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)

Sialic acid (SA) is responsible for the composition of different isoforms of transferrin and is reported to be a marker of microvascular complications in type 2 diabetes mellitus. Therefore, we explored the serum concentration of SA, and the less sialylated isoforms of transferrin, termed carbohydrate-deficient transferrin (CDT), in relation to the presence of microvascular complications in type 2 diabetes mellitus. We studied 21 patients with type 2 diabetes with microangiopathy and 22 patients without complications who were hospitalized at a diabetic clinic. The prevalence of microvascular complications was based on clinical history, fundoscopy, and laboratory tests. Blood samples were taken for measurements of SA, CDT, total transferrin, glucose, HbA1c, fibrinogen, C-reactive protein (CRP), and indicators of renal dysfunction (i.e., creatinine, urea, albumin excretion rate (AER), and glomerular filtration rate (GFR)). A rise in serum SA and a decrease in CDT concentrations were observed in both diabetic groups with and without complications, and there were no differences between the two groups of patients. There was a statistically significant correlation between serum SA and CDT in diabetic subjects with microvascular complications, but not in patients without such complications. This proves that the serum changes in CDT and SA levels in the course of type 2 diabetes mellitus are associated with each other in the presence of microangiopathy.
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PMID:Serum level of sialic acid (SA) and carbohydrate-deficient transferrin (CDT) in type 2 diabetes mellitus with microvascular complications. 1653 41

We recently reported that in subjects with untreated type 2 diabetes a 5-wk diet of 30:30:40 carbohydrate/protein/fat ratio resulted in a significant decrease in 24-h integrated glucose, total %glycohemoglobin, and total cholesterol compared with a control diet of 55:15:30 carbohydrate/protein/fat given at the beginning of the 5-wk period. Body weight was stable and insulin was unchanged. We now present data on other hormones and metabolites considered to be affected by dietary macronutrient changes. The test diet resulted in an elevated fasting plasma total IGF-I, but not growth hormone. Urinary free cortisol was increased. Serum renin and urinary aldosterone remained unchanged. Blood pressure was stable. Serum creatinine and uric acid were increased. Urinary microalbumin was decreased. Creatinine clearance, serum B(12), folate, homocysteine, TSH, and free thyroxine were unchanged. Total triiodothyronine was decreased. Plasma alpha-amino nitrogen, urea nitrogen, and serum albumin were increased. Urea production rate was increased such that a new steady state was present. The calculated urea production rate accounted for 84% of protein ingested on the control diet but only 68% on the test diet, suggesting net nitrogen retention on the latter. Overall, the lack of negative effects, the improved glucose control, and the positive nitrogen balance suggest such a diet will be beneficial for older subjects with type 2 diabetes. Nevertheless, the long-term effects and general applicability of the diet remain to be determined.
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PMID:Metabolic effect of a LoBAG30 diet in men with type 2 diabetes. 1672 Jun 31

Glipizide is one of the most commonly prescribed drugs for treatment of type 2 diabetes. Oral therapy with glipizide comprises problems of bioavailability fluctuations and may be associated with severe hypoglycaemia and gastric disturbances. As a potential for convenient, safe and effective antidiabetic therapy, the rationale of this study was to develop a transdermal delivery system for glipizide. For this purpose, inclusion complexes of the drug in beta-cyclodextrin (beta-CyD), dimethyl-beta-cyclodextrin (DM-beta-CyD), hydroxypropyl-beta-cyclodextrin (HP-beta-CyD), and hydroxypropyl-gamma-cyclodextrin (HP-gamma-CyD) were prepared. Several percutaneous formulations of the drug and the prepared complexes in different bases (o/w emulsion, polyethylene glycol, carboxymethyl cellulose and Carbopol) were developed. Release studies revealed an improved release of the drug from formulations containing glipizide-CyD complexes. Ex vivo permeation studies through full thickness rat abdominal skin were conducted, whereby the effect of several conventional penetration enhancers (propylene glycol [PG], oleic acid, urea, dimethyl sulfoxide, menthol, limonene and cineole) was monitored. Highest flux was obtained from ointments prepared with Carbopol gel base containing a combination of PG and oleic acid as well as ointments prepared in the same base utilizing glipizide-DM-beta-CyD complex and urea. In vivo studies on diabetic male Wistar rats revealed a marked therapeutic efficacy sustained for about 48 hours. In this respect, two formulations showed best biological performance. In the first formulation, the drug was incorporated in Carbopol gel base in the presence of 20% PG together with 15% oleic acid. The second was prepared by incorporating glipizide-DM-beta-CyD complex in Carbopol gel base in presence of 15% urea. The glucose tolerance test showed suppression of hyperglycaemia induced in glucose-loaded rats. The above-mentioned results might shed a strong beam of light on the feasibility of using glipizide in a transdermal delivery system for treatment of type 2 diabetes with the aim of improving both patient compliance and pathophysiology of the disease.
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PMID:A transdermal delivery system for glipizide. 1684 35

