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)

Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.
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PMID:Childhood obesity and type 2 diabetes mellitus. 1606 6

Although hyperhomocysteinemia, an independent cardiovascular risk factor, is common in type 2 diabetes with nephropathy, the mechanism(s) of this alteration is not known. In healthy humans, hyperinsulinemia increases methionine transmethylation, homocysteine transsulfuration, and clearance. No such data exist in type 2 diabetes either in the fasting state or in response to hyperinsulinemia. To this purpose, seven male type 2 diabetic patients with albuminuria (1.2 +/- 0.4 g/day, three with mild to moderate renal insufficiency) and seven matched control subjects were infused for 6 h with L-[methyl-(2)H(3), 1-(13)C]methionine. Methionine flux, transmethylation, and disposal into proteins as well as homocysteine remethylation, transsulfuration, and clearance were determined before and after euglycemic hyperinsulinemia (approximately 1,000 pmol/l). In type 2 diabetic subjects, homocysteine concentration was twofold greater (P < 0.01) and methionine transmethylation and homocysteine clearance lower (from approximately 15 to >50% and from approximately 40 to >100%, respectively; P < 0.05) than in control subjects. The insulin-induced increments of methionine transmethylation, homocysteine transsulfuration, and clearance were markedly reduced in type 2 diabetic subjects (by more than threefold, P < 0.05 or less vs. control subjects). In contrast, methionine methyl and carbon flux were not increased in the patients. In conclusion, pathways of homocysteine disposal are impaired in type 2 diabetes with nephropathy, both in postabsorptive and insulin-stimulated states, possibly accounting for the hyperhomocysteinemia of this condition.
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PMID:Effects of insulin on methionine and homocysteine kinetics in type 2 diabetes with nephropathy. 1618

Lactic acidosis is a serious clinical situation associated with a high case fatality rate. Lactic acidosis is particularly found in conditions with an insufficient supply of oxigen in the tissue. Other causes for lactic acidosis can be hepatic or renal insufficiency. For the therapy of overweight patients with type 2 diabetes metformin is the first choice if diet and physical training have been ineffective. Metformin, however, has the potential to increase serumlactate. Therefore its ability to cause lactic acidosis is controversely discussed. We present a 64-year-old female patient with metformin-associated lactic acidosis. She had several pre-existing risk factors to develop a lactic acidosis. On her referral to the hospital she suffered from acute renal failure which is considered to be a contraindication for the use of metformin.
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PMID:[Metformin-associated lactic acidosis in a patient with pre-existing risk factors]. 1619 Mar 74

Patients with diabetes mellitus are at increased risk for repeat interventions and mortality after coronary angioplasty and stenting. The efficacy of sirolimus-eluting stents (SESs) to improve the outcomes of these patients is a focus of interest. In the first 1,407 patients treated with SESs at our institution, 492 were diabetic (insulin dependent diabetes mellitus [IDDM], n = 160 and non-insulin-dependent DM [NIDDM], n = 332). The in-hospital and 1- and 6-month clinical outcomes were compared with those of 915 patients without DM (non-DM). The baseline characteristics were similar, except for more women, obesity, previous myocardial infarction, coronary artery bypass grafting, and renal insufficiency in the DM group (p <0.001). Compared with non-DM patients, DM patients had higher in-hospital (p <0.05) and 1-month mortality (p = 0.02). IDDM patients had more in-hospital renal failure (p = 0.04) and Q-wave myocardial infarctions (1.6% vs 0%, p = 0.04) compared with NIDDM patients, and higher mortality (3.1% vs 0.8%, p = 0.04) and subacute stent thromboses (2.3% vs 0.5%, p = 0.07) than non-DM patients at 30 days. At 6 months, DM patients had a higher incidence of Q-wave myocardial infarction, target lesion revascularization-major adverse cardiac events, and composite of death and Q-wave myocardial infarction than non-DM patients (6.0% vs 2.7%, p = 0.01). Late outcomes between the IDDM and NIDDM groups were similar. Multivariate analysis showed diabetes and acute renal failure as independent predictors of target lesion revascularization-major adverse cardiac events. In conclusion, our data showed that, despite a reduction in repeat revascularization, coronary intervention with SESs in diabetic patients is limited by higher mortality at 1 month and a higher incidence of Q-wave myocardial infarction and target lesion revascularization-major adverse cardiac events at 6 months compared with non-DM patients. Careful surveillance is required in IDDM patients undergoing SES implantation.
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PMID:Impact of treatment of coronary artery disease with sirolimus-eluting stents on outcomes of diabetic and nondiabetic patients. 1621 45

