ACIDO CETOSE DIABETIQUE. ASPECTS PHYSIOPATHOLOGIQUES ET THERAPEUTIQUES RECENTS

Diabetic hyperketonemia results primarily from an excessive production of ketone bodies by the liver. Two factors ought to be present in order to induce hyperketogenesis: increased amounts of free fatty acids should be delivered to the liver from adipose tissue; and the liver should be in a ketogenic state. These two conditions are present in diabetic ketoacidosis owing to the simultaneous existence of insulinopenia and hyperglucagonemia. Under the influence of a low insulin/glucagon ratio, adipose tissue lipolysis is enhanced and intrahepatic fatty acid metabolism is switched towards β oxidation and ketogenesis, away from triglyceride synthesis. Thus, the bi hormonal insulin glucagon system is implicated in the regulation of ketone metabolism as it is in glucose homeostasis. Another recent step in our knowledge on ketone metabolism is the in vitro and in vivo demonstration of a reduced capacity of certain extrahepatic tissues to utilize ketones in diabetic ketosis. This defect probably results from insulin lack. Thus, both increased production and relative underutilization of ketones contribute to diabetic hyperketonemia. Finally, it has recently been suggested that several homeostatic feed back mechanisms involving ketone bodies could be operative in diabetic ketosis as they are in starvation ketosis. For instance, ketone bodies could inhibit mobilization of gluconeogenic aminoacids and thus contribute to protein sparing; according to their antilipolytic properties, ketones could also tend to restrain the development of diabetic ketosis. The classical treatment of diabetic coma with high doses of insulin has been recently questioned by several authors who showed that small doses (5-10 U/hr) can be equally effective. Another controversy has emerged regarding the mode of administration of insulin. Arguments are developed in this review in favor of the following therapeutic regimen: insulin should not be given by the i.m. route; insulin should be given i.v. either as a constant infusion or, more simply, as repeated i.v. boluses; and the dose of insulin should not be lower than 15-20 U/hr owing to the possible resistance to smaller doses, especially in infected patients. The possible mechanisms of cerebral edema occasionally seen during treatment of diabetic coma are discussed, and the factors which can be held responsible for an osmotic dysequilibrium between brain and plasma are analyzed. Finally, regarding the bicarbonate controversy, we emphasize the fact that possible drawbacks of alcali administration (cerebrospinal fluid acidosis, cerebral anoxia, hypokaliemic action) should not preclude its use in severe acidosis, which can markedly depress myocardial and respiratory functions.SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Monosaccharide esters: Clinically relevant?

SCOPUS: sh.jinfo:eu-repo/semantics/publishe

MECANISME DE L'HYPOGLYCEMIE INDUITE PAR LES CORPS CETONIQUES

SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Inhibition of Free Fatty Acid Oxidation by Acetoacetate in Normal Dogs

Abstract The rate of turnover and oxidation of plasma free fatty acids (FITA) was measured in 7 normal anaesthetized dogs infused at a constant rate with l‐14C‐palmitate for 5 h. After a control period, sustained hyperketonaemia was induced by infusing sodium aceto‐acetate (AA). This produced a fall in plasma FFA (33%) and in blood sugar (24%), without changes in immuno‐reactive insulin (IRI) concentrations. During the control period, the turnover rate of carbon of FFA averaged 131 μat./kg/min, 32% of which were oxidized, thus supplying 17.7% of the total CO2 production. At the end of the AA infusion, the mean turnover rate of FFA was reduced to 75μat.C/kg/min; since only 13.9 % of these were oxidized, the contribution of FFA to total CO2 production was reduced to 4.3%. In the light of previous work showing that ketone infusions also reduce the rate of turnover and oxidation of glucose in dogs, we conclude that, under appropriate experimental conditions, ketones may strongly reduce the role of FFA and glucose as sources of energy. Copyright © 1970, Wiley Blackwell. All rights reservedSCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

Kinetics of ketone body metabolism in fasting humans

The rates of production of total ketone bodies (acetoacetate + β-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(-)-β-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 μmole/ml 1908 ± 80 μmole/min and 167 ± 14 μmole/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 9 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 μmole/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.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Influence of norepinephrine, growth hormone and fasting on FFA mobilization and glucose metabolism in lean and obese subjects

The influence of norepinephrine (NE), human growth hormone (HGH) and fasting on FFA mobilization and carbohydrate metabolism has been studied in 47 obese females and 72 nonobese control subjects (35 females and 37 males). - Weight-related doses of NE infused for 2 h (0.1 γ/kg/min) induced a much greater rise in plasma FFA and blood glucose concentrations in obese than in normal subjects. With a fixed dose (10 γ/min for 2 h), FFA response was still significantly higher in the overweight than in the lean subjects, while glucose réponses were similar in both groups. Among the control subjects, males and females behaved similarily. - The plasma FFA rise observed in the 4 h following the i. v. injection of HGH (10 mg) was not statistically different in obese females, normal males and normal females. - These results suggest that human obese adipose tissue has no impaired sensitivity toward the lipolytic action of NE and HGH. - During fasting, obese, when compared with normal subjects, showed a smaller increase in plasma FFA level together with a smaller decrease in glucose flux. The possible relationship between these 2 anomalies is discussed, considering that glucose deficiency has a major role in regulating FFA mobilization during fasting. © 1968 Springer-Verlag.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prix Maurice Dérot 2003. A la recherche du "signal portal" chez l'homme.

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Maladies du métabolisme et de la nutrition

1e doctorat en médecineinfo:eu-repo/semantics/published

Importance of ketone bodies in endogenous fat transport

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Diabétologie et maladies du métabolisme et de la nutrition

7e édition 1995-1996/1MEDinfo:eu-repo/semantics/published