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Role of sex and gender-related variables in development of metabolic syndrome: A prospective cohort study.
Alipour, P, Azizi, Z, Raparelli, V, Norris, CM, Kautzky-Willer, A, Kublickiene, K, Herrero, MT, Emam, KE, Vollenweider, P, Preisig, M, et al
European journal of internal medicine. 2024;:63-75
Abstract
INTRODUCTION The burden of metabolic syndrome (MetS) and its components has been increasing mainly amongst male individuals. Nevertheless, clinical outcomes related to MetS (i.e., cardiovascular diseases), are worse among female individuals. Whether these sex differences in the components and sequalae of MetS are influenced by gender (i.e., psycho-socio-cultural factors)) is a matter of debate. Therefore, the purpose of this study was to determine the association between gender-related factors and the development of MetS, and to assess if the magnitude of the associations vary by sex. METHOD Data from the Colaus/PsyColaus study, a prospective population-based cohort of 6,734 middle-aged participants in Lausanne (Switzerland) (2003-2006) were used. The primary endpoint was the development of MetS as defined by the Adult Treatment Panel III of the National Cholesterol Education Program. Multivariable models were estimated using logistic regression to assess the association between gender-related factors and the development of MetS. Two-way interactions between sex, age and gender-related factors were also tested. RESULTS Among 5,195 participants without MetS (mean age=51.3 ± 10.6, 56.1 % females), 27.9 % developed MetS during a mean follow-up of 10.9 years. Female sex (OR:0.48, 95 %CI:0.41-0.55) was associated with decreased risk of developing MetS. Conversely, older age, educational attainment less than university, and low income were associated with an increased risk of developing MetS. Statistically significant interaction between sex and strata of age, education, income, smoking, and employment were identified showing that the reduced risk of MetS in female individuals was attenuated in the lowest education, income, and advanced age strata. However, females who smoke and reported being employed demonstrated a decreased risk of MetS compared to males. Conversely smoking and unemployment were significant risk factors for MetS development among male adults. CONCLUSIONS Gender-related factors such as income level and educational attainment play a greater role in the development of MetS in female than individuals. These factors represent novel modifiable targets for implementation of sex- and gender-specific strategies to achieve health equity for all people.
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Correlation between skeletal muscle acetylcarnitine and phosphocreatine metabolism during submaximal exercise and recovery: interleaved 1H/31P MRS 7 T study.
Klepochová, R, Niess, F, Meyerspeer, M, Slukova, D, Just, I, Trattnig, S, Ukropec, J, Ukropcová, B, Kautzky-Willer, A, Leutner, M, et al
Scientific reports. 2024;(1):3254
Abstract
Acetylcarnitine is an essential metabolite for maintaining metabolic flexibility and glucose homeostasis. The in vivo behavior of muscle acetylcarnitine content during exercise has not been shown with magnetic resonance spectroscopy. Therefore, this study aimed to explore the behavior of skeletal muscle acetylcarnitine during rest, plantar flexion exercise, and recovery in the human gastrocnemius muscle under aerobic conditions. Ten lean volunteers and nine overweight volunteers participated in the study. A 7 T whole-body MR system with a double-tuned surface coil was used to acquire spectra from the gastrocnemius medialis. An MR-compatible ergometer was used for the plantar flexion exercise. Semi-LASER-localized 1H MR spectra and slab-localized 31P MR spectra were acquired simultaneously in one interleaved exercise/recovery session. The time-resolved interleaved 1H/31P MRS acquisition yielded excellent data quality. A between-group difference in acetylcarnitine metabolism over time was detected. Significantly slower τPCr recovery, τPCr on-kinetics, and lower Qmax in the overweight group, compared to the lean group was found. Linear relations between τPCr on-kinetics, τPCr recovery, VO2max and acetylcarnitine content were identified. In conclusion, we are the first to show in vivo changes of skeletal muscle acetylcarnitine during acute exercise and immediate exercise recovery with a submaximal aerobic workload using interleaved 1H/31P MRS at 7 T.
