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M Krempf

Publications and source records attributed to M Krempf.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Skin and osteoarticular infections of the diabetic foot. Role of infection].

A MAJOR PROBLEM: Two-thirds of all amputations involve infection. Infection is favored by dysfunction of the antibacterial defense systems due to high blood glucose and vascular disorders. DIAGNOSIS: General signs of infection are usually not found. A careful exploration is required to rule out or confirm osteitis in order to guide surgery and plan the antibiotic regimen. A history of chronic and/or recurrent ulceration or direct signs at inspection may be suggestive of osteitis. Radiographic signs are late and nonspecific. Scintigraphy scans are difficult to interpret. Magnetic resonance imaging can be quite helpful in difficult cases. BACTERIOLOGICAL PROOF: Staphylococcus aureus and to a lesser extent streptococci account for almost all of the superficial infections in the diabetic foot. In case of deep ulceration, it is important to obtain deep specimens at surgical cleansing as more superficial samples are easily contaminated. Nevertheless, if Staphylococcus aureus is isolated from pus coming from a deep zone fistulizing to the skin, it is likely the causal agent since 80% of all bone infections involve S. aureus. Other germs besides staphylococci and streptococci include enterobacteria (40%), enterococci (26%) and pseudomonas (7%). Several germs are involved in about 70% of cases with a probable synergetic effect between the different bacterial colonies within the infected tissues.

Amputation, Surgical↗
PubMed2000

[Skin and osteoarticular bacterial infections of the diabetic foot. Treatment].

MULTIDISCIPLINARY CARE: A multidisciplinary approach is essential. General measures include immobilization of the focus, controlling blood glucose, anticoagulation, and anti-tetanus vaccination. Topical application of growth factors is currently under evaluation. ANTIBIOTIC THERAPY: The antibiotics chosen should diffuse well into bone tissue. Combinations with synergetic or additive effects against Staphylococcus aureus are best. Treatment duration depends on the depth of the ulceration. Two weeks is generally advised for superficial ulcers. For deep ulcers, treatment duration depends on the presence or not of osteitis and the quality of surgical debridement. In case of osteitis, after amputation with a healthy margin, antibiotics can generally be discontinued 2 weeks after surgery. Six weeks are required if the amputation margins do not lie in healthy zones. Finally, if no surgery is attempted, the antibiotic regimen should be continued for 3 months, or even longer, with a risk of failure greater than 50%. The best criterion for successful treatment is the absence of late recurrence. SURGERY: Surgery is an indispensable element in the overall treatment of deep infections and/or osteitis. The operation should be performed as early as possible to improve prognosis. Well-conducted early surgical debridement can prevent the infection from spreading and avoid the need for much more mutilating "salvage" procedures. Vascular surgery can help maintain sufficient blood supply for wound healing and antibacterial defense. Plastic surgery can be very helpful. PREVENTION: A certain number of simple measures help reduce the risk of diabetic foot ulcers. However, many patients, and practitioners, are insufficiently aware of their effectiveness. Prevention and treatment can best be accomplished by a multidisciplinary approach calling upon the endocrinologist and the vascular and orthopedic surgery teams. A carefully planned rehabilitation program using adapted soles, orthesis, orthopedic shoes or prostheses as needed can considerably reduce the frequency of recurrence. The risk of recurrence in a patient wearing adapted footwear is only 26% at 5 years compared with 83% in other cases.

Anti-Bacterial Agents↗
PubMed2000

Autosomal dominant type IIa hypercholesterolemia: evaluation of the respective contributions of LDLR and APOB gene defects as well as a third major group of defects.

Autosomal dominant type IIa hypercholesterolaemia (ADH) is characterised by an elevation of total plasma cholesterol associated with increased LDL particles. Numerous different molecular defects have been identified in the LDL receptor (LDLR) and few specific mutations in the apolipoprotein B (APOB) gene resulting in familial hypercholesterolaemia and familial defective apoB-100 respectively. To estimate the respective contribution of LDLR, APOB and other gene defects in this disease, we studied 33 well characterised French families diagnosed over at least three generations with ADH through the candidate gene approach. An estimation of the proportions performed with the HOMOG3R program showed that an LDLR gene defect was involved in approximately 50% of the families (P = 0.001). On the other hand, the estimated contribution of an APOB gene defect was only 15%. This low estimation of ADH due to an APOB gene defect is further strengthened by the existence of only two probands carrying the APOB (R3500Q) mutation in the sample. More importantly and surprisingly, 35% of the families in the sample were estimated to be linked to neither LDLR nor APOB genes. These data were confirmed by the exclusion of both genes through direct haplotyping in three families. Our results demonstrate that the relative contributions of LDLR and APOB gene defects to the disease are very different. Furthermore, our results also show that genetic heterogeneity is, generally, underestimated in ADH, and that at least three major groups of defects are involved. At this point, the contribution of the recently mapped FH3 gene to ADH cannot be assessed nor its importance in the group of 'non LDLR/non APOB' families.

