Double-blind controlled study on the effects of dietary diacylglycerol on postprandial serum and chylomicron triacylglycerol responses in healthy humans

OBJECTIVE: The effects of dietary diacylglycerol (DG) on postprandial lipemia in healthy humans were investigated. METHODS: Forty normolipidemic male volunteers ingested fat emulsions containing either DG oil or triacylglycerol (TG) oil, at different doses: 10 g (n = 13), 20 g (n = 10) and 44 g (n = 17). Two test emulsions were given at seven-days intervals in random order. Fatty acid compositions of the test oils had been adjusted to be equal. Fasting and postprandial serum lipid concentrations in each group and plasma lipoprotein lipids in the 20 g-fat ingestion group were measured during the postprandial intervals. RESULTS: When DG emulsion was ingested, serum TG concentrations were significantly lower (p < 0.05) in the late postprandial phase, i.e., 4 hours, 6 hours as compared to the TG emulsion. The magnitude of postprandial lipemia (the area bounded by the curve above the fasting concentration) after ingestion of 44 g-DG emulsion was significantly less than that of 44 g-TG emulsion (6.54 +/- 5.12 and 8.45 +/- 7.54 mmol x h/L, mean +/- SD, respectively). Chylomicron TG, cholesterol, and phospholipid concentrations at 4 hours after ingestion of DG emulsion were significantly lower (p < 0.05) than those after the ingestion of TG emulsion at the same time point. No marked differences were observed for VLDL, LDL and HDL lipids between the test emulsions. CONCLUSION: In the usual range of fat intake (10-44 g), postprandial response after ingestion of DG emulsion was significantly less than that after ingestion of TG emulsion in healthy human subjects.     

Short-term effects of fat emulsion on serum lipids in postoperative patients

The effect of short-term infusion of intravenous fat on serum lipids was assessed in 23 patients who had elective cancer operations and were given 20% Intralipid for 5 days postoperatively as part of a standard total parenteral nutrition regimen. Serum lipids were measured prior to, during and after the 5-day infusion period. The percentage of cholesterol as high-density lipoproteins (HDL) fell from a mean preinfusion value of 34.7 +/- 2.8 to 27.9 +/- 2.5 (p less than 0.05), while the percentage of cholesterol as low-density lipoproteins (LDL) increased from 40.7 +/- 2.2 to 46.8 +/- 3.4 (p less than 0.05). Serum triglycerides fell significantly (p less than 0.01) from 106.2 +/- 13.7 mg/dl to 64.6 +/- 8.8 mg/dl at 3 days, being 85.3 +/- 3.7 mg/dl at 5 days. No significant change in percent cholesterol as very low-density lipoproteins (VLDL), or levels of serum total cholesterol or phospholipids occurred. Lipoprotein X was detectable in six patients after 5 days. To study triglyceride clearance 1.7 g/kg of fat emulsion was infused over 8 hr and serial blood samples obtained. Within 3 hr of stopping the fat infusion, triglyceride levels had fallen to preinfusion values.     

Physical stability of 20% lipid injectable emulsions via simulated syringe infusion: effects of glass vs plastic product packaging

BACKGROUND: The United States Pharmacopeia (USP) has proposed large-globule-size limits to ensure the physical stability of lipid injectable emulsions, expressed as the percent fat >5 microm, or PFAT(5), not exceeding 0.05%. Visibly obvious phase separation as free oil has been shown to occur in some samples if PFAT(5) is >0.4%. We recently found that lipids, newly packaged in plastic (P), exceed the proposed USP limits and seem to produce less stable total nutrient admixtures compared with those made from conventional glass (G), which do meet proposed USP standards. We tested the possible stability differences between 20% lipid injectable emulsions in either P or G in a simulated neonatal syringe infusion study. METHODS: Eighteen individual syringes were prepared from each 20% lipid injectable emulsion product (n = 36) and attached to a syringe pump set at an infusion rate of 0.5 mL/hour. The starting PFAT(5) levels were measured at time 0 and after 24 hours of infusion, using a laser-based light obscuration technique as described by the USP Chapter <729>. The data were assessed by a 2-way analysis of variance (ANOVA) with Container (G vs P) and Time as the independent variables and PFAT as the dependent variable. RESULTS: At time 0, the starting PFAT(5) level for lipids packaged in G was 0.006% +/- 0.001% vs 0.162% +/- 0.026% for P, whereas at the end of the infusion they were 0.013% +/- 0.003% and 0.328% +/- 0.046%, respectively. Significant differences were noted overall between groups for Container, Time, and Container-Time interaction (all p < .001). Bonferroni tests showed significant differences in PFAT(5) levels between Containers at time 0 (T-0; p < .001) and T-0 vs T-24 for P-based lipids (p < .001), whereas no such differences were noted for Time for the G-based lipids. Similar results were noted for PFAT(10) levels. CONCLUSIONS: We confirm that presently available lipid injectable emulsions packaged in newly introduced plastic containers exceed the proposed USP <729> PFAT(5) limits and subsequently become significantly less stable during a simulated syringe-based infusion. Although modest growth (p = NS) in large-diameter fat globules was observed for the glass-based lipids, they remained within proposed USP globule size limits throughout the study. Glass-based lipids seem to be a more stable dosage form and potentially a safer way to deliver lipids via syringe infusion to critically ill neonates.     