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Insulin degludec versus insulin detemir, both in combination with insulin aspart, in the treatment of pregnant women with type 1 diabetes (EXPECT): an open‑label, multinational, randomised, controlled, non-inferiority trial.
Mathiesen, ER, Alibegovic, AC, Corcoy, R, Dunne, F, Feig, DS, Hod, M, Jia, T, Kalyanam, B, Kar, S, Kautzky-Willer, A, et al
The lancet. Diabetes & endocrinology. 2023;(2):86-95
Abstract
BACKGROUND Insulin degludec (degludec) is a second-generation basal insulin with an improved pharmacokinetic-pharmacodynamic profile compared with first-generation basal insulins, but there are few data regarding its use during pregnancy. In this non-inferiority trial, we aimed to compare the efficacy and safety of degludec with insulin detemir (detemir), both in combination with insulin aspart (aspart), in pregnant women with type 1 diabetes. METHODS This open-label, multinational, randomised, controlled, non-inferiority trial (EXPECT) was conducted at 56 sites (hospitals and medical centres) in 14 countries. Women aged at least 18 years with type 1 diabetes who were between gestational age 8 weeks (+0 days) and 13 weeks (+6 days) or planned to become pregnant were randomly assigned (1:1), via an interactive web response system, to degludec (100 U/mL) once daily or detemir (100 U/mL) once or twice daily, both with mealtime insulin aspart (100 U/mL), all via subcutaneous injection. Participants who were pregnant received the trial drug at randomisation, throughout pregnancy and until 28 days post-delivery (end of treatment). Participants not pregnant at randomisation initiated the trial drug before conception. The primary endpoint was the last planned HbA1c measurement before delivery (non-inferiority margin of 0·4% for degludec vs detemir). Secondary endpoints included efficacy, maternal safety, and pregnancy outcomes. The primary endpoint was assessed in all randomly assigned participants who were pregnant during the trial. Safety was assessed in all randomly assigned participants who were pregnant during the trial and exposed to at least one dose of trial drug. This study is registered with ClinicalTrials.gov, NCT03377699, and is now completed. FINDINGS Between Nov 22, 2017, and Nov 8, 2019, from 296 women screened, 225 women were randomly assigned to degludec (n=111) or detemir (n=114). Mean HbA1c at pregnancy baseline was 6·6% (SD 0·6%; approximately 49 mmol/mol; SD 7 mmol/mol) in the degludec group and 6·5% (0·8%; approximately 48 mmol/mol; 9 mmol/mol) in the detemir group. Mean last planned HbA1c measurement before delivery was 6·2% (SE 0·07%; approximately 45 mmol/mol; SE 0·8 mmol/mol) in the degludec group and 6·3% (SE 0·07%; approximately 46 mmol/mol; SE 0·8 mmol/mol) in the detemir group (estimated treatment difference -0·11% [95% CI -0·31 to 0·08]; -1·2 mmol/mol [95% CI: -3·4 to 0·9]; pnon-inferiority<0·0001), confirming non-inferiority. Compared with detemir, no additional safety issues were observed with degludec. INTERPRETATION In pregnant women with type 1 diabetes, degludec was found to be non-inferior to detemir. FUNDING Novo Nordisk.
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Magnesium in Kidney Function and Disease-Implications for Aging and Sex-A Narrative Review.
Macías Ruiz, MDC, Cuenca Bermejo, L, Veronese, N, Fernández Villalba, E, González Cuello, AM, Kublickiene, K, Raparelli, V, Norris, CM, Kautzky-Willer, A, Pilote, L, et al
Nutrients. 2023;(7)
Abstract
Magnesium (Mg) has a vital role in the human body, and the kidney is a key organ in the metabolism and excretion of this cation. The objective of this work is to compile the available evidence regarding the role that Mg plays in health and disease, with a special focus on the elderly population with chronic kidney disease (CKD) and the eventual sex differences. A narrative review was carried out by executing an exhaustive search in the PubMed, Scopus, and Cochrane databases. Ten studies were found in which the role of Mg and sex was evaluated in elderly patients with CKD in the last 10 years (2012-2022). The progression of CKD leads to alterations in mineral metabolism, which worsen as the disease progresses. Mg can be used as a coadjuvant in the treatment of CKD patients to improve glomerular filtration, but its use in clinical applications needs to be further characterized. In conclusion, there's a need for well-designed prospective clinical trials to advise and standardize Mg supplementation in daily clinical practice, taking age and sex into consideration.
