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J F Gautier

Publications and source records attributed to J F Gautier.

At least 19 recordsLinked to original sources
PubMed2000

Differential brain responses to satiation in obese and lean men.

Knowledge of how the brain contributes to the regulation of food intake in humans is limited. We used positron emission tomography and measures of regional cerebral blood flow (rCBF) (a marker of neuronal activity) to describe the functional anatomy of satiation (i.e., the response to a liquid meal) in the context of extreme hunger (36-h fast) in 11 obese (BMI > or =35 kg/m2, age 27+/-5 years, weight 115+/-11 kg, 38+/-7% body fat; mean +/- SD) and 11 lean (BMI < or =25 kg/m2, age 35+/-8 years, weight 73+/-9 kg, 19+/-6% body fat) men. As in lean men, satiation in obese men produced significant increases in rCBF in the vicinity of the ventromedial and dorsolateral prefrontal cortex and significant decreases in rCBF in the vicinity of the limbic/paralimbic areas (i.e., hippocampal formation, temporal pole), striatum (i.e., caudate, putamen), precuneus, and cerebellum. However, rCBF increases in the prefrontal cortex were significantly greater in obese men than in lean men (P < 0.005). rCBF decreases in limbic/paralimbic areas, temporal and occipital cortex, and cerebellum were also significantly greater in obese men than in lean men (P < 0.005), whereas rCBF decreases in the hypothalamus and thalamus were attenuated in obese men compared with lean men (P < 0.05). This study raises the possibility that the brain responses to a meal in the prefrontal areas (which may be involved in the inhibition of inappropriate response tendencies) and limbic/paralimbic areas (commonly associated with the regulation of emotion) may be different in obese and lean men. Additional studies are required to investigate how these differential responses are related to the pathophysiology of obesity.

Adult↗
PubMed1999

Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography.

The central role of the hypothalamus in the origination and/or processing of feeding-related stimuli may be modulated by the activity of other functional areas of the brain including the insular cortex (involved in enteroceptive monitoring) and the prefrontal cortex (involved in the inhibition of inappropriate response tendencies). Regional cerebral blood flow (rCBF), a marker of neuronal activity, was measured in 11 healthy, normal-weight men by using positron emission tomography in a state of hunger (after 36-h fast) and a state of satiation (after a liquid meal). Hunger was associated with significantly increased rCBF in the vicinity of the hypothalamus and insular cortex and in additional paralimbic and limbic areas (orbitofrontal cortex, anterior cingulate cortex, and parahippocampal and hippocampal formation), thalamus, caudate, precuneus, putamen, and cerebellum. Satiation was associated with increased rCBF in the vicinity of the ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and inferior parietal lobule. Changes in plasma insulin concentrations in response to the meal were negatively correlated with changes in rCBF in the insular and orbitofrontal cortex. Changes in plasma free fatty acid concentrations in response to the meal were negatively correlated with changes in rCBF in the anterior cingulate and positively correlated with changes in rCBF in the dorsolateral prefrontal cortex. In conclusion, these findings raise the possibility that several regions of the brain participate in the regulation of hunger and satiation and that insulin and free fatty acids may be metabolic modulators of postprandial brain neuronal events. Although exploratory, the present study provides a foundation for investigating the human brain regions and cognitive operations that respond to nutritional stimuli.

Adult↗
PubMed1999

Visceral adipose tissue is not increased in Pima Indians compared with equally obese Caucasians and is not related to insulin action or secretion.