The aim of this study was to compare the nutritional status of zinc and copper in patients with and without diabetes submitted to chronic hemodialysis. Thirty-three patients with type 2 diabetes (DM group), 30 nondiabetic patients (NDM group), and 20 healthy individuals (control group) were studied. Plasma, erythrocyte, and urinary zinc and plasma copper were obtained from atomic absorption spectrophotometry and ceruloplasmin by immunonephelometry. The anthropometric parameters were similar among the groups. Plasma zinc was lower and erythrocyte zinc was higher in the DM and NDM groups in relation to the control group. No difference in urinary zinc was observed comparing the groups. Plasma copper was higher in the DM group when compared to the NDM and control groups. Ceruloplasmin was similar in the three groups. Serum urea was a positive independent determinant of plasma zinc concentrations. The determinants of erythrocyte zinc were MAMC midarm muscle circumference and Kt/V dialysis adequacy. The determinants of plasma copper concentration were serum creatinine and serum glucose. The results of this study demonstrate an alteration in the distribution of zinc in patients with chronic kidney disease (CKD) independently of the presence of DM. Also, the status of copper seems not to be influenced by CKD, but only by the metabolic derangements associated with diabetes.
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PMID:Effect of end-stage renal disease and diabetes on zinc and copper status. 1694 12

The effect of olmesartan medoxomil (OLM), an angiotensin II receptor blocker (ARB), on advanced nephropathy and mortality was evaluated in Zucker Diabetic Fatty (ZDF) rats, a type 2 diabetes model. OLM was administered from 36 weeks of age, when the animals developed advanced proteinuria. OLM effectively suppressed the progression of proteinuria. The ZDF rats started to die at 50 weeks of age, which was accompanied by abrupt increase in blood urea nitrogen, suggesting that the cause of death was renal insufficiency. OLM suppressed increases in blood urea nitrogen and increased the survival rate of the ZDF rats. The histological examination revealed that the renal damage was ameliorated by OLM. The macrophage infiltration and monocyte chemoattractant protein-1 (MCP-1) expression was increased in the glomeruli and tubulointerstitium of the ZDF rat kidneys, and the increase was lessened by OLM. In a separate study, albumin increased MCP-1 release from cultured tubular epithelial cells. These results suggest that protein leakage from the glomeruli stimulates MCP-1 production in tubular cells and that MCP-1 released into the interstitial space induces macrophage infiltration and inflammation. It is conceivable that the beneficial actions of ARB on diabetic nephropathy are, at least in part, due to decrease of proteinuria and the subsequent reduction of inflammatory changes in tubular cells.
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PMID:The effect of angiotensin II receptor blockade on an end-stage renal failure model of type 2 diabetes. 1708 90

