Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A thiazolidinedione compound, pioglitazone(Actos) has been used for type 2 diabetes. It ameliorates the insulin resistance of type 2 diabetes and improves hyperglycemia, resulting in the decrease of HbA1c. Pioglitazone activates the nuclear peroxisome proliferator activated receptor-gamma(PPAR gamma) which leads to increased transcription of various proteins. These proteins enhance insulin action. Another thiazolidinedione(troglitazone, Noscal) has been prohibited for description due to its idiosyncratic hepatic toxicity. Actos has never been reported to induce hepatotoxicity but has shown side effects of edema, dysfunction of the liver, and anemia, etc. Nevertheless we would like to recommend the use of Actos for type 2 diabetes mellitus in monotherapy or combination therapy with other antidiabetic drugs because of its benefits.
 ...
PMID:[Evaluation of a thiazolidinedione compound as a new antidiabetic drug]. 1171 10

Thiazolidinediones are a new class of drugs for the treatment of type 2 diabetes, and act by improving insulin sensitivity in adipose tissue, liver and skeletal muscle. Rosiglitazone and pioglitazone are registered for use in monotherapy, and in combination with sulfonylureas and metformin. Pioglitazone is also licensed for use in combination with insulin. There is level II evidence that in patients with inadequate glycaemic control both drugs reduce the level of HbA1c and fasting plasma glucose (FPG) when used as monotherapy and in combination with sulfonylurea or metformin or insulin; and both drugs increase levels of HDL and LDL and lower free fatty acid levels, but only pioglitazone significantly lowers triglyceride levels. Both drugs lower fasting insulin and C-peptide levels. In monotherapy, they may be slightly less potent at reducing the level of HbA1c than sulfonylureas or metformin. The maximal effect of these agents may not be seen for 6-14 weeks after commencement. Both drugs are well tolerated but liver function must be checked at baseline every second month for the first year, and periodically thereafter. The drugs are currently contraindicated in patients with moderate to severe liver dysfunction and alanine aminotransferase levels more than 2.5 times normal, New York Heart Association III-IV cardiac status, pregnancy, lactation and in children. The main side effects include weight gain, oedema, and mild dilutional anaemia.
 ...
PMID:Thiazolidinediones and type 2 diabetes: new drugs for an old disease. 1204 35

Diabetes represents a conglomerate of diseases with chronic hyperglycaemia as hallmark. The present review discusses those diabetic cases that associate with variants in genes that affect the magnitude of the glycolytic flux and oxidative disposal of glucose by mitochondria in pancreatic beta-cells. These genetic variants result in an attenuated secretion of insulin in response to glucose stimulation. The diabetic states that associate with these genetic variants are MODY 2, thiamine responsive anaemia syndrome (TRAS) and mitochondrial diabetes. These disease states highlight the critical contribution of the carbohydrate flux through glycolysis and mitochondria and its coupling to ATP production in determining insulin secretion.
 ...
PMID:Mitochondrial diabetes, diabetes and the thiamine-responsive megaloblastic anaemia syndrome and MODY-2. Diseases with common pathophysiology? 1243 22

(1) Treatment of type 2 (non insulin-dependent) diabetes is based on lifestyle measures and management of cardiovascular risk. (2) The reference first-line drug therapy for type 2 diabetes, when drug therapy is needed, is single-agent treatment with metformin (a biguanide) for overweight patients, or with glibenclamide (a glucose-lowering sulphonylurea) for other patients. (3) If monotherapy fails to control blood glucose levels adequately, most clinical guidelines then recommend a combination of metformin with a glucose-lowering sulphonylurea, although the few available comparative clinical data raise the possibility of excess mortality with this treatment. (4) Rosiglitazone and pioglitazone (glitazones that reduce insulin resistance) have been authorized in the European Union for combination with a glucose-lowering sulphonylurea (for patients in whom metformin is ineffective or poorly tolerated) or with metformin (for obese patients). (5) None of the available trials of rosiglitazone and pioglitazone include data on mortality or morbidity. (6) There are fewer data on pioglitazone than on rosiglitazone. (7) According to short-term comparative trials, rosiglitazone and pioglitazone are more effective than placebo on blood glucose levels. Combinations of rosiglitazone or pioglitazone with metformin or with glucose-lowering sulphonylureas have not been compared with the metformin + glucose-lowering sulphonylurea combination or with insulin. (8) Rosiglitazone and pioglitazone frequently cause weight gain. (9) Pioglitazone has a slightly favourable effect on lipid profiles, unlike rosiglitazone, which increases LDL-cholesterol levels. (10) The main side effect of rosiglitazone and pioglitazone is sodium and water retention, which can provoke oedema, anaemia (by haemodilution), and even heart failure. Rosiglitazone and pioglitazone are also hepatotoxic. (11) Combining rosiglitazone with insulin is contraindicated, owing to the increased risk of heart failure. The same applies to pioglitazone. (12) In practice, neither rosiglitazone nor pioglitazone has a place in the management of type 2 diabetes, except in the context of strictly controlled long-term comparative clinical trials.
 ...
PMID:Rosiglitazone and pioglitazone: new preparations. Two new oral antidiabetics both poorly assessed. 1246 95

