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Biomedical subjects

A Tremblay

Publications and source records attributed to A Tremblay.

At least 55 records · Page 3Linked to original sources

Gender-based differences in cardiac repolarization in mouse ventricle.

The mouse heart has become a widely used model for genetic studies of heart diseases. Thus, understanding gender differences in mouse cardiac repolarization is crucial to the interpretation of such studies. The objective of this study was to evaluate whether there are gender differences in cardiac repolarization in mouse ventricle and to gain insights into the ionic and molecular mechanisms underlying these differences. Action potential durations (APDs) and K(+) currents in male and female ventricular myocytes were compared using a patch-clamp technique. APD(20), APD(50), and APD(90) were found to be significantly longer in females than males. Examination of the different K(+) currents revealed that a significantly lower current density exists in female ventricular myocytes compared with male myocytes for the ultrarapid delayed rectifier K(+) current, I(Kur) (at +30 mV, male, 33.2+/-2.9 pA/pF [n= 22]; female, 20.9+/-1.73 pA/pF [n= 19], P<0.001). Consistent with these findings were the results of the ribonuclease protection assay, Western blots, and confocal analysis that showed a significantly lower expression level of Kv1.5 (coding for I(Kur)) in female compared with male ventricle. The additional K(+) currents present in mouse ventricle exhibited no gender differences. In agreement with these electrophysiological data, no differences in the expression levels for the K(+) channels underlying these currents were detected between both sexes. This study demonstrates that adult mice exhibit gender differences in cardiac repolarization. The expression of Kv1.5 and of its corresponding K(+) current, I(Kur), is significantly lower in female mouse ventricle, and as a result, the APD is lengthened.

4-Aminopyridine↗

Glucocorticoid receptor Bcl I variant is associated with an increased atherogenic profile in response to long-term overfeeding.

The effect of the glucocorticoid receptor (GRL) gene Bcl I polymorphism on body composition and metabolic changes in response to overfeeding was studied. Twenty-four men (mean age 21+/-2 years) who constituted 12 pairs of identical twins ate a 4.2 MJ/day energy surplus, 6 days a week, during a period of 100 days. The GRL Bcl I marker was identified by Southern Blot technique. Total body fat was assessed by hydrodensitometry and abdominal fat areas were measured by computed tomography. Fasting plasma glucose and insulin during an oral glucose tolerance test (OGTT) were assayed. The insulin and glucose areas were computed using the trapezoidal method. Triglyceride and cholesterol concentrations in plasma and lipoprotein fractions were determined enzymatically. The results showed that overfeeding induced a greater increase in body weight (p=0.002) in the 2.3/2.3 kb (n=12) than in the 4.5/2.3 kb (n=12) subjects. In addition, plasma levels of total (p=0.007) and low-density lipoprotein (LDL) cholesterol (p=0.003), as well as systolic blood pressure (p=0.036) increased more in the 2.3/2.3 kb than in the 4.5/2.3 kb subjects. The 2.3/2.3 kb genotype was also associated with a greater increase in abdominal visceral fat (p=0.040) compared to the 4.5/2.3 kb genotype. In conclusion, 2.3/2.3 kb subjects of the GRL Bcl I polymorphism experience greater increases in body weight, blood pressure and cholesterol levels as well as visceral fat than 4.5/2.3 kb subjects in response to overfeeding. These data suggest that overfeeding induces an atherogenic profile in subjects who are homozygotes for the 2.3 kb allele.

Adult↗

Psychiatric dimensions of palliative care.

A critically important aspect of palliative care is the prompt recognition and effective treatment of psychiatric complications. Psychiatric syndromes such as depression, anxiety, confusion, suicidal ideation, and wish for hastened death or assisted-suicide occur in a significant percentage of patients with advanced illness. This article reviews their frequency, diagnosis, associated factors, and management to help expand the focus of palliative care beyond pain and physical symptom control.

Anxiety↗

Contribution of steroid receptor coactivator-1 and CREB binding protein in ligand-independent activity of estrogen receptor beta.

