Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 189
Filtrar
1.
Endocr Pract ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34823000

RESUMO

Adiposity-Based Chronic Disease (ABCD) is a chronic disease and requires life-long treatment and follow-up. Obesity protects obesity through altered regulation of caloric intake and set point mechanisms that maintains a high equilibrium body weight. Lifestyle interventions and obesity medications do not permanently alter the set point which often makes weight loss achieved by lifestyle short-lived and operates to drive weight regain once medications are discontinued. Bariatric surgery procedures can alter appetite and lower the "set point" for equilibrium body weight via unknown mechanisms. However, few patients attain ideal body weight following surgery, many regain weight, and all require long-term follow-up for the disease. The excess adiposity of ABCD gives rise to complications that impair health and confer morbidity and mortality; however, the genetic risks and potential interactions between genes and environment that give rise to complications also cannot be eliminated. The equilibrium body weight around which set point mechanisms operate can be modified by environment, which underscores the importance of a less obesogenic environment for prevention and treatment of ABCD on a population basis. If ABCD will eventually be curable, this will depend on a clear understanding of the molecular mechanisms that determine the set point regulation of body weight, and an ability to permanently modulate the set point to oscillate around and a lean body mass. The conceptualization of ABCD as a chronic disease, however, does present us with opportunities for primary, secondary, and tertiary prevention to avert disease progression. For tertiary care, the advent of new, more effective, second-generation obesity medications will allow clinicians to treat-to-target via active management of body weight into a target range that will ameliorate specific complications.

2.
Physiol Rep ; 9(19): e15049, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34605220

RESUMO

OBJECTIVE: Insulin sensitivity is lower in African American (AA) versus Caucasian American (CA). We tested the hypothesis that lower insulin sensitivity in AA could be explained by mitochondrial respiratory rates, coupling efficiency, myofiber composition, or H2 O2 emission. A secondary aim was to determine whether sex affected the results. METHODS: AA and CA men and women, 19-45 years, BMI 17-43 kg m2 , were assessed for insulin sensitivity (SIClamp ) using a euglycemic clamp at 120 mU/m2 /min, muscle mitochondrial function using high-resolution respirometry, H2 O2 emission using amplex red, and % myofiber composition. RESULTS: SIClamp was greater in CA (p < 0.01) and women (p < 0.01). Proportion of type I myofibers was lower in AA (p < 0.01). Mitochondrial respiratory rates, coupling efficiency, and H2 O2 production did not differ with race. Mitochondrial function was positively associated with insulin sensitivity in women but not men. Statistical adjustment for mitochondrial function, H2 O2 production, or fiber composition did not eliminate the race difference in SIClamp . CONCLUSION: Neither mitochondrial respiratory rates, coupling efficiency, myofiber composition, nor mitochondrial reactive oxygen species production explained lower SIClamp in AA compared to CA. The source of lower insulin sensitivity in AA may be due to other aspects of skeletal muscle that have yet to be identified.

5.
Sci Rep ; 11(1): 14182, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244538

RESUMO

In type 2 diabetes, hyperuricemia is associated with cardiovascular disease (CVD) and the metabolic syndrome (MetS), but associations in type 1 diabetes (T1D) have not been well-defined. This study examined the relationships between serum urate (SU) concentrations, clinical and biochemical factors, and subsequent cardiovascular events in a well-characterized cohort of adults with T1D. In 973 participants with T1D in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), associations were defined between SU, measured once in blood collected 1997-2000, and (a) concurrent MetS and (b) incident 'any CVD' and major adverse cardiovascular events (MACE) through 2013. SU was higher in men than women [mean (SD): 4.47 (0.99) vs. 3.39 (0.97) mg/dl, respectively, p < 0.0001], and was associated with MetS features in both (men: p = 0.0016; women: p < 0.0001). During follow-up, 110 participants (11%) experienced "any CVD", and 53 (5%) a MACE. Analyzed by quartiles, SU was not associated with subsequent CVD or MACE. In women, SU as a continuous variable was associated with MACE (unadjusted HR: 1.52; 95% CI 1.07-2.16; p = 0.0211) even after adjustment for age and HbA1c (HR: 1.47; 95% CI 1.01-2.14; p = 0.0467). Predominantly normal range serum urate concentrations in T1D were higher in men than women and were associated with features of the MetS. In some analyses of women only, SU was associated with subsequent MACE. Routine measurement of SU to assess cardiovascular risk in T1D is not merited.Trial registration clinicaltrials.gov NCT00360815 and NCT00360893.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 1/sangue , Ácido Úrico/sangue , Adulto , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 1/complicações , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade
6.
Am J Phys Anthropol ; 175(4): 905-919, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34008864