Apolipoproteins B↗
PubMed2000

Bioavailability of starch and postprandial changes in splanchnic glucose metabolism in pigs.

Changes in splanchnic metabolism in pigs were assessed after meals containing slowly or rapidly digested starch. The pigs were fed a mixed meal containing a "slow" native (n = 5) or a "rapid" pregelatinized (n = 5) cornstarch naturally enriched with [(13)C]glucose. Absorption of [(13)C]glucose was monitored by the arteriovenous difference technique, and infusion of D-[6, 6-(2)H(2)]glucose in the jugular vein was used to calculate the systemic appearance of [(13)C]glucose. Arteriovenous balance data obtained during a 12-h study period showed that the fraction of ingested glucose equivalent appearing as glucose in the portal vein was 49.7 +/- 7.2% for the slow starch and 48.2 +/- 7.5% for the rapid starch (P = 0.86). These values, corrected for the gut extraction of circulating [(13)C]glucose, became 66.4 +/- 5.6 and 65. 3 +/- 5.6%, respectively (P = 0.35). Isotope dilution data indicated that systemic appearance of exogenous [(13)C]glucose represented 62. 9 +/- 7.6 and 67.4 +/- 3.0% of the oral load for slow and rapid starch, respectively (P = 0.68). Arterial glucose utilization by the gut increased from 7.3 +/- 0.9 micromol x kg(-1) x min(-1) before the meal to 8.5 +/- 1.6 micromol x kg(-1) x min(-1) during absorption, independently of the nature of the starch. Thus splanchnic glucose metabolism was unaffected by the nature of starch ingested.

Animals↗
PubMed2000

R3531C mutation in the apolipoprotein B gene is not sufficient to cause hypercholesterolemia.

Familial hypercholesterolemia and familial ligand-defective apolipoprotein B-100 (FDB) are dominantly inherited disorders leading to impaired low-density lipoprotein receptor (LDLR) and apolipoprotein B-100 (APOB) interaction, plasma LDL elevation, and hypercholesterolemia. We previously identified the first French FDB-R3531C proband, a woman with very high total cholesterol, in a group of type IIa hypercholesterolemic families. We report here the investigation of her family at large that revealed the total absence of cosegregation with hypercholesterolemia. Six of the 10 subjects heterozygous for the R3531C mutation had plasma cholesterol lower than the 97.5th percentile for their age and gender, and mean cholesterol levels were not significantly different between affected and unaffected persons. Furthermore, 2 family members with similar high LDL-cholesterol levels were not carriers of the R3531C substitution, suggesting the implication of another mutation. Segregation analysis of the LDLR gene revealed statistically significant genetic linkage with hypercholesterolemia, and analysis of the proband LDLR gene led to the identification of the 664 proline to leucine defective mutation and its detection in all 6 hypercholesterolemic-related members of this family. Therefore, our results show that the family presents with familial hypercholesterolemia and give evidence that the R3531C substitution in the APOB gene is not an allelic variant leading to FDB. Furthermore, thorough analysis of our data suggests that the APOB-R3531C mutation enhances the hypercholesterolemic effect of the LDLR-P664L defect, suggesting that it is a susceptibility mutation.

Adolescent↗
PubMed2000

Efficacy and safety of micronised fenofibrate in a randomised double-blind study comparing four doses from 200 mg to 400 mg daily with placebo in patients with hypercholesterolemia.

