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Just as the type and duration of physical activity can have variable effects on the glucose levels and other cardiometabolic parameters among patients with type 2 diabetes mellitus (T2DM), so can the types of foods have variable effects as well. This 12-week randomized study of 51 study participants evaluated the impact of routine consumption of dark raisins versus alternative processed snacks on glucose levels and other cardiovascular risk factors among patients with type T2DM. In this study, compared to alternative processed snacks, those who consumed raisins had a significant 23% reduction in postprandial glucose levels (P = 0.024). Also compared to snacks, those who consumed raisins had a 19% reduction in fasting glucose and 0.12% reduction in hemoglobin A1c, although these latter findings did not achieve statistical significance. Regarding blood pressure, compared to alternative processed snacks, those who consumed raisins had a significant 8.7 mmHg reduction in systolic blood pressure (P = 0.035) (7.5% [P = 0.031]) but did not experience a significant reduction in diastolic blood pressure. Compared to alternative processed snacks, those who consumed raisins did not have a significant improvement in body weight, body mass index, waist circumference, fasting insulin, homeostatic model assessment of insulin resistance, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL), triglyceride, or non-HDL cholesterol levels. Overall, these data support raisins as a healthy alternative compare to processed snacks in patients with T2DM.

This study validates and expands on our previous work that assessed three-dimensional (3D) nuclear telomere profiling in buccal cells of Alzheimer's disease (AD) patients and non-AD controls (Mathur et al., J Alzheimers Dis 39, 35-48, 2014). While the previous study used age- and gender-matched caregiver controls, the current study consented a new cohort of 44 age- and gender-matched healthy non-caregiver controls and 44 AD study participants. 3D telomeric profiles of buccal cells of AD patients and their non-AD controls were examined with participant information blinded to the analysis. In agreement with our previous study, we demonstrate that 3D telomeric profiles allow for the distinction between AD and non-AD individuals. This validation cohort provides an indication that the total number of 3D telomeric signals and their telomere lengths may be a suitable biomarker to differentiate between AD and non-AD and between mild, moderate, and severe AD. Further studies with larger sample sizes are required to move this technology further toward the clinic.

Aims: Cognitive decline disproportionately affects older adult type 2 diabetes. We tested whether randomized intensive glucose-lowering reduces the rate(s) of cognitive decline in adults with advanced type 2 diabetes (mean: age, 60 years; diabetes duration, 11 years) from the Veterans Affairs Diabetes Trial. Methods: A battery of neuropsychological tests (digit span, digit symbol substitution (DSym), and Trails-making Part B (TMT-B)) was administered at baseline in ~1700 participants and repeated at year 5. Thirty-six risk factors were evaluated as predictors of cognitive decline in multivariable regression analyses.Results: The mean age-adjusted, DSym or TMT-B declined significantly in all study participants (P < 0.001). Randomized intensive glucose-lowering did not significantly alter the rate of cognitive decline. The final model of risk factors associated with 5-year decline in age-adjusted TMT-B included as significant predictors: longer baseline diabetes duration (beta = -0.028; P = 0.0057), lower baseline diastolic blood pressure (beta = 0.028; P < 0.001), and baseline calcium channel blocker medication use (beta = -0.639; P < 0.001). Higher baseline pulse pressure was significantly associated with decline in age-adjusted TMT-B suggesting a role for both higher systolic and lower diastolic blood pressure. Baseline thiazide diuretic use (beta= -0.549; P =0.015) was an additional significant predictor of 5-year decline in age-adjusted digit symbol score. Post-baseline systolic blood pressure-lowering was significantly associated (P < 0.001) with decline in TMT-B performance. There was a significant inverse association between post-baseline plasma triglyceride- lowering (P = 0.045) and decline in digit symbol substitution task performance.Conclusions: A five-year period of randomized intensive glucose-lowering did not significantly reduce the rate of cognitive decline in older-aged adults with type 2 diabetes. Systolic and diastolic blood pressure as well as plasma triglycerides were modifiable risk factors of the rate of cognitive decline in older adult type 2 diabetes.

Many randomized controlled trials (RCTs) have assessed the effects of soy protein on serum lipoprotein risk factors for coronary heart disease (CHD). This review and meta-analysis assessed the quality of these RCTs and estimated the effects of soy protein consumption on serum lipoproteins.A comprehensive search using multiple databases was conducted for the years 1996 through 2008 to identify clinical trials related to soy protein intake and serum lipoprotein changes.RCTs were assessed that met these requirements: soy protein intake compared with nonsoy protein, provided information on serum low-density lipoprotein (LDL)-cholesterol values, provided no more than 65 g of soy protein daily, and obtained LDL-cholesterol measurements between 4 and 18 weeks of treatment. Randomized parallel and crossover studies were evaluated.Studies were graded for quality using 12 criteria with a possible maximum grade of 24. Net changes in lipoproteins with soy protein consumption compared with nonsoy control diets were analyzed by meta-analyses and funnel plots. Confidence intervals were constructed using inverse weighting. Analyses compared parallel to crossover studies and studies with lower and higher grades.Analyses included 20 parallel-design studies and 23 crossover studies. Parallel studies scored significantly higher (p0.001) in study quality, with a mean grade of 15.8 (95% confidence interval [CI], 14.3 to 17.3) compared with 10.1 (95% CI, 8.2 to 11.9) for crossover trials. Soy protein intake was associated with net changes in serum LDL-cholesterol values of -0.23 mmol/l (95% CI, -0.28 to -0.18 mmol/l) or a 5.5% reduction in parallel studies and -0.16 mmol/l (95% CI, -0.22 to -0.11 mmol/l) or a reduction of 4.2% with crossover studies (p0.001 for parallel vs crossover). In parallel studies, net serum HDL-cholesterol values were 3.2% higher (p0.007) with soy vs control, and fasting serum triacylglycerol values were 10.7% lower (p0.008) for soy vs control.Soy protein consumption with a median of 30 g/d was associated with a significant improvement in lipoprotein risk factors for CHD. Compared with crossover RCTs, parallel RCTs had significantly higher quality grades and were associated with significantly greater improvements in serum LDL-cholesterol values. Regular consumption of 1 to 2 servings of soy protein daily (15 to 30 g) has a significant favorable impact on serum lipoprotein risk factors for CHD.

Context: Ghrelin and peptide YY (PYY) are two hormones produced by the gastrointestinal tract that have effects on appetite. However, little is known about their secretion in response to meals high in individual macronutrients in prepubertal children. Objective: We sought to understand how meals high in carbohydrate, protein, and fat affect serum concentrations of total ghrelin and total PYY, hypothesizing that these macronutrients would exert differential effects on their secretion. Design and Setting: This was a cross-sectional study at one tertiary care center. Subjects: Subjects were 7- to 11-yr-old healthy normal-weight (NW) and obese (OB) volunteers recruited from local advertisements. Interventions: After an overnight fast, the subjects were given a breakfast high in carbohydrate, protein, or fat at 0800 h. Blood samples for total ghrelin and total PYY were taken at baseline, 30 min, and hourly from 0900 to 1200 h. Main Outcome Measure: We assessed postprandial ghrelin suppression and PYY elevation, as well as changes in reported hunger and satiety, after the three test meals. Results: After the high-protein meal, ghrelin declined gradually in both groups over the study period without subsequent increase, whereas ghrelin suppressed more rapidly to a nadir at 60 min after the high-carbohydrate meal in both NW and OB children, followed by rebound in ghrelin levels. Similarly, after the high-protein meal, PYY concentrations increased steadily over the course of the morning in both groups without decline, whereas PYY levels peaked 30 min after the high-carbohydrate meal in both NW and OB subjects with significant decline thereafter. Ghrelin and PYY responses to the high-fat meal were somewhat intermediate between that observed with high carbohydrate and high protein. The OB children reported higher hunger and lower satiety after the high-carbohydrate meal compared to the NW subjects, whereas appetite ratings were similar between the groups after the high-protein and high-fat meals. Additionally, within the OB group, area under the curve (AUC) analysis revealed significantly greater PYY response, as well as lower AUC hunger and higher AUC satiety, to the high-protein meal than the high-carbohydrate and high-fat meals. Conclusions: The patterns of secretion of ghrelin and PYY in our study of prepubertal children suggest that they may play a role in the effectiveness of high-protein/low-carbohydrate diets in promoting weight loss.