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Vitamin D3 Supplementation in Overweight/Obese Pregnant Women: No Effects on the Maternal or Fetal Lipid Profile and Body Fat Distribution-A Secondary Analysis of the Multicentric, Randomized, Controlled Vitamin D and Lifestyle for Gestational Diabetes Prevention Trial (DALI).
Harreiter, J, Mendoza, LC, Simmons, D, Desoye, G, Devlieger, R, Galjaard, S, Damm, P, Mathiesen, ER, Jensen, DM, Andersen, LLT, et al
Nutrients. 2022;14(18)
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Plain language summary
Vitamin D is an important fat-soluble vitamin with steroid hormone function. It is predominately known for its essential role in calcium homeostasis and bone mineralisation. The aim of this study was to assess the effects of a vitamin D supplementation with 1600 IU Vitamin D3 per day starting in early pregnancy versus placebo on maternal and foetal lipid parameters, body fat distribution as well as pregnancy outcomes. This study is a secondary analysis of the vitamin D And LIfestyle for gestational diabetes prevention trial (DALI) Vitamin D study, including overweight/obese pregnant women with normal glucose tolerance at randomization before 20 weeks’ gestation. Results show a significant increase of maternal vitamin D levels throughout pregnancy and in cord blood in the supplementation group compared with the placebo group. However, there weren’t any significant differences between the treatment arms in maternal lipid parameters nor in foetal lipid parameters or birth outcomes. Authors conclude that daily vitamin D3 supplementation in overweight/obese pregnant women with high levels of vitamin D sufficiency does not improve maternal or foetal lipid parameters, body fat distribution or pregnancy outcomes and should not be used in pregnancy for these indications.
Abstract
Vitamin D deficiency is a common finding in overweight/obese pregnant women and is associated with increased risk for adverse pregnancy outcome. Both maternal vitamin D deficiency and maternal obesity contribute to metabolic derangements in pregnancy. We aimed to assess the effects of vitamin D3 supplementation in pregnancy versus placebo on maternal and fetal lipids. Main inclusion criteria were: women <20 weeks' gestation, BMI ≥ 29 kg/m2. Eligible women (n = 154) were randomized to receive vitamin D3 (1600 IU/day) or placebo. Assessments were performed <20, 24-28 and 35-37 weeks and at birth. Linear regression models were used to assess effects of vitamin D on maternal and cord blood lipids. In the vitamin D group significantly higher total 25-OHD and 25-OHD3 levels were found in maternal and cord blood compared with placebo. Adjusted regression models did not reveal any differences in triglycerides, LDL-C, HDL-C, free fatty acids, ketone bodies or leptin between groups. Neonatal sum of skinfolds was comparable between the two groups, but correlated positively with cord blood 25-OH-D3 (r = 0.34, p = 0.012). Vitamin D supplementation in pregnancy increases maternal and cord blood vitamin D significantly resulting in high rates of vitamin D sufficiency. Maternal and cord blood lipid parameters were unaffected by Vitamin D3 supplementation.
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The Weak Relationship between Vitamin D Compounds and Glucose Homeostasis Measures in Pregnant Women with Obesity: An Exploratory Sub-Analysis of the DALI Study.
