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2.
Endocr Pract ; 24(2): 205-219, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29466062

RESUMEN

OBJECTIVE: Individuals with diabetes are increasingly seeking pretravel advice, but updated professional recommendations remain scant. We performed a systematic review on diabetes management during air travel to summarize current recommendations, assess supporting evidence, and identify areas of future research. METHODS: A systematic review of the English literature on diabetes management during air travel was undertaken utilizing PubMed and MEDLINE. Publications regarding general travel advice; adjustment of insulin and noninsulin therapies; and the use of insulin pumps, glucometers and subcutaneous glucose sensors at altitude were included. Gathered information was used to create an updated summary of glucose-lowering medication adjustment during air travel. RESULTS: Sixty-one publications were identified, most providing expert opinion and few offering primary data (47 expert opinion, 2 observational studies, 2 case reports, 10 device studies). General travel advice was uniform, with increasing attention to preflight security. Indications for oral antihyperglycemic therapy adjustments varied. There were few recommendations on contemporary agents and on nonhypoglycemic adverse events. There was little consensus on insulin adjustment protocols, many antedating current insulin formulations. Most publications advocated adjusting insulin pump time settings after arrival; however, there was disagreement on timing and rate adjustments. Glucometers and subcutaneous glucose sensors were reported to be less accurate at altitude, but not to an extent that would preclude their clinical use. CONCLUSION: Recommendations for diabetes management during air travel vary significantly and are mostly based on expert opinion. Data from systematic investigation on glucose-lowering medication adjustment protocols may support the development of a future consensus statement. ABBREVIATIONS: CSII = continuous subcutaneous insulin infusion (device) DPP-4 = dipeptidyl peptidase 4 EGA = error grid analysis GDH = glucose dehydrogenase GOX = glucose oxidase GLP1 = glucagon-like peptide-1 NPH = neutral protamine Hagedorn SGLT2 = sodium-glucose cotransporter-2.


Asunto(s)
Viaje en Avión , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Práctica Clínica Basada en la Evidencia , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Guías de Práctica Clínica como Asunto , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 2/sangre , Práctica Clínica Basada en la Evidencia/normas , Humanos , Sistemas de Infusión de Insulina
3.
Physiol Genomics ; 47(6): 215-24, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25759378

RESUMEN

Overweight/obese individuals with Type 2 diabetes have low adiponectin levels, which may improve with lifestyle changes. We investigated whether genetic variants associated with adiponectin levels in genome-wide association studies (GWAS) would also be related with adiponectin changes in response to an intensive lifestyle intervention (ILI), potentially through mechanisms altering the adipose microenvironment via weight loss and/or improved cardiorespiratory fitness. Look AHEAD was a randomized trial comparing the cardiovascular benefits of ILI-induced weight loss and physical activity compared with diabetes support and education among overweight/obese individuals with Type 2 diabetes. In a subsample of Look AHEAD with adiponectin data and genetic consent (n=1,351), we evaluated the effects of 24 genetic variants, demonstrated by GWAS to be cross-sectionally associated with adiponectin, on adiponectin change 1-yr postintervention. We explored via mediational analyses whether any differential effects by treatment arm were occurring through weight loss and/or improved fitness. A variant, rs222857, in the CLDN7 locus, potentially associated with epithelial barrier integrity and tight junction physiology, and a putative cis expression quantitative trail locus for elongator acetyltransferase complex subunit 5 (ELP5), predicted adiponectin increases within ILI (log-adiponectin in overall sample per copy: ß±SE=0.05±0.02, P=0.008; in non-Hispanic whites: 0.06±0.02, P=0.009). The favorable effects of rs222857 (minor allele frequency 45.5%) appeared to be mediated by mechanisms associated with improved fitness, and not weight loss. This is the first study to identify a genetic variant that modifies adiponectin response to lifestyle intervention in overweight/obese diabetic individuals.