Pima Indians are insulin resistant and hyperinsulinaemic compared with Caucasians. We investigated whether abdominal fat distribution was different between Pimas and Caucasians and whether differences in the amount of visceral fat explained metabolic differences between the groups. Total body fat (absorptiometry) and abdominal fat distribution at L4-L5 (magnetic resonance imaging) were compared in 20 Pima Indians (10 men/10 women) and 20 age-, sex- and BMI-matched Caucasians. Insulin action was measured as glucose disposal during a two-step hyperinsulinaemic-euglycaemic glucose clamp and insulin secretion was assessed in response to oral and intravenous glucose tolerance tests. By design, percent body fat was similar in Pimas and Caucasians. Abdominal visceral and subcutaneous adipose tissue areas were also similar in the two groups (151+/-16 vs 139+/-15 cm2 and 489+/-61 vs 441+/-7 cm2 respectively). Plasma insulin concentrations were higher in Pimas than Caucasians in the fasting state (27+/-6 vs 11+/-2 mU/ml; p < 0.01) and after a 75-g oral glucose load (area under the curve 19975+/-2626 vs 9293+/-1847 mU x l(-1) x 180 min(-1); p < 0.005). Glucose disposal was lower in Pimas than Caucasians during both steps of the clamp and negatively correlated (after adjustment for percent body fat and sex) with visceral adipose tissue in Caucasians (partial r = -0.51, p = 0.03), but not in Pima Indians (r = -0.03, p = 0.92). Insulin secretion was not related to visceral fat independently of percent body fat in either group. We conclude that a relative increase in visceral fat does not explain insulin resistance and hyperinsulinaemia in Pima Indians.

Adipose Tissue↗
PubMed1999

Metabolic predictors of weight gain.

Human obesity is the result of both environmental and genetic factors. In this manuscript, we briefly review the metabolic factors predicting body weight gain in Pima Indians, a population prone to obesity. The metabolic predictors of weight gain are: 1) a low metabolic rate, 2) low levels of physical activity, 3) low rates of fat oxidation, 4) insulin sensitivity, 5) low sympathetic nervous system activity, and 6) low plasma leptin concentrations. In contrast, obesity is associated with high metabolic rate, high fat oxidation, low insulin sensitivity and high plasma leptin concentration. This observation emphasizes the need to conduct prospective studies to obtain a better understanding of the etiology of obesity. In addition, genetic studies will help to identify new pathways involved in the pathophysiology of obesity.

Basal Metabolism↗
PubMed1999

Regions of the human brain affected during a liquid-meal taste perception in the fasting state: a positron emission tomography study.

BACKGROUND: The sensation of taste provides reinforcement for eating and is of possible relevance to the clinical problem of obesity. OBJECTIVE: Positron emission tomography (PET) was used to explore regions of the brain that were preferentially affected during the taste perception of a liquid meal by 11 right-handed, lean men in the fasting state. DESIGN: After subjects had fasted for 36 h, 2 measurements of regional cerebral blood flow (rCBF) obtained immediately after subjects retained and swallowed 2 mL of a flavored liquid meal (the taste condition) were compared with 2 measurements of rCBF obtained immediately after subjects retained and swallowed 2 mL of water (the baseline condition). RESULTS: Compared with the baseline condition, taste was associated with increased rCBF (P < 0.005) in the left dorsolateral prefrontal cortex and superior temporal gyrus; the right ventrolateral prefrontal cortex, supramarginal gyrus, and anterior thalamus; and bilaterally in the hippocampal formation, posterior cingulate, midbrain, occipital cortex, and cerebellum. Taste was also associated with decreased rCBF (P < 0.005) in the right dorsolateral prefrontal cortex, superior temporal gyrus, and supplementary motor area, and bilaterally in the medial prefrontal cortex and inferior parietal lobule. CONCLUSIONS: This exploratory study provides additional evidence that the temporal cortex, thalamus, cingulate cortex, caudate, and hippocampal formation are preferentially affected by taste stimulation. The asymmetric pattern of activity in the dorsolateral prefrontal cortex and superior temporal gyrus may contribute to the taste perception of a liquid meal perceived as pleasant. Additional studies are required to determine how these regions are affected in patients with obesity or anorexia.

Adult↗
PubMed1999

Development of beta 3-adrenoceptor agonists for the treatment of obesity and diabetes--an update.