RESUMO

OBJECTIVES: Gullah African Americans are descendants of formerly enslaved Africans living in the Sea Islands along the coast of the southeastern U.S., from North Carolina to Florida. Their relatively high numbers and geographic isolation were conducive to the development and preservation of a unique culture that retains deep African features. Although historical evidence supports a West-Central African ancestry for the Gullah, linguistic and cultural evidence of a connection to Sierra Leone has led to the suggestion of this country/region as their ancestral home. This study sought to elucidate the genetic structure and ancestry of the Gullah. MATERIALS AND METHODS: We leveraged whole-genome genotype data from Gullah, African Americans from Jackson, Mississippi, African populations from Sierra Leone, and population reference panels from Africa and Europe to infer population structure, ancestry proportions, and global estimates of admixture. RESULTS: Relative to non-Gullah African Americans from the Southeast US, the Gullah exhibited higher mean African ancestry, lower European admixture, a similarly small Native American contribution, and increased male-biased European admixture. A slightly tighter bottleneck in the Gullah 13 generations ago suggests a largely shared demographic history with non-Gullah African Americans. Despite a slightly higher relatedness to populations from Sierra Leone, our data demonstrate that the Gullah are genetically related to many West African populations. DISCUSSION: This study confirms that subtle differences in African American population structure exist at finer regional levels. Such observations can help to inform medical genetics research in African Americans, and guide the interpretation of genetic data used by African Americans seeking to explore ancestral identities.


Assuntos
Afro-Americanos , Grupo com Ancestrais do Continente Africano , África , Afro-Americanos/genética , Grupo com Ancestrais do Continente Africano/genética , Europa (Continente) , Genótipo , Humanos , Masculino
7.
Diabetes ; 70(8): 1738-1753, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33975909

RESUMO

The current understanding of the molecular pathogenesis of diabetic retinopathy does not provide a mechanistic link between early molecular changes and the subsequent progression of the disease. In this study, we found that human diabetic retinas overexpressed TRIB3 and investigated the role of TRIB3 in diabetic retinal pathobiology in mice. We discovered that TRIB3 controlled major molecular events in early diabetic retinas via HIF1α-mediated regulation of retinal glucose flux, reprogramming cellular metabolism, and governing of inflammatory gene expression. These early molecular events further defined the development of neurovascular deficit observed in mice with diabetic retinopathy. TRIB3 ablation in the streptozotocin-induced mouse model led to significant retinal ganglion cell survival and functional restoration accompanied by a dramatic reduction in pericyte loss and acellular capillary formation. Under hypoxic conditions, TRIB3 contributed to advanced proliferative stages by significant upregulation of GFAP and VEGF expression, thus controlling gliosis and aberrant vascularization in oxygen-induced retinopathy mouse retinas. Overall, our data reveal that TRIB3 is a master regulator of diabetic retinal pathophysiology that may accelerate the onset and progression of diabetic retinopathy to proliferative stages in humans and present TRIB3 as a potentially novel therapeutic target for diabetic retinopathy.


Assuntos
Proteínas de Ciclo Celular/genética , Retinopatia Diabética/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Repressoras/genética , Retina/metabolismo , Animais , Capilares/metabolismo , Capilares/patologia , Proteínas de Ciclo Celular/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Progressão da Doença , Humanos , Camundongos , Pericitos/metabolismo , Pericitos/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Repressoras/metabolismo , Retina/patologia
9.
Am J Physiol Endocrinol Metab ; 320(5): E864-E873, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33645254