Protein metabolism in adult patients with phenylketonuria

OBJECTIVE: Protein intake recommendations in phenylketonuria (PKU) are frequently the subject of discussion. For healthy adults, the recommended daily allowance (RDA) is 0.8 g.kg(-1).d(-1), which is generally lower than that observed in the general Western population. We investigated whether whole-body protein metabolism in patients with PKU is comparable to that of healthy controls at a RDA rate of protein intake. METHODS: Six adult patients with well-controlled PKU and six healthy subjects of comparable age, height, and weight were studied using a primed continuous infusion of [1-(13)C]-valine for 8 h after an overnight fast before and during frequent meals. Normal protein was given to controls, whereas patients with PKU received a combination of an amino acid mixture and natural protein. RESULTS: No significant differences were observed between patients with PKU and controls in preprandial and prandial rates of valine appearance and oxidation and protein breakdown, protein synthesis, and net protein balance. Feeding resulted in a significant (P < 0.01) decrease in protein breakdown (PKU: 94 +/- 15 micromol.kg(-1).h(-1) preprandial to 49 +/- 10 micromol.kg(-1).h(-1) prandial; controls: 97 +/- 10 micromol.kg(-1).h(-1) preprandial to 55 +/- 10 micromol.kg(-1).h(-1) prandial), whereas no effects were observed in protein synthesis (PKU: 77 +/- 10 micromol.kg(-1).h(-1) preprandial to 73 +/- 7 micromol.kg(-1).h(-1) prandial; controls: 76 +/- 8 micromol.kg(-1).h(-1) preprandial to 71 +/- 5 micromol.kg(-1).h(-1) prandial). Net protein balance increased from negative prandial to positive preprandial values (PKU: -17 +/- 6 micromol.kg(-1).h(-1) preprandial to +23 +/- 8 micromol.kg(-1).h(-1) prandial; controls: -21 +/- 4 micromol.kg(-1).h(-1) preprandial to +16 +/- 9 micromol.kg(-1).h(-1) prandial). CONCLUSION: Whole-body protein metabolism in adult patients with PKU is fully comparable to that in healthy controls at the RDA level of protein intake.     

25-Hydroxyvitamin D and 1,25-dihydroxyvitamin D of D2 and D3 origin in maternal and umbilical cord serum after vitamin D2 supplementation in human pregnancy

Serum concentrations of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] of vitamin D2 and D3 origin were determined separately in 10 women before vitamin intake in early pregnancy, and repeated in maternal and cord serum obtained at delivery after 20 to 30 wk of vitamin D2 supplementation in a dose of 400 IU/day. Before supplementation 25-OHD2 and 1,25-(OH)D2D2 were present in just traceable or nondetectable concentrations, but the levels increased in all to a mean +/- 1 SD of 7.3 +/- 3.7 ng/ml and 37.2 +/- 18.1 pg/ml, respectively (p less than 0.0025), by the time of delivery. At delivery the total 25-OHD and 1,25-(OH)2D levels were always lower in the cord than in the maternal serum (30.7 +/- 14.2 versus 20.1 +/- 9.1 ng/ml, and 90.1 +/- 31.2 versus 37.3 +/- 11.6 pg/ml, p less than 0.0025). The paired concentrations of 25-OHD were closely related (r = 0.89, p less than 0.0005), while the association for 1,25-(OH)2D was not statistically significant (r = 0.53, p less than .01). The 25-OHD of D2 and D3 origin accounted for a similar proportion of the total 25-OHD in the maternal and cord serum (ratio of 25-OHD2 to 25-OHD3: 0.40 +/- 0.28 versus 0.45 +/- 0.29, p = NS), as did the respective 1,25-(OH)2D metabolites [ratio of 1,25-(OH)2D2 to 1,25-(OH)2D3: 0.73 +/- 0.35 versus 0.90 +/- 0.50, p = NS].(ABSTRACT TRUNCATED AT 250 WORDS)     

