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)

This study, conducted under the Metabolic Disorders Steering Committee of the Biomarkers Consortium (a public-private partnership managed by the Foundation for the National Institutes of Health (FNIH)), analyzed blinded data on 2,688 type 2 diabetes (T2D) patients from randomized clinical trials conducted by four pharmaceutical companies. An increase in the levels of adiponectin was observed after peroxisome proliferator-activated receptor (PPAR)-agonist treatment (P < 0.0001), but not after treatment with non-PPAR drugs. This increase correlated with decreases in levels of glucose, hemoglobin A(1c) (Hb(A1c)), hematocrit, and triglycerides, and increases in levels of blood urea nitrogen, creatinine, and high-density lipoprotein cholesterol (HDL-C). Early (6-8 weeks) increases in levels of adiponectin after treatment with PPAR agonists showed a negative correlation (r = -0.21, P < 0.0001) with subsequent changes in levels of Hb(A1c). Changes in adiponectin level did not appear to be associated with baseline level of Hb(A1c). Logistic regression demonstrated that an increase in the level of adiponectin predicts a decrease in the level of Hb(A1c). These analyses confirm previously demonstrated relationships between adiponectin levels and metabolic parameters and support the robust predictive utility of adiponectin across the spectrum of glucose tolerance. Cross-company precompetitive collaboration is a feasible and powerful approach to biomarker qualification.
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PMID:Utility of adiponectin as a biomarker predictive of glycemic efficacy is demonstrated by collaborative pooling of data from clinical trials conducted by multiple sponsors. 2001 97

Diabetes has become the most common single cause of end-stage renal disease (ESRD) in the United States and Europe. Approximately 30-40% of patients with type I and 15% with type II diabetes mellitus develop end ESRD. The study was designed to evaluate the impact of sesamol on renal function and renoinflammatory cascade in streptozotocin (STZ)-induced diabetes. STZ-induced diabetic rats were treated with sesamol (2, 4, and 8 mg/kg/day; po) or with vehicle from the fifth to eighth weeks. After 8 weeks, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine, and urea clearance were measured. Cytoplasmic and nuclear fractions of kidney were prepared for the quantification of oxidative-nitrosative stress (lipid peroxidation, superoxide dismutase, catalase, nonprotein thiols, total nitric oxide), tumor necrosis factor-alpha (TNF-alpha), tissue growth factor-1 beta (TGF-beta1), p65 subunit of NFkappabeta, and caspase-3. After 8 weeks of STZ injection, the rats produced significant alteration in renal function, increased oxidative-nitrosative stress, TNF-alpha, TGF-beta1, caspase-3 activity in cytoplasmic lysate, and active p65 subunit of NFkappabeta in nuclear lysate of kidney of diabetic rats. Interestingly, co-administration of sesamol significantly and dose-dependently prevented biochemical and molecular changes associated with diabetes. Moreover, diabetic rats treated with insulin-sesamol combination produced more pronounced effect on molecular parameters as compared to their respective groups. The data reveal that sesamol modulates the release of profibrotic cytokines, oxidative stress, ongoing chronic inflammation, and apoptosis and thus exerts a marked renoprotective effect.
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PMID:Attenuation of renoinflammatory cascade in experimental model of diabetic nephropathy by sesamol. 1960 60

Obesity is a major cause of insulin resistance and type 2 diabetes. The altered glucose homeostasis is caused by faulty insulin signal transduction, which results in decreased glucose uptake by the muscle, altered lipogenesis, and increased glucose output by the liver. The etiology of this derangement in insulin signaling is related to a chronic inflammatory state, leading to the induction of inducible nitric oxide synthase and release of high levels of nitric oxide and reactive nitrogen species, which together cause posttranslational modifications in the signaling proteins. There are substantial differences in the molecular mechanisms of insulin resistance in muscle versus liver. Hormones and cytokines from adipocytes can enhance or inhibit both glycemic sensing and insulin signaling. The role of the central nervous system in glucose homeostasis also has been well established. Multi-pronged therapies aimed at rectifying obesity induced anomalies in both central nervous system and peripheral tissues may prove to be beneficial. The golden standard method to evaluate the insulin sensitivity is hyperinsulinemic euglycemic clamp.
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PMID:[Mechanism, treatment, and evaluation of obesity-induced insulin resistance and type 2 diabetes]. 2023 79

