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)

Diabetes as the dominant cause of ESRD is also the major cause of renal anaemia. However, most patients with diabetic kidney disease will succumb to co-morbid vascular disease or heart failure before developing severe renal impairment. In these patients, anaemia is also common finding, with a 2-3 times greater prevalence and earlier onset than in patients with renal impairment from other causes. We have recently shown that at least one in five outpatients with type 1 or type 2 diabetes in tertiary referral clinics have anaemia, in whom it constitutes a significant additional burden. Impaired renal erythropoietin release in response to declining haemoglobin levels appears to be the major contributor to anaemia in diabetes. This may be due to the predominance of damage to cells and vascular architecture of the renal tubulointerstitium associated with diabetic nephropathy that may be apparent, like albuminuria, before demonstrable changes in renal function. In addition, systemic inflammation, autonomic neuropathy and reduce red cell survival may also compound anaemia in diabetes. While anaemia may be considered a marker of diabetic kidney disease, reduced haemoglobin levels, even within the normal range, identify diabetic patients with an increased risk of hospitalisation and mortality. Anaemia may also be significant in determining the outcome of heart failure and hypoxia-induced organ damage in patients with diabetes. Upcoming studies will determine whether correction of anaemia in diabetes will lead to improved outcomes in these patients.
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PMID:Anaemia in diabetes: an emerging complication of microvascular disease. 1822 May 87

The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) plays central roles in adipogenesis and glucose homeostasis and is the molecular target for the thiazolidinedione (TZD) class of antidiabetic drugs. Activation of PPARgamma by TZDs improves insulin sensitivity; however, this is accompanied by the induction of several undesirable side effects. We have identified a novel synthetic PPARgamma ligand, T2384, to explore the biological activities associated with occupying different regions of the receptor ligand-binding pocket. X-ray crystallography studies revealed that T2384 can adopt two distinct binding modes, which we have termed "U" and "S", interacting with the ligand-binding pocket of PPARgamma primarily via hydrophobic contacts that are distinct from full agonists. The different binding modes occupied by T2384 induced distinct patterns of coregulatory protein interaction with PPARgamma in vitro and displayed unique receptor function in cell-based activity assays. We speculate that these unique biochemical and cellular activities may be responsible for the novel in vivo profile observed in animals treated systemically with T2384. When administered to diabetic KKAy mice, T2384 rapidly improved insulin sensitivity in the absence of weight gain, hemodilution, and anemia characteristics of treatment with rosiglitazone (a TZD). Moreover, upon coadministration with rosiglitazone, T2384 was able to antagonize the side effects induced by rosiglitazone treatment alone while retaining robust effects on glucose disposal. These results are consistent with the hypothesis that interactions between ligands and specific regions of the receptor ligand-binding pocket might selectively trigger a subset of receptor-mediated biological responses leading to the improvement of insulin sensitivity, without eliciting less desirable responses associated with full activation of the receptor. We suggest that T2384 may represent a prototype for a novel class of PPARgamma ligand and, furthermore, that molecules sharing some of these properties would be useful for treatment of type 2 diabetes.
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PMID:T2384, a novel antidiabetic agent with unique peroxisome proliferator-activated receptor gamma binding properties. 1826 87

Burning mouth syndrome (BMS) is a complex disease of unknown cause. It is characterized by a burning sensation in the oral mucosa, notwithstanding its clinical normal aspect. BMS is particularly seen in postmenopausal women. The purpose of this study was to investigate this syndrome on a clinical basis and, in addition, to analyze its possible relation to the frequency of Candida species. Thirty-one patients (28 women and 3 men; 13 Caucasians and 18 non-Caucasians; mean age = 61.3, range 30-85 years) were evaluated. Most patients (80.6%) were under long-term medication, antihypertensive, ansiolitic and antidepressant drugs being the most used. Burning mouth complaint was associated with other secondary oral complaints in 83.8% of the cases. Tongue was the most commonly affected site (70.9%), followed by the vermillion border of the lower lip (38.7%) and hard palate (32.2%). The association of the burning sensation with oral cancer (cancer phobia) was reported by 67.7% of the patients. Haematologic examination (hematocrit, haemoglobin and fasting blood glucose level) revealed 2 cases each of anemia and type 2 diabetes. Local factors, tooth extractions and dentures wearing, were associated with the onset of symptoms in 35.5% of the cases. Daily activities were changed as a consequence of BMS in 29% of the patients. Among the species of the genus Candida, C. albicans was the most frequent in BMS patients (9 - 29.03%) and controls (12 - 38.70%), followed respectively by C. parapsilosis (2 - 6.45% and 0 - 0%); C. tropicalis (1 - 3.22% and 2 - 6.45%); C. krusei and C. kefyr (1 - 3.22% and 0 - 0%). Therefore, such difference did not reach valuable results. In conclusion, these data were similar to those reported in other studies. The highlights of the present findings were the possible relation of BMS with chronic drug use, depression, menopause and cancer phobia. No association was found between BMS and the prevalence of Candida species.
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PMID:Burning mouth syndrome: clinical profile of Brazilian patients and oral carriage of Candida species. 1827 6

