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Knockout mice for the kisspeptin receptor, Kiss1r (Kiss1r-/-) and its ligand kisspeptin, Kiss1 (Kiss1-/-) replicate the phenotype of isolated hypogonadotropic hypogonadism (IHH) associated with variants of these genes in humans. A recent report suggests that kisspeptin may be involved in human fetal adrenocortical development and function. Herein, we characterized the adrenal function and morphology in Kiss1-/- mice that do not go through normal puberty. Two fetal markers were expressed in eosinophilic cells potentially derived from the X-zone that should disappear at puberty in male mice and during the first pregnancy in female animals. Although the hypercorticosteronism observed in Kiss1-/- females corrected overtime, hyperaldosteronism persisted at 14 months and correlated with the overexpression of Star. To determine if KISS1 and KISS1R genes are involved in the development of primary aldosteronism (PA) and hypercortisolism [Cushing's syndrome (CS)] in humans, we sequenced these 2 genes in 65 patients with PA and/or CS. Interestingly, a patient with CS presented with a germline KISS1 variant (p.H90D, rs201073751). We also found three rare variants in the KISS1R gene in three patients with PA: p.C95W (rs141767649), p.A189T (rs73507527) and p.R229R (rs115335009). The two missense variants have been previously associated with IHH. Our findings suggest that KISS1 may play a role in adrenal function in mice and possibly adrenocortical steroid hormone secretion in humans, beyond its recently described role in human fetal adrenocortical development.
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Neoplasias de las Glándulas Suprarrenales/complicaciones , Glándulas Suprarrenales/anomalías , Síndrome de Cushing/patología , Kisspeptinas/deficiencia , Mutación , Receptores de Kisspeptina-1/metabolismo , Esteroides/metabolismo , Glándulas Suprarrenales/metabolismo , Animales , Síndrome de Cushing/etiología , Femenino , Humanos , Kisspeptinas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Receptores de Kisspeptina-1/genéticaRESUMEN
Achieving target inpatient glycemic management outcomes has been shown to influence important clinical outcomes such as hospital length of stay and readmission rates. However, arguably the most profound, lasting impact of inpatient diabetes management is achieved at the time of discharge-namely reconciling and prescribing the right medications and making referrals for follow-up. Discharge planning offers a unique opportunity to break through therapeutic inertia, offer diabetes self-management education, and institute an individualized treatment plan that prepares the patient for discharge and promotes self-care and engagement. However, the path to a successful discharge plan can be fraught with potential pitfalls for clinicians, including lack of knowledge and experience with newer diabetes medications, costs, concerns over insurance coverage, and lack of time and resources. This article presents an algorithm to assist clinicians in selecting discharge regimens that maximize benefits and reduce barriers to self-care for patients and a framework for creating an interdisciplinary hospital diabetes discharge program.
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CONTEXT: Diabetes is a leading metabolic disorder with a substantial cost burden, especially in inpatient settings. The complexity of inpatient glycemic management has led to the emergence of inpatient diabetes management service (IDMS), a multidisciplinary team approach to glycemic management. OBJECTIVE: To review recent literature on the financial and clinical impact of IDMS in hospital settings. METHODS: We searched PubMed using a combination of controlled vocabulary and keyword terms to describe the concept of IDMS and combined the search terms with a comparative effectiveness filter for costs and cost analysis developed by the National Library of Medicine. FINDINGS: In addition to several improved clinical endpoints such as glycemic management outcomes, IDMS implementation is associated with hospital cost savings through decreased length of stay, preventing hospital readmissions, hypoglycemia reduction, and optimizing resource allocation. There are other downstream potential cost savings in long-term patient health outcomes and avoidance of litigation related to suboptimal glycemic management. CONCLUSION: IDMS may play an important role in helping both academic and community hospitals to improve the quality of diabetes care and reduce costs. Clinicians and policymakers can utilize existing literature to build a compelling business case for IDMS to hospital administrations and state legislatures in the era of value-based healthcare.
