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Biomedical subjects

Samuel Klein

Publications and source records attributed to Samuel Klein.

At least 37 records · Page 2Linked to original sources

Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society.

Obesity causes serious medical complications and impairs quality of life. Moreover, in older persons, obesity can exacerbate the age-related decline in physical function and lead to frailty. However, appropriate treatment for obesity in older persons is controversial because of the reduction in relative health risks associated with increasing body mass index and the concern that weight loss could have potential harmful effects in the older population. This joint position statement from the American Society for Nutrition and NAASO, The Obesity Society reviews the clinical issues related to obesity in older persons and provides health professionals with appropriate weight-management guidelines for obese older patients. The current data show that weight-loss therapy improves physical function, quality of life, and the medical complications associated with obesity in older persons. Therefore, weight-loss therapy that minimizes muscle and bone losses is recommended for older persons who are obese and who have functional impairments or medical complications that can benefit from weight loss.

Aged↗

Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society.

Obesity causes serious medical complications and impairs quality of life. Moreover, in older persons, obesity can exacerbate the age-related decline in physical function and lead to frailty. However, appropriate treatment for obesity in older persons is controversial because of the reduction in relative health risks associated with increasing body mass index and the concern that weight loss could have potential harmful effects in the older population. This joint position statement from the American Society for Nutrition and the NAASO, The Obesity Society reviews the clinical issues related to obesity in older persons and provides health professionals with appropriate weight-management guidelines for obese older patients. The current data show that weight-loss therapy improves physical function, quality of life, and the medical complications associated with obesity in older persons. Therefore, weight-loss therapy that minimizes muscle and bone losses is recommended for older persons who are obese and who have functional impairments or medical complications that can benefit from weight loss.

Aged↗

A multicompartmental model of in vivo adipose tissue glycerol kinetics and capillary permeability in lean and obese humans.

Lipolysis of adipose tissue triglycerides releases glycerol. Twenty-four volunteers, of whom 6 were obese and 13 were women, received a primed-constant infusion of 2H5-glycerol for 120 min during postabsorptive steady-state conditions. Arterial, abdominal venous, and interstitial (microdialysis) samples were taken, and a four-compartment model was applied to assess subcutaneous abdominal adipose tissue glycerol kinetics. Adipose tissue blood flow was measured using 133Xe washout. Venous glycerol concentrations (median 230 micromol/l [interquartile range 210-268]) were consistently greater than those of arterial blood (69.1 micromol/l [56.5-85.5]), while glycerol isotopic enrichments (tracer-to-tracee ratio) were greater in arterial blood (8.34% [7.44-10.1]) than venous blood (2.34% [1.71-2.69], P < 0.01). Microdialysate glycerol enrichment was 1.44% (1.11-1.79), indicating incomplete permeability of glycerol between capillary blood and interstitium. Calculated interstitial glycerol concentrations were between 270 micromol/l (256-350) and 332 micromol/l (281-371) (examining different boundary conditions). The calculated capillary diffusion capacity (ps) was between 2.21 ml . 100 g tissue(-1) . min(-1) (1.31-3.13) and 3.09 ml . 100 g tissue(-1) . min(-1) (1.52-4.90) and correlated inversely with adiposity (Rs< or = -0.45, P < 0.05). Our results support previous estimates of interstitial glycerol concentration within adipose tissue and reveal capillary diffusion capacity is reduced in obesity.

Adipose Tissue↗

Clinical implications of obesity with specific focus on cardiovascular disease: a statement for professionals from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation.

Obesity adversely affects cardiac function, increases the risk factors for coronary heart disease, and is an independent risk factor for cardiovascular disease. The risk of developing coronary heart disease is directly related to the concomitant burden of obesity-related risk factors. Modest weight loss can improve diastolic function and affect the entire cluster of coronary heart disease risk factors simultaneously. This statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism reviews the relationship between obesity and the cardiovascular system, evaluates the effect of weight loss on coronary heart disease risk factors and coronary heart disease, and provides practical weight management treatment guidelines for cardiovascular healthcare professionals. The data demonstrate that weight loss and physical activity can prevent and treat obesity-related coronary heart disease risk factors and should be considered a primary therapy for obese patients with cardiovascular disease.