Beta 3-adrenoceptor (beta 3-AR) agonists were found to have remarkable anti-obesity and anti-diabetic effects in rodents shortly after their discovery in the early 1980s. Despite these promising qualities, several pharmaceutical problems and theoretical concerns have slowed the development of these products as therapeutic agents in humans during the last 15 years. To date, the pharmaceutical industry has not been successful in developing a beta 3-AR agonist for use in the treatment of human obesity and type 2 diabetes. Pharmaceutical problems in this area concern important differences between rodent and human beta 3-AR and the difficulty in finding a compound with sufficient bioavailability that is a highly selective and full agonist at the human receptor. Some of these problems seem to have been solved with the cloning of the human beta 3-AR, which has made it possible to develop novel compounds directly and specifically against the human receptor. However, several theoretical concerns still remain. These include the major question as to whether the number of biologically active beta 3-ARs in adult humans is sufficient to produce relevant metabolic effects and, if so, whether their long-term stimulation is safe and free of unwarranted side effects. In addition, the mechanisms of action of beta 3-AR agonists remain poorly understood. Recent studies using CL 316,243, a highly selective beta 3-adrenergic compound, have provided new insights into the potential mechanisms of action of these drugs in rodents as well as the first evidence that treatment with a highly selective beta 3-AR agonist exerts relevant metabolic effects in humans. It appears that chronic beta 3-adrenergic stimulation in white adipose tissue increases the expression of newly discovered mitochondrial uncoupling proteins (UCP 2 and 3) and a "reawakening" of dormant brown adipocytes. In addition, beta 3-ARs may be present in skeletal muscle where ectopic expression of UCP-1 has been reported. If these findings are confirmed, tissues other than brown fat may play an important role in mediating beta 3-adrenergic effects on thermogenesis and substrate oxidation. In humans, treatment with CL 316,243 for 8 weeks, in spite of limited bioavailability, induced marked plasma concentration-dependent increases in insulin sensitivity, lipolysis, and fat oxidation in lean volunteers, without causing beta 1-, or beta 2-mediated side effects. These results clearly indicate that favourable metabolic effects can be achieved by selective beta 3-AR stimulation in humans. The compounds of the next generation currently emerging from preclinical development are full agonists at the human beta 3-AR. These agents have demonstrated promising results in non-human primates. It will be interesting to see whether their efficacy in clinical trials is superior to that achieved with previous (rodent) beta 3-AR agonists and, if so, whether their effects will eventually translate into weight loss and improved metabolic control that could facilitate their use as effective drugs for the treatment of obesity and Type 2 diabetes in humans.

Adrenergic beta-Agonists↗
PubMed1998

Evaluation of abdominal fat distribution in noninsulin-dependent diabetes mellitus: relationship to insulin resistance.

Accumulation of visceral adipose tissue is associated with metabolic complications such as noninsulin-dependent diabetes mellitus. The aim of this study was to evaluate the effect of abdominal adipose tissue on insulin sensitivity in subjects with noninsulin-dependent diabetes mellitus (NIDDM). Areas of abdominal fat were calculated from axial magnetic resonance images obtained at the level of the umbilicus in 21 men with NIDDM [age, 45.6 +/- 8.3 (+/-SD) yr; body mass index, 29.3 +/- 4.5 kg/m(-2); total body fat (skinfold thickness), 26.8 +/- 5.4%; waist to hip ratio, 0.97 +/- 0.07; duration of diabetes, 59 +/- 47 months; hemoglobin A1c, 8.1 +/- 1.5%]. Insulin sensitivity was evaluated by an insulin tolerance test. The areas of deep abdominal fat and sc abdominal fat were, respectively, 135.3 +/- 55.1 and 211.8 +/- 99.1 cm2. The blood glucose disappearance rate was 2.11 +/- 0.87%/min and was negatively related to deep abdominal fat (r = 0.72; P = 0.0025). In contrast, areas of sc abdominal fat, total body fat, body mass index, and waist to hip ratio were not related to the blood glucose disappearance rate. Plasma triglyceride concentrations averaged 1.8 +/- 0.8 mmol/L and were positively related to deep abdominal fat (r = 0.69; P = 0.0018). We conclude that insulin sensitivity is strongly related to visceral adipose tissue accumulation in NIDDM.

