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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postprandial lipemia has emerged as an independent risk factor for coronary artery disease. In this systematic review we examined the effect of the medications used for the management of diabetes, obesity and dyslipidemia on postprandial lipemia. It should be mentioned that no standardization exists for a test meal and for the duration of observation postprandially to allow for direct comparisons between the published studies. Type 2 diabetes mellitus and insulin resistance are associated with enhanced postprandial lipemia. Insulin is effective in reducing both fasting and post prandial total triglyceride levels as well as triglycerides contained in the triglyceride-rich lipoprotein sub-fractions. Additionally, the newer rapid-acting insulin analogues seem to be more effective in the reduction of postprandial lipemia than the short-acting human insulins. Acarbose ameliorates postprandial lipemia and reduces the atherogenic chylomicron and very low density lipoprotein remnants. Metformin reduces both fasting and postprandial triglyceridemia, fasting and post-prandial free fatty acids and may increase the concentrations of the high density lipoprotein cholesterol. Sulfonylureas reduce fasting and postprandial triglyceride levels while data on the effect on high density lipoprotein levels are inconsistent. The effect of meglitinides on postprandial lipid metabolism is neutral. Rosiglitazone decreases fasting and postprandial free fatty acids but has no significant effect on fasting and postprandial triglycerides. Pioglitazone has additional beneficial effects on lipid metabolism because it reduces postprandial free fatty acids, fasting and postprandial triglycerides and increases high density lipoprotein cholesterol levels. Limited available data suggest that glucagon-like peptide-1 analogues and vildagliptin reduce postprandial lipemia through reduction of intestinally-derived triglycerides. No data exist on the effect of sitagliptin on postprandial lipemia. Orlistat improves postprandial lipemia by reducing the absorption of the dietary fat; no data exist on the effect of sibutramine and rimonabant on the metabolism of lipids in the postprandial state.
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PMID:The effects of medications used for the management of diabetes and obesity on postprandial lipid metabolism. 1899 2

Thiazolidinediones (TZDs) are widely used in the type 2 diabetes mellitus (DMT2) treatment but have also been tested in cardiovascular prevention. DMT2 is associated with a marked increment in cardiovascular risk, and its prevention represents a main target in cardiometabolic protection. Both Troglitazone (Troglitazone in Prevention of Diabetes study) and Rosiglitazone (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication study) significantly reduced new-onset diabetes. A similar topic will be investigated with pioglitazone (Actos Now for Prevention of Diabetes). In the Prospective Pioglitazone Clinical Trial in Macrovascular events the primary end point (all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndromes, endovascular or surgical intervention in the coronary/leg arteries and amputation above ankles) was unaffected, whereas the secondary one (all-cause mortality, nonfatal myocardial infarction and stroke) was reduced by pioglitazone (-16%, p=0.027) compared to placebo in 5,238 patients with DMT2 and macrovascular disease. In contrast, a meta-analysis (Nissen and Wolski, N Engl J Med. 2007;356:2457-2471) reported that rosiglitazone treatment is associated with a significant increase in myocardial infarction risk (p=0.03) and a borderline significant increase in the risk of death from cardiovascular causes (p=0.06). Nevertheless, the possibility that rosiglitazone might affect cardiovascular events should be evaluated by the ongoing trial Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD). Interim findings early from RECORD did not show significant differences between the rosiglitazone and the control group regarding myocardial infarction and death from cardiovascular and any cause. Additional large-scale trials are awaited to clarify the of role TZDs in cardiovascular outcomes.
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PMID:Cardiovascular risk and cardiometabolic protection: role of glitazones. 1903 66

A recent meta-analysis suggested that the use of rosiglitazone increases the risk of myocardial infarction (MI) in patients with type 2 diabetes mellitus. It is unclear whether this is a class effect of thiazolidinediones (TZD). We did a meta-analysis to evaluate cardiovascular outcomes with the use of pioglitazone. Randomized, controlled trials in which pioglitazone was compared with placebo or other hypoglycemic agents were considered for analysis. Studies were included if the data for MI were available. Studies were identified with use of relevant search words in Medline, Pubmed, EMBASE, CINAHL, and Cochrane databases. Data abstraction was done by 2 individual authors using a standardized protocol. The relative risk across all study groups was computed by the Mantel-Haenszel method, and interstudy heterogeneity was assessed by the chi method. All results were computed according to 95% confidence intervals. Five trials (N = 9965) met the inclusion criteria for analysis. The relative risk for MI was 0.86 (0.69-1.07; P = 0.17). The relative risks for stroke and revascularization were 0.79 (0.61-1.02; P = 0.07) and 0.40 (0.13-1.23; P = 0.11), respectively. Pioglitazone does not increase the risk for MI and may decrease the risk for stroke and revascularization.
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PMID:Pioglitazone and the risk of myocardial infarction and other major adverse cardiac events: a meta-analysis of randomized, controlled trials. 1912 32

