Dataset Information

Sex Differences in Lipid Profile across the Life Span in Patients with Type 2 Diabetes: A Primary Care-Based Study.

ABSTRACT: We assessed sex differences across the life span in the lipid profile of type 2 diabetes (T2D) patients treated and not treated with statins. We used the Groningen Initiative to ANalyze Type 2 diabetes Treatment database, which includes T2D patients from the north of the Netherlands. Patients with a full lipid profile determined between 2010 and 2012 were included. We excluded patients treated with other lipid-lowering drugs than statins. Sex differences in low- and high-density lipoprotein cholesterol (LDL-c and HDL-c) and triglyceride (TG) levels across 11 age groups stratified by statin treatment were assessed using linear regression. We included 26,849 patients (51% women, 55% treated with statins). Without statins, women had significantly lower LDL-c levels than men before the age of 45 years, similar levels between 45 and 49 years, and higher levels thereafter. With statins, similar LDL-c levels were shown up to the age of 55, and higher levels in women thereafter. Women had significantly higher HDL-c levels than men, regardless of age or statin treatment. Men had significantly higher TG levels up to the age of 55 and 60, depending on whether they did not take or took statins, respectively, and similar levels thereafter. When managing cardiovascular risk in patients with T2D, attention is needed for the menopausal status of women and for TG levels in younger men.

SUBMITTER: Ambroz M

PROVIDER: S-EPMC8072568 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Sex Differences in Lipid Profile across the Life Span in Patients with Type 2 Diabetes: A Primary Care-Based Study.

Ambrož Martina M de Vries Sieta T ST Vart Priya P Dullaart Robin P F RPF Roeters van Lennep Jeanine J Denig Petra P Hoogenberg Klaas K

Journal of clinical medicine 20210419 8

We assessed sex differences across the life span in the lipid profile of type 2 diabetes (T2D) patients treated and not treated with statins. We used the Groningen Initiative to ANalyze Type 2 diabetes Treatment database, which includes T2D patients from the north of the Netherlands. Patients with a full lipid profile determined between 2010 and 2012 were included. We excluded patients treated with other lipid-lowering drugs than statins. Sex differences in low- and high-density lipoprotein chol ...[more]

PMID: 33921745

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Project description:Females and males often have markedly different mortality rates and life spans, but it is unclear why these forms of sexual dimorphism evolve. The unguarded X hypothesis contends that dimorphic life spans arise from sex differences in X or Z chromosome copy number (i.e., one copy in the "heterogametic" sex; two copies in the "homogametic" sex), which leads to a disproportionate expression of deleterious mutations by the heterogametic sex (e.g., mammalian males; avian females). Although data on adult sex ratios and sex-specific longevity are consistent with predictions of the unguarded X hypothesis, direct experimental evidence remains scant, and alternative explanations are difficult to rule out. Using a simple population genetic model, we show that the unguarded X effect on sex differential mortality is a function of several reasonably well-studied evolutionary parameters, including the proportion of the genome that is sex linked, the genomic deleterious mutation rate, the mean dominance of deleterious mutations, the relative rates of mutation and strengths of selection in each sex, and the average effect of mutations on survival and longevity relative to their effects on fitness. We review published estimates of these parameters, parameterize our model with them, and show that unguarded X effects are too small to explain observed sex differences in life span across species. For example, sex differences in mean life span are known to often exceed 20% (e.g., in mammals), whereas our parameterized models predict unguarded X effects of a few percent (e.g., 1-3% in Drosophila and mammals). Indeed, these predicted unguarded X effects fall below statistical thresholds of detectability in most experiments, potentially explaining why direct tests of the hypothesis have generated little support for it. Our results suggest that evolution of sexually dimorphic life spans is predominantly attributable to other mechanisms, potentially including "toxic Y" effects and sexual dimorphism for optimal investment in survival versus reproduction.

