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)

The prevalence of type 2 diabetes mellitus is rising rapidly in all developed countries, particularly in the growing population of persons >50 years of age. As a dangerous consequence, this is accompanied by a proportionate increase in the incidence of chronic renal disease. Evidence-based medicine has shown that tight blood glucose control can delay the onset and retard the progression of diabetic complications, and while it is a challenge to closely manage the complexity of diabetes, it is more difficult to effectively treat the multiple associated comorbidities that develop. Best practice guidelines support early intervention and aggressive treatment of hypertension, hyperglycaemia, proteinuria, hypercholesterolemia, and anaemia. To date, guideline-based management has been proven to be difficult. This article describes the concept of the IRIDIEM studies. The objective of these studies is to endorse and facilitate the use of current best practice guidelines for the management of frequent comorbid diseases and established risk factors in the treatment of type 2 diabetes associated with chronic kidney disease. Additionally, IRIDIEM will assess the impact of this improved disease management model on the progression of chronic kidney disease that can result from electronically prompting clinicians with evidence-based treatment advice.
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PMID:Individualized risk management in diabetics: how to implement best practice guidelines--design and concept of the IRIDIEM studies. 1511 29

Insulin resistance is a characteristic feature of obesity and type 2 diabetes mellitus, but it is also present in up to 25% of healthy nonobese individuals. The molecular mechanisms causing insulin resistance are not yet fully understood. Recently, overexpression of several potential inhibitors of the insulin receptor tyrosine-kinase activity, a key step in insulin signaling, has been described in insulin-resistant subjects . PC-1 is expressed in many tissues and inhibits insulin signaling either at the level of the insulin receptor or downstream at a postreceptor site. An elevated PC-1 content in insulin target tissues may play an important role in the development of insulin resistance in obesity and type 2 diabetes mellitus. A polymorphism in PC-1 has been demonstrated to be associated with insulin resistance. This was a DNA polymorphism in exon 4 that causes an amino acid change from lysine to glutamine at codon 121 (K121Q). PC-1 121Q allele might predispose independently of other well established risk factors for early myocardial infarction. Testing for the PC-1 K121Q polymorphism might be valuable in patients with a family history of atherosclerotic vascular disease and myocardial infarction. There is growing evidence that genetic factors play an important role in the development of diabetic nephropathy (DN). Efforts to identify these factors rely primarily on the candidate gene approach; candidate genes for insulin resistance may be considered candidates for DN as well. In a stratified analysis according to duration of diabetes, the risk of early-onset end-stage renal disease (ESRD) for carriers of the Q variant was 2.3 times that for noncarriers. The cellular mechanisms for the insulin resistance of pregnancy and gestational diabetes mellitus (GDM) are unknown. Women with GDM have an increased PC-1 content and excessive phosphorylation of serine/threonine residues in muscle insulin receptors. The postreceptor defects in insulin signaling may contribute to the pathogenesis of GDM and the increased risk for type 2 diabetes later in life. Although widely explored, the true cause of insulin resistance in uremic patients is not entirely elucidated yet. During the last decade it was found that erythropoietin (EPO) therapy, used for correction of anemia in patients with end stage renal failure, ameliorates insulin resistance. An increased lymphocyte PC-1 activity over control was found in hemodialysis patients. A two-month EPO therapy significantly decreased PC-1 activity to the control values, suggesting that an effect on PC-1 expression could be implicated in the amelioration of insulin resistance in uremic patients treated with EPO. Current investigations implicate that therapeutic modification of PC-1 expression would be of great benefit for insulin-resistant type 2 diabetics. Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics. Thiazolidinedione (TZD) insulin-sensitizing drugs are a class of compounds that improve insulin action in vivo. Treatment of patients with TZDs seems to have a beneficial effect on most, if not all, components of metabolic syndrome. TZDs have also been used in the treatment of nondiabetic human insulin-resistant states, and have demonstrated an improvement in insulin sensitivity. Although much remains to be learned about PPAR gamma receptor and TZD action, the advent of TZD insulin-sensitizing agents has an enormous impact on our understanding of insulin resistance. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms.
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PMID:Plasma cell membrane glycoprotein 1 (PC-1): a marker of insulin resistance in obesity, uremia and diabetes mellitus. 1520 35

