Impact of thiazolidenediones on serum lipoprotein levels

Goldberg, Ronald

doi:10.1007/s11883-006-0037-5

Cited by 26 publications

(16 citation statements)

References 53 publications

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“…2 Potential biologic mechanisms for our observations may include the effect of rosiglitazone on lipid profile. 14 We attempted to account for this by adjusting for predialytic serum lipid levels, although our analysis was limited because fasting levels were unavailable. Another potential explanation is the reported risk for CHF associated with rosiglitazone, 8 which evidence suggests may be related to an increase in distal tubular nephron sodium retention 15 ; however, this may be irrelevant in patients with ESRD.…”

Section: Discussionmentioning

confidence: 99%

Rosiglitazone Is Associated with Mortality in Chronic Hemodialysis Patients

Ramirez

Albert

Blayney

et al. 2009

Journal of the American Society of Nephrology

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Recent studies have associated rosiglitazone, a thiazolidinedione drug, with adverse cardiovascular outcomes in the general population with diabetes. Using data from the Dialysis Outcomes and Practice Patterns Study in the United States, we examined cardiovascular hospitalization and mortality associated with prescription of rosiglitazone, compared with other oral hypoglycemic agents, among 2393 long-term hemodialysis patients who were followed for a median of 1.1 yr. We assessed mortality risk using Cox models in patient-level and dialysis facility-level analyses that used the facility proportion of patients on rosiglitazone as the predictor (instrumental variable approach) and adjusted the models for demographics, comorbid conditions, laboratory values, and achieved dialysis dosage. Compared with patients prescribed other oral hypoglycemic agents, patients prescribed rosiglitazone had significantly higher all-cause (hazard ratio [HR] 1.38; 95% confidence interval [CI] 1.05 to 1.82) and cardiovascular (HR 1.59; 95% CI 1.14 to 2.22) mortality, and their adjusted HR for hospitalization with myocardial infarction was 3.5-fold higher (P ϭ 0.02). We did not observe similar associations in a secondary analysis evaluating pioglitazone. By the instrumental variable approach, facilities with more than the median adjusted percentage (6.2%) of patients who had diabetes and were prescribed rosiglitazone had significantly higher all-cause mortality (HR 1.36; 95% CI 1.15 to 1.62) and cardiovascular mortality (HR 1.42; 95% CI 1.07 to 1.88) than facilities with less than the median expected percentage prescribed rosiglitazone. Our practice-based findings suggest significant associations of rosiglitazone use with higher cardiovascular and all-cause mortality among hemodialysis patients with diabetes. 20: 109420: -110120: , 200920: . doi: 10.1681 Thiazolidinedione (TZD) use is increasing in patients with diabetes. For example, its reported use rose from 7.2% in 1998 to 16.2% in 2001 in a population of Medicare patients who were hospitalized for diabetes 1 ; however, concern exists that the TZD rosiglitazone may increase the risk for adverse outcomes. A meta-analysis of 42 randomized, controlled trials comparing rosiglitazone with other oral hypoglycemic agents (OHAs), insulin, or placebo in the general population suggested a significantly higher risk for myocardial infarction (MI) and a borderline increased risk for death from cardiovascular causes. 2 Another meta-analysis of four randomized, controlled clinical trials demonstrated a 42% significantly increased risk for MI and a twofold significantly increased risk for congestive heart failure (CHF). 3 Whether rosiglitazone results in adverse clinical outcomes remains uncertain, given the limitations of meta-analysis design 2 and literature demonstrating rosiglitazone's favorable influence on glycemic control. 4,5 J Am Soc Nephrol

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Section: Discussionmentioning

confidence: 99%

Rosiglitazone Is Associated with Mortality in Chronic Hemodialysis Patients

Ramirez

Albert

Blayney

et al. 2009

Journal of the American Society of Nephrology

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“…Pioglitazone lowers TG by about 15-20%, raises HDL cholesterol by 10-13% and has a negligible effect on LDL cholesterol (either no change or an increase by 5%), whereas rosiglitazone may raise TG by 10-20%, and raise HDL cholesterol by 5-7% and LDL cholesterol by 5-20%. 209 Meta-analyses of clinical trials indicate that metformin treatment results in a decrease in LDL cholesterol and TG, each of about 10 mg/dL, compared with second generation sulphonylureas, with minimal or no effect on HDL cholesterol. 210 While pioglitazone treatment has been associated with reduction in hard clinical end points in high-risk patients with type 2 diabetes, 211,212 considerable uncertainty remains regarding the aggregate CVD effects of the PPARγ agonists, and data are awaited from further prospective trials.…”

Section: Omega-3 Fatty Acidsmentioning

confidence: 99%

The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients

Fruchart

Sacks

Hermans

et al. 2008

Diabetes and Vascular Disease Research

240

145

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This position paper aims to highlight evidence that atherogenic dyslipidaemia contributes to residual macrovascular risk and microvascular complications despite current standards of care for dyslipidaemia and diabetes, and to recommend therapeutic intervention for reducing this, supported by evidence and expert consensus. Lifestyle modification is an important first step. Additionally, pharmacotherapy is often required. Adding niacin, a fibrate or omega-3 fatty acids to statin therapy improves achievement of all lipid risk factors. Outcomes studies are evaluating whether these strategies translate to greater clinical benefit than statin therapy alone. In conclusion, the R 3 i highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual vascular risk among dyslipidaemic patients who are treated in accordance with current standards of care.

