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Biomedical subjects

Samuel Klein

Publications and source records attributed to Samuel Klein.

63 records · Page 4Linked to original sources

Regional muscle and adipose tissue amino acid metabolism in lean and obese women.

The effect of obesity on regional skeletal muscle and adipose tissue amino acid metabolism is not known. We evaluated systemic and regional (forearm and abdominal subcutaneous adipose tissue) amino acid metabolism, by use of a combination of stable isotope tracer and arteriovenous balance methods, in five lean women [body mass index (BMI) <25 kg/m(2)] and five women with abdominal obesity (BMI 35.0-39.9 kg/m(2); waist circumference >100 cm) who were matched on fat-free mass (FFM). All subjects were studied at 22 h of fasting to ensure that the subjects were in net protein breakdown during this early phase of starvation. Leucine rate of appearance in plasma (an index of whole body proteolysis), expressed per unit of FFM, was not significantly different between lean and obese groups (2.05 +/- 0.18 and 2.34 +/- 0.04 micromol x kg FFM(-1) x min(-1), respectively). However, the rate of leucine release from forearm and adipose tissues in obese women (24.0 +/- 4.8 and 16.6 +/- 6.5 nmol x 100 g(-1) x min(-1), respectively) was lower than in lean women (66.8 +/- 10.6 and 38.6 +/- 7.0 nmol x 100 g(-1) x min(-1), respectively; P < 0.05). Approximately 5-10% of total whole body leucine release into plasma was derived from adipose tissue in lean and obese women. The results of this study demonstrate that the rate of release of amino acids per unit of forearm and adipose tissue at 22 h of fasting is lower in women with abdominal obesity than in lean women, which may help obese women decrease body protein losses during fasting. In addition, adipose tissue is a quantitatively important site for proteolysis in both lean and obese subjects.

Abdomen↗

Effect of gender on lipid kinetics during endurance exercise of moderate intensity in untrained subjects.

We evaluated lipid metabolism during 90 min of moderate-intensity (50% VO(2) peak) cycle ergometer exercise in five men and five women who were matched on adiposity (24 +/- 2 and 25 +/- 1% body fat, respectively) and aerobic fitness (VO(2) peak: 49 +/- 2 and 47 +/- 1 ml x kg fat-free mass(-1) x min(-1), respectively). Substrate oxidation and lipid kinetics were measured by using indirect calorimetry and [(13)C]palmitate and [(2)H(5)]glycerol tracer infusion. The total increase in glycerol and free fatty acid (FFA) rate of appearance (R(a)) in plasma during exercise (area under the curve above baseline) was approximately 65% greater in women than in men (glycerol R(a): 317 +/- 40 and 195 +/- 33 micromol/kg, respectively; FFA R(a): 652 +/- 46 and 453 +/- 70 micromol/kg, respectively; both P < 0.05). Total fatty acid oxidation was similar in men and women, but the relative contribution of plasma FFA to total fatty acid oxidation was higher in women (76 +/- 5%) than in men (46 +/- 5%; P < 0.05). We conclude that lipolysis of adipose tissue triglycerides during moderate-intensity exercise is greater in women than in men, who are matched on adiposity and fitness. The increase in plasma fatty acid availability leads to a greater rate of plasma FFA tissue uptake and oxidation in women than in men. However, total fat oxidation is the same in both groups because of a reciprocal decrease in the oxidation rate of fatty acids derived from nonplasma sources, presumably intramuscular and possibly plasma triglycerides, in women.

Adult↗

Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: A 1-year randomized controlled trial.

UNLABELLED: OBJECTIVE; Weight loss improves glycemic control, lipid profiles, and blood pressure in patients with type 2 diabetes. However, successful long-term weight loss is difficult for these patients, particularly those treated with insulin. The aim of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on weight loss, glycemic control, and cardiovascular risk factors in overweight or obese insulin-treated type 2 diabetic patients. RESEARCH DESIGN AND METHODS: This study was a 1-year multicenter, randomized, double-blind, placebo-controlled trial of orlistat (120 mg three times a day) or placebo combined with a reduced-calorie diet in overweight or obese adults (BMI 28-40 kg/m(2)) with type 2 diabetes treated with insulin alone or combined with oral agents, but with suboptimal metabolic control (HbA(1c) 7.5-12.0%). Outcome measurements included changes in body weight, glycemic control, blood pressure, and serum lipids. RESULTS; After 1 year, the orlistat group lost significantly more weight (-3.89 +/- 0.3% of baseline body weight, means +/- SE) than the placebo group (-1.27 +/- 0.3%, P < 0.001). Orlistat treatment, compared with placebo, produced greater decreases in HbA(1c) (-0.62 +/- 0.08 vs. -0.27 +/- 0.08%, P = 0.002), fasting serum glucose (-1.63 +/- 0.3 vs. -1.08 +/- 0.3 mmol/l, P = 0.02), and the required doses of insulin and other diabetic medications. Orlistat also produced greater improvements than placebo in serum total cholesterol (P = 0.0002) and LDL cholesterol concentrations (P = 0.001) and LDL/HDL ratio (P = 0.01). CONCLUSIONS; Orlistat therapy produces clinically significant weight loss, with improvements in glycemic control and cardiovascular disease risk factors, in overweight or obese patients with type 2 diabetes who have suboptimal metabolic control with insulin therapy.

