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1.
J Intern Med ; 285(5): 533-549, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30772945

RESUMEN

Our understanding of human evolution has improved rapidly over recent decades, facilitated by large-scale cataloguing of genomic variability amongst both modern and archaic humans. It seems clear that the evolution of the ancestors of chimpanzees and hominins separated 7-9 million years ago with some migration out of Africa by the earlier hominins; Homo sapiens slowly emerged as climate change resulted in drier, less forested African conditions. The African populations expanded and evolved in many different conditions with slow mutation and selection rates in the human genome, but with much more rapid mutation occurring in mitochondrial DNA. We now have evidence stretching back 300 000 years of humans in their current form, but there are clearly four very different large African language groups that correlate with population DNA differences. Then, about 50 000-100 000 years ago a small subset of modern humans also migrated out of Africa resulting in a persistent signature of more limited genetic diversity amongst non-African populations. Hybridization with archaic hominins occurred around this time such that all non-African modern humans possess some Neanderthal ancestry and Melanesian populations additionally possess some Denisovan ancestry. Human populations both within and outside Africa also adapted to diverse aspects of their local environment including altitude, climate, UV exposure, diet and pathogens, in some cases leaving clear signatures of patterns of genetic variation. Notable examples include haemoglobin changes conferring resistance to malaria, other immune changes and the skin adaptations favouring the synthesis of vitamin D. As humans migrated across Eurasia, further major mitochondrial changes occurred with some interbreeding with ancient hominins and the development of alcohol intolerance. More recently, an ability to retain lactase persistence into adulthood has evolved rapidly under the environmental stimulus of pastoralism with the ability to husband lactating ruminants. Increased amylase copy numbers seem to relate to the availability of starchy foods, whereas the capacity to desaturase and elongate monounsaturated fatty acids in different societies seems to be influenced by whether there is a lack of supply of readily available dietary sources of long-chain polyunsaturated fatty acids. The process of human evolution includes genetic drift and adaptation to local environments, in part through changes in mitochondrial and nuclear DNA. These genetic changes may underlie susceptibilities to some modern human pathologies including folate-responsive neural tube defects, diabetes, other age-related pathologies and mental health disorders.


Asunto(s)
Evolución Biológica , Hominidae/fisiología , Fenómenos Fisiológicos de la Nutrición , Animales , ADN Mitocondrial/genética , Emigración e Inmigración , Hominidae/genética , Humanos , Mutación
2.
J Intern Med ; 284(1): 37-49, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29706028

RESUMEN

Understanding the physiological and metabolic underpinnings that confer individual differences in responses to diet and diet-related chronic disease is essential to advance the field of nutrition. This includes elucidating the differences in gene expression that are mediated through programming of the genome through epigenetic chromatin modifications. Epigenetic landscapes are influenced by age, genetics, toxins and other environmental factors, including dietary exposures and nutritional status. Epigenetic modifications influence transcription and genome stability are established during development with life-long consequences. They can be inherited from one generation to the next. The covalent modifications of chromatin, which include methylation and acetylation, on DNA nucleotide bases, histone proteins and RNA are derived from intermediates of one-carbon metabolism and central metabolism. They influence key physiological processes throughout life, and together with inherited DNA primary sequence, contribute to responsiveness to environmental stresses, diet and risk for age-related chronic disease. Revealing diet-epigenetic relationships has the potential to transform nutrition science by increasing our fundamental understanding of: (i) the role of nutrients in biological systems, (ii) the resilience of living organisms in responding to environmental perturbations, and (iii) the development of dietary patterns that programme physiology for life-long health. Epigenetics may also enable the classification of individuals with chronic disease for specific dietary management and/or for efficacious diet-pharmaceutical combination therapies. These new emerging concepts at the interface of nutrition and epigenetics were discussed, and future research needs identified by leading experts at the 26th Marabou Symposium entitled 'Nutrition, Epigenetics, Genetics: Impact on Health and Disease'. For a compilation of the general discussion at the marabou symposium, click here http://www.marabousymposium.org/.


