Sex differences in diabetes and kidney disease: mechanisms and consequences.
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ABSTRACT:
SUBMITTER: Shepard BD
PROVIDER: S-EPMC6732459 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Sex differences in diabetes and kidney disease: mechanisms and consequences.
American journal of physiology. Renal physiology 20190626 2
Type 1 and type 2 diabetes, along with their accompanying hyperglycemia, are associated with a multitude of comorbidities including the development of diabetic kidney disease. Although the hallmarks of these metabolic disorders have been well characterized in population and animal studies, it is becoming increasingly apparent that diabetes manifests itself differently in men and women. This review summarizes the recent diabetic literature with a focus on known sex differences in clinical and pre ...[more]
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Project description:ObjectivesTo investigate the characteristics of kidney stone disease (KSD) among the Chinese population with type 2 diabetes mellitus (T2DM) and identify sex-specific factors associated with KSD.MethodsA single-center, cross-sectional analysis was performed among Chinese patients with T2DM. KSD was identified by ultrasonography or computed tomography results. Demographic data, physical measurements, laboratory measurements, comorbidities, and related medication data were collected and analyzed. Binary logistic regression was used to explore the associated factors.ResultsA total of 7,257 patients with T2DM were included in the study, of which 56.1% were male and 15.0% were diagnosed with KSD. The male-to-female ratio for KSD among T2DM patients was 1.35. Among all the T2DM patients, male gender, HOMA2-IR, uric acid, and renal cysts were independent risk factors for KSD development, whereas serum phosphorus and the use of angiotensin-converting enzyme inhibitors (ACEIs) were independent protective factors for KSD. Among male diabetic patients, triglycerides, HOMA2-IR, renal cysts, and urinary tract infections were all associated with a greater risk of KSD. In contrast, serum phosphorus was associated with a lower risk of KSD. Among female diabetic patients, systolic blood pressure and HOMA2-B were both contributing factors, and ACEIs acted as a protective factor for KSD.ConclusionAmong Chinese patients with T2DM, approximately 1 in 7 patients was affected by KSD, and the prevalence was twice as high as that in the general Chinese population. The factors associated with KSD varied by sex among T2DM patients. Focusing on these factors is beneficial for reducing the risk of KSD and delaying kidney damage in diabetic patients.
| S-EPMC7265720 | biostudies-literature
Project description:Vascular dysfunction plays an important role in the etiology of chronic kidney disease (CKD) and is associated with cardiovascular diseases. Sex differences in vascular function are common in clinical and nonclinical populations. However, no data exist in individuals with CKD. The present study tested the hypothesis that sex and/or aging differences exist in vascular function in patients with CKD. Endothelium-dependent dilation (EDD; measured via brachial artery flow-mediated dilation) and endothelium-independent dilation (EID; measured via nitroglycerin-mediated dilation) were assessed. Analyses were adjusted for several variables that could influence vascular function (diabetes, cardiovascular disease, and blood pressure). Women, in general, had higher EDD values than men (6.5 ± 4.9% vs. 4.4 ± 3.4%); however, EID did not differ among these groups. In younger men and women (<55 yr old), EDD and EID were higher (P < 0.05) than their older (≥55 yr old) counterparts (EDD: 7.0 ± 4.1% vs. 4.4 ± 3.8% and EID: 24.0 ± 9.6% vs. 18.3 ± 9.2%). Additionally, younger women exhibited higher (P < 0.05) EDD and EID compared with younger men (EDD: 9.5 ± 6.4% vs. 5.1 ± 3.8%, P = 0.01, and EID: 24.0 ± 9.6% vs. 18.3 ± 9.2%). No differences in EDD and EID were present between older men and women with CKD. Diabetes independently predicted lower EID but not EDD in men and women. Blood pressure and cardiovascular disease did not predict EDD or EID. This is the first study to show significant sex differences in vascular function. Moreover, these differences are evident between younger men and women with CKD but are abolished with age. Additional studies are needed to better understand the mechanisms that may underlie sex differences in vascular dysfunction with CKD.