Intestinal consumption of intravenously administered fuels

Total parenteral nutrition has been extensively used to feed patients with a variety of gastrointestinal diseases, but little attention has focused on the nutritional requirements of the gut. To investigate intestinal consumption of intravenously administered nutrients, uptake of three principal fuels determined from in vitro studies was quantitated in seven awake, unrestrained dogs. Portal blood flow was measured by a dye dilution technique and, simultaneously, substrate samples were obtained from chronic indwelling arterial and portal venous catheters. Studies were performed during a postabsorptive basal period and during separate infusions of glutamine (0.10 mmol/kg X min), glucose (0.10 mmol/kg X min), and beta-hydroxybutyrate, (0.40 mmol/kg X min). During the basal period there was a significant arterial-portal vein gradient for glucose (144 +/- 26 mumol/liter) and glutamine (49 +/- 11 mumol/liter). These substances were taken up by the gut at rates of 4.11 +/- 1.23 and 1.43 +/- 0.19 mumol/kg X min, respectively. No significant uptake of beta-hydroxybutyrate was determined in the basal studies (0.27 +/- 0.10 mumol/kg X min). During substrate infusion, gut glucose uptake was unchanged (2.68 +/- 1.67 mumol/kg X min, NS), but consumption of glutamine (4.60 +/- 0.66 mumol/kg X min, p less than 0.001) and beta-hydroxybutyrate (4.33 +/- 0.71 mumol/kg X min, p less than 0.001) increased significantly. During parenteral feedings in patients with gastrointestinal disorders, circulating levels of beta-hydroxybutyrate and glutamine are often low, and glutamine is absent from standard amino acid solutions. Current parenteral formulation may not provide appropriate fuels for the gastrointestinal tract.     

Postprandial effects of dietary trans fatty acids on apolipoprotein(a) and cholesteryl ester transfer

BACKGROUND: The consumption of trans fatty acids adversely affects fasting plasma lipoprotein concentrations. OBJECTIVE: This study aimed to investigate whether postprandial lipoprotein metabolism is affected by the consumption of trans fatty acids. DESIGN: In a randomized crossover study, 19 healthy men consumed fatty meals that were identical except that 10% of energy was provided as trans 18:1 acids in the trans meal and as oleic acid in the cis meal. RESULTS: The meals induced similar responses in plasma lipids. Cholesteryl ester transfer (CET) was activated after consumption of both meals (P < 0.0001); however, it was 28% higher after the trans meal than after the cis meal (280 +/- 129 compared with 219 +/- 116 nmol cholesteryl ester/mL plasma * 6 h; time x diet interaction: P < 0.0001). Plasma apolipoprotein(a) [apo(a)] concentrations remained constant; however, triacylglycerol-rich lipoproteins formed 4 h after ingestion of the trans meal contained a higher concentration of apo(a) than did those formed after ingestion of the cis meal (48.9 +/- 6.6 compared with 39.6 +/- 5.4 U/L; P < 0.02). The change in CET and in the proportion of plasma apo(a) in the triacylglycerol-rich lipoprotein fractions correlated with indexes of alimentary lipemia. CONCLUSIONS: Consumption of meals high in trans fatty acids results in higher CET and postprandial lipoprotein concentrations enriched in apo(a) than does consumption of meals free of trans fatty acids. This study highlights the importance of double-bond configuration in determining postprandial lipoprotein composition.     