Asunto(s)
Enfermedad Crónica/terapia , Epigenómica/métodos , Trastornos Nutricionales/genética , Terapia Combinada , Humanos , Individualidad , Trastornos Nutricionales/dietoterapia , Trastornos Nutricionales/fisiopatología , Pronóstico
6.
Obes Rev ; 17(10): 1001-11, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27324830

RESUMEN

Overweight and obesity increase the risks of diabetes and cardiovascular disease (CVD). This has been shown to be reversed with weight loss. A systematic review and meta-analysis were performed to determine the effect of weight loss in the primary prevention of CVD. PubMed, Embase and the Cochrane Library databases were searched electronically through to May 2013. Randomized controlled trials assessing weight loss and cardiovascular risk factors and outcomes were included. A random effects meta-analysis, with sub-group analyses for degree of weight loss, and age were performed. Because few studies reported clinical outcomes of CVD, analyses were limited to cardiovascular risk factors (83 studies). Interventions that caused any weight loss significantly reduced systolic blood pressure (-2.68 mmHg, 95% CI -3.37, -2.11), diastolic blood pressure (-1.34 mmHg, 95% CI -1.71, -0.97), low-density lipoprotein cholesterol (-0.20 mmol L(-1) , 95% CI -0.29, -0.10), triglycerides (-0.13 mmol L(-1) , 95% CI -0.22, -0.03), fasting plasma glucose (-0.32 mmol L(-1) , 95% CI -0.43, -0.22) and haemoglobin A1c(-0.40%, 95% CI -0.52, -0.28) over 6-12 months. Significant changes remained after 2 years for several risk factors. Similar results were seen in sub-group analyses. Interventions that cause weight loss are effective at improving cardiovascular risk factors at least for 2 years. © 2016 World Obesity.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/prevención & control , Angiopatías Diabéticas/prevención & control , Dieta Reductora , Ejercicio Físico , Obesidad/complicaciones , Prevención Primaria/métodos , Pérdida de Peso , Presión Sanguínea , Humanos , Obesidad/fisiopatología , Obesidad/prevención & control , Resultado del Tratamiento
7.
J Dent Res ; 95(5): 598, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26868327

Asunto(s)
Caries Dental
8.
J Dent Res ; 94(10): 1341-7, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26261186

RESUMEN

The importance of sugars as a cause of caries is underemphasized and not prominent in preventive strategies. This is despite overwhelming evidence of its unique role in causing a worldwide caries epidemic. Why this neglect? One reason is that researchers mistakenly consider caries to be a multifactorial disease; they also concentrate mainly on mitigating factors, particularly fluoride. However, this is to misunderstand that the only cause of caries is dietary sugars. These provide a substrate for cariogenic oral bacteria to flourish and to generate enamel-demineralizing acids. Modifying factors such as fluoride and dental hygiene would not be needed if we tackled the single cause--sugars. In this article, we demonstrate the sensitivity of cariogenesis to even very low sugars intakes. Quantitative analyses show a log-linear dose-response relationship between the sucrose or its monosaccharide intakes and the progressive lifelong development of caries. This results in a substantial dental health burden throughout life. Processed starches have cariogenic potential when accompanying sucrose, but human studies do not provide unequivocal data of their cariogenicity. The long-standing failure to identify the need for drastic national reductions in sugars intakes reflects scientific confusion partly induced by pressure from major industrial sugar interests.


Asunto(s)
Caries Dental/etiología , Carbohidratos de la Dieta/efectos adversos , Política de Salud , Caries Dental/prevención & control , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/normas , Predicción , Política de Salud/tendencias , Humanos , Política Nutricional
9.
J Intern Med ; 278(2): 99-109, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25832550

RESUMEN

MicroRNAs (miRNAs) are one of a growing class of noncoding RNAs that are involved in the regulation of a wide range of metabolic processes including cellular differentiation, cell proliferation and apoptosis. The generation of miRNA is regulated in complex ways, for example by small interfering RNAs (small nucleolar and nuclear RNAs) and various other metabolites. This complexity of control is likely to explain how a relatively small part of the DNA that codes for proteins has enabled the evolution of such complex organisms as mammals. Non-protein-coding DNA is therefore thought to carry the memory of early evolutionary steps that led to progressively complex metabolic controls. Clinically, miRNAs are becoming increasingly important following the recognition that some congenital abnormalities can be traced to defects in miRNA processing. The potential for manipulating metabolism and affecting disease processes by the pharmaceutical or biological targeting of specific miRNA pathways is now being tested. miRNAs are also released into the extracellular milieu after packaging by cells into nano-sized extracellular vesicles. Such vesicles can be taken up by adjacent and possibly more distant cells, thereby allowing coordinated intercellular communication in specific tissues. Extracellular miRNAs found in the blood stream may also serve as novel biomarkers for both diagnosing specific forms of cancer and assessing the likelihood of metastasis, and as powerful prognostic indices for various cancers. Here, we discuss the role of intracellular and extracellular miRNAs in nutritional control of various (patho)physiological processes. In this review, we provide an update of the presentations from the 25th Marabou Symposium (Stockholm, 14-16 June 2013) entitled 'Role of miRNA in health and nutrition', attended by 50 international experts