Combined antihypertensive therapy plays a crucial role in achieving targeted blood pressure reductions and renoprotection. We therefore compared the antihypertensive and antiproteinuric effects of combined therapy with either a calcium channel blocker (CCB) plus an angiotensin II receptor blocker (ARB) or an angiotensin converting enzyme inhibitor (ACE-I) plus an ARB in patients with type 2 diabetes mellitus complicated by overt nephropathy and mild to moderate hypertension. After a 12-week dietary control period, diabetic patients with mildly to moderately impaired renal function were randomly assigned to either a CCB (amlodipine 5 mg once daily) or an ACE-I (temocapril 2 mg once daily) for 12 weeks (monotherapy period). Both groups then received add-on therapy with an ARB (candesartan 4 mg once daily) for an additional 12 weeks. During the monotherapy period, blood pressure was decreased equally well in both groups. Daily urinary protein excretion remained unchanged in the CCB-treated group (control period, 4.0 +/- 1.8 g/day vs. CCB period, 4.1 +/- 1.9 g/day; ns; n = 8), but decreased in the ACE-I-treated group (control period, 4.3 +/- 1.8 g/day vs. ACE-I period, 3.5 +/- 1.7 g/day; p < 0.05; n = 9). After the combined therapy period, blood pressure was decreased to the same degree in both groups. Although ARB plus CCB significantly reduced urinary protein excretion (to 3.5 +/- 1.5 g/day; p < 0.05 vs. control period; n = 8), a more profound reduction was achieved with ARB plus ACE-I (to 2.6 +/- 1.3 g/day; p < 0.01 vs. control period; n = 9). Monotherapy with the ACE-I increased the serum potassium concentration, and this elevation was sustained after addition of the ARB. In contrast, the serum potassium concentration was not influenced by monotherapy with the CCB, but was significantly increased after addition of the ARB. A decreased hematocrit was observed in the ARB plus ACE-I group. The present study suggests that combined antihypertensive therapy with either a CCB plus an ARB or an ACE-I plus an ARB exerts an antiproteinuric effect in patients with type 2 diabetic nephropathy with mildly impaired renal function. Although the latter combination had a more profound effect, it was associated with an increased serum potassium concentration and worsening of renal anemia. Thus, the combination of a CCB and an ARB should be the first line antihypertensive therapy in those with overt diabetic nephropathy. The long-term efficacy of these combined antihypertensive therapies will need to be further addressed in a future study.
 ...
PMID:Antiproteinuric effects of combined antihypertensive therapies in patients with overt type 2 diabetic nephropathy. 1248 8

Tagatose, a low-calorie, full-bulk natural sugar, has just attained GRAS (Generally Recognized As Safe) status under U.S. Food and Drug Administration (FDA) regulations, thereby permitting its use as a sweetener in foods and beverages. This paper presents all current aspects of tagatose with respect to demonstrated food and beverage applications and the potential health and medical benefits of this unique substance. Summarized studies are referenced to detailed peer-reviewed papers. The safety studies followed the recommendations in the FDA "Red Book." Results were submitted to an Expert Panel for determination of GRAS status under FDA regulation. Small phase 2 clinical trials showed tagatose to be effective in treating type 2 diabetes. The results, buttressed by the references cited, support the efficacy of the various applications disclosed for tagatose. Tagatose has been found to be safe and efficacious for use as a low-calorie, full-bulk sweetener in a wide variety of foods, beverages, health foods, and dietary supplements. It fills broad, heretofore unmet needs for a low-calorie sweetener in products in which the bulk of sugar is important, such as chocolates, chewing gum, cakes, ice cream, and frosted cereals. Its synergism with high-intensity sweeteners also makes it useful in sodas. Various health and medical benefits are indicated, including the treatment of type 2 diabetes, hyperglycemia, anemia, and hemophilia and the improvement of fetal development.
 ...
PMID:Tagatose, the new GRAS sweetener and health product. 1251 Nov 10

In Japan, mass screening tests on newborns for Cretinism have been performed since 1984, Cretinism is a very rare condition. We report the clinical course and complications of longitudinal thyroid hormone replacement therapy (liothyronine sodium: T3) of two women with Cretinism and ectopic thyroid gland for the past 33 years until 2001. They were born in April 1951 (Case 1) and in January 1952 (Case 2). On admission in June 1968, they were 17 and 16 years old. They had short stature, mental retardation, macroglossia, saddle nose, retardation of bone maturation, edematous face, coexistence of permanent teeth and deciduous teeth, abdominal distention, hypotonia, anemia, hypophosphatemia and hypercholesterolemia. After admission, Case 2 had an appendectomy for appendicitis. She was found to have a right ovarian cyst, but was not operated upon. Later, the right ovarian cyst disappeared during thyroid hormone replacement therapy. The complication in this case was NIDDM. Over secretion of thyroid hormone in for example, hyperthyroidism sometimes induces NIDDM. On their admission, a levothyroxine sodium (T4: Thyradin S) was unavailable in Japan, so we had no choice but to treat them with liothyronine sodium for thyroid hormone replacement therapy. We suspect that liothyronine sodium replacement therapy probably induced NIDDM. They experienced improved bone maturation, anemia, hypophsphatemia and hypercholesterolemia, but their intellectual and mental disabilities were not improved.
 ...
PMID:The longitudinal course of two cases with cretinism diagnosed after adolescence. 1280 80