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Diabetes Mellitus , Pacientes Internos , Atención a la Salud , Diabetes Mellitus/terapia , Humanos , Readmisión del Paciente , Estados UnidosRESUMEN
OBJECTIVE: Recent clinical trials have demonstrated that colchicine may have metabolic and cardiovascular and benefits in at-risk patients; however, the mechanisms through which colchicine may improve outcomes are still unclear. We sought to examine colchicine's effects on circulating inflammatory and metabolic molecules in adults with obesity and metabolic syndrome (MetS). METHODS: Blood samples were collected pre- and post-intervention during a double-blind randomized controlled trial in which 40 adults with obesity and MetS were randomized to colchicine 0.6 mg or placebo twice-daily for 3 months. Serum samples were analyzed for 1305 circulating factors using the SomaScan Platform. The Benjamini-Hochberg procedure was used to adjust the false discovery rate (FDR) for multiple testing. RESULTS: At baseline, age (48.0 ± 13.8 vs. 44.7 ± 10.3 years) and BMI (39.8 ± 6.4 vs. 41.8 ± 8.2 kg/m2) were not different between groups. After controlling for the FDR, 34 molecules were significantly changed by colchicine. Colchicine decreased concentrations of multiple inflammatory molecules, including C-reactive protein, interleukin 6, and resistin, in addition to vascular-related proteins (e.g., oxidized low-density lipoprotein receptor, phosphodiesterase 5A). Conversely, relative to placebo, colchicine significantly increased concentrations of eight molecules including secreted factors associated with metabolism and anti-thrombosis. CONCLUSIONS: In adults with obesity, colchicine significantly affected concentrations of proteins involved in the innate immune system, endothelial function and atherosclerosis, uncovering new mechanisms behind its cardiometabolic effects. Further research is warranted to investigate whether colchicine's IL-6 suppressive effects may be beneficial in COVID-19.
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Antiinflamatorios/uso terapéutico , Colchicina/uso terapéutico , Infecciones por Coronavirus/inmunología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/inmunología , Obesidad/inmunología , Neumonía Viral/inmunología , Adulto , Antiinflamatorios/farmacología , Betacoronavirus/efectos de los fármacos , Proteína C-Reactiva , COVID-19 , Colchicina/farmacología , Infecciones por Coronavirus/tratamiento farmacológico , Método Doble Ciego , Femenino , Humanos , Interleucina-6 , Masculino , Síndrome Metabólico/tratamiento farmacológico , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Pandemias , Proyectos Piloto , Neumonía Viral/tratamiento farmacológico , SARS-CoV-2 , Resultado del Tratamiento , Adulto JovenRESUMEN
Haemolysis of serially collected insulin serum samples frequently causes falsely-low measured concentrations because of the release of intracellular insulin degrading enzyme (IDE). We investigated if bacitracin, an in vitro IDE inhibitor, could prevent haemolysis-induced insulin degradation during insulin sensitivity testing. Blood samples were collected from adults undergoing serial sampling for insulin sensitivity. A dose-finding study measured insulin from experimentally haemolysed samples containing five bacitracin concentrations (0-2.5 g/L) and from non-experimentally haemolysed samples. To confirm the utility of bacitracin in the clinical setting, we compared insulin in samples collected with and without 1 g/L bacitracin from a frequently sampled intravenous glucose tolerance test (FSIVGTT), where haemolysis often occurs accidentally. In the dose-finding study, bacitracin 0.25, 1 and 2.5 g/L all maximally prevented insulin degradation in experimentally haemolysed samples. Among FSIVGTT unintentionally haemolysed samples, insulin concentrations from bacitracin-containing samples were significantly higher than from those without bacitracin (P < .01), and not different from non-haemolysed samples obtained simultaneously from a second intravenous catheter (P = .07). Bacitracin did not significantly alter insulin concentrations in non-haemolysed samples. Bacitracin attenuates haemolysis-associated insulin degradation in clinical samples, enabling a more accurate assessment of insulin sensitivity and glucose homeostasis.