Asunto(s)
Adiponectina/genética , Claudinas/genética , Diabetes Mellitus Tipo 2/genética , Estilo de Vida , Obesidad/genética , Aptitud Física , Polimorfismo de Nucleótido Simple/genética , Adiposidad/genética , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Sitios Genéticos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones
5.
J Lipid Res ; 53(12): 2726-33, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22956782

RESUMEN

Adipose tissue dysfunction plays a key role in the development of the metabolic abnormalities characteristic of type 2 diabetes (T2DM) and participates actively in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of adipose health, is decreased in obese persons with T2DM. We investigated whether the changes in adiponectin with an intensive lifestyle intervention (ILI) for weight loss could potentially mediate the increase in low HDL-cholesterol (HDL-C) with ILI. Adiponectin and its fractions were determined using an ELISA with selective protease treatment in 1,397 participants from Look AHEAD, a trial examining whether ILI will reduce cardiovascular events in overweight/obese subjects with T2DM when compared with a control arm, diabetes support and education (DSE). Multivariable regression and mediational analyses were performed for adiponectin and its high-molecular-weight (HMW) and non-HMW fractions. ILI increased baseline HDL-C by 9.7% and adiponectin by 11.9%; changes with DSE were 1.3% and 0.2%, respectively (P < 0.0001). In a model including changes in weight, fitness, triglycerides, and glucose control and that adjusted for demographics and medical history, adiponectin changes remained significantly associated with HDL-C change. Data supported the contribution of changes in both HMW- and non-HMW-adiponectin to the improvement in HDL-C with ILI.


Asunto(s)
Adiponectina/sangre , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/prevención & control , Pérdida de Peso , Adiponectina/metabolismo , HDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Análisis Multivariante
6.
Arterioscler Thromb Vasc Biol ; 31(7): 1689-95, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21512162

RESUMEN

OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1) production by adipose tissue is increased in obesity, and its circulating levels are high in type 2 diabetes. PAI-1 increases cardiovascular risk by favoring clot stability, interfering with vascular remodeling, or both. We investigated in obese diabetic persons whether an intensive lifestyle intervention for weight loss (ILI) would decrease PAI-1 levels independently of weight loss and whether PAI-1 reduction would be associated with changes in fibrinogen, an acute phase reactant, or fibrin fragment D-dimer (D-dimer), a marker of ambient coagulation balance. METHODS AND RESULTS: We examined 1-year changes in PAI-1, D-dimer, and fibrinogen levels; adiposity; fitness; glucose; and lipid control with ILI in 1817 participants from Look AHEAD, a randomized trial investigating the effects of ILI, compared with usual care, on cardiovascular events in overweight or obese diabetic persons. Median PAI-1 levels decreased 29% with ILI and 2.5% with usual care (P < 0.0001). Improvements in fitness, glucose control, and high-density lipoprotein cholesterol were associated with decreased PAI-1, independently of weight loss (P = 0.03 for fitness, P < 0.0001 for others). Fibrinogen and D-dimer remained unchanged. CONCLUSIONS: Reductions in PAI-1 levels with ILI in obese diabetic individuals may reflect an improvement in adipose tissue health that could affect cardiovascular risk without changing fibrinogen or d-dimer levels. Clinical Trial Registration- URL: http://clinicaltrials.gov/ct2/show/NCT00017953. Unique identifier: NCT00017953.


Asunto(s)
Tejido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/sangre , Obesidad/terapia , Inhibidor 1 de Activador Plasminogénico/sangre , Conducta de Reducción del Riesgo , Tejido Adiposo/fisiopatología , Adiposidad , Biomarcadores/sangre , Glucemia/metabolismo , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Dieta , Ejercicio Físico , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinógeno/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/fisiopatología , Aptitud Física , Análisis de Regresión , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Pérdida de Peso
7.
Crit Care Explor ; 2(11): e0260, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33196048

