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Biomedical subjects

F Féry

Publications and source records attributed to F Féry.

11 recordsLinked to original sources
PubMed1989

Ketone body production and disposal: effects of fasting, diabetes, and exercise.

Turnover studies performed during progressive fasting in normal subjects indicate that the production rate and the concentration of KB rise markedly during the early phase of fasting and start reaching a plateau after about 5 days. In addition to increased production, a reduction in the metabolic clearance rate of KB contributes to the hyperketonemia. This reduced metabolic clearance rate reflects essentially the progressive saturation of muscular ketone uptake that occurs with increasing ketonemia. The hormonal and metabolic environment of fasting plays only a minor role in this process, since a fall in KB metabolic clearance similar to that observed during fasting is observed if hyperketonemia is artificially induced in the postabsorptive state by the infusion of exogenous ketones. As extraction of KB by muscle becomes limited during ongoing fasting, KB are preferentially taken up by the brain to serve as a substrate replacing glucose. The remarkable stability of ketonemia during prolonged fasting is maintained through the operation of a negative feedback mechanism whereby KB tend to restrain their own production rate. The antilipolytic and insulinotropic effects of KB are instrumental in this process. This homeostatic mechanism maintains ketogenesis only slightly above the maximal metabolic disposal rate, the difference corresponding to urinary excretion, which is always below 10% of total turnover under physiologic conditions. When type I insulin-deprived diabetic patients are compared at the same KB concentration with control subjects with fasting ketosis, the characteristics of KB kinetics are comparable in the two groups. The maximal KB removal capacity is identical in the two situations, and it is not possible to identify a ketone removal defect specific to diabetes. Thus, these data favor the concept that excessive production of KB represent the main factor leading to uncontrolled hyperketonemia. It should be realized that a production exceeding only slightly that prevailing during prolonged fasting is sufficient to cause a progressive build-up in concentration, leading to uncontrolled diabetic ketosis. In the overnight-fasted state, a prolonged exercise (2 h) performed at moderate intensity (50% VO2 max) stimulates the capacity of muscle to extract ketones from blood as evidenced by a stimulation of the metabolic clearance rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus↗
PubMed1989

Nocturnal decrease in glucose tolerance during constant glucose infusion.

Studies comparing glucose tolerance in the morning vs. that in the evening have suggested that time of day may influence glucose regulation. To examine the variation in glucose tolerance throughout the 24-h span, normal subjects were given an iv glucose infusion at a constant rate of either 5 or 8 g/kg.24 h during 30 h, and plasma levels of insulin and glucose were measured at 15-min intervals for the last 24 h of the infusion. The timing of initiation of the infusion was varied to differentiate effects of time of day from effects of duration of the infusion. A nocturnal elevation of glucose levels, culminating around midsleep and corresponding to an increase of about 15% above daytime levels, was observed in all subjects. The timing of this nocturnal maximum was not dependent on the rate of the infusion or on the time elapsed since the beginning of the infusion. Insulin levels did not show a consistent diurnal pattern. Both insulin and glucose exhibited large ultradian oscillations recurring at 100- to 150-min intervals. The amplitude of these oscillations increased with the rate of glucose infusion. These ultradian oscillations of glucose and insulin levels were temporally correlated, with a tendency for glucose pulses to lead insulin pulses by 15-30 min. These results demonstrate in normal subjects the existence of a diurnal variation in glucose tolerance distinct from the dawn phenomenon observed in diabetic subjects and indicate that spontaneous 100- to 150-min oscillations in peripheral glucose and insulin levels characterize stimulated pancreatic function, with the amplitude of the oscillations being dependent on the size of the stimulus.

Activity Cycles↗
PubMed1988

Effect of exercise on the disposal of infused ketone bodies in humans.

We previously reported that the stimulatory effect of exercise on the metabolic clearance of ketone bodies in postabsorptive subjects is abolished when plasma ketone body concentrations are elevated above 4 mmol/L by prior fasting. In this study we determined whether this process is related to fasting or to hyperketonemia itself. Eight normal postabsorptive subjects were rendered artificially hyperketonemic (approximately 6 mmol/L) by a constant infusion of acetoacetate and exercised moderately for 2 h. The kinetics of ketone bodies were determined with [14C]acetoacetate or beta-[14C]hydroxybutyrate. The metabolic clearance was slightly increased (approximately 25%) at the beginning of exercise, but this phenomenon was subsequently amplified by the progressive fall in ketonemia, which decreased to about 4 mmol/L at the end of exercise. Taking into account the fact that the metabolic clearance of ketones is inversely related to their concentration, it could be estimated that the direct effect of exercise on the metabolic clearance is negligible. Thus, the inability of exercise to enhance the metabolic clearance of ketones at high physiological plasma ketone levels is a general phenomenon that applies to both endogenous and exogenous ketosis.