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Resistencia a la Insulina , Preparaciones Farmacéuticas , Adulto , Bacitracina , Reposicionamiento de Medicamentos , Hemólisis , Humanos , InsulinaRESUMEN
Few studies have characterized the relation between parent's depression symptoms and adolescent's depression symptoms in adolescents at-risk for type 2 diabetes (T2D). We evaluated the associations of parental depression symptoms with the depression symptoms and metabolic functioning of adolescent offspring at-risk for T2D. One-hundred sixteen parents and adolescent girls with a family history of diabetes completed surveys of depression symptoms. Adolescents' degree of metabolic risk for T2D was estimated from body mass index (BMI; kg/m2) standard score, percent adiposity from dual-energy x-ray absorptiometry scan, and whole body insulin sensitivity index determined from glucose/insulin concentrations during a two-hour oral glucose tolerance test. Parents' and adolescents' depression symptoms were significantly associated, even after accounting for race/ethnicity, age, puberty, body composition, and parental diabetes/BMI. Adjusting for similar covariates, parent depression symptoms also were positively related to adolescents' BMI standard score and had a trend-level association with adiposity. There was an inverse relation between parental depression symptoms and adolescent insulin sensitivity, which was entirely accounted for by adolescent body composition. The associations of parental depression symptoms with more elevated depression symptoms and higher BMI in adolescents at-risk for T2D has potential implications for interventions addressing these co-morbid health conditions.
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Hijo de Padres Discapacitados/psicología , Depresión/psicología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/psicología , Padres/psicología , Adolescente , Adulto , Femenino , Humanos , RiesgoRESUMEN
In adipose tissue, resistance to insulin's ability to increase glucose uptake can be induced by multiple factors, including obesity. Impaired insulin action may take place at different spatial loci at the cellular or subcellular level. To begin to understand the spatial response to insulin in human subcutaneous adipose tissue (hSAT), we developed a quantitative imaging method for activation of a major signaling node in the glucoregulatory insulin signaling pathway. After treatment with insulin or control media, biopsied tissues were immunostained for Akt phosphorylation at Thr-308/9 (pAkt) and then imaged by confocal fluorescence microscopy automated to collect a large grid of high resolution fields. In hSAT from 40 men and women with obesity, substantial heterogeneity of pAkt densities in adipocyte membranes were quantified in each image mosaic using a spatial unit of at least twice the size of the point spread function. Statistical analysis of the distribution of pAkt spatial units was best fit as the weighted sum of two separate distributions, corresponding to either a low or high pAkt density. A "high pAkt fraction" metric was calculated from the fraction of high pAkt distributed units over the total units. Importantly, upon insulin stimulation, tissues from the same biopsy showed either a minimal or a substantial change in the high pAkt fraction. Further supporting a two-state response to insulin stimulation, subjects with similar insulin sensitivity indices are also segregated into either of two clusters identified by the amount of membrane-localized pAkt.
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Adipocitos/metabolismo , Insulina/metabolismo , Obesidad/metabolismo , Grasa Subcutánea/metabolismo , Adipocitos/enzimología , Adulto , Anciano , Membrana Celular/metabolismo , Estudios de Cohortes , Activación Enzimática , Femenino , Transportador de Glucosa de Tipo 4/metabolismo , Humanos , Resistencia a la Insulina , Masculino , Microscopía Confocal , Microscopía Fluorescente , Persona de Mediana Edad , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Grasa Subcutánea/enzimología , Adulto JovenRESUMEN
BACKGROUND: The MC3R haplotype C17A + G241A, which encodes a partially inactivated receptor, has high prevalence in individuals of predominately African ancestry. In pediatric cohorts, homozygosity for this common variant has been associated with obesity, reduced lean mass, and greater fasting insulin. However, metabolic and body composition measures have not been well studied in adults with this haplotype. METHODS: A convenience sample of 237 healthy African-American adult volunteers was studied. TaqMan assays were used to genotype MC3R variants. Labs were drawn in the morning in the fasted state. Body composition data was obtained via dual-energy X-ray absorptiometry. An analysis of covariance was used to examine the associations of genotype with metabolic and body composition measures controlling for age and sex. RESULTS: Individuals homozygous for the MC3R C17A + G241A haplotype had significantly greater body mass index, fat mass, fat mass percentage, and C-reactive protein, with reduced lean mass percentage as compared to heterozygous and wild-type participants (all ps < 0.05); fasting insulin was marginally nonsignificant between groups (p = 0.053). After adjusting for fat mass, laboratory differences no longer remained significant. CONCLUSIONS: Homozygosity for MC3R C17A + G241A is associated with increased adiposity in African-American adults. Further studies are needed to elucidate the mechanisms behind these associations.