Asunto(s)
MicroARNs/genética , Neoplasias/genética , Evaluación Nutricional , Animales , Comunicación Celular , Humanos , Pronóstico
10.
Int J Obes (Lond) ; 39(5): 849-57, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25520249

RESUMEN

BACKGROUND/OBJECTIVES: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in pulse rate, and the impact of these changes on subsequent cardiovascular outcome events in both the placebo and sibutramine groups. SUBJECTS/METHODS: 9804 males and females, aged ⩾55 years, with a body mass index of 27-45 kg m(-)(2) were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor, to assess cardiovascular outcomes. The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models. RESULTS: During the initial 6-week sibutramine treatment period, the induced pulse rate increase was related to weight change (1.9±7.7 beats per minute (bpm) with weight increase; 1.4±7.3 bpm, 0-5 kg weight loss; 0.6±7.4 bpm, ⩾5 kg weight loss). Throughout the subsequent treatment period, those continuing on sibutramine showed a consistently higher mean pulse rate than the placebo group. There was no difference in POE rates with either an increase or decrease in pulse rate over the lead-in period, or during lead-in baseline to 12 months post randomization. There was also no relationship between pulse rate at lead-in baseline and subsequent cardiovascular events in subjects with or without a cardiac arrhythmia. CONCLUSION: Baseline pulse rate and changes in pulse rate may not be an important modifier nor a clinically useful predictor of outcome in an individual elderly cardiovascular obese subject exposed to weight management.


Asunto(s)
Depresores del Apetito/administración & dosificación , Enfermedades Cardiovasculares/prevención & control , Ciclobutanos/administración & dosificación , Angiopatías Diabéticas/prevención & control , Frecuencia Cardíaca/efectos de los fármacos , Obesidad/fisiopatología , Anciano , Índice de Masa Corporal , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Angiopatías Diabéticas/tratamiento farmacológico , Angiopatías Diabéticas/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/epidemiología , Valor Predictivo de las Pruebas , Factores de Riesgo , Resultado del Tratamiento , Reino Unido/epidemiología , Pérdida de Peso
11.
Nutr Metab Cardiovasc Dis ; 24(6): 656-62, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24534073

RESUMEN

BACKGROUND AND AIMS: An inverse relationship between (serum) total bilirubin and risk of cardiovascular disease has been reported previously, but longitudinal data on overweight and obese patients are lacking. We have investigated the relationship between total bilirubin and cardiovascular adverse events in a large group of patients with risk factors for cardiovascular disease who were enrolled in a large weight loss trial. METHODS AND RESULTS: Data from the Sibutramine Cardiovascular Outcomes (SCOUT) trial, including almost 10.000 overweight/obese high cardiovascular risk patients, were used. The relationship between total bilirubin level at screening and the primary outcome (i.e. non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death) for the entire study period was investigated using Cox proportional hazards models. The population was divided into four groups based on total bilirubin levels (normal range 5-25 µmol/L). Time-dependent Cox analyses were also performed to adjust for weight loss over time. Initial analyses adjusted for sex, age and treatment allocation showed significantly reduced hazard ratios of 0.80 (95% confidence interval 0.68-0.94), 0.73 (0.62-0.86) and 0.77 (0.65-0.91), for the three higher total bilirubin groups: >8 and ≤10 µmol/L, >10 and ≤13 µmol/L and >13 µmol/L (5-95 interpercentile range for total bilirubin at screening; 6-19 µmol/L), compared to the lowest total bilirubin group ≤8 µmol/L. When adjusting for classical cardiovascular risk factors, estimates increased towards unity. Additional adjustment for indicators of liver function did not alter the results. A time-dependent Cox model, adjusted for weight loss, demonstrated a similar trend. CONCLUSION: Bilirubin was not a risk-factor independent from other traditional cardiovascular risk-factors in our population.


