Therapeutic Advances in Endocrinology and Metabolism最新文献

Background: As a part of metabolic syndrome, hyperuricemia has a higher incidence in patients with diabetes than in the general population owing to various underlying factors.

Objectives: The objective of the present study was to investigate the prevalence of hyperuricemia among patients with diabetes and identify associated factors.

Design: A cross-sectional study.

Methods: Herein, we included patients with diabetes managed at nine healthcare centers in Chenghua District, Chengdu, from February 2021 to November 2021. Clinical data, lifestyle habits, and laboratory data were collected to determine the prevalence and factors associated with hyperuricemia.

Results: In total, we included 1577 patients with diabetes (males, 50.35%; females, 49.65%). The median serum uric acid level was 337.9 μmol/L, and the prevalence of hyperuricemia in patients with diabetes was 21.24%. The prevalence of hyperuricemia in male patients was significantly higher than in females (29.35% in males versus 13.03% in females, p < 0.001). Male patients with obesity (p = 0.006) or triglyceride (TG) ⩾ 1.7 mmol/L (p < 0.001) had a high risk of developing hyperuricemia, and hyperuricemia was negatively associated with estimated glomerular filtration rate (eGFR) ⩾ 60 mL/min/1.73 m² (p < 0.001), glycosylated hemoglobin (HbA1c) ⩾ 7% (p < 0.001), fenofibrate (p = 0.010), and sodium-glucose cotransporter 2 (SGLT-2) inhibitors (p = 0.035). Considering females, overweight (p = 0.004), alanine transaminase (ALT) > 40 U/L (p < 0.001), and TG ⩾ 1.7 mmol/L (p = 0.015) showed a significant positive correlation with hyperuricemia, while eGFR ⩾ 60 mL/min/1.73 m² (p < 0.001) was negatively associated with the risk of hyperuricemia.

Conclusion: Hyperuricemia is highly prevalent in patients with diabetes, especially in males. In addition to traditionally associated factors, fenofibrate and SGLT-2 inhibitors were also associated with the risk of hyperuricemia.

Registration: The study protocol was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/), and the registration number was ChiCTR 2100042742.

There are well-described sex-based differences in how the immune system operates. In particular, cisgender (cis) females have a more easily activated immune system; associated with an increased prevalence of autoimmune diseases and adverse events following vaccinations. Conversely, cis males have a higher threshold for immune activation, and are more prone to certain infectious diseases, such as coronavirus disease (COVID-19). Oestrogen and testosterone have immune-modulatory properties, and it is likely that these contribute to the sexual dimorphism of the immune system. There are also important immune-related genes located on the X chromosome, such as toll-like receptor (TLR) 7/8; and the mosaic bi-allelic expression of such genes may contribute to the state of immune hyperactivation in cis females. The scientific literature strongly suggests that sex-based differences in the functioning of the immune system are related to both X-linked genes and immune modulation by sex hormones. However, it is currently not clear how this impacts transgender (trans) people receiving gender-affirming hormonal therapy. Moreover, it is estimated that in Australia, at least 2.3% of adolescents identify as trans and/or gender diverse, and referrals to specialist gender-affirming care are increasing each year. Despite the improving social awareness of trans people, they remain chronically underrepresented in the scientific literature. In addition, a small number of case studies describe new onset autoimmune disorders in adult trans females following oestrogen use. However, there is currently minimal long-term research with an immunological focus on trans people. Therefore, to ensure the positive health outcomes of trans people, it is crucial that the role of sex hormones in immune modulation is investigated further.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has appeared as the leading liver disease worldwide. Whereas the terminology nonalcoholic fatty liver disease (NAFLD) mainly reflected a negative selection and exclusion of alcohol-related liver disease (ALD), the new definition made its focus on the association of MAFLD with overweight/obesity, type 2 diabetes and metabolic risk factors especially also in normal weight/lean subjects. Several studies from the past 2 years have now used the new definition and have provided substantial information that this new definition might be accurate. Studies from the past 2 years have provided evidence that the new definition might be especially advantageous in the characterization and identification of patients with significant fibrosis. This has also been demonstrated in the well-known Rotterdam study in which the MAFLD-only group showed a higher rate of fibrosis and liver stiffness. MAFLD might also be able to predict all-cause mortality as demonstrated in the Third National Health and Nutrition Examination Survey. Furthermore, MAFLD might improve characterization of the cardiovascular risk of this patient population. As the term MAFLD has not yet been accepted universally, it remains important to coordinate efforts globally to adapt to this new definition and especially involve all specialities dealing with metabolic disorders such as diabetologists to further improve its definition and to prepare the medical community for its future use. The aim of this review is to summarize and critically address evidence emerging over the past 2 years that usage of the term MAFLD could be helpful in daily clinical practice.

