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AIM: To assess the effect of tirzepatide on long-term risk of atherosclerotic cardiovascular disease (ASCVD) among people with obesity or overweight without diabetes from SURMOUNT-1. MATERIALS AND METHODS: SURMOUNT-1, a phase 3 trial, evaluated the efficacy and safety of tirzepatide in adults with body mass index ≥30 or ≥27 kg/m2 and at least one weight-related complication, excluding diabetes. Participants were randomly assigned to tirzepatide (5/10/15 mg) or placebo. Changes from baseline in cardiometabolic variables were assessed. The predicted 10-year ASCVD risk scores were calculated (American College of Cardiology/American Heart Association risk engine) at baseline, week 24, and week 72 in SURMOUNT-1 participants without a history of ASCVD. Percent change in risk scores from baseline to weeks 24 and 72 was compared between tirzepatide and placebo using mixed model for repeated measures analysis. Analyses were also conducted in participants with intermediate to high risk at baseline. RESULTS: Tirzepatide-treated groups demonstrated reductions in cardiometabolic variables over 72 weeks. In participants without a history of ASCVD (N = 2461), the baseline median risk score was low and did not differ across groups (1.5%-1.6%). Relative change in risk from baseline to week 72 was greater for tirzepatide (-23.5% to -16.4%) than placebo (12.7%; P < 0.001). Relative change among participants with intermediate-to-high baseline risk was significantly greater for tirzepatide (P < 0.05). Intermediate-to-high-risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population. CONCLUSION: Tirzepatide treatment significantly reduced the 10-year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes.
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Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Adulto , Humanos , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes , Obesidade/complicações , Obesidade/tratamento farmacológico , Sobrepeso/complicações , Sobrepeso/tratamento farmacológicoRESUMO
RESEARCH QUESTION: Are gravidity, parity and breastfeeding history associated with anti-Müllerian hormone concentration among African-American women of reproductive age? DESIGN: This study included baseline data from the Study of the Environment, Lifestyle and Fibroids, a 5-year longitudinal study of African-American women. Within this community cohort, data from 1392 women aged 25-35 years were analysed. The primary outcome was serum anti-Müllerian hormone concentration measured using the Ansh Labs picoAMH assay, an enzyme-linked immunosorbent assay. Multivariable linear regression models were used to estimate mean differences in anti-Müllerian hormone concentration (ß) and 95% CI by self-reported gravidity, parity and breastfeeding history, with adjustment for potential confounders. RESULTS: Of the 1392 participants, 1063 had a history of gravidity (76.4%). Of these, 891 (83.8%) were parous and 564 had breastfed. Multivariable-adjusted regression analyses found no appreciable difference in anti-Müllerian hormone concentration between nulligravid participants and those with a history of gravidity (ßâ¯=â¯-0.025, 95% CI -0.145 to 0.094). Among participants with a history of gravidity, there was little difference in anti-Müllerian hormone concentration between parous and nulliparous participants (ßâ¯=â¯0.085, 95% CI -0.062 to 0.232). There was also little association between anti-Müllerian hormone concentration and breastfeeding history (ever versus never: ßâ¯=â¯0.009, 95% CI -0.093 to 0.111) or duration of breastfeeding (per 1-month increase: ßâ¯=â¯-0.002, 95% CI -0.010 to 0.006). CONCLUSIONS: Gravidity, parity and breastfeeding history were not meaningfully associated with anti-Müllerian hormone concentration in this large sample of the Study of the Environment, Lifestyle and Fibroids cohort.
