Mario Vaz

Neural mechanisms in human obesity-related hypertension.

OBJECTIVE Two hypotheses concerning mechanisms of weight gain and of blood pressure elevation in obesity were tested. The first hypothesis is that in human obesity sympathetic nervous system underactivity is present, as a metabolic basis for the obesity. The second hypothesis, attributable to Landsberg, is that sympathetic nervous activation occurs with chronic overeating, elevating blood pressure. These are not mutually exclusive hypotheses, since obesity is a heterogeneous disorder. DESIGN AND METHODS Whole body and regional sympathetic nervous system activity, in the kidneys and heart, was measured at rest using noradrenaline isotope dilution methodology in a total of 86 research voluteers in four different subject groups, in lean and in obese people who either did, or did not, have high blood pressure. RESULTS In the lean hypertensive patients, noradrenaline spillover for the whole body, and from the heart and kidneys was substantially higher than in the healthy lean volunteers. In normotensive obesity, the whole body noradrenaline spillover rate was normal, mean renal noradrenaline spillover was elevated (twice normal), and cardiac noradrenaline spillover reduced by approximately 50%. In obesity-related hypertension, there was elevation of renal noradrenaline spillover, comparable to that present in normotensive obese individuals but not accompanied by suppression of cardiac noradrenaline spillover, which was more than double that of normotensive obese individuals (P<0.05), and 25% higher than in healthy volunteers. There was a parallel elevation of heart rate in hypertensive obese individuals. CONCLUSIONS The sympathetic underactivity hypothesis of obesity causation now looks untenable, as based on measures of noradrenaline spillover, sympathetic nervous system activity was normal for the whole body and increased for the kidneys; the low sympathetic activity in the heart would have only a trifling impact on total energy balance. The increase in renal sympathetic activity in obesity may possibly be a necessary cause for the development of hypertension in obese individuals, although clearly not a sufficient cause, being present in both normotensive and hypertensive obese individuals. The discriminating feature of obesity-related hypertension was an absence of the suppression of the cardiac sympathetic outflow seen in normotensive obese individuals. Sympathetic nervous changes in obesity-related hypertension conformed rather closely to those expected from the Landsberg hypothesis.

The Prospective Urban Rural Epidemiology (PURE) study: Examining the impact of societal influences on chronic noncommunicable diseases in low-, middle-, and high-income countries

BACKGROUND Marked changes in the prevalence of noncommunicable diseases such as obesity, diabetes, and cardiovascular disease have occurred in developed and developing countries in recent decades. The overarching aim of the study is to examine the relationship of societal influences on human lifestyle behaviors, cardiovascular risk factors, and incidence of chronic noncommunicable diseases. METHODS The Prospective Urban Rural Epidemiology (PURE) study is a large-scale epidemiological study that plans to recruit approximately 140,000 individuals residing in >600 communities in 17 low-, middle-, and high-income countries around the world. Individual data collection includes medical history, lifestyle behaviors (physical activity and dietary profile), blood collection and storage for biochemistry and future genetic analysis, electrocardiogram, and anthropometric measures. In addition, detailed information is being collected with respect to 4 environmental domains of interest-the built environment, nutrition and associated food policy, psychosocial/socioeconomic factors, and tobacco environment. A minimum follow-up of 10 years is currently planned. RESULTS This report describes the design, justification, and methodology of the PURE study. The PURE study has been recruiting since 2002 and has enrolled 139,506 individuals by March 31, 2009. CONCLUSIONS The PURE study builds on the work and experience gained through conduct of the INTERHEART study. Its design and extensive data collection are geared toward addressing major questions on causation and development of the underlying determinants of cardiovascular disease in populations at varying stages of epidemiologic transition.

Low maternal vitamin B12 status is associated with intrauterine growth retardation in urban South Indians.