Anti-Obesity Agents↗

NMR and MD studies on the interaction between ligand peptides and alpha-bungarotoxin.

The interaction between alpha-bungarotoxin and linear synthetic peptides, mimotope of the nicotinic acetylcholine receptor binding site, has been characterised extensively by several methods and a wealth of functional, kinetic and structural data are available. Hence, this system represents a suitable model to explore in detail the dynamics of a peptide-protein interaction. Here, the solution structure of a new complex of the protein toxin with a tridecapeptide ligand exhibiting high affinity has been determined by NMR. As observed for three other previously reported mimotope-alpha-bungarotoxin complexes, also in this case correlations between biological activity and kinetic data are not fully consistent with a static discussion of structural data. Molecular dynamics simulations of the four mimotope-toxin complexes indicate that a relevant contribution to the complex stability is given by the extent of the residual flexibility that the protein maintains upon peptide binding. This feature, limiting the entropy loss caused by protein folding and binding, ought to be generally considered in a rational design of specific protein ligands.

Bungarotoxins↗

Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease.

BACKGROUND: Liposuction has been proposed as a potential treatment for the metabolic complications of obesity. We evaluated the effect of large-volume abdominal liposuction on metabolic risk factors for coronary heart disease in women with abdominal obesity. METHODS: We evaluated the insulin sensitivity of liver, skeletal muscle, and adipose tissue (with a euglycemic-hyperinsulinemic clamp procedure and isotope-tracer infusions) as well as levels of inflammatory mediators and other risk factors for coronary heart disease in 15 obese women before and 10 to 12 weeks after abdominal liposuction. Eight of the women had normal glucose tolerance (mean [+/-SD] body-mass index, 35.1+/-2.4), and seven had type 2 diabetes (body-mass index, 39.9+/-5.6). RESULTS: Liposuction decreased the volume of subcutaneous abdominal adipose tissue by 44 percent in the subjects with normal glucose tolerance and 28 percent in those with diabetes; those with normal oral glucose tolerance lost 9.1+/-3.7 kg of fat (18+/-3 percent decrease in total fat, P=0.002), and those with type 2 diabetes lost 10.5+/-3.3 kg of fat (19+/-2 percent decrease in total fat, P<0.001). Liposuction did not significantly alter the insulin sensitivity of muscle, liver, or adipose tissue (assessed by the stimulation of glucose disposal, the suppression of glucose production, and the suppression of lipolysis, respectively); did not significantly alter plasma concentrations of C-reactive protein, interleukin-6, tumor necrosis factor alpha, and adiponectin; and did not significantly affect other risk factors for coronary heart disease (blood pressure and plasma glucose, insulin, and lipid concentrations) in either group. CONCLUSIONS: Abdominal liposuction does not significantly improve obesity-associated metabolic abnormalities. Decreasing adipose tissue mass alone will not achieve the metabolic benefits of weight loss.

Abdomen↗

Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women.