Almonds decrease postprandial glycemia, insulinemia, and oxidative damage in healthy individuals

Strategies that decrease postprandial glucose excursions, including digestive enzyme inhibition, and low glycemic index diets result in lower diabetes incidence and coronary heart disease (CHD) risk, possibly through lower postprandial oxidative damage to lipids and proteins. We therefore assessed the effect of decreasing postprandial glucose excursions on measures of oxidative damage. Fifteen healthy subjects ate 2 bread control meals and 3 test meals: almonds and bread; parboiled rice; and instant mashed potatoes, balanced in carbohydrate, fat, and protein, using butter and cheese. We obtained blood samples at baseline and for 4 h postprandially. Glycemic indices for the rice (38 +/- 6) and almond meals (55 +/- 7) were less than for the potato meal (94 +/- 11) (P < 0.003), as were the postprandial areas under the insulin concentration time curve (P < 0.001). No postmeal treatment differences were seen in total antioxidant capacity. However, the serum protein thiol concentration increased following the almond meal (15 +/- 14 mmol/L), indicating less oxidative protein damage, and decreased after the control bread, rice, and potato meals (-10 +/- 8 mmol/L), when data from these 3 meals were pooled (P = 0.021). The change in protein thiols was also negatively related to the postprandial incremental peak glucose (r = -0.29, n = 60 observations, P = 0.026) and peak insulin responses (r = -0.26, n = 60 observations, P = 0.046). Therefore, lowering postprandial glucose excursions may decrease the risk of oxidative damage to proteins. Almonds are likely to lower this risk by decreasing the glycemic excursion and by providing antioxidants. These actions may relate to mechanisms by which nuts are associated with a decreased risk of CHD.     

Intravenous fat emulsion acutely suppresses neutrophil chemiluminescence

The immediate effect of intravenous fat emulsion on neutrophil oxidant release was studied. Opsonized nonencapsulated S. aureus was used to stimulate neutrophil activity. Luminol enhanced chemiluminescence was followed over 15 min and recorded as peak output (P; mV), integral under the curve (I; V-sec) and rate of increase (R; mV/sec). Eighteen chronically ill patients receiving glucose based total parenteral nutrition were studied before and after a 4- to 6-hr test infusion of 500 ml of 10% fat emulsion. P decreased from 719 +/- 46 to 461 +/- 42 mV (p less than 0.001), I decreased from 169 +/- 17 to 111 +/- 12 V-sec (p less than 0.001) and R decreased from 6.9 +/- 1.0 to 4.0 +/- 0.6 mV/sec (p less than 0.001). Preincubation of normal whole blood with fat emulsion in vitro did not adversely affect chemiluminescence (11 studies), nor did incubation of normal neutrophils with patient postinfusion plasma (10 studies). We conclude that fat emulsion infusion acutely suppresses neutrophil chemiluminescence. The suppression is not a direct effect of the fat emulsion per se and is not due to inhibitory substances in the plasma following infusion.     

Ethnic differences in the responsiveness of adipocyte lipolytic activity to insulin

OBJECTIVE: The goal of this study was to quantify differences in lipid metabolism and insulin sensitivity in black and white subjects to explain ethnic clinicopathological differences in type 2 diabetes. RESEARCH METHODS AND PROCEDURES: The in vitro lipolytic activity of adipocytes isolated from obese black and white women was measured in the presence of insulin and isoproterenol. Insulin resistance was assessed in vivo using the euglycemic hyperinsulinemic clamp technique. RESULTS: Fasting plasma levels of insulin and nonesterified fatty acid (NEFA) in black and white women were 67 +/- 5 pM vs. 152 +/- 20 pM (p < 0.01) and 863 +/- 93 microM vs. 412 +/- 34 microM (p < 0.01), respectively. Euglycemic hyperinsulinemic clamp studies showed that obese black subjects were more insulin-resistant than their white counterparts (glucose infusion rates: 1.3 +/- 0.2 vs. 2.2 +/- 0.3 mg/kg per min; p < 0.05). Isolated adipocytes from white women were more responsive to insulin than those from black women with 0.7 nM insulin causing a 55 +/- 4% inhibition of isoproterenol-stimulated lipolysis compared with 27 +/- 10% in black women (p < 0.05). DISCUSSION: The low responsiveness of adipocyte lipolytic activity to insulin in black women in the presence of a relative insulinopenia may account for the high plasma NEFA levels seen in these women, which may, in turn, account for their higher in vivo insulin resistance. High NEFA levels may also contribute to the low insulin secretory activity observed in the obese black females. These data suggest that the pathogenesis of insulin resistance and type 2 diabetes within the black obese community is strongly influenced by their adipocyte metabolism.     