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Hormônio Antimülleriano , Aleitamento Materno , Feminino , Humanos , Gravidez , Hormônio Antimülleriano/sangue , Negro ou Afro-Americano , Estudos Longitudinais , AdultoRESUMO
AIM: We assessed the impact of tirzepatide on 10-year predicted risk of developing type 2 diabetes (T2D) among participants in the SURMOUNT-1 trial. MATERIALS AND METHODS: In this post hoc analysis of SURMOUNT-1, the Cardiometabolic Disease Staging risk engine was used to calculate the 10-year predicted risk of T2D at baseline, week 24 and week 72 among participants randomized to receive 5, 10, or 15 mg tirzepatide or placebo. Mean changes in risk scores from baseline to weeks 24 and 72 were compared between tirzepatide and placebo groups. Subgroup analyses were conducted based on participants' glycaemic status and body mass index at baseline. RESULTS: Mean baseline T2D predicted risk scores did not differ between tirzepatide and placebo groups (range: 22.9%-24.3%). At week 72, mean absolute T2D predicted risk score reductions were significantly greater in tirzepatide groups (5 mg, 12.4%; 10 mg, 14.4%; 15 mg, 14.7%) versus placebo (0.7%). At week 72, median relative predicted risk reductions following tirzepatide treatment ranged from 60.3% to 69.0%. For participants with and without prediabetes, risk reductions were significantly greater in tirzepatide groups versus placebo. At week 72, participants with prediabetes (range: 16.0%-20.3%) had greater mean risk score reductions from baseline versus those without prediabetes (range: 10.1%-11.3%). Across body mass index subgroups, mean reductions from baseline were significantly greater in tirzepatide groups versus placebo. CONCLUSION: Tirzepatide treatment significantly reduced the 10-year predicted risk of developing T2D compared with placebo in participants with obesity or overweight, regardless of baseline glycaemic status.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Estado Pré-Diabético/tratamento farmacológico , Obesidade/complicações , Obesidade/tratamento farmacológico , Hipoglicemiantes/uso terapêuticoRESUMO
BACKGROUND: Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS: We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS: A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS: Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.).
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Colecalciferol/uso terapêutico , Diabetes Mellitus Tipo 2/prevenção & controle , Suplementos Nutricionais , Estado Pré-Diabético/tratamento farmacológico , Vitaminas/uso terapêutico , Administração Oral , Idoso , Colecalciferol/administração & dosagem , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Fatores de Risco , Falha de Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitaminas/administração & dosagemRESUMO
BACKGROUND: Uterine leiomyomas, commonly known as fibroids, are benign tumors in postmenarchal females. By the age of 35 years, approximately 30% of females will have fibroids, and by the age of 50 years, the prevalence approaches 70% with some studies reporting >85% prevalence in African American females. Previous studies evaluating the prevalence of fibroids have largely relied on self-reported fibroid diagnoses, which could have falsely underestimated prevalence because many females with fibroids are asymptomatic. Despite known differences in fibroid prevalence by race, there are very limited data on fibroid prevalence by ethnicity. The Latino population is the largest ethnic minority in the United States, yet there is no large study that utilizes ultrasound to confirm the presence of fibroids in Latina/Latinx females. In addition, fibroids have been associated with obesity and with diabetes mellitus, but the data have been inconsistent and at times conflicting. OBJECTIVE: The Environment, Leiomyomas, Latinas, and Adiposity Study was designed to quantify the prevalence of uterine fibroids among Latina/Latinx females and understand the relationships between obesity, glucose dysregulation, and fibroid prevalence and growth. This article presents the study's design and reports early enrollment data. STUDY DESIGN: The Environment, Leiomyomas, Latinas, and Adiposity Study is a 5-year longitudinal cohort study based in Southeast Michigan with the goal of recruiting 600 Latina/Latinx females between the ages of 21 and 50 years. Given the recruitment goals, developing a respectful, transparent, and trusting relationship between the study investigators and the community was a major priority. Thus, a community-engaged research approach was utilized in the design of the Environment, Leiomyomas, Latinas, and Adiposity Study. A community advisory board containing community leaders, largely from the Latinx community, provided input and direction during the entirety of the Environment, Leiomyomas, Latinas, and Adiposity Study design and rollout process. A minimum of 3 visits (orientation and consent, baseline, follow-up) will be conducted for each participant, with baseline and follow-up visits approximately 18 to 30 months apart. At each visit, interviewer and self-administered surveys will assess sociodemographic factors, health behaviors, health history, and social determinants of health. In addition, participants undergo a pelvic ultrasound examination and biologic samples are collected. RESULTS: Using community-engaged approaches, we have successfully enrolled 633 Latina/Latinx females. The mean participant age is 37.5±7.04 years. The mean body mass index is 30.0±6.54 kg/m2. First study visits have been initiated. CONCLUSION: The objective of the Environment, Leiomyomas, Latinas, and Adiposity Study is to address the knowledge gap regarding uterine fibroids in the Latina/Latinx population. The Environment, Leiomyomas, Latinas, and Adiposity Study will generate ultrasound-confirmed evidence of the prevalence and growth patterns of uterine fibroids in this specific population while also examining the associations between obesity and laboratory-confirmed glucose dysregulation with uterine fibroid prevalence and growth patterns.