Evidence exists that some clinical, metabolic and genetic risk factors are associated with the development of diabetic retinopathy (DR). The aim of the study was: (1) to define the prevalence of DR in the examined group of 267 patients with type 2 diabetes mellitus (T2DM) from a Polish population; (2) to identify in cross-sectional analysis, the clinical features associated with DR in the study group; and (3) to search for the association of 4 markers of vitamin D receptor (VDR), a candidate gene for vascular complications in diabetes, with DR. The examined group consisted of 146 female and 121 male T2DM patients (mean age at examination: 61.3+/-9.4 years; age at T2DM diagnosis: 50.0+/-9.2; T2DM duration: 11.3+/-7.8 years; body mass index (BMI): 30.5+/-5.5 kg/m(2); HbA1c: 7.8+/-1.5%). In all patients, the clinical and metabolic profile was determined. Diagnosis of DR was determined by a trained ophthalmologist by ophthalmoscopy after pupillary dilatation. Colour photographic documentation was made. The examined T2DM patients were genotyped for FokI, ApaI, BsmI and TaqI frequent VDR polymorphisms based on the restriction fragment length polymorphism method. The statistical analysis was performed using univariate and multivariate logistic regression (SAS) and haplotype analysis (Haplostat). DR was detected in 85 (31.8%) patients with T2DM. The multivariate analysis revealed that significant predictors of this complication were: never-smoking status (odds ratio 2.2, 95% confidence interval 1.2-4), urea serum level (1.3, 1.1-1.5), HbA1c level (1.4, 1.1-1.8) and insulin treatment (2.7, 1.4-5.1). Other features such as age of T2DM diagnosis, T2DM duration prior to ophthalmic exam, obesity (BMI>30), serum creatinine level, albumin/creatinine ratio and arterial hypertension were univariate predictors of DR, however they lost significance as independent predictors in multivariate analysis. Similarly, the alleles, genotypes, haplotype and haplotype combination of VDR were not associated with the examined complication. However, there was a suggestion of a possible slight association between the fbaT haplotype and DR (p=0.11). In conclusion, our study showed that DR in T2DM patients remains a frequent complication in Polish T2DM patients. We were able to confirm the role of some clinical risk factors, surprisingly including not-smoking status, as was previously shown in the UK Prospective Diabetes Study (UKPDS). VDR gene polymorphisms did not constitute a risk factor for this size of study group.
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PMID:Clinical risk factors and the role of VDR gene polymorphisms in diabetic retinopathy in Polish type 2 diabetes patients. 1721 61

Chromium supplements are widely used as an alternative remedy for type 2 diabetes mellitus (T2DM). In vitro study findings show that chromium picolinate (CrPic) may improve insulin sensitivity by enhancing intracellular insulin receptor. In this study, we evaluated the metabolic effects of CrPic in a rat model of T2DM. Male Sprague-Dawley rats (n = 45, 8 weeks old) were divided into 3 groups. The controls (group I) received a standard diet (12% of calories as fat); group II received a high-fat diet (HFD; 40% of calories as fat) for 2 weeks and then were intraperitoneally injected with streptozotocin (STZ, 40 mg/kg; HFD/STZ) on day 14; group III rats were given group II diets with the addition of 80 microg CrPic per kilogram body weight per day. The addition of CrPic in the group III treatment lowered glucose by an average of 63% (P < .001), total cholesterol by 9.7% (P < .001), and triglycerides by 6.6% (P < .001) compared with group II treatment. Compared with group II, CrPic treatment also lowered free fatty acid levels by 24% (P < .001), blood urea by 33% (P < .05), and creatinine level by 25% (P < .01), and reduced the severity of glomerular sclerosis (P < .0001). Histopathologic findings suggest that the CrPic-treated group had normal renal tubular appearance compared with the HFD/STZ-treated group. Normal appearance of hepatocytes was observed in the CrPic-treated group. These results showed that CrPic has marked beneficial effects against microvascular complications. In conclusion, HFD/STZ rats provide a novel animal model for T2DM. Further treatment with CrPic for 10 weeks significantly ameliorated changes in metabolic risk factors including favorable changes in histopathology of the liver, kidney, and pancreas, suggesting its potential role in the management of diabetes.
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PMID:Effect of chromium on carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus: the fat-fed, streptozotocin-treated rat. 1769 67