Existing obesity therapies are limited by safety concerns and modest efficacy reflecting a weight loss plateau. Here, we explore combination therapy with bupropion (BUP), a putative stimulator of melanocortin pathways, and an opioid antagonist, naltrexone (NAL), to antagonize an inhibitory feedback loop that limits sustained weight reduction. In vitro electrophysiologic experiments were conducted to determine the extent to which BUP+NAL stimulated hypothalamic pro-opiomelanocortin (POMC) neurons in mouse brain. A subsequent study further characterized the effect of combination BUP+NAL treatment on food intake in lean and obese mice. Finally, a randomized, blinded, placebo-controlled trial in obese adult subjects was conducted. Randomization included: BUP (300 mg) + NAL (50 mg), BUP (300 mg) + placebo (P), NAL (50 mg) + P or P+P for up to 24 weeks. BUP+NAL stimulated murine POMC neurons in vitro and caused a greater reduction in acute food intake than either monotherapy, an effect consistent with synergism. Combined BUP+NAL provided sustained weight loss without evidence of an efficacy plateau through 24 weeks of treatment. BUP+NAL completers diverged from NAL+P (P < 0.01) and P+P (P < 0.001) at week 16 and from BUP+P by week 24 (P < 0.05). The combination was also well tolerated. Translational studies indicated that BUP+NAL therapy produced synergistic weight loss which exceeded either BUP or NAL alone. These results supported the hypothesis that NAL, through blockade of β-endorphin mediated POMC autoinhibition, prevents the classic weight loss plateau observed with monotherapies such as BUP. This novel treatment approach (BUP+NAL) holds promise for the treatment of obesity.

Background Prior clinical trials suggest that the Transcendental Meditation technique may decrease blood pressure of normotensive and hypertensive individuals but study-quality issues have been raised. This study was designed to assess effects of Transcendental Meditation on blood pressure using objective quality assessments and meta-analyses. Methods PubMed and Cochrane databases through December 2006 and collected publications on Transcendental Meditation were searched. Randomized, controlled trials comparing blood pressure responses to the Transcendental Meditation technique with a control group were evaluated. Primary outcome measures were changes in systolic and diastolic blood pressure after practicing Transcendental Meditation or following control procedures. A specific rating system (0-20 points) was used to evaluate studies and random-effects models were used for meta-analyses. Results Nine randomized, controlled trials met eligibility criteria. Study-quality scores ranged from low (score, 7) to high (16) with three studies of high quality (15 or 16) and three of acceptable quality (11 or 12). The random-effects meta-analysis model for systolic and diastolic blood pressure, respectively, indicated that Transcendental Meditation, compared to control, was associated with the following changes: -4.7 mm Hg (95% confidence interval (CI), -7.4 to -1.9 mm Hg) and -3.2 mm Hg (95% CI, -5.4 to -1.3 mm Hg). Subgroup analyses of hypertensive groups and high-quality studies showed similar reductions. Conclusions The regular practice of Transcendental Meditation may have the potential to reduce systolic and diastolic blood pressure by approximately 4.7 and 3.2 mm Hg, respectively. These are clinically meaningful changes.

Orlistat, in the 60-mg over-the-counter dose, was recently approved by the FDA. This lipase inhibitor blocks absorption of ~25% of ingested fat and has ~85% of the efficacy of the 120-mg dose for weight loss. Over 16 weeks weight loss with diet and orlistat 60 mg averages ~5% of initial body weight. The 60-mg dose is better tolerated than the 120-mg dose and the gastrointestinal side effects are minimal when individuals consume < 30% of their energy from fat. In addition to facilitating modest weight loss, orlistat use decreases serum LDL-cholesterol values by ~10%. When taken three times daily before meals, orlistat 60 mg modifies lifestyle behavior, encourages lower fat-consumption and sets the stage for other healthy lifestyle changes.

Recent studies suggest that obese individuals lose weight more rapidly and lose more total weight with soy protein than with animal protein as a major diet component. The purpose of the present study was to evaluate the weight-loss efficacy and changes in body composition, waist circumference, blood pressure, and levels of plasma glucose, insulin, serum lipids, C-reactive protein, and homocysteine from consumption of either 3 soy shakes or 3 casein shakes daily as part of a 16-week, energy-restricted diet for obese women. Forty-three women with body mass index values of 30 to 40 kg/m(2) were randomized to intensive dietary interventions using either casein (n = 21) or soy (n = 22) shakes. Subjects were instructed to consume 3 shakes, 1 prepackaged entrée, and 5 servings of fruits or vegetables daily to achieve an energy intake of 4.5 to 5.0 MJ/d. Subjects attended classes weekly or biweekly. Weight, body fat, lipid, and glucose measurements were obtained at baseline and at 8 and 16 weeks. For both groups combined, subjects lost 8.1% of initial body weight (7.7 kg) at 8 weeks and 13.4% (12.7 kg) at 16 weeks. Weight loss from baseline did not differ significantly by group and, for completing subjects, was 14.0% +/- 1.2% (mean +/- SE) for casein and 12.8% +/- 1.4% for soy. With the intention-to-treat analysis, weight losses at 16 weeks were 12.5% +/- 1.4% for casein and 11.3% +/- 1.2% for soy. Body fat losses were 23.7% +/- 2.0% for casein and 21.8% +/- 2.4% for soy and did not differ significantly. Both study groups lost significant amounts of weight with a highly structured behavioral program incorporating 4 meal replacements and vegetables and fruits. Differences in weight loss and body composition changes between casein and soy treatments were not significant.

Background: Lifestyle measures are considered the first line of therapy for treating overweight individuals, but many are unable to achieve a meaningful weight loss. Objective: To determine the efficacy and safety of orlistat 60 mg, given 3 times daily, for weight loss in mildly to moderately overweight individuals. Methods: A multicenter, 16 week, randomized, double-blind, placebo-controlled study was conducted in 391 overweight subjects at 20 US centers. The main outcome measure was change in weight from baseline to week 16; secondary measures included changes in body mass index, waist circumference, blood pressure, and fasting lipoprotein and glucose levels. Results: Subjects in both groups lost weight over the treatment period; however, orlistat-treated subjects lost significantly more weight than placebo-treated subjects beyond 2 weeks of treatment. Weight loss from baseline to week 16 was significantly greater in participants receiving orlistat versus those receiving placebo (3.05 vs 1.90 kg; p < 0.001, intent-to-treat analysis). Orlistat-treated subjects who completed 16 weeks of treatment lost 4.8 ± 0.35% (mean ± SE) of baseline weight compared with 3.1 ± 0.38% for the placebo group (p < 0.001). Orlistat-treated subjects, compared with those receiving placebo, also demonstrated a greater relative reduction in total (–4.4% vs 0.0%; p = 0.004) and low-density lipoprotein cholesterol (–7.2% vs -0.6%; p = 0.005) and both diastolic (-3.9% vs -0.5%; p = 0.001) and systolic blood pressure (-4.7% vs -1.8%; p = 0.004). Both groups showed a similar safety profile; gastrointestinal events were significantly more common in the orlistat-treated subjects. Conclusions: The use of orlistat 60 mg by mildly to moderately overweight individuals produced significant weight loss in conjunction with a reduced calorie diet and self-instructional materials. This amount of weight loss was associated with improvements in several weight-related risk factors. Orlistat 60 mg may be a useful adjunct to lifestyle measures and has the potential to contribute significantly to weight and risk factor improvement for overweight individuals.