RESUMEN

BACKGROUND: There is a paucity of clinical data on corticosteroid replacement in patients with adrenal insufficiency who present with nonsevere noncomplicated diabetic ketoacidosis. CASE SUMMARY: We analyzed five consecutive admissions for diabetic ketoacidosis of mild/moderate severity due to insulin omission in a 21-year-old man with type 1 diabetes and stable Addison disease. Despite similar presentations, the approach to steroid replacement differed: maintenance/moderate doses of hydrocortisone (< 60 mg/d) or high stress-doses (≥ 120 mg/d). Resolution of diabetic ketoacidosis and ICU and hospital length of stay were prolonged when high-dose versus maintenance/moderate glucocorticoids were provided: 45.5, 47.0, and 63.0 versus 12.0, 24.5, and 31 hours, respectively. CONCLUSIONS: Although our findings remain hypothesis-generating, our case study raises awareness on the importance of categorizing diabetic ketoacidosis by severity and complication status when deciding on the intensity of steroid replacement in patients with stable Addison disease. Excessive glucocorticoid administration may delay the resolution of nonsevere and otherwise noncomplicated diabetic ketoacidosis and prolong ICU and hospital stays.

8.
AACE Clin Case Rep ; 6(6): e346-e348, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33244500

RESUMEN

OBJECTIVE: Topical steroid use is common, but its association with Cushing syndrome is rare. We report the rapid development of iatrogenic Cushing syndrome in a patient on ritonavir who applied a moderate-potency topical steroid cream, triamcinolone, on his genital mucosa for treatment of phimosis. METHODS: Clinical and diagnostic challenges associated with topical steroid use are presented and discussed. RESULTS: A 41-year-old man with human immunodeficiency virus infection on stable antiretroviral therapy that included ritonavir, a cytochrome P450 3A4 inhibitor, presented with new onset diabetes and development of overt cushingoid features over a 4-week period. He reported no known history of steroid use. A midnight salivary cortisol using a quantitative enzyme immunoassay was obtained and reported at >15.0 µg/dL (normal, <0.112 µg/dL). However, free cortisol in a 24-hour urine collection was undetectable by high-performance liquid chromatography and morning plasma cortisol was also unexpectedly low at 1.1 µg/dL (normal, 4.5 to 23.0 µg/dL). Further investigation revealed that the patient had been applying a topical cream with triamcinolone acetonide (0.1%) on the glans penis for treatment of phimosis. The salivary enzyme immunoassay for cortisol appears to have detected the absorbed triamcinolone, a compound known to cross-react with cortisol in this assay. CONCLUSION: This case raises awareness on the severe metabolic consequence resulting from the seemingly benign use of a topical steroid medication when applied to the genital mucosa in the setting of stable therapy with ritonavir and illustrates the limitations of salivary cortisol enzyme immunoassays for the evaluation of Cushing syndrome in this setting.

10.
Am J Med ; 135(5): 550-551, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35101423
12.
Circ Cardiovasc Genet ; 9(1): 71-8, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26578543