Objective:To assess the maternal sociodemographic, anthropometric, dietary and micronutrient status in apparently healthy pregnant women in order to determine their associations with intrauterine growth retardation (IUGR).Design:Prospective observational study.Setting:Bangalore City, India.Subjects:A total of 478 women were recruited at 12.9±3.3 weeks of gestation and followed up at the first, second and third trimesters of pregnancy and at delivery. The dropout rate was 8.5%.Interventions:None.Main outcome measures:Birth weight was measured at hospital delivery.Results:The mean birth weight was 2.85±0.45 kg. In all, 28.6% of newborns were IUGR. There was a strong inverse relationship between maternal educational level and risk of IUGR. A low body weight at baseline was also associated with a high risk of IUGR. Compared with women in the highest quartile for second trimester weight gain, those in the lowest quartile had a significantly higher adjusted odds ratio (AOR: 3.98; 95% CI: 1.83, 8.65) for IUGR. Women in the lowest tertile for serum vitamin B12 concentration during each of the three trimesters of pregnancy had significantly higher risk of IUGR (AOR: 5.98, 9.28 and 2.81 for trimesters 1–3, respectively).Conclusions:The present study demonstrates associations between educational status, maternal weight and gestational weight gain with IUGR. Importantly, in a subsample, there were strong associations of vitamin B12 status with IUGR, suggesting that better socioeconomic conditions, improved nutritional status and early detection of vitamin B12 deficiency in pregnancy combined with appropriate interventions are likely to play an important role in reducing IUGR.Sponsorship:This research was partly supported by the GlaxoSmithKline Consumer Healthcare Ltd, India.

Sociodemographic patterning of non-communicable disease risk factors in rural India: a cross sectional study.

Objectives To investigate the sociodemographic patterning of non-communicable disease risk factors in rural India. Design Cross sectional study. Setting About 1600 villages from 18 states in India. Most were from four large states due to a convenience sampling strategy. Participants 1983 (31% women) people aged 20–69 years (49% response rate). Main outcome measures Prevalence of tobacco use, alcohol use, low fruit and vegetable intake, low physical activity, obesity, central adiposity, hypertension, dyslipidaemia, diabetes, and underweight. Results Prevalence of most risk factors increased with age. Tobacco and alcohol use, low intake of fruit and vegetables, and underweight were more common in lower socioeconomic positions; whereas obesity, dyslipidaemia, and diabetes (men only) and hypertension (women only) were more prevalent in higher socioeconomic positions. For example, 37% (95% CI 30% to 44%) of men smoked tobacco in the lowest socioeconomic group compared with 15% (12% to 17%) in the highest, while 35% (30% to 40%) of women in the highest socioeconomic group were obese compared with 13% (7% to 19%) in the lowest. The age standardised prevalence of some risk factors was: tobacco use (40% (37% to 42%) men, 4% (3% to 6%) women); low fruit and vegetable intake (69% (66% to 71%) men, 75% (71% to 78%) women); obesity (19% (17% to 21%) men, 28% (24% to 31%) women); dyslipidaemia (33% (31% to 36%) men, 35% (31% to 38%) women); hypertension (20% (18% to 22%) men, 22% (19% to 25%) women); diabetes (6% (5% to 7%) men, 5% (4% to 7%) women); and underweight (21% (19% to 23%) men, 18% (15% to 21%) women). Risk factors were generally more prevalent in south Indians compared with north Indians. For example, the prevalence of dyslipidaemia was 21% (17% to 33%) in north Indian men compared with 33% (29% to 38%) in south Indian men, while the prevalence of obesity was 13% (9% to 17%) in north Indian women compared with 24% (19% to 30%) in south Indian women. Conclusions The prevalence of most risk factors was generally high across a range of sociodemographic groups in this sample of rural villagers in India; in particular, the prevalence of tobacco use in men and obesity in women was striking. However, given the limitations of the study (convenience sampling design and low response rate), cautious interpretation of the results is warranted. These data highlight the need for careful monitoring and control of non-communicable disease risk factors in rural areas of India.

Maximal voluntary contraction as a functional indicator of adult chronic undernutrition

Maximal voluntary contraction (MVC) using a handgrip dynamometer was assessed in seventy-two young adult males. The subjects were divided into two groups on the basis of a BMI of 18.5 kg/m2. The subjects with a BMI < 18.5 kg/m2 (n 38) were further divided into an underweight (UW; n 20) group and a chronically energy-deficient (CED; n 18) group. The CED subjects had significantly lower MVC (30.1, SD 5.9 kg) than either the well-nourished controls (BMI > 18.5 kg/m2: 39.8, SD 5.8 kg) or the underweight group (37.6, SD 4.9 kg). The differences between the CED and UW groups persisted even after the MVC were corrected for forearm muscle area and stature. The results suggest that MVC may be a useful functional indicator of nutritional status particularly in differentiating subjects with chronic undernutrition from individuals who are underweight and not undernourished but have similar BMI.

