Abstract-Evidence suggests that obesity may raise blood pressure (BP) through oxidative stress-sensitive mechanisms and that the Dietary Approaches to Stop Hypertension combination diet (DASH-CD) may decrease BP by enhancing antioxidant capacity. To address this question, 12 obese patients with high-normal-to-stage 1 hypertension (hypertensives) and 12 lean normotensives were studied on their usual diets and after following the DASH-CD and a low-antioxidant diet in random sequence for 4 weeks each. Acute oxidative stress was induced by a 4-hour infusion of intralipid and heparin. Ferric-reducing activity of plasma (FRAP) and plasma F 2 -isoprostanes were measured as biomarkers of antioxidant capacity and oxidative stress, respectively. BP was lower in obese hypertensives on the DASH-CD than on the usual and low-antioxidant diets (Ϫ8.1Ϯ1.5/Ϫ7.4Ϯ1.6 mm Hg, PϽ0.05). BP did not change significantly in lean normotensives after 4 weeks on the DASH-CD but tended to rise on the low-antioxidant diet. FRAP on usual diets was higher in lean subjects than in obese subjects. FRAP increased in obese but not lean volunteers on the DASH-CD compared with usual diet, and the group difference disappeared. F 2 -isoprostanes increased from baseline during intralipid and heparin in both groups on the low-antioxidant diet but not in obese hypertensives on the DASH-CD. Among free-living obese hypertensives, the DASH-CD raises antioxidant capacity, lowers BP, and reduces oxidative stress induced by acute hyperlipidemia. The findings are consistent with evidence that elevated BP in obese subjects may reflect an imbalance between antioxidant capacity and oxidative stress that is improved by the DASH-CD. Key Words: obesity Ⅲ insulin resistance Ⅲ fatty acids Ⅲ F 2 -isoprostanes Ⅲ oxidative stress Ⅲ antioxidants P atients with high-normal blood pressure (BP) and hypertension are more obese and insulin resistant than are normotensives. Reduced antioxidant capacity and oxidative stress represent a potential mechanism linking obesity with insulin resistance, elevated BP, and cardiovascular disease. 1-10 For example, acutely raising lipids with a short-term infusion of intralipid and heparin, which mimics and/or exacerbates the dyslipidemia seen with insulin resistance, increases BP and raises F 2 -isoprostanes, a biomarker of oxidative stress. 11,12 Moreover, in experimental models, increasing oxidative stress with a long-term low-dose infusion of angiotensin and reducing antioxidant capacity by depletion of glutathione produce severe hypertension. 2,13 In these models, BP declines when antioxidant defenses are augmented by providing either superoxide dismutase 13,14 or vitamins C and E. 13 Vitamin C also lowers BP in humans, which implicates a role for antioxidant capacity in human hypertension. 15 In the Dietary Approaches to Stop Hypertension (DASH) Study, a diet rich in fruits and vegetables, either with or without low-fat dairy products, reduced BP significantly more in hypertensives than in normotensives. 16 Both diets are rich in a varie...

OBJECTIVE -To evaluate the impact of diabetes status and race, in addition to other covariables, on the estimation of resting energy expenditure (REE).RESEARCH DESIGN AND METHODS -Demographic, anthropometric, and clinical parameters were assessed in 166 adults of varying weights. Subjects were categorized by race (white versus black) and into three subgroups based on glucose tolerance (normoglycemia, impaired glucose tolerance, and type 2 diabetes), termed the diabetes status index (DSI). REE was measured by indirect calorimetry. A multiple regression model was established for optimal prediction of REE based on covariables.RESULTS -An average decrease in REE of 135 kcal/day independent of all other variables was observed in blacks (P Ͻ 0.001). DSI was found to be a significant covariable (P ϭ 0.002) in predicting REE, which was observed to be higher in diabetic women. Therefore, race and DSI entered the multiple regression equation to predict REE as significant independent variables, together with lean body mass (LBM) and age ϫ BMI interaction (P Ͻ 0.001). Overall, REE prediction resulted in an R 2 of 0.79 and a root mean square error of 136 kcal/day. These values indicate that the resultant equations could offer advantages over other key published prediction equations. The equations are: 1) REE female ϭ 803.8 ϩ 0.3505 ϫ age ϫ (BMI -34.524) -135.0 ϫ race ϩ 15.866 ϫ LBM ϩ 50.90 ϫ DSI; and 2) REE male ϭ 909.4 ϩ 0.3505 ϫ age ϫ (BMI -34.524) -135.0 ϫ race ϩ 15.866 ϫ LBM -9.10 ϫ DSI. The predictive value of the equations did not diminish substantially when fat-free mass estimated by skinfold calipers was substituted for dual-energy X-ray absorptiometry scan measurements of LBM.CONCLUSIONS -Race and diabetes status are important when predicting REE, coupled with LBM, age, BMI, and sex. Race and DSI have not been considered in equations commonly used to predict REE. Their inclusion could improve individualization of dietary prescriptions for type 2 diabetic subjects and heterogeneous populations. Diabetes Care 27:1405-1411, 2004T ype 2 diabetes and obesity have emerged as leading public health challenges in western societies and constitute an increasing health burden in developing countries. Obesity increases risk for diabetes in the context of the insulin resistance syndrome, a trait cluster consisting of insulin resistance, obesity, glucose intolerance, upper body fat distribution, hypertension, dyslipidemia, and dysfibrinolysis (1-4). The insulin resistance syndrome is a major factor conferring increased risk for cardiovascular disease (1-4). Therefore, type 2 diabetes, obesity, and the insulin resistance syndrome are important targets for dietetic intervention. Often, nutrition professionals must estimate energy expenditure when measurements of metabolic rate are unavailable and must consider the potential influence of obesity, glucose intolerance, and diabetes, which could alter energy metabolism. As current dietary recommendations in the treatment of diabetes include care plans based on lifestyle factors and diab...