The aim of this study was to evaluate the efficacy on LDL-cholesterol (LDL-C) of micronised fenofibrate given for three months at doses ranging from 200 to 400 mg once daily, compared with placebo. A double-blind, randomised, parallel-group, multi-centre trial was performed in four centers of France in 340 hypercholesterolemic patients (163M, 177F) aged 18-75 years. After a 2-3 month single-blind run-in period on placebo and diet, patients with LDL-C greater than or equal to 4.65 mmol/l (180 mg/dl) maintained on the same diet throughout the study were randomly allocated to placebo or to 200, 267, 340 or 400 mg micronised fenofibrate, given once daily with the evening meal for 3 months. LDL-C, total cholesterol (TC), total triglycerides (TG) and apolipoprotein B (Apo B) significantly decreased compared with placebo in all four fenofibrate groups. For all randomised patients, the decrease in the fenofibrate groups ranged from 31.6-38.8% for LDL-C, 24.5-31.9% for TC, 26.7-40.8% for TG, and 27.3-35.0% for Apo B. An increase in HDL-cholesterol of 4.1-8.2% was observed in the fenofibrate groups, but did not reach statistical significance. Lipid values in the placebo group remained unchanged. The therapeutic goal of LDL-C<3.36 mmol/l (130 mg/dl) was reached in 27% in the 200 mg group and increased to 56% in the 300 mg group. There were no major clinical or biological adverse events in the dose interval from 200 mg to 400 mg of micronised fenofibrate per day. This study showed treatment for 3 months with micronised fenofibrate at doses up to 400 mg per day is effective and can reduce LDL-cholesterol up to 30% allowing further evaluation of these doses on longer trials.

Adult↗
PubMed2000

[Pulmonary hypertension in patient with beta-thalassemia major].

We report a case of pulmonary hypertension (PH) in a 35-year old patient with beta-thalassemia major; he had commenced blood transfusions after the age of 4 years and had been splenectomised at the age of 6 years. PH clinical presentation was not uncommon. Hemodynamic study revealed precapillary PH with high cardiac output; vasodilators agents led to significant pulmonary responsiveness. In beta-thalassemia, whereas congestive heart failure is common and due to cardiac hemosiderin deposition, PH appears to be non rare but its etiopathogenic mechanism remain unclear and probably non univoqual. Hypoxemia as well as hemodynamic changes related to chronic anemia including increased pulmonary flow might play an important role. Management should include blood transfusions to correct anemia, the indication and the choice of vasodilator agents need to be evaluated.

Adult↗
PubMed2000

[Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients].

BACKGROUND: We undertook a randomised controlled trial to assess the efficacy and tolerance of orlistat, a gastrointestinal lipase inhibitor, in promoting weight loss and preventing weight regain in obese patients over a 2-year period. METHODS: 743 patients (body-mass index 28-47 kg/m2), recruited at 15 European centres, entered a 4-week, single-blind, placebo lead-in period on a slightly hypocaloric diet (600 kcal/day deficit). 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg (three times a day) or placebo for 1 year in conjunction with the hypocaloric diet. In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance (eucaloric) diet. FINDINGS: From the start of lead-in to the end of year 1, the orlistat group lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 kg]; LSM difference 3.9 kg [p < 0.001] from randomisation to the end of year 1). During year 2, patients who continued with orlistat regained, on average, half as much weight as those patients switched to placebo (p < 0.001). Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2, compared with a mean regain of 2.5 kg in patients who continued on placebo (p < 0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein ratio, and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group. Gastrointestinal adverse events were more common in the orlistat group. Other adverse symptoms occurred at a similar frequency during both treatments. INTERPRETATION: Orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight regain in obese patients over a 2-year period. The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events.

Adolescent↗
PubMed1999

Improvement of blood glucose control in Type 1 diabetic patients treated with lispro and multiple NPH injections.

AIMS: To evaluate a multiple daily injections (MDI) regimen combining lispro with multiple NPH insulin injections in order to replace basal insulin optimally. METHODS: Twenty-five C-peptide negative Type 1 patients already trained to MDI were randomized to lispro (lispro + NPH 5 min before breakfast and lunch, lispro before dinner, NPH at bedtime) or soluble insulin (20-30 min before each meal and NPH at bed-time) for 3 months before crossing over to the other regimen for another 3 months. The mean initial HbA1c level was 8.32+/-1.5%. RESULTS: The variability of capillary blood glucose values was significantly lower with lispro (MAGE 0.75+/-0.36 g/l vs. 0.99+/-0.50, P<0.01; MODD 0.64+/-0.26 g/l vs. 0.80+/-0.40, P<0.05). There was a nonsignificant reduction in HbA1c with lispro: -0.40+/-0.86 vs. -0.08+/-0.71. Mean daily blood glucose levels were significantly lower with lispro (1.53+/-0.48 g/l vs. 1.82+/-0.57 g/l, P<0.05). The frequency of all hypoglycaemic episodes was the same with both regimens but the number of severe hypoglycaemic events was reduced with lispro, P = 0.048. At the end of the study, 75% of the patients chose the lispro associated with multiple NPH regimen for their own treatment. The total insulin doses was the same with both regimens but the proportion of NPH was higher with lispro (53% vs. 34%). CONCLUSIONS: An MDI regimen using lispro combined with multiple NPH compared to a standard MDI regimen using soluble insulin reduced day-to-day blood glucose fluctuations, was generally preferred by patients and was associated with a reduced incidence of severe hypoglycaemia with no loss of overall control.