Foot ulceration is a prominent cause of diabetes mellitus morbidity and mortality in developing countries. This is an observational study in which 47 consecutive diabetes mellitus patients with foot ulcers were studied over a 2-year period. Each patient's medical history, physical examination findings, and hematological and radiological features were documented. The mean age of the patients was 56 (11) years. The majority of the patients (40, 85%) had type 2 diabetes mellitus; 25% of patients with type 2 diabetes mellitus were diagnosed when they presented with foot ulceration. Grades 2 and 3 Wagner lesions were the most frequently noted grades of foot ulceration. The risk factors/precipitants of foot ulceration included neuropathy, vasculopathy, spontaneous blisters, walking unshoed, and wearing inadequate shoes. Prominent hematologic abnormalities included anemia and leucocytosis. Diabetes mellitus foot ulceration often occurs in middle-aged Nigerians with diabetes mellitus, and this diabetes mellitus complication may be present at diagnosis of type 2 diabetes mellitus. Subcutaneous emphysema, osteolysis, and soft tissue swelling are often documented radiological features of DFU in our patients.
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PMID:Common clinical features of diabetic foot ulcers: perspectives from a developing nation. 1849 76

Cardiovascular risk profiling and therapy have traditionally been based on established risk factors, such as age, smoking, sex, hypertension, dyslipidemia, body weight, and diabetes mellitus. Despite optimum therapy, cardiovascular mortality and morbidity remain high. Attention is being devoted, therefore, to identifying new risk factors that can also be used as therapeutic targets. Renal dysfunction manifesting as low glomerular filtration rate, albuminuria, or anemia is a strong risk factor for cardiovascular disease and is prevalent in the general population and among patients with cardiovascular disease. Epidemiological data suggest that 10-11% of the general population have low glomerular filtration rates, 5-7% have increased urinary albumin excretion, and 5-10% have anemia. Each of these features represents an independent but additive cardiovascular risk. Treatments for all these indications can reduce cardiovascular mortality and morbidity as well as renal risk. Such findings suggest that treatment should be directed towards improving renal function in order to achieve optimum cardiovascular benefit. Such a strategy would offer the possibility of multiorgan therapy in diseases characterized by multiorgan impairment, such as type 2 diabetes. I present the evidence that renal dysfunction is a common and powerful cardiovascular risk factor and that treatment strategies intervening in the renin-angiotensin-aldosterone system can be used to target albuminuria and reduce cardiovascular and renal risk.
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PMID:Renal disease: a common and a silent killer. 1858 Aug 63

Testosterone plays a critical role in male reproductive and metabolic functioning. Serum testosterone levels decrease with age, and low testosterone is associated with a variety of comorbidities, including insulin resistance, type 2 diabetes, obesity, metabolic syndrome, and cardiovascular disease. Men with type 2 diabetes have been shown to have significantly lower testosterone levels than men without diabetes. Several forms of testosterone replacement therapy (eg, oral, injectable, buccal, transdermal preparations) are available for use in the United States. The primary goals of testosterone therapy are to restore physiologic testosterone levels and reduce the symptoms of hypogonadism. Testosterone therapy may be a viable option in some men with diabetes and low testosterone; however, clinicians must be aware of contraindications to therapy (eg, prostate cancer and male breast cancer), implement appropriate monitoring procedures, and ensure that patient expectations are realistic regarding treatment outcome. Data suggest that testosterone therapy may have a positive effect on bones, muscles, erythropoiesis and anemia, libido, mood and cognition, penile erection, cholesterol, fasting blood glucose, glycated hemoglobin, insulin resistance, visceral adiposity, and quality of life. Sexual health may be a window into men's health; thus, more effective communication strategies are needed between clinicians and men with diabetes to ensure that sexual health topics are adequately addressed. Diabetes educators can play a key role in screening for low testosterone, providing relevant information to patients, and increasing clinician awareness of the need to address men's sexual health and implement appropriate strategies. Multidisciplinary care and individualized treatment are needed to optimize outcome.
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PMID:Men's health, low testosterone, and diabetes: individualized treatment and a multidisciplinary approach. 1902 Feb 65