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Leiomioma , Neoplasias Uterinas , Adiposidade , Adulto , Etnicidade , Feminino , Hispânico ou Latino , Humanos , Leiomioma/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Grupos Minoritários , Obesidade/epidemiologia , Neoplasias Uterinas/epidemiologia , Adulto JovemRESUMO
PURPOSE: To implement quantitative Dixon magnetic resonance imaging (MRI) methods for brown adipose tissue (BAT) characterization at inactive and cold-activated states in normal weight, overweight, and obese subjects. The hypotheses are that MRI characteristics of BAT would differentiate between nonobese and obese subjects, and activation of BAT in response to thermal challenges that are detected by MRI would be correlated with BAT activity measured by positron emission tomography / computed tomography (PET/CT). MATERIALS AND METHODS: Fifteen male subjects (20.7 ± 1.5 years old) including six normal weight, five overweight, and four obese subjects participated in the study. A multiecho Dixon MRI sequence was performed on a 1.5T scanner. MRI was acquired under thermoneutral, nonshivering thermogenesis, and subsequent warm-up conditions. Fat fraction (FF), R2*, and the number of double bonds (ndb) were measured by solving an optimization problem that fits in- and out-of-phase MR signal intensities to the fat-water interference models. Imaging acquisition and postprocessing were performed by two MRI physicists. In each subject, Dixon MRI measurements of FF, R2*, and ndb were calculated for each voxel within all BAT regions of interest (ROIs) under each thermal condition. Mean FF, R2*, and ndb were compared between nonobese (ie, normal-weight/overweight) and obese subjects using the two-sample t-test. Receiver operating characteristic (ROC) analyses were performed to differentiate nonobese vs. obese subjects. BAT MRI measurement changes in response to thermal condition changes were compared with hypermetabolic BAT volume/activity measured by PET/CT using the Pearson's correlation. In addition, BAT MRI measurements were compared with body adiposity using the Pearson's correlation. P < 0.05 was considered statistically significant. RESULTS: Obese subjects showed higher FF and lower R2* than nonobese subjects under all three thermal conditions (P < 0.01). ROC analyses demonstrated that FF and R2* were excellent predictors for the differentiation of nonobese from obese subjects (100% specificity and 100% sensitivity). FF changes under thermal challenges were correlated with hypermetabolic BAT volume (r = -0.55, P = 0.04 during activation, and r = 0.72, P = 0.003 during deactivation), and with BAT activity (r = 0.69, P = 0.006 during deactivation), as measured by PET/CT. FF and R2* under all three thermal conditions were highly correlated with body adiposity (P ≤ 0.002). CONCLUSION: MRI characteristics of BAT differentiated between nonobese and obese subjects in both inactivated and activated states. BAT activation detected by Dixon MRI in response to thermal challenges were correlated with glucose uptake of metabolically active BAT. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:936-947.
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Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Sobrepeso/diagnóstico por imagem , Sobrepeso/fisiopatologia , Termogênese/fisiologia , Adulto , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Obesidade/diagnóstico por imagem , Obesidade/fisiopatologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sensibilidade e Especificidade , Adulto JovemRESUMO
The improved efficacy and generally favorable safety profile of recently approved and emerging antiobesity medications (AOMs), which result in an average weight reduction of ≥15%, represent significant advancement in the treatment of obesity. This narrative review aims to provide practical evidence-based recommendations for nutritional assessment, management, and monitoring of patients treated with AOMs. Prior to treatment, clinicians can identify preexisting nutritional risk factors and counsel their patients on recommended intakes of protein, dietary fiber, micronutrients, and fluids. During treatment with AOMs, ongoing monitoring can facilitate early recognition and management of gastrointestinal symptoms or inadequate nutrient or fluid intake. Attention should also be paid to other factors that can impact response to treatment and quality of life, such as physical activity and social and emotional health. In the context of treatment with AOMs, clinicians can play an active role in supporting their patients with obesity to improve their health and well-being and promote optimal nutritional and medical outcomes.