Prostacyclin synthase (PGIS) is tyrosine nitrated in diseased animals. Whether PGIS nitration occurs in human diabetic atherosclerotic arteries has not been reported. The present study was designed to determine PGIS nitration and its association with the inflammatory response in atherosclerotic carotid arteries from patients with or without type 2 diabetes, and carotid plaques were obtained from patients who underwent carotid endarterectomy. PGIS nitration, nitric oxide synthases, adhesion molecules, myeloperoxidase, osteopontin, and matrix metalloproteinase (MMP) were measured by using immunohistochemistry and Western blotting. In low stenosis areas, diabetes enhanced reactive nitrogen species production, as evidenced by increases in 3-nitrotyrosine and PGIS nitration. In parallel, diabetes dramatically increased inflammatory markers including intracellular adhesion molecule-1, vascular adhesion molecule-1, and osteopontin. In both diabetic and nondiabetic patients, MMP-2 and MMP-9 protein levels were significantly increased in the arteries with high stenosis as compared with those with low stenosis. Moreover, diabetes enhanced inducible nitric oxide synthase expression in the plaques from low stenosis areas and up-regulated myeloperoxidase expression in the plaques from both high and low stenosis areas. These data demonstrate that diabetes preferentially increases PGIS nitration that is associated with excessive vascular inflammation in atherosclerotic carotid arteries from patients with type 2 diabetes, suggesting a possible role of tyrosine nitration of PGIS in the development of atherosclerosis in patients with diabetes.
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PMID:Enhanced tyrosine nitration of prostacyclin synthase is associated with increased inflammation in atherosclerotic carotid arteries from type 2 diabetic patients. 2034 34

Recently it has been reported that low serum IL-10 levels are associated with an increased susceptibility for metabolic syndrome and type 2 diabetes mellitus (T2DM). We investigated whether the -1087G/A (rs1800896), -824C/T (rs1800871), -597C/A (rs1800872) IL-10 polymorphisms were associated with type 2 diabetes in a study on a cohort of Italian Caucasians comprising 490 type 2 diabetic and 349 control subjects. Stratifying the data according to IL-10 genotypes, trends for the progressive increase of glucose and neutrophil levels were observed in -1087GG vs. -1087GA vs. -1087AA positive diabetic patients (-1087GG<-1087GA<-1087AA). In addition, evaluating the laboratory parameters according to the -597/-824/-1087 derived haplotypes a significant increase of neutrophils was found in diabetic vs. non-diabetic -597A/ -824T/-1087A positive subjects (Student t test = 3.707, p<0.01). In an attempt to integrate clinical laboratory and immunogenetic data to determine whether these factors taken together define sufficient risk sets for type 2 diabetes we performed the grade-of-membership analysis (GoM). GoM allowed to identify a population of subjects negative for IL-10 -824T allele, 74.4% of which were diabetic patients characterised by vascular damages (Chronic kidney failure and/or Myocardial Infarction), reduction of haematocrit, increase of blood urea nitrogen, creatinin and monocyte levels. These data seem to suggest that -597A/-824T/-1087A negative subjects are more prone to the major type 2 diabetic vascular damages and allow to hypothesise that the contemporary evaluation of some simple hematochemical parameters and IL-10 SNPs may allow identifying diabetic patients with the worse prognostic profile, needing both better complication prevention planning and therapeutic strategies.
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PMID:Risk profiles in type 2 diabetes (metabolic syndrome): integration of IL-10 polymorphisms and laboratory parameters to identify vascular damages related complications. 2038 4

Diabetes mellitus (DM) is closely associated with cardiovascular (CV) diseases. These are the main cause of death in patients not only with type 2 but also type 1 diabetes. Apart from the traditional risk factors such as arterial hypertension, dyslipidemia and obesity, hyperglycaemia is an independent risk factor for the development of ischemic heart disease (IHD). Long-term hyperglycaemia leads to vascular damage through several mechanisms. These include oxidative stress, formation of advanced glycation end products, activation of the nuclear factor kappa B and decreased production of nitrogen monoxide (NO). Insulin resistance is believed to have an important bearing on pathogenesis of IHD in type 2 diabetes (DM2) patients. The course of IHD in diabetic patients is usually more complicated. Direct percutaneous coronary intervention (PCI) is the gold standard in the treatment of myocardial infarction (MI) in diabetic as well as non-diabetic patients. Drug-eluting stents, associated with fewer reocclusions, have also proved useful. In addition to drug-eluting stent implantation, surgical revascularization, preferably utilizing internal thoracic artery, is a suitable technique in patients without acute coronary syndrome indicated for an intervention. Conservative approach should be applied in less severely affected patients. IHD prevention should include appropriate control of arterial hypertension, dyslipidemia and weigh reduction. Diabetes treatment should be managed individually and with respect to the potential risk of hypoglycaemia in high-risk patients with longer duration of diabetes and known CV disease. Newly diagnosed type 2 diabetes patients should from the onset be treated with metformin and tight compensation should be aimed for with target value for glycated haemoglobin of less than 4.5% (IFCC methodology). Evidence exists that this approach may significantly reduce the CV risk. Intensified insulin regimen is the most suitable treatment approach for the type 1 diabetes patients also with respect to microvascular and macrovascular complication prevention. Treatment of hyperglycaemia is one of the set of measures that may contribute to CV risk reduction in diabetic patients.
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PMID:[Diabetes mellitus and ischemic heart disease]. 2046