Adult↗
PubMed1999

A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.

Autosomal dominant hypercholesterolemia (ADH), one of the most frequent hereditary disorders, is characterized by an isolated elevation of LDL particles that leads to premature mortality from cardiovascular complications. It is generally assumed that mutations in the LDLR and APOB genes account for ADH. We identified one large French pedigree (HC2) and 12 additional white families with ADH in which we excluded linkage to the LDLR and APOB, implicating a new locus we named "FH3." A LOD score of 3.13 at a recombination fraction of 0 was obtained at markers D1S2892 and D1S2722. We localized the FH3 locus to a 9-cM interval at 1p34.1-p32. We tested four regional markers in another set of 12 ADH families. Positive LOD scores were obtained in three pedigrees, whereas linkage was excluded in the others. Heterogeneity tests indicated linkage to FH3 in approximately 27% of these non-LDLR/non-APOB ADH families and implied a fourth locus. Radiation hybrid mapping located four candidate genes at 1p34.1-p32, outside the critical region, showing no identity with FH3. Our results show that ADH is genetically more heterogeneous than conventionally accepted.

Adult↗
PubMed1999

Effect of intravenous glutamine on duodenal mucosa protein synthesis in healthy growing dogs.

To determine whether glutamine acutely stimulates protein synthesis in the duodenal mucosa, five healthy growing dogs underwent endoscopic biopsies of duodenal mucosa at the end of three 4-h primed, continuous intravenous infusions of L-[1-13C]leucine on three separate days, while receiving intravenous infusion of 1) saline, 2) L-glutamine (800 micromol. kg-1. h-1), and 3) isonitrogenous amounts of glycine. The three infusions were performed after 24 h of fasting, a week apart from each other and in a randomized order. Glutamine infusion induced a doubling in plasma glutamine level, and glycine caused a >10-fold rise in plasma glycine level. During intravenous infusions of [13C]leucine, the plasma leucine labeling attained a plateau value between 3.22 and 3.68 mole % excess (MPE) and [13C]ketoisocaproate ([13C]KIC) of 2.91-2. 84 MPE; there were no significant differences between glutamine, glycine, and saline infusion days. Plasma leucine appearance rate was 354 +/- 33 (SE), 414 +/- 28, and 351 +/- 35 micromol. kg-1. h-1 (not significant) during glycine, saline, and glutamine infusion, respectively. The fractional synthetic rate (FSR) of duodenal mucosa protein was calculated from the rise in protein-bound [13C]leucine enrichment in the biopsy sample, divided by time and with either plasma [13C]KIC or tissue free [13C]leucine as precursor pool enrichment. Regardless of the precursor pool used in calculations, duodenal protein FSR failed to rise significantly during glutamine infusion (65 +/- 11%/day) compared either with saline (84 +/- 18%/day) or glycine infusion days (80 +/- 15%/day). We conclude that 1) plasma [13C]KIC and tissue free [13C]leucine can be used interchangeably as precursor pools to calculate gut protein FSR; and 2) short intravenous infusion of glutamine does not acutely stimulate duodenal protein synthesis in well-nourished, growing dogs.

Aging↗
PubMed1999

Noninvasive tracing of human liver metabolism: comparison of phenylacetate and apoB-100 to sample glutamine.