RESUMEN

BACKGROUND: Glucokinase regulatory protein (GCKR) inhibitors offer a novel treatment approach for glucose control in diabetes mellitus; however, their cardiometabolic effects, particularly in relation to increased triglycerides and C-reactive protein (CRP) levels, are of concern. GCKR Leu446Pro is a common variant associated with reduced GCKR function, increased triglycerides, and CRP. METHODS AND RESULTS: We investigated whether a 1-year intensive lifestyle intervention (ILI) for weight loss would avert the unfavorable cardiometabolic effects associated with GCKR Leu446Pro when compared with a diabetes mellitus support and education arm in overweight/obese individuals with type 2 diabetes mellitus with triglyceride (n=3214) and CRP (n=1411) data participating in a randomized lifestyle intervention study for weight loss, Action for Health in Diabetes Mellitus (Look AHEAD). Once demographics, medication use and baseline adiposity, and fitness were accounted for, ILI did not modify the baseline association of GCKR-Leu446Pro with elevated triglycerides (ß±SE=0.067±0.013, P=1.5×10(-7) and ß±SE=0.052±0.015, P=5×10(-4)) or with elevated CRP (ß±SE=0.136±0.034, P=5.1×10(-5)and ß±SE=0.903±0.038, P=0.015) in the overall sample and Non-Hispanic Whites, respectively. The lack of a protective effect from ILI at 1 year when compared with diabetes mellitus support and education (ILI versus diabetes mellitus support and education interaction for triglyceride and CRP change, respectively: P=0.64 and 0.37 in the overall sample; P=0.27 and 0.05 in Non-Hispanic Whites) persisted after additional adjustment for changes in adiposity and fitness. CONCLUSIONS: Moderate improvements in adiposity and fitness with ILI did not mitigate the adverse cardiometabolic effects of GCKR inhibition in overweight/obese individuals with diabetes mellitus.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Adiposidad/genética , Diabetes Mellitus Tipo 2/genética , Estilo de Vida , Mutación Missense , Obesidad/genética , Pérdida de Peso/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Anciano , Sustitución de Aminoácidos , Glucemia/genética , Glucemia/metabolismo , Proteína C-Reactiva/metabolismo , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Triglicéridos/sangre , Triglicéridos/genética
13.
Circulation ; 107(21): 2726-32, 2003 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-12742997

RESUMEN

BACKGROUND: Epidemiologic studies and transgenic mouse experiments indicate that high plasma HDL and apolipoprotein (apo) A-I protect against atherosclerosis. We used helper-dependent adenovirus (HD-Ad) gene transfer to examine the effect of long-term hepatic apoA-I expression on atherosclerotic lesion progression and remodeling in a mouse model of familial hypercholesterolemia. METHODS AND RESULTS: We treated LDL receptor-deficient (LDLR-/-) mice maintained on a high-cholesterol diet for 6 weeks with either a HD-Ad containing human apoA-I gene (HD-Ad-AI) or saline (control). HD-Ad-AI treatment did not affect plasma liver enzymes but induced the appearance of plasma human apoA-I at or above human levels for the duration of the study. Substantial amounts of human apoA-I existed in lipid-free plasma. Compared with controls, HDLs from treated mice were larger and had a greater inhibitory effect on tumor necrosis factor-alpha-induced vascular cellular adhesion molecule-1 expression in cultured endothelial cells. Twenty-four weeks after injection, aortic atherosclerotic lesion area in saline-treated mice progressed approximately 700%; the rate of progression was reduced by >50% by HD-Ad-AI treatment. The lesions in HD-Ad-AI-treated mice contained human apoA-I that colocalized mainly with macrophages; they also contained less lipid, fewer macrophages, and less vascular cellular adhesion molecule-1 immunostaining but more smooth muscle cells (alpha-actin staining) and collagen. CONCLUSIONS: HD-Ad-AI treatment of LDLR-/- mice leads to long-term overexpression of apoA-I, retards atherosclerosis progression, and remodels the lesions to a more stable-appearing phenotype. HD-Ad-mediated transfer of apoA-I may be a useful clinical approach for protecting against atherosclerosis progression and stabilizing atherosclerotic lesions associated with dyslipidemia in human patients.


Asunto(s)
Adenoviridae/genética , Apolipoproteína A-I/biosíntesis , Arteriosclerosis/terapia , Terapia Genética/métodos , Hiperlipoproteinemia Tipo II/complicaciones , Animales , Aorta/patología , Apolipoproteína A-I/sangre , Apolipoproteína A-I/genética , Arteriosclerosis/complicaciones , Arteriosclerosis/patología , Colesterol/sangre , Colesterol en la Dieta , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Expresión Génica , Técnicas de Transferencia de Gen , Humanos , Hiperlipoproteinemia Tipo II/genética , Inmunohistoquímica , Lipoproteínas HDL/sangre , Ratones , Ratones Noqueados , Receptores de LDL/deficiencia , Receptores de LDL/genética , Tiempo , Resultado del Tratamiento
14.
Diabetes Care ; 38(8): 1544-50, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25972574