Lipoprotein changes when a reported diet is tested in distance runners

Diet records previously recorded by distance runners indicated that runners consumed considerably more calories, largely as carbohydrates, than did inactive controls. We examined the effect of this reported diet on the serum lipids and lipoproteins of active men. Ten male runners ran 16 km daily and were provided defined diets containing 3587 +/- 233 kcal/day (mean +/- SD) and composed of 53% (486 +/- 31 g/day) carbohydrates, 15% (134 +/- 8 g/day) protein, and 32% (131 +/- 9 g/day) fat for 21 days. Serum samples were obtained before and during the diet period. Low-density lipoprotein cholesterol fell 5 +/- 12 mg/dl before (p = NS) and 15 +/- 13 mg/dl (p less than 0.01) during the diet. High-density lipoprotein (HDL) cholesterol did not change during the week before, but decreased 6 +/- 2 mg/dl (p less than 0.001) while subjects consumed the defined diet. This decrease was due to a 7 +/- 6 mg/dl (p less than 0.01) fall in HDL2 cholesterol (1.063 less than rho less than 1.125 g/ml). Alterations in HDL cholesterol were accompanied by reductions in apo A-1, the major HDL apoprotein. After 14 days on the defined diet no additional changes in serum lipids occurred. Lipoprotein changes of this magnitude were unexpected and suggest that the diet diaries used to design the defined diet were unreliable or that factors not accounted for in diet records had significant effects in these subjects.     

Central but not peripheral glucocorticoid infusion in adrenalectomized male rats increases basal and substrate-induced insulinemia through a parasympathetic pathway

OBJECTIVE: Glucocorticoids acting through the central nervous system are postulated to play a role in the hyperinsulinemia and increased adiposity of obesity. We investigated the role of parasympathetic activation in glucocorticoid-induced hyperinsulinemia. RESEARCH METHODS AND PROCEDURES: Plasma pancreatic polypeptide (PP) levels were used as an index of parasympathetic output. Insulinemia and plasma PP levels were measured basally and after intravenous glucose injection (300 mg/kg) in adrenalectomized male rats infused with dexamethasone (7.5 microg/kg per day) intracerebroventricularly (ICV) or subcutaneously (SC) for 3 to 6 days in the presence or absence of acute atropine blockade (1.0 mg/kg). Food intake was controlled between groups. RESULTS: Compared with normal rats, adrenalectomy decreased white adipose tissue depot weights and leptinemia, and these were restored to normal values by ICV but not SC dexamethasone infusion. Adrenalectomy significantly reduced insulinemia below normal levels, which was restored by SC dexamethasone replacement. However, ICV dexamethasone replacement increased insulinemia of adrenalectomized rats to levels higher than normal control values (basal, 500 +/- 40 pM vs. 280 +/- 40 pM; 1-minute postglucose, 2500 +/- 180 pM vs. 1240 +/- 260 pM; p < 0.0001) and increased plasma PP levels, which were correlated with insulinemia. Atropine significantly reduced plasma insulin and PP to levels similar to normal controls but had no effect in any other group. DISCUSSION: These data show that glucocorticoids act within the brain to increase insulinemia, most likely through activation of parasympathetic efferent fibers. Such an affect would contribute to the adipogenic effects of central glucocorticoids.     

小儿单纯性肥胖症胰腺内分泌功能研究

目的:探讨单纯性肥胖(SO)患儿胰腺内分泌功能。方法:采用放射免疫分析法测定SO患儿空腹和摄入液体实验餐60 min时外周血胰岛素、胰高血糖素和生长抑素(SS)水平。结果:与对照组比较,SO患儿空腹时血中胰岛素、胰高血糖素明显升高(P<0.01),而SS水平无明显差异(P>0.05),其餐后血中胰岛素、胰高血糖素也明显升高(P<0.01),而SS水平则明显降低(P<0.01);空腹与餐后比较,SO患儿餐后血中胰岛素水平明显升高(P<0.01),胰高血糖素及SS水平无明显变化(P>0.05),对照组则血中胰岛素和SS水平升高(P<0.01),胰高血糖素水平无明显变化(P>0.05)。结论:SO患儿存在明显的胰腺内分泌功能紊乱,应引起高度重视。     