Soy protein intake has favorable effects on body weight and fat distribution in experimental animals but these effects have not been demonstrated in humans. To compare effects of soy- vs. milk-based meal replacements (MR) we assessed weight loss and serum lipoproteins changes for obese subjects who consumed low-energy diets (LED) including either milk-based or soy-based MR.Overweight or obese women and men (body mass indices 27-40 kg/m(2)) were randomly assigned to LED providing 1200 kcal/day, with consumption of five soy-based or two milk-based liquid MR for a 12-week weight loss trial. Serum lipoprotein measurements were obtained at baseline, 6 and 12 weeks.For soy and milk MR groups, subject numbers were, respectively, 51 and 39 randomized and 30 and 22 completers. MR use averaged: soy, 3.7/day; and milk, 1.9/day. Weight losses for completers at 12 weeks were: soy MR, 9.0% of initial body weight (95% confidence intervals, 7.3-10.6%); and milk MR, 7.9% (5.8-8.8%) with no significant differences. Reductions from baseline in serum cholesterol and LDL-cholesterol values, respectively, at six weeks were significantly greater (P0.015) with soy MR (15.2% and 17.4%) than with milk MR (7.9% and 7.7%). Soy MR use was associated with significant reductions in serum triglycerides at 6 and 12 weeks while milk MR use was not.Soy MR use, as part of a low-energy diet, was associated with slightly but not significantly greater weight loss over a 12-week period than milk MR use. These observations confirm previous studies documenting the effectiveness of MR use for weight loss.

To review international nutrition recommendations with a special emphasis on carbohydrate and fiber, analyze clinical trial information, and provide an evidence-based recommendation for medical nutrition therapy for individuals with diabetes. Relevant articles were identified by a thorough review of the literature and the data tabulated. Fixed-effects meta-analyses techniques were used to obtain mean estimates of changes in outcome measures in response to diet interventions. Most international organizations recommend that diabetic individuals achieve and maintain a desirable body weight with a body mass index of/=25 kg/m(2). For diabetic subjects moderate carbohydrate, high fiber diets compared to moderate carbohydrate, low fiber diets are associated with significantly lower values for: postprandial plasma glucose, total and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. High carbohydrate, high fiber diets compared to moderate carbohydrate, low fiber diets are associated with lower values for: fasting, postprandial and average plasma glucose; hemoglobin A(1c); total, LDL-cholesterol, HDL-cholesterol and triglycerides. Low glycemic index diets compared to high glycemic index diets are associated with lower fasting plasma glucose values and lower glycated protein values. Based on these analyses we recommend that the diabetic individual should be encouraged to achieve and maintain a desirable body weight and that the diet should provide these percentages of nutrients: carbohydrate,/=55%; protein, 12-16%; fat,30%; and monounsaturated fat, 12-15%. The diet should provide 25-50 g/day of dietary fiber (15-25 g/1000 kcal). Glycemic index information should be incorporated into exchanges and teaching material.

Obesity is a major risk factor for development of diabetes, and excessive energy intake is a major contributor to poor glycemic control in Type 2 diabetes. The impact of obesity on risk for diabetes as well as coronary heart disease (CHD) risk factors and the benefits of weight loss in decreasing risk for developing diabetes and improving glycemia and CHD risks were reviewed. A systematic review of the medical literature to assess the impact of obesity and weight gain on risk for diabetes and CHD was done. We performed a meta-analysis of the effects of weight loss for obese diabetic individuals. Controlled clinical trials assessing lifestyle changes on risk for developing diabetes and weight loss effects on glycemia and CHD risk factors were reviewed. Obesity and weight gain can increase risk for diabetes by greater than ninetyfold and CHD by about sixfold. Very-low-energy diets (VLED) decrease fasting plasma glucose values by approximately 50% within two weeks and these changes are sustained with continued energy restriction. Twelve weeks of energy-restricted diets were associated with these significant decreases: body weight, 9.6%; fasting plasma glucose, 25.7%; serum cholesterol, 9.2%; serum triglycerides, 26.7%; systolic blood pressure, 8.1%; and diastolic blood pressure, 8.6%. Larger weight losses were associated with larger reductions in these values. The reviewed data suggest that US health care providers should endorse the American Heart Association's and European diabetes associations' recommendations that diabetic persons achieve and maintain a BMI of

OBJECTIVE—To assess the effect of insulin resistance and the benefit of the fibrate, gemfibrozil, on the incidence of major cardiovascular events in subjects with low HDL cholesterol and a broad range of triglyceride values who participated in the Veterans Affairs High Density Lipoprotein Intervention Trial (VA-HIT). RESEARCH DESIGN AND METHODS—This intention-to-treat analysis, specified as a secondary objective in VA-HIT, determined using Cox proportional hazards models the 5-year combined incidence of nonfatal myocardial infarction, coronary heart disease (CHD) death, or stroke in relation to the presence or absence of insulin resistance (defined by the highest tertile of the homeostasis model assessment of insulin resistance, HOMA-IR) in conjunction with lower and higher levels of HDL cholesterol and triglycerides. The study population consisted of 2,283 men with known coronary heart disease (CHD), treated with either placebo or gemfibrozil, who could be subdivided into groups with diabetes with or without insulin resistance, with no diabetes but insulin resistance, and with neither diabetes nor insulin resistance. RESULTS—With insulin resistance there was a significantly higher relative risk (RR) of a cardiovascular event both with diabetes (RR of 1.62 with 95% CI of 1.28–2.06) and without diabetes (RR of 1.43 with 95% CI of 1.03–1.98) than without insulin resistance. Throughout both lower and higher ranges of HDL cholesterol and triglycerides, the rate of new cardiovascular events and the reduction of events with gemfibrozil was greater in subjects with insulin resistance than without, despite the finding that an increase in HDL cholesterol and a decrease in triglycerides with gemfibrozil was less with insulin resistance than without insulin resistance. CONCLUSIONS—Results show that in VA-HIT the occurrence of a new cardiovascular event and the benefit of fibrate therapy was much less dependent on levels of HDL cholesterol or triglycerides than on the presence or absence of insulin resistance.

Aims: To evaluate the efficacy of a lifestyle intervention programme including meal replacements and increased physical activity upon body weight, diabetes control and other cardiovascular risk factors in obese, poorly controlled, insulin-treated, type-2-diabetic individuals and to assess the impact of concomitant rosiglitazone (RSG) therapy. Methods: This 6-month intervention study included 21 patients with type 2 diabetes mellitus (DM) requiring insulin therapy with haemoglobin A1c (HbA1c) > 7% and with a body mass index (b.m.i.) > 27. All subjects were enrolled in a 6-month lifestyle intervention programme and randomized to placebo or RSG 4 mg/day. Participation in the lifestyle programme included meal replacements, increased intake of fruits and vegetables and increased daily physical activity. Measured end-points included body weight, waist circumference, blood pressure, HbA1c and serum lipids, before entry into the study. Results: The baseline mean b.m.i. was 36.4 and the mean HbA1c was 9.0%. The greatest weight losses occurred during the first 12 weeks (19 lbs for RSG, 13.4 lbs for placebo) with a greater weight loss at each point for the group receiving RSG. Waist circumference declined by 2.8 and 4.0 inches for the placebo and RSG groups. Systolic BP declined 16.2 mmHg in the placebo group and 14.3 mmHg in the RSG group. Diastolic blood pressure decreased by 12.8 mmHg in the placebo group. HbA1c was reduced significantly by 1.3% for the placebo group and 1.1% in the RSG group. Discussion: This study demonstrates the benefits of lifestyle intervention using meal replacements and increased physical activity with resultant modest weight loss in long-standing, poorly controlled type 2 diabetes. RSG did not impede weight loss and, in fact, amplified some of the positive benefits of lifestyle intervention.

