Effect of lipid oxidation on the regulation of glucose utilization in obese patients.

The effect of changes in lipid oxidation on glucose utilization (storage and oxidation) was studied in seven nondiabetic obese patients. They participated in three protocols in which: (1) Intralipid (to raise plasma FFA concentrations), (2) beta-pyridylcarbinol [a precursor of nicotinic acid, to lower plasma free fatty acids (FFA) concentrations], or (3) isotonic saline were infused over 2 h. Thereafter, these infusions were discontinued, and a 2-h euglycemic, hyperinsulinemic clamp was performed to measure glucose uptake. All studies were carried out in combination with indirect calorimetry to measure oxidative and nonoxidative glucose disposal (glucose storage). The high plasma FFA concentrations (1024 +/- 57 mumol/l) and lipid oxidation rates (1.1 +/- 0.1 mg/kg.min) found at the end of the Intralipid infusion and the low plasma FFA concentrations (264 +/- 26 mumol/l) and lipid oxidation rates (0.7 +/- 0.1 mg/kg.min) found at the end of the beta-pyridylcarbinol infusions resulted in significantly different rates of total and nonoxidative glucose disposal during the insulin clamp. The values were 2.6 +/- 0.6 mg/kg.min after Intralipid and 4.1 +/- 1.0 mg/kg.min after beta-pyridylcarbinol for total glucose disposal, and 0.4 +/- 0.4 and 1.6 +/- 0.8, respectively for nonoxidative glucose disposal. In conclusion, these observations show that changes in lipid oxidation rates preceding a glucose load influence glucose disposal and glycogen storage in obese subjects.

Correlations of glycogen synthase and phosphorylase activities with glycogen concentration in human muscle biopsies. Evidence for a double-feedback mechanism regulating glycogen synthesis and breakdown.

The purpose of this study was to verify in man the relationships of muscle glycogen synthase and phosphorylase activities with glycogen concentration that were reported in animal studies. The upper level of glycogen concentration in muscle is known to be tightly controlled, and glycogen concentration was reported to have an inhibitory effect on synthase activity and a stimulatory effect on phosphorylase activity. Glycogen synthase and phosphorylase activity and glycogen concentration were measured in muscle biopsies in a group of nine normal subjects after stimulating an increase of their muscle glycogen concentration through either an intravenous glucose-insulin infusion to stimulate glycogen synthesis, or an Intralipid (Vitrum, Stockholm, Sweden) infusion in the basal state to inhibit glycogen mobilization by favoring lipid oxidation at the expense of glucose oxidation. Phosphorylase activity increased from 71.3 +/- 21.0 to 152.8 +/- 20.0 nmol/min/mg protein (P < .005) after the glucose-insulin infusion. Phosphorylase activity was positively correlated with glycogen concentration (P = .005 and P = .0001) after the glucose-insulin and Intralipid infusions, respectively. Insulin-stimulated glycogen synthase activity was significantly negatively correlated with glycogen concentration at the end of the Intralipid infusion (P < .005). In conclusion, by demonstrating a negative correlation of glycogen concentration with glycogen synthase and a positive correlation with phosphorylase, this study might confirm in man the double-feedback mechanism by which changes in glycogen concentration regulate glycogen synthase and phosphorylase activities. It suggests that this mechanism might play an important role in the regulation of glucose storage.

Interaction of lipid and carbohydrate metabolism after infusions of lipids or of lipid lowering agents: lack of a direct relationship between free fatty acid concentrations and glucose disposal.