The labeling pattern of hepatic glutamine during infusion of [3-13C]lactate provides information on liver intermediary metabolism and allows us to correct apparent gluconeogenic rates for isotopic dilution in the oxaloacetate (OAA) pool. Liver glutamine can be sampled by its conjugation with phenylacetate to form phenylacetylglutamine (PAGN) but also by purifying the glutamine of the apolipoproteinB-100 of very low-density lipoprotein (apoB-100-VLDL). We compared these methods in normal and non-insulin dependent diabetes subjects. We tested also whether apoB-100-VLDL alanine enrichment could solve the problem of dilution of gluconeogenic precursor enrichments between peripheral blood and liver (prehepatic dilution). In both normal and diabetic subjects, the labeling patterns of glutamine obtained from PAGN or apoB-100-VLDL were comparable. Therefore, metabolic fluxes and correction factors for dilution in the OAA pool were also comparable. With both methods, gluconeogenic rates were not increased in diabetic patients. Use of the enrichment of apoB-100-VLDL alanine to correct for prehepatic dilution led to high estimates of gluconeogenesis; it remains uncertain whether this enrichment provides a correct estimate of liver pyruvate enrichment.

Adult↗
PubMed1999

["Buffalo neck": an unintended secondary effect of treatment with anti-HIV protease inhibitors].

BACKGROUND: Lipodystrophy and other fat distribution disorders have been reported in patients receiving protease inhibitor therapy for HIV infection. CASE REPORT: A 50-year-old HIV-positive patient was given protease inhibitor therapy (indinavir) for 6 months when he developed a lipomatous formation in the retrocervical area. Abdominal fat also increased in volume and the subcutaneous fat on the lower limbs decreased. DISCUSSION: We describe the main clinical features of these fat distribution disorders and discuss the pathogenic hypothesis of an interaction between antiprotease activity and hepatic lipoprotein receptor binding.

Abdomen↗
PubMed1999

Apolipoprotein A-I kinetics in heterozygous familial hypercholesterolemia: a stable isotope study.

Heterozygous familial hypercholesterolemia (FH) is associated with a moderate decrease of plasma apoA-I and HDL-cholesterol levels. The aim of the study was to test the hypothesis that these abnormalities were related to an increase of HDL-apoA-I fractional catabolic rate (FCR). We performed a 14-h infusion of [5,5,5-(2)H(3)]leucine in seven control subjects and seven heterozygous FH patients (plasma total cholesterol 422 +/- 27 vs. 186 +/- 42 mg/dL, P < 0.001, respectively). Plasma apoA-I concentration was not changed in FH compared to controls (respectively 115 +/- 18 vs. 122 +/- 15 mg/dL, NS), and HDL-cholesterol level was decreased (37 +/- 7 vs. 46 +/- 19 mg/dL, NS). Kinetics of HDL metabolism were modeled as a single compartment as no differences were observed between HDL(2) and HDL(3) subclasses. Both mean apoA-I FCR and absolute production rate (APR) were increased in FH (respectively, 0.36 +/- 0.14 vs. 0.22 +/- 0.05 pool/d, P < 0.05, and 18.0 +/- 7.7 and 11.2 +/- 2.3 mg/kg/d, P < 0.05). Higher HDL-triglyceride and HDL-apoE levels were observed in patients with heterozygous FH. (Respectively 19 +/- 8 vs. 8 +/- 3 mg/dL, P < 0.05, and 5.3 +/- 0.8 vs. 3.7 +/- 0.9 mg/dL, P < 0.05). We conclude that the catabolism of HDL-apoA-I is increased in heterozygous FH patients. However, plasma apoA-I concentration was maintained because of an increased HDL-apoA-I production rate.

Adult↗
PubMed1998

Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group.

BACKGROUND: We undertook a randomised controlled trial to assess the efficacy and tolerability of orlistat, a gastrointestinal lipase inhibitor, in promoting weight loss and preventing weight regain in obese patients over a 2-year period. METHODS: 743 patients (body-mass index 28-47 kg/m2), recruited at 15 European centres, entered a 4-week, single-blind, placebo lead-in period on a slightly hypocaloric diet (600 kcal/day deficit). 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg (three times a day) or placebo for 1 year in conjunction with the hypocaloric diet. In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance (eucaloric) diet. FINDINGS: From the start of lead-in to the end of year 1, the orlistat group lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 kg]; LSM difference 3.9 kg [p<0.001] from randomisation to the end of year 1). During year 2, patients who continued with orlistat regained, on average, half as much weight as those patients switched to placebo (p<0.001). Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2, compared with a mean regain of 2.5 kg in patients who continued on placebo (p<0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein ratio, and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group. Gastrointestinal adverse events were more common in the orlistat group. Other adverse symptoms occurred at a similar frequency during both treatments. INTERPRETATION: Orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight regain in obese patients over a 2-year period. The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events.

