes mellitus (DM). Lactic acidosis, a potentially life-threatening metabolic disorder, may be due to a number of different causes, including metformin therapy. We present a case of a severe metformin-induced lactic acidosis in a patient with type 2 DM, admitted to the emergency department with a history of dehydration due to diarrhoea and complicated by acute renal failure. Patient complained malaise and severe weakness and was tachypneic (Kussmaul's respiration), agitated and confused, with a Glasgow Coma Scale score of 13/15. Heart rate was 75 b/min and blood pressure 110/80 mmHg. The pH was 6.87, HCO3- 3 mmol/l, lactate 15 mmol/l, potassium 6.9 mEq/l. The renal function was markedly impaired with a creatinine of 9.75 mg/dl, and pancreatic enzymes, amylase and lipase, were also increased in absence of abdominal pain. Patient was treated with intravenous fluids, bicarbonate infusion and haemodialysis with bicarbonate buffered replacement fluid. Clinical conditions improved rapidly, with a progressive normalization of the acid-base balance and the other laboratory data. Authors discuss the pathophysiologic mechanisms of these alterations with particular regard to the role played by metformin as potential cause of lactic acidosis.
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PMID:Metformin-induced lactic acidosis in a type 2 diabetic patient with acute renal failure. 1846 66

The maintenance of normal metabolism and body defenses depends on the balance between cellular antioxidant and anti-inflammatory factors. This balance can be disrupted by agents/mechanisms in the extracellular milieu that induce excess reactive oxygen species (ROS) and inflammation. Cytopathic advanced glycation endproducts, present in ever increasing amounts in the modern diet, are one of the major environmental factors that cause excess ROS and/or inflammation at all ages and induce complications in aging, such as chronic kidney disease (CKD) and type 2 diabetes. Increased ROS and/or inflammation are present in both aging and CKD, and are associated with reduced cellular defenses against ROS and/or inflammation. Affected individuals have reduced defenses against further stress and are predisposed to organ failure, now a well-known phenomenon in aging. Thus, new methods are urgently needed to safely reduce ROS and/or inflammation in the aging type 2 diabetes patient with CKD. Studies of both normal aging and diabetic patients with kidney disease underline the fact that increased ROS and/or inflammation can be managed in these conditions by economical, safe, and effective interventions that reduce the uptake of advanced glycation endproducts by either modifying preparation of food or an oral drug. This communication reviews these data and adds new information on the efficacy of a drug, sevelamer carbonate, required to reduce ROS and/or inflammation in the aging type 2 diabetes patient complicated by CKD. If larger and longer studies confirm the hypothesis that one or both of these interventions reduce progression of CKD, it could represent a new paradigm in the management of complications in the type 2 diabetes patient with CKD.
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PMID:Managing chronic inflammation in the aging diabetic patient with CKD by diet or sevelamer carbonate: a modern paradigm shift. 2310 77

The study investigated the effects of type 2 diabetes mellitus on salivary flow and composition in humans compared to healthy sex and age matched controls. Forty adult human subjects divided into 20 diabetic and 20 non-diabetic healthy subjects were included. Saliva samples were collected and analysed for glucose, total protein, calcium, sodium, potassium, chloride and bicarbonate. Salivary flow rate was also determined. The results showed that salivary glucose and potassium levels were significantly higher (p = 0.01 and 0.002 respectively) in diabetic patients compared with non-diabetic participants. It was also found that the diabetic patients had significant reduction in salivary flow rate when compared with non-diabetic individuals. In contrast, there was no significant difference in levels of total protein, Na+, Ca++, Cl- and HCO3- between the two groups. These results suggest that some oral diseases associated with diabetes mellitus may be due to altered levels of salivary glucose, potassium and flow.
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PMID:Salivary flow and composition in diabetic and non-diabetic subjects. 2323 12

Contamination of soils with depleted uranium (DU) from munitions firing occurs in conflict zones and at test firing sites. This study reports the development of a chemical extraction methodology for remediation of soils contaminated with particulate DU. Uranium phases in soils from two sites at a UK firing range, MOD Eskmeals, were characterised by electron microscopy and sequential extraction. Uranium rich particles with characteristic spherical morphologies were observed in soils, consistent with other instances of DU munitions contamination. Batch extraction efficiencies for aqueous ammonium bicarbonate (42-50% total DU extracted), citric acid (30-42% total DU) and sulphuric acid (13-19% total DU) were evaluated. Characterisation of residues from bicarbonate-treated soils by synchrotron microfocus X-ray diffraction and X-ray absorption spectroscopy revealed partially leached U(IV)-oxide particles and some secondary uranyl-carbonate phases. Based on these data, a multi-stage extraction scheme was developed utilising leaching in ammonium bicarbonate followed by citric acid to dissolve secondary carbonate species. Site specific U extraction was improved to 68-87% total U by the application of this methodology, potentially providing a route to efficient DU decontamination using low cost, environmentally compatible reagents.
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PMID:Remediation of soils contaminated with particulate depleted uranium by multi stage chemical extraction. 2399 94

Our previous study indicates that hyperinsulinemia in metabolic syndrome in the absence of nephropathy may promote hypertension by stimulating renal proximal tubule (PT) sodium transport via insulin receptor substrate (IRS) 2/phosphoinositide 3-kinase pathway. In the present study we showed that the stimulatory effect of insulin on the Na(+)-HCO3(-) cotransporter NBCe1 in isolated PTs was completely preserved in type 2 diabetic rats with overt nephropathy. Furthermore, the IRS2 expression and insulin-induced Akt phosphorylation in kidney cortex were preserved in these rats. By contrast, the IRS1 expression in kidney cortex was markedly reduced, which might be relevant to enhanced renal gluconeogenesis consistently reported in diabetes. The stimulatory effect of insulin on NBCe1 was preserved also in a human type 2 diabetic patient with advanced nephropathy. These results revealed that insulin can stimulate PT sodium transport even in type 2 diabetes with overt nephropathy. In addition to hypoglycemia, insulin-induced renal sodium retention might also play a role in increased cardiovascular risk associated with intensive glycemic control in type 2 diabetic patients with nephropathy.
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PMID:Stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in type 2 diabetes with nephropathy. 2586 80


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