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Adiposidad/genética , Negro o Afroamericano/genética , Inflamación/genética , Receptor de Melanocortina Tipo 3/genética , Adulto , Índice de Masa Corporal , Femenino , Haplotipos , Humanos , Masculino , Adulto JovenRESUMEN
AIM: To evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in people with obesity and metabolic syndrome (MetS). MATERIALS AND METHODS: Adults with obesity and MetS, but who did not have diabetes, were randomized to colchicine 0.6 mg or placebo capsules twice daily for 3 months. The primary outcome was change in insulin sensitivity (SI ) as estimated by insulin-modified frequently sampled intravenous glucose tolerance tests. Secondary outcomes included changes in other metabolic variables and inflammatory markers. RESULTS: Of 40 participants randomized (21 colchicine, 19 placebo), 37 completed the trial. Compared with placebo, colchicine significantly reduced C-reactive protein (P <0.005), erythrocyte sedimentation rate (P <0.01), white blood cell count (P <0.005), and absolute neutrophil count (P <0.001). Change in SI was not significantly different between colchicine and placebo arms (difference: +0.21 × 10-5 ; CI -1.70 to +2.13 × 10-5 min-1 mU-1 mL; P = 0.82). However, changes in some secondary outcomes, including homeostatic model assessment of insulin resistance (P = 0.0499), fasting insulin (P = 0.07) and glucose effectiveness (P = 0.08), suggested metabolic improvements in the colchicine versus placebo group. Adverse events were generally mild and similar in both groups. CONCLUSIONS: This pilot study found colchicine significantly improved obesity-associated inflammatory variables and showed a good safety profile among adults with obesity and MetS who did not have diabetes. These results suggest a larger, adequately powered study should be conducted to determine whether colchicine improves insulin resistance and other measures of metabolic health in at-risk individuals.
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Antiinflamatorios , Colchicina , Síndrome Metabólico , Adulto , Antiinflamatorios/efectos adversos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Glucemia/análisis , Glucemia/efectos de los fármacos , Proteína C-Reactiva/análisis , Colchicina/efectos adversos , Colchicina/farmacología , Colchicina/uso terapéutico , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina/fisiología , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/tratamiento farmacológico , Persona de Mediana Edad , Obesidad/complicaciones , Proyectos PilotoRESUMEN
Objective: Pediatric loss-of-control (LOC) eating is associated with, and predictive of, gains in adiposity and adverse metabolic outcomes. In addition, some preliminary data suggest that anxiety may exacerbate the relationship of LOC eating with weight and metabolic syndrome (MetS)-related measures. We therefore examined whether anxiety moderated the relationship between LOC eating and body mass index z (BMIz), adiposity, and MetS-related measures in youth. Methods: A convenience sample of non-treatment-seeking boys and girls of varying weight strata were interviewed to determine the presence of LOC eating and completed a questionnaire assessing trait anxiety. BMIz and MetS-related measures (blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucose, and insulin) were measured after an overnight fast. Adiposity was assessed by air displacement plethysmography or dual-energy x-ray absorptiometry. Analyses adjusted for age, sex, race, height, fat mass, and depressive symptoms, as appropriate. Results: In all, 379 youths (13.0 ± 2.8 years; 53% female; BMIz = 0.8 ± 1.1; 22% with LOC eating) were studied. Anxiety was not significantly related to BMIz, adiposity, or MetS-related measures. However, anxiety and LOC eating interacted such that only among youth with LOC eating, anxiety was positively associated with fasting insulin (p = .02) and insulin resistance (p = .01). The interaction of anxiety and LOC eating was not significantly related to BMIz, adiposity, or any other MetS-related measure (ps = ns). Conclusions: Only among non-treatment-seeking youth with LOC eating, anxiety may be associated with increased insulin secretion and insulin resistance. Longitudinal studies are required to confirm these findings and explore mechanisms for these relationships.