Abdomen↗
PubMed1997

Glucose turnover in humans in the basal state and after intravenous glucose: a comparison of two models.

This study investigated the ability of two models to represent glucose kinetics in the basal steady state and during an intravenous glucose tolerance test (IVGTT). Six young nonobese male subjects were studied after an overnight fast. Two bolus injections of [U-13C]glucose were given 150 min apart, the first without and the second together with concomitant injection of unlabeled glucose. [3-3H]glucose was constantly infused throughout the study and served to provide an independent means for evaluation of system responses. A linear time-invariant three-compartmental model and the two-compartment time-variant model proposed by Caumo and Cobelli were used to interpret measured time courses of [U-13C]glucose and to reconstruct endogenous glucose production and glucose removal. The ability of the two models to describe the glucose tracer time course was comparable. Simulation studies showed that the two-compartmental time-variant system better predicted measured [3-3H]glucose concentration profiles than did the three-compartmental time-invariant model. However, endogenous glucose production and the integral of excess glucose removal over basal during the IVGTT derived from the two models were almost identical.

Adult↗
PubMed1997

Mobilization of visceral adipose tissue related to the improvement in insulin sensitivity in response to physical training in NIDDM. Effects of branched-chain amino acid supplements.

OBJECTIVE: To evaluate the effects of an intense physical training program on abdominal fat distribution, glycemic control, and insulin sensitivity in patients with NIDDM and to determine whether branched-chain amino acid (BCAA) supplements influence these effects. RESEARCH DESIGN AND METHODS: Twenty-four patients (ages 45 +/- 2 [mean +/- SE] years, BMI 30.2 +/- 0.9 kg/m2, HbA1c 7.9 +/- 0.3%) were randomly assigned to four groups: training plus BCAA supplement (n = 6), training plus placebo (n = 6), sedentary plus BCAA supplement (n = 6), and sedentary plus placebo (n = 6). Physical training consisted of a supervised 45-min cycling exercise at 75% of their oxygen uptake peak (VO2 peak) two times per week and an intermittent exercise one time per week for 2 months. RESULTS: Patients who exercised increased their VO2 peak by 41% and their insulin sensitivity by 46%. Physical training significantly decreased abdominal fat evaluated by magnetic resonance imaging (umbilicus), with a greater loss of visceral adipose tissue (VAT) (48%) in comparison with the loss of subcutaneous adipose tissue (18%), but did not significantly affect body weight. The change in visceral abdominal fat was associated with the improvement in insulin sensitivity (r = 0.84, P = 0.001). BCAA supplementation had no effect on abdominal fat and glucose metabolism. CONCLUSIONS: Physical training resulted in an improvement in insulin sensitivity with concomitant loss of VAT and should be included in the treatment program for patients with NIDDM.

Adipose Tissue↗
PubMed1997

[Amylin].

Explore the source record for details and available documents.

Amyloid↗
PubMed1997

[Insulin sensitivity and hepatic glucose production: nycthemeral variations].

Glucose tolerance is subject to circadian variations and has been found to be better in the morning or afternoon. An increase in plasma glucose and insulin concentrations has recently been observed between 5 and 9 a.m. These physiological changes correspond to an increase in insulin requirements in patients with insulin-dependent diabetes mellitus (the "dawn phenomenon"). In patients with non-insulin-dependent diabetes mellitus, the circadian rhythm of insulin secretion is suppressed. Studies of insulin sensitivity during a hyperinsulinaemic hyperglycaemic clamp (a supraphysiological experimental condition) indicated that: i) insulin-induced glucose utilization is decreased in the morning according to a circadian rhythm; ii) this change results from an increase in hepatic glucose production but not from a decrease in glucose uptake; and iii) a circadian rhythm is also observed for plasma free fatty acids and cortisol concentrations, which could account in part for the circadian changes in insulin sensitivity. Recognition of these circadian changes has implications for the treatment of non-insulin-dependent diabetes mellitus.