Metabolic effects of a low-glycemic-index diet

Six healthy male volunteers underwent 2-wk metabolically controlled high-glycemic-index (GI) and low-GI diets in random order. Over the low-GI diet significant reductions were seen in serum fructosamine (7.0 +/- 1.0%, p less than 0.01), 12-h blood glucose profile (37 +/- 7%, p less than 0.01), and total serum cholesterol (15 +/- 3%, p less than 0.01). As a measure of insulin secretion, 24-h urinary C-peptide levels were 32 +/- 10% lower (p less than 0.05) after the low-GI than after the high-GI diet. Lower C-peptide levels were maintained after a standard carbohydrate challenge after the low-GI diet despite higher blood glucose levels. Differences in blood glucose were not seen after a 5-g intravenous glucose challenge. These results are of interest with respect to the effect that prolonged postprandial reductions in nutrient fluxes and insulin secretion may have on carbohydrate and lipid metabolism and renal function.     

Optimal levels of arginine in maintenance intravenous hyperalimentation

The optimal levels of arginine (Arg) for growth and immunity were studied in mildly depleted, noninjured rats maintained on intravenous hyperalimentation. Three groups of S-D rats (eight/group, weighing 275-300 g) underwent catheter insertion, 1 day of fasting, and then 7 days of intravenous hyperalimentation consisting of 20% dextrose, adequate minerals and vitamins, and three amino acid regimens: (1) FreAmine II (1.55 g Arg/liter); (2) FreAmine III (4.05 g Arg/liter); (3) experimental (7.5 g Arg/liter). The increase in arginine levels was achieved by lowering the glycine levels. There were no differences among the groups in terms of body weight gain (6.9 vs 8.3 vs 10.0 g) or in cumulative N balance (574 vs 660 vs 642 mg). Liver, spleen, and adrenal weights did not differ. Thymus weight was greater in groups B and C: (A) 345 +/- 27 mg vs (B) 445 +/- 34 mg, p less than 0.05, vs (C) 438 +/- 26 mg, p less than 0.05) as were the total number of lymphocytes/thymus (X 10(-9) (A) 0.93 +/- 0.12 vs (B) 1.37 +/- 0.18, p less than 0.05, vs (C) 1.46 +/- 0.15, p less than 0.05). Mitogen-induced thymocyte blastogenesis (cpm) was greatest in group C in response to phytohemagglutinin: (A) 9.558 +/- 3,799 vs (B) 20,088 +/- 5,890, NS, vs (C) 37,234 +/- 6,209, p less than 0.01 vs A and p less than 0.05 vs B) and Concanavalin A: (A) 71,035 +/- 15,228 vs (B) 111,734 +/- 15,021, NS, vs (C) 172,967 +/- 19,861, p less than 0.01 vs A and p less than 0.05 vs B). In the intravenous hyperalimentation-maintained noninjured rat ARG concentrations more than 1.55 g/liter do not enhance N retention or growth. Larger doses of ARG have strong thymic immunostimulatory effects without any toxicity or growth reduction.     

Effects of dinner composition on postprandial macronutrient oxidation in prepubertal girls

OBJECTIVE: To see whether a fat-rich (50%) evening meal promoted fat oxidation and a different spontaneous food intake on the following day at breakfast than a meal with a lower fat content (20%) in 10 prepubertal obese girls. RESEARCH METHODS AND PROCEDURES: The postabsorptive and postprandial (10.5 hours) energy expenditure after a low-fat (LF) (20% fat, 68% carbohydrate, 12% protein) and an isocaloric (2.1 MJ) and isoproteic high-fat (HF; 50% fat, 38% carbohydrate, 12% protein) meal were measured by indirect calorimetry. RESULTS: Fat oxidation was not significantly different after the two meals [LF, 31 +/- 9 vs. HF, 35 +/- 9 g/10.5 hours, p = not significant (NS)]. The girls oxidized 1.8 +/- 0.9 times more fat than that ingested (11.1 grams) with the LF meal vs. 0.3 +/- 0.3 times more fat than that ingested (27.1 grams) with the HF meal (p < 0.001). Carbohydrate oxidation was significantly higher after an LF than an HF meal (39 +/- 12 vs. 29 +/- 9 g/10.5 hours, p < 0,05). At breakfast, the girls spontaneously ingested a similar amount of energy (1.5 +/- 0.7 vs. 1.5 +/- 0.6 MJ, p = NS) and macronutrient proportions (fat, 23% vs. 26%, p = NS; protein, 9% vs. 10%; carbohydrate, 68% vs. 64%,) independently of their having eaten an HF or an LF dinner. DISCUSSION: An HF dinner did not stimulate fat oxidation, and no compensatory effect in spontaneous food intake was observed during breakfast the following morning. Cumulated total fat oxidation after dinner was higher than total fat ingested at dinner, but a much larger negative fat balance was observed after the LF meal. Spontaneous energy and nutrient intakes at breakfast were similar after LF and HF isocaloric, isoproteic dinners. This study points out the lack of sensitivity of short-term fat balance to subsequently readjust fat intake and emphasizes the importance of an LF meal to avoid transient positive fat imbalance.     