Mendoza, LC, Harreiter, J, Desoye, G, Simmons, D, Adelantado, JM, Kautzky-Willer, A, Zawiejska, A, Wender-Ozegowska, E, Lapolla, A, Dalfra, MG, et al
Nutrients. 2022;(16)
Abstract
Studies on the relationship between vitamin D (VitD) and glucose homeostasis usually consider either total VitD or 25OHD3 but not 25OHD2 and epimers. We aimed to evaluate the cross-sectional association of VitD compounds with glucose homeostasis measurements in pregnant women with overweight/obesity participating in the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention study. Methods: The analysis included 912 women. Inclusion criteria: <20 weeks gestation, body mass index ≥29 kg/m2 and information on exposure and outcome variables at baseline. Measurements: A 75 g OGTT at <20, 24−28 and 35−37 weeks gestation (except if previous diabetes diagnosis). Exposure variables: 25OHD2, 25OHD3 and C3-epimer. Outcome variables: fasting and post-challenge insulin sensitivity and secretion indices, corresponding disposition indices (DI), plasma glucose at fasting and 1 and 2 h, hyperglycemia in pregnancy (HiP). Statistics: Multivariate regression analyses with adjustment. Results: Baseline VitD sufficiency was 66.3%. Overall, VitD compounds did not show strong associations with any glucose homeostasis measures. 25OHD3 showed direct significant associations with: FPG at <20 and 24−28 weeks (standardized β coefficient (β) 0.124, p = 0.030 and 0.111, p = 0.026 respectively), 2 h plasma glucose at 24−28 weeks (β 0.120, p = 0.018), and insulin sensitivity (1/HOMA-IR, β 0.127, p = 0.027) at 35−37 weeks; it showed an inverse association with fasting DI (QUCKI*HOMA-β) at <20 and 24−28 weeks (β −0.124, p = 0.045 and β −0.148, p = 0.004 respectively). 25OHD2 showed direct associations with post-challenge insulin sensitivity (Matsuda, β 0.149, p = 0.048) at 24−28 weeks) and post-challenge DI (Matsuda*Stumvoll phase 1) at 24−28 and 35−37 weeks (β 0.168, p = 0.030, β 0.239, p = 0.006). No significant association with C3-epimer was observed at any time period. Conclusions: In these women with average baseline VitD in sufficiency range, VitD compounds did not show clear beneficial associations with glucose homeostasis measures.
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The unexplored role of sedentary time and physical activity in glucose and lipid metabolism-related placental mRNAs in pregnant women who are obese: the DALI lifestyle randomised controlled trial.
Acosta-Manzano, P, Leopold-Posch, B, Simmons, D, Devlieger, R, Galjaard, S, Corcoy, R, Adelantado, JM, Dunne, F, Harreiter, J, Kautzky-Willer, A, et al
BJOG : an international journal of obstetrics and gynaecology. 2022;(5):708-721
Abstract
OBJECTIVE We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. DESIGN Multicentre randomised controlled trial. SETTING Hospitals in nine European countries. POPULATION A cohort of 112 pregnant women with placental tissue. METHODS Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. MAIN OUTCOME MEASURES Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. RESULTS Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin-glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P < 0.05). CONCLUSIONS In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. TWEETABLE ABSTRACT Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese.
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Evaluation of a Bariatric Monitoring Pass for Primary Care Physicians.
Ranzenberger-Haider, T, Meyer, EL, Stamm, T, Dreschl, B, Itariu, B, Prager, G, Stangl, A, Kautzky-Willer, A, Schindler, K, Krebs, M
Obesity facts. 2022;(5):629-637
Abstract
INTRODUCTION There are a growing number of patients undergoing bariatric surgery requiring lifelong follow-up. Therefore, follow-up care can no longer be covered by specialized outpatient clinics alone due to the sharp rise in the number of bariatric patients. Bariatric Patients in Primary Care: Postoperative Nutrition and Lifestyle Management (BagEL) is a survey to evaluate a newly developed structured disease management program including nutrition and lifestyle management in primary care. METHODS The study is conceived as a randomized cohort study with a control group. An expert questionnaire for general practitioners (GPs) was developed to assess the usability of a structured postoperative care system regarding nutrition and lifestyle management for bariatric patients in primary care. A structured follow-up program in primary care with a so-called bariatric monitoring passport (BMP) was provided for patients in the intervention (INT) group and the existing information sheet "Metabolic surgery and perioperative care" for the control (CON) group. 124 patients, who met inclusion criteria and who underwent a bariatric procedure first time, served as ambassadors for delivery of the expert questionnaire and study documents to their individual GPs. RESULTS A total of 39 (31.5%) different GPs from 124 ambassador patients responded. For the primary outcome "Does the aftercare-booklets support treatment of bariatric patients?" GPs of the INT group rated the new designed aftercare booklet (INT) significantly more helpful for treating bariatric patients than the one from the CON group (p = 0.041). DISCUSSION/CONCLUSION These results suggest that GPs are welcoming supportive tools like our BMP to improve the care of long-term follow-up of bariatric patients and should actively participate in the development of lifelong disease management plans necessary to cope with the rapidly growing number of patients.