Adult↗
PubMed1998

Hyperglucagonemia and the immediate fate of dietary leucine: a kinetic study in humans.

The possible role of glucagon in determining the fate of dietary absorbed amino acids within the splanchnic bed was investigated in five healthy male volunteers. A kinetic study was performed involving a continuous 240-minute infusion of L-[5,5,5-2H3]leucine and D-[6,6-2H2]glucose by vein, while L-[1-13C]leucine was infused by a feeding tube into the duodenum (intragut [i.g.]) along with a constant intravenous (i.v.) infusion of somatotropin release-inhibitory factor (SRIF) combined with insulin, growth hormone, and glucagon. In random order, glucagon was infused at a rate of 0.4 ng x kg(-1) x min(-1) in one experiment and 1.2 ng x kg(-1) x min(-1) in the other experiment, while insulin and growth hormone were kept at constant serum levels, respectively, 37+/-13 pmol x L(-1) and 5+/-0.2 microg x L(-1). The diet was provided as an L-amino acid solution including 60 micromol x kg(-1) x h(-1) leucine without fat and carbohydrate. During the higher rate of glucagon infusion, there was an increase in plasma glucagon and glucose concentrations, glucose flux, and net dietary leucine release into the periphery from the splanchnic bed. Splanchnic removal and uptake of leucine were decreased with increased glucagon infusion. There were no statistical differences in the plasma leucine level and i.v. and i.g. leucine fluxes at the two glucagon levels, although leucine metabolic clearance increased (0.74 v 0.85 L x kg(-1) x h(-1), P=.08) in the case of glucagon excess. Plasma glucose increased with glucagon excess and was negatively correlated (P < .05) with the plasma leucine level (r=-.348) and i.v. (r=-.459) or i.g. (r=-.359) leucine fluxes. The negative correlation between plasma glucagon and leucine levels was also significant (r=-.684). No significant correlation was found between dietary leucine splanchnic removal and glucose, glucagon, or leucine plasma concentrations. We conclude that glucagon in excess has only a small quantitative effect on the overall handling of dietary leucine, and hypothesize that more leucine is exported to the peripheral tissues under these hormonal conditions.

Adult↗
PubMed1998

Role of glucose and glutamine synthesis in the differential recovery of 13CO2 from infused [2-13C] versus [1-13C] acetate.

Carbon exchange in the Krebs cycle may result in underestimation of substrate oxidation measured with 13C-labeled substrates, since carbon labeled in position 2 of acetyl-coenzyme A (CoA) could be incorporated into glucose (via gluconeogenesis) and glutamine. Five healthy volunteers were therefore infused with [1-13C] and [2-13C] acetate at a rate of 0.5 micromol x kg(-1) x min(-1) for 165 minutes on two different occasions in randomized order. Whole body acetate turnover did not differ between the two tracers: 7.9+/-0.3 and 7.5+/-0.6 micromol x kg(-1) x min(-1) (nonsignificant [NS]) for [1-13C] and [2-13C] acetate, respectively. Isotopic 13C enrichment was higher in expired CO2 (0.177+/-0.021 v 0.089+/-0.009 atom percent excess [APE], P < .01) and lower in glucose (0.074+/-0.017 v0.291+/-0.061 mole percent excess [MPE], P < .01) for [1-13C] acetate compared with [2-13C] acetate, respectively, at the end of the infusions. Glutamine isotopic enrichment was slightly but not significantly higher when infusing [1-13C] acetate versus [2-13C] acetate (0.348+/-0.038 v0.495+/-0.069 MPE, NS, respectively). At the end of the experiment, the recovery of 13CO2 from [1-13C] acetate was 44.8%+/-2.7%, and from [2-13C] acetate, 22.6%+/-1.3%. A significant correlation was observed between the differences in 13C enrichment of CO2 for the two tracers and glucose (deltaCO2=0.424 x deltaglucose + 0.001, R2=.9856, P=.0007) or glutamine (deltaCO2=0.621 x deltaglutamine + 0.004, R2=.9573, P=.0038) during the infusion. These results suggest that (1) although gluconeogenesis appears to be more responsible than glutamine for the differential recovery of [2-13C] versus [1-13C] acetate, other secondary pathways are probably also implicated; and (2) different recovery correction factors should be applied when measuring substrate oxidation with a stable isotope tracer depending on the expected position of 13C in acetyl-CoA.

Acetates↗