Estrogens are essential regulators in the development and control of reproductive functions. The estrogenic signal is now known to be transduced by two estrogen receptors, ERalpha and ERbeta. Hormone-dependent transcriptional activation of ER and other nuclear receptors involves assembly of a coactivation complex which includes various cofactors such as the steroid receptor-coactivators (SRC) and CREB binding protein (CBP). Our findings on ERbeta have revealed a ligand-independent activation pathway which involves growth factor-mediated phosphorylation of ERbeta activation function-1 (AF-1) and subsequent recruitment of SRC-1 independently of the presence of estrogens. The presence of the cointegrator CBP is also shown to potentiate the SRC-1-mediated ERbeta ligand-independent activation, suggesting that CBP may participate in unliganded ERbeta coactivation. These findings demonstrate the ability of alternate signaling pathways to mediate coregulator assembly, hence resulting in ligand-independent activation of ERbeta.

CREB-Binding Protein↗

EM-652 (SCH57068), a pure SERM having complete antiestrogenic activity in the mammary gland and endometrium.

In order to minimize the risks of endometrial cancer and the development of resistance to antiestrogen therapy, we have synthesized the orally active antiestrogen EM-652 which is the most potent of the known antiestrogens and exerts pure antiestrogenic activity in the mammary gland and endometrium. EM-652 inhibits the AF-1 and AF-2 functions of both ERalpha and beta while the inhibitory action of OH-TAM is limited to AF-2. EM-652, thus, inhibits Ras-induced transcriptional activity and blocks SRC-1-stimulated activity of the two receptors. The absence of blockade of AF-1 by OH-TAM could explain why resistance develops to Tamoxifen treatment. Not only the development, but also the growth of established DMBA-induced mammary carcinoma is inhibited by treatment with EM-800, the prodrug of EM-652. EM-652 is the most potent antiestrogen to inhibit the growth of human breast cancer ZR-75-1, MCF-7 and T-47D cells in vitro. When incubated with human Ishikawa endometrial carcinoma cells, EM-800 has no stimulatory effect on the estrogen-sensitive parameter alkaline phosphatase activity. When administered to ovariectomized animals, EM-800 prevents bone loss, and lowers serum cholesterol and triglyceride levels. EM-800 has shown benefits in women with breast cancer who had failed Tamoxifen. The above-summarized preclinical and clinical data clearly suggest the interest of studying this compounds in the neoadjuvant and adjuvant settings and, most importantly, for the prevention of breast and uterine cancer.

Animals↗

Effects of the FABP2 A54T mutation on triglyceride metabolism of viscerally obese men.

OBJECTIVE: Viscerally obese individuals are frequently characterized by a proatherogenic condition. A missense mutation (A54T) in the fatty acid binding protein type 2 (FABP2) gene has been associated with insulin resistance and obesity. This study examined the effect of this mutation on lipoprotein levels in viscerally obese hyperinsulinemic condition. RESEARCH METHODS AND PROCEDURES: A total of 217 men were assigned to one of two groups based on their FABP2 A54T polymorphism. RESULTS: The two genotypic groups showed no difference in either physiological characteristics or lipoprotein/lipid profile, before or after statistical adjustment for age. From this initial sample, 50 men accepted to have their postprandial lipid response assessed and 10 T54/A54 heterozygotes were then individually matched for visceral adipose tissue accumulation and fasting plasma triglyceride (TG) levels with 10 A54/A54 homozygotes. High-density lipoprotein (HDL)-TG levels were significantly increased in the fasting state as well as 4 hours after the test meal (p = 0.04 and p = 0.0008, respectively) in men bearing the A54T mutation. In addition, the area under the curve of postprandial HDL-TG levels was also significantly higher among T54/A54 heterozygotes than among A54/A54 homozygotes (p = 0.04). Interestingly, fasting TG concentrations in large TG-rich lipoproteins (large-TRL; S(f) > 400) were correlated with HDL-TG levels at 4 (r = 0.74, p = 0.01) and 8 hours (r = 0.73, p = 0.01) after the test meal in T54/A54 heterozygotes only. DISCUSSION: The FABP2 A54T missense mutation may contribute to the TG enrichment of HDL in the postprandial state that, in turn, may alter the risk of atherosclerotic vascular disease.

Adipose Tissue↗

Genetic variation at the uncoupling protein 1, 2 and 3 loci and the response to long-term overfeeding.