Thirty-three patients with type 2 diabetes mellitus (16 men, 17 women) were divided into 3 groups based on urinary excretion of albumin (U-Alb)--group A: U-Alb < 30 mg/d; group B: 30 mg/d < or = U-Alb < or = 300 mg/d; and group C: 300 mg/d < U-Alb. Serum creatinine levels were lower than 2.0 mg/dL in all the subjects. There was no difference in age, sex, therapy, body weight, body mass index (BMI), lean body mass (LBM), or hemoglobin A(1c) (HbA(1c)) levels among the 3 groups. Resting metabolic rate (RMR) (kJ/h/m(2)) and adjusted RMR for lean body mass (kJ/h/m(2)) were significantly increased in group C compared with groups A and B. Hb concentrations, serum albumin levels, and creatinine clearance were much lower in group C than in groups A and B (P < .001). There were no difference in serum urea nitrogen, total cholesterol, cholinesterase and free thyroxine, or plasma insulin-like growth factor I (IGF-I) levels among the 3 groups. Linear regression analysis revealed an inverse correlation between RMR and serum albumin levels, correlation between RMR and U-Alb, and inverse correlation between RMR and Hb concentrations, respectively, in these patients. In conclusion, RMR in diabetic patients correlated directly with U-Alb and inversely with serum albumin and Hb concentration. These findings suggest that RMR is related with urinary albumin loss and anemia in patients with type 2 diabetes mellitus accompanied by diabetic nephropathy.
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PMID:Increased resting metabolic rate in patients with type 2 diabetes mellitus accompanied by advanced diabetic nephropathy. 1553 91

Male hypogonadism has a multifactorial etiology that includes genetic conditions, anatomic abnormalities, infection, tumor, and injury. Defects in the hypothalamic-pituitary-gonadal axis may also result from type II diabetes mellitus and treatment with a range of medications. Circulating testosterone levels have been associated with sexual function, cognitive function, and body composition. Apart from reduced levels of testosterone, clinical hallmarks of hypogonadism include absence or regression of secondary sex characteristics, reduced fertility (oligospermia, azoospermia), anemia, muscle wasting, reduced bone mass (and bone mineral density), and/or abdominal adiposity. Some patients, particularly those with partial androgen deficiency of the aging male, also experience sexual dysfunction, reduced sense of vitality, depressed mood, increased irritability, difficulty concentrating, and/or hot flushes in certain cases of acute onset. As many patients with male hypogonadism-like patients with erectile dysfunction-do not seek medical attention, it is important for clinicians to be acquainted with the signs and symptoms of hypogonadism, and to conduct appropriate laboratory testing and other assessments to determine the causes and inform the treatment of this condition.
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PMID:Male hypogonadism. Part II: etiology, pathophysiology, and diagnosis. 1609 14