Maintenance of skeletal muscle intracellular glutamine during standard surgical trauma

Skeletal muscle glutamine (GLN) concentration falls following injury and infection. In an attempt to prevent this decline and to characterize its influence on the efflux of amino acid (AA) from skeletal muscle, we administered varying quantities of AA (0,2, and 4 g/kg X day) as saline or AA solutions with or without GLN enrichment to 22 postoperative dogs. Plasma and muscle AA were determined before and 24 hr after standard laparotomy. Hindquarter AA efflux was measured at 6 and 24 hr. Skeletal muscle nitrogen declined in saline controls (69.8 +/- 8.5 vs 52.8 +/- 8.4 mmol/liter; p less than 0.01), largely due to the fall in intracellular GLN (21.48 +/- 3.21 vs 15.86 +/- 3.80; p less than 0.05). Similar alterations were seen in the animals receiving 2 g/kg. However, both intracellular nitrogen and GLN were maintained in animals receiving 4 g/kg, whether the AA solutions contained GLN or not (skeletal muscle nitrogen before 64.3 +/- 8.6 mmol/l vs 65.4 +/- 7.0 after, GLN 19.2 +/- 3.4 vs 19.9 +/- 3.0). Hindquarter AA efflux was reduced in those animals at 6 hr compared with saline-treated animals (-6.52 +/- 1.8 and -7.70 +/- 5.90 vs -19.05 +/- 4.06 mumol/kg X min; p less than 0.05). Intracellular GLN can be maintained during operative stress with adequate nitrogen infusion. Replacing 50% of the balanced AA solution with GLN resulted in equally effective maintenance of intracellular GLN levels and a comparable reduction in skeletal muscle AA efflux. Preservation of normal intracellular GLN levels with adequate AA nutrition may be essential for the conservation of muscle protein.     

The effect of combination treatment with acarbose and glibenclamide on postprandial glucose and insulin profiles: additive blood glucose lowering effect and decreased hypoglycaemia

This study compared the effects of acarbose plus glibenclamide combination therapy with acarbose or glibenclamide treatment alone on postprandial blood glucose, serum insulin and C-peptide levels, and the tendency to develop hypoglycaemia. A total of 84 patients with Type 2 diabetes (fasting blood glucose: 120-180 mg/dl; postprandial blood glucose: 140-240 mg/dl) was included in this two-centre, double-blind, double-dummy, placebo-controlled study. Patients were randomised to one of 4 treatment groups: acarbose (100 mg); glibenclamide (3.5 mg); acarbose plus glibenclamide; or placebo. Treatment was administered before a standard breakfast, and fasting (07.30 h, 08.00 h) and postprandial (09.00, 10.00, 11.00, 12.00 h) blood glucose, serum insulin and C-peptide levels were determined. Acarbose plus glibenclamide treatment significantly reduced the mean increase in postprandial blood glucose levels (23.7+/-17.3 mg/dl) compared with either acarbose (58.4+/-31.6 mg/dl), glibenclamide (56.9+/-42.8 mg/dl) or placebo (101.6+/-49.2 mg/dl) (p<0.05 for all). Serum insulin levels (mean AUC(7.30-12 h)) observed with acarbose plus glibenclamide combination therapy were significantly lower than those observed with glibenclamide monotherapy (243.5+/-161.1 vs 383.4+/-215.8 hr x microU/ml; p=0.02), and comparable with the values seen with placebo (226.0+/-166.6 hr x microU/ml), suggesting that acarbose modifies the insulin secretion induced by glibenclamide. Glibenclamide monotherapy resulted in a significantly higher rate of decrease in blood glucose level than with acarbose plus glibenclamide (71.8+/-29.9 vs 46.2+/-18.0 mg/dl x h(-1); p=0.0003), and blood glucose levels at 11.00 h were also markedly lower with glibenclamide (84.4+/-29 mg/dl) than acarbose plus glibenclamide (102.0+/-41 mg/dl), suggesting a reduced tendency for hypoglycaemic episodes with acarbose plus glibenclamide than with glibenclamide alone. In all, 6 (29%) hypoglycaemic episodes occurred with glibenclamide, 2 (10%) with acarbose plus glibenclamide and none with acarbose. Acarbose plus glibenclamide combination therapy results in an additive glucose lowering effect and reduced risk for hypoglycaemia. Acarbose modifies the insulin secretion induced by glibenclamide, which explains the lower risk of hypoglycaemia compared with glibenclamide monotherapy.     

