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)

In various renal diseases, including diabetic nephropathy, detection of podocytes in the urine indicates severe injury to podocytes in the glomeruli. Pioglitazone is a newly developed antidiabetic agent that attenuates insulin resistance. The aim of the present study was to determine whether pioglitazone affects urinary albumin excretion (UAE) or the number of urinary podocytes or both in type 2 diabetes patients with microalbuminuria. Twenty-eight patients with normotensive type 2 diabetes and microalbuminuria (18 men and 10 women; mean age, 52.5 years) and 30 age-matched normotensive controls (20 men and 10 women; mean age, 51.5 years) were included in the study. Urinary podocytes were detected by immunofluorescence with a monoclonal antibody against podocalyxin. Patients were randomly assigned to 2 groups: a pioglitazone-treatment group (30 mg/day, n = 14) and a placebo group (n = 14). Treatment was continued for 6 months. Podocytes were absent in the urine of healthy controls, but detected in 17 of 28 diabetic patients (60.7%). UAE was reduced from 96.7 +/- 50.5 microg/min to 39.7 +/- 22.9 microg/min (P <.01) in the pioglitazone-treatment group, and the number of urinary podocytes was reduced from 0.9 +/- 1.0 cells/mL to 0.1 +/- 0.2 cells/mL (P <.001). Neither UAE nor the number of urinary podocytes was affected in the placebo group. These data indicate that pioglitazone is effective for reducing UAE and podocyte injury in early-stage diabetic nephropathy.
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PMID:Pioglitazone reduces urinary podocyte excretion in type 2 diabetes patients with microalbuminuria. 1158 92

Pioglitazone (Actos-Takeda) and rosiglitazone (Avandia-GlaxoSmithKline) belong to a new class of oral antidiabetic medicines (the glitazones or thiazolidinediones). Both are licensed in the UK for "oral combination treatment of type 2 diabetes mellitus in [narrowly defined groups of] patients with insufficient glycaemic control despite maximal tolerated dose of oral monotherapy with either metformin or a sulphonylurea". They are not licensed for use as monotherapy, in combination with insulin, or as part of triple therapy with metformin or a sulphonylurea. What can pioglitazone and rosiglitazone offer in the management of patients with type 2 diabetes?
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PMID:Pioglitazone and rosiglitazone for diabetes. 1158 2

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.
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PMID:[Evaluation of a thiazolidinedione compound as a new antidiabetic drug]. 1171 10

Pioglitazone, a new thiazolidinedione agent,has been shown to increase insulin sensitivity in clinical trials. Pioglitazone HCI was rapidly absorbed within one hour, achieved peak concentrations at 2-3 h, and was eliminated from serum at 24-36 h. Pioglitazone demonstrated dose-dependent pharmacokinetics. Food did not significantly affect the pharmacokinetic profile of pioglitazone. The pharmacokinetic profile of sulfonylurea agents was not significantly altered by concurrent administration with pioglitazone. Pharmacokinetic studies in healthy volunteers and in patients with type 2 diabetes indicated that pioglitazone may be administered once daily. In patients with type 2 diabetes, pioglitazone as monotherapy and in combination with sulfonylureas or an alpha-glucosidase inhibitor significantly reduced fasting blood glucose, HbA1c, triglycerides, and free fatty acids, and significantly increased HDL-cholesterol. Pioglitazone demonstrated either minor increases or decreases in cholesterol with no adverse effect on LDL-cholesterol. No patients experienced jaundice or ALT elevations > or = three times the upper limit of normal. Adverse events were mild and transient; all subjects returned to their baseline health status or laboratory tests upon withdrawal from, or completion of, the studies. Based upon these preliminary studies, full-scale clinical investigations were conducted in Japan, the United States, and Europe. As a result, in many countries pioglitazone has gained approval for use in patients with type 2 diabetes.
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PMID:Pioglitazone: a review of Japanese clinical studies. 1190 Mar 11

