Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New-onset diabetes mellitus in a previously non-diabetic transplant recipient is a serious adverse event that confers significant morbidity and mortality. The most significant consequences of post-transplant diabetes mellitus (PTDM) in solid organ transplant recipients include decreased patient and graft survival, an increased risk of infectious complications, and morbid cardiovascular events. The development of PTDM in the elderly is of particular concern because this group is already at increased risk of progression of cardiovascular disease. Because the elderly, especially those aged >65 years, are the fastest-growing segment of the renal transplant population, attention needs to be given to PTDM risk reduction and post-transplant management. PTDM develops as a consequence of both impaired insulin production and enhanced peripheral insulin resistance. A number of non-modifiable factors such as age, race, family history, hepatitis C, polycystic kidney disease and emerging genetic causes have been identified as risk factors for PTDM. However, a number of modifiable factors can be targets for intervention in high-risk patients, including bodyweight (through dietary restriction and exercise), hypertension, hyperlipidaemia and the effects of certain immunosuppressive agents. The two agents most responsible for PTDM are tacrolimus and corticosteroids, especially when used in combination. Attempts to modify doses and regimens designed to eliminate or avoid these drugs should be considered. Use of HMG-CoA reductase inhibitors ('statins') and ACE inhibitors is particularly helpful in controlling hypertension and hyperlipidaemia in the elderly because these agents confer protection against future adverse cardiovascular events. Bisphosphonates are also advantageous in controlling the progression of osteoporosis and possible increased risk of bone fractures. Future trials in the elderly should focus on such endpoints as PTDM, post-transplant neoplasia, cardiovascular events and bone fracture events in order to identify the safest regimens that provide the optimal control of rejection while limiting the morbidity from these secondary events.
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PMID:Post-transplant diabetes mellitus: risk reduction strategies in the elderly. 1706 82

The 'Stichting Werkgroep Antibioticabeleid' (SWAB; Dutch Working Party on Antibiotic Policy) has developed an evidence-based guideline for the empirical antimicrobial treatment of complicated urinary tract infections (UTIs) in hospitalised adult patients. The choice of treatment is based on recent Dutch data on the resistance ofuropathogens to the most frequently used antibiotics. The first choice for empirical antibiotic treatment in a patient with a complicated UTI is a 2nd or 3rd generation cephalosporin or the combination of amoxicillin and gentamicin. Amoxicillin-clavulanic-acid intravenously is the second empirical choice. The treatment duration must be at least 10 days. The treatment must be adjusted after the results of the urine culture become known and made more specific if possible. Oral treatment can be given if the patient's clinical situation allows it. There are separate recommendations for the treatment ofUTIs in the following patient categories: men, pregnant women, patients with a urinary catheter, patients with diabetes mellitus and patients with renal diseases, congenital polycystic kidney disease or pyocystis.
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PMID:[Optimisation of the antibiotic policy in the Netherlands. X. The SWAB guideline for antimicrobial treatment of complicated urinary tract infections]. 1710 Jan 28

Post-transplant erythrocytosis (PTE) is defined as an increase in hematocrit greater than 51%. This phenomenon affects 5 to 17% of renal transplant patients within two years of transplantation. Its etiology is not clearly known, but several factors have been implicated in its pathogenesis. We report on a 50-year-old male, known to have autosomal dominant polycystic kidney disease, diabetes mellitus and hypertension for 20 years, who underwent a living unrelated donor transplantation. Three years following renal transplan-tation, he was noted to have high hemogloblin and hematocrit (18.3 gm%, 53.8%). This erythrocytosis persisted for nine months during which period he underwent multiple phlebotomies before undergoing spontaneous remission. He did not develop any compli-cations of erythrocytosis. Our patient had multiple factors to account for occurrence of PTE: diabetes mellitus, hypertension, mild allograft dysfunction, polycystic kidney disease and cyclosporin therapy. Our case suggests that multiple factors may be operative in a given patient leading to the development of PTE.
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PMID:Post-transplant erythrocytosis: a disease with multifactorial etiology. 1729 38