| S-EPMC7468834 | biostudies-literature
Project description:Kidney disease in patients with type 1 diabetes historically has been believed to be more prevalent in men. Because recent data do not reflect this pattern, we evaluated whether a sex difference persists.Prospective cohort study.We used 18-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study (n = 788; baseline mean age, 27 years; diabetes duration, 19 years).Sex and diagnosis interval (1950-1964 or 1965-1980).Cumulative incidences of macroalbuminuria (albumin excretion rate >200 ?g/min) and end-stage renal disease (ESRD; kidney failure, dialysis, or transplant) were evaluated at 20, 25, and 30 years of diabetes duration. To address potential survival bias, death certificate information was included in determining ESRD for those who died before baseline (n = 145). Analyses were stratified by diagnosis year (1950-1964 or 1965-1980).Kidney disease risk factor information was available.A significant interaction was noted between sex and diagnosis cohort for ESRD incidence by 25 (P = 0.002) and 30 (P < 0.001) years' duration. Thus, within the 1950-1964 cohort (210 men and 180 women), ESRD incidence was higher in men compared with women by 25 (30.6% vs 18.0%, respectively) and 30 (43.4% vs 24.6%, respectively) years' duration of type 1 diabetes. However, in the 1965-1980 cohort (260 men and 283 women), the incidence was higher in women (7.6% vs 13.8% by 25 years [P = 0.04] and 13.7% vs 21.0% by 30 years' duration [P = 0.09] in men vs women, respectively). Results were similar for macroalbuminuria.Study participants were not followed up from the onset of diabetes; thus, risk-factor data from that period are lacking.Our data suggest that the male excess of type 1 diabetic kidney disease cases observed in the earlier cohort has been eliminated in the younger cohort. The reason for this dramatic change presently is unclear, but should be addressed in subsequent studies.
| S-EPMC3183221 | biostudies-literature
Project description:We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex hormone actions. Sexual differentiation begins with fertilization and continues beyond menopause. It affects virtually every body system, resulting in marked sex differences in such areas as growth, lifespan, metabolism, and immunity, all of which can impact on cancer progression, treatment response, and survival. These organismal level differences have correlates at the cellular level, and thus, males and females can fundamentally differ in their protections and vulnerabilities to cancer, from cellular transformation through all stages of progression, spread, and response to treatment. Our goal in this review is to cover some of the robust sex differences that exist in core cancer pathways and to make the case for inclusion of sex as a biological variable in all laboratory and clinical cancer research. We finish with a discussion of lab- and clinic-based experimental design that should be used when testing whether sex matters and the appropriate statistical models to apply in data analysis for rigorous evaluations of potential sex effects. It is our goal to facilitate the evaluation of sex differences in cancer in order to improve outcomes for all patients.
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Project description:Cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic heart disease (IHD) are the main cause of mortality in industrialized countries. Although it is well known that there is a difference in the risk of these diseases in women and men, current therapy does not consider the sexual dimorphism; i.e., differences in anatomical structures and metabolism of tissues. Here, we discuss how genetic, epigenetic, hormonal, cellular or molecular factors may explain the different CVD risk, especially in high-risk groups such as women with diabetes. We analyze whether sex may modify the effects of diabetes at risk of CAD. Finally, we discuss current diagnostic techniques in the evaluation of CAD and IHD in diabetic women.
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Project description:BackgroundChronic kidney disease (CKD) is less prevalent among men than women, but more men than women initiate kidney replacement therapy. Differences in CKD awareness may contribute to this gender gap, which may further vary by race/ethnicity. We aimed to investigate trends in CKD awareness and the association between individual characteristics and CKD awareness among US men versus women.Methods and findingsWe conducted a serial, cross-sectional analysis of 10 cycles (1999-2018) from the National Health and Nutrition Examination Survey (NHANES). Adult participants with CKD stages G3-G5 (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2) were included, unless they were on dialysis or medical information was missing. Serum creatinine was measured during NHANES medical exams. CKD stage was classified by eGFR, based on the CKD-EPI formula. CKD awareness was assessed with the question: "Have you ever been told by a health care professional you had weak or failing kidneys", asked in standardized NHANES questionnaires on each survey. Using logistic regression models, we evaluated the association between sex and CKD awareness, adjusting for potential confounders including age, race/ethnicity and comorbidities. We stratified CKD awareness by 5 pre-defined calendar-year periods and conducted all analyses for the complete study population as well as the Caucasian and African American subpopulations. We found that among 101871 US persons participating in NHANES, 4411 (2232 women) had CKD in stages G3-G5. These participants were, on average, 73±10 years old, 25.3% reported diabetes, 78.0% reported hypertension or had elevated blood pressure during medical examinations and 39.8% were obese (percentages were survey-weighted). CKD awareness was more prevalent among those with higher CKD stage, younger age, diabetes, hypertension and higher body mass index. CKD awareness was generally low (<22.5%), though it increased throughout the study period, remaining consistently higher among men compared to women, with a decreasing gender gap over time (adjusted odds ratio [men-to-women] for CKD awareness = 2.71 [1.31-5.64] in period 1; = 1.32 [0.82-2.12] in period 5). The sex difference in CKD awareness was smaller in African American participants, in whom CKD awareness was generally higher. Using serum creatinine rather than eGFR as the CKD-defining exposure, CKD awareness increased with rising serum creatinine, in a close to identical fashion among both sexes during 1999-2008, while during 2009-2018, CKD awareness among women increased earlier than among men (i.e. with lower serum creatinine levels).ConclusionsCKD awareness is lower among US women than men. The narrowing gap between the sexes in more recent years and the results on CKD awareness by serum creatinine indicate that health care professionals have previously been relying on serum creatinine to inform patients about their condition, but in more recent years have been using eGFR, which accounts for women's lower serum creatinine levels due to their lower muscle mass. Additional efforts should be made to increase CKD awareness among both sexes.