RESUMEN

OBJECTIVE: This study investigated whether fitness changes resulting from lifestyle interventions for weight loss may independently contribute to the improvement of low adiponectin levels in obese individuals with diabetes. RESEARCH DESIGN AND METHODS: Look AHEAD (Action for Health in Diabetes) randomized overweight/obese individuals with type 2 diabetes to intensive lifestyle intervention (ILI) for weight loss or to diabetes support and education (DSE). Total and high-molecular weight adiponectin (adiponectins), weight, and cardiorespiratory fitness (submaximal exercise stress test) were measured in 1,397 participants at baseline and at 1 year, when ILI was most intense. Regression analyses examined the associations of 1-year weight and fitness changes with change in adiponectins. RESULTS: ILI resulted in greater improvements in weight, fitness, and adiponectins at 1 year compared with DSE (P < 0.0001). Weight loss and improved fitness were each associated with changes in adiponectins in men and women (P < 0.001 for all), after adjusting for baseline adiponectins, demographics, clinical variables, and treatment arm. Weight loss contributed an additional 4-5% to the variance of change in adiponectins than did increased fitness in men; in women, the contributions of improved fitness (1% greater) and of weight loss were similar. When weight and fitness changes were both accounted for, weight loss in men and increased fitness in women retained their strong associations (P < 0.0001) with adiponectin change. CONCLUSIONS: Improvements in fitness and weight with ILI were favorably but distinctly associated with changes in adiponectin levels in overweight/obese men and women with diabetes. Future studies need to investigate whether sex-specific biological determinants contribute to the observed associations.


Asunto(s)
Adiponectina/metabolismo , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/sangre , Sobrepeso/sangre , Conducta de Reducción del Riesgo , Pérdida de Peso/fisiología , Adulto , Diabetes Mellitus Tipo 2/prevención & control , Angiopatías Diabéticas/prevención & control , Prueba de Esfuerzo , Terapia por Ejercicio/métodos , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Obesidad/sangre , Sobrepeso/prevención & control , Aptitud Física/fisiología
15.
Physiol Genomics ; 19(1): 131-42, 2004 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-15238619

RESUMEN

Diet-induced changes in serum lipoproteins are a major risk factor for the development of atherosclerosis, the leading cause of mortality in Westernized countries. Atherosclerosis is now appreciated to be a systemic inflammatory disease where increased synthesis of inducible proteins by the liver, such as C-reactive protein (CRP) and others, may play roles in accelerating the disease process. To systematically investigate the genetic response of the liver to diet-induced atherosclerosis, we applied high-density microarray technology in a mouse model of atherosclerosis (LDLR-/- mouse). LDLR-/- mice and congenic (LDLR+/+) controls were placed on low-fat (LF) or high-fat (HF) Western-style diets. The Western diet produced sustained elevations in total cholesterol (2.5-fold for LDLR+/+, 5.0-fold LDLR-/-) relative to the respective LF groups. Tissues were harvested after 12 wk when significant atherosclerotic lesion development was first detectable by en face histomorphometry of oil red O-stained aortas. Diet, rather than genotype, was most highly associated with development of atherosclerotic lesions. Liver mRNA expression profiles of triplicate animals from each group were determined by high-density oligonucleotide microarrays; and genes with transcript levels influenced by genotype and diet were identified by two-way ANOVA. Approximately one-third of the 102 genes identified to be altered by diet [Pr(F) < 0.0005] were involved in lipid metabolism. In addition, we identified components of the alternative complement pathway, including C3, properdin, and factor D, for which mRNA levels were independently confirmed by quantitative real-time RT-PCR analysis, and C3 protein was demonstrated in aortic lesions by immunostaining. These findings suggest that induction of the alternative complement pathway may be an additional mechanism by which a high-fat/Western diet accelerates atherosclerosis.