Thermogenesis from intravenous medium-chain triglycerides

Eighteen hospitalized patients dependent on total parenteral nutrition (TPN) were randomly enrolled into a prospective study comparing intravenous long-chain triglycerides (LCT) with a physical mixture of 75% medium-chain triglycerides (MCT) and 25% LCT. The TPN was given continuously as amino acids and glucose over 5 days with the respective lipid emulsion given intermittently during each day for 10 hr. Indirect calorimetry was measured on each patient before the lipid emulsion was administered in the morning and again 10 hr later near the end of the lipid infusion, on days 1, 3, and 5. Resting energy expenditure, VO2, VCO2, and calculated fat oxidation were shown to increase during MCT infusion but not during LCT administration, (resting energy expenditure 899 +/- 37 to 1085 +/- 40, compared with 978 +/- 23 to 976 +/- 39, kcal/m2 body surface area [BSA]/day, respectively, p less than 0.0002; VO2: 129.9 +/- 5.2 to 157.2 +/- 5.9, compared with 140.9 +/- 3.6 to 141.2 +/- 5.9 ml O2/min/m2 BSA, respectively, p less than 0.0005; and VCO2: 110.7 +/- 4.4 to 127.5 +/- 4.3, compared with 118.3 +/- 2.8 to 118.0 +/- 5.3, ml CO2/min/m2 BSA, respectively, p less than 0.0076; calculated fat oxidation 10.7 +/- 1.5 to 19.3 +/- 2.4, compared with 20.0 +/- 2.7 to 20.0 +/- 3.6, kcal/m2 BSA/hr, respectively, p less than 0.014). Respiratory quotient tended to fall with lipid infusion but did not change statistically. Body temperatures were unaltered by either fat infusion. It is concluded that TPN consisting of MCT causes an increased thermogenesis, most likely through increased fat oxidation, reflective of MCT's property as an obligate fuel. The increased thermogenesis occurs without an increase in body temperature.     

Metabolic consequences of the alpha-glucosidase inhibitor BAY-M-1099 given to nondiabetic and diabetic rats fed a high-carbohydrate diet

The effect of a new alpha-glucosidase inhibitor BAY-M-1099 on postprandial glucose levels in nondiabetic and diabetic rats after sucrose loading was studied. Evaluation was also made of the metabolic consequences of the addition of BAY-M-1099 to a high-carbohydrate diet consisting of equal quantities of wheat starch and sucrose (Diet A). This drug significantly reduced (p less than 0.05) postprandial glucose levels in nondiabetic and diabetic rats after sucrose loading. BAY-M-1099 led to a significant reduction in urinary glucose loss (177.8 +/- 54.2 vs 98.9 +/- 35.6 mmol/L) and in postprandial plasma glucose levels in diabetic rats fed diet A. Addition of BAY-M-1099 to the diet of nondiabetic rats significantly (p less than 0.05) decreased the postprandial plasma glucose level at 45, 90, 180, and 225 min after a meal test. Addition of BAY-M-1099 to a diet containing starch plus sucrose led to reduced glycosuria and serum glucose levels and may have potential benefit in the management of diabetes mellitus.