Anti-Obesity Agents↗

Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin.

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 HbA(1c), 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 HbA(1c) of > or = 0.5 and > or = 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.

Adult↗

Use of stable isotopically labeled tracers to measure very low density lipoprotein-triglyceride turnover.

Tracer methods for VLDL-TG kinetics vary in their ability to account for the effect of tracer recycling, which can influence the calculation of VLDL-TG fractional catabolic rates (FCRs). We evaluated a novel approach, involving stable isotopically labeled glycerol or palmitate tracers in conjunction with compartmental modeling, for measuring VLDL-TG kinetics in normolipidemic human subjects. When administered as a bolus simultaneously, both tracers provided identical VLDL-TG FCRs when the data were analyzed by a compartmental model that accounted for hepatic lipid tracer recycling, but not by non-compartmental analysis. The model-derived FCR was greater than that determined using a non-compartmental approach, and was 2- to 3-fold higher than that usually reported by using a bolus of radioactive [3H]glycerol. When palmitate tracer was given as a constant infusion, VLDL-TG turnover appeared 5-fold slower, because tracer recycling through hepatic lipid pools could not be resolved with the infusion protocol. We conclude that accounting for tracer recycling, particularly the contribution of hepatic glycerolipid pools, is essential to accurately measure VLDL-TG kinetics, and that bolus injection of stable isotopically labeled glycerol or palmitate tracers in conjunction with compartmental modeling analysis offers a reliable approach for measuring VLDL-TG kinetics.

Adult↗

Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial.

BACKGROUND: Bone loss often accompanies weight loss induced by caloric restriction (CR), but whether bone loss accompanies similar weight loss induced by exercise (EX) is unknown. We tested the hypothesis that EX-induced weight loss is associated with less bone loss compared with CR-induced weight loss. METHODS: Forty-eight adults (30 women; 18 men; mean +/- SD age, 57 +/- 3 years; and mean +/- SD body mass index, 27 +/- 2 kg/m2) were randomized to 1 of 3 groups for 1 year: CR group (n = 19), regular EX group (n = 19), or a healthy lifestyle (HL) control group (n = 10). Primary outcome measure was change in hip and spine bone mineral density (BMD). Secondary outcomes were bone markers and hormones. RESULTS: Body weight decreased similarly in the CR and EX groups (10.7% +/- 6.3% [-8.2 +/- 4.8 kg] vs 8.4% +/- 6.3% [-6.7 +/- 5.6 kg]; P = .21), whereas weight did not change in the HL group (-1.2% +/- 2.5% [-0.9 +/- 2.0 kg]). Compared with the HL group, the CR group had decreases in BMD at the total hip (-2.2% +/- 3.1% vs 1.2% +/- 2.1%; P = .02) and intertrochanter (-2.1% +/- 3.4% vs 1.7 +/- 2.8%; P = .03). The CR group had a decrease in spine BMD (-2.2% +/- 3.3%; P = .009). Despite weight loss, the EX group did not demonstrate a decrease in BMD at any site. Body weight changes correlated with BMD changes in the CR (R = 0.61; P = .007) but not in the EX group. Bone turnover increased in both CR and EX groups. CONCLUSIONS: CR-induced weight loss, but not EX-induced weight loss, is associated with reductions in BMD at clinically important sites of fracture. These data suggest that EX should be an important component of a weight loss program to offset adverse effects of CR on bone.

Alkaline Phosphatase↗

Use of clonidine to decrease intestinal fluid losses in patients with high-output short-bowel syndrome.

BACKGROUND: Some patients who have short bowel syndrome (SBS) have high intestinal outputs, which increases the risk of dehydration and fluid-electrolyte abnormalities and impairs quality of life. METHODS: We evaluated the use of clonidine, an alpha2-adrenergic receptor agonist, in 2 patients with SBS and high intestinal outputs, who were refractory to conventional therapy with antidiarrheal and antisecretory agents (loperamide, belladonna, opiates, somatostatin, histamine2 receptor antagonists and proton pump inhibitors). The first patient (case 1) was a 29-year-old woman who had 175 cm of small bowel anastamosed to 8 cm of descending colon, ending in a colostomy. The second patient (case 2) was a 22-year-old man who had 30 cm of jejunum anastomosed to 30 cm of sigmoid colon and rectum. RESULTS: The addition of clonidine, 0.1 mg per os (PO) 2 times per day, to the treatment regimen of case 1 decreased her ostomy output from approximately 4 L/day to approximately 1 L/day, eliminating the need for parenteral nutrition and fluids and decreasing the need for opiate therapy. The addition of clonidine, 0.2 mg PO 2 times per day in case 2 resulted in decreased rectal outputs from approximately 4 L/day to approximately 1.5 L/day. CONCLUSIONS: These results demonstrate that clonidine can effectively reduce intestinal fluid and electrolyte losses and should be considered as an additional treatment option in patients with SBS and high intestinal outputs.

Adrenergic alpha-Agonists↗