Pioglitazone, a thiazolidinedione (TZD) commonly used to treat type 2 diabetes, is associated with weight gain. Our study was designed to examine the effectiveness of three lifestyle-treatment programs of varying intensity on prevention of pioglitazone-induced weight gain and to measure the composition of the change in body weight. Thirty-nine adult overweight and obese subjects with type 2 diabetes mellitus were all treated with pioglitazone and prospectively randomized to one of three lifestyle-treatment programs with increasing level of intensity for 24 weeks. Body composition was measured by dual-energy X-ray absorptiometry (DXA), computed tomography, and multifrequency bioimpedance analysis both before and after therapy. Subjects demonstrated a "dose-response" effectiveness to three levels of lifestyle intervention to mitigate pioglitazone-induced weight gain. Mean (s.d.) weight change (kg) for the usual, standard, and intensive lifestyle groups were 4.9 +/- 4.9 (P = 0.005), 1.8 +/- 3.4 (P = 0.02), and -0.2 +/- 4.4 (NS) respectively. Total body fat increased 2.6 +/- 3.4 kg (P = 0.04) for the usual group and decreased for the intensive group -0.4 +/- 3.5 (NS). Change in abdominal subcutaneous and visceral adipose tissue (VAT) did not differ between groups, although ratio of visceral/subcutaneous fat decreased for the standard and intensive groups (NS). Both usual (P < 0.05) and standard care (NS) groups gained total body water. This is the first prospective, randomized study that demonstrates the beneficial effect of participation in a comprehensive lifestyle-weight-management program on lessening of weight gain associated with pioglitazone.
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PMID:Prevention of weight gain in adult patients with type 2 diabetes treated with pioglitazone. 1918 65

Oral anti-diabetic agents have been associated with adverse cardiovascular events in type 2 diabetes (DM2). We investigated the risk of coronary artery disease (CAD), congestive heart failure (CHF), and mortality using multivariable Cox models in a retrospective cohort of 20,450 DM2 patients from our electronic health record (EHR). We observed no differences in CAD risk among the agents. Metformin was associated with a reduced risk of CHF (HR 0.76, 95% CI 0.64-0.91) and mortality (HR 0.54, 95% CI 0.46-0.64) when compared to sulfonylurea. Pioglitazone was also associated with a lower risk of mortality when compared to sulfonylurea (HR 0.59, 95% CI 0.43-0.81). No other significant differences were found between the oral agents. In conclusions, our results did not identify an increased CAD risk with rosiglitazone in clinical practice. However, the results do reinforce a possible increased risk of adverse events in DM2 patients prescribed sulfonylureas.
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PMID:The risk of developing coronary artery disease or congestive heart failure, and overall mortality, in type 2 diabetic patients receiving rosiglitazone, pioglitazone, metformin, or sulfonylureas: a retrospective analysis. 1930 Aug 99

The aim of the study was to compare the long-term effect of 4 antidiabetic treatment protocols on insulin resistance evaluated by euglycemic hyperinsulinemic clamp in type 2 diabetes mellitus patients. Two hundred seventy-one type 2 diabetes mellitus patients with poor glycemic control and who were overweight were enrolled in this study. Patients were randomized and titrated to take pioglitazone, metformin, pioglitazone + metformin, or glimepiride + metformin for 15 months. They underwent a euglycemic hyperinsulinemic clamp at baseline, after 3 months, and after 15 months. Anthropometric and metabolic measurements were assessed at baseline, after 3 months, and after 15 months. There was a decrease in glycated hemoglobin in all groups, but glycated hemoglobin value was lower in the group treated with pioglitazone + metformin compared with the groups treated with metformin alone and with pioglitazone alone. There was a decrease in fasting plasma glucose and postprandial plasma glucose values in all groups, but values obtained with pioglitazone + metformin were lower compared with values in the groups treated with metformin alone and with pioglitazone alone. Fasting plasma insulin and postprandial plasma insulin values were higher in the group treated with glimepiride + metformin compared with the other groups. After 15 months, glucose infusion rate and total glucose requirement values observed in the groups treated with pioglitazone alone and with pioglitazone + metformin were higher compared with the values in the group treated with metformin alone and with glimepiride + metformin; furthermore, values obtained in the group treated with pioglitazone + metformin were higher than the value obtained with pioglitazone alone. Pioglitazone-metformin-based therapeutic control is associated with the most quantitatively relevant improvement in insulin resistance-related parameters, whereas the sulfonylurea-metformin-including protocol has less relevant effects.
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PMID:Direct comparison among oral hypoglycemic agents and their association with insulin resistance evaluated by euglycemic hyperinsulinemic clamp: the 60's study. 1939 76