Asunto(s)
Bilirrubina/sangre , Enfermedades Cardiovasculares/etiología , Obesidad/fisiopatología , Sobrepeso/fisiopatología , Anciano , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Estudios de Cohortes , Método Doble Ciego , Femenino , Paro Cardíaco/epidemiología , Paro Cardíaco/etiología , Paro Cardíaco/prevención & control , Paro Cardíaco/terapia , Humanos , Incidencia , Estilo de Vida , Masculino , Persona de Mediana Edad , Mortalidad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Infarto del Miocardio/prevención & control , Obesidad/sangre , Obesidad/terapia , Sobrepeso/sangre , Sobrepeso/terapia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Regulación hacia Arriba , Pérdida de Peso
12.
Int J Obes (Lond) ; 38(9): 1165-71, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24406481

RESUMEN

BACKGROUND/OBJECTIVES: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in body weight and blood pressure, and the impact of these changes on subsequent cardiovascular outcome events. SUBJECTS/METHODS: A total of 9804 male and female subjects, aged 55 years or older, with a body mass index of 27-45 kg m(-2) were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor (hypertension, dyslipidemia, current smoking or diabetic nephropathy) to assess cardiovascular outcomes. Post hoc subgroup analyses of weight change (categories) and blood pressure were performed overall and by treatment group (6-week sibutramine followed by randomized placebo or continued sibutramine). The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models with factors for treatment, subgroups and interactions. RESULTS: During the initial 6-week sibutramine treatment period, systolic blood pressure decreased progressively with increasing weight loss in hypertensive subjects (-8.1±10.5 mm Hg with <5 kg weight loss to -10.8±11.0 mm Hg with ⩾5 kg weight loss). The highest POE incidence occurred mainly in groups with increases in both weight and blood pressure. However, with long-term sibutramine treatment, a markedly lower blood pressure tended to increase POEs. CONCLUSION: Modest weight loss and modest lower blood pressure each reduced the incidence of cardiovascular events, as expected. However, the combination of early marked weight loss and rapid blood pressure reduction seems to be harmful in this obese elderly cardiovascular diseased population.


Asunto(s)
Depresores del Apetito/uso terapéutico , Presión Sanguínea , Enfermedades Cardiovasculares/complicaciones , Ciclobutanos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/prevención & control , Obesidad/tratamiento farmacológico , Pérdida de Peso , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/prevención & control , Diabetes Mellitus Tipo 2/terapia , Angiopatías Diabéticas/fisiopatología , Angiopatías Diabéticas/terapia , Método Doble Ciego , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Obesidad/prevención & control , Sobrepeso/tratamiento farmacológico , Estudios Prospectivos , Factores de Riesgo , Conducta de Reducción del Riesgo , Resultado del Tratamiento
13.
Diabetologia ; 55(9): 2348-55, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22638548

RESUMEN

AIMS/HYPOTHESIS: The optimal HbA(1c) concentration for prevention of macrovascular complications and deaths in obese cardiovascular high-risk patients with type 2 diabetes remains to be established and was therefore studied in this post hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial, which enrolled overweight and obese patients with type 2 diabetes and/or cardiovascular disease. METHODS: HRs for meeting the primary endpoint (nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality were analysed using Cox regression models. RESULTS: Of 8,252 patients with type 2 diabetes included in SCOUT, 7,479 had measurements of HbA(1c) available at baseline (i.e. study randomisation). Median age was 62 years (range 51-86 years), median BMI was 34.0 kg/m(2) (24.8-65.1 kg/m(2)) and 44% were women. The median HbA(1c) concentration was 7.2% (3.8-15.9%) (55 mmol/l [18-150 mmol/l]) and median diabetes duration was 7 years (0-57 years). For each 1 percentage point HbA(1c) increase, the adjusted HR for the primary endpoint was 1.17 (95% CI 1.11, 1.23); no differential sex effect was observed (p = 0.12 for interaction). In contrast, the risk of all-cause mortality was found to be greater in women than in men: HR 1.22 (1.10, 1.34) vs 1.12 (1.04, 1.20) for each 1 percentage point HbA(1c) increase (p = 0.02 for interaction). There was no evidence of increased risk associated with HbA(1c) ≤ 6.4% (≤ 46 mmol/l). Glucose-lowering treatment regimens, diabetes duration or a history of cardiovascular disease did not modify the associations. CONCLUSIONS/INTERPRETATION: In overweight, cardiovascular high-risk patients with type 2 diabetes, increasing HbA(1c) concentrations were associated with increasing risks of cardiovascular adverse outcomes and all-cause mortality.