Adult↗
PubMed1987

Mechanism of the hyperketonaemic effect of prolonged exercise in insulin-deprived type 1 (insulin-dependent) diabetic patients.

The effects of moderate exercise of 2-h duration on the concentration and turnover rate of total ketone bodies were assessed in 7 acutely insulin-deprived Type 1 (insulin-dependent) diabetic patients with an isotope tracer technique using a constant infusion of 14C-beta-hydroxybutyrate. These results were compared to those obtained in 13 normal control subjects in whom a similar range of hyperketonaemia (approximately 1-6 mmol/l) was induced by fasting. In all subjects, the concentration and the rate of production of ketone bodies followed a biphasic pattern with an initial fall lasting for about 20 min followed by a secondary rise. When integrated over the entire working period, the exercise-induced changes in ketone turnover were markedly dependent on the initial ketone body concentrations in both groups: at low ketonaemia (approximately 1 mmol/l), exercise increased the rate of production and disposal of ketones. These effects were progressively attenuated as basal ketonaemia rose and were reversed to an inhibitory action in markedly ketotic subjects (greater than 4 mmol/l). Despite the finding that, at high ketosis, exercise inhibited ketogenesis to a similar degree in control subjects and diabetic patients, the changes in concentration recorded at the end of exercise were different in the 2 groups: ketonaemia was reduced in fasted control subjects and increased in the diabetic patients. These data suggest that, contrary to a widely accepted opinion, the hyperketonaemic effect of prolonged exercise in ketotic diabetic patients does not result from an exaggerated stimulation of ketogenesis, but from some defect in their removal capacities for ketones, possibly related to insulinopenia.

Adult↗
PubMed1986

Response of ketone body metabolism to exercise during transition from postabsorptive to fasted state.

This study examines the effects of a 2-h exercise of moderate intensity (50% of VO2 max) on the tracer-determined turnover rate of ketone bodies (KB) in 21 normal subjects fasted for 16 h, 5 days, whose basal ketonemia ranged between 0.09 and 6.16 mM. The KB response observed at the end of exercise is a function of the initial degree of ketosis. When basal ketonemia is below 0.6 mM, exercise enhances ketogenesis (Ra), the amplitude of this process being positively correlated with KB level. There is a concomitant acceleration of the metabolic clearance rate (MCR) of KB attaining 40-50%. When ketonemia exceeds 2.5 mM, the stimulatory effects of exercise on Ra and on MCR become less marked as basal ketonemia rises and are completely abolished or even reversed when initial KB level is higher than 3-4 mM. The pattern of changes in the concentration and in the overall disposal rate of KB were similar to that of Ra. It is suggested that the parallel inhibition of the stimulatory effect of work on hepatic ketogenesis and on muscular extraction of ketones associated with increasing degrees of fasting hyperketonemia has two physiological implications: it maintains the preferential utilization of KB by nonmuscular tissues (presumably the brain) and prevents the development of uncontrolled hyperketonemia, despite the intense catabolic situation created by the combination of exercise and starvation.

3-Hydroxybutyric Acid↗
PubMed1985

Ketone body production and disposal in diabetic ketosis. A comparison with fasting ketosis.

This work compares the metabolism of total ketone bodies in 13 insulin-deprived, type I diabetic subjects and 26 control subjects fasted for 15 h to 23 days, with the two groups showing a similar range of ketone body levels (1-12 mM). Ketone turnover rate was measured using a primed, constant infusion of either 14C-acetoacetate or 14C-beta-hydroxybutyrate, both tracers yielding comparable results. The major conclusions of this study are the following: the kinetics of ketone bodies are comparable in the two groups within the range of concentrations tested. The hyperketonemia of fasting and diabetes is primarily caused by an increased production of ketone bodies, but the phenomenon is amplified by a progressive limitation in the ability of tissues to remove ketones from blood as the concentration rises. The inverse relationship between the metabolic clearance and the plasma levels of ketones, which underlies this process, represents a general characteristic of ketone body metabolism that applies to both types of ketosis. A maximal metabolic disposal rate of about 2.3 mmol/min/1.73 m2 is attained in both groups at concentrations of 10-12 mM, which correspond to the highest ketone body levels encountered during prolonged fasting. Thus, up to these levels, there is no evidence for the existence of a ketone body removal defect specific to diabetes.