OBJECTIVE: To evaluate the effects of uncoupling protein (UCP) 1, UCP2 and UCP3 gene variants on body composition and metabolic changes in response to chronic overfeeding and the recovery after the period of overfeeding. SUBJECTS AND DESIGN: Twenty-four normal weight men (21+/-2 y), who constituted 12 pairs of identical twins, ate a 4.2 MJ/day energy surplus, 6 days a week, during a period of 100 days. The subjects were asked to return to the laboratory for testing at 4 months and for a final examination 5 y after completion of the overfeeding protocol. METHODS: Resting metabolic rate (RMR) measurements were performed before and after overfeeding. A 4.2 MJ test meal was consumed, after which calorimetric measurements were continued for 240 min. Total body fat was assessed by hydrodensitometry and total subcutaneous fat by the sum of eight skinfolds. Polymorphisms were typed by PCR and PCR-RFLP-techniques. Thyroid stimulating hormone (TSH) concentrations after a thyrotropin releasing hormone (TRH) injection were measured by radioimmunoassay (RIA). RESULTS: The changes in body weight and adiposity were not different between UCP1 Bcl I, UCP2 alanine to valine (A55V), UCP2 insertion/deletion (I/D) or UCP3 Rsa I genotypes. However, the recovery from overfeeding was worse among G-allele carriers of the UCP1 Bcl I, I allele non-carriers of the UCP2 I/D, AV heterozygote subjects of the UCP2 A55V and CC subjects of the UCP3 Rsa I polymorphisms. RMR was lower both before (P=0.01) and after (P=0.001) overfeeding in subjects with the CC genotype of the UCP3 Rsa I polymorphism. Moreover, after overfeeding, the UCP2 A55V heterozygote and UCP3 Rsa I CC homozygote subjects had significantly higher respiratory quotient (RQ) values at rest (P<0.01) and during the meal test (P from<0.01 to<0.05). Also mean plasma TSH concentrations 20, 30 and 45 min after the TRH injection increased more with overfeeding among UCP2 A55V (P<0.005) and UCP3 Rsa I CC (P=0.017) subjects. CONCLUSIONS: These data suggest that UCP polymorphisms may play a role in the recovery from the overfeeding by regulating substrate oxidation in response to long-term caloric surplus. The association of the UCP2 A55V and UCP3 Rsa I CC genotypes with a greater increase in the TSH response to TRH load could reflect a compensatory mechanism counteracting the effects of overfeeding. A longer period of exposure to chronic positive energy balance conditions may be necessary before sequence variation in UCP2 and UCP3 makes an impact on thyroid metabolism to influence body mass and composition changes.

Adult↗

Impact of high-intensity exercise on energy expenditure, lipid oxidation and body fatness.

OBJECTIVE: Two studies were conducted to assess the potential of an increase in exercise intensity to alter energy and lipid metabolism and body fatness under conditions mimicking real life. METHODS: Study 1 was based on the comparison of adiposity markers obtained in 352 male healthy adults who participated in the Québec Family Study who either regularly participated in high-intensity physical activities or did not. Study 2 was designed to determine the effects of high-intensity exercise on post-exercise post-prandial energy and lipid metabolism as well as the contribution of beta-adrenergic stimulation to such differences under a real-life setting. RESULTS: Results from Study 1 showed that men who regularly take part in intense physical activities display lower fat percentage and subcutaneous adiposity than men who never perform such activities, and this was true even if the latter group reported a lower energy intake (917 kJ/day, P<0.05). In Study 2, the high-intensity exercise stimulus produced a greater post-exercise post-prandial oxygen consumption as well as fat oxidation than the resting session, an effect which disappeared with the addition of propranolol. In addition, the increase in post-prandial oxygen consumption observed after the high-intensity exercise session was also significantly greater than that promoted by the low-intensity exercise session. CONCLUSION: These results suggest that high-intensity exercise favors a lesser body fat deposition which might be related to an increase in post-exercise energy metabolism that is mediated by beta-adrenergic stimulation.

Adipose Tissue↗

Obesity treatment with a progressive clinical tri-therapy combining sibutramine and a supervised diet--exercise intervention.