The two major metabolic perturbations resulting in hyperglycaemia in type 2 diabetes are insulin resistance and insulin deficiency. Insulin resistance occurs in peripheral organs (muscle and fat), leading to decreased glucose uptake and utilisation, and in liver, leading to increased hepatic glucose production. Thiazolidinediones, pharmacological ligands for PPAR gamma, can modulate the expression of genes influencing carbohydrate and lipid metabolism. Pioglitazone, a recently introduced thiazolidinedione, improves glycaemic control and lipid profiles in people with type 2 diabetes. Some of the possible mechanisms of improving glycaemic control include (a) increase in GLUT-1 and GLUT-4, (b) enhancement of insulin signalling, (c) decrease in tumour necrosis factor-alpha action, (d) reduction in plasma free fatty acid and (e) decrease in PEPCK. Together these can increase glucose uptake and utilisation in the peripheral organs and decrease gluconeogenesis in the liver. Possible mechanisms resulting in more desirable lipid profiles include an increase in phosphodiesterase-3B resulting in reduced intra-cellular lipolysis in adipocytes and an increase in lipoprotein lipase resulting in enhanced clearance of triglyceride-rich lipoproteins(TRLs). Pioglitazone, used as monotherapy or in combination with sulphonylurea, biguanide or insulin, improves glycaemic control, lowers serum triglycerides and raises high density lipoprotein (HDL)-cholesterol. It enhances hepatic and peripheral insulin sensitivity. In clinical trials, there has been no evidence of hepatotoxicity or increased incidence of elevated serum ALT in subjects taking pioglitazone compared with placebo.
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PMID:Current treatment of insulin resistance in type 2 diabetes mellitus. 1196 33

1. The effects of combined treatment with pioglitazone.HCl and metformin on diabetes and obesity were investigated in Wistar fatty rats, which are hyperglycaemic and hypertriglyceridaemic and have higher plasma levels of total ketone bodies than lean rats. 2. Plasma glucose was significantly decreased when pioglitazone.HCl or metformin was administered alone and combined treatment accentuated this decrease. The administration of pioglitazone.HCl, but not metformin, also decreased plasma levels of triglyceride and total ketone bodies. 3. The glycogen content of skeletal muscle was not increased by pioglitazone.HCl or metformin alone, but was increased by combined treatment (P=0.003, ANOVA). 4. Pioglitazone.HCl produced increased food intake and bodyweight in hyperphagic Wistar fatty rats; however, concurrent administration of metformin significantly ameliorated these pioglitazone.HCl-induced increases. 5. These results indicate that combined treatment with pioglitazone.HCl and metformin induces a marked hypoglycaemic effect accompanied by a reduction in plasma levels of total ketone bodies and prevention of excessive bodyweight gain in Wistar fatty rats. These favourable effects suggest that the combination would be beneficial in treating patients with type 2 diabetes.
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PMID:Effects of combined pioglitazone and metformin on diabetes and obesity in Wistar fatty rats. 1198 34

Type 2 diabetes mellitus remains a significant burden to the Canadian healthcare system. Over 2 million Canadians have diabetes, with 85 to 90% having type 2 diabetes. Insulin resistance is a major pathophysiological mechanism in the development of type 2 diabetes. Insulin resistance can be defined as an impaired biological response to the metabolic and/or mitogenic effects of either exogenous or endogenous insulin. As a consequence of insulin resistance, type 2 diabetes is characterised by decreased glucose transport and utilisation at the level of muscle and adipose tissue and increased glucose production by the liver. The traditional oral agents used to treat type 2 diabetes clearly do not address the underlying insulin resistance responsible for the development of diabetes. Thiazolidinediones (TZDs) represent a relatively new class of oral hypoglycaemic medications that have been shown to reverse some of the metabolic processes believed responsible for the development of insulin resistance and, ultimately, type 2 diabetes. Research has demonstrated that TZDs activate peroxisome proliferator activator receptors, in particular, the gamma-receptor isoform. Pioglitazone is a TZD that reduces plasma glucose levels by increasing peripheral glucose utilisation and decreasing hepatic glucose production. Clinical studies with pioglitazone have demonstrated the following: absolute reductions in glycosylated haemoglobin of 0.8 to 2.6%; reductions in fasting plasma glucose of 1.7 to 4.4 mmol/L; an increase in high density lipoprotein cholesterol of 8.7 to 12.6%; and a decrease in triglycerides of 18.2 to 26.0%, with no significant effects on low density lipoprotein or total cholesterol.
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PMID:New solutions for type 2 diabetes mellitus: the role of pioglitazone. 1203 79