Mammalian TRP channel proteins form six-transmembrane cation-permeable channels that may be grouped into six subfamilies on the basis of amino acid sequence homology (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Recent studies of TRP channels indicate that they are involved in numerous fundamental cell functions and are considered to play an important role in the pathophysiology of many diseases. Many TRPs are expressed in kidney along different parts of the nephron and growing evidence suggest that these channels are involved in hereditary, as well as acquired kidney disorders. TRPC6, TRPM6, and TRPP2 have been implicated in hereditary focal segmental glomerulosclerosis (FSGS), hypomagnesemia with secondary hypocalcemia (HSH), and polycystic kidney disease (PKD), respectively. In addition, the highly Ca(2+)-selective channel, TRPV5, contributes to several acquired mineral (dys)regulation, such as diabetes mellitus (DM), acid-base disorders, diuretics, immunosuppressant agents, and vitamin D analogues-associated Ca(2+) imbalance whereas TRPV4 may function as an osmoreceptor in kidney and participate in the regulation of sodium and water balance. This review presents an overview of the current knowledge concerning the distribution of TRP channels in kidney and their possible roles in renal physiology and kidney diseases.
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PMID:TRP channels in kidney disease. 1734 47

In the current decade, 2001 to 2010, the number of patients undergoing renal replacement therapy worldwide will increase from 1.5 to 2.5 mln. This requires considerable financial input, thus limiting treatment access in 90% to the inhabitants of North America, Europe and Japan, that constitutes less than 20% of the world's population. It is presumed that about 1 mln people die every year, a death rate which could be avoidable, were the proper funds for renal replacement therapy obtained. Over the last five years, Poland has joined the elite group of countries fully covering the needs in this respect. Modern nephrology gradually focuses on reducing the incidence of end-stage renal disease, through more effective treatment of diabetes, glomerulonephritis and polycystic kidney disease. Reducing morbidity and mortality rates in dialysis treatment and post-kidney transplant follow-up is another key issue. This overview discusses the modern options and perspectives to face those challenges.
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PMID:[Modern nephrology--new methods, new treatments and still numerous difficult challenges]. 1771 51

Collectrin is a type I membrane protein and shares significant homology with C-terminal domain of angiotensin-converting enzyme-2 (ACE2). However, collectrin lacks catalytic domain and it suggests the presence of uncharacterized physiological functions of collectrin. Collectrin is transcriptionally regulated by hepatocyte nuclear factor-alpha and -beta and is highly expressed on renal proximal tubules and collecting ducts as well as pancreatic beta-cells. Recent in vitro and in vivo studies demonstrated interesting physiological roles of collectrin related to insulin secretion, formation of primary cilia, renal cyst formation and amino acid transport. The common underlying molecular mechanism may be suggested by the evidence that collectrin binds to SNARE complex by interacting with snapin. Collectrin is involved in the process of vesicle transport and membrane fusion and thus it delivers insulin for exocytosis or various membrane proteins to apical plasmalemma and primary cilia. Collectrin may be the new therapeutic target for various pathological processes such as diabetes, polycystic kidney disease, hypertension and aminoaciduria.
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PMID:Collectrin, a homologue of ACE2, its transcriptional control and functional perspectives. 1782 89

TCF2, the gene encoding for hepatocyte nuclear factor 1beta, is involved in early renal development. Mutations in TCF2 lead to heterogeneous renal phenotypes. Antenatal ultrasonography may show unilateral/bilateral hyperechogenic or enlarged cystic kidneys. In children or adults, cystic renal hypoplasia/dysplasia is a common feature, occasionally associated with maturity-onset diabetes of the young type 5 and genital tract abnormalities. We report an unusual presentation characterized by massively enlarged polycystic kidneys mimicking autosomal dominant polycystic kidney disease in monozygotic twins. Bilateral enlarged cystic kidneys were discovered in week 13 of a gemellic pregnancy. Postnatally, kidney size increased in both children, reaching 16 cm at 20 years. Nephromegaly was associated with bilateral cysts and a slowly decreasing glomerular filtration rate (40 mL/min/1.73 m(2) at 20 years). There was neither pancreatic nor genital malformation. Non-type 1 diabetes mellitus was diagnosed incidentally in both twins at 20 years. Knowledge of early-onset diabetes (at age 19 years) in their father prompted us to search for the TCF2 mutation. Genetic analysis showed complete TCF2 heterozygous whole-gene deletion in both twins. Genetic testing could not be performed in the father. Bilateral massively enlarged polycystic kidneys mimicking autosomal dominant polycystic kidney disease in young adults may be related to TCF2 mutation. Although uncommon, this new phenotype enlarges the clinical spectrum of kidney involvement associated with TCF2 mutation. In this case, maturity-onset diabetes of the young-type diabetes paved the way to accurate diagnosis.
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PMID:Massively enlarged polycystic kidneys in monozygotic twins with TCF2/HNF-1beta (hepatocyte nuclear factor-1beta) heterozygous whole-gene deletion. 1803 3