OBJECTIVE: : Sibutramine favors a negative energy balance and also has the potential to increase heart rate and blood pressure. We investigated if a progressive supervised sibutramine--diet--exercise clinical intervention could increase the body weight loss previously reported while minimizing the potential cardiostimulatory effects of this drug. DESIGN AND SUBJECTS: : The tri-therapy intervention was divided into two phases of 6 weeks each in which sibutramine (10 mg) was taken once daily by eight obese men (body mass index (BMI) between 30 and 40 kg/m(2)). Part A consisted of a dietary follow-up with an energy restriction, whereas in part B an aerobic exercise program combined with a low-fat diet was introduced. Systolic (SBP) and diastolic (DBP) blood pressure, resting heart rate (RHR) and body weight were measured every 2 weeks while body density, resting metabolic rate (RMR) and respiratory quotient (RQ) were determined before and after the intervention. RESULTS: : This clinical intervention produced a substantial body weight loss (-10.7 kg, P<0.01) which was about twice as much as other 12-week studies. In part A, both RHR (+4 beats/min) and DBP (+5 mmHg, P<0.01) were increased. However, after part B, RHR (-8 beats/min, P=0.02) and DBP (-3 mmHg, P<0.01) were significantly decreased. RMR was decreased at the end of the program but this effect did not persist after adjustments for fat-free mass. RQ was also reduced (-0.05, P<0.01) following the clinical tri-therapy. CONCLUSION: : In conclusion, these observations suggest that this clinical tri-therapy favored a satisfactory benefit--risk profile since it enhanced weight loss without inducing increases in heart rate and blood pressure or detrimental changes in RMR and substrate oxidation.

Adult↗

Beta-2 adrenergic receptor variants are associated with subcutaneous fat accumulation in response to long-term overfeeding.

OBJECTIVE: The effects of alpha-2A (A2A)-, beta-2 (B2)- and beta-3 (B3)-adrenergic receptor (ADR) gene polymorphisms on adiposity, fat distribution and plasma insulin and leptin changes in response to long-term overfeeding were explored. METHODS: Twenty four men (mean (+/-s.d.) age 21+/-2 y) who constituted 12 pairs of identical twins ate a 4.2 MJ/day energy surplus, 6 days a week, for a period of 100 days. Total body fat was assessed by hydrodensitometry and total subcutaneous fat by the sum of eight skinfolds. Abdominal fat areas were measured by computerized tomography (CT). Plasma glucose and insulin during fasting and in response to an oral glucose tolerance test (OGTT) were assayed. The insulin and glucose areas were computed using the trapezoidal method. Plasma leptin was measured with an enzyme-linked immunosorbent assay. The ADR polymorphisms were identified by PCR or Southern blot technique. RESULTS: The ADRB2 Gln27Gln genotype (n=10) was associated with a larger gain (percentage change) in weight (P<0.001) and total subcutaneous (P<0.005) fat than the Glu27Glu/Gln27Glu genotype (n=14). In addition, overfeeding induced greater increases in the insulin areas under the curve during the OGTT and the fasting plasma level of leptin (P<0.01 and <0.03, respectively) among Gln27Gln than in the Glu27Glu/Gln27Glu subjects. The body composition and metabolic changes among the ADRB2 BanI 3.7/3.4 kb subjects (n=10) were similar to those of Gln27Gln subjects. ADRA2A DraI (n=4) 6.3/6.3 kb subjects experienced a decrease (-8%) while 6.7/6.3 kb subjects (n=20) registered an increase (+10%; P=0.017) of OGTT glucose area after the 100-day caloric surplus. The four carriers of the ADRB3 variant (Trp64Arg) experienced the same magnitude of changes as the 20 homozygotes for the Trp allele. In general, comparisons based on the 24 subjects considered as unrelated men and the mean values for each of the 12 pairs yielded similar results. CONCLUSION: The ADRB2 Gln27Gln subjects gained more weight and total subcutaneous fatness and also experienced a greater increase in insulin resistance than Glu27Glu/Gln27Glu subjects with exposure to long-term overfeeding. Similar differences were observed between carriers and non-carriers of the ADRB2 3.7/3.4 kb BanI variant. Genetic variation at the ADRB2 locus could thus be one of the factors responsible for the large inter-individual differences observed in the response to long-term alterations in energy balance and should be further investigated.

Abdomen↗

Increase in plasma pollutant levels in response to weight loss in humans is related to in vitro subcutaneous adipocyte basal lipolysis.