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Characterization of endogenous bile acid composition in individuals with cold-activated brown adipose tissue.
Herz, CT, Kulterer, OC, Prager, M, Langer, FB, Prager, G, Marculescu, R, Fauler, G, Hacker, M, Kautzky-Willer, A, Trauner, M, et al
Molecular and cellular endocrinology. 2021;:111403
Abstract
INTRODUCTION Bile acid signaling has been suggested to promote BAT activity in various experimental models. However, little is known if and how physiologic bile acid metabolism is linked to BAT function in humans. Here we investigated the association between BAT activity and circulating bile acid concentrations in lean and obese individuals. METHODS BAT 18F-fluorodeoxyglucose uptake was measured after a standardized cooling protocol by positron emission tomography/computed tomography. Cold-induced thermogenesis was assessed by indirect calorimetry. Fasting bile acid concentrations were determined by high performance liquid chromatography-high-resolution mass spectrometry. RESULTS In a cohort of 24 BAT-negative and 20 BAT-positive individuals matched by age, sex, and body mass index, circulating bile acid levels were similar between groups except for higher ursodeoxycholic acid and a trend towards a lower 12α-OH/non-12α-OH bile acid ratio in lean participants with active BAT compared to those without. Moreover, the 12α-OH/non-12α-OH ratio, a marker of CYP8B1 activity, correlated negatively with BAT volume and activity. CONCLUSION Fasting concentrations of major bile acids are not associated with cold-induced BAT activity in humans. However, the inverse association between BAT activity and 12α-OH/non-12α-OH ratio may suggest CYP8B1 as a potential new target in BAT function and warrants additional investigation.
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Positioning sulphonylureas in a modern treatment algorithm for patients with type 2 diabetes: Expert opinion from a European consensus panel.
Consoli, A, Czupryniak, L, Duarte, R, Jermendy, G, Kautzky-Willer, A, Mathieu, C, Melo, M, Mosenzon, O, Nobels, F, Papanas, N, et al
Diabetes, obesity & metabolism. 2020;(10):1705-1713
Abstract
The large number of pharmacological agents available to treat type 2 diabetes (T2D) makes choosing the optimal drug for any given patient a complex task. Because newer agents offer several advantages, whether and when sulphonylureas (SUs) should still be used to treat T2D is controversial. Published treatment guidelines and recommendations should govern the general approach to diabetes management. However, expert opinions can aid in better understanding local practices and in formulating individual choices. The current consensus paper aims to provide additional guidance on the use of SUs in T2D. We summarize current local treatment guidelines in European countries, showing that SUs are still widely proposed as second-line treatment after metformin and are often ranked at the same level as newer glucose-lowering medications. Strong evidence now shows that sodium-glucose co-transporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with low hypoglycaemia risk, promote weight loss, and exert a positive impact on vascular, cardiac and renal endpoints. Thus, using SUs in place of SGLT-2is and GLP-1RAs may deprive patients of key advantages and potentially important cardiorenal benefits. In subjects with ascertained cardiovascular disease or at very high cardiovascular risk, SGLT-2is and/or GLP-1RAs should be used as part of diabetes management, in the absence of contraindications. Routine utilization of SUs as second-line agents continues to be acceptable in resource-constrained settings.