(1) When single-agent therapy provides inadequate glycaemic control for patients with type 2 diabetes, most guidelines recommend metformin in combination with a glucose-lowering sulphonylurea as standard treatment, despite the lack of any proven impact on morbidity or mortality. Other options include switching to insulin or abandoning the target of strict glycaemic control. (2) Pioglitazone and rosiglitazone are approved for use in combination with a glucose-lowering sulphonylurea when metformin is poorly tolerated or contraindicated, and in combination with metformin in overweight patients. (3) A fixed-dose combination containing 1 or 2 mg of rosiglitazone plus 500 mg of metformin (hydrochloride) was launched onto the French market in October 2004. (4) The indication for rosiglitazone was extended to include its use as triple-agent therapy in combination with metformin and a glucose-lowering sulphonylurea. (5) No clinical trials assessing effects on mortality or morbidity have evaluated rosiglitazone or pioglitazone in combination with other oral antidiabetic drugs. (6) Several trials have compared the glucose-lowering effects of dual-agent therapy using rosiglitazone or pioglitazone plus a glucose-lowering sulphonylurea or metformin versus dual-agent therapy with metformin and a glucose-lowering sulphonylurea. (7) These clinical trials indicate that in terms of HbA1c level, dual-agent therapy based on rosiglitazone or pioglitazone is about as effective as combination therapy with metformin plus a glucose-lowering sulphonylurea. (8) The main known adverse effect of pioglitazone and rosiglitazone is water-sodium retention, which can provoke oedema and haemodilution anaemia, and can aggravate or reveal heart failure. (9) Pioglitazone has a positive effect on the lipid profile, whereas rosiglitazone increases the LDL-cholesterol level. (10) Dual-agent therapy with pioglitazone and a sulphonylurea causes more weight gain than metformin plus a sulphonylurea. (11) Several trials have assessed triple-agent regimens containing a glitazone. Three placebo-controlled double-blind trials have tested pioglitazone (one trial, nearly 300 patients) or rosiglitazone (two trials, about 1200 patients) for 12 to 26 weeks in patients whose glycaemia was poorly controlled by dual-agent therapy with a sulphonylurea plus metformin. The glycated haemoglobin level fell by 0.3% to 1.1% (in absolute values), depending on the trial and the dosage, but at a cost of the usual adverse effects such as weight gain, anaemia and oedema. Three unblinded trials have compared oral triple-agent regimens containing glitazone versus insulin plus metformin, alone or in combination with a glucose-lowering sulphonylurea; the treatment including glitazone was no more effective in terms of the glycated haemoglobin level, but was associated with an increase in adverse effects and dropouts. (12) Given the limited clinical data available in early 2005, pioglitazone and rosiglitazone have no place in the management of type 2 diabetes.
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PMID:Pioglitazone, rosiglitazone, and rosiglitazone + metformin: new drugs. Glitazone + oral antidiabetic combination: inadequately evaluated. 1610 95

We investigated erythropoietin (Epo) response in a cohort of diabetic patients with various types of anemia to approach the pathogenesis of some cases of "unexplained" anemia encountered among diabetics. Serum Epo levels were determined totally in 747 evaluable subjects with normal renal and hepatic function, of whom 694 had anemia. Among anemic patients, 237 were diabetics, while among the 53 nonanemic persons, there were also 21 diabetics. Diabetic and nondiabetic subjects were uniformly balanced in relation to their demographic features and were categorized according to the etiology of their anemia. Hemoglobin (Hb) did not differ between diabetic and nondiabetic subjects in all the etiological groups and in the whole population. Diabetic patients had significantly lower serum Epo levels as compared to nondiabetics (36.5+/-61 vs 69.4+/-191 IU/ml, p<0.0001), and this was true for all etiologic groups of anemia with the exception of patients with myeloproliferative disorders and those with megaloblastic anemia. The natural logarithmic (ln)-EpoxHb component was used as an index of response to anemia and was found to be significantly decreased in almost all subgroups of diabetic patients. Serum Epo levels were also negatively correlated with the percentage of glycosylated Hb, HbA1(C) (r=-0.446), and the correlation was stronger with the ln of serum Epo (r=-0.638, p<0.001). Inappropriately low serum Epo level is a uniform feature in patients with type II diabetes mellitus and may represent a constitutive blunted response to anemia or an altered metabolic rate of Epo, probably as a result of abnormal glycosylation of the cytokine.
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PMID:Inappropriately low erythropoietin response for the degree of anemia in patients with noninsulin-dependent diabetes mellitus. 1613 4

The rising incidence of type 2 diabetes mellitus and of its complications will make it the most important health care challenge in the first quarter of the 21st Century. Diabetic nephropathy left unchecked will overwhelm the renal resources. Simple methods (proper diet and exercise, prevention of obesity) are successful in preventing type 2 diabetes in the great majority of the persons at risk. In patients with established type 2 diabetes, nephropathy can be prevented or greatly delayed by strict metabolic control, strict control of blood pressure using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers as the first line of drugs, tight control of serum lipids using statins as indicated, low protein diet, avoidance of smoking and other nephrotoxic influences, prevention of abnormalities in calcium/phosphorus metabolism, and prevention of renal anemia by the early use of erythropoietin. Current research offers the promise of definitive prevention of both type 2 diabetes and diabetic nephropathy.
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PMID:Prevention of nephropathy in patients with type 2 diabetes mellitus. 1630 58