Asunto(s)
Arteriosclerosis/genética , Arteriosclerosis/patología , Vía Alternativa del Complemento/efectos de los fármacos , Grasas de la Dieta/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Animales , Arteriosclerosis/sangre , Arteriosclerosis/inducido químicamente , Complemento C3/análisis , Complemento C3/inmunología , Vía Alternativa del Complemento/genética , Vía Alternativa del Complemento/inmunología , Dieta , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Genotipo , Lípidos/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/sangre , Obesidad/inducido químicamente , Obesidad/genética , Obesidad/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Receptores de LDL/deficiencia , Receptores de LDL/genética
16.
Gene ; 327(2): 153-60, 2004 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-14980712

RESUMEN

Apolipoprotein A-I (APOA-I) is the major protein component of high-density lipoproteins (HDL). It has been shown that over-expression of human APOA-I increases HDL cholesterol and decreases atherosclerosis. We constructed a helper-dependent adenoviral (HD-Ad) vector that contains the entire human APOA-I gene (hgAI). Intravenous delivery of 1x10(13) viral particles/kg of this vector was followed by high levels of human APOA-I expression (up to 200 mg/dl) in the absence of detectable hepatic toxicity. We treated apo E-deficient mice with the hgAI vector and fed them either with a high-fat diet or with regular chow. As a control, two groups of mice were treated with PBS. The apo E-deficient mice treated with the hgAI vector showed supraphysiological levels of expression of human APOA-I at week 4 and high levels of HDL cholesterol compared to the control groups. Analysis of aortic atherosclerotic lesions 20 weeks after treatment, showed a significant reduction of lesion size in the treated mice with both diets. In conclusion, liver-directed gene transfer of human APOA-I using a HD-Ad vector resulted in a reduction of the development of atherosclerosis with the absence of significant toxicity.


Asunto(s)
Apolipoproteína A-I/metabolismo , Apolipoproteínas E/deficiencia , Arteriosclerosis/patología , Vectores Genéticos/genética , Adenoviridae/genética , Animales , Aorta/efectos de los fármacos , Aorta/patología , Apolipoproteína A-I/genética , Apolipoproteínas E/genética , Arteriosclerosis/sangre , Arteriosclerosis/prevención & control , HDL-Colesterol/sangre , Expresión Génica , Vectores Genéticos/administración & dosificación , Virus Helper/genética , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factores de Tiempo
17.
Med Sci Sports Exerc ; 46(2): 302-11, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23899896

RESUMEN

PURPOSE: Numerous prospective studies indicate that improved cardiorespiratory fitness reduces type 2 diabetes risk and delays disease progression. We hypothesized that genetic variants modify fitness response to an intensive lifestyle intervention (ILI) in the Action for Health in Diabetes (Look AHEAD) randomized clinical trial, aimed to detect whether ILI will reduce cardiovascular events in overweight/obese subjects with type 2 diabetes compared with a standard of care. METHODS: Polymorphisms in established fitness genes and in all loci assayed on the Illumina CARe iSelect chip were examined as predictors of change in MET level, estimated using a treadmill test, in response to a 1-yr intervention in 3899 participants. RESULTS: We identified a significant signal in previously reported fitness-related gene RUNX1 that was associated with 1-yr METs response in ILI (0.19 ± 0.04 MET less improvement per minor allele copy; P = 1.9 × 10(-5)) and genotype-intervention interaction (P = 4.8 × 10(-3)). In the chipwide analysis, FKBP7 rs17225700 showed a significant association with ILI response among subjects not receiving beta-blocker medications (0.47 ± 0.09 METs less improvement; P = 5.3 × 10(-5)) and genotype-treatment interaction (P = 5.3 × 10(-7)). The Gene Relationships Among Implicated Loci pathway-based analysis identified connections between associated genes, including those influencing vascular tone, muscle contraction, cardiac energy substrate dynamics, and muscle protein synthesis. CONCLUSIONS: This is the first study to identify genetic variants associated with fitness responses to a randomized lifestyle intervention in overweight/obese diabetic individuals. RUNX1 and FKBP7, involved in erythropoesis and muscle protein synthesis, respectively, are related to change in cardiorespiratory fitness in response to exercise.


