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Biomedical subjects

E O Balasse

Publications and source records attributed to E O Balasse.

18 recordsLinked to original sources
PubMed1990

Mechanisms of starvation diabetes: a study with double tracer and indirect calorimetry.

To analyze the mechanisms of fasting-induced glucose intolerance, glucose metabolism was studied before and after the ingestion of 75 g glucose in 24 normal subjects fasted for either 14 h (n = 12) or 4 days (n = 12). The techniques included intravenous infusion of [6-3H]glucose and oral administration of [1-14C]glucose combined with indirect calorimetry. Compared with the controls, the starved subjects exhibited the following differences in glucose metabolism during the 5 h after glucose ingestion. 1) Mean incremental levels were fourfold higher for glucose and 40% higher for insulin. 2) Absorption of oral glucose was delayed and prolonged, but total amount reaching systemic circulation in 5 h was identical in the two groups (approximately 63 g). 3) Suppression of hepatic glucose output was reduced (-12 +/- 1 vs. -22 +/- 2 g). 4) Consequently, the increment in peripheral appearance of total glucose (exogenous plus endogenous) was augmented (+ 52 +/- 2 vs. +41 +/- 2 g). 5) Mean glucose clearance increased significantly less (+28 +/- 7 vs. +96 +/- 10 ml/min). 6) Oxidation of oral glucose was reduced (9 +/- 2 vs. 36 +/- 3 g), and nonoxidative disposal (presumably storage) was enhanced (56 +/- 2 vs. 36 +/- 3 g) in the presence of an elevated fat oxidation (35 +/- 2 vs. 22 +/- 4 g). Thus the alterations in glucose homeostasis responsible for the starvation-induced glucose intolerance are located both at the splanchnic (hepatic) and peripheral levels.

3-Hydroxybutyric Acid↗
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↗
PubMed1979

Kinetics of ketone body metabolism in fasting humans.

The rates of production of total ketone bodies (acetoacetate + beta-hydroxybutyrate) were determined using an isotope tracer technique in 23 obese subjects submitted to a fast of variable duration (15 hr--23 days). Constant infusions of 14C-acetoacetate were used in most studies, but similar results were obtained with pulse injections of this tracer or with constant infusions of 14C-D(-)-beta-hydroxybutyrate. Blood concentration, production rate, and urinary elimination of total ketones rose during approximately the first 3 days of fast and plateaued thereafter at values amounting, respectively, to 7.09 +/- 0.32 mumole/ml, 1908 +/- 80 mumole/min and 167 +/- 14 mumole/min. The rates of ketogenesis are significantly higher than those usually reported in the literature. Ketonemia was an exponential function of production rate suggesting that tissue uptake becomes progressively saturated as inflow rate rises. The same type of relationship between concentration and inflow rate was observed in nine control overnight fasted obese subjects rendered hyperketonemic with infusions of variable amounts of unlabeled acetoacetate. The comparison between the fasted and the control subjects at ketone concentrations of 3--10 mumole/ml showed that on an average, starvation is associated with a 35% decrease in the metabolic clearance rate of ketones. These data suggest that fasting is associated with an impairment of mechanisms for utilizing ketones, this defect contributing to the hyperketonemia of food deprivation.

Acetoacetates↗
PubMed1978

Changes induced by exercise in rates of turnover and oxidation of ketone bodies in fasting man.

Seven normal subjects fasted for 3 days were exercised for 30 min on a bicycle ergometer at 60 +/- 30% (mean +/- SE) of their maximal aerobic capacity. Rates of transport and oxidation of ketone bodies were determined at rest and during exercise using a primed constant infusion of [14C]acetoacetate. During the initial 7.5 min of exercise, ketone concentration abruptly decreased (-19.4 +/- 3.1%; P less than 0.001) as the result of a 22.2 +/- 7.0% reduction (P less than 0.05) in ketone production rate (Ra) and a 30.4 +/- 7.5% increase (P less than 0.01) in the rate of uptake (Rd) of ketones. As work progressed, blood ketones continued to fall slowly until the 15th min of exercise and thereafter plateaued at a level which was 21.9 +/- 4.1% lower (P less than 0.005) than resting values. During this apparent new steady state, both Ra and Rd were below control values but tended to be equal and to return simultaneously to their preexercise level. The metabolic clearance rate was increased throughout the entire period of exercise, the rise being more marked during the initial 7.5 min (+40.7 +/- 7.5%; P less than 0.01) than at later periods (+19.0 +/- 7.4%; P less than 0.05). Exercise greatly enhanced ketone oxidation which became virtually complete; despite this, the %CO2 derived from ketones, which averaged 17.6 +/- 1.6% at rest, decreased to 10.1 +/- 0.6% (P less than 0.01) after 30 min of work. This indicates that even during the hyperketonemia of fasting, the increased energy needs related to exercise are met primarily by fuels other than ketones.