Diabetic nephropathy is currently the most common cause of end-stage renal disease. Diabetic nephropathy patients, whether insulin dependent or not, develop fibrotic changes in glomeruli that manifest as overt nephropathy. Previously, we demonstrated that 5-chloro-2-{(1E)-3-[2-(4-methoxybenzoyl)-4-methyl-1H-pyrrol-1-yl]prop-1-en-1-yl}-N-(methylsulfonyl)benzamide (SMP-534) reduces extracellular matrix (ECM) production induced by transforming growth factor-beta (TGF-beta) in vitro and prevents the accumulation of ECM in glomeruli in rat Thy-1 nephritis models. In this study, we examined the long-term effects of SMP-534 on renal insufficiency and glomerulosclerosis in db/db mice, which are models of type 2 diabetes. A diet containing SMP-534 was given to the mice from the age of 9 to 25 wk, and blood and urine analysis were performed at 8, 17, and 25 wk. At the end of study, kidney tissues were analyzed histologically. Treatment with SMP-534 dose dependently suppressed the increase of urinary albumin and type IV collagen excretion in db/db mice. The renal histological analysis showed that SMP-534 dose dependently suppressed the increase of mesangial expansion in the kidney. In the immunohistological analysis, fibronectin and type IV collagen expression were lower in SMP-534-treated db/db mice compared with vehicle-treated db/db mice. This study suggested that SMP-534 ameliorated the increase of ECM production in kidney of db/db mice, possibly through the inhibition of TGF-beta action. Hence, antifibrotic agents such as SMP-534 might be a new therapeutic option for the treatment of diabetic nephropathy.
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PMID:SMP-534 ameliorates progression of glomerular fibrosis and urinary albumin in diabetic db/db mice. 1627 77

Dyslipidemia and inflammation may promote renal disease via mechanisms of vascular endothelial cell dysfunction in type II diabetes mellitus (DM). Sparse data, however, are available on the relation of lipids and inflammatory biomarkers and glomerular filtration rate (GFR) in type II DM. We performed a cross-sectional study of 732 men with type II DM enrolled in the Health Professionals' Follow-Up Study. Plasma creatinine was used to estimate GFR by the simplified Modification of Diet in Renal Disease (MDRD) equation. In men with a GFR <60 ml/min/1.73 m(2), triglycerides, non-high-density lipoprotein (HDL), apoprotein B, fibrinogen, soluble tumor necrosis factor receptor (sTNFR-2) and vascular cell adhesion molecule-1 (VCAM) were significantly higher when compared to the referent group (GFR> or =90 ml/min/1.73 m(2)). In multivariable logistic regression, those in the highest quartiles of the following biomarkers had increased odds of having a GFR <60 ml/min/1.73 m(2) when compared to those in the lowest quartiles: triglycerides (odds ratio (OR) 3.11; 95% CI, 1.52-6.36), fibrinogen (OR 5.40; 95% CI 2.14-13.65), sTNFR-2 (OR 8.34; 95% CI 3.50-19.88) and VCAM (OR 4.50; 95% CI 1.98-10.23). An inverse association was observed for HDL (OR 0.48; 95% CI 0.24-0.98). We found no association between C-reactive protein and GFR. The results were similar when creatinine clearance by Cockcroft-Gault was used to estimate kidney function. We conclude that several potentially modifiable lipid and inflammatory biomarkers are elevated in the setting of moderately decreased GFR in men with type II DM and may be the link between renal insufficiency and increased risk for cardiovascular events in this population.
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PMID:The association of serum lipids and inflammatory biomarkers with renal function in men with type II diabetes mellitus. 1640 7