OBJECTIVE: To examine whether weight loss-induced changes in in vitro basal lipolysis of subcutaneous abdominal and femoral fat cells were related to those in plasma organochlorine levels. DESIGN: A 15 week weight loss program induced by a moderate caloric restriction. SUBJECTS: Seventeen men and 20 women (age 36-50 y, body fat 25-50%). MEASUREMENTS: In vitro basal lipolysis of subcutaneous abdominal and femoral adipocytes and plasma levels of five polychlorinated biphenyl congeners (Aroclor 1260, PCBs 118, 138, 153 and 180) and three chlorinated pesticides (dichlorodiphenyl dichloroethene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH) and hexachlorobenzene (HCB)) were measured before and after the weight reducing program. RESULTS: Both genders showed a similar reduction in body weight (approximately 11 kg) in response to treatment, although men lost significantly more fat mass than women (mean+/-s.d., 9.4+/-4.1 vs 5.9+/-5 kg, respectively, P<0.05). Mean basal fat cell lipolysis did not vary before and after weight reduction, regardless of depots and genders. In response to weight loss, significant increases of all organochlorines investigated were observed in men, whereas only p,p'-DDE, Aroclor 1260, PCBs 153 and 180 significantly rose in women. In men, higher the increase in basal lipolysis of subcutaneous abdominal or femoral adipocytes, greater the rise in plasma levels of most pollutants (HCB, Aroclor 1260, PCBs 118, 138 and 153) was in response to weight loss (0.51<r<0.70, P<0.05). Similar positive correlations were also observed in women but only a few reached statistical significance (p,p'-DDE, PCBs 118 and 180). CONCLUSION: The weight loss-induced increase in plasma pollutant levels is related to the rise in subcutaneous abdominal and femoral adipocyte basal lipolysis, especially in men.

Abdomen↗

Difference in leptin response to a high-fat meal between lean and obese men.

The aim of this study was to compare the leptin responses to a high-fat meal in lean and obese men, and to investigate whether the net leptin response (area under the incremental curve) after the meal was related to the thermic effect of food (TEF). Blood samples were collected after an overnight fast and every 2 h for 8 h after a high-fat breakfast (60 g of fat/m(2) body surface area) in 12 lean and 12 obese men for determination of glucose, insulin and leptin. The TEF was calculated as postprandial energy expenditure minus fasting energy expenditure, as measured by indirect calorimetry. Fasting plasma glucose levels were similar in lean and obese men, and increased in the same way after the meal. Fasting and postprandial plasma insulin concentrations were significantly greater in obese than in lean men (P<0.01 and P<0.05 respectively). Accordingly, obese men showed a significantly higher net insulin response than lean subjects (P<0.001). Fasting plasma leptin levels were greater in obese than in lean men (P<0.001). After the meal, plasma leptin increased significantly in lean men, whereas it decreased in obese men (group by time interaction, P<0.01). The net response of leptin was greater in lean than in obese men, but this did not reach statistical significance (P=0.07). Moreover, the TEF was similar in the two groups. No significant relationship was observed between either the net insulin response or the net leptin response after the high-fat meal and the TEF of lean subjects (-0.05 <r<0.31). In obese men, the net response of insulin was correlated significantly with TEF (r=0.70, P<0.05), whereas the net response of leptin was not (r=-0.40). These results suggest that obesity is related to an impaired regulation of leptin by insulin, since leptin levels increased in lean men but decreased in obese men following a high-fat meal. Moreover, the fact that the postprandial leptin responses of both lean and obese men were not significantly related to the TEF suggests that the ob gene product is probably not acutely involved in the control of this energy expenditure component in humans.

Adult↗

Combined effects of red pepper and caffeine consumption on 24 h energy balance in subjects given free access to foods.

