Estrogens and Progression of Diabetic Kidney Damage

Doublier, Sophie; Lupia, Enrico; Catanuto, Paola; Elliot, Sharon J.

doi:10.2174/157339911794273982

Cited by 30 publications

(18 citation statements)

References 101 publications

(148 reference statements)

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“…75 In contrast, women are thought to be somewhat protected from renal injury associated with DM and hypertension perhaps because of the presence of estrogens. 75,76 Because we now know that androgen levels are decreased with obesity and chronic diseases, 77 including hypertension and DM, the model that androgens are bad and estrogens are good is overly simplistic to adequately account for the mechanisms responsible for hypertension in DM and obesity.…”

Section: Sex Differences: Dm and Hypertensionmentioning

confidence: 99%

Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus

et al. 2015

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Currently, ≈1 in 13 people living in the United States has DM, and 90% to 95% of these individuals have type 2 DM (T2DM).2 Overall, the prevalence of T2DM is similar in women and men. In the United States, ≈12.6 million women (10.8%) and 13 million men (11.8%) ≥20 years of age are currently estimated to have T2DM. 2 Among individuals with T2DM, cardiovascular disease (CVD) is the leading cause of morbidity and mortality and accounts for >75% of hospitalizations and >50% of all deaths.3 Although nondiabetic women have fewer cardiovascular events than nondiabetic men of the same age, this advantage appears to be lost in the context of T2DM. 4,5 The reasons for this advantage are not entirely clear but are likely multifactorial with contributions from inherent physiological differences, including the impact of the sex hormones, differences in cardiovascular risk factors, and differences between the sexes in the diagnosis and treatment of DM and CVD. 6 In addition, there are racial and ethnic factors to consider because women of ethnic minority backgrounds have a higher prevalence of DM than non-Hispanic white (NHW) women.This scientific statement was designed to provide the current state of knowledge about sex differences in the cardiovascular consequences of DM, and it will identify areas that would benefit from further research because much is still unknown about sex differences in DM and CVD. Areas that are discussed include hormonal differences between the sexes and their possible effects on the interaction between DM and CVD, sex differences in epidemiology, ethnic and racial differences and risk factors for CVD in DM across the life span, sex differences in various types of CVD and heart failure, and sex differences in the effects of treatments for DM, including both medications and lifestyle. In addition, there is discussion about risk factors that are specific to women, including gestational diabetes mellitus (GDM) and polycystic ovarian syndrome (PCOS), which affect CVD risk. Table 1 focuses on sex differences in CVD risk factors and outcomes in DM, and Table 2 provides information about sex differences in CVD treatments and interventions in DM. Table 3 contains some of the important ideas for research in sex differences in the cardiovascular consequences of DM. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on July 31, 2015, and the American Heart Association Executive Committee on September 5, 2015. A copy of the document is available at http://my.americanheart.org/statements by selecting either the "By...

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Section: Sex Differences: Dm and Hypertensionmentioning

confidence: 99%

Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus

et al. 2015

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“…However, there is less evidence that female gender is protective in DKD 54 . Nonetheless, a number of reports suggest that podocyte estrogen receptor signaling may be protective in DKD.…”

Section: Podocyte Signaling Pathways In Dkdmentioning

confidence: 99%

“…Nonetheless, a number of reports suggest that podocyte estrogen receptor signaling may be protective in DKD. Estrogen effects are mediated by two distinct estrogen receptor subtypes, ERá and ERâ and both receptors are present in podocytes 54 . Estradiol has been shown to stimulate ERá protein expression as well as to reduce podocyte apopotosis after puromycin aminonucleoside exposure 55 .…”