Aims: Diabetic foot ulcers (DFUs) have a significant impact on a patient's quality of life and life expectancy, with mortality rates comparable with malignant diseases. However, there is a lack of data regarding palliative care needs in this population. We aimed to characterize palliative care needs in people under diabetic foot surveillance using the Integrated Palliative care Outcome Scale (IPOS) and EuroQol-5D three-level version (EQ-5D-3L) and to assess differences between those with and without a DFU.

Methods: We conducted a cross-sectional study with consecutive sampling inclusion of patients followed in a tertiary hospital's Diabetic Foot Clinic between February and October 2019 with (n = 20) and without (n = 42) active DFU.

Results: The most frequent symptoms encountered were pain, weakness or lack of energy, sore or dry mouth and drowsiness. Patients with an active DFU were significantly more likely to report feeling anxious or worried in comparison with those without (95% versus 55%, p = 0.002). Only 10% of the participants with an active DFU said that they were always able to share how they felt with family and friends as much as they wanted in comparison with 45% of those without (p = 0.006).

Conclusion: Our study identified palliative care needs in patients under diabetic foot surveillance with and without DFU, including a significant presence of physical symptoms. Patients in both groups showed signs of emotional/psychological distress, with a higher manifestation in patients with DFU. To the best of our knowledge, this is the first study addressing and characterizing palliative care needs in this population.

Nonalcoholic fatty liver disease (NAFLD) is becoming the most frequent chronic liver disease worldwide. Metabolic (dysfunction) associated fatty liver disease (MAFLD) is suggested to replace the nomenclature of NAFLD. For individuals with metabolic dysfunction, multiple NAFLD-related factors also contribute to the development and progression of MAFLD including genetics and epigenetics. The application of genome-wide association study (GWAS) and exome-wide association study (EWAS) uncovers single-nucleotide polymorphisms (SNPs) in MAFLD. In addition to the classic SNPs in PNPLA3, TM6SF2, and GCKR, some new SNPs have been found recently to contribute to the pathogenesis of liver steatosis. Epigenetic factors involving DNA methylation, histone modifications, non-coding RNAs regulations, and RNA methylation also play a critical role in MAFLD. DNA methylation is the most reported epigenetic modification. Developing a non-invasion biomarker to distinguish metabolic steatohepatitis (MASH) or liver fibrosis is ongoing. In this review, we summarized and discussed the latest progress in genetic and epigenetic factors of NAFLD/MAFLD, in order to provide potential clues for MAFLD treatment.

Cardiovascular disease is the leading cause of death worldwide; however, women tend to be less affected than men during their reproductive years. The female cardiovascular risk increases significantly around the time of the menopausal transition. The loss of the protective action of ovarian oestrogens and the circulating androgens has been implicated in possibly inducing subclinical and overt changes in the cardiovascular system after the menopausal transition. In vitro studies performed in human or animal cell lines demonstrate an adverse effect of testosterone on endothelial cell function and nitric oxide bioavailability. Cohort studies evaluating associations between testosterone and/or dehydroepiandrosterone and subclinical vascular disease and clinical cardiovascular events show an increased risk for women with more pronounced androgenicity. However, a mediating effect of insulin resistance is possible. Data on cardiovascular implications following low-dose testosterone treatment in middle-aged women or high-dose testosterone supplementation for gender affirmatory purposes remain primarily inconsistent. It is prudent to consider the possible adverse association between testosterone and endothelial function during the decision-making process of the most appropriate treatment for a postmenopausal woman.

Context: Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age, and metformin is a widely used medication in managing this condition.

Aim: To review the available literature comprehensively on the therapeutic impact of metformin on the clinical and metabolic parameters of women with PCOS.

Data source: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science and selected sources for grey literature from their inception to April 2020. An updated search in PubMed was performed in June 2022.

Data synthesis: Two reviewers selected eligible studies and extracted data, and the review is reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Results: In 24 eligible randomised controlled trials (RCTs) involving 564 participants who received metformin therapy, metformin was associated with significant reduction in body weight by 3.13 kg (95% CI: -5.33, -0.93), body mass index (BMI) by 0.82 kg/m² (95% CI: -1.22, -0.41), fasting blood glucose [standardised mean difference (SMD): -0.23; 95% CI: -0.40, -0.06], low-density lipoprotein cholesterol (LDL-C) (SMD: -0.41; 95% CI: -0.85, 0.03), total testosterone (SMD: -0.33; 95% CI: -0.49, -0.17), androstenedione (SMD: -0.45; 95% CI: -0.70, -0.20), 17-hydroxyprogesterone (17-OHP) (SMD: -0.58; 95% CI: -1.16, 0.00) and increase the likelihood of clinical pregnancy rate [odds ratio (OR): 3.00; 95% CI: 1.95, 4.59] compared with placebo.