Blood Glucose↗
PubMed1996

Changes in breath 13CO2/12CO2 during exercise of different intensities.

The measurement of breath 13CO2/12CO2 is commonly used during exercise to evaluate the oxidation rate of exogenous carbohydrates enriched in 13C. The aim of this study was to investigate whether exercise itself affects the 13C/12C ratio in expired air CO2 in relation to exercise intensity. The relative abundance of 13C and 12C in expired air CO2 was determined by isotoperatio mass spectrometry and expressed as delta 13C (in %o) by using Craig's formula and calibrated standards. Five healthy young men exercised on a treadmill after an overnight fast during > or = 105 min on four occasions and in a randomized order. Work rates were performed at approximately 30, 45, 60, and 75% of their maximal O2 uptake (VO2max). Delta 13C in expired air CO2 and respiratory exchange ratio (RER) were determined every 15 or 30 min during exercise. At 30 and 45% VO2max, a slight and not statistically significant increase in delta 13C was observed at 30 min. In contrast, at 60 75% VO2max, the rise was statistically significant and averaged 0.83 and 0.99%o, respectively. Average delta 13C (between 0 and 105 min) progressively increased with the intensity of exercise. Individual values of delta 13C and RER were positively correlated (r = 0.653, P = 0.002) as were values of delta 13C and endogenous carbohydrates utilized (r = 0.752, P < 0.001). Factitious or "pseudooxidation" of a 13C-enriched exogenous glucose load (indeed noningested) was calculated from the changes in expired air delta 13C. Over the whole period of exercise it was not statistically significant at 30 and 40% VO2max. However, over the first 60 min of exercise, such pseudooxidation of exogenous glucose was significant at 30 and 45% VO2max. In conclusion, by modifying the mix of endogenous substrates oxidized, exercise at 60% VO2max and above significantly increases the 13C/12C ratio in expired air CO2. At these intensities, this could lead to overestimation of the oxidation of 13C-labeled substrates given orally. At lower intensities of exercise, such overestimation is much smaller an affects mainly the values recorded during the initial part of the exercise bout.

Adult↗
PubMed1996

Influence of simulated altitude on the performance of five blood glucose meters.

OBJECTIVE: To determine the reliability of five blood glucose meters (BGMs) at various simulated altitudes using a hypobaric chamber. RESEARCH DESIGN AND METHODS: Blood glucose levels (ranged from 1.5 to 26.3 mmol/l, according to the reference method) were measured in 18 venous blood samples by each BGM at 200, 1,000, and every 500 m up to 4,000 m in a hypobaric chamber, where temperature and humidity were held constant. RESULTS: Four BGMs underestimated and one overestimated blood glucose concentration while barometric pressure decreased. The average percent error varied in relation to simulated altitude from 0.26 +/- 4.8% (SD) at 200 m to -28.9 +/- 4.5% at 4,000 m (Glucometer 3; P < 0.05), from 28.4 +/- 5.7 to 49.3 +/- 5.9% (Accu-Chek Easy; P < 0.05), from -10.5 +/- 2.6 to 19.8 +/- 4.3% (Tracer, P < 0.05), from -5.5 +/- 2.6 to -11.2 +/- 3.0% (Reflolux; NS), and from 17.8 +/- 4.3 to 14.8 +/- 3.6% (One Touch; NS). The most accurate seemed to be the Reflolux, except for high blood glucose levels at simulated high altitudes. The One Touch II showed a good agreement, whatever the barometric pressure and the range of blood glucose concentrations. The highest underestimation was seen with the Glucometer 3. CONCLUSIONS: Except for the Accu-Chek Easy, low barometric pressure underestimated the BGM results in comparison with measurements taken at simulated low altitudes. The lack of accuracy and consistency of performance > 2,000 m should be known by diabetic patients practicing sports activities, such as trekking or skiing at high altitudes.