The effects of red pepper and caffeine ingestion on energy and macronutrient balances were examined in eight Caucasian male subjects. All subjects participated in two randomly assigned conditions: control and experimental (red pepper and caffeine). After ingesting a standardized breakfast, subjects ate three meals ad libitum (lunch, dinner and breakfast) and snacks which were served approximately 2 h after the lunch and dinner over a 24 h period. Two appetizers with or without 3 g red pepper) were given before lunch and dinner, and a drink (decaffeinated coffee with or without 200 mg caffeine) was served at all meals and snacks except for the after-dinner snack. It is also important to note that on the experimental day, 8.6 and 7.2 g red pepper were also added to lunch and dinner respectively. Red pepper and caffeine consumption significantly reduced the cumulative ad libitum energy intake and increased energy expenditure. The mean difference in energy balance between both conditions was 4000 kJ/d. Moreover, the power spectral analysis of heart rate suggested that this effect of red pepper was associated with an increase in sympathetic:parasympathetic nervous system activity ratio. These results indicate that the consumption of red pepper and caffeine can induce a considerable change in energy balance when individuals are given free access to foods.

Adult↗

Evidence for the existence of adaptive thermogenesis during weight loss.

The present study was performed to further investigate the adaptive component of thermogenesis that appears during prolonged energy restriction. Fifteen obese men and twenty obese women underwent a 15-week weight-loss programme. During this programme, body weight and composition as well as resting energy expenditure (REE) were measured at baseline, after 2 and 8 weeks of energy restriction (-2929 kJ/d) and drug therapy (or placebo), and finally 2-4 weeks after the end of the 15-week drug therapy and energy restriction intervention, when subjects were weight stable. Regression equations were established in a control population of the same age. These equations were then used to predict REE in obese men and women at baseline, after 2 and 8 weeks, as well as after the completion of the programme. In both men and women body weight and fat mass were significantly reduced in all cases) while fat-free mass remained unchanged throughout the programme. At baseline, REE predicted from the regression equation was not significantly different from the measured REE in men, while in women the measured REE was 13 % greater than predicted. After 2 weeks of energy restriction, measured REE had fallen by 469 and 635 kJ/d more than predicted and this difference reached 963 and 614 kJ/d by week 8 of treatment in men and women respectively. Once body-weight stability was recovered at the end of the programme, changes in REE remained below predicted changes in men (-622 kJ/d). However, in women changes in predicted and measured REE were no longer different at this time, even if the women were maintaining a reduced body weight. In summary, the present results confirm the existence of adaptive thermogenesis and give objective measurements of this component during weight loss in obese men and women, while they also emphasize that in women this component seems to be essentially explained by the energy restriction.

Adaptation, Physiological↗

Effect of a low-glycaemic index--low-fat--high protein diet on the atherogenic metabolic risk profile of abdominally obese men.

It has been suggested that the current dietary recommendations (low-fat-high-carbohydrate diet) may promote the intake of sugar and highly refined starches which could have adverse effects on the metabolic risk profile. We have investigated the short-term (6-d) nutritional and metabolic effects of an ad libitum low-glycaemic index-low-fat-high-protein diet (prepared according to the Montignac method) compared with the American Heart Association (AHA) phase I diet consumed ad libitum as well as with a pair-fed session consisting of the same daily energy intake as the former but with the same macronutrient composition as the AHA phase I diet. Twelve overweight men (BMI 33.0 (sd 3.5) kg/m2) without other diseases were involved in three experimental conditions with a minimal washout period of 2 weeks separating each intervention. By protocol design, the first two conditions were administered randomly whereas the pair-fed session had to be administered last. During the ad libitum version of the AHA diet, subjects consumed 11695.0 (sd 1163.0) kJ/d and this diet induced a 28 % increase in plasma triacylglycerol levels (1.77 (sd 0.79) v. 2.27 (sd 0.92) mmol/l, P<0.05) and a 10 % reduction in plasma HDL-cholesterol concentrations (0.92 (sd 0.16) v. 0.83 (sd 0.09) mmol/l, P<0.01) which contributed to a significant increase in cholesterol:HDL-cholesterol ratio (P<0.05), this lipid index being commonly used to assess the risk of coronary heart disease. In contrast, the low-glycaemic index-low-fat-high-protein diet consumed ad libitum resulted in a spontaneous 25 % decrease (P<0.001) in total energy intake which averaged 8815.0 (sd 738.0) kJ/d. As opposed to the AHA diet, the low-glycaemic index-low-fat-high-protein diet produced a substantial decrease (-35 %) in plasma triacylglycerol levels (2.00 (sd 0.83) v. 1.31 (sd 0.38) mmol/l, P<0.0005), a significant increase (+1.6 %) in LDL peak particle diameter (251 (sd 5) v. 255 (sd 5) A, P<0.02) and marked decreases in plasma insulin levels measured either in the fasting state, over daytime and following a 75 g oral glucose load. During the pair-fed session, in which subjects were exposed to a diet with the same macronutrient composition as the AHA diet but restricted to the same energy intake as during the low-glycaemic index-low-fat-high-protein diet, there was a trend for a decrease in plasma HDL-cholesterol levels which contributed to the significant increase in cholesterol:HDL-cholesterol ratio noted with this condition. Furthermore, a marked increase in hunger (P<0.0002) and a significant decrease in satiety (P<0.007) were also noted with this energy-restricted diet. Finally, favourable changes in the metabolic risk profile noted with the ad libitum consumption of the low-glycaemic index-low-fat-high-protein diet (decreases in triacyglycerols, lack of increase in cholesterol:HDL-cholesterol ratio, increase in LDL particle size) were significantly different from the response of these variables to the AHA phase I diet. Thus, a low-glycaemic index-low-fat-high-protein content diet may have unique beneficial effects compared with the conventional AHA diet for the treatment of the atherogenic metabolic risk profile of abdominally obese patients. However, the present study was a short-term intervention and additional trials are clearly needed to document the long-term efficacy of this dietary approach with regard to compliance and effects on the metabolic risk profile.