OBJECTIVE—The purpose of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on body weight, glycemic control, and cardiovascular risk factors in metformin-treated type 2 diabetic patients. RESEARCH DESIGN AND METHODS—A 1-year multicenter, randomized, double-blind, placebo-controlled trial of 120 mg orlistat t.i.d. (n = 249) or placebo (n = 254) combined with a reduced-calorie diet was conducted in overweight and obese patients with suboptimal control of type 2 diabetes. RESULTS—After 1 year of treatment, mean (±SE) weight loss was greater in the orlistat than in the placebo group (−4.6 ± 0.3% vs. −1.7 ± 0.3% of baseline wt, P < 0.001). Orlistat treatment caused a greater improvement in glycemic control than placebo, as evidenced by a greater reduction in serum HbA1c, adjusted for changes in metformin and sulfonylurea therapy (−0.90 ± 0.08 vs. −0.61 ± 0.08, P = 0.014); a greater proportion of patients achieving decreases in HbA1c of ≥0.5 and ≥1.0% (both P < 0.01); and a greater reduction in fasting serum glucose (−2.0 ± 0.2 vs. −0.7 ± 0.2 mmol/l, P = 0.001). Compared with the placebo group, patients treated with orlistat also had greater decreases in total cholesterol, LDL cholesterol, and systolic blood pressure (all P < 0.05). Although more subjects treated with orlistat experienced gastrointestinal side effects than placebo (83 vs. 62%, P < 0.05), more subjects in the placebo group withdrew prematurely from the study than in the orlistat group (44 vs. 35%, P < 0.05). CONCLUSIONS—Orlistat is a useful adjunctive treatment for producing weight loss and improving glycemic control, serum lipid levels, and blood pressure in obese patients with type 2 diabetes who are being treated with metformin.

ANDERSON, JAMES W. AND ELIZABETH C. KONZ. Obesity and disease management: effects of weight loss on comorbid conditions. Obes Res. 2001;9:326S‐334S. Objective: This review is designed to quantitate the effects of obesity and weight gain on risk for coronary heart disease (CHD) and to review the effects of weight loss on CHD risk factors. Research Methods and Procedures: After a comprehensive review of the literature related to body weight and weight gain on CHD risk, the relative risks (RRs) were tabulated. Values were averaged and meta-analysis techniques were used to estimate the variance-adjusted RR. Results: Young persons with higher body mass index values have a significantly higher risk for CHD than do slender young people. For every 1% above a desirable body mass index, the risk for CHD increases by 3.3% for women and by 3.6% for men. Every kilogram of weight gain after high school increases risk for CHD by 5.7% for women and 3.1% for men. Weight loss significantly decreases major CHD risk factors. For every kilogram of weight loss the following favorable changes occur: fasting serum cholesterol, 21.0%; low-density lipoprotein cholesterol, 20.7%; triglycerides, 21.9%; high-density lipoprotein cholesterol, 10.2%; systolic blood pressure, 20.5%; diastolic blood pressure, 20.4%; and blood glucose, 20.2 mM. Discussion: Obesity and/or weight gain are associated with major risk for CHD. Weight loss significantly improves serum lipid parameters, blood pressure, and fasting blood glucose values. Effective treatment approaches are available for most overweight or obese individuals but a major challenge is to enable these individuals to engage in these programs. Professional and consumer education is essential for advancing effective intervention strategies for overweight individuals.

The constancy of plasma osmolality demands that salt and water concentration within the extracellular fluid be constantly monitored and regulated within a few percentage points. The circumventricular organs in general, and the subfornical organ in particular, have long been proposed to be the site of the osmosensitivity. Isolated subfornical organ neurons of male rats were studied using the whole-cell patch-clamp technique and both action potential frequency and whole cell currents were measured as bath osmolality was changed, from 240 to 330 mOsm, by altering the amount of mannitol and maintaining the concentrations of electrolytes constant. Out of 64 cells, 66% responded to changes in bath osmolality in a predictable manner, exhibiting a hyperpolarization and decrease in spike frequency in hypo-osmotic solutions and a depolarization and increase in action potential frequency during hyperosmotic exposure. Cells (34%) defined as non-responders exhibited no significant modulation during identical changes in extracellular osmolality. The responses to changing extracellular osmolality were dose dependent; the activity of subfornical organ neurons was significantly modulated by changes in extracellular osmolality of less than 10 mOsm. By regression analysis, this osmosensitivity was approximately 0.1 Hz/mOsm change throughout a ±10 mOsm range and was maintained throughout the range of osmolalities studied (270–330 mOsm). The mechanism underlying this osmosensitivity remains unclear, although the non-selective cation conductance and the volume-activated chloride conductance do not seem to be involved. This intrinsic osmosensitivity of subfornical organ within the normal physiological range supports the view that this circumventricular structure plays a role in normal osmoregulation.

Background: Hypercholesterolemia is a major risk factor for coronary heart disease and nutrition management is the initial therapeutic approach. Objective: This multicenter study evaluated the long-term effectiveness of psyllium husk fiber as an adjunct to diet in the treatment of persons with primary hypercholesterolemia. Design: Men and women with hypercholesterolemia were recruited. After following an American Heart Association Step I diet for 8 wk (dietary adaptation phase), eligible subjects ts with serum LDL-cholesterol concentrations between 3.36 and 4.91 mmol/L were randomly assigned to receive either 5.1 g psyllium or a cellulose placebo twice daily for 26 wk while continuing diet therapy. Results: Serum total and LDL-cholesterol concentrations were 4.7% and 6.7% lower in the psyllium group than in the placebo group after 24-26 wk (P < 0.001). Other outcome measures did not differ significantly between groups. Conclusions: Treatment with 5.1 g psyllium twice daily produces significant net reductions in serum total and LDL-cholesterol concentrations in men and women with primary hypercholesterolemia. Psyllium therapy is an effective adjunct to diet therapy and may provide an alternative to drug therapy for some patients.

Background: Soluble fibers, including those from psyllium husk, have been shown to augment the cholesterol-lowering effects of a low-fat diet in persons with hypercholesterolemia. As evidence of this, the US Food and Drug Administration recently authorized the use of health claims on food products containing soluble fiber from psyllium that state that they are associated with a decreased risk of coronary heart disease. Objective: This meta-analysis was conducted to more precisely define the hypolipidemic effects and safety of psyllium when used adjunctive to a low-fat diet in men and women with hypercholesterolemia. Design: The 8 studies in the meta-analysis included a total of 384 and 272 subjects receiving psyllium or cellulose placebo, respectively. All studies evaluated the hypocholesterolemic effects of 10.2 g psyllium/d adjunctive to a low-fat diet for ≥8 wk in individuals with mild-to-moderate hypercholesterolemia after a low-fat diet lead-in phase lasting ≥ 8 wk. The safety and adverse events associated with psyllium consumption were summarized from pooled data of 19 clinical studies ranging from 6 wk to 6 mo in duration. Results: Consumption of 10.2 g psyllium/d lowered serum total cholesterol by 4% (P < 0.0001), LDL cholesterol by 7% (P < 0.0001), and the ratio of apolipoprotein (apo) B to apo A-I by 6% (P < 0.05) relative to placebo in subjects already consuming a low-fat diet, with no effect on serum HDL or triacylglycerol concentrations. Conclusions: Psyllium supplementation significantly lowered serum total and LDL-cholesterol concentrations in subjects consuming a low-fat diet. Psyllium is well tolerated and safe when used adjunctive to a low-fat diet in individuals with mild-to-moderate hypercholesterolemia.