Asunto(s)
Enfermedades Cardiovasculares/sangre , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada , Obesidad/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Glucemia/metabolismo , Índice de Masa Corporal , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Obesidad/mortalidad , Obesidad/fisiopatología , Valor Predictivo de las Pruebas , Factores de Riesgo
14.
Diabetes Obes Metab ; 14(6): 523-30, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22192338

RESUMEN

AIM: The Sibutramine Cardiovascular OUTcomes trial showed that sibutramine produced greater mean weight loss than placebo but increased cardiovascular morbidity but not mortality. The relationship between 12-month weight loss and subsequent cardiovascular outcomes is explored. METHODS: Overweight/obese subjects (N = 10 744), ≥55 years with cardiovascular disease and/or type 2 diabetes mellitus, received sibutramine plus weight management during a 6-week Lead-in Period before randomization to continue sibutramine (N = 4906) or to receive placebo (N = 4898). The primary endpoint was the time from randomization to first occurrence of a primary outcome event (non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death). RESULTS: For the total population, mean weight change during Lead-in Period (sibutramine) was -2.54 kg. Post-randomization, mean total weight change to Month 12 was -4.18 kg (sibutramine) or -1.87 kg (placebo). Degree of weight loss during Lead-in Period or through Month 12 was associated with a progressive reduction in risk for the total population in primary outcome events and cardiovascular mortality over the 5-year assessment. Although more events occurred in the randomized sibutramine group, on an average, a modest weight loss of approximately 3 kg achieved in the Lead-in Period appeared to offset this increased event rate. Moderate weight loss (3-10 kg) reduced cardiovascular deaths in those with severe, moderate or mild cardiovascular disease. CONCLUSIONS: Modest weight loss over short-term (6 weeks) and longer-term (6-12 months) periods is associated with reduction in subsequent cardiovascular mortality for the following 4-5 years even in those with pre-existing cardiovascular disease. While the sibutramine group experienced more primary outcome events than the placebo group, greater weight loss reduced overall risk of these occurring in both groups.


Asunto(s)
Depresores del Apetito/administración & dosificación , Enfermedades Cardiovasculares/prevención & control , Ciclobutanos/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Pérdida de Peso/efectos de los fármacos , Depresores del Apetito/farmacología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Ciclobutanos/farmacología , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/mortalidad , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Obesidad/complicaciones , Obesidad/mortalidad , Factores de Riesgo , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento
15.
Diabetes Obes Metab ; 12(1): 26-34, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19758358

RESUMEN

OBJECTIVE: To assess treatment responses to sibutramine and weight management in diabetic patients during the lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, prospective, randomized, double-blind, placebo-controlled outcome trial in cardiovascular high-risk overweight/obese patients. A total of 10 742 patients received single-blind sibutramine and individualized weight management during the 6-week lead-in period; 84% had a history of type 2 diabetes mellitus and additional co-morbidities. Post-hoc analyses assessed anthropomorphic and vital sign responses between patients with and without diabetes. RESULTS: Concomitant antidiabetic medication use was reported by 86% of the diabetic patients (approximately 30% required insulin-alone or in combination). Body weight and waist circumference decreased in diabetic patients: median 2.1 kg; 2.0 cm (both men and women); for those on insulin: 1.9 kg; 1.5/2.0 cm (men/women); without insulin: 2.3 kg; 2.0 cm (both men and women); blood pressure (BP) was also reduced (median systolic/diastolic 3.5/1.0 mmHg) with larger reductions in diabetic patients who were hypertensive and/or lost the most weight (>5%). In diabetic patients who entered with BP at target (<130/<85 mmHg) but did not lose weight (N = 245), increases of 3.5/2.0 mmHg were observed. Non-diabetic patients had greater weight losses (2.5 kg) but smaller reductions in BP (systolic/diastolic -2.5/-0.5 mmHg). Pulse rate increases were less in diabetic vs. non-diabetic patients (1.5 vs. 2.0 bpm). CONCLUSION: In these high-risk diabetic patients, sibutramine and lifestyle modifications for 6 weeks resulted in small, but clinically relevant, median reductions in body weight, waist circumference and BP. A small median increase in pulse rate was recorded.