Analysis of Variance↗

Prior meal enhances the plasma glucose lowering effect of exercise in type 2 diabetes.

PURPOSE: To compare the changes in plasma glucose and insulin levels in response to 1 h of exercise performed at 60% of VO(2peak) either in the fasted state or 2 h after a standardized breakfast in subjects with type 2 diabetes. METHODS: Ten sedentary men with type 2 diabetes treated with oral agents and not under strict metabolic control were tested on two occasions (fasted and fed state) in a random order at a 1-wk interval. RESULTS: Plasma glucose was slightly but not significantly higher at the beginning of exercise performed in the fed state versus the fasted state (12.4 +/- 1.3 vs 11.1 +/- 1.1 mmol x L(-1) respectively; mean +/- SE, P = 0.06). However, after exercise, plasma glucose levels were much lower in the fed state (7.6 +/- 1.1 mmol x L(-1)) compared with the fasted state (10.0 +/- 1.0 mmol x L(-1); P = 0.009). Insulin levels were higher at the beginning of the exercise bout performed in the fed state (177 +/- 26 vs 108 +/- 19 pmol x L(-1); P < 0.05) and during exercise. Similar respiratory exchange ratio at identical workload indicated that the difference in glycemic response was not due to differences in whole body substrate utilization. Plasma concentrations of free fatty acids, glucagon, epinephrine, and norepinephrine were also similar during both experiments. CONCLUSIONS: One hour of aerobic exercise has a minimal impact on plasma glucose level when performed in fasted moderately hyperglycemic men with type 2 diabetes but induces an important decrease in plasma glucose level when performed 2 h after breakfast. Because glucose utilization increased similarly during exercise in both conditions, the higher insulin levels after the meal might have blunted glucose production, creating an imbalance between total glucose production and total peripheral utilization in the fed state in contrast to the fasted state.

Blood Glucose↗

Increased risk for falling associated with obesity: mathematical modeling of postural control.

Recent epidemiological studies report that obesity is positively related to fracture incidence. In the present experiment, a model of postural control was used to examine the impact of an abnormal distribution of body fat in the abdominal area upon postural stability. Obese and lightweight humanoids were destabilized by imposing a small initial angular speed from a neutral standing position. To avoid a loss of stability yielding a stepping reaction or a fall, an ankle torque is necessary to counteract the perturbation. Three torque parameters--ankle torque onset, time to peak torque, and muscular ankle torque--were entered in a program to simulate the intrinsic variability of the human postural control system. A loss of stability was detected when the center of pressure exceeded stability margins. The most striking observation is the nonlinear increase of torque needed to stabilize the humanoid when the motor response was characterized by delayed temporal parameters. The effect was more pronounced when an anterior position of the center of mass was included in the simulations. This suggests that, when submitted to daily postural stresses and perturbations, obese persons (particularly those with an abnormal distribution of body fat in the abdominal area) may be at higher risk of falling than lightweight individuals.

Abdomen↗