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INTRODUCTION: Understanding how race may influence the association between A1c and glycemia can improve diabetes screening. We sought to determine whether, for a given A1c level, glucose levels during an oral glucose tolerance test (OGTT) differed by race. RESEARCH DESIGN AND METHODS: From data collected at 22 US clinical sites, we conducted a cross-sectional study of concurrently measured A1c and OGTT and observational longitudinal follow-up of the subset with high-risk pre-diabetes. Numerical integration methods were used to calculate area under the glycemic curve (AUCglu) during OGTT and least squares regression model to estimate A1c for a given AUCglu by race, controlling for potential confounders. RESULTS: 1016 black, 2658 white, and 193 Asian persons at risk of diabetes were included in cross-sectional analysis. Of these, 2154 with high-risk pre-diabetes were followed for 2.5 years. For a given A1c level, AUCglu was lower in black versus white participants. After adjustment for potential confounders, A1c levels for a given AUCglu quintile were 0.15-0.20 and 0.02-0.19 percentage points higher in black and Asian compared with white participants, respectively (p<0.05). In longitudinal analyses, black participants were more likely to be diagnosed with diabetes by A1c than white participants (28% vs 10%, respectively; p<0.01). Black and Asian participants were less likely to be diagnosed by fasting glucose than white participants (16% vs 15% vs 37%, respectively; p<0.05). Black participants with A1c levels in the lower-level quintiles had greater increase in A1c over time compared with white participants. CONCLUSIONS: Use of additional testing beyond A1c to screen for diabetes may better stratify diabetes risk in the diverse US population.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/diagnóstico , Vitamina D , Estudos Transversais , Hemoglobinas Glicadas , Glicemia/análise , Fatores Raciais , Vitaminas , BrancosRESUMO
This prospective survey study assessed the knowledge of reproductive outcomes that are affected by obesity among women in an urban community. A total of 207 women attending a community fair on the south side of Chicago participated in the study. A survey assessing knowledge of BMI and of the effects of obesity on general, cardiometabolic and reproductive health outcomes was administered. Subjects ranged in age from 18 to 70 years (mean ± SD, 48.6 ± 12.9 years) and ranged in BMI from 17.3 to 52.1 kg/m(2) (mean ± SD, 31.2 ± 6.7 kg/m(2)). The following percentages of women were aware that obesity increases the risk of miscarriage (37.5 %), irregular periods (35.8 %), infertility (33.9 %), cesarean section (30.8 %), breast cancer (28.0 %), birth defects (23.7 %), stillbirth (14.1 %), and endometrial cancer (18.1 %). This study found that while women in an urban community are aware of the cardiometabolic risks associated with obesity, they demonstrate limited knowledge of the effects of obesity on reproductive outcomes. Public education is needed to increase knowledge and awareness of the reproductive consequences of obesity. Women of reproductive age may be uniquely responsive to obesity education and weight loss intervention.
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Conhecimentos, Atitudes e Prática em Saúde , Obesidade/complicações , Complicações na Gravidez/etiologia , Saúde Reprodutiva , População Urbana , Adolescente , Adulto , Idoso , Chicago , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , Inquéritos e Questionários , Adulto JovemRESUMO
Objectives: Prediabetes represents a spectrum of metabolic abnormalities, including insulin resistance and secretory impairment, that carries increased cardiovascular disease (CVD) risk. It is unclear whether specific glycemic and metabolic sub-classifications are associated with CVD risk. This cross-sectional analysis of 3946 participants from the Vitamin D and Type 2 Diabetes (D2d) study cohort aimed to determine the associations between various baseline CVD risk factors, glycemic sub-classifications of prediabetes (FPG, 2hPG, and HbA1c), and measures of insulin sensitivity and secretion from an OGTT. Methods: The metabolic syndrome and atherosclerotic cardiovascular disease (ASCVD) risk scores were determined for tertiles of insulin sensitivity (HOMA2S) and insulinogenic index (IGI). Unadjusted analyses showed elevated CVD risk factors in the lowest tertile for both IGI and HOMA2S. Results: After adjustment for age, gender, race, obesity, and smoking status, the association remained between HOMA2S and ASCVD score (r = -0.11, p< 0.001) but not for IGI. Those who met at least 2 diagnosic criteria for prediabetes had the largest proportion (> 40%) of participants with high ASCVD risk score >20. A higher percentage of individuals that met all 3 criteria for prediabetes had metabolic syndrome and ASCVD risk score >20 (87.2% and 15.3%, respectively) than those who only met 1 prediabetes criterion (51.6% and 7.1%, respectively). Conclusions: In conclusion, multiple metabolic (HOMA2S, IGI) and glycemic criteria of prediabetes (FPG, 2hPG, & HbA1c) are needed to fully recognize the elevated CVD risk profile that can manifest in prediabetes.
