Sexual Dimorphic Regulation of Body Weight Dynamics and Adipose Tissue Lipolysis

BACKGROUND: Successful reduction of body weight (BW) is often followed by recidivism to obesity. BW-changes including BW-loss and -regain is associated with marked alterations in energy expenditure (EE) and adipose tissue (AT) metabolism. Since these processes are sex-specifically controlled, we investigated sexual dimorphisms in metabolic processes during BW-dynamics (gain-loss-regain). RESEARCH DESIGN: Obesity was induced in C57BL/6J male (m) and female (f) mice by 15 weeks high-fat diet (HFD) feeding. Subsequently BW was reduced (-20%) by caloric restriction (CR) followed by adaptive feeding, and a regain-phase. Measurement of EE, body composition, blood/organ sampling were performed after each feeding period. Lipolysis was analyzed ex-vivo in gonadal AT. RESULTS: Male mice exhibited accelerated BW-gain compared to females (relative BW-gain m:140.5±3.2%; f:103.7±6.5%; p<0.001). In consonance, lean mass-specific EE was significantly higher in females compared to males during BW-gain. Under CR female mice reached their target-BW significantly faster than male mice (m:12.2 days; f:7.6 days; p<0.001) accompanied by a sustained sex-difference in EE. In addition, female mice predominantly downsized gonadal AT whereas the relation between gonadal and total body fat was not altered in males. Accordingly, only females exhibited an increased rate of forskolin-stimulated lipolysis in AT associated with significantly higher glycerol concentrations, lower RER-values, and increased AT expression of adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). Analysis of AT lipolysis in estrogen receptor alpha (ERα)-deficient mice revealed a reduced lipolytic rate in the absence of ERα exclusively in females. Finally, re-feeding caused BW-regain faster in males than in females. CONCLUSION: The present study shows sex-specific dynamics during BW-gain-loss-regain. Female mice responded to CR with an increase in lipolytic activity, and augmented lipid-oxidation leading to more efficient weight loss. These processes likely involve ERα-dependent signaling in AT and sexual dimorphic regulation of genes involved in lipid metabolism

Ratio of fat to energy intake independently associated with the duration of diabetes and total cholesterol levels in type 2 diabetes

The importance of dietary intake in the treatment of type 2 diabetes was emphasized. This study was performed to investigate the dietary intakes of Korean type 2 diabetes patients according to the treatment and duration of diabetes and to examine the relationships between their diet and serum lipid profiles. The subjects were 111 type 2 diabetic patients who were treated by medical nutrition therapy only, oral hypoglycemic agents (OHA), or insulin with medical nutrition therapy. Dietary intake was assessed by a registered dietitian using semi-quantitative food frequency questionnaires. Comparisons according to treatment type were made using covariance analyses. General linear models identified the independent effects of the different treatments after covarying for age, duration of diabetes, and 2-way interactions. There were no significant differences in age and BMI but was in duration of diabetes according to treatment type in these subjects. Carbohydrate to energy ratio was higher in the OHA group (P < 0.05), whereas the fat to energy ratio was higher in the insulin group for males (P < 0.05). Carbohydrate (R2 = 0.24, P = 0.005) and fat (R2 = 0.26, P = 0.02) to energy ratios were independently associated with the duration of diabetes after covarying for age, sex, treatment, and 2-way interactions. The levels of triglyceride (TG; R2 = 0.32, P = 0.02) and total cholesterol (TC) were associated independently with energy intake and the carbohydrate (R2 = 0.15, P = 0.02) and fat (R2 = 0.15, P = 0.01) to energy ratios, respectively. The concern that the independent association of dietary intake with either duration of diabetes or dietary factors affects blood lipid levels could suggest that specific dietary recommendations may work better for identifiable groups of diabetes patients

Diabetes MILES – The Netherlands: rationale, design and sample characteristics of a national survey examining the psychosocial aspects of living with diabetes in Dutch adults

Background : As the number of people with diabetes is increasing rapidly worldwide, a more thorough understanding of the psychosocial aspects of living with this condition has become an important health care priority. While our knowledge has grown substantially over the past two decades with respect to the physical, emotional and social difficulties that people with diabetes may encounter, many important issues remain to be elucidated. Under the umbrella of the Diabetes MILES (Management and Impact for Long-term Empowerment and Success) Study International Collaborative, Diabetes MILES &ndash; The Netherlands aims to examine how Dutch adults with diabetes manage their condition and how it affects their lives. Topics of special interest in Diabetes MILES - The Netherlands include subtypes of depression, Type D personality, mindfulness, sleep and sexual functioning. Methods/design : Diabetes MILES &ndash; The Netherlands was designed as a national online observational study among adults with diabetes. In addition to a main set of self-report measures, the survey consisted of five complementary modules to which participants were allocated randomly. From September to October 2011, a total of 3,960 individuals with diabetes (40% type 1, 53% type 2) completed the battery of questionnaires covering a broad range of topics, including general health, self-management, emotional well-being and contact with health care providers. People with self-reported type 1 diabetes (specifically those on insulin pump therapy) were over-represented, as were those using insulin among respondents with self-reported type 2 diabetes. People from ethnic minorities were under-represented. The sex distribution was fairly equal in the total sample, participants spanned a broad age range (19&ndash;90 years), and diabetes duration ranged from recent diagnosis to living with the condition for over fifty years. Discussion : The Diabetes MILES Study enables detailed investigation of the psychosocial aspects of living with diabetes and an opportunity to put these findings in an international context. With several papers planned resulting from a pooled Australian-Dutch dataset and data collections planned in other countries, the Diabetes MILES Study International Collaborative will contribute substantially to identifying potentially unmet needs of those living with diabetes and to inform clinical research and care across the globe. <br /

Advancing Research on Racial–Ethnic Health Disparities: Improving Measurement Equivalence in Studies with Diverse Samples

To conduct meaningful, epidemiologic research on racial–ethnic health disparities, racial–ethnic samples must be rendered equivalent on other social status and contextual variables via statistical controls of those extraneous factors. The racial–ethnic groups must also be equally familiar with and have similar responses to the methods and measures used to collect health data, must have equal opportunity to participate in the research, and must be equally representative of their respective populations. In the absence of such measurement equivalence, studies of racial–ethnic health disparities are confounded by a plethora of unmeasured, uncontrolled correlates of race–ethnicity. Those correlates render the samples, methods, and measures incomparable across racial–ethnic groups, and diminish the ability to attribute health differences discovered to race–ethnicity vs. to its correlates. This paper reviews the non-equivalent yet normative samples, methodologies and measures used in epidemiologic studies of racial–ethnic health disparities, and provides concrete suggestions for improving sample, method, and scalar measurement equivalence

A time-resolved proteomic and prognostic map of COVID-19

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Measurement of associated W plus charm production in pp collisions at √s=7 TeV

Peer reviewe

[Schleiermacher, Friedrich]

http://tartu.ester.ee/record=b1964949~S1*es