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Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/psicología , Conducta Alimentaria/psicología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/psicología , Obesidad/complicaciones , Obesidad/psicología , Adiposidad , Adolescente , Conducta del Adolescente/psicología , Índice de Masa Corporal , Femenino , Humanos , MasculinoRESUMEN
Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is an uncommon cause of adrenal Cushing syndrome (CS) in which cortisol and occasionally other steroid hormones can be secreted under the influence of aberrantly expressed G-protein coupled receptors (GPCRs) in the adrenal cortex. We describe the unique case of a 64-year-old postmenopausal female with PBMAH whose adrenal lesions expressed luteinizing hormone receptors (LHr). She presented initially with CS and underwent right adrenalectomy; a few years later she presented with macromastia and mastodynia, possibly due to estrogen excess from her remaining left adrenocortical masses. Testing before and after treatment with quarterly leuprolide acetate therapy and immunohistochemistry on tissue and targeted sequencing of the genes of interest were performed. Tissue from the patient's right adrenal was tested for P450 aromatase (CYP19A1) and LHr expression; both were expressed throughout the hyperplastic cortex, although expression was more intense in the adenomatous areas. Targeted sequencing revealed a pathogenic PDE11A mutation, as well as variants in the ARMC5 and INHA genes. PDE11A expression was decreased in the adenoma but there was no loss of heterozygosity for the PDE11A locus. Because of the clinical presentation and LHr expression, quarterly leuprolide acetate therapy was started. Shortly after initiation of therapy, the patient reported decreased breast size and pain; she remains well controlled to date, after 10 years of treatment. This is the first description of a patient with PBMAH presenting with severe macromastia and mastodynia from what appears to be excess estrogen production from her adrenal tumor. The patient had a long-lasting response to chronic leuprolide acetate treatment, showing that drug therapy exploiting the aberrant receptor expression in PBMAH is possible even in the absence of cortisol overproduction.
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Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Estrógenos/metabolismo , Leuprolida/uso terapéutico , 3',5'-GMP Cíclico Fosfodiesterasas , Hiperplasia Suprarrenal Congénita/diagnóstico por imagen , Anciano , Secuencia de Bases , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Hidrolasas Diéster Fosfóricas/genética , Receptores de HL/genética , Análisis de Secuencia de ADN , Coloración y Etiquetado , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Inactivating mutations in the melanocortin 3 receptor (Mc3r) have been described as causing obesity in mice, but the physiologic effects of MC3R mutations in humans have been less clear. Here we review the MC3R polymorphisms and mutations identified in humans, and the in vitro, murine, and human cohort studies examining their putative effects. Some, but not all, studies suggest that the common human MC3R variant T6K+V81I, as well as several other rare, function-altering mutations, are associated with greater adiposity and hyperleptinemia with altered energy partitioning. In vitro, the T6K+V81I variant appears to decrease MC3R expression and therefore cAMP generation in response to ligand binding. Knockin mouse studies confirm that the T6K+V81I variant increases feeding efficiency and the avidity with which adipocytes derived from bone or adipose tissue stem cells store triglycerides. Other MC3R mutations occur too infrequently in the human population to make definitive conclusions regarding their clinical effects. This article is part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong Tao.
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Mutación , Obesidad/genética , Polimorfismo Genético , Receptor de Melanocortina Tipo 3/genética , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Predisposición Genética a la Enfermedad , Humanos , Ratones , Obesidad/patologíaRESUMEN
BACKGROUND: Depression is associated with poor insulin sensitivity. We evaluated the long-term effects of a cognitive behavioral therapy (CBT) program for prevention of depression on insulin sensitivity in adolescents at risk for type 2 diabetes (T2D) with depressive symptoms. METHODS: One-hundred nineteen adolescent females with overweight/obesity, T2D family history, and mild-to-moderate depressive symptoms were randomized to a 6-week CBT group (n = 61) or 6-week health education (HE) control group (n = 58). At baseline, posttreatment, and 1 year, depressive symptoms were assessed, and whole body insulin sensitivity (WBISI) was estimated from oral glucose tolerance tests. Dual energy X-ray absorptiometry assessed fat mass at baseline and 1 year. Primary outcomes were 1-year changes in depression and insulin sensitivity, adjusting for adiposity and other relevant covariates. Secondary outcomes were fasting and 2-hr insulin and glucose. We also evaluated the moderating effect of baseline depressive symptom severity. RESULTS: Depressive symptoms decreased in both groups (P < .001). Insulin sensitivity was stable in CBT and HE (ΔWBISI: .1 vs. .3) and did not differ between groups (P = .63). However, among girls with greater (moderate) baseline depressive symptoms (N = 78), those in CBT developed lower 2-hr insulin than those in HE (Δ-16 vs. 16 µIU/mL, P < .05). Additional metabolic benefits of CBT were seen for this subgroup in post hoc analyses of posttreatment to 1-year change. CONCLUSIONS: Adolescent females at risk for T2D decreased depressive symptoms and stabilized insulin sensitivity 1 year following brief CBT or HE. Further studies are required to determine if adolescents with moderate depression show metabolic benefits after CBT.