Project description:The prevalence of type 2 diabetes mellitus is increasing in both sexes, but men are usually diagnosed at a younger age and lower body fat mass than women. Worldwide, an estimated 17.7 million more men than women have diabetes mellitus. Women appear to bear a greater risk factor burden at the time of their type 2 diabetes diagnosis, especially obesity. Moreover, psychosocial stress might play a more prominent role in diabetes risk in women. Across their lifespan, women experience greater hormone fluctuations and body changes due to reproductive factors than men. Pregnancies can unmask pre-existing metabolic abnormalities, resulting in the diagnosis of gestational diabetes, which appears to be the most prominent risk factor for progression to type 2 diabetes in women. Additionally, menopause increases women's cardiometabolic risk profile. Due to the progressive rise in obesity, there is a global increase in women with pregestational type 2 diabetes, often with inadequate preconceptual care. There are differences between men and women regarding type 2 diabetes and other cardiovascular risk factors with respect to comorbidities, the manifestation of complications and the initiation of and adherence to therapy. Women with type 2 diabetes show greater relative risk of CVD and mortality than men. Moreover, young women with type 2 diabetes are currently less likely than men to receive the treatment and CVD risk reduction recommended by guidelines. Current medical recommendations do not provide information on sex-specific or gender-sensitive prevention strategies and management. Thus, more research on sex differences, including the underlying mechanisms, is necessary to increase the evidence in the future. Nonetheless, intensified efforts to screen for glucose metabolism disorders and other cardiovascular risk factors, as well as the early establishment of prophylactic measures and aggressive risk management strategies, are still required for both men and women at increased risk of type 2 diabetes. In this narrative review we aim to summarise sex-specific clinical features and differences between women and men with type 2 diabetes into risk factors, screening, diagnosis, complications and treatment.

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Project description:BackgroundGrowing evidence suggests that epigenetic mechanisms of gene regulation may play a role in susceptibilities to specific toxicities and adverse drug reactions. MiRNAs in particular have been shown to be important regulators in cancer and other diseases and show promise as predictive biomarkers for diagnosis and prognosis. In this study, we characterized the global kidney miRNA expression profile in untreated male and female F344 rats throughout the life span. These findings were correlated with sex-specific susceptibilities to adverse renal events, such as male-biased renal fibrosis and inflammation in old age.MethodsKidney miRNA expression was examined in F344 rats at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age in both sexes using Agilent miRNA microarrays. Differential expression was determined using filtering criteria of ≥1.5 fold change and ANOVA or pairwise t-test (FDR <5%) to determine significant age and sex effects, respectively. Pathway analysis software was used to investigate the possible roles of these target genes in age- and sex-specific differences.ResultsThree hundred eleven miRNAs were found to be expressed in at least one age and sex. Filtering criteria revealed 174 differentially expressed miRNAs in the kidney; 173 and 34 miRNAs exhibiting age and sex effects, respectively. Principal component analysis revealed age effects predominated over sex effects, with 2-week miRNA expression being much different from other ages. No significant sexually dimorphic miRNA expression was observed from 5 to 8 weeks, while the most differential expression (13 miRNAs) was observed at 21 weeks. Potential target genes of these differentially expressed miRNAs were identified.ConclusionsThe expression of 56% of detected renal miRNAs was found to vary significantly with age and/or sex during the life span of F344 rats. Pathway analysis suggested that 2-week-expressed miRNAs may be related to organ and cellular development and proliferation pathways. Male-biased miRNA expression at older ages correlated with male-biased renal fibrosis and mononuclear cell infiltration. These miRNAs showed high representation in renal inflammation and nephritis pathways, and included miR-214, miR-130b, miR-150, miR-223, miR-142-5p, miR-185, and miR-296*. Analysis of kidney miRNA expression throughout the rat life span will improve the use of current and future renal biomarkers and inform our assessments of kidney injury and disease.

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Dataset Information

Sex Differences in Lipid Profile across the Life Span in Patients with Type 2 Diabetes: A Primary Care-Based Study.

Publications

Sex Differences in Lipid Profile across the Life Span in Patients with Type 2 Diabetes: A Primary Care-Based Study.

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