Acetoacetates↗
PubMed1978

Influence of short-term administration of clofibrate on insulin and glucagon response to protein ingestion in man.

Nine normal and two mildly hypertriglyceridemic subjects were treated with 2 g of clofibrate per day for 8 days. A significant fall in serum triglyceride and cholesterol concentration was observed from the second day onwards whereas free fatty acid levels were minimally affected. Insulin and glucagon responses to the ingestion of 200 g of meat were tested before and at the end of clofibrate treatment. Insulin response was significantly depressed (-28 +/- 12%) by the drug whereas glucagon response was enhanced but not to a significant degree. The ratio between insulin response and glucagon response was decreased by 38 +/- 11% (p less than 0.01) after treatment. A positive correlation was observed between the effects of clofibrate on basal triglyceride concentration on one hand and the effects of the drug on insulin and insulin/glucagon response to the protein meal on the other hand. Since insulin and glucagon are known to influence triglyceride metabolism, our data are compatible with the concept that the hypotriglyceridemic effect of clofibrate is--at least partly--related to the observed changes in insulin and glucagon reactivity.

Adult↗
PubMed1977

Lactic acidosis complicating diabetic ketosis in a patient with hyperthyroidism.

The present report describes a patient with insulin-dependent diabetes who developed simultaneously lactic acidosis and ketoacidosis following insulin deprivation. Administration of insulin at low doses rapidly corrected both ketosis and lactic acidosis. There had been neither circulatory collapse, nor phenformin intake, and hepatic function was normal. The development of lactic acidosis in this case was possibly precipitated by hyperthyroidism. A review of the literature indicates that lactic acidosis is a very rare complication of diabetic ketosis per se.

Acidosis↗
PubMed1976

Treatment of diabetic coma with small intravenous insulin boluses.

The clinical efficacy of small intravenous boluses of insulin in treating diabetic decompensation was tested in 23 patients presenting in either a ketoacidotic or a nonketotic diabetic coma. In addition to the usual ionic and fluid replacement, the patients received hourly intravenous injections of insulin 5 IU. This dose lowered blood glucose levels in all but two patients. In the patients who responded the percentage decrease in glycaemia was similar whatever the initial glucose concentration and averaged (+/-SE of mean) 50+/-3% in five hours. Close monitoring of insulin and glucose concentrations after intravenous insulin in three patients showed that despite the short half life of insulin the effect of the intravenous bolus lasted for about 60 minutes. The overall clinical effectiveness of this type of treatment is comparable to that of the other low-dose regimens. Owing to its simplicity, this technique of insulin administration seems most suitable for the routine treatment of diabetic coma.

Blood Glucose↗
PubMed1975

Inhibition of ketogenesis by ketone bodies in fasting humans.

Although there exists some indirect evidence that circulating ketone bodies might inhibit their own production rate, the direct demonstration of this homeostatic feed-back phenomenon is still lacking. The present work aims at demonstrating the operation of this control mechanism in human fasting ketosis. Six obese subjects, who fasted 2-23 days, were given a primed constant i.v. infusion of 3- 14C-acetoacetate for 4 hr. After a control period of 2 hr, unlabeled sodium acetoacetate was administered as a primed constant i.v. infusion at the rate of 0.688-1.960 mmol/min until the end of the study. During both periods, the rates of inflow of ketones were estimated from the specific activity of total ketones measured under near isotopic steady state conditions. During the control period, total ketone concentration amounted to 3.98-9.65 mumol/ml and production rates of total ketones ranged between 1.450 and 2.053 mmol/min. The levels of free fatty acids, glycerol, glucose, and insulin averaged respecitvely 1.30 mumol/ml, 0.11 mumol/ml, 74 mg/100 ml, and 5.2 muU/ml. The administration of exogenous ketones during the second phase of the study induced a 47%-92% increase in total ketone levels. During this period, the endogenous production of ketones (calculated as the difference between total inflow rate and acetoacetate infusion rate) amounted only to 67%-90% of control values. Among other factors, this inhibition of ketogenesis was probably partially related to the direct antilipolytic effect of infused ketones. Indeed, there was a concomitant fall in FFA and in glycerol levels averaging respectively 13.5% and 17.3%, without significant changes in peripheral insulin concentrations. Our results demonstrate that during fasting, circulating ketone bodies exert an inhibitory influence on the rate of ketogenesis. This mechanism might play an important role in preventing the development of uncontrolled hyperketonemia during starvation.

Acetoacetates↗
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↗