We reported the first case of simultaneous pancreas-kidney transplantation (SPK) in our hospital. The recipient is a 65 year old male, who suffered type 2 diabetes for 15 years and renal dysfunction for 5 years and other diabetic complications such as retinopathy, peripheral neuropathy. SPK was performed successfully for him in March, 2007, in which the donor kidney was put in left iliac fossa, while the donor pancreas grafted to set in right iliac fossa of recipient, with pancreas exocrine drainage controlled by anastomosis to the small bowel and endocrine release done to the circulatory system. Serum C-peptide, Creatinine and Blood urea nitrogen became normal levels at day 1, 4 and 11 of post-operation respectively. The concentration of blood glucose was stabilized gradually to normal level and therefore the injected insulin was stopped using to the patient at day 16 of post-operative days. OGTT test showed the function of grafted pancreas was normal 3 weeks after transplant, and no transplantation-related complications occurred. With the recipient followed up for 6 months, both his blood glucose level and renal function maintained normal without using injected insulin, and he was getting to recover from other diabetic complications also.
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PMID:[Simultaneous pancreas-kidney transplantation (SPK) for an old age male with type 2 diabetes complicated with end-stage renal disease (ESRD): a case report]. 1809 18

Glycogen phosphorylase (GP) is a validated target for the treatment of type 2 diabetes. Here we describe highly potent GP inhibitors, AVE5688, AVE2865, and AVE9423. The first two compounds are optimized members of the acyl urea series. The latter represents a novel quinolone class of GP inhibitors, which is introduced in this study. In the enzyme assay, both inhibitor types compete with the physiological activator AMP and act synergistically with glucose. Isothermal titration calorimetry (ITC) shows that the compounds strongly bind to nonphosphorylated, inactive GP (GPb). Binding to phosphorylated, active GP (GPa) is substantially weaker, and the thermodynamic profile reflects a coupled transition to the inactive (tense) conformation. Crystal structures confirm that the three inhibitors bind to the AMP site of tense state GP. These data provide the first direct evidence that acyl urea and quinolone compounds are allosteric inhibitors that selectively bind to and stabilize the inactive conformation of the enzyme. Furthermore, ITC reveals markedly different thermodynamic contributions to inhibitor potency that can be related to the binding modes observed in the cocrystal structures. For AVE5688, which occupies only the lower part of the bifurcated AMP site, binding to GPb (Kd = 170 nM) is exclusively enthalpic (Delta H = -9.0 kcal/mol, TDelta S = 0.3 kcal/mol). The inhibitors AVE2865 (Kd = 9 nM, Delta H = -6.8 kcal/mol, TDelta S = 4.2 kcal/mol) and AVE9423 (Kd = 24 nM, Delta H = -5.9 kcal/mol, TDelta S = 4.6 kcal/mol) fully exploit the volume of the binding pocket. Their pronounced binding entropy can be attributed to the extensive displacement of solvent molecules as well as to ionic interactions with the phosphate recognition site.
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PMID:Thermodynamic characterization of allosteric glycogen phosphorylase inhibitors. 1837 53

To document clinical, serum and urinary parameters in patients with features of diabetic nephropathy in type 2 diabetes mellitus and to correlate light microscopical findings of the renal biopsy specimen with the clinical, serum and urinary parameters, a study was conducted among 30 patients of type 2 diabetes mellitus with features of nephropathy attended Medical College, Kolkata with special emphasis given on neurological and fundoscopic examination. The patients were investigated with fasting and postprandial venous plasma glucose, glycosylated haemoglobin (HbA1c), serum urea, creatinine, sodium, potassium, 24-hour urinary protein/micro-albumin and lipid profile. Percutaneous renal biopsy was performed after taking informed consent from the patients and sent for histopathological examination. Obtained data were tabulated and analysed. Among 30 patients (male-16; female-14; proteinuric-23, micro-albuminuric-6) diabetic nephropathy was detected in 28 patients (diffuse-15, nodular-9, 4 had focal segmental glomerulosclerosis) and 2 had normal renal biopsy. Retinopathy was detected in 16 patients; 12 had autonomic neuropathy and 3 had peripheral neuropathy.
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PMID:A study on nephropathy in type 2 diabetes mellitus: histology and its correlation with clinical and biochemical parameters. 1838 54


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