The present work was planned to study the effects of changes in lipid metabolism irrespective of FFA concentrations (FFA) on the regulation of oxidative and nonoxidative disposal of a glucose infusion during hyperinsulinaemia. Fifteen normal volunteers participated in the 3 protocols, in which 1) Intralipid 2) beta-pyridylcarbinol or 3) isotonic saline were infused during 2 hours. Thereafter, these infusions were discontinued and a two-hour euglycaemic hyperinsulinaemic clamp was performed. All three studies were carried out in combination with indirect calorimetry to measure glucose uptake, and oxidative and nonoxidative glucose disposal (corresponding essentially to glucose storage). Plasma FFA concentrations were 508 +/- 34, 601 +/- 43 and 546 +/- 45 mumol/l in the basal state during the Intralipid, beta-pyridylcarbinol and control protocols. It increased to 960 +/- 71 mumol/l after the Intralipid infusion, fell to 246 +/- 17 mumol/l after the beta-pyridylcarbinol infusion, vs 600 +/- 48 mumol/l in the control. At the end of the glucose-insulin clamp the values were low in the 3 protocols: 263 +/- 17, 233 +/- 19 and 204 +/- 14 mumol/l. Intralipid infusion prior to the clamp protocol induced a suppression of both insulin-mediated glucose uptake (4.91 +/- 0.46 (Intralipid) vs 6.83 +/- 0.63 mg.kg-1.min-1 (saline)) and storage (1.61 +/- 0.34 vs 2.99 +/- 0.53 mg.kg-1.min-1) while beta-pyridylcarbinol infusion induced an increased insulin-mediated glucose uptake (8.58 +/- 0.37 mg.kg-1.min-1) and in glucose storage (4.29 +/- 0.31 mg.kg-1.min-1) (p less than 0.5 vs Intralipid). These changes occurred even though FFA plasma concentrations were similar in the 3 experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Evolution of glucose induced thermogenesis in obese subjects with and without diabetes: a six-year follow-up study.

The thermogenic response to a 100 g oral glucose load was measured prospectively (by indirect calorimetry) in three groups of obese subjects: (1) normal glucose tolerance (n = 12, initial weight 86.4 +/- 3.9 kg, BMI 30.4 +/- 1.1 kg/m2; (2) impaired glucose tolerance (n = 8, initial weight 105.3 +/- 7.6 kg, body mass index (BMI) 37.6 +/- 2.9 kg/m2; (3) diabetes (n = 12), initial weight 102.1 +/- 5.3 kg, BMI 36.2 +/- 2.0 kg/m2). The thermogenic response to glucose averaged 6.8 +/- 1.1 and 7.0 +/- 1.0 per cent, in the two non-diabetic obese groups respectively, and was significantly lower in the obese diabetic group (3.1 +/- 0.8 per cent). With the evolution of obesity (i.e. 6 years later), the glucose-induced thermogenesis (GIT) was significantly reduced in the non-diabetic groups (P less than 0.05) to 4.1 +/- 0.8 and 3.0 +/- 1.1 per cent respectively, and was still blunted in the diabetic group (2.1 +/- 0.7 per cent). The decrease in GIT was accompanied by a reduction in glucose tolerance and insulin response with no change in fasting plasma insulin. These effects were observed despite the fact that the body weight of the subject did not change significantly over the 6-year period. It is concluded that the decrease in GIT which accompanies the worsening of glucose tolerance and the occurrence of diabetes is a mechanism which may contribute to maintain the obesity state by a reduction of energy expenditure.

Energy balance in elderly patients after surgery for a femoral neck fracture.

To study energy and protein balances in elderly patients after surgery, spontaneous energy and protein intake and resting energy expenditure (REE) were measured in 20 elderly female patients with a femoral neck fracture (mean age 81 +/- 4, SD, range 74-87 years; weight 53 +/- 8, range 42-68 kg) during a 5-6 day period following surgery. REE, measured over 20-40 min by indirect calorimetry using a ventilated canopy, averaged 0.98 +/- 0.15 kcal/min on day 3 and decreased to 0.93 +/- 0.15 kcal/min on day 8-9 postsurgery (p less than 0.02). REE was positively correlated with body weight (r = 0.69, p less than 0.005). Mean REE extrapolated to 24 hr (24-REE) was 1283 +/- 194 kcal/day. Mean daily food energy intake measured over the 5-day follow-up period was 1097 +/- 333 kcal/day and was positively correlated with 24-REE (r = 0.50, p less than 0.05). Daily energy balance was -235 +/- 351 kcal/day on day 3 (p less than 0.01 vs zero) and -13 +/- 392 kcal/day on day 8-9 postsurgery (NS vs zero) with a mean over the study period of -185 +/- 289 kcal/day (p less than 0.01 vs zero). When an extra 100 kcal/day was allowed for the energy cost of physical activity, mean daily energy balance over the 5-day study period was calculated to be -285 +/- 289 kcal/day (p less than 0.01 vs zero). Measurements of total 24-hr urinary nitrogen (N) excretion were obtained in a subgroup of 14 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired glucose tolerance and diabetes in obesity: a 6-year follow-up study of glucose metabolism.