Asunto(s)
Depresores del Apetito/uso terapéutico , Ciclobutanos/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Anciano , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Angiopatías Diabéticas/prevención & control , Método Doble Ciego , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/etiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/fisiopatología , Pérdida de Peso/efectos de los fármacos
16.
Int J Obes (Lond) ; 33(12): 1437-45, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19752876

RESUMEN

OBJECTIVE: To determine cutoff points of anthropometric variables for predicting incident cardiovascular disease (CVD) in Iranian adults. DESIGN: It is a population-based longitudinal study. SUBJECTS: A total of 1614 men and 2006 women, aged > or =40 years, free of CVD at baseline were included in the study. MEASUREMENTS: Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and cardiovascular risks were assessed. Incident CVD was ascertained over a median of 7.6 years follow-up. The adjusted hazard ratios (HRs) for CVD were calculated for 1 s.d. change in all obesity variables using Cox proportional hazards regression analysis. Receiver operator characteristic (ROC) curve analysis was used as the method of defining the points of the maximum sum of sensitivity and specificity (MAXss) of each variable as a predictor of CVD. RESULTS: We found 333 CVD events during follow-up. The risk-factor-adjusted HRs were significant for all anthropometric variables in males and WHR in females and were 1.19, 1.24, 1.21 and 1.24 for BMI, WC, WHR and WHtR in males and 1.27 for WHR in females, respectively (all P<0.05). ROC analysis showed the highest area under curve (AUC) for WHR, WHtR and WC, followed by BMI in males and both genders aged< or =60 years. In females, WHR and WHtR had the highest AUC, followed by WC and BMI. Among those >60 years old, all the anthropometric variables showed same CVD predicting power. The cutoff values (MAXss) for CVD prediction in males and females were BMIs 26.95 and 29.19 kg m(-2),WCs 94.5 and 94.5 cm, WHRs 0.95 and 0.90, and WHtR 0.55 and 0.62, respectively. CONCLUSION: There was no difference between central obesity variables in predicting CVD in males, whereas in females WHR and WHtR were more appropriate. The cutoff values of anthropometric variables were higher in the Iranian than in other Asian populations.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Hipertensión/epidemiología , Obesidad Abdominal/epidemiología , Índice de Masa Corporal , Enfermedades Cardiovasculares/etiología , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Obesidad Abdominal/complicaciones , Valor Predictivo de las Pruebas , Prevalencia , Curva ROC , Valores de Referencia , Factores de Riesgo , Factores Sexuales , Circunferencia de la Cintura , Relación Cintura-Cadera
17.
Diabetes Obes Metab ; 11(3): 239-50, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18671798

RESUMEN

OBJECTIVE: To explore vital sign changes among patient subgroups during the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, double-blind, randomized, placebo-controlled outcome trial in overweight/obese patients at high risk of a cardiovascular event. During the 6-week lead-in period, 10,742 patients received sibutramine and weight management. Vital sign changes were assessed post hoc by initial blood pressure (mmHg) categorized as normal (<130/<85), high-normal (130 to <140/85 to <90) or hypertensive (>or=140/>or=90); weight change categories (weight gain/no weight change, >0 to 2.5% weight loss, >2.5 to 5% weight loss and >5% weight loss) and current antihypertensive medication class use (none, one, or two or more). To assess the impact of sibutramine on blood pressure and pulse rate, only patients (N = 10,025) who reported no change in the class of antihypertensive medication used and who did not report an increase in antihypertensive medication use were analysed. RESULTS: At entry, approximately 50% of patients were hypertensive and 26% were high-normal. In hypertensive patients, blood pressure changes (mmHg) decreased by median [5th, 95th percentile] of -6.5 systolic [-27.0, 8.0] and -2.0 diastolic [-15.0, 8.0] (p < 0.001). Hypertensive patients with no weight loss or with weight gain had median decreases of -3.5 systolic [-26.0, 10.0] and -1.5 diastolic [-16.0, 9.0] (p < 0.001). Normotensive patients had median increases of 1.5 systolic [-15.0, 19.5] and 1.0 diastolic [-10.5, 13.0] (p < 0.001) attenuated with increasing weight loss. Approximately 43% of patients initially categorized as hypertensive had a lower blood pressure category at end-point. Concomitant antihypertensive medication classes did not affect blood pressure reductions. Pulse rates were uniformly elevated (median 1-4 bpm, p < 0.001) across blood pressure and weight change categories. CONCLUSIONS: In hypertensive patients (>or=140/>or=90), blood pressure decreases were observed during 6-week treatment with sibutramine even when body weight was unchanged. In patients with normal blood pressure (<130/<85), weight loss of >5% induced decreases in systolic blood pressure; otherwise, small increases were observed. Small pulse rate increases were observed regardless of blood pressure or weight change status.