Conclusion: In women with PCOS, metformin use has shown a positive impact in reducing body weight, BMI, total testosterone, androstenedione, 17-OHP, LDL-C, fasting blood glucose and increasing the likelihood of pregnancy in women with PCOS.

This study seeks to evaluate the effects of a reversal of sedentary lifestyles on the improvement of metabolic profiles in patients with NAFLD. The PubMed, Cochrane Library, Web of Science, and CNKI databases were searched up to May 15, 2021. Ten randomized controlled trials on changes in the sedentary lifestyle of patients with NAFLD were included in the analysis. Data from self-controlled case arms of randomized controlled trials investigating sedentary lifestyle alterations were extracted, and the effect size was reported as the MD and 95% CI. A total of 455 participants in 10 studies met the selection criteria. The results showed that changing a sedentary lifestyle can significantly improve ALT [MD = 4.35 (U/L), 95% CI: 0.53, 8.17], CHOL [MD = 0.31 (mmol/L), 95% CI: 0.19, 0.43], TG [MD = 0.22 (mmol/L), 95% CI: 0.10~0.34], LDL-C [MD = 0.30 (mmol/L), 95% CI: 0.02, 0.57], fasting blood glucose [MD = 0.17 (mmol/L), 95% CI: 0.03, 0.31], insulin [MD = 3.23 (pmol/L), 95% CI: 1.37~5.08], and HOMA-IR levels (MD = 0.39, 95% CI: 0.15, 0.63). Changing sedentary lifestyle can also significantly improve body mass index (BMI) [MD = 1.12 (kg/m²), 95% CI: 0.66, 0.58], body fat (%) [MD = 0.34 (%), 95% CI: 0.13, 0.55] and VO_2peak levels [MD = -4.00 (mL/kg/min), 95% CI: -5.93, -2.06]. No differences in AST or GGT were noted before or after lifestyle changes. Altering a sedentary lifestyle to a lifestyle with regular exercise can slightly improve the levels of liver enzymes, blood lipids, blood glucose, insulin resistance, and body mass index in NAFLD patients.

Background and purpose: With the progressive increase in the prevalence of type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN) - one of the most common chronic microvascular complications - has evolved into a significant cause of death worldwide among end-stage renal disease patients. Academic researchers have for decades focused on the development of DN and recently found that free fatty acids (FFAs) constituted an independent risk factor for vascular complications in T2DM patients. It is therefore critical to determine whether the metabolic profile of FFAs is related to DN.

Methods: This study comprised 611 research subjects in Dalian, a city in northeast China: 52 DN patients, 115 T2DM patients, and 444 healthy controls. We determined 15 forms of serum FFAs, including arachidonic acid (AA, C20:4), docosahexaenoic acid (DHA, C22:6), erucic acid (C22:1), nervonic acid (NA, C24:1), estimated total omega-3s, total omega-6s, the omega-3/omega-6 ratio, and total FFA content by liquid chromatography-mass spectrometry (LC-MS).

Results: The levels of NA (mean = 45.27, range = 0.84-76.57) and DHA (mean = 324.58, range = 205.38-450.03) in DN patients were slightly lower than those in T2DM patients or healthy controls. The serum omega-3 polyunsaturated fatty acid (PUFA) DHA (C22:6) was significantly negatively correlated with microalbuminuria (MAU), the albumin/creatinine ratio (ACR), body mass index (BMI), fasting plasma glucose (FPG), and glycosylated hemoglobin (HbA1c). The serum monounsaturated fatty acid (MUFA) NA (C24:1) was significantly negatively correlated with BMI, FPG, and HbA1c. After adjustment of variables, multiple logistic regression analysis revealed significant odds ratios (ORs) [with confidence intervals (CIs)] for DHA (0.991, 0.985-0.997; p = 0.002) and NA (0.978, 0.958-0.999; p = 0.037).

Conclusion: In this study, we ascertained that the contents of NA and DHA in patients with DN were relatively low, and that DHA was negatively correlated with MAU and the ACR. However, large-scale, population-based studies focusing on the role of NA and DHA in the pathogenesis of DN are still required in the future.