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Project description:Introduction: Though disease-related differences between the sexes have increasingly attracted attention, the renal impact of pulse pressure (PP) in patients with chronic kidney disease (CKD) has never been investigated comprehensively in relation to differences associated with sex. We aimed to examine sex differences in PP as a related factor of CKD progression from the perspective of atherosclerosis. Methods: A total of 156 patients with CKD matched according to age and estimated glomerular filtration rate (eGFR) were separated into sex-based cohorts. Multivariate Cox proportional hazards analyses were performed to identify factors associated with renal outcomes. Kaplan-Meier analyses were performed to assess disease progression, which was defined as a ?50% estimated glomerular filtration rate (eGFR) decline or end-stage renal disease. Results: The mean age of the study participants was 58.9 ± 13.1 years, and the median follow-up period was 114.0 months. A multivariate Cox regression analysis showed that PP was significantly associated with disease progression among the entire cohort (P = 0.007). In the sex-based sub-cohort analyses, PP was significantly associated with disease progression in men (P = 0.0004) but not in women. Among the entire cohort, PP was correlated positively with age (P = 0.03) and negatively with high-density lipoprotein-cholesterol (HDL-C) level (P = 0.003). PP was significantly correlated with visceral fat area (VFA) (P = 0.04) and hemoglobin level (P = 0.04) in men and with HDL-C level (P = 0.003) in women. Conclusion: A high PP is a significant related factor of CKD progression, especially in men, in whom it is significantly associated with greater VFA and lower hemoglobin level.
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Project description:Sex differences are an important component of National Institutes of Health rigor. The goal of this investigation was to test the hypothesis that female mice have greater exercise capacity than male mice, and that it is due to estrogen, nitric oxide, and myosin heavy chain expression. Female C57BL6/J wild-type mice exhibited greater (P < 0.05) maximal exercise capacity for running distance (489?±?15 m) than age-matched male counterparts (318?±?15 m), as well as 20% greater work to exhaustion. When matched for weight or muscle mass, females still maintained greater exercise capacity than males. Increased type I and decreased type II myosin heavy chain fibers in the soleus muscle from females are consistent with fatigue resistance and better endurance in females compared with males. After ovariectomy, female mice no longer demonstrated enhanced exercise, and treatment of male mice with estrogen resulted in exercise capacity similar to that of intact females (485?±?37 m). Nitric oxide synthase, a downstream target of estrogen, exhibited higher activity in female mice compared with male mice, P < 0.05, whereas ovariectomized females exhibited nitric oxide synthase levels similar to males. Nitric oxide synthase activity also increased in males treated with chronic estrogen to levels of intact females. Nitric oxide synthase blockade with N?-nitro-l-arginine methyl ester eliminated the sex differences in exercise capacity. Thus estrogen, nitric oxide, and myosin heavy chain expression are important mechanisms mediating the enhanced exercise performance in females.
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Project description:Individualized outcome prediction classifiers were successfully constructed through expression profiling of a total of 779 genes in microglial cells from 36 mice, which had been consecutively operated on within a defined short period of time
2022-05-20 | GSE203202 | GEO
Project description:Men are consistently overrepresented in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and coronavirus disease 2019 (COVID-19) severe outcomes, including higher fatality rates. These differences are likely due to gender-specific behaviors, genetic and hormonal factors, and sex differences in biological pathways related to SARS-CoV-2 infection. Several social, behavioral, and comorbid factors are implicated in the generally worse outcomes in men compared with women. Underlying biological sex differences and their effects on COVID-19 outcomes, however, have received less attention. The present review summarizes the available literature regarding proposed molecular and cellular markers of COVID-19 infection, their associations with health outcomes, and any reported modification by sex. Biological sex differences characterized by such biomarkers exist within healthy populations and also differ with age- and sex-specific conditions, such as pregnancy and menopause. In the context of COVID-19, descriptive biomarker levels are often reported by sex, but data pertaining to the effect of patient sex on the relationship between biomarkers and COVID-19 disease severity/outcomes are scarce. Such biomarkers may offer plausible explanations for the worse COVID-19 outcomes seen in men. There is the need for larger studies with sex-specific reporting and robust analyses to elucidate how sex modifies cellular and molecular pathways associated with SARS-CoV-2. This will improve interpretation of biomarkers and clinical management of COVID-19 patients by facilitating a personalized medical approach to risk stratification, prevention, and treatment.
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