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“…Troglitazone 14) was employed as a reference compound and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was chosen for the house keeping gene. The LPL/GAPDH mRNA ratio was evaluated as the relative values of LPL/GAPDH ratio from vehicle control group and tests were done in triplicate.…”

Section: Resultsmentioning

confidence: 99%

Polycyclic N-Heterocyclic Compounds. Part 64: Synthesis of 5-Amino-1,2,6,7-tetrahydrobenzo[f]furo[2,3-c]isoquinolines and Related Compounds. Evaluation of Their Bronchodilator Activity and Effects on Lipoprotein Lipase mRNA Expression

Okuda

Deguchi

Kashino

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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Regular ArticleThe Truce-Smiles rearrangement features an intramolecular aromatic substitution reaction by a C-nucleophile making it a particularly useful rearrangement reaction because of the formation of a new C-C bonds.2-6) Recently, we found that this rearrangement could be extended to aliphatic electrondeficient alkenes as well as aromatic substrates.7) Thus, treatment of 2-(3-cyanopropoxy)cyclohexene-1-carbonitrile (1) with base gives a modest yield (15-43%) of 5-amino-1, 2,6,7,8,9-hexahydrofuro[2,3-c]isoquinoline (2) by a sequence that includes a Truce-Smiles rearrangement followed by cyclization (Chart 1). This sequence was initiated by Michael addition of a carbanion nucleophile adjacent to nitrile group, followed by b-elimination and intramolecular trapping of the resulting oxyanion by the nitrile group. We then decided to investigate application of this unique procedure to derivatives of tetralin and its seven-membered ring homologue (3,4-dihydro-1-(3-cyanopropoxy)naphthalene-2-carbonitrile (3a) and 9-(3-cyanopropoxy)-6,7-dihydro-5H-benzo[f]cycloheptane-8-carbonitrile (3b), respectively). Like 1, these compounds would be susceptible to Michael addition. Moreover the conjugated benzene ring should facilitate this attack, leading to improved yields that would make the method synthetically more practical. Herein we report the details of the Truce-Smiles type rearrangement reaction for a series of 3. We also report a dihydrofuran ring cleavage reaction by an amide nucleophile. In addition, since current bronchodilator drugs are known to have certain detrimental side effects (e.g. increased heart rate) and reduced efficacy, we tested these new analogues for bronchodilator activity. The effect on lipoprotein lipase (LPL) mRNA expression, which is one of key targets for diabetes drug, was also evaluated. Results and DiscussionChemistry The starting compounds were readily obtained from commercially available 1-tetralone and/or benzocycloheptan-5-one, which were transformed to cyclic ketonitriles (4a, 4b) in three steps.8,9) Reaction of 4a with 4-bromobutyronitrile in the presence of potassium carbonate in dioxane gave the desired 3a (75%) along with a C-alkylated minor by-product 3Ј Јa (18%) (Chart 2). In the IR spectrum of 3a, the carbonyl band disappeared, strongly indicating that 3a is an O-alkyl derivative, not a C-alkyl derivative. A similar reaction of 4b in N,N-dimethylformamide (DMF) afforded the desired 3b (71%) as the sole product. When the conditions for the Truce-Smiles rearrangement were applied to compound 3a using potassium tert-butoxide in dry dioxane, the expected 5-amino-1,2,6,7-tetrahydrobenzo-[f]furo[2,3-c]isoquinoline (5a) was obtained in 68% yield as the sole product. In the IR spectrum of 5a, the cyano band disappeared and amino bands were observed at 3300 and 3180 cm Ϫ1 . In the 1 H-NMR spectrum of 5a, two dihydrofuran methylene resonances appeared at 3.48 and 4.59 ppm, respectively. The two deuterium oxide exchangeable protons of the amino group appeared at 4.29 ppm. These data are co...

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Impact of thiazolidenediones on serum lipoprotein levels

Cited by 26 publications

References 53 publications

Rosiglitazone Is Associated with Mortality in Chronic Hemodialysis Patients

Rosiglitazone Is Associated with Mortality in Chronic Hemodialysis Patients

The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients

Polycyclic N-Heterocyclic Compounds. Part 64: Synthesis of 5-Amino-1,2,6,7-tetrahydrobenzo[f]furo[2,3-c]isoquinolines and Related Compounds. Evaluation of Their Bronchodilator Activity and Effects on Lipoprotein Lipase mRNA Expression

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