To investigate the time course of glucose metabolism in obesity 33 patients (21 to 69 years old; body mass index [BMI], 25.7 to 53.3 kg/m2) with different degrees of glucose intolerance or diabetes who had been studied initially and 6 years later were submitted to the same 100-g oral glucose tolerance test (OGTT) with indirect calorimetry. From a group of 13 obese subjects with normal glucose tolerance (NGT), four developed impaired glucose tolerance (IGT); from a group of nine patients with IGT, three developed non-insulin-dependent diabetes mellitus (NIDDM); five of six obese NIDDM subjects with high insulin response developed NIDDM with low insulin response. Five patients had diabetes with hypoinsulinemia initially. As previously seen in a cross-sectional study, the 3-hour glucose storage measured by continuous indirect calorimetry remained unaltered in patients with IGT, whereas it decreased in NIDDM patients. A further decrease in glucose storage was observed with the lowering of the insulin response in the previously hyperinsulinemic diabetics. These results confirm cross-sectional studies that suggest successive phases in the evolution of obesity to diabetes: A, NGT; B, IGT (the hyperglycemia normalizing the glucose storage over 3 hours); C, diabetes with increased insulin response, where hyperglycemia does not correct the resistance to glucose storage anymore; and D, diabetes with low insulin response, with a low glucose storage and an elevated fasting and postload glycemia.

[The dual protective effect of fish oil in preventing coronary diseases]. / Le double effet protecteur des huiles de poisson dans la prévention des maladies coronariennes.

We studied the effect of incorporation of eicosapentaenoic and docosahexaenoic acid into the normal Western diet in nine human volunteers for 6 weeks. They received 1.5 g per day of omega 3-polyunsaturated fatty acids (W3-PUFA) for 3 weeks followed by 3 weeks with supplementation of 3.0 g per day. A control period of 3 weeks preceded PUFA supplementation. A significant effect on lipids was found in the total triglycerides and VLDL-triglyceride fractions (p less than 0.025). The ratio VLDL-triglyceride over HDL-cholesterol was also significantly diminished after 6 weeks of treatment (0.86 +/- 0.15 vs 1.01 +/- 0.19, p less than 0.02). Prolongation of the bleeding time was clearly demonstrated after 6 weeks of supplementation (10.6 +/- 1.3 min vs 6.2 +/- 0.6 min). Platelet aggregation stimulated by either ADP or collagen was significantly diminished after W3-PUFA supplementation (p less than 0.025 and p less than 0.005 after ADP and collagen respectively). The lag time of platelet aggregation was significantly prolonged (94 +/- 12 vs 56 +/- 2 sec, p less than 0.005) and the maximum speed reaction of the primary phase of the reaction was significantly diminished (1.3 +/- 0.2 vs 1.6 +/- 0.2 mm/sec, p less than 0.02). In conclusion, in the light of this study W3-PUFA supplementation leads to two different benefits in cardiovascular prevention. First, a significant diminution of total plasma triglyceride has been shown and, second, prolongation of the bleeding time and diminution of the platelet aggregation have been demonstrated.

Blunted glucose-induced thermogenesis in 'overweight' patients: a factor contributing to relapse of obesity.

Glucose-induced thermogenesis was studied in 12 overweight patients (9F and 3M) before (mean body weight +/- s.e.m. 83 +/- 2 kg) and after weight loss (68 +/- 2 kg), and in eight of the same patients following relapse of body weight gain (84 +/- 5 kg). Expressed as a percentage of the energy content of the 100 g oral glucose load, glucose-induced thermogenesis was lower in the overweight before weight loss (6.5 +/- 0.5 per cent, P less than 0.05), after weight loss (3.9 +/- 0.6 per cent, P less than 0.01) and after weight regain (6.3 +/- 0.9 per cent, P less than 0.05) than in a group of lean control subjects, matched for sex and age (8.3 +/- 0.5 per cent). Basal energy expenditure was lower after weight reduction than before (1.16 +/- 0.04 vs 1.41 +/- 0.08 kcal/min, P less than 0.01). In the formerly overweight patients, the combined effect of a decreased basal energy expenditure and an attenuation of glucose induced thermogenesis resulted in a postprandial energy expenditure which was markedly lower than in the overweight state (P less than 0.001). Following relapse of obesity, glucose-induced thermogenesis remained attenuated compared to control subjects. These results suggest that a lowered basal energy expenditure and a reduced glucose-induced thermogenesis contribute to the positive energy balance which results in relapse of body weight gain after cessation of a hypocaloric diet.