We describe here four male patients with long-term and poorly controlled type 2 diabetes mellitus. They shared many common characteristic complications, such as severe autonomic neuropathy, proliferative retinopathy and normocytic normochromic anemia without progressive renal failure and macroangiopathy. They also showed normal levels of erythropoietin and reticulocyte, which was considered relatively low. The coefficient of variation of R-R, a useful method to estimate autonomic failure, showed markedly advanced autonomic neuropathy in all four patients. Coronary angiography did not reveal stenosis, anomaly or collateral vessels, but left ventriclography showed diffuse or partial hypokinesis. Massive proteinuria, high urinary levels of N-acetyl-beta-D-glucosamidase (NAG) and beta2-microglobulin (beta2M) were detected, though creatinine clearance (Ccr) was not so deteriorated. Treatment with recombinant erythropoietin increased their hemoglobin and hematocrit levels. These common points have a possibility to be brought about by tubulointerstitial damage and microangiopathy may be involved in it.
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PMID:Normocytic normochromic anemia due to automatic neuropathy in type 2 diabetic patients without severe nephropathy: a possible role of microangiopathy. 1632 60

Analysis of the biologic effects of erythropoietin and pathophysiology of chronic kidney diseases (CKD) suggests that treatment with erythropoiesis-stimulating agents (ESA) could slow the progression of CKD. By decreasing hypoxia and oxidative stress, it could prevent the development of interstitial fibrosis and the destruction of tubular cells. It could have direct protective effects on tubular cells through its antiapoptotic properties. It could help maintain the integrity of the interstitial capillary network through its effects on endothelial cells. Thus, suggesting that correcting anemia with ESA could slow the progression of CKD is biologically plausible. In patients with CKD, three small prospective studies and a retrospective study have suggested that treatment with ESA may have protective effects. Post-hoc analysis of the Reduction in Endpoints in Noninsulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan study has also shown that anemia was an independent risk factor for progression of nephropathy in patients with type 2 diabetes. In addition, a large clinical trial, which had to be stopped prematurely because of labeling change for subcutaneous administration of epoetin alfa, suggests that complete normalization of hemoglobin levels is safe in CKD patients not on dialysis and without severe cardiovascular disease. Thus, it seems reasonable to advocate starting a large randomized, prospective study to determine if normalization of hemoglobin concentration can effectively slow the progression of CKD.
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PMID:Anemia management and chronic renal failure progression. 1633 82

Biliopancreatic diversion (BPD) is a bariatric operation of proved efficacy especially in patients with metabolic comorbidities. The aim was to assess the results of BPD in relation to weight loss and coexisting lipid and glucose metabolism disturbances in the Polish population. Between October 2001 and December 2003 57 morbidly obese patients (24 male and 33 female) underwent BPD. Median age was 46 years (range: 17-58) and median body mass index (BMI) was 50.2 kg/m(2) (range: 40.1-73 kg/m(2)). Type 2 diabetes mellitus was observed in 11 patients (19.3%), hypercholesterolaemia in 38 patients (66.7%) and hypertriglyceridaemia in 37 patients (64.9%). Median value of BMI decreased at three months to 40.0 kg/m(2), at six months to 36.7 kg/m(2), and after a year to 32.3 kg/m2. Diabetes was completely resolved in all patients. After six months, triglycerides and cholesterol levels were higher than normal only in one patient. Early specific complications that manifested as seroma and nosocomial pneumonia occurred in 5.3% and 3.5% patients, respectively. The following specific late complications were observed: ulceration of stomach stump (3.4%), anaemia (14.0%), hypoalbuminaemia (8.8%), deterioration of haemorrhoids (15.8). All of above complications were treated conservatively expect two haemorrhoidectomies. One patient died due to myocardial infarction eight months after BPD. Five cases of incisional hernias (8.8%) were found. BPD is an effective bariatric procedure also in the Polish population, resulting not only in weight loss but also in the improvement of lipid and glucose metabolism.
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PMID:Biliopancreatic diversion in Poland. 1634 45


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