Phenotypic Evidence of Faulty Neuronal Norepinephrine Reuptake in Essential Hypertension

Previous reports suggest that neuronal norepinephrine (NE) reuptake may be impaired in essential hypertension, perhaps because of dysfunction of the NE transporter, although the evidence is inconclusive. To further test this proposition, we applied phenotypically relevant radiotracer methodology, infusion of tritiated NE and quantification of NE metabolites, to 34 healthy lean subjects (body mass index <27.0 kg/m2), 19 overweight (body mass index >28.0 kg/m2) but otherwise healthy normotensive subjects, 13 untreated lean patients with essential hypertension, and 14 obesity-related hypertensives. Spillover of NE from the heart was increased in lean hypertensives only (mean±SD 33.4±20.6 versus 16.1±11.7 ng/min in lean normotensives, P <0.05), but this could have resulted from high cardiac sympathetic nerve firing rates, faulty NE reuptake, or both. The arterial plasma concentration of 3-methoxy-4-hydroxylphenylglycol, an extraneuronal metabolite of NE, was elevated in lean hypertensives only (3942±1068 versus 3055±888 pg/mL in healthy subjects, P <0.05). The fractional extraction of plasma tritiated NE in passage through the heart, determined on the basis of neuronal NE uptake, was reduced in lean essential hypertensives (0.65±0.19 versus 0.81±0.11 in healthy subjects, P <0.05). Cardiac release of the tritiated NE metabolite [3H]dihydroxylphenylglycol, produced intraneuronally by monoamine oxidase after uptake of [3H]NE by the transporter, was reduced in lean hypertensives only (992±1435 versus 4588±3189 dpm/min in healthy subjects, P <0.01) These findings suggest that neuronal reuptake of NE is impaired in essential hypertension. Through amplification of the neural signal, such a defect could constitute a neurogenic variant of essential hypertension. In obesity-related hypertension, there was no phenotypic evidence of NE transporter dysfunction.

Leptin in human plasma is derived in part from the brain, and cleared by the kidneys

Leptin is believed to exert a regulatory influence on food intake and use of energy after gaining access to the brain, possibly via a specific transfer mechanism. It has been suggested that in obesity the primary flaw may be an inability of leptin to enter the central nervous system. We tested, with simultaneous arterial and internal jugular venous sampling, whether uptake of leptin occurs in the brain, and whether this process might be defective in obesity. In 39 fasting men aged 44 (SE 3) years, age range 19–76 years, and of body mass index (BMI) 27·2 (0·7) kg/m (range 19·6–38·5), arteriovenous plasma concentration gradients of leptin were measured across the brain (n=15), kidneys (13), gut and liver (11), heart (nine), and forearm (15), by way of simultaneous venous and radial or brachial arterial blood sampling. With repositioning of the central venous catheter, sampling was done in up to four venous sites. 20 men were obese (BMI >28) and 19 were lean (BMI <26). Central venous catheterisation and measurement of internal jugular and renal plasma flows was performed with our previously described techniques, with appropriate consent by the volunteers, and institutional ethics committee review. Leptin was measured by a radioimmunoassay (RIA; Linco, St Charles, MO, USA), with a sensitivity limit of 0·5 ng/mL and intra-assay coefficient of variation 5%. The concentration of leptin in arterial plasma overall was 7·2 (1·1) ng/mL. The leptin concentration in internal jugular venous plasma was on average 21% higher than the corresponding arterial value (6·58 vs 5·53 ng/mL [p<0·03]), which with the existing mean plasma flow of 205 mL/min equated to a unilateral overflow of leptin into the internal jugular vein of 208 (126) ng/min. In contrast, there was a mean extraction of leptin from plasma of 17% in passage through the kidneys, with a mean removal rate of 1833 ng/min, equivalent to a renal plasma clearance of 145 (92) mL/min at the existing mean renal plasma flow of 832 mL/min. There was no detectable net flux of leptin to or from plasma in passage through the heart, the gut and liver, or the forearm. In the five obese men in which this was measured, cerebral leptin overflow was 451 (349) ng/min, compared with 86 (24) ng/min in ten lean men (p<0·05). Renal clearance of leptin was unaffected by obesity. Our results suggest that the brain is a source of leptin circulating in plasma. Alternative explanations, such as modification of the extent to which leptin is bound to plasma protein during passage through the cerebrovascular circulation are less likely. This is an unexpected finding, as tissue expression of leptin to date has been described only in adipose tissue and placenta. Release of leptin from the brain to the circulation was higher in obese than lean men, suggesting that the rise in plasma leptin concentration in human obesity is not entirely attributable to increased release of leptin from adipose tissue.