RESUMO

Regular exercise has profound metabolic influence on the liver, but effects on bile acid (BA) metabolism are less well known. BAs are synthesized exclusively in the liver from cholesterol via the rate-limiting enzyme cholesterol 7 alpha-hydroxylase (CYP7A1). BAs contribute to the solubilization and absorption of lipids and serve as important signaling molecules, capable of systemic endocrine function. Circulating BAs increase with obesity and insulin resistance, but effects following exercise and diet-induced weight loss are unknown. To test if improvements in fitness and weight loss as a result of exercise training enhance BA metabolism, we measured serum concentrations of total BAs (conjugated and unconjugated primary and secondary BAs) in sedentary, obese, insulin-resistant women (N = 11) before (PRE) and after (POST) a ∼14-wk exercise and diet-induced weight loss intervention. BAs were measured in serum collected after an overnight fast and during an oral glucose tolerance test (OGTT). Serum fibroblast growth factor 19 (FGF19; a regulator of BA synthesis) and 7-alpha-hydroxy-cholesten-3-one (C4, a marker of CYP7A1 enzymatic activity) also were measured. Using linear mixed-model analyses and the change in V̇O2peak (mL/min/kg) as a covariate, we observed that exercise and weight loss intervention decreased total fasting serum BA by ∼30% (P = 0.001) and increased fasting serum C4 concentrations by 55% (P = 0.004). C4 was significantly correlated with serum total BAs only in the POST condition, whereas serum FGF19 was unchanged. These data indicate that a fitness and weight loss intervention modifies BA metabolism in obese women and suggest that improved metabolic health associates with higher postabsorptive (fasting) BA synthesis. Furthermore, pre- vs. postintervention patterns of serum C4 following an OGTT support the hypothesis that responsiveness of BA synthesis to postprandial inhibition is improved after exercise and weight loss.NEW & NOTEWORTHY Exercise and weight loss in previously sedentary, insulin-resistant women facilitates a significant improvement in insulin sensitivity and fitness that may be linked to changes in bile acid metabolism. Diet-induced weight loss plus exercise-induced increases in fitness promote greater postabsorptive bile acid synthesis while also sensitizing the bile acid metabolic system to feedback inhibition during a glucose challenge when glucose and insulin are elevated.


Assuntos
Ácidos e Sais Biliares/metabolismo , Biomarcadores/sangue , Exercício Físico/fisiologia , Obesidade/metabolismo , Perda de Peso/fisiologia , Adulto , Ácidos e Sais Biliares/biossíntese , Ácidos e Sais Biliares/sangue , Biomarcadores/metabolismo , Glicemia/metabolismo , Dieta Redutora , Terapia por Exercício , Feminino , Humanos , Resistência à Insulina/fisiologia , Fígado/metabolismo , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/terapia , Regulação para Cima
10.
Popul Health Manag ; 24(5): 548-559, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33784483

RESUMO

Although several obesity clinical practice guidelines are available and relevant for primary care, a practical and effective medical model for treating obesity is necessary. The aim of this study was to develop and implement a holistic population health-based framework with components to support primary care-based obesity management in US health care organizations. The Obesity Care Model Collaborative (OCMC) was conducted with guidance and expertise of an advisory committee, which selected participating health care organizations based on prespecified criteria. A committee comprising obesity and quality improvement specialists and representatives from each organization developed and refined the obesity care framework for testing and implementing guideline-based practical interventions targeting obesity. These interventions were tracked over time, from an established baseline to 18 months post implementation. Ten geographically diverse organizations, treating patients with diverse demographics, insurance coverage, and health status, participated in the collaborative. The key interventions identified for managing obesity in primary care were applicable across the 4 OCMC framework domains: community, health care organization, care team, and patient/family. Care model components were developed within each domain to guide the primary care of obesity based on each organization's structure, resources, and culture. Key interventions included development of quality monitoring systems, training of leadership and staff, identifying clinical champions, patient education, electronic health record best practice alerts, and establishment of community partnerships, including the identification of external resources. This article describes the interventions developed based on the framework, with a focus on implementation of the model and lessons learned.


Assuntos
Atenção à Saúde , Atenção Primária à Saúde , Adulto , Humanos , Liderança , Obesidade/terapia , Melhoria de Qualidade
11.
JAMA ; 325(14): 1403-1413, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33625476

RESUMO

Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. Objective: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. Design, Setting, and Participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). Interventions: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. Main Outcomes and Measures: The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. Results: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants. Conclusions and Relevance: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03611582.