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OBJECTIVE: The objective of the study was to assess the infertility patient knowledge of reproductive outcomes affected by obesity. STUDY DESIGN: This was a prospective survey study of 150 female infertility patients in an academic medical center. Subjects were administered the Rapid Estimate of Adult Literacy in Medicine-Short Form and a questionnaire on the health risks of obesity, and investigators obtained height and weight measurements. RESULTS: Subjects' age ranged from 21 to 45 years (mean 34.8 ± 4.94 SD) and body mass index ranged from 17.9 to 62.9 kg/m(2) (mean 26.5 ± 7.54 SD). The following percentages of women were aware that obesity increases the risk of infertility (82.7%), irregular periods (70.0%), miscarriage (60.7%), cesarean section (48.7%), breast cancer (38.7%), birth defects (29.3%), stillbirth (22.7%), and endometrial cancer (20.7%). CONCLUSION: Among women with infertility, there is limited knowledge of reproductive outcomes affected by obesity. Public education is needed to increase awareness. Women undergoing fertility treatment are motivated for reproductive success and may be uniquely receptive to obesity education and weight loss intervention.
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Conhecimentos, Atitudes e Prática em Saúde , Infertilidade Feminina/etiologia , Obesidade/complicações , Adulto , Índice de Massa Corporal , Estudos de Coortes , Escolaridade , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Saúde Reprodutiva , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To compare the proteomic composition of follicular fluid from women with normal weight vs. women with obesity but without a history of polycystic ovary syndrome or known ovarian dysfunction undergoing in vitro fertilization. DESIGN: Cross-sectional. SETTING: Academic medical center. PATIENT(S): Eight women with normal weight and 8 women with obesity undergoing in vitro fertilization and without a history of polycystic ovary syndrome, ovulatory dysfunction, diminished ovarian reserve, or known endometriosis were included in the analysis. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Proteomic assessment using liquid chromatography-mass spectrometry analysis. RESULT(S): The mean age of women with normal weight was similar to that of women with obesity (32.9 vs. 32.6 years, not significant). The mean body mass index of women with normal weight was 21.2 kg/m2 compared with a body mass index of 37.1 kg/m2 in women with obesity. A total of 1,174 proteins were identified with ≥2 peptides present. Twenty-five proteins were found to be significantly altered in the follicular fluid from women with obesity. Of these 25 proteins, 19 were up-regulated and 6 were down-regulated. Notably, C-reactive protein was 11-fold higher in the follicular fluid from women with obesity than in the follicular fluid from women with normal weight. CONCLUSION(S): Obesity is associated with dysregulation at the level of the follicle, including alterations in proteins related to inflammation and metabolism. These include proteins with emerging roles in energy homeostasis and follicular regulation.
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Líquido Folicular , Síndrome do Ovário Policístico , Humanos , Feminino , Líquido Folicular/metabolismo , Síndrome do Ovário Policístico/metabolismo , Proteômica , Estudos Transversais , Fertilização in vitro , Obesidade/metabolismoRESUMO
OBJECTIVE: Despite obesity's significant impact on reproduction, its influence on the physiology of the human endometrium is largely understudied. We hypothesized that endometrial proteomic differences exist between obese (OW; body mass index [BMI] ≥30 kg/m2) and normal-weight women (NWW; BMI, 18.5-24.9 kg/m2). DESIGN: Clinical cross-sectional study. SETTING: Academic Medical Center. PATIENT(S): Healthy, normally-cycling, 18 to 40-year-old women (n = 6 OW and n = 6 NWW). MAIN OUTCOME MEASURE(S): Participants underwent screening and midfollicular phase visits. Demographic and anthropometric characteristics, blood samples, ultrasounds, and follicular phase endometrial biopsies were collected. Proteomic analyses of endometrial samples (liquid chromatography-mass spectrometry) were performed. Proteins with ≥2-fold difference and a false discovery rate of <0.1 were considered statistically significant (Benjamini-Hochberg adjustment). RESULT(S): Reproductive hormone levels did not differ between the two groups. Mean BMI, serum leptin concentration, and bioelectrical impedance analysis indices of adiposity were higher in OW than in NWW. Histological examination of the endometrial samples confirmed normal-appearing endometrium in both OW and NWW. A total of 2,930 proteins were detected across all samples, with an average number of proteins per sample of 2,059 ± 482 in NWW and 2,437 ± 187 in OW. A total of 17 proteins were differentially expressed in OW vs. NWW; 2 were more abundant, whereas 15 were underexpressed in OW, including the progesterone receptor. CONCLUSION(S): In this well-phenotyped population of healthy women, obesity was associated with significant endometrial proliferative phase proteomic differences affecting the hormonal and immunologic pathways. These could contribute to an increased risk of menstrual bleeding abnormalities and create an altered environment for future luteinization.