Television viewing and sleep are associated with overweight among urban and semi-urban South Indian children

BackgroundChildhood obesity is an emerging problem in urban Indian children and increases in childhood overweight and obesity may be major contributors to the adult obesity epidemic. Thus, identifying potential risk factors for childhood obesity and formulating early interventions is crucial in the management of the obesity epidemic. The present study was aimed at evaluating dietary and physical activity patterns as determinants of overweight in a sample of children.MethodsFive hundred and ninety eight children aged 6–16 years, visiting St. Johns Medical College Hospital, Bangalore City, India for minor complaints or routine checkups were recruited into the study. These children were studied for their physical activity patterns, sleep duration, sedentary habits and eating behaviours as potential determinants of overweight.ResultsDecreased duration of sleep and increased television viewing were significantly associated with overweight. Among the eating behaviours, increased consumption of fried foods was significantly associated with overweight.ConclusionOur data suggests that duration of sleep, television viewing and consumption of fried foods may be significant factors that contribute to overweight. Further longitudinal studies are needed to confirm these findings.

Effect of Caralluma Fimbriata extract on appetite, food intake and anthropometry in adult indian men and women

Caralluma fimbriata is an edible cactus, used by tribal Indians to suppress hunger and enhance endurance. The effect of Caralluma extract was assessed in overweight individuals by a placebo controlled randomized trial. Fifty adult men and women (25-60 years) with a body mass index (BMI) greater than 25 kg/m2 were randomly assigned into a placebo or experimental group; the latter received 1 g of Caralluma extract per day for 60 days. All subjects were given standard advice regarding a weight reducing diet and physical activity. At the end of 30 and 60 days of intervention, blood glucose and lipids, anthropometric measurements, dietary intake and assessment of appetite was performed. Waist circumference and hunger levels over the observation period showed a significant decline in the experimental group when compared to the placebo group. While there was a trend towards a greater decrease in body weight, body mass index, hip circumference, body fat and energy intake between assessment time points in the experimental group, these were not significantly different between experimental and placebo groups. Caralluma extract appears to suppress appetite, and reduce waist circumference when compared to placebo over a 2 month period.

The effect of fish and ω-3 LCPUFA intake on low birth weight in Indian pregnant women

Background:Inadequate consumption of fish could be a risk factor for low birth weight (LBW). This study assessed fish intake and ω-3 LCPUFA intake and status for their association with LBW in a cohort of urban, south Indian pregnant women.Subjects/methods:In a prospective cohort study, data on maternal fish intake and ω-3 LCPUFA intake and status of 676 women were obtained at baseline (first trimester), the second and third trimesters of pregnancy. Infant birth weight was measured immediately following hospital delivery. The dropout rate was 7.6%.Results:Fifty-six percent of the study women consumed fish with low daily median intakes (3.4, 4.1 and 3.8 g day−1 at the three trimesters, respectively). Consequently, the median intakes of EPA and DHA during pregnancy were also low at 2.1 and 10.1 mg day−1, respectively. EPA and DHA intakes were associated with their status in erythrocyte membrane phospholipids during pregnancy (r=0.40 and 0.36, r=0.34 and 0.32 and r=0.37 and 0.41, at the three trimesters, respectively, all P<0.001). Women who did not eat fish during the third trimester had a significantly higher risk of LBW (OR: 2.49, P=0.019). Similarly, low EPA intake during the third trimester had an association with a higher risk of LBW (OR: 2.75, P=0.011).Conclusions:Among low fish-eating pregnant women, fish intake in the third trimester was closely associated with birth weight. Supplementation with ω-3 LCPUFA during pregnancy may have important implications for fetal development in India.