OBJECTIVE -Pharmacologic agents currently approved for use in children with type 2 diabetes (metformin and insulin) are less than optimal for some patients. We evaluated the use of a ketogenic, very-low-calorie diet (VLCD) in the treatment of type 2 diabetes.RESEARCH DESIGN AND METHODS -We conducted a chart review of 20 children (mean age 14.5 Ϯ 0.4 years) who consumed a ketogenic VLCD in the treatment of type 2 diabetes. Several response variables (BMI, blood pressure, HbA 1c , blood glucose, and treatment regimens) were examined before, during, and up to 2 years after the diet and compared with a matched diabetic control group.RESULTS -Before starting the diet, 11 of 20 patients were treated with insulin and 6 with metformin. Mean daily blood glucose values fell from 8.9 Ϯ 1.1 to 5.5 Ϯ 0.38 mmol/l (P Ͻ 0.0001) in the first 3 days of the VLCD, allowing insulin and oral agents to be discontinued in all but one subject. BMI fell from 43.5 Ϯ 1.8 to 39.3 Ϯ 1.8 kg/m 2 (P Ͻ 0.0001) and HbA 1c dropped from 8.8 Ϯ 0.6 to 7.4 Ϯ 0.6% (P Ͻ 0.005) as the diet was continued for a mean of 60 Ϯ 8 days (range 4 -130 days), and none required resumption of antidiabetic medications. Sustained decreases in BMI and insulin requirements were observed in patients remaining on the VLCD for at least 6 weeks when compared with those of the control group.CONCLUSIONS -The ketogenic VLCD is an effective short-term, and possibly long-term, therapy for pediatric patients with type 2 diabetes. Blood glucose control and BMI improve, allowing the discontinuation of exogenous insulin and other antidiabetic agents. This diet, although strict, has potential as an alternative to pharmacologic therapies for this emerging subset of diabetic individuals. Diabetes Care 27:348 -353, 2004T he prevalence of obesity in adolescence has increased dramatically within the past two decades, with at least 12% of adolescents defined as overweight (BMI above the 95th percentile for age and sex) (1). The U.S. National Diabetes Commission and the Nurse's Health Study have both found a direct relationship between weight gain and the risk for diabetes (2,3). Excessive weight among adolescents threatens to become a major public health problem, as the emergence of type 2 diabetes in this age-group has risen exponentially (4). A number of groups have reported a profound increase in the incidence of type 2 diabetes among minority children in North America (5-9). Among African-American adolescents, this subset of diabetes is frequently associated with morbid obesity and hypertension (8,10). This condition is characterized by the absence of islet cell antibodies, normal to elevated fasting C-peptide levels, acanthosis nigricans, and a parental history of type 2 diabetes (11). At the time of presentation, many of the signs of type 1 diabetes (weight loss, polyuria, and polydipsia) may be lacking, while variable degrees of ketosis and even ketoacidosis are quite common (12). Obesity and puberty appear to combine with genetic predisposition to result in disease presentation (13...

Purpose To investigate white matter (WM) structural alterations using diffusion tensor imaging (DTI) in obstructive sleep apnea (OSA) patients, with or without residual sleepiness, following adherent continuous positive airway pressure (CPAP) treatment. Possible quantitative relationships were explored between the DTI metrics and two clinical assessments of somnolence. Methods Twenty nine male patients (30–55 years old) with a confirmed diagnosis of OSA were recruited. The patients were treated with CPAP therapy only. The Psychomotor Vigilance Task (PVT) and Epworth Sleepiness Scale (ESS) were performed after CPAP treatment and additionally administered at the time of MRI scan. Based on the PVT results, the patients were divided into a non-sleepy group (lapses≤5) and a sleepy group (lapses > 5). DTI was performed at 3T, followed by an analysis using tract-based spatial statistics (TBSS) to investigate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), and radial diffusivity (λ23) between the two groups. Results A higher MD (p < 0.05) was observed in the sleepy group than the non-sleepy group in the whole-brain TBSS analysis in the WM. The increased MD (17.8% of the fiber tracts; p<0.05) was caused primarily by an elevated λ23. Axial diffusivity (λ1) exhibited no significant difference (p > 0.17). The alterations in FA or MD of individual fiber tracts occurred mainly in the internal/external capsule, corona radiata, corpus callosum, and sagittal stratum regions. The FA and MD values correlated with the PVT and ESS assessments from all patients (R ≥ 0.517, p < 0.05). Conclusions Global and regional WM alterations, as revealed by DTI, can be a possible mechanism to explain why OSA patients with high levels of CPAP use can have differing responses to treatment. Compromised myelin sheath, indicated by increased radial diffusivity, can be involved in the underlying WM changes.