Altitude↗
PubMed1996

Are the implications of the Diabetes Control and Complications Trial (DCCT) feasible in daily clinical practice?

The Diabetes Control and Complications Trial was conducted in heavily-equipped centres on a selected and motivated patient cohort. The aim of the present study was to evaluate at one-year follow-up the results of intensive insulin therapy in patients with insulin-dependent diabetes mellitus attending a department of diabetology. From October 1, 1993, to December 31, 1994, all our hospitalised patients under 55 years of age with HbA1c levels above 8% and receiving 2 daily insulin injections were offered the opportunity to shift to 3 daily injections (short-acting insulin in the morning and at midday, and a mixture of short-acting and intermediate insulin in the evening). Patients were instructed to increase blood glucose self-monitoring and to see their diabetologist more often (once every two months). Five patients refused and 45 accepted this proposal: 22 women and 23 men (mean age 31.8 +/- 10.9 yr), BMI 23.5 +/- 2.9 kg/m2, duration of diabetes 12.8 +/- 10.1 yr, HbA1c 10.0 +/- 2.0%. Five patients were lost to follow-up, 2 asked to have their medical file transferred, 3 returned to 2 daily injections, and 5 consulted only once during the year of follow-up. For the 29 patients seen after one-year follow-up, the decrease in HbA1c levels from 10.0 +/- 1.9% to 9.5 +/- 1.8% was not statistically significant. Sixteen patients complained of increased occurrence of hypoglycaemia (3 comas). In routine clinical practice, the prescription of intensive insulin therapy to non-selected insulin-dependent diabetic patients can be associated with a high number of patients lost to follow-up (17% in our study). An increase in the number of daily insulin injections will improve glycaemic control only if self-monitoring and medical surveillance are also intensified. However, many long-term poorly-controlled insulin-dependent diabetic patients are reluctant to comply with these recommendations.

Adult↗
PubMed1995

Exogenous glucose oxidation during exercise in relation to the power output.

In order to study the influence of the power output on the oxidation rate of exogenous glucose and on the contribution of the various substrates to the energy demand, we combined the use of artificially enriched 13C-glucose with classical indirect calorimetry during uphill treadmill exercise. Six young male healthy subjects underwent three exercise bouts, in a randomized order and at least two weeks apart, at a low (45% VO2max, 1822 +/- 194 ml O2/min for 4 hours), moderate (60% VO2max, 2582 +/- 226 ml O2/min for 3 hours), and high intensity (75% VO2max, 3036 +/- 287 ml O2/min for 2 hours). After 10 min of exercise, each subject ingested 100 g of artificially 13C-labelled glucose dissolved in 400 ml of water. Over the four hours of the exercise at 45% VO2max, the amount of exogenous glucose oxidized was 89.5 +/- 5.9 g from the 100 g ingested. In all exercise bouts, the oxidation of exogenous glucose already began during the first 30 min after ingestion and peaked at 120 min. The maximum oxidation rates averaged 0.64 +/- 0.07, 0.75 +/- 0.04, and 0.63 +/- 0.08 g/min, and the mean amounts of exogenous glucose oxidized over the first two hours averaged 51.7 +/- 8.0, 61.5 +/- 6.6 and 50.9 +/- 8.45 g, at 45, 60 and 75% VO2max respectively. The contribution of the oxidation of exogenous glucose to the total energy supply progressively decreased when the power output increased, from 19.6 to 12.2%. In the meantime, the contribution of total carbohydrates (exogenous+endogenous) progressively increased from 55.1 to 77.8% while the contribution of lipids decreased from 35.5 to 16.6%. In conclusion, exogenous glucose ingested during exercise is largely oxidized and strongly contributes to the energy supply. The oxidation rate first increases with the power output, but levels off or even decreases at high intensity exercise.

Adult↗