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Fase Folicular , Proteoma , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Proteoma/metabolismo , Proteômica , Estudos Transversais , Endométrio/metabolismo , Obesidade/metabolismoRESUMO
Fish oils containing both EPA and DHA have been shown to have beneficial cardiovascular effects, but less is known about the independent effects of DHA. This study was designed to examine the effects of DHA on plasma lipid and lipoprotein concentrations and other biomarkers of cardiovascular risk in the absence of weight loss. In this randomized, controlled, double-blind trial, 36 overweight or obese adults were treated with 2 g/d of algal DHA or placebo for 4.5 mo. Markers of cardiovascular risk were assessed before and after treatment. In the DHA-supplemented group, the decrease in mean VLDL particle size (P ≤ 0.001) and increases in mean LDL (P ≤ 0.001) and HDL (P ≤ 0.001) particle sizes were significantly greater than changes in the placebo group. DHA supplementation also increased the concentrations of large LDL (P ≤ 0.001) and large HDL particles (P = 0.001) and decreased the concentrations of small LDL (P = 0.009) and medium HDL particles (P = 0.001). As calculated using NMR-derived data, DHA supplementation reduced VLDL TG (P = 0.009) and total TG concentrations (P = 0.006). Plasma IL-10 increased with DHA supplementation to a greater extent than placebo (P = 0.021), but no other significant changes were observed in glucose metabolism, insulin sensitivity, blood pressure, or markers of inflammation with DHA. In summary, DHA supplementation resulted in potentially beneficial changes in some markers of cardiometabolic risk, whereas other markers were unchanged.
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Doenças Cardiovasculares/sangue , Gorduras na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacologia , Lipoproteínas/sangue , Obesidade/sangue , Extratos Vegetais/farmacologia , Rodófitas/química , Adulto , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Interleucina-10/sangue , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Tamanho da Partícula , Extratos Vegetais/uso terapêutico , Fatores de Risco , Triglicerídeos/sangue , Adulto JovemRESUMO
Objective: To explore relationships between PET/CT characteristics of cold-activated brown adipose tissue (BAT), measures of adiposity and metabolic markers.Methods: We conducted a post-hoc analysis of a study which utilized PET/CT to characterize BAT. 25 men ages 18-24 (BMI 19.4 to 35.9 kg/m2) were studied. Fasting blood samples were collected. Body composition was measured using DXA. An individualized cooling protocol was utilized to activate BAT prior to imaging with PET/CT.Results: There was an inverse relationship between fasting serum glucose and BAT volume (r = -0.40, p = 0.048). A marginally significant inverse relationship was also noted between fasting glucose and total BAT activity (r = -0.40, p = 0.05). In addition, a positive correlation was observed between serum FGF21 and SUVmax (r = 0.51, p = 0.01). No significant correlations were noted for measures of BAT activity or volume and other indicators of adiposity or glucose metabolism.Conclusions: The presence of active BAT may be associated with lower fasting glucose in young men. BAT activity may also be correlated with levels of FGF21, suggesting that BAT may lower glucose levels via an FGF21 dependent pathway. Further studies are needed to clarify mechanisms by which BAT may impact glucose metabolism.