3-Hydroxybutyric Acid↗
PubMed1976

Pituitary and extrapituitary effects of somatostatin in normal man.

The effects of synthetic linear somatostatin on basal circulating levels on several pituitary and pancreatic hormones, and of glucose and free fatty acids (FFA) were studied in 6 normal men after an overnight fast. A priming intravenous infusion of 250 mug of somatostatin in 18 sec was followed by a constant infusion of 500 mug over a period of 60 min. A decrease in plasma values of GH, prolactin, TSH, insulin and glucagon and in blood glucose was observed during somatostatin infusion, while FFA levels increased progressively. Plasma IRI and blood glucose increased rapidly when the somatostatin infusion was stopped, while FFA decreased progressively; GH, prolactin, TSH and glucagon remained low as compared to basal levels for one hour after the end of the infusion, i.e. until the end of the experiment. A slight but significant increase of LH and ACTH was observed after the end of the infusion.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Residual effects of a short-term intensified insulin therapy in type 2 diabetic patients with oral drug failure.

The present study was designed to evaluate the long-term effects of a short course of insulin therapy on glycaemic control in type 2 diabetic patients after failure with oral therapy. Twenty type 2 diabetic patients poorly controlled with maximal doses of sulfonylurea were given intensified insulin treatment for 12-14 days adjusted so as to achieve near normoglycaemia. They were then restarted on their previous oral medication to which one bedtime injection of NPH insulin was added if the mean diurnal glucose profile exceeded 10 mM (n = 8). At the follow up evaluation (n = 18), 6 +/- 1 months later, fasting glucose (12.3 +/- 1.1 to 8.3 +/- 0.6 mM) and HbA1c (10.2 +/- 0.5 to 8.5 +/- 0.5%) levels were significantly improved in the patients receiving a combined therapy. In the group maintained on sulfonylurea alone, fasting glucose (13.2 +/- 0.7 to 6.9 +/- 0.7 mM) and HbA1c (9.6 +/- 0.6 to 6.9 +/- 0.6%) were also significantly improved in 5 patients who had lost weight (-6 +/- 1 kg) whereas none of these parameters were significantly different from the preinsulin value in the 6 patients whose weight remained unchanged. In conclusion, the current results do not provide any evidence that short-term insulin therapy is able to reinduce the efficacy of a previously ineffective sulfonylurea treatment, on a long term basis.

Administration, Oral↗
PubMedDate not supplied

Effect of short term fasting on glucose tolerance and insulin secretion: influence of the initial glucose level.

To evaluate the effect of fasting on glucose tolerance (GT) and insulin secretion, a 5 h oral glucose tolerance test was performed after an overnight fast and after 3-6 days of fasting in 66 obese subjects presenting a normal (n = 22), impaired (n = 23) or diabetic (n = 21) GT. Insulin secretory capacity was assessed using two glucose-independent parameters of beta cell function. In the normal group, fasting induced a fall in basal glycemia from 84 +/- 1 to 58 +/- 2 mg/dl (P less than 0.001) and an increase in the area of glucose (+58 +/- 8%, P less than 0.001), insulin (+75 +/- 10%; P less than 0.001) and C-peptide (+58 +/- 10%; P less than 0.001) during OGTT, these responses were consistent with the emergence of insulin resistance. The insulin secretory capacity was significantly decreased. In the diabetic group, fasting was associated with an increase in insulin (+34 +/- 10%; P less than 0.005) and C-peptide (+34 +/- 8%; P less than 0.001) responses to OGTT despite a reduction in basal glycemia from 174 +/- 11 to 86 +/- 4 mg/dl (P less than 0.001) and in glucose response (-20 +/- 3%; P less than 0.001), indicating an improvement of insulin secretory capacity. In the group with impaired GT, basal glycemia decreased from 97 +/- 2 to 70 +/- 2 mg/dl (P less than 0.001) but glucose, insulin and C-peptide curves were not significantly affected by fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