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Terapia Cognitivo-Conductual/métodos , Depresión/terapia , Diabetes Mellitus Tipo 2/prevención & control , Resistencia a la Insulina , Evaluación de Resultado en la Atención de Salud , Adolescente , Comorbilidad , Depresión/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Educación del Paciente como Asunto , Psicoterapia de Grupo/métodosRESUMEN
OBJECTIVE: Adolescent emotional-eating, referring to eating in response to negative affective states, is frequently reported by those with loss of control (LOC) eating. Although LOC eating has been shown to predict exacerbated disordered eating and excess weight/adiposity gain, the extent to which emotional-eating, either alone or in combination with LOC, predicts adverse outcomes has not been determined. Thus, we examined associations of baseline emotional-eating with changes in disordered eating, BMI, and adiposity over 1-year, and to what degree the presence or absence of baseline LOC moderated these associations. METHODS: 189 non-treatment-seeking youth (15.4 ± 1.4y; 66% female; 67% non-Hispanic White, 38% overweight [BMI ≥ 85th %ile]) completed the emotional-eating Scale for Children/Adolescents and the Eating Disorder Examination interview at baseline and again at 1-year. Air displacement plethysmography assessed adiposity at both time points. RESULTS: Baseline emotional-eating alone was not significantly associated with the development of objective binge eating or changes in disordered eating attitudes, BMI or adiposity 1-year later. However, baseline emotional-eating interacted with the presence of baseline LOC in the prediction of 1-year outcomes. Among adolescents with LOC eating, greater baseline emotional-eating was related to increased disordered eating attitudes (p = .03), BMI (p = .04), and adiposity (p = .04) at 1-year, after correcting for false discovery rate. DISCUSSION: Emotional-eating among youth also reporting LOC was associated with adverse outcomes over 1-year. Adolescents who report both behaviors may represent a subset of individuals at especially high risk for exacerbated disordered eating and excess weight gain. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:551-560).
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Adiposidad/fisiología , Trastorno por Atracón/psicología , Peso Corporal/fisiología , Emociones/fisiología , Adolescente , Femenino , Humanos , Masculino , Factores de TiempoRESUMEN
BACKGROUND: Prospective data suggest depressive symptoms worsen insulin resistance and accelerate type 2 diabetes (T2D) onset. PURPOSE: We sought to determine whether reducing depressive symptoms in overweight/obese adolescents at risk for T2D would increase insulin sensitivity and mitigate T2D risk. METHOD: We conducted a parallel-group, randomized controlled trial comparing a 6-week cognitive-behavioral (CB) depression prevention group with a 6-week health education (HE) control group in 119 overweight/obese adolescent girls with mild-to-moderate depressive symptoms (Center for Epidemiological Studies-Depression Scale [CES-D] ≥16) and T2D family history. Primary outcomes were baseline to post-intervention changes in CES-D and whole body insulin sensitivity index (WBISI), derived from 2-h oral glucose tolerance tests. Outcome changes were compared between groups using ANCOVA, adjusting for respective baseline outcome, puberty, race, facilitator, T2D family history degree, baseline age, adiposity, and adiposity change. Multiple imputation was used for missing data. RESULTS: Depressive symptoms decreased (p < 0.001) in CB and HE from baseline to posttreatment, but did not differ between groups (ΔCESD = -12 vs. -11, 95 % CI difference = -4 to +1, p = 0.31). Insulin sensitivity was stable (p > 0.29) in CB and HE (ΔWBISI = 0.1 vs. 0.2, 95 % CI difference = -0.6 to +0.4, p = 0.63). Among all participants, reductions in depressive symptoms were associated with improvements in insulin sensitivity (p = 0.02). CONCLUSIONS: Girls at risk for T2D displayed reduced depressive symptoms following 6 weeks of CB or HE. Decreases in depressive symptoms related to improvements in insulin sensitivity. Longer-term follow-up is needed to determine whether either program causes sustained decreases in depressive symptoms and improvements in insulin sensitivity. TRIAL REGISTRATION NUMBER: The trial was registered with clinicaltrials.gov (NCT01425905).