Pioglitazone has been shown to reduce fasting triglyceride levels. The mechanisms of this effect have not been fully elucidated, but decreased lipolysis may contribute to blunt the hypertriglyceridemic response to a meal. To test this hypothesis, we studied 27 type 2 diabetes mellitus (T2DM) patients and 7 sex-, age-, and body mass index-matched nondiabetic controls. Patients were randomized to pioglitazone (45 mg/day) or placebo for 16 wk. Whole body lipolysis was measured [as the [(2)H(5)]glycerol rate of appearance (R(a))] in the fasting state and for 6 h following a mixed meal. Compared with controls, T2DM had higher postprandial profiles of plasma triglycerides, free fatty acid (FFA), and beta-hydroxybutyrate, and a decreased suppression of glycerol R(a) (P < 0.04) despite higher insulin levels [268 (156) vs. 190 (123) pmol/l, median (interquartile range)]. Following pioglitazone, triglycerides and FFA were reduced (P = 0.05 and P < 0.04, respectively), and glycerol R(a) was more suppressed [-40 (137) vs. +7 (202) mumol/min of placebo, P < 0.05] despite a greater fall in insulin [-85 (176) vs. -20 (58) pmol/l, P = 0.05]. We conclude that, in well-controlled T2DM patients, whole body lipolysis is insulin resistant, and pioglitazone improves the insulin sensitivity of lipolysis.
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PMID:Decreased whole body lipolysis as a mechanism of the lipid-lowering effect of pioglitazone in type 2 diabetic patients. 1941 25

Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 +/- 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A(1c) and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.
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PMID:Long-term pioglitazone therapy improves arterial stiffness in patients with type 2 diabetes mellitus. 1944 10

Pioglitazone, a thiazolidinedione, has established efficacy in improving glycaemic control in patients with type 2 diabetes. Pioglitazone also improves components of the mixed dyslipidaemia profile common in these patients, as typified by raised levels of plasma triglycerides, low levels of HDL cholesterol (HDL-C) and a raised proportion of LDL cholesterol (LDL-C) occurring as the small dense subfraction. In head-to-head trials, pioglitazone has consistently shown superior benefits on LDL-C and HDL-C as well as triglycerides compared with rosiglitazone and sulphonylureas. Pioglitazone used as monotherapy or combination therapy reduces levels of small dense LDL3 particles while raising levels of larger and less atherogenic LDL fractions. In addition, pioglitazone reduces cholesterol load and particle numbers of LDL3. Importantly, the differential effects of pioglitazone on LDL subfractions are complimentary and additive to those of simvastatin. Pioglitazone increases total HDL-C levels by 10-20%, mainly because of an increase in the larger HDL2 subfraction. Pioglitazone also significantly reduces plasma triglyceride levels by 10-25%. In recent studies, pioglitazone significantly reduced carotid and coronary atherosclerosis compared with the sulphonylurea glimepiride. The antidyslipidaemic effects of pioglitazone--in particular, improvements in HDL-C and reduction of small dense LDL3--may have contributed to these effects.
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PMID:The role of pioglitazone in modifying the atherogenic lipoprotein profile. 1951 69

Studies have shown that pioglitazone treatment in patients with type 2 diabetes mellitus can improve parameters of diabetic dyslipidemia. The aim of this study was to examine the effect of pioglitazone on triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels in patients from the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) to determine whether pioglitazone-induced lipid effects were altered by different baseline antihyperglycemia medication or statin use. PROactive was a long-term, randomized, double-blind, cardiovascular outcomes study in patients with type 2 diabetes at high cardiovascular risk who had pioglitazone or placebo added to existing treatment. The present post hoc study analyzed lipid results from patients who received different baseline antihyperglycemia regimens and the presence or absence of baseline statin use. Independent of antihyperglycemia medication and statin use, triglyceride levels decreased in all subgroups treated with pioglitazone (-9.9% to -12.3%), whereas little change was observed in placebo groups. High-density lipoprotein cholesterol increased nearly twice as much with pioglitazone (18.1% to 20.3%) as with placebo (8.1% to 11.8%) across all subgroups. Low-density lipoprotein cholesterol increased moderately with pioglitazone (5.2% to 9.6%) compared with placebo (3.3% to 7.6%) (placebo-adjusted range 1.11% to 4.37%). In conclusion, long-term pioglitazone therapy led to durable improvements in triglyceride and high-density lipoprotein cholesterol levels, irrespective of baseline antihyperglycemia therapy or statin use.
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PMID:Long-term lipid effects of pioglitazone by baseline anti-hyperglycemia medication therapy and statin use from the PROactive experience (PROactive 14). 1957 53


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