BACKGROUND: Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance. In the present study, we tested the hypothesis that myocardial fatty acid metabolism and efficiency are abnormal in obese women. METHODS AND RESULTS: We studied 31 young women (body mass index [BMI] 19 to 52 kg/m2); 19 were obese (BMI >30 kg/m2). Myocardial oxygen consumption (MVO2) and fatty acid uptake (MFAUp), utilization (MFAU), and oxidation (MFAO) were quantified by positron emission tomography. Cardiac work was measured by echocardiography, and efficiency was calculated as work/MVO2. BMI correlated with MVO2 (r=0.58, P=0.0006), MFAUp (r=0.42, P<0.05), and efficiency (r=-0.40, P<0.05). Insulin resistance, quantified by the glucose area under the curve (AUC) during an oral glucose tolerance test, correlated with MFAUp (r=0.55, P<0.005), MFAU (r=0.62, P<0.001), and MFAO (r=0.58, P<0.005). A multivariate, stepwise regression analysis showed that BMI was the only independent predictor of MVO2 and efficiency (P=0.0005 and P<0.05, respectively). Glucose AUC was the only independent predictor of MFAUp, MFAU, and MFAO (P<0.05, <0.005, and <0.005, respectively). CONCLUSIONS: In young women, obesity is a significant predictor of increased MVO2 and decreased efficiency, and insulin resistance is a robust predictor of MFAUp, MFAU, and MFAO. This increase in fatty acid metabolism and decrease in efficiency is concordant with observations made in experimental models of obesity. These metabolic changes may play a role in the pathogenesis of decreased cardiac performance in obese women.

Adult↗

Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans.

Little is known regarding the long-term effects of caloric restriction (CR) on the risk for atherosclerosis. We evaluated the effect of CR on risk factors for atherosclerosis in individuals who are restricting food intake to slow aging. We studied 18 individuals who had been on CR for an average of 6 years and 18 age-matched healthy individuals on typical American diets. We measured serum lipids and lipoproteins, fasting plasma glucose and insulin, blood pressure (BP), high-sensitivity C-reactive protein (CRP), platelet-derived growth factor AB (PDGF-AB), body composition, and carotid artery intima-media thickness (IMT). The CR group were leaner than the comparison group (body mass index, 19.6 +/- 1.9 vs. 25.9 +/- 3.2 kg/m(2); percent body fat, 8.7 +/- 7% vs. 24 +/- 8%). Serum total cholesterol (Tchol), low-density lipoprotein cholesterol, ratio of Tchol to high-density lipoprotein cholesterol (HDL-C), triglycerides, fasting glucose, fasting insulin, CRP, PDFG-AB, and systolic and diastolic BP were all markedly lower, whereas HDL-C was higher, in the CR than in the American diet group. Medical records indicated that the CR group had serum lipid-lipoprotein and BP levels in the usual range for individuals on typical American diets, and similar to those of the comparison group, before they began CR. Carotid artery IMT was approximately 40% less in the CR group than in the comparison group. Based on a range of risk factors, it appears that long-term CR has a powerful protective effect against atherosclerosis. This interpretation is supported by the finding of a low carotid artery IMT.

Adult↗

Are peristaltic pumps as reliable as syringe pumps for metabolic research? Assessment of accuracy, precision, and metabolic kinetics.

Syringe pumps are traditionally used to infuse tracers in metabolic research because they are perceived to be more accurate and precise than peristaltic pumps. This study evaluated the accuracy (actual v programmed infusion rate) and precision (reproducibility of infusion) of a peristaltic pump (Gemini PC 2; IMED, San Diego, CA) and a syringe pump (Model 22; Harvard Apparatus, Natick, MA) for metabolic research. In one protocol, saline delivery was measured in vitro in 5 trials at 4 flow rates: 3, 30, 150, and 300 mL/h. In the second protocol, basal glycerol rate of appearance (Ra) was determined in vivo in 5 women on 2 consecutive days. On day 1, [2-(13C)]glycerol was infused with 1 pump and [1,1,2,3,3-(2H5)]glycerol with the other. On day 2, the opposite pattern was used. The accuracy of the 2 pumps was the same (error approximately 2%). In addition, both the syringe and the peristaltic pumps were very precise, with coefficients of variation (CV) <1% at all flow rates. Glycerol Ra values were the same when tracer was infused with either a syringe or peristaltic pump on day 1 and day 2: 4.1 +/- 1.7 (syringe pump) and 4.2 +/- 1.9 (peristaltic pump) micromol. kg fat mass (FM)(-1). min(-1) on day 1; 4.2 +/- 1.2 (syringe pump) and 4.2 +/- 1.3 (peristaltic pump) micromol. kg FM(-1). min(-1) on day 2. These data demonstrate that both syringe and peristaltic pumps are very accurate and precise across a large range of flow rates. Moreover, the assessment of in vivo substrate kinetics in human subjects is the same when either pump is used to infuse isotope tracers.