Background Although it is generally accepted that lowering elevated serum levels of low-density lipoprotein (LDL) cholesterol in patients with coronary heart disease is beneficial, there are few data to guide decisions about therapy for patients whose primary lipid abnormality is a low level of high-density lipoprotein (HDL) cholesterol. Methods We conducted a double-blind trial comparing gemfibrozil (1200 mg per day) with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg per deciliter (1.0 mmol per liter) or less, and an LDL cholesterol level of 140 mg per deciliter (3.6 mmol per liter) or less. The primary study outcome was nonfatal myocardial infarction or death from coronary causes. Results The median follow-up was 5.1 years. At one year, the mean HDL cholesterol level was 6 percent higher, the mean triglyceride level was 31 percent lower, and the mean total cholesterol level was 4 percent lower in the gemfibrozil group than in the placebo group. LDL cholesterol levels...

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the U.S. and in most developed countries. Many nutritional factors contribute to risk for ASCVD including total and saturated fat consumption, fruits and vegetables in the diet and dietary fiber intake. This review will focus on the relationship of dietary fiber intake to risk for coronary heart disease (CHD) and ASCVD (which includes, principally, CHD, cerebral vascular disease and peripheral vascular disease). Fiber-rich foods such as vegetables, fruits, whole-grain cereals and legumes are rich sources of nutrients, phytochemicals and antioxidants. For example, most high fiber foods contain soluble and insoluble fiber, minerals, vitamins, other micronutrients and phytochemicals. Cereals and legumes also contain complex carbohydrates and unsaturated fatty acids. Some high fiber foods are rich in monounsaturated fatty acids, whereas others provide (n-3) fatty acids. Legumes and certain vegetables provide oligosaccharides. When assessing the health benefits of dietary fiber, one should consider the potential effects of associated nutrients, micronutrients and phytochemicals. These interactions will be reviewed as we discuss relationships of dietary fiber to ASCVD.

Background: Long-term maintenance of weight loss remains a therapeutic challenge in obesity treatment. Objective: This multicenter, double-blind, placebo-controlled study was designed to test the hypothesis that orlistat, a gastrointestinal lipase inhibitor, is significantly more effective than a placebo in preventing weight regain. Design: Obese subjects who lost ≥8% of their initial body weight during a 6-mo lead-in of a prescribed hypoenergetic diet (4180-kJ/d deficit) with no adjunctive pharmacotherapy were randomly assigned to receive placebo, 30 mg orlistat, 60 mg orlistat, or 120 mg orlistat 3 times daily for I y in combination with a maintenance diet to help prevent weight regain. Of 1313 recruited subjects [body mass index (in kg/m 2 ): 28-43], 729 subjects lost ≥8% of their initial body weight during the 6-mo weight-loss lead-in period and were enrolled in the double-blind phase. Results: After 1 y, subjects treated with 120 mg orlistat 3 times daily regained less weight than did placebo-treated subjects (32.8 ± 4.5% compared with 58.7 ± 5.8% regain of lost weight; P < 0.001). Moreover, more subjects in the 120-mg orlistat group than in the placebo group regained ≤25% of lost weight (47.5% of subjects compared with 29.9%). In addition, orlistat treatment (120 mg 3 times daily) was associated with significantly greater reductions in total and LDL-cholesterol concentrations than was placebo (P < 0.001). Conclusion: The use of orlistat during periods of attempted weight maintenance minimizes weight readjustment and facilitates long-term improvement in obesity-related disease risk factors.

Levels of antioxidants, activities of free radical scavenging enzymes and extent of lipid peroxidation were determined in the blood of 37 elderly diabetic men and 30 control elderly men, 16 without cardiovascular disease (CVD) and 14 with CVD. The mean +/-S.D. of the ages of the diabetic men was 66+/-5 and those of the control men was 69+/-5, while serum glucose levels of diabetic men were 213+/-81 mg/dl and that of control subjects were 95+/-14 mg/dl. Among the diabetic men, 13 men were obese with body mass index>30, 26 men had poor control of diabetes (glycohemoglobin>7%) and 25 men had retinopathy. The diets of the control and diabetic men were evaluated. Blood samples were collected and analyzed for major endogenous antioxidant defense parameters and lipid peroxidation. The results show that diabetic men had significantly lower blood reduced glutathione levels (p

For > 150 y, clinicians and investigators have observed that high protein intakes accelerate the progression of renal disease and that low protein intakes have beneficial effects. Some studies suggest that the effects of soy-protein intake resemble those of a low-protein diet. The Brenner hypothesis suggests that high protein intakes by diabetic individuals create hyperfiltration and glomerular hypertension eventuating in renal damage. On the basis of the available evidence, we are proposing the soy-protein hypothesis, which states that substituting soy protein for animal protein in diabetes patients results in less hyperfiltration and glomerular hypertension and, therefore, resultant protection from diabetic nephropathy. Furthermore, substituting soy protein for animal protein should have therapeutic value in diabetic nephropathy with resultant slowing of deterioration of renal function and decreasing proteinuria. The preliminary results of the study of 8 type 2 diabetes patients with obesity, hypertension, and proteinuria are reported. Under the conditions of the study, providing soy protein as half of the daily protein intake had no distinct effects on renal function or proteinuria in these subjects. Soy-protein intake was associated with a significant reduction in serum cholesterol and triacylglycerol concentrations. Further studies are required to critically examine the effects of soy-protein intake on the renal function of diabetes patients.

OBJECTIVE To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbAlc levels of ≥8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required antihypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI 34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS IIP therapy in insulinrequiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels

Objective. —To determine whether implantable insulin pump (IIP) therapy and multiple daily insulin (MDI) injections could equally attain improved blood glucose control, and to compare the 2 treatments with respect to reducing daily blood glucose fluctuations, reducing serious hypoglycemic insulin reactions, and improving patients' quality of life. Design. —Randomized clinical trial. Setting. —Seven Veterans Affairs medical centers. Patients. —One hundred twenty-one male type II diabetic patients between the ages of 40 and 69 years, receiving at least 1 injection of insulin per day and having hemoglobin A1c(HbA1c) levels of 8% or above. Intervention. —Intensive therapy (IIP or MDI) for 1 year. Main Outcome Measures. —Hemoglobin A1cand blood glucose levels. Results. —Blood glucose levels declined to 7.96±1.08 mmol/L (143.4±19.5 mg/dL) and 8.30±1.52 mmol/L (149.6±27.4 mg/dL) (mean ± SD) for IIP and MDI, respectively (P=.57). Hemoglobin A1clevels improved in both groups (time effectP Conclusions. —Intensive insulin therapy with IIP and MDI is effective in controlling non—insulin-dependent diabetes mellitus. IIP has significant advantages in reducing glycemic variability, clinical hypoglycemia, and weight gain, while improving aspects of quality of life.