Recent work shows a high prevalence of low testosterone and inappropriately low LH and FSH concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity, and other features of the metabolic syndrome (obesity and overweight, hypertension and hyperlipidemia) in patients with type 2 diabetes. However, the duration of diabetes or HbA1c were not related to HH. Furthermore, recent data show that HH is also observed frequently in patients with the metabolic syndrome without diabetes but is not associated with type 1 diabetes. Thus, HH appears be related to the two major conditions associated with insulin resistance: type 2 diabetes and the metabolic syndrome. CRP concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and CRP concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations in type 2 diabetic men have also been related to a significantly lower hematocrit and thus to an increased frequency of mild anemia. Low testosterone concentrations are also related to an increase in total and regional adiposity, and to lower bone density. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates symptoms related to sexual dysfunction, and features of the metabolic syndrome, insulin resistance and inflammation.
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PMID:Hypogonadotrophic hypogonadism in type 2 diabetes, obesity and the metabolic syndrome. 1907 78

Clinicians are faced with an expansive array of treatment choices when caring for patients with type 2 diabetes. Because patient compliance may be affected when media sensationalism about controversial findings is misunderstood, we sought to clarify the recent controversy surrounding the cardiovascular and bone-health risks of thiazolidinediones, the risk of lactic acidosis with metformin, and the risk of hypoglycemia with oral therapies. The side effect profile of thiazolidinediones includes fluid retention, heart failure; and an increased risk of fracture. A recent controversial meta-analysis suggested that rosiglitazone increases the risk of myocardial infarction, which is possibly related to thiazolidinedione-induced lipid changes, weight gain, congestive heart failure, and anemia. Metformin is restricted to patients with normal renal function because of concerns that metformin may cause lactic acidosis. However, few cases of metformin-associated lactic acidosis have been reported, and most have occurred in patients with other reasons for developing lactic acidosis, such as sepsis or renal failure. Although the use of metformin continues to increase, observational studies have not been able to demonstrate an increased incidence of lactic acidosis in metformin-treated patients, even when it is used in populations with relative contraindications. Some oral hypoglycemic medications can cause hypoglycemia. Hypoglycemia is especially common in older patients, alcoholics, and patients with liver or renal disease. Patients on sulfonylureas and meglitinides have the highest incidence of hypoglycemia because of their pharmacological action of increasing insulin secretion. Of the sulfonylureas, glyburide presents the highest risk of hypoglycemia. Combination therapies, especially those regimens containing a sulfonylurea, increase the risk of hypoglycemia.
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PMID:Balancing risk and benefit with oral hypoglycemic drugs. 1942 67

Patients with chronic kidney disease (CKD) have a high burden of mortality and cardiovascular morbidity. Additional strategies to modulate cardiovascular risk in this population are needed. Anaemia has been associated with adverse outcomes in CKD populations, and the ability to modify this parameter with the use of erythropoiesis-stimulating agents has been a topic of much debate. Data on the effects of anaemia correction on cardiovascular outcomes and survival in CKD have been both discordant and controversial. It is hoped that the ongoing Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT) will help to redress the current clinical gaps and the uncertainty over the optimal management of anaemia in patients with CKD and type 2 diabetes mellitus. Anaemia is also increasingly being recognized as an important comorbid condition in patients with symptomatic heart failure. The ongoing Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF(TM)) trial is designed to determine whether the treatment of anaemia improves outcomes in such patients.
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PMID:Future perspectives on treatment with erythropoiesis-stimulating agents in high-risk patients. 1946 57

Low serum adiponectin is associated with a high incidence of type 2 diabetes or coronary artery disease in the general population. Paradoxically, serum adiponectin is elevated in patients with chronic kidney disease (CKD), such as overt diabetic nephropathy. The current study aimed to investigate whether anemia was independently associated with the serum level of high-molecular-weight (HMW) adiponectin in patients with type 2 diabetes. We studied 207 type 2 diabetic patients (92 women and 115 men). Anemia was defined as a hemoglobin (Hb) <13.0g/dL in men and <12.0g/dL in women according to the guidelines of the World Health Organization (WHO). Overt nephropathy (CKD) was defined as clinical proteinuria and /or estimated glomerular filtration rate (eGFR) lower than 60mL/min for more than 3 months. The diabetic patients were divided into 4 groups according to the presence or absence of anemia and/or CKD. Serum HMW adiponectin levels were measured by a sandwich enzyme-linked immunosorbent assay. In all 207 patients with type 2 diabetes, serum total and HMW adiponectin levels were correlated positively with age, the duration of diabetes, high-density lipoprotein (HDL) cholesterol, urinary albumin, and serum erythropoietin, whereas negative correlations were found with body mass index, triglyceride, eGFR, Hb, hematocrit, and high sensitivity C-reactive protein. A stepwise regression analysis demonstrated that among several significant variables, Hb had the strongest independent influence on HMW adiponectin (beta =-0.487, P < 0.001). Diabetic patients of both sexes with anemia and CKD had the highest serum levels of HMW adiponectin among the 4 groups. In conclusion, anemia is associated with marked elevation of serum HMW adiponectin levels in diabetic patients who have CKD, and this elevation is independent of renal function.
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PMID:Anemia is associated with an elevated serum level of high-molecular-weight adiponectin in patients with type 2 diabetes independently of renal dysfunction. 1976 61


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