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Tecido Adiposo Marrom/metabolismo , Adiposidade , Adiponectina/metabolismo , Adolescente , Biomarcadores/metabolismo , Estudos Transversais , Fatores de Crescimento de Fibroblastos/metabolismo , Glucose/metabolismo , Humanos , Insulina/metabolismo , Interleucina-6/metabolismo , Leptina/metabolismo , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Hormônios Tireóideos/metabolismo , Adulto JovemRESUMO
OBJECTIVE: Postrandomization biases may influence the estimate of efficacy of supplemental vitamin D in diabetes prevention trials. In the Vitamin D and Type 2 Diabetes (D2d) study, repeated measures of serum 25-hydroxyvitamin D [25(OH)D] level provided an opportunity to test whether intratrial vitamin D exposure affected diabetes risk and whether the effect was modified by trial assignment (vitamin D vs. placebo). RESEARCH DESIGN AND METHODS: The D2d study compared the effect of daily supplementation with 100 µg (4,000 units) of vitamin D3 versus placebo on new-onset diabetes in adults with prediabetes. Intratrial vitamin D exposure was calculated as the cumulative rolling mean of annual serum 25(OH)D measurements. Hazard ratios for diabetes among participants who had intratrial 25(OH)D levels of <50, 75-99, 100-124, and ≥125 nmol/L were compared with those with levels of 50-74 nmol/L (the range considered adequate by the National Academy of Medicine) in the entire cohort and by trial assignment. RESULTS: There was an interaction of trial assignment with intratrial 25(OH)D level in predicting diabetes risk (interaction P = 0.018). The hazard ratio for diabetes for an increase of 25 nmol/L in intratrial 25(OH)D level was 0.75 (95% CI 0.68-0.82) among those assigned to vitamin D and 0.90 (0.80-1.02) among those assigned to placebo. The hazard ratios for diabetes among participants treated with vitamin D who maintained intratrial 25(OH)D levels of 100-124 and ≥125 nmol/L were 0.48 (0.29-0.80) and 0.29 (0.17-0.50), respectively, compared with those who maintained a level of 50-74 nmol/L. CONCLUSIONS: Daily vitamin D supplementation to maintain a serum 25(OH)D level ≥100 nmol/L is a promising approach to reducing the risk of diabetes in adults with prediabetes.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Adulto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Estado Pré-Diabético/tratamento farmacológico , Vitamina D/sangueRESUMO
INTRODUCTION: Technology-enhanced antenatal diet and lifestyle intervention could prevent excess gestational weight gain and benefit mother and child. STUDY DESIGN: A randomized clinical trial. SETTING/PARTICIPANTS: Overweight and obese ethnically diverse pregnant women in Chicago, Illinois, were enrolled between October 2012 and December 2015, with antenatal data collection completed by July 2016. Analysis was completed June 2017. INTERVENTION: Participants were randomized when their fetus was gestational age 16 weeks to dietitian-led Dietary Approaches to Stop Hypertension diet and physical activity coaching that was received as three individual and six group counseling sessions by phone and webinar. A commercially available smartphone application was used for self-monitoring diet and physical activity. Telephone, text message prompts, and e-mail reminders encouraged adherence and website viewing. Usual-care, "web-watcher" participants were e-mailed biweekly newsletters and publicly available maternity website links. MAIN OUTCOME MEASURES: The primary outcome was gestational weight gain measured at baseline, 24 weeks, and 35.0-36.6 weeks. Secondary outcomes included weekly rate of gestational weight gain, newborn anthropometrics, maternal diet quality, physical activity, and blood pressure. RESULTS: Among 281 participants randomized (n=140 in intervention, n=141 in usual care, BMI 25 to <40, and age range 18-40 years), 37% were non-white and 274 completed antenatal data collection (n=139 in the intervention group and n=135 in the usual-care group). Gestational weight gain differed significantly by intervention group (difference, 1.7kg, p=0.01) and rate of weight gain was 0.4 (SD=0.2) vs 0.5 (SD=0.2) kg/week. No significant differences were noted in birth weight, percentage body fat, or adverse pregnancy outcomes, but more cesarean sections (55 [40%] vs 37 [27%]) occurred among the intervention group. CONCLUSIONS: Technology-enhanced Dietary Approaches to Stop Hypertension diet and lifestyle intervention resulted in significantly less total gestational weight gain over 35 weeks with no adverse infant outcomes. Nutrient quality improved without an adverse impact on rate of prematurity. Increased cesarean delivery requires further exploration. The National Academy of Medicine goals were not achieved by the majority of participants. Obesity prevention preconception is needed. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT01631747.