We addressed the role of muscarinic receptor subtypes in neurally mediated bronchoconstriction in vivo and airway smooth muscle contraction in vitro in the newborn dog. The in vivo dosenresponse effects of iselectivei muscarinic antagonists on changes in lung resistance (RL) and heart rate (HR) in response to electrical stimulation of the vagus nerves were obtained in four groups of newborns. Each group was exposed to a different muscarinic antagonist: M1-selective pirenzepine (pir), M2-selective AF-DX 116 (11-(2-((diethylamino)methyl)-1-piperidinyl)acetyl-5,11-dihydro-6H- pyrido-(2,3-b)-(1,4)-benzodiazepine-6-one), M3-selective p-F-HHSiD (p-fluoro-hexahydro-sila-difenidol), and nonselective atropine (atr). In vitro concentrationnresponse effects of pir and AF-DX 116 were obtained for neurally induced contractions of tracheal smooth muscle, elicited by electrical field stimulation. In a separate series of experiments we measured the bronchoconstrictor response to the muscarinic agonist acetylcholine delivered by right heart injection. Muscarinic antagonists reduced RL and HR responses to vagal stimulation in a dose-dependant fashion; however, ED50 values and selectivity for airway and cardiac responses (HR/RL ED50 ratio) were significantly different between antagonists. The rank order of potencies for inhibition of the increase in RL was atr > pir, M1 > p-F-HHSiD, M3 > AF-DX 116, M2, while that for HR was atr > AF-DX 116 > pir > p-F-HHSiD. AF-DX 116 preferentially inhibited the HR response, as reflected by the lowest HR/RL ED50 ratio (p < 0.001). The remaining antagonists preferentially inhibited RL, with the highest HR/RL ED50 ratio seen for p-F-HHSiD. These data suggest that muscarinic receptor subtypes are differentiated at birth and mediate cardiac and airway responses to vagal stimulation. We did not find autoinhibitory actions of airway M2 receptors on either the in vivo bronchoconstrictor response or the in vitro contractile response to electrical field stimulation. This suggests that neonatal airway M2 receptors, but not myocardial M2 receptors, are reduced in number or weakly coupled to muscarinic signal transduction mechanisms. Direct activation of airway smooth muscle by acetylcholine caused dose-dependent increases in RL that reached a plateau at ≈200% at 100 μg, similar to values reported for vagal stimulation.

In the present study we measured fasting lipid profiles in over 8,500 community-living men with coronary artery disease (CAD) to determine the distribution of lipid abnormalities in this population: 81% were white and 16% black; mean age 62.9 +/- 8 years; mean total cholesterol 214 +/- 41 mg/dl; low-density lipoprotein (LDL) cholesterol 140 +/- 37 mg/dl; high-density lipoprotein (HDL) cholesterol 39 +/- 11 mg/dl; and triglycerides 190 +/- 142 mg/dl. After adjusting for age, the only significant difference between blacks and whites was a higher HDL cholesterol in blacks (45 vs 38 mg/dl, p or = 100 mg/dl), 38% had low HDL cholesterol ( 200 mg/dl). We estimated that 42% of men with CAD would be definite candidates for cholesterol-lowering medication according to the National Cholesterol Education Program guidelines and that 41% of those in whom cholesterol-lowering medication would not be definitely indicated had low levels of HDL cholesterol. We conclude that (1) black men with CAD have substantially higher HDL cholesterol than white men, (2) almost 90% of male patients with CAD are candidates for dietary intervention and > 40% may need medications to lower LDL cholesterol, and (3) 40% of patients without a definite indication for cholesterol-lowering medications have low levels of HDL cholesterol.

BACKGROUND/OBJECTIVES: Elevated oxidized low-density lipoprotein (OxLDL) may promote inflammation, and is associated with increased risk of atherosclerotic coronary heart disease and worsening complications of diabetes mellitus. The primary objective of this study was to evaluate the efficacy of chitin-glucan (CG), alone and in combination with a potentially anti-inflammatory olive oil (OO) extract, for reducing OxLDL in subjects with borderline to high LDL cholesterol (LDL-C) levels. SUBJECTS/METHODS: This 6-week, randomized, double-blind, placebo-controlled study of a novel, insoluble fiber derived from the Aspergillus niger mycelium, CG, evaluated 130 subjects free of diabetes mellitus with fasting LDL-C 3.37–4.92 mmol/l and glucose p6.94 mmol/l. Participants were randomly assigned to receive CG (4.5 g/day; n ¼ 33), CG (1.5 g/day; n ¼ 32), CG (1.5 g/day) plus OO extract (135 mg/day; n ¼ 30), or matching placebo (n ¼ 35). RESULTS: Administration of 4.5 g/day CG for 6 weeks significantly reduced OxLDL compared with placebo (P ¼ 0.035). At the end of study, CG was associated with lower LDL-C levels relative to placebo, although this difference was statistically significant only for the CG 1.5 g/day group (P ¼ 0.019). CG did not significantly affect high-density lipoprotein cholesterol, triglycerides, glucose, insulin or F2-isoprostane levels. Adverse events did not substantively differ between treatments and placebo. CONCLUSIONS: In this 6-week study, CG (4.5 g/day) reduced OxLDL, an effect that might affect the risk for atherosclerosis.

Oxidized low-density lipoprotein (OxLDL) is believed to play a role in the progression of atherosclerotic coronary heart disease (CHD) and the development of diabetes complications. This randomized, double-blind, placebo-controlled study of a novel insoluble fiber derived from the mycelium Aspergillus niger , chitin-glucan (CG) (ARTINIA™), evaluated 135 patients with fasting LDL-cholesterol 130-189.9 mg/dl and fasting glucose P =0.006), and reduced OxLDL 4.97 U/L compared to placebo (P=

Background Prior studies suggest soluble fibers may favorably affect glucose/insulin metabolism. Methods This prospective, randomized, placebo controlled, double blind, parallel group trial evaluated 50 generally healthy subjects without prior diagnosis of diabetes mellitus (44 completers), who were administered beverages containing placebo (control), lower dose (3 g/d), or higher dose (6 g/d) reduced viscosity barley β-glucan (BBG) extract. Subjects (68% women) mean age 56 years, Body Mass Index (BMI) 32 kg/m2 and baseline fasting plasma glucose 102 mg/dl were instructed to follow a weight-maintaining Therapeutic Lifestyle Changes (TLC) diet and consumed three 11 oz study beverages daily with meals for 12 weeks. The four primary study endpoint measures were plasma glucose and insulin [each fasting and post-Oral Glucose Tolerance Testing (OGTT)]. Results Compared to placebo, administration of 3 g/d BBG over 12 weeks significantly reduced glucose incremental Area Under the Curve (iAUC) measures during OGTT and 6 g/d BBG over 12 weeks significantly reduced fasting insulin as well as the related homeostasis model assessment of insulin resistance (HOMA-IR). Beverages were generally well tolerated with no serious adverse experiences and no significant differences between groups for adverse experiences. Per protocol instruction, subjects maintained body weight. Conclusions These findings suggest 6 g/d BBG consumed in a beverage over 12 weeks may improve insulin sensitivity among hyperglycemic individuals with no prior diagnosis of diabetes mellitus, and who experience no change in body weight. Trial Registration ClinicalTrials.gov Identifier: NCT01375803http://www.clinicaltrials.gov/ct2/show/NCT00820807.

Medical costs of obesity in the United States exceed $147 billion annually with medication costs making a sizable contribution. We examined medication costs associated with substantial weight losses in an intensive behavioral weight loss program. Inclusion criteria were medication use for obesity co-morbidities: hypertension, diabetes, dyslipidemia, degenerative joint disease, or gastroesophageal reflux disease. Group A, 83 obese patients on medications completed 8 weeks of classes, lost 19 kg in 20 weeks. Group B, 100 severely obese patients, lost 59 kg in 45 weeks. Medications were discontinued: Group A, 18%; Group B, 64%. Mean numbers of medications decreased significantly for all co-morbidities. Mean numbers of daily medications, initial and final, respectively were: Group A, total, 3.0 ± 0.2 (mean ± SEM) and 1.7 ± 0.2; Group B, total, 2.5 ± 0.2 and 0.7 ± 0.1. Monthly costs for all medications decreased significantly for all co-morbidities and were as follows: Group A, total, $249 ± 25 and $153 ± 19; Group B: total, $237 ± 27 and $65 ± 12. Medically supervised weight loss is very effective approach for improving cardiovascular risk factors and reducing medical costs.