Adult↗

Physical frailty and body composition in obese elderly men and women.

OBJECTIVE: To evaluate the prevalence of frailty and interrelationships among body composition, physical function, and quality of life in community-dwelling obese elderly (OE) persons. RESEARCH METHODS AND PROCEDURES: Fifty-two OE, 52 nonobese frail, and 52 nonobese nonfrail subjects, matched for age and sex, were studied. Subjective and objective measures of functional status were evaluated by using the physical performance test, exercise stress test, lower extremity (LE) strength, gait speed, static and dynamic balance, functional status questionnaires, and health-related quality-of-life questionnaire (Medical Outcomes Short Form). Body composition was evaluated by using DXA, and muscle quality was evaluated by determining the ratio of LE strength to LE lean mass. RESULTS: Among OE subjects, 96% met our standard criteria for mild to moderate frailty. Compared with the nonobese nonfrail group, the OE and nonobese frail groups had lower and similar scores in physical performance test, peak aerobic power, and functional status questionnaire, and exhibited similar impairments in strength, walking speed, balance, and health-related quality of life. Although absolute fat-free mass (FFM) was greater, the percentage body weight as FFM and muscle quality was lower in the OE group than in the other two groups. DISCUSSION: Physical frailty, which predisposes to loss of independence, is common in community-living OE men and women. Physical frailty in OE subjects was associated with low percentage FFM, poor muscle quality, and decreased quality of life. These findings suggest that weight loss therapy may be particularly important in OE persons to improve physical function, in addition to improving the medical complications associated with obesity.

Aged↗

Clinical trial experience with fat-restricted vs. carbohydrate-restricted weight-loss diets.

It is unlikely that one diet is optimal for all overweight or obese persons. Both low-fat and low-carbohydrate diets have been shown to induce weight loss and reduce obesity-related comorbidities. Low-carbohydrate diets cause greater short-term (up to 6 months) weight loss than low-fat diets, but the long-term clinical safety and efficacy of these diets has not been studied.

Body Composition↗

Long-term pharmacotherapy for obesity.

Obese patients unable to achieve significant weight loss with lifestyle changes alone may require drug therapy, and such therapy may be needed long term lest weight lost be regained. In the United States, only sibutramine and orlistat are available for the long-term treatment of obesity. Clinical trials have shown that both drugs can induce and maintain weight loss, even in patients with comorbid conditions such as hypertension or type 2 diabetes. Their use must be combined with behavior modification and a structured meal plan, however, for patients to reap the full benefits of such treatment.

Anti-Obesity Agents↗

Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies. A statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition.

Overweight and obesity are important risk factors for type 2 diabetes. The marked increase in the prevalence of overweight and obesity is presumably responsible for the recent increase in the prevalence of type 2 diabetes. Lifestyle modification aimed at reducing energy intake and increasing physical activity is the principal therapy for overweight and obese patients with type 2 diabetes. Even moderate weight loss in combination with increased activity can improve insulin sensitivity and glycemic control in patients with type 2 diabetes and prevent the development of type 2 diabetes in high-risk persons (ie, those with impaired glucose tolerance). The American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition have joined together to issue this statement on the use of lifestyle modification in the prevention and management of type 2 diabetes.

Adult↗

The case of visceral fat: argument for the defense.

Increased plasma fatty acid concentrations may be responsible for many of the metabolic abnormalities associated with abdominal obesity. Excessive visceral fat is associated with insulin resistance and other metabolic risk factors for coronary heart disease. A study reported in this issue of the JCI evaluates the relative contribution of fatty acids released during lipolysis of visceral adipose tissue triglycerides to portal and systemic fatty acid flux in human subjects.

Adipose Tissue↗