C peptide is an active peptide hormone with potentially important physiological effects. C peptide has the capacity to diminish glomerular hyperfiltration and reduce urinary albumin excretion in both experimental and human type 1 diabetes. The present study is aimed at correlating the serum C peptide level with that of renal clearance, urinary albumin excretion and duration of diabetes. This is a prospective cross sectional study. Patients with diagnosis of type 2 diabetes mellitus were evaluated for their baseline clinical and laboratory profile. Both males and females above the age of 18 years were included in the study. The laboratory investigations include fasting serum C peptide, HbA(1C), serum creatinine, blood urea nitrogen, urine albumin and creatinine. Creatinine clearance was calculated using modification of diet in renal disease formula from serum creatinine value. A total of 168 patients were included in the study, among them 90 were females (53.57%) and 78 males (46.43%). Mean age of the patients was 57.64 years. Pearson correlation test showed negative correlation of serum C peptide level with creatinine clearance, though statistically not significant. Negative correlation was also seen between serum C peptide, and urine albumin, urine albumin creatinine ratio, HbA(1C) and duration of diabetes. Mean urine albumin was higher in patients with subnormal C peptide level. Duration of disease was more in patients with lower serum C peptide level. The study has shown weak association of serum C peptide level with microalbuminuria and creatinine clearance. Risk of albuminuria is more in patients with low serum C peptide level.
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PMID:Serum C peptide level and renal function in diabetes mellitus. 2053 67

The hypoglycemic effect of cinnamon oil (CO) in a type 2 diabetic animal model (KK-A(y) mice) was studied. The main component of CO was cinnamaldehyde, and other nineteen components were also determined. CO was administrated at doses of 25, 50 and 100mg/kg for 35 days. It was found that fasting blood glucose concentration was significantly decreased (P<0.05) with the 100mg/kg group (P<0.01) the most efficient compared with the diabetic control group. In addition, there was significant decrease in plasma C-peptide, serum triglyceride, total cholesterol and blood urea nitrogen levels while serum high density lipoprotein (HDL)-cholesterol levels were significantly increased after 35 days. Meanwhile, glucose tolerance was improved, and the immunoreactive of pancreatic islets beta-cells was promoted. These results suggest that CO had a regulative role in blood glucose level and lipids, and improved the function of pancreatic islets. Cinnamon oil may be useful in the treatment of type 2 diabetes mellitus.
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PMID:Antidiabetic effects of cinnamon oil in diabetic KK-Ay mice. 2056 48

Extreme hyperkalaemia is a life-threatening electrolyte disorder. It is relatively common in patients with severe renal insufficiency. This report describes a case of extreme hyperkalaemia caused by drugs in an 82-year-old female patient without severe renal insufficiency, who was successfully treated without haemodialysis. The patient had been treated for arterial hypertension and type 2 diabetes mellitus for 30 years. Over the last years she had been receiving enalapril and metformin. Three weeks before the admission to the hospital, she was receiving a non-steroidal anti-inflammatory drug (NSAID) because of the back pain. She was admitted to hospital due to a collapse and weakness in the limbs. Laboratory tests showed extreme hyperkalaemia, high blood sugar, metabolic acidosis, elevated serum creatinine and blood urea nitrogen (BUN), and a slightly elevated serum sodium. On ECG, we noticed typical signs of hyperkalaemia.The patient was treated with a slow intravenous bolus of calcium gluconate and intravenous infusion of sodium chloride with insulin, glucose with insulin and sodium bicarbonte. After the treatment, all laboratory findings normalised together and the patient felt better. This case shows that physicians should be very careful when prescribing NSAIDs to elderly patients treated with drugs that affect renal function.
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PMID:Extreme hyperkalaemia caused by concomitant use of a NSAID and an ace inhibitor in an elderly patient. 2058 99

The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to nitrite and then NO and other bioactive nitrogen oxides. Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary nitrate source. Nitrate administration increased tissue and plasma levels of bioactive nitrogen oxides. Moreover, chronic nitrate treatment reduced visceral fat accumulation and circulating levels of triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary nitrate fuels a nitrate-nitrite-NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against cardiovascular disease and type 2 diabetes.
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PMID:Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice. 2087 22


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