Previous studies examining the hypocholesterolemic effects of high-soluble-fiber diets have not been designed to control for dietary fat intake. Serum cholesterol reductions may therefore be accounted for by differences in consumption of fat. Moderately hypercholesterolemic, nonobese, Caucasian men and women, 30-50 y old were randomly assigned to low-fat, low-fat plus high-fiber, or usual-diet groups and followed for 12 mo. At 12 mo the high-fiber group consumed significantly more soluble fiber than both the low-fat and usual-diet groups (P = 0.0063 and P = 0.0001); the high-fiber group did not differ from the low-fat group in quantity of dietary fat consumed. The high-fiber group experienced a greater average reduction (13%) in serum cholesterol than did the low-fat (9%) and usual-diet (7%) groups. After adjustment for relevant covariates, the reduction in the high-fiber group was significantly greater than that in the low-fat group (P = 0.0482). Supplementation with soluble fiber reduces serum cholesterol beyond the reduction observed with low-fat diet alone.

Mechanisms for the hypocholesterolemic effects of oat bran remain unclear. Soluble fibers such as oat bran are fermented in the colon to short-chain fatty acids (SCFAs), which may enter the portal vein and attenuate hepatic cholesterol synthesis. To compare effects of oat bran and wheat bran on serum SCFA concentrations, 20 hypercholesterolemic men entered a metabolic ward and received control diets for 1 wk followed by oat-bran or wheat-bran diets for 3 wk. Oat bran decreased serum cholesterol 12.8% (P less than 0.001) whereas wheat bran had no effect. Peripheral serum SCFA concentrations were measured seven times over 14 h at the end of each diet. Serum acetate values from 1200 to 2200 were significantly higher in subjects fed oat-bran vs wheat-bran diets. Peak and incremental peak acetate values were also significantly higher than control values in subjects fed oat bran but not in subjects fed wheat bran. SCFA responses may contribute to the hypocholesterolemic effects of oat bran.

A food can be regarded as ‘functional’ if it can demonstrate a beneficial efficacy on one or more target functions in the body in a convincing way. Beyond adequate nutritional qualities, functional foods should either improve the state of health and wellbeing and/or reduce the risk of disease. Functional foods that are marketed with claims of heart disease reduction focus primarily on the major risk factors, i.e. cholesterol, diabetes and hypertension. Some of the most innovative products are designed to be enriched with ‘protective’ ingredients, believed to reduce risk. They may contain, for example, soluble fibre (from oat and psyllium), useful both for lowering cholesterol and blood pressure, or fructans, effective in diabetes. Phytosterols and stanols lower LDL-cholesterol in a dose-dependent manner. Soya protein is more hypocholesterolaemic in subjects with very high initial cholesterol and recent data indicate also favourable activities in the metabolic syndrome.n-3 Fatty acids appear to exert significant hypotriacylglycerolaemic effects, possibly partly responsible for their preventive activity. Dark chocolate is gaining much attention for its multifunctional activities, useful both for the prevention of dyslipidaemia as well as hypertension. Finally, consensus opinions about tea and coffee have not emerged yet, and the benefits of vitamin E, garlic, fenugreek and policosanols in the management of dyslipidaemia and prevention of arterial disease are still controversial.

Background: Glucagon-like peptide 1 (GLP-1) and pancreatic polypeptide (PP) are intestinal hormones that are involved in the post-prandial satiety response. We sought to assess meal-related changes in these hormones in young children and determine whether differences exist between normal weight (NW) and overweight (OW) children. Methods: Seven to 11 year-old healthy NW (n = 20) and OW (n = 12) volunteers were given a standardized breakfast and lunch following an overnight fast and had measurements of GLP-1 and PP over 9 hours. We characterized whether GLP-1 and PP changed from the pre-prandial to the post-prandial state and whether the serum levels corresponded to reported appetite. Results: GLP-1 did not increase after eating, did not decline prior to the next meal, and did not correspond to satiety ratings in either group. PP increased post-prandially in OW children after both breakfast and lunch, but in the NW group PP only increased after breakfast. PP levels did not decline in either group as the next meal approached. Conclusions: In our study of school-age children, feeding had little effect on GLP-1 secretion and a variable effect on serum PP levels. Observed differences in the GLP-1 and PP responses between the NW and OW groups do not suggest there is an intrinsic abnormality in their secretion that causes weight gain.

Dietary fiber intake provides many health benefits. However, average fiber intakes for US children and adults are less than half of the recommended levels. Individuals with high intakes of dietary fiber appear to be at significantly lower risk for developing coronary heart disease, stroke, hypertension, diabetes, obesity, and certain gastrointestinal diseases. Increasing fiber intake lowers blood pressure and serum cholesterol levels. Increased intake of soluble fiber improves glycemia and insulin sensitivity in non-diabetic and diabetic individuals. Fiber supplementation in obese individuals significantly enhances weight loss. Increased fiber intake benefits a number of gastrointestinal disorders including the following: gastroesophageal reflux disease, duodenal ulcer, diverticulitis, constipation, and hemorrhoids. Prebiotic fibers appear to enhance immune function. Dietary fiber intake provides similar benefits for children as for adults. The recommended dietary fiber intakes for children and adults are 14 g/1000 kcal. More effective communication and consumer education is required to enhance fiber consumption from foods or supplements. © 2009 International Life Sciences Institute.

The metabolic effects of high-carbohydrate (70%), high-fiber (70 g) (HCHF) and low-carbohydrate (39%), low-fiber (10 g) (LCLF) diets were examined for 10 subjects with insulin-dependent diabetes mellitus (IDDM). After a 1-wk control period subjects on a metabolic ward were randomly allocated to HCHF or LCLF diets for 4 wk. After a 6-wk washout period subjects re-entered the metabolic ward for 4 wk on the alternate diet. Artificial-pancreas studies were performed on each diet for measurement of insulin requirements. Compared with the LCLF diet, the HCHF diet reduced basal insulin requirements (P less than 0.025), increased carbohydrate disposed of per unit insulin (P less than 0.0008), and lowered total (P less than 0.0004) and high-density-lipoprotein cholesterol (P less than 0.0013). Glycemic control and other lipid fractions did not differ significantly. These results suggest that in IDDM patients, HCHF diets enhance peripheral glucose disposal, decrease basal insulin requirements, and lower total cholesterol without altering glycemic control or triglycerides.

The hypocholesterolemic effects of oat bran (OB) have been recently challenged. To carefully document the hypocholesterolemic effects of OB, 20 hypercholesterolemic men admitted to a metabolic ward were randomly allocated to either OB or wheat bran (WB) for 21 d after a 7-d control-diet period. Control and treatment diets were designed to be identical in energy content and nutrients, differing only in the amount of soluble fiber. After 21 d, OB significantly decreased total cholesterol by 12.8% (P less than 0.001), low-density-lipoprotein cholesterol by 12.1% (P less than 0.004), and apolipoprotein B-100 by 13.7% (P less than 0.001) whereas WB had no significant effect. High-density-lipoprotein cholesterol and apolipoprotein A-I did not change significantly in either group. Serum triglycerides decreased by 10% in both groups but the decrease was only significant (P less than 0.04) in WB subjects. OB but not WB significantly reduced total cholesterol and other atherogenic lipoprotein fractions independent of other dietary changes.