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.
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PMID:Thiazolidinediones and type 2 diabetes: new drugs for an old disease. 1204 35

The glycaemic and lipid effects of treatment with pioglitazone in combination with a stable insulin regimen were evaluated in patients with type 2 diabetes. Patients (n=566) receiving stable insulin regimens for > or = 30 days yet who had HbA1c > or = 8.0% and C-peptide > 0.7 microg/l were randomised to receive once-daily 15 mg pioglitazone, 30 mg pioglitazone, or placebo in a 16-week multicentre, double-blind, placebo-controlled trial. Per study protocol, the insulin dose was to remain unchanged, but could be decreased in response to hypoglycaemia. At the end of double-blind treatment, patients receiving pioglitazone (15 mg or 30 mg) showed statistically significant mean decreases relative to baseline HbA1c (-1.0 and -1.3, respectively; p<0.0001) and fasting plasma glucose (FPG) (-34.5 mg/dl [-1.92 mmol/l] and -48.0 mg/dl [-2.67 mmol/l], respectively; p<0.0001); these differences compared with placebo were also significant (p<0.0001). Pioglitazone (15 or 30 mg) yielded significant increases in HDL-C levels (mean increases ranging from +7.1% to + 9.3%) compared with baseline or placebo (p<0.01). The 30 mg dose also significantly reduced mean triglyceride levels (-23.7%) compared with placebo (p=0.0218). No consistent changes in TC or LDL-C levels were observed. The incidence of adverse events was similar in all treatment groups, although the incidences of weight increase, hypoglycaemia and oedema were higher among patients receiving insulin plus pioglitazone. There was no evidence of hepatotoxicity or drug-induced elevations of serum ALT > or = 3 x ULN. Pioglitazone, when added to stable insulin regimens, significantly improved HbA1c and FPG in type 2 diabetes. Pioglitazone treatment also provided significant benefit with respect to plasma HDL-C and triglyceride levels. Whether these lipid changes have an impact on overall diabetic complications remains to be determined.
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PMID:Efficacy and safety of pioglitazone in type 2 diabetes: a randomised, placebo-controlled study in patients receiving stable insulin therapy. 1207 6

The objective of this study was to determine whether improvements in the lipid profile observed in controlled clinical trials with pioglitazone are seen in the clinical practice setting, and to ascertain the influence of concurrent statin treatment. Charts of 100 consecutive patients with type 2 diabetes (mean age 56.8 years) treated with pioglitazone (45 mg/day) for 2-4 months were retrospectively analyzed for changes in serum lipids, glycemic parameters, and body weight. Subanalyses were performed on the relationship of lipid changes to baseline lipid values and to concurrent statin therapy. Pioglitazone was associated with statistically significant (p < 0.001) changes from baseline in HbA(1C) (mean decrease 1.09%), body weight (mean increase 1.76 kg), HDL cholesterol (HDL-C) levels (mean increase 15.6%), and triglycerides (mean decrease 9.9%). There was an increase (+ 1.09%) in mean individual LDL-C levels from baseline values, but this change was not statistically significant. The greatest absolute and percentage improvements in HDL-C and triglycerides were observed in patients who had the greatest lipid abnormalities at baseline: in patients with baseline HDL-C < 35 mg/dL, mean individual HDL-C values increased by 31% (p < 0.001); in those with baseline triglycerides >399 mg/dL, triglyceride levels decreased by 46% (p < 0.001); and in patients with baseline LDL-C > 129 mg/dL, mean individual LDL-C values decreased by 10.6% (p < 0.001). Subgroup analysis showed similar beneficial changes in HDL-C and triglycerides in patients who were not receiving concurrent statin therapy (n = 48) as in those who were receiving statins (n = 49). This observational study demonstrated that significant improvements in HDL-C and triglyceride levels can be achieved with pioglitazone in the clinical practice setting. The greatest improvements occurred in patients with the worst baseline lipid levels, and benefits were seen regardless of whether patients were receiving concurrent statin therapy.
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PMID:Lipid response to pioglitazone in diabetic patients: clinical observations from a retrospective chart review. 1207 18


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