Asunto(s)
Proteínas de Unión al Calcio/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Obesidad/genética , Obesidad/terapia , Aptitud Física , Proteínas de Unión a Tacrolimus/genética , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Alelos , Diabetes Mellitus Tipo 2/fisiopatología , Prueba de Esfuerzo , Femenino , Conductas Relacionadas con la Salud , Heterocigoto , Humanos , Estilo de Vida , Desequilibrio de Ligamiento , Masculino , Equivalente Metabólico , Persona de Mediana Edad , Obesidad/fisiopatología , Esfuerzo Físico/fisiología , Polimorfismo de Nucleótido Simple , Conducta de Reducción del Riesgo
18.
J Acad Nutr Diet ; 114(11): 1800-10.e2, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25131348

RESUMEN

Plasminogen activator inhibitor 1 (PAI-1) is elevated in obese individuals with type 2 diabetes and may contribute, independently of traditional factors, to increased cardiovascular disease risk. Fiber intake may decrease PAI-1 levels. We examined the associations of fiber intake and its changes with PAI-1 before and during an intensive lifestyle intervention (ILI) for weight loss in 1,701 Look AHEAD (Action for Health in Diabetes) participants with dietary, fitness, and PAI-1 data at baseline and 1 year. Look AHEAD was a randomized cardiovascular disease trial in 5,145 overweight/obese patients with type 2 diabetes, comparing ILI (goal of ≥7% reduction in baseline weight) with a control arm of diabetes support and education. ILI participants were encouraged to consume vegetables, fruits, and grain products low in sugar and fat. At baseline, median fiber intake was 17.9 g/day. Each 8.3 g/day higher fiber intake was associated with a 9.2% lower PAI-1 level (P=0.008); this association persisted after weight and fitness adjustments (P=0.03). Higher baseline intake of fruit (P=0.019) and high-fiber grain and cereal (P=0.029) were related to lower PAI-1 levels. Although successful in improving weight and physical fitness at 1 year, the ILI in Look AHEAD resulted in small increases in fiber intake (4.1 g/day, compared with -2.35 g/day with diabetes support and education) that were not related to PAI-1 change (P=0.34). Only 31.3% of ILI participants (39.8% of women, 19.1% of men) met daily fiber intake recommendations. Increasing fiber intake in overweight/obese individuals with diabetes interested in weight loss is challenging. Future studies evaluating changes in fiber consumption during weight loss interventions are warranted.


Asunto(s)
Terapia Conductista , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/terapia , Fibras de la Dieta/uso terapéutico , Estilo de Vida , Sobrepeso/terapia , Inhibidor 1 de Activador Plasminogénico/sangre , Índice de Masa Corporal , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios de Cohortes , Terapia Combinada , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/dietoterapia , Angiopatías Diabéticas/complicaciones , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/prevención & control , Cardiomiopatías Diabéticas/complicaciones , Cardiomiopatías Diabéticas/epidemiología , Cardiomiopatías Diabéticas/prevención & control , Dieta Reductora , Ejercicio Físico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Sobrepeso/sangre , Sobrepeso/complicaciones , Sobrepeso/dietoterapia , Cooperación del Paciente , Aptitud Física , Riesgo , Texas/epidemiología , Pérdida de Peso
19.
Obesity (Silver Spring) ; 21(5): 944-50, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23512860