Assuntos
Abordagens Dietéticas para Conter a Hipertensão , Exercício Físico , Ganho de Peso na Gestação , Obesidade/terapia , Sobrepeso/terapia , Adolescente , Adulto , Peso ao Nascer , Cesárea/estatística & dados numéricos , Chicago , Aconselhamento , Feminino , Humanos , Recém-Nascido , Aplicativos Móveis , Gravidez , Adulto JovemRESUMO
OBJECTIVE: To describe baseline characteristics of the Vitamin D and Type 2 Diabetes (D2d) study, the first large U.S. diabetes prevention clinical trial to apply current American Diabetes Association (ADA) criteria for prediabetes. RESEARCH DESIGN AND METHODS: This is a multicenter (n = 22 sites), randomized, double-blind, placebo-controlled, primary prevention clinical trial testing effects of oral daily 4,000 IU cholecalciferol (D3) compared with placebo on incident diabetes in U.S. adults at risk for diabetes. Eligible participants were at risk for diabetes, defined as not meeting criteria for diabetes but meeting at least two 2010 ADA glycemic criteria for prediabetes: fasting plasma glucose (FPG) 100-125 mg/dL, 2-h postload glucose (2hPG) after a 75-g oral glucose load 140-199 mg/dL, and/or a hemoglobin A1c (HbA1c) 5.7-6.4% (39-46 mmol/mol). RESULTS: A total of 2,423 participants (45% of whom were women and 33% nonwhite) were randomized to cholecalciferol or placebo. Mean (SD) age was 59 (9.9) years and BMI 32 (4.5) kg/m2. Thirty-five percent met all three prediabetes criteria, 49% met the FPG/HbA1c criteria only, 9.5% met the 2hPG/FPG criteria only, and 6.3% met the 2hPG/HbA1c criteria only. Black participants had the highest mean HbA1c and lowest FPG concentration compared with white, Asian, and other races (P < 0.01); 2hPG concentration did not differ among racial groups. When compared with previous prediabetes cohorts, the D2d cohort had lower mean 2hPG concentration but similar HbA1c and FPG concentrations. CONCLUSIONS: D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria.
Assuntos
Colecalciferol/uso terapêutico , Diabetes Mellitus Tipo 2/prevenção & controle , Estado Pré-Diabético/tratamento farmacológico , Vitamina D/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Hemoglobinas Glicadas/análise , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologiaRESUMO
Obesity is a chronic metabolic disorder that affects one third of American adults. Modest weight losses of just 5% to 10% of body weight, which are achievable with lifestyle modification and pharmacotherapy, can lead to remarkable improvements in many obesity-associated co-morbidities, including dyslipidemia, hypertension, and type 2 diabetes. In this review, the indications for pharmacotherapy and the goals of treatment are discussed, and current and future pharmacologic approaches to the treatment of obesity are examined. Current pharmacologic therapies for obesity are limited, but recent advances in our understanding of the complex and overlapping endocrine pathways that regulate body weight have led to new opportunities for antiobesity drug development. Important drug targets that are highlighted in this review include adipocyte-derived hormones, hypothalamic neuropeptides, and gastrointestinal hormones.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Peso Corporal/efeitos dos fármacos , Ciclobutanos/farmacologia , Obesidade/tratamento farmacológico , Amiloide/farmacologia , Amiloide/uso terapêutico , Fármacos Antiobesidade/farmacologia , Depressores do Apetite/farmacologia , Depressores do Apetite/uso terapêutico , Doença Crônica , Comorbidade , Ciclobutanos/uso terapêutico , Exenatida , Hormônios Gastrointestinais/farmacologia , Hormônios Gastrointestinais/uso terapêutico , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Lactonas/farmacologia , Lactonas/uso terapêutico , Leptina/fisiologia , Metformina/farmacologia , Metformina/uso terapêutico , Obesidade/epidemiologia , Obesidade/fisiopatologia , Orlistate , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rimonabanto , Peçonhas/farmacologia , Peçonhas/uso terapêuticoRESUMO
OBJECTIVE: To determine whether there is an association between obesity and anti-Müllerian hormone (AMH) among reproductive-aged African American women (AAW). METHODS: From the women participating in an ongoing National Institute of Environmental Health Sciences study, 1,654 AAW aged 23 to 35 were included in this study. Anthropometric measurements, personal health information, and serum AMH and adipokine levels were analyzed. RESULTS: The median body mass index (BMI) was 32.4 kg/m2 , and the median AMH was 3.18 ng/mL. Participants with obesity had AMH concentrations that were 23.7% lower than those with a BMI ≤25 kg/m2 (2.9 ng/mL vs. 3.8 ng/mL). In multivariable linear regression models, current BMI (ß = -0.015; 95% CI -0.021 to -0.009), BMI at age 18 (ß = -0.016; 95% CI -0.024 to -0.008), heaviest reported lifetime weight (ß = -0.002; 95% CI -0.003 to -0.001), and leptin (ß = -0.016; 95% CI -0.025 to -0.007) were inversely associated with AMH. There was no significant association between adiponectin and AMH. AMH was significantly lower (mean log = 0.91, SE = 0.11) in participants with obesity at age 18 and at enrollment when compared with those who were underweight or normal weight at age 18 but had obesity at enrollment (mean log = 1.16, SE = 0.12). CONCLUSIONS: In reproductive-aged AAW there is a significant association between obesity and AMH, suggesting that excess adiposity may compromise ovarian reserve. Effects of obesity on AMH may be cumulative.