Post-transplant diabetes mellitus (PTDM) is a type 2 diabetes that has been described in a high percentage of transplanted patients. This complication has a peak incidence in the first few months after transplantation and increases progressively with the length of observation. PTDM is an independent factor for increased cardiovascular risk among solid-organ transplant recipients. New-onset diabetes after transplantation causes a reduction of patient and graft survival. Factors predisposing to the development of diabetes are Afro-American or Hispanic ethnicity, age above 40 years at transplantation, a cadaver kidney donor, HLA, a positive family history, impaired glucose metabolism, HCV positivity, obesity, autosomal polycystic kidney disease, and immunosuppressive therapy. Immunosuppressive therapy is a strong factor for the development of PTDM with a relative risk of 1.557, 3.060 and 5.568 for rapamycin-, cyclosporine- and tacrolimus-based immunosuppression, respectively. The attention of the transplant physician should focus mainly on preventive measures and intervention directed at modifiable risk factors. Of great importance among the latter is an adequate choice of immunosuppressive regimen, particularly in high-risk patients.
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PMID:[Post-transplant diabetes mellitus: diagnosis and treatment]. 1827 58

MAP kinases transduce signals that are involved in a multitude of cellular pathways and functions in response to a variety of ligands and cell stimuli. Aberrant or inappropriate functions of MAPKs have now been identified in diseases ranging from cancer to inflammatory disease to obesity and diabetes. In many cell types, the MAPKs ERK1/2 are linked to cell proliferation. ERK1/2 are thought to play a role in some cancers, because mutations in Ras and B-Raf, which can activate the ERK1/2 cascade, are found in many human tumors. Abnormal ERK1/2 signaling has also been found in polycystic kidney disease, and serious developmental disorders such as cardio-facio-cutaneous syndrome arise from mutations in components of the ERK1/2 cascade. ERK1/2 are essential in well-differentiated cells and have been linked to long-term potentiation in neurons and in maintenance of epithelial polarity. Additionally, ERK1/2 are important for insulin gene transcription in pancreatic beta cells, which produce insulin in response to increases in circulating glucose to permit efficient glucose utilization and storage in the organism. Nutrients and hormones that induce or repress insulin secretion activate and/or inhibit ERK1/2 in a manner that reflects the secretory demand on beta cells. Disturbances in this and other regulatory pathways may result in the contribution of ERK1/2 to the etiology of certain human disorders.
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PMID:The roles of MAPKs in disease. 1834 14

Patient survival is a key index of the overall adequacy of treatment in most chronic diseases. Analyses of survival of patients undergoing haemodialysis is very important, as it may offer clues and ideas for prolonging survival of patients with end-stage renal disease (ESRD). The aims of this study were to describe the characteristics of the patients on maintenance haemodialysis therapy over a period of 20 years, to determine the survival rate of these patients according to ages at the onset of haemodialysis, the primary renal diseases, and the cause of death, and to determine the survival rate at five, ten, fifteen and twenty years of haemodialysis treatment at our centre. The charts of 518 unselected patients, 282 male and 236 female, treated with maintenance haemodialysis therapy in a period of 20 years (1985-2005) were reviewed. At the time of evaluation, 164 patients were currently being treated, and 354 patients overall had been diseased. Statistical analysis was performed to evaluate the relationship between survival and patient characteristics such as age, gender, primary renal disease, and age at dialysis onset. Actual survival rates were determined by the Kaplan-Meier method. The survival rate of our patients treated with maintenance haemodialysis was 60% at 5 years, 37% at 10 years, 25% at 15 years and 9% at 20 years. Female patient survival was superior to male. Patients aged under 40 at the start of dialysis had a better survival probability compared to older patients. Patients with diabetes mellitus and nephroangiosclerosis, had a lower survival rate compared to patients with glomerulonephritis and with adult dominant polycystic kidney disease. Cardiac death was the most common cause of death in patients involved in the study. About 52% of the patients died from cardiovascular disease. Death is the most severe consequence of inadequate dialysis and can be used as an index of the adequacy of the dialysis therapy. Treatment factors that may improve outcomes include an early start of dialysis therapy, a high dose of dialysis (Kt/V over 1.2), correction of anemia, adequate protein and caloric intake, control of calcium and phosphate metabolism, and the use of biocompatible dialyzers.
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PMID:Survival of patients on maintenance haemodialysis over a twenty-year period. 1835 82


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