RESUMEN

OBJECTIVE: Cardiovascular risk remains high despite statin use. Overweight/obese diabetic persons usually have normal/low LDL-cholesterol but high C-reactive protein (CRP) levels. We aimed to examine the effects of intensive lifestyle intervention for weight loss (ILI) on CRP levels in overweight/obese diabetic individuals by statin use. DESIGN AND METHODS: Look AHEAD was a randomized trial in overweight/obese type 2 diabetic individuals testing whether ILI would reduce cardiovascular mortality, when compared to usual care. CRP changes in 1,431 participants with biomarker levels, who remained on or off statin treatment for 1 year, were evaluated. RESULTS: The reduction in CRP levels with ILI at 1 year in men and women on statins was -44.9 and -42.3%, respectively, compared to -13.7 and -21.0% for those on statins and usual care (P < 0.0001). At 1 year, median CRP levels were: 1.8 mg L(-1) in participants randomized to ILI on statin therapy; 2.6 mg L(-1) for those on statins randomized to usual care and 2.9 mg L(-1) for participants not on statins but randomized to ILI. Weight loss was associated with 1-year CRP reduction (P < 0.0001) in statin and nonstatin users. CONCLUSIONS: Our findings suggest that in overweight/obese diabetic persons, ILI and statin therapy may have substantial additive anti-inflammatory benefits.


Asunto(s)
Proteína C-Reactiva/metabolismo , Diabetes Mellitus Tipo 2/terapia , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inflamación/terapia , Estilo de Vida , Obesidad/terapia , Pérdida de Peso/fisiología , Anciano , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dieta , Ejercicio Físico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inflamación/tratamiento farmacológico , Inflamación/etiología , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Programas de Reducción de Peso
20.
Circ Cardiovasc Genet ; 6(4): 391-9, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23861364

RESUMEN

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and triglycerides are cardiovascular risk factors susceptible to lifestyle behavior modification and genetics. We hypothesized that genetic variants identified by genome-wide association studies as associated with HDL-C or triglyceride levels modify 1-year treatment response to an intensive lifestyle intervention, relative to a usual care of diabetes mellitus support and education. METHODS AND RESULTS: We evaluated 82 single-nucleotide polymorphisms, which represent 31 loci demonstrated by genome-wide association studies to be associated with HDL-C and triglycerides, in 3561 participants who consented for genetic studies and met eligibility criteria. Variants associated with higher baseline HDL-C levels, cholesterol ester transfer protein (CETP) rs3764261 and hepatic lipase (LIPC) rs8034802, were found to be associated with HDL-C increases with intensive lifestyle intervention (P=0.0038 and 0.013, respectively) and had nominally significant treatment interactions (P=0.047 and 0.046, respectively). The fatty acid desaturase-2 rs1535 variant, associated with low baseline HDL-C (P=0.017), was associated with HDL-C increases with intensive lifestyle intervention (0.0037) and had a nominal treatment interaction (P=0.035). Apolipoprotein B (rs693) and LIPC (rs8034802) single-nucleotide polymorphisms showed nominally significant associations with HDL-C and triglyceride changes with intensive lifestyle intervention and a treatment interaction (P<0.05). Phosphatidylglycerophosphate synthase-1 single-nucleotide polymorphisms (rs4082919) showed the most significant triglyceride treatment interaction in the full cohort (P=0.0009). CONCLUSIONS: This is the first study to identify genetic variants modifying lipid responses to a randomized lifestyle behavior intervention in overweight or obese individuals with diabetes mellitus. The effects of genetic factors on lipid changes may differ from the effects on baseline lipids and are modifiable by behavioral intervention.


Asunto(s)
HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/genética , Obesidad/genética , Triglicéridos/sangre , Anciano , Apolipoproteínas B/genética , Terapia Conductista , Proteínas de Transferencia de Ésteres de Colesterol/genética , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Ácido Graso Desaturasas/genética , Femenino , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Lipasa/genética , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/terapia , Polimorfismo de Nucleótido Simple , Transferasas (Grupos de Otros Fosfatos Sustitutos)/genética
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