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Terapia Cognitivo-Conductual/métodos , Depresión/prevención & control , Diabetes Mellitus Tipo 2/prevención & control , Resistencia a la Insulina , Adolescente , Niño , Femenino , Humanos , Resultado del TratamientoRESUMEN
The interpersonal model of loss of control (LOC) eating proposes that socially distressing situations lead to anxious states that trigger excessive food consumption. Self-reports support these links, but the neurobiological underpinnings of these relationships remain unclear. We therefore examined brain regions associated with anxiety in relation to LOC eating and energy intake in the laboratory. Twenty-two overweight and obese (BMIz: 1.9±0.4) adolescent (15.8±1.6y) girls with LOC eating (LOC+, n=10) and without LOC eating (LOC-, n=12) underwent functional magnetic resonance imaging (fMRI) during a simulated peer interaction chatroom paradigm. Immediately after the fMRI scan, girls consumed lunch ad libitum from a 10,934-kcal laboratory buffet meal with the instruction to "let yourself go and eat as much as you want." Pre-specified hypotheses regarding activation of five regions of interest were tested. Analysis of fMRI data revealed a significant group by peer feedback interaction in the ventromedial prefrontal cortex (vmPFC), such that LOC+ had less activity following peer rejection (vs. acceptance), while LOC- had increased activity (p<.005). Moreover, functional coupling between vmPFC and striatum for peer rejection (vs. acceptance) interacted with LOC status: coupling was positive for LOC+, but negative in LOC- (p<.005). Activity of fusiform face area (FFA) during negative peer feedback from high-value peers also interacted with LOC status (p<.005). A positive association between FFA activation and intake during the meal was observed among only those with LOC eating. In conclusion, overweight and obese girls with LOC eating may be distinguished by a failure to engage regions of prefrontal cortex implicated in emotion regulation in response to social distress. The relationship between FFA activation and food intake supports the notion that heightened sensitivity to incoming interpersonal cues and perturbations in socio-emotional neural circuits may lead to overeating in order to cope with negative affect elicited by social discomfort in susceptible youth.
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Encéfalo/fisiopatología , Ingestión de Alimentos , Red Nerviosa/fisiopatología , Sobrepeso/fisiopatología , Sobrepeso/psicología , Influencia de los Compañeros , Adolescente , Niño , Femenino , Humanos , Obesidad/fisiopatología , Obesidad/psicologíaRESUMEN
Emerging data indicate that adults with binge eating may exhibit an attentional bias toward highly palatable foods, which may promote obesogenic eating patterns and excess weight gain. However, it is unknown to what extent youth with loss of control (LOC) eating display a similar bias. We therefore studied 76 youth (14.5 ± 2.3 years; 86.8% female; BMI-z 1.7 ± .73) with (n = 47) and without (n = 29) reported LOC eating. Following a breakfast to reduce hunger, youth participated in a computerized visual probe task of sustained attention that assessed reaction time to pairs of pictures consisting of high palatable foods, low palatable foods, and neutral household objects. Although sustained attentional bias did not differ by LOC eating presence and was unrelated to body weight, a two-way interaction between BMI-z and LOC eating was observed (p = .01), such that only among youth with LOC eating, attentional bias toward high palatable foods versus neutral objects was positively associated with BMI-z. These findings suggest that LOC eating and body weight interact in their association with attentional bias to highly palatable foods cues, and may partially explain the mixed literature linking attentional bias to food cues with excess body weight.