Glinides represent a chemically heterogeneous new class of insulin-secreting agents characterized by a rapid onset and short duration of action. They act by closure of the ATP-dependant K channel. Repaglinide, the only glinide available in France, has an equivalent HbA1c lowering effect to conventional sulfonylureas but reduces predominantly postprandial glucose levels. Several studies indicate a decreased risk of hypoglycaemias, particularly nocturnal or in case of a shift or omission of a meal. This drug appears particularly useful in early stage type 2 diabetes or in combination with metformin. The only significant drug-drug interaction concerns gemfibrozil. Due to its hepatic metabolism and biliary elimination, repaglinide can be used in patients with renal insufficiency. Nateglinide has a even shorter duration of action and has almost no effect on fasting plasma glucose levels. For this reason, this drug is only indicated in combination with metformin in the countries where it is licensed. Several experimental data suggest that glinides could preserve B cell function over time better than hypoglycaemic sulfonylureas, and that the improvement of post-prandial glucose levels could exert a long term protective cardiovascular effect.
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PMID:Meglitinide analogues: a review of clinical data focused on recent trials. 1673 59

The Centers for Disease Control and Prevention estimate that 6% of the US population meets diagnostic criteria for diabetes mellitus, with at least one third of this group being undiagnosed. A majority of adult blindness, renal insufficiency, and limb amputation may be directly attributed to diabetes. Although the incidence of type 1, autoimmune-mediated diabetes remains relatively stable, increasing age, physical inactivity, and obesity have produced explosive growth in insulin resistance and type 2 diabetes. A direct association between diabetes and atherothrombotic disease remains indisputable. However, recent data further suggest that even minor elevations of fasting plasma glucose, in "nondiabetic" subjects, increase cardiovascular risk. Alterations in hemostasis may play an important contributory role. Both hyperglycemia and hyperinsulinemia induce prothrombotic characteristics, including overexpression of vascular endothelial plasminogen activator inhibitor-1 (PAI-1), down-regulation of fibrinolysis, elevation of plasma coagulation proteins (ie, fibrinogen, factor VII, factor X), and enhanced platelet activation. Furthermore, endothelial dysfunction-characterized by an inflammatory phenotype-commonly accompanies diabetes. Given data supporting prothrombotic potential of both acute and chronic hyperglycemia, aggressive perioperative glucose control appears imperative.
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PMID:Hemostasis and glycemic control in the cardiac surgical patient. 1695 46

Diabetes mellitus is a global health problem of steadily increasing proportions, with approximately 95% of patients being affected by the type 2 form of the disease. The growing challenge to healthcare systems presented by this disorder has prompted ongoing research into novel therapies with which to improve management. The sulfonylureas constitute a long-established group of drugs with a proven track record in the treatment of type 2 diabetes, but efforts to improve the overall metabolic profile and safety of these agents have led over time to the addition of newer agents such as the second-generation benzenesulfonylurea gliquidone. Gliquidone has extrapancreatic effects that result in increased numbers of insulin receptors in peripheral tissues. The drug is rapidly and almost completely absorbed after oral administration, and has a short elimination half-life (around 1.5 hours). Metabolism is maintained in patients with hepatic insufficiency, and accumulation does not take place in patients with impaired renal function. Plasma glucose levels are controlled for several hours as a result of glucose-induced insulin secretion, and beneficial effects on plasma lipids have been described. In clinical studies, gliquidone has been associated with less hypoglycaemia than glibenclamide (glyburide), and with metabolic control at least as good as that seen with a number of other sulfonylureas. Beneficial effects on platelet aggregation have been documented, and the drug is described by WHO as the preferred sulfonylurea for patients with mild to moderate renal insufficiency. Importantly, in the light of the well documented consequences of increased bodyweight and the large growth in obesity worldwide, gliquidone is not associated with significant bodyweight gain. Thus, gliquidone is a sulfonylurea with proven efficacy and good safety and metabolic profiles that is only rarely associated with hypoglycaemia. In particular, the metabolism and route of excretion of the drug allow its use in patients who have or may be at risk of diabetic nephropathy.
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PMID:Gliquidone contributes to improvement of type 2 diabetes mellitus management: a review of pharmacokinetic and clinical trial data. 1707 16

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


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