The TRansplant European Survey on Anemia Management (TRESAM) documented the prevalence and management of anemia in kidney transplant recipients. Data from 72 transplant centers in 16 countries were screened, involving 4263 patients who had received transplants 6 months, 1, 3 or 5 years earlier. The mean age of transplant recipients was 45.5 years at transplantation. The most common etiology was chronic glomerulonephritis. The most common comorbidities were coronary artery disease, hepatitis B/C, and type 2 diabetes. The mean hemoglobin levels before transplantation were significantly higher in the more recently transplanted recipients. At enrollment, 38.6% of patients were found to be anemic. Of the 8.5% of patients who were considered severely anemic, only 17.8% were treated with epoetin. There was a strong association between hemoglobin and graft function; of the 904 patients with serum creatinine > 2 mg/dL, 60.1% were anemic, vs. 29.0% of those with serum creatinine <or= 2 mg/dL (p < 0.01). Therapy with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, mycophenolate mofetil (MMF) or azathioprine was also associated with a higher likelihood of anemia. The prevalence of anemia in the transplant recipients was remarkably high and appeared to be associated with impaired renal function and with ACE inhibitors and angiotensin II receptor antagonist use. Further studies should be carried out to interpret whether appropriate management of anemia after kidney transplantation may improve long-term outcome.
 ...
PMID:Prevalence and management of anemia in renal transplant recipients: a European survey. 1281 67

Ragaglitazar is a novel dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist intended to restore insulin sensitivity and correct diabetic dyslipidemia. These studies assessed single-dose pharmacokinetics and tolerability of ragaglitazar in healthy subjects, as well as multiple-dose pharmacokinetics, pharmacodynamics, and tolerability of ragaglitazar in healthy subjects and in patients with type 2 diabetes. Healthy subjects received a single oral dose (1-120 mg), and healthy subjects and type 2 diabetic patients received a loading dose and thereafter once-daily doses (0.5-16 mg) of ragaglitazar for 6 and 20 days, respectively. Ragaglitazar was rapidly absorbed (tmax: 1.5-1.7 h), with mean AUC0-24 h and Cmax proportional to dose after single and multiple dosing; t1/2 was 80 hours following a single dose and 104 hours in healthy subjects and 122 hours in patients after multiple dosing. Administration of 4 mg ragaglitazar to patients (n = 4) for 21 days resulted in mean decreases from baseline in fasting levels of plasma glucose (18%), C-peptide (18%), fructosamine (6%), triglycerides (36%), free fatty acids (49%), total cholesterol (11%), low-density lipoprotein (LDL) cholesterol (21%), and very low-density lipoprotein (VLDL) cholesterol (15%), as well as an increase in high-density lipoprotein (HDL) cholesterol (33%). Overall, ragaglitazar was well tolerated; with multiple dosing, there was a higher incidence of adverse events for patients that, at the highest dose level (16 mg), included peripheral edema and anemia.
 ...
PMID:Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPAR alpha and gamma agonist in healthy subjects and patients with type 2 diabetes. 1455 Nov 79

Anaemia is a common complication of chronic kidney disease (CKD). It is often more severe and occurs at an earlier stage in patients with diabetic nephropathy than in patients with CKD of other causes. This anaemia results from erythropoietin deficiency, which seems to develop in patients with type 1 diabetes even at relatively "normal" levels of serum creatinine. Early erythropoietin- deficiency anaemia occurs in both type 1 and type 2 diabetes, although the prevalence may be higher in type 1 diabetes. However, numerically most patients with erythropoietin-deficiency anaemia have type 2 diabetes as it is a much more common disease. There is also a greater prevalence in women than men but this is not related to iron stores. In addition, erythropoietin-deficiency anaemia is associated with the presence of autonomic neuropathy in patients with diabetes. Small studies have suggested that recombinant human erythropoietin (rhEPO; epoetin) treatment is effective in correcting erythropoietin-deficiency anaemia in patients with diabetes. Additionally, rhEPO therapy improves quality of life and well-being in these patients. Studies also suggest that treatment with rhEPO to restore a normal haematocrit ameliorates orthostatic hypotension. Given the high cardiovascular risk in patients with diabetic nephropathy, it is important to determine in prospective clinical trials whether early anaemia correction can also improve cardiovascular outcomes.
 ...
PMID:Anaemia in diabetes. 1510 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>