Sex-Specific Differences in Type 2 Diabetes Mellitus and Dyslipidemia Therapy: PPAR Agonists

Benz, Verena; Kintscher, Ulrich; Foryst‐Ludwig, Anna

doi:10.1007/978-3-642-30726-3_18

Cited by 30 publications

(29 citation statements)

References 128 publications

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“…The concomitant increase in PPAR target genes involved in lipid synthesis (FAS) or transport (FAT) in lungs of female fetuses of diabetic rats fed the 6% olive-oil-or the 6% safflower-oil-supplemented diets indicates that this increase may contribute to the accumulation of triglycerides and to providing lipid substrates needed for the production of surfactant lipids in these experimental groups (Rehan & Torday 2012). The sex differences observed can be explained by the complex effects of estrogens, which induce profound changes in lipid metabolic pathways and regulate PPARs expression, and of androgens, which induce changes in the expression of multiple genes, including several PPAR coactivators and corepressors (Bresson et al 2010, Benz et al 2012, Oosthuyse & Bosch 2012.…”

Section: Discussionmentioning

confidence: 99%

“…There is strong evidence of diabetes-induced changes in lipid metabolism, sex-dependent changes in lipid metabolic pathways, and of the role of estrogens in lipid metabolism (Kautzky-Willer & Handisurya 2009, Benz et al 2012, Oosthuyse & Bosch 2012. Also estrogen-responsive elements are found in PPARs promoters, and estrogens can regulate PPARs expression and activation (Yoon 2009, Oosthuyse & Bosch 2012.…”

Section: Discussionmentioning

confidence: 99%

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Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats

Kurtz¹,

Capobianco²,

Careaga³

et al. 2014

Journal of Endocrinology

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Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B 4 (LTB 4 , PPARa ligand) or 15deoxyD 12,14 prostaglandin J 2 (15dPGJ 2 , PPARg ligand) and ii) fed during pregnancy with 6% olive oil-or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB 4 and partially restored by 15dPGJ 2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil-and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats

Kurtz¹,

Capobianco²,

Careaga³

et al. 2014

Journal of Endocrinology

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“…TZDs are PPARγ agonists; insulin-sensitizing drugs used in the treatment of T2D 93. Although some studies have suggested that TZDs may be more effective in women compared with men,94–96 the majority of larger studies have not reported sex-specific differences 93.…”

Section: Glucose-lowering Therapymentioning

confidence: 99%

Sex differences in type 2 diabetes: focus on disease course and outcomes

Arnetz¹,

Ekberg²,

Alvarsson³

2014

DMSO

151

112

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BackgroundWomen with type 2 diabetes (T2D) are less likely to reach the goals for hemoglobin A1c compared with men, and have higher all-cause mortality. The risk of cardiovascular disease is elevated among both men and women with T2D, however, the risk has declined among men over recent years while it remains stationary in women. Reasons for these sex differences remain unclear, and guidelines for diabetes treatment do not differentiate between sexes. Possible causes for varying outcome include differences in physiology, treatment response, and psychological factors. This review briefly outlines sex differences in hormonal pathophysiology, and thereafter summarizes the literature to date on sex differences in disease course and outcome.MethodsSystematic searches were performed on PubMed using “sex”, “gender”, and various glucose-lowering therapies as keywords. Earlier reviews are summarized and results from individual studies are reported. Reference lists from studies were used to augment the search.ResultsThere is an increased risk of missing the diagnosis of T2D when screening women with only fasting plasma glucose instead of with an oral glucose tolerance test. The impact of various risk factors for complications may differ by sex. Efficacy and side effects of some glucose-lowering drugs differ between men and women. Men with T2D appear to suffer more microvascular complications, while women have higher morbidity and mortality in cardiovascular disease and also fare worse psychologically.ConclusionFew studies to date have focused on sex differences in T2D. Several questions demand further study, such as whether risk factors and treatment guidelines should be sex-specific. There is a need for clinical trials designed specifically to evaluate sex differences in efficacy and outcome of the available treatments.

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“…Both, pioglitazone and rosiglitazone, increase the risk of heart failure with high strength of evidence (SOE), and also oedema (high SOE) and fractures in women (moderate SOE) (Habib et al 2010;Jonas et al 2011) (see also Benz et al 2012).…”

Section: Glitazonesmentioning

confidence: 95%