Section: Podocyte Signaling Pathways In Dkdmentioning

confidence: 99%

Podocytes, Signaling Pathways, and Vascular Factors in Diabetic Kidney Disease

Brosius

Coward

2014

Advances in Chronic Kidney Disease

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Alterations and injury to glomerular podocytes play a key role in the initiation and early progression of diabetic kidney disease. Multiple factors in the diabetic milieu cause abnormalities in podocyte signaling that lead to podocyte foot process effacement, hypertrophy, detachment, loss and death. Alterations in insulin action and mTOR activation have been well documented to lead to pathology. For example, reduced insulin action directly leads to albuminuria, increased glomerular matrix accumulation, thickening of the glomerular basement membrane, podocyte apoptosis and glomerulosclerosis. In addition, the podocyte generates factors that alter signaling in other glomerular cells. Prominent among these is VEGF-A which plays a complex role in maintaining glomerular endothelium viability but causes endothelial cell pathology when generated at too high a level. Finally, circulating vascular factors, such as activated protein C have a profound effect on podocyte stability and survival. This cytoprotective factor is critical for podocyte health and its deficiency promotes podocyte injury and apoptosis. Thus, the podocyte sits in the center of a network of paracrine and hormonal signaling systems that in health keep the podocyte adaptable and viable, but in diabetes can lead to pathologic changes, detachment and death. This podocyte injury is a critical determinant of the progression of diabetic kidney disease.

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“…On the basis of these data and studies showing that close control of glycemia reduces the risk of DKD progression (15) and that inflammation correlates with DKD (4), we hypothesized that a longer and larger trial might show that SC could also reduce albuminuria. Finally, because age (2), sex (16), and race (17) have been shown to affect DKD, these factors were chosen for secondary analysis.…”

Section: Introductionmentioning

confidence: 99%

Effects of Sevelamer Carbonate on Advanced Glycation End Products and Antioxidant/Pro-Oxidant Status in Patients with Diabetic Kidney Disease

Yubero‐Serrano

Woodward

Poretsky³

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives The primary goals were to re-examine whether sevelamer carbonate (SC) reduces advanced glycation end products (AGEs) (methylglyoxal and carboxymethyllysine [CML]), increases antioxidant defenses, reduces pro-oxidants, and improves hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Secondary goals examined albuminuria, age, race, sex, and metformin prescription.Design, setting, participants, & measurements This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM (HbA1c .6.5%) and stages 2-4 DKD (urinary albumin/creatinine ratio $200 mg/g) treated with SC (1600 mg) or calcium carbonate (1200 mg), three times a day, without changing medications or diet. Statistical analyses used linear mixed models adjusted for randomization levels. Preselected subgroup analyses of sex, race, age, and metformin were conducted.Results SC lowered serum methylglyoxal (95% confidence interval [CI], 20.72 to 20.29; P,0.001), serum CML (95% CI, 25.08 to 21.35; P#0.001), and intracellular CML (95% CI, 21.63 to 20.28; P=0.01). SC increased anti-inflammatory defenses, including nuclear factor like-2 (95% CI, 0.58 to 1.29; P=0.001), AGE receptor 1 (95% CI, 0.23 to 0.96; P=0.001), NAD-dependent deacetylase sirtuin-1 (95% CI, 0.20 to 0.86; P=0.002), and estrogen receptor a (95% CI, 1.38 to 2.73; P #0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, 21.56 to 20.72; P#0.001) and the receptor for AGEs (95% CI, 20.58 to 1.53; P#0.001). There were no differences in HbA1c, GFR, or albuminuria in the overall group. Subanalyses showed that SC lowered HbA1c in women (95% CI, 21.71 to 20.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged ,65 years (95% CI, 21.15 to 20.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, 21.11 to 20.22; P=0.003, interaction P#0.001), whereas albuminuria increased after SC and calcium carbonate in Caucasians.Conclusions SC reduced circulating and cellular AGEs, increased antioxidants, and decreased pro-oxidants, but did not change HbA1c or the albumin/creatinine ratio overall in patients with T2DM and DKD. Because subanalyses revealed that SC may reduce HbA1c and albuminuria in some patients with T2DM with DKD, further studies may be warranted.

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Estrogens and Progression of Diabetic Kidney Damage

Cited by 30 publications

References 101 publications

Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus

Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus

Podocytes, Signaling Pathways, and Vascular Factors in Diabetic Kidney Disease

Effects of Sevelamer Carbonate on Advanced Glycation End Products and Antioxidant/Pro-Oxidant Status in Patients with Diabetic Kidney Disease

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