Assuntos
Terapia Cognitivo-Comportamental , Dieta Redutora , Peptídeo 1 Semelhante ao Glucagon/agonistas , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Sobrepeso/terapia , Perda de Peso/efeitos dos fármacos , Adulto , Fármacos Antiobesidade/uso terapêutico , Terapia Combinada , Método Duplo-Cego , Feminino , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/tratamento farmacológico , Obesidade/terapia , Sobrepeso/dietoterapia , Sobrepeso/tratamento farmacológico
12.
Obesity (Silver Spring) ; 28(12): 2305-2309, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33029901

RESUMO

OBJECTIVE: This study aimed to explore the relationship between an obesity diagnosis and weight loss as a percentage of total body weight loss over 9 to 15 months, using electronic health record data. METHODS: An observational study of 688,878 adult patients at 15 health systems with BMI ≥ 30 kg/m2 examined the relationship between weight loss and documentation of obesity diagnosis. Multivariable logistic regression models were created using a stepwise backwards elimination procedure to identify potential predictors of weight loss. RESULTS: Of patients with BMI ≥ 30, 44.9% had an obesity diagnosis on a claim or electronic health record problem list; 16.9% and 5.9% lost ≥ 5% and ≥ 10% of their body weight, respectively. Multivariable logistic regression models revealed a diagnosis of obesity on the same day as the initial weight (odds ratio [OR] = 1.3; CI: 1.2-1.3; P < 0.001) as a predictor of ≥ 5% total body weight loss in 9 to 15 months. Other significant predictors included an antiobesity medication prescription, female sex, diagnosis of type 2 diabetes, Medicare/Medicaid insurance, and number of ambulatory visits. CONCLUSIONS: While controlling for potentially confounding factors, documentation of an obesity diagnosis remained independently predictive of at least 5% weight loss. This suggests that documenting a diagnosis of obesity may be an important step toward engaging patients to lose weight.


Assuntos
Obesidade/diagnóstico , Perda de Peso/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos
13.
JCI Insight ; 5(21)2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32990681

RESUMO

Canagliflozin (Cana) is an FDA-approved diabetes drug that protects against cardiovascular and kidney diseases. It also inhibits the sodium glucose transporter 2 by blocking renal reuptake and intestinal absorption of glucose. In the context of the mouse Interventions Testing Program, genetically heterogeneous mice were given chow containing Cana at 180 ppm at 7 months of age until their death. Cana extended median survival of male mice by 14%. Cana also increased by 9% the age for 90th percentile survival, with parallel effects seen at each of 3 test sites. Neither the distribution of inferred cause of death nor incidental pathology findings at end-of-life necropsies were altered by Cana. Moreover, although no life span benefits were seen in female mice, Cana led to lower fasting glucose and improved glucose tolerance in both sexes, diminishing fat mass in females only. Therefore, the life span benefit of Cana is likely to reflect blunting of peak glucose levels, because similar longevity effects are seen in male mice given acarbose, a diabetes drug that blocks glucose surges through a distinct mechanism, i.e., slowing breakdown of carbohydrate in the intestine. Interventions that control daily peak glucose levels deserve attention as possible preventive medicines to protect from a wide range of late-life neoplastic and degenerative diseases.


Assuntos
Glicemia/análise , Canagliflozina/farmacologia , Intolerância à Glucose/tratamento farmacológico , Longevidade , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Animais , Feminino , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Fatores Sexuais
14.
Physiol Rep ; 8(17): e14547, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32869956

RESUMO

Very little is known about how metabolic health status, insulin resistance or metabolic challenges modulate the endocannabinoid (eCB) or polyunsaturated fatty acid (PUFA)-derived oxylipin (OxL) lipid classes. To address these questions, plasma eCB and OxL concentrations were determined at rest, 10 and 20 min during an acute exercise bout (30 min total, ~45% of preintervention V̇O2peak , ~63 W), and following 20 min recovery in overnight-fasted sedentary, obese, insulin-resistant women under controlled diet conditions. We hypothesized that increased fitness and insulin sensitivity following a ~14-week training and weight loss intervention would lead to significant changes in lipid signatures using an identical acute exercise protocol to preintervention. In the first 10 min of exercise, concentrations of a suite of OxL diols and hydroxyeicosatetraenoic acid (HETE) metabolites dropped significantly. There was no increase in 12,13-DiHOME, previously reported to increase with exercise and proposed to activate muscle fatty acid uptake and tissue metabolism. Following weight loss intervention, exercise-associated reductions were more pronounced for several linoleate and alpha-linolenate metabolites including DiHOMEs, DiHODEs, KODEs, and EpODEs, and fasting concentrations of 9,10-DiHODE, 12,13-DiHODE, and 9,10-DiHOME were reduced. These findings suggest that improved metabolic health modifies soluble epoxide hydrolase, cytochrome P450 epoxygenase (CYP), and lipoxygenase (LOX) systems. Acute exercise led to reductions for most eCB metabolites, with no evidence for concentration increases even at recovery. It is proposed that during submaximal aerobic exercise, nonoxidative fates of long-chain saturated, monounsaturated, and PUFAs are attenuated in tissues that are important contributors to the blood OxL and eCB pools.


Assuntos
Terapia por Exercício/métodos , Obesidade/terapia , Oxilipinas/sangue , Programas de Redução de Peso/métodos , Adulto , Sistema Enzimático do Citocromo P-450/sangue , Epóxido Hidrolases/sangue , Feminino , Humanos , Resistência à Insulina , Ácido Linoleico/sangue , Lipoxigenase/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Comportamento Sedentário
15.
PLoS Med ; 17(8): e1003232, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32764746

RESUMO

BACKGROUND: Obesity is closely related to the development of insulin resistance and type 2 diabetes (T2D). The prevention of T2D has become imperative to stem the rising rates of this disease. Weight loss is highly effective in preventing T2D; however, the at-risk pool is large, and a clinically meaningful metric for risk stratification to guide interventions remains a challenge. The objective of this study is to predict T2D risk using full-information continuous analysis of nationally sampled data from white and black American adults age ≥45 years. METHODS AND FINDINGS: A sample of 12,043 black (33%) and white individuals from a population-based cohort, REasons for Geographic And Racial Differences in Stroke (REGARDS) (enrolled 2003-2007), was observed through 2013-2016. The mean participant age was 63.12 ± 8.62 years, and 43.7% were male. Mean BMI was 28.55 ± 5.61 kg/m2. Risk factors for T2D regularly recorded in the primary care setting were used to evaluate future T2D risk using Bayesian logistic regression. External validation was performed using 9,710 participants (19% black) from Atherosclerotic Risk in Communities (ARIC) (enrolled 1987-1989), observed through 1996-1998. The mean participant age in this cohort was 53.86 ± 5.65 years, and 44.6% were male. Mean BMI was 27.15 ± 4.92 kg/m2. Predictive performance was assessed using the receiver operating characteristic (ROC) curves and area under the curve (AUC) statistics. The primary outcome was incident T2D. By 2016 in REGARDS, there were 1,602 incident cases of T2D. Risk factors used to predict T2D progression included age, sex, race, BMI, triglycerides, high-density lipoprotein, blood pressure, and blood glucose. The Bayesian logistic model (AUC = 0.79) outperformed the Framingham risk score (AUC = 0.76), the American Diabetes Association risk score (AUC = 0.64), and a cardiometabolic disease system (using Adult Treatment Panel III criteria) (AUC = 0.75). Validation in ARIC was robust (AUC = 0.85). Main limitations include the limited generalizability of the REGARDS sample to black and white, older Americans, and no time to diagnosis for T2D. CONCLUSIONS: Our results show that a Bayesian logistic model using full-information continuous predictors has high predictive discrimination, and can be used to quantify race- and sex-specific T2D risk, providing a new, powerful predictive tool. This tool can be used for T2D prevention efforts including weight loss therapy by allowing clinicians to target high-risk individuals in a manner that could be used to optimize outcomes.


Assuntos
Afro-Americanos , Interpretação Estatística de Dados , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Grupo com Ancestrais do Continente Europeu , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Glicemia/metabolismo , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Seguimentos , Humanos , Incidência , Resistência à Insulina/fisiologia , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/epidemiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
17.
Life Sci ; 254: 117764, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407841

RESUMO

AIMS: Emerging evidence suggests that during gestation the in utero environment programs metabolism and can increase risk of obesity in adult offspring. Our aim was to study how alterations in maternal diets during gestation might alter body weight evolution, circulating leptin levels and caloric intake in offspring, leading to changes in body composition. MATERIALS AND METHODS: We fed gestating rats either a control diet (CD), high fat diet (HFD) or an isocaloric low protein diet (LPD), and examined the repercussions in offspring fed similar diets post-weaning on birth weight, body weight evolution, body composition, insulin sensitivity, glucose tolerance and in the relationship between plasma leptin concentration and caloric intake in offspring during growth and development. KEY FINDS: Offspring from dams fed LPD maintained reduced body weight with greater % lean mass and consumed fewer calories despite having leptin levels similar to controls. On the other hand, offspring from dams fed a HFD were insulin resistant and maintained increased body weight and % fat mass, while consuming more calories than controls despite elevated leptin concentrations. Therefore the uterine environment, modulated primarily through maternal nutrition, modified the relationship between circulating leptin levels, body fat, and caloric intake in the offspring, and dams fed a HFD produced offspring with excess adiposity, insulin resistance, and leptin resistance into adulthood. SIGNIFICANCE: Our data indicates that in utero environmental factors affected by maternal diet program alterations in the set point around which leptin regulates body weight in offspring into adulthood contributing to obesity.


Assuntos
Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Obesidade/etiologia , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Tecido Adiposo/metabolismo , Adiposidade/fisiologia , Animais , Animais Recém-Nascidos , Peso ao Nascer , Composição Corporal , Peso Corporal , Dieta Hiperlipídica , Gorduras na Dieta , Ingestão de Energia , Feminino , Resistência à Insulina , Lactação , Leptina/metabolismo , Masculino , Obesidade/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Sprague-Dawley , Desmame
18.
Obesity (Silver Spring) ; 28(6): 1050-1061, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32441473

RESUMO

OBJECTIVE: The obesity epidemic is a public health concern, warranting further research into pharmacological treatments for weight management (WM) as an adjunct to lifestyle interventions. The Semaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with obesity or overweight. METHODS: Across five phase 3 trials (NCT03548935, WM; NCT03552757, WM in type 2 diabetes; NCT03611582, WM with intensive behavioral therapy; NCT03548987, sustained WM; and NCT03693430, long-term WM), ~5,000 participants are being randomly assigned to receive semaglutide 2.4 mg once weekly subcutaneously versus placebo. Results will be available in 2020/2021. For all trials, the primary end point is change from baseline to end of treatment in body weight. RESULTS: Participants have a mean age of 46.2 to 55.3 years, are mostly female (mean: 74.1%-81.0%), and have a mean BMI of 35.7 to 38.5 kg/m2 and a mean waist circumference of 113.0 to 115.7 cm. CONCLUSIONS: The STEP program evaluates the efficacy and safety of semaglutide 2.4 mg subcutaneously once weekly in a broad population. The trials will provide insights on WM in people with obesity with and without type 2 diabetes and on long-term follow-up.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Hipoglicemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Método Duplo-Cego , Feminino , Peptídeos Semelhantes ao Glucagon/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Diabetes Care ; 43(5): 1085-1093, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139381

RESUMO

OBJECTIVE: Most individuals with type 2 diabetes also have obesity, and treatment with some diabetes medications, including insulin, can cause further weight gain. No approved chronic weight management medications have been prospectively investigated in individuals with overweight or obesity and insulin-treated type 2 diabetes. The primary objective of this study was to assess the effect of liraglutide 3.0 mg versus placebo on weight loss in this population. RESEARCH DESIGN AND METHODS: Satiety and Clinical Adiposity-Liraglutide Evidence (SCALE) Insulin was a 56-week, randomized, double-blind, placebo-controlled, multinational, multicenter trial in individuals with overweight or obesity and type 2 diabetes treated with basal insulin and ≤2 oral antidiabetic drugs. RESULTS: Individuals were randomized to liraglutide 3.0 mg (n = 198) or placebo (n = 198), combined with intensive behavioral therapy (IBT). At 56 weeks, mean weight change was -5.8% for liraglutide 3.0 mg versus -1.5% with placebo (estimated treatment difference -4.3% [95% CI -5.5; -3.2]; P < 0.0001). With liraglutide 3.0 mg, 51.8% of individuals achieved ≥5% weight loss versus 24.0% with placebo (odds ratio 3.41 [95% CI 2.19; 5.31]; P < 0.0001). Liraglutide 3.0 mg was associated with significantly greater reductions in mean HbA1c and mean daytime glucose values and less need for insulin versus placebo, despite a treat-to-glycemic-target protocol. More hypoglycemic events were observed with placebo than liraglutide 3.0 mg. No new safety or tolerability issues were observed. CONCLUSIONS: In individuals with overweight or obesity and insulin-treated type 2 diabetes, liraglutide 3.0 mg as an adjunct to IBT was superior to placebo regarding weight loss and improved glycemic control despite lower doses of basal insulin and without increases in hypoglycemic events.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/administração & dosagem , Liraglutida/administração & dosagem , Liraglutida/efeitos adversos , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Adiposidade/efeitos dos fármacos , Adiposidade/fisiologia , Adulto , Idoso , Terapia Comportamental , Glicemia/efeitos dos fármacos , Terapia Combinada , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/terapia , Sobrepeso/sangue , Sobrepeso/complicações , Sobrepeso/terapia , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...