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Atención , Índice de Masa Corporal , Bulimia/psicología , Señales (Psicología) , Ingestión de Alimentos/psicología , Obesidad/etiología , Gusto , Adolescente , Peso Corporal , Niño , Ingestión de Energía , Conducta Alimentaria , Femenino , Alimentos , Humanos , Hambre , Masculino , Obesidad/psicología , Controles Informales de la Sociedad , Aumento de PesoRESUMEN
OBJECTIVE: We investigated the manifestations of pediatric loss of control (LOC) eating at different stages of pubertal development. METHOD: Participants were a nonclinical sample of 468 youth (8-17 years). Physical examination determined pubertal stage. LOC eating and disordered eating attitudes were assessed with the Eating Disorder Examination. In a randomized crossover design, a subset (n = 244) ate ad libitum from two test meals designed to capture normal and LOC eating. RESULTS: There were no differences in the prevalence rates or frequency of reported LOC eating episodes across pubertal stages (ps ≥ 0.50). There were, however, puberty by LOC eating interactions in disordered eating attitudes and palatable food consumption (ps ≤ .05), even after adjusting for age and body composition. LOC eating was associated with elevated global disordered eating attitudes, weight concern, and shape concern in post-pubertal youth (ps ≤ .001), but not pre-pubertal youth (ps ≥ .49). In late-puberty, youth with LOC eating consumed less energy from protein (p < .001) and more from carbohydrate (p = .003) and snack-type foods (p = .02) than those without LOC eating, whereas endorsement of LOC eating in pre- or early-to-mid-puberty was not associated with differences in eating behavior (ps ≥ 0.20). CONCLUSIONS: Findings suggest that puberty may be a critical risk period, when LOC eating behaviors in boys and girls may become accompanied by greater weight and shape concerns and more obesogenic food consumption patterns. Interventions for LOC eating during pre-puberty should be evaluated to determine if they are particularly beneficial for the prevention of exacerbated eating disorder psychopathology and adverse weight outcomes.
Asunto(s)
Conducta Alimentaria/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Pubertad/fisiología , Adolescente , Composición Corporal , Peso Corporal , Niño , Estudios Cruzados , Femenino , Humanos , Masculino , Pubertad/psicologíaRESUMEN
Diabetes mellitus is currently approaching epidemic proportions and disproportionately affects patients in the hospital setting. In the United States, individuals living with diabetes represent over 17 million emergency department visits and 8 million admissions annually. The management of these patients in the hospital setting is complex and differs considerably from the outpatient setting. All patients with hyperglycemia should be screened for diabetes, as in-hospital hyperglycemia portends a greater risk for morbidity, mortality, admission to an intensive care unit, and increased hospital length of stay. However, the definition of hyperglycemia, glycemic targets, and strategies to manage hyperglycemia in the inpatient setting can vary greatly depending on the population considered. Moreover, the presenting illness, changing nutritional status, and concurrent hospital medications often necessitate thoughtful consideration to adjustments of home diabetes regimens and/or the initiation of new insulin doses. This review article will examine core concepts and emerging new literature surrounding inpatient diabetes management, including glycemic targets, insulin dosing strategies, noninsulin medications, new diabetes technologies, inpatient diabetes management teams, and discharge planning strategies, to optimize patient safety and satisfaction, clinical outcomes, and even hospital financial health.
Asunto(s)
Diabetes Mellitus , Hipoglucemiantes , Pacientes Internos , Humanos , Diabetes Mellitus/terapia , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Hospitalización , Hiperglucemia/terapia , Hiperglucemia/tratamiento farmacológico , Glucemia/metabolismo , Manejo de la EnfermedadRESUMEN
AIMS: Hospitalized patients can have inconsistent nutritional intake due to acute illness, changing diet, or unpredictable meal delivery. The aim of this study was to evaluate whether implementation of a hospital-wide policy shifting nutritional insulin administration from pre-meal to post-meal was associated with changes in glycemic control or length of stay (LOS). METHODS: This retrospective study performed at a community hospital evaluated adult inpatients receiving nutritional insulin across three time periods. pre-intervention, immediate post-intervention, and distant post-intervention. Outcomes included rates of hypoglycemia (glucose ≤ 70 mg/dL), moderate hypoglycemia (< 54 mg/dL), severe hypoglycemia (≤ 40 mg/dL), severe hyperglycemia (≥ 300 mg/dL), daily mean glucose level, and LOS. RESULTS: The number of patient-days analyzed across the cohorts were 1948, 1751, and 3244, respectively. After multivariate adjustment, risk of developing any hypoglycemia and severe hypoglycemia significantly decreased over time (p = 0.001 and p = 0.009, respectively). Daily mean glucose increased over time (194.6 ± 62.5 vs 196.8 ± 65.5 vs 199.3 ± 61.5 mg/dL; p = 0.003), but there were no significant differences among rates of severe hyperglycemia (p = 0.10) or LOS (p = 0.74). CONCLUSIONS: Implementing a hospital-wide shift to postprandial nutritional insulin administration significantly reduced hypoglycemia rates without increasing severe hyperglycemia. This suggests a promising strategy for improving patient safety, but further prospective randomized controlled trials are warranted to confirm these findings.