Asunto(s)
Depresores del Apetito/uso terapéutico , Ciclobutanos/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Pérdida de Peso/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Método Doble Ciego , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Pérdida de Peso/fisiología
18.
J Intern Med ; 263(4): 336-52, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18312311

RESUMEN

The epidemic of obesity took off from about 1980 and in almost all countries has been rising inexorably ever since. Only in 1997 did WHO accept that this was a major public health problem and, even then, there was no accepted method for monitoring the problem in children. It was soon evident, however, that the optimum population body mass index is about 21 and this is particularly true in Asia and Latin America where the populations are very prone to developing abdominal obesity, type 2 diabetes and hypertension. These features are now being increasingly linked to epigenetic programming of gene expression and body composition in utero and early childhood, both in terms of fat/lean tissue ratios and also in terms of organ size and metabolic pathway regulation. New Indian evidence suggests that insulin resistance at birth seems linked to low birth weight and a higher proportion of body fat with selective B12 deficiency and abnormalities of one carbon pool metabolism potentially responsible and affecting 75% of Indians and many populations in the developing world. Biologically there are also adaptive biological mechanisms which limit weight loss after weight gain and thereby in part account for the continuing epidemic despite the widespread desire to slim. Logically, the burden of disease induced by inappropriate diets and widespread physical inactivity can be addressed by increasing physical activity (PA), but simply advocating more leisure time activity is unrealistic. Substantial changes in urban planning and diet are needed to counter the removal of any every day need for PA and the decades of misdirected food policies which with free market forces have induced our current 'toxic environment'. Counteracting this requires unusual policy initiatives.


Asunto(s)
Índice de Masa Corporal , Industria de Alimentos/normas , Desnutrición/epidemiología , Obesidad/epidemiología , Salud Urbana/normas , Composición Corporal , Niño , Femenino , Industria de Alimentos/legislación & jurisprudencia , Humanos , Resistencia a la Insulina/etnología , Masculino , Actividad Motora , Obesidad/economía , Obesidad/prevención & control , Formulación de Políticas , Sensibilidad y Especificidad , Salud Urbana/tendencias , Organización Mundial de la Salud
19.
20.
Obes Rev ; 9 Suppl 1: 6-13, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18307693

RESUMEN

Most policy makers do not yet understand that the obesity epidemic is a normal population response to the dramatic reduction in the demand for physical activity and the major changes in the food supply of countries over the last 40 years. A national focus on individual behaviour reflects a failure to confront the facts. Thus, the changes in food supply and physical environment are socioeconomically driven, and the health sector simply picks up the consequences. Urbanization alone in China has reduced daily energy expenditure by about 300-400 kcal d(-1) and cycling/bussing or going to work by car determines another variation of 200 kcal d(-1). Thus, energy demands may have dropped with additional TV/media, mechanization and computerized changes by 400-800 kcal d(-1), so weight gain and obesity are inevitable for most or all the population. Food intake should have fallen substantially despite the community's focus on the value of food after all the food crises of the past. Yet, Chinese fat and sugar intakes are escalating, and these policy-mediated features are amplified by the primeval biological drive for those commodities with specialized taste buds for fatty acids, meat, sugar and salt. Yet, traditionally, Chinese diets had negligible sugar, and 25-year-old data show that the optimum diet for Chinese contains 15% fat. Policies relating to food imports, agriculture, food quality standards, appropriate food traffic light labelling, price adjustments and controlled access to unhealthy foods are all within the grasp of the Chinese government. China has traditionally been far more responsive to the value of policies which limit inequalities and establish standards of care than many western governments, who have yet to recognize that the individualistic free-market approach to obesity prevention is guaranteed to fail. China could therefore lead the way: if it follows western approaches, the health and economic burden will become unsustainable.


Asunto(s)
Dieta/efectos adversos , Grasas de la Dieta/efectos adversos , Brotes de Enfermedades , Ejercicio Físico/fisiología , Obesidad/epidemiología , Urbanización/tendencias , Adulto , Niño , Desarrollo Infantil/fisiología , China/epidemiología , Humanos , Obesidad/fisiopatología , Obesidad/prevención & control , Factores Socioeconómicos , Transportes
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