In the past quarter century, dietary fiber has emerged as a leading dietary component in chronic disease prevention. High fiber intake lowers risk for cardiovascular disease (Kromhout et al.. 1982). some cancers (Kromhout, 1982a). hypertension (Anderson. 1983a). diabetes (Anderson, 1986) and obesity (Anderson and Bryant. 1986a). In addition. dietary fiber has therapeutic value in treatment of coronary heart disease (CHD) (Arntzenius et al.. 1985). hyperlipidemia (Anderson and Tietyen-Clark, 1986). hypertension (Anderson, 1983). diabetes (Anderson and Bryant. 1986b). obesity (Anderson and Bryant, 1986c). and gastrointestinal diseases (Anderson, 1985a). An overwhelming consensus recommendation now advises an intake of five to six servings of vegetables and fruits daily (National Academy of Sciences, 1989: U.S. Dept. of Health and Human Services. 1988a), for a dietary fiber intake of 20 to 35 g/day or 10 to 13 g/1000 kcal for healthy adults (Pilch. 1987a).

The purpose of this study was to relate the carbon dioxide (CO2) response of laryngeal receptors to their behavior during the breathing cycle (i.e, their response to transmural pressure changes, laryngeal movement or decreases in temperature)_or during exposure to irritant stimuli (water or cigarette smoke). In 9 anesthetized mongrel dogs breathing spontaneously through a tracheostomy, unit activity from the superior laryngeal nerve was recorded while warmed and humidified gas mixtures (air or 10% CO2 in O2) were passed, for 1 min, through the functionally isolated upper airway in the expiratory direction. None of the 10 cold receptors studied were affected by CO2. Eleven of 20 laryngeal non-modulated mechanoreceptors were stimulated (from 0.3 to 1.6 imp/sec) by exposure to CO2. These CO2-responsive receptors were also stimulated by known irritant stimuli (cigarette smoke, water), although not all receptors which responded to these irritants were stimulated by CO2. Twelve of 33 respiratory-modulated receptors were affected by CO2; 4 were stimulated and 8 inhibited. Receptors inhibited by CO2 were also inhibited by negative pressure while receptors stimulated by CO2 were also stimulated by negative pressure. These results show that CO2-responsive laryngeal receptors are not specialized endings. Although it is not clear to what extent each separate group of laryngeal receptors is involved, each may contribute to the reflex bradypnea which has been observed during exposure of the upper airway to elevated levels of CO2. However, the importance of CO2-responsive laryngeal receptors in physiological conditions remains unclear.

Oat bran lowers serum lipid concentrations in healthy and hyperlipidemic subjects. To determine the effects of a ready-to-eat oat-bran cereal on lipid concentrations, we fed control (corn flakes) and oat-bran cereal diets for 2 wk to 12 men with undesirably high serum total-cholesterol concentrations. Subjects were randomly assigned to one of the two diets upon admission to the metabolic ward. After completing the first diet, subjects completed 2 wk on the alternate diet. Intakes of carbohydrate, protein, fat, and cholesterol were virtually identical on the two diets. The oat-bran cereal provided 25 g oat bran/d. The oat-bran cereal diet compared with the corn flakes diet lowered serum total-cholesterol and serum LDL-cholesterol concentrations significantly by 5.4% (p less than 0.05) and 8.5% (p less than 0.025), respectively. Final body weights on each of the diets were similar. Ready-to-eat oat-bran cereal provides a practical means to incorporate soluble fiber into the diet to lower serum cholesterol.

Dried beans lower serum lipid concentrations in healthy and hyperlipidemic subjects. To determine the effects of canned beans on serum lipid concentrations, 24 hyperlipidemic men ate one of three bean diets for 21 d in a metabolic ward. Diets A and B included 227 g canned beans (120 g beans with 107 g tomato sauce) daily, in a single dose for diet A and in a divided dose for diet B. Diet C included 182 g canned beans (162 g beans with 20 g tomato sauce) daily in a divided dose. All bean diets combined lowered serum cholesterol and triglyceride concentrations 10.4% (p less than 0.001) and 10.8% (p less than 0.025), respectively. Diet B was as effective as diet C, and the groups on those diets had greater cholesterol reductions than did the group on diet A. Serum cholesterol reduction was positively correlated (p less than 0.01) with intake of total dietary fiber and soluble fiber. The ratios of low- to high-density-lipoprotein cholesterol remained constant for all groups. Body weight decreased 1.0-1.5 kg for all groups despite constant energy intakes. Canned beans may make an important contribution to hyperlipidemia management.

To investigate whether osmoreceptor mechanisms or the renin-angiotensin system might be involved in respiratory regulation of H+ homeostasis, plasma osmolality was acutely lowered by approximately 10 mOsm in 7 awake mongrel dogs by a gastric water load (20 ml.kg-1 distilled, deionized water). Plasma renin activity (PRA) was measured as an indicator of angiotensin II levels. During these studies PaCO2 and [H+]a reflected the spontaneous level of ventilation (VE); higher levels of VE were correlated with lower PaCO2 and [H+]a, indicating a nonchemical drive to breathe. Stimulation of ventilation to lower PaCO2 following the water load was positively correlated with increase in PRA and decrease in plasma osmolality, but not with change in osmolality alone. An increased VE, a decreased ventilatory response curve (VRC) threshold for PaCO2, and a lower PaCO2 occurred with increase in PRA. Conversely, a lower or acutely decreased PRA, due to administration of arginine vasopressin, was correlated with a lower VE, an increase in the VRC threshold for PaCO2, and a higher PaCO2. Ventilatory control of PaCO2 during acute lowering of osmolality may be related to a central inter-action between osmolality and the renin-angiotensin system.

Substantial evidence indicates that psychosocial stress contributes to hypertension and cardiovascular disease (CVD). Previous meta-analyses of stress reduction and high blood pressure (BP) were outdated and/or methodologically limited. Therefore, we conducted an updated systematic review of the published literature and identified 107 studies on stress reduction and BP. Seventeen trials with 23 treatment comparisons and 960 participants with elevated BP met criteria for well-designed randomized controlled trials and were replicated within intervention categories. Meta-analysis was used to calculate BP changes for biofeedback, −0.8/−2.0 mm Hg (P = NS); relaxation-assisted biofeedback, +4.3/+2.4 mm Hg (P = NS); progressive muscle relaxation, −1.9/−1.4 mm Hg (P = NS); stress management training, −2.3/−1.3 mm (P = NS); and the Transcendental Meditation program, −5.0/−2.8 mm Hg (P = 0.002/0.02). Available evidence indicates that among stress reduction approaches, the Transcendental Meditation program is associated with significant reductions in BP. Related data suggest improvements in other CVD risk factors and clinical outcomes.

A correct lifestyle is crucial in the primary and secondary prevention of cardiovascular disease. Innovative nutritional strategies to reduce the main risk factors have been developed including either dietary changes or consumption of specifically targeted functional foods and dietary supplements. These nutraceutical products may also provide an alternative to lipid lowering, antihypertensive, and antidiabetic drugs. Functional foods and beverages have the appearance of normal foods, but contain specific components whose activity on at least one measurable risk factor has been scientifically demonstrated. Dietary supplements, having formulations similar to drugs, allow the delivery of a bioactive ingredient in dosages that exceed those obtainable from food products. Among bioactive components, at present dietary proteins from both vegetable and animal sources are of high interest, because of their specific effects on cholesterolemia and blood pressure. Active peptides have been identified for the latter